While lower hemoglobin is generally associated with adverse events in diabetes, we have recently observed in type 1 diabetes that those with overt nephropathy had hemoglobin levels as high as 18.8 g/dL. We thus explored whether hemoglobin concentrations are generally higher in type 1 diabetes.

Baseline (1986-1988) hemoglobin levels from the Pittsburgh Epidemiology of Diabetes Complications (EDC) of type 1 diabetes study were compared to general population data from the NHANES III in the same age range as the EDC population (8-48 years).

Both male and female EDC study participants had significantly higher hemoglobin levels than their NHANES III counterparts (men: 16.0 vs 15.1 g/dL, p<0.0001; women: 14.1 vs 13.3 g/dL, p<0.0001). The difference between the two populations was greatest in adolescent females.

Hemoglobin levels maybe higher in type 1 diabetes than in the general population which may have important clinical implications.

To assess the new quantitative bone scan parameters as markers of Charcot neuroosteoarthropathy (CNO) activity.

Forty-two patients with acute (n=21) and non-acute (n=21) CNO underwent quantitative bone scanning. Patients with acute CNO were followed for 3-12 months and bone scans were repeated after treatment. New quantitative parameters were assessed and compared with markers of bone turnover and with skin temperature difference (STD).

Significant correlations between quantitative bone scan parameters and bone turnover markers were observed (all p<0.05). These parameters decreased after treatment of CNO and its reduction to the baseline value correlated with differences of bone turnover markers and STD (all p<0.05).

Our study suggests that bone scanning can be used not only for diagnosis of CNO, but also for monitoring disease activity by quantitative bone scan parameters.

To prospectively examine the association of depression with risks for advanced macrovascular and microvascular complications among patients with type 2 diabetes.

A longitudinal cohort of 4,623 primary care patients with type 2 diabetes was enrolled in 2000-2002, and followed through 2005-2007. Advanced microvascular complications included blindness, end-stage renal disease, amputations, and renal failure deaths. Advanced macrovascular complications included myocardial infarction, stroke, cardiovascular procedures and deaths. Medical record review, ICD-9 diagnostic and procedural codes, and death certificate data were used to ascertain outcomes in the 5 year follow-up. Proportional hazard models analyzed the association between baseline depression and risks of adverse outcomes.

After adjustment for prior complications, demographic, clinical and diabetes self-care variables, major depression was associated with significantly higher risks of adverse microvascular outcomes [hazard ratio (HR) 1.36, 95% confidence interval (CI): 1.05 to 1.75], and adverse macrovascular outcomes [HR: 1.24, 95% CI: (1.0 to 1.54)].

Among people with type 2 diabetes, major depression is associated with an increased risk of clinically significant microvascular and macrovascular complications over the ensuing 5 years, even after adjusting for diabetes severity and self-care activities. Clinical and public health significance of these findings rises as the incidence of type 2 diabetes soars. Further research is needed to clarify the underlying mechanisms for this association and to test interventions to reduce the risk of diabetes complications among patients with co-morbid depression.

It is believed that disruption of vulnerable atherosclerotic plaque and subsequent thrombus formation play critical roles in the pathogenesis of cerebral infarction. We simultaneously determined 4 relatively common genetic variants related to plaque rupture or subsequent local thrombus formation, and evaluated the combined effect on cerebral infarction.

We enrolled 3094 Japanese type 2 diabetic subjects (males 62.7%; 61.5±8.4 years old) and determined their genotypes regarding matrix metalloproteinase 9 (MMP9) C-1562T, Coagulation factor XII (FXII) C46T, von Willebrand factor (VWF) G-1051A, and plasminogen activator inhibitor (PAI-1) -675 4G/5G polymorphisms. The diagnosis of cerebral infarction was performed based on history, physical examination, and neuroimaging.

The single association analysis revealed that there were no statistically significant associations between each polymorphism and the prevalence of cerebral infarction. Interestingly, the prevalence of cerebral infarction was higher with the increase of the total number of 4 concomitant unfavorable "pro-atherothrombotic alleles" in each subject (p value for linear trend=0.004). Furthermore, a multiple logistic regression analysis showed that the number of pro-atherothrombotic alleles was a risk factor for cerebral infarction independently of conventional risk factors (Odds ratio for 1-point increase in the number of pro-atherothrombotic allele=1.15 with 95%CI 1.05-1.26, p=0.004).

Accumulation of gene polymorphisms related to plaque rupture and thrombus formation is likely associated with the prevalence of cerebral infarction in type 2 diabetic patients, suggesting that the combined information about these variants is useful to assess the risk of cerebral infarction.

The Diabetes Care Protocol (DCP), a multifaceted computerized decision support diabetes management intervention, reduces cardiovascular risk of type 2 diabetes (DM2) patients. We performed a cost-effectiveness analysis of DCP from a Dutch health care perspective.

A cluster randomized trial provided data of DCP versus usual care. The 1-year follow-up patient data were extrapolated using a modified Dutch micro-simulation diabetes model, computing individual lifetime, health related costs and health effects. Incremental costs and effectiveness (quality-adjusted life-years (QALY)) were estimated using multivariate generalized estimating equations to correct for practice-level clustering and confounding. Incremental cost-effectiveness ratios (ICER) were calculated and cost-effectiveness acceptability curves were created. Stroke costs were calculated separately. Subgroup analyses examined patients with and without cardiovascular disease (CVD+, CVD-).

Excluding stroke, DCP patients lived longer (0.14 life-years, ns), experienced more QALYs (0.037, ns) and incurred higher total costs (1,415, ns), resulting in an ICER of 38,243 per QALY gained. The likelihood of cost-effectiveness given a willingness-to-pay threshold of 20,000 per QALY gained is 30%. DCP had a more favorable effect on CVD+ patients (ICER=14,814) than for CVD- patients (ICER=121,285). Coronary heart disease costs were reduced (-587 (p<0.05)).

DCP reduces cardiovascular risk, resulting in only a slight improvement in QALYs, lower CVD costs, but higher total costs, with a high cost-effectiveness ratio. Cost-effective care can be achieved by focusing on cardiovascular risk factors in DM2 patients with a history of cardiovascular disease.

Assigning the correct molecular diagnosis in diabetes informs treatment and prognosis. Better clinical markers would facilitate discrimination and prioritisation for genetic testing between diabetes subtypes. Serum 1,5 Anhydroglucitol (1,5AG) levels were reported to differentiate Maturity-onset diabetes of the young due to HNF1A mutations (HNF1A-MODY) from type 2 diabetes, but this requires further validation. We evaluated serum 1,5AG in a range of diabetes subtypes as an adjunct for defining diabetes aetiology.

1,5AG was measured in UK subjects with: HNF1A-MODY (n=23), MODY due to glucokinase mutations (GCK-MODY, n=23), type 1 diabetes (n=29), latent autoimmune diabetes of adults (LADA, n=42) and type 2 diabetes (n=206). ROC curve analysis was performed to assess discriminative accuracy of 1,5AG for diabetes aetiology.

Mean [SD range] 1,5AG levels (µg/ml) were: GCK-MODY 13.06 [5.74-29.74]; HNF1A-MODY 4.23 [2.12-8.44]; type 1 diabetes 3.09 [1.45-6.57]; LADA 3.46 [1.42-8.45] and type 2 diabetes 5.43 [2.12-13.23]. Levels in GCK-MODY were higher than other groups [p<10^–4 vs. each group]. HNF1A-MODY subjects showed no difference in unadjusted 1,5AG levels from type 2 diabetes, type 1 diabetes or LADA. Adjusting for HbA1c revealed a difference between HNF1A-MODY and type 2 diabetes [p=0.001]. The discriminative accuracy of unadjusted 1,5AG levels were 0.79 for GCK-MODY vs. type 2 diabetes, 0.86 for GCK-MODY vs. HNF1A-MODY, but only 0.60 for HNF1A-MODY vs. type 2 diabetes.

In our dataset serum 1,5AG performed well in discriminating GCK-MODY from other diabetes subtypes, particularly HNF1A-MODY. Measurement of 1,5AG levels could inform decisions regarding MODY diagnostic testing.

To identify factors associated with declining β-cell compensation for insulin resistance.

In a cohort of Hispanic women with recent gestational diabetes mellitus, oral (OGTT) and intravenous (IVGTT) glucose tolerance tests and bioelectrical impedance measurements were performed at 15-month intervals for up to five years or until fasting plasma glucose exceeded 140 mg/dl (7.8 mmol/l). Data were analyzed to identify predictors of declining β-cell compensation for insulin resistance (the disposition index; "DI") and to examine the mechanism of weight gain and changes in circulating levels of selected adipokines and inflammatory markers on β-cell compensation decline.

60 non-diabetic women had a median of four sets of OGTT+IVGTT during a median follow-up of 52 months. Fourteen of the women developed diabetes. None of the baseline characteristics were significantly predictive of a decline in DI. There were significant univariate associations between declining DI and weight gain (specifically fat gain), declining adiponectin and rising C-reactive protein (CRP). Multivariate analysis showed that the weight gain was the most significant factor associated with declining DI, The amount of association between weight gain and declining DI was explained 31% by changes in adiponectin and CRP, and 40% by changes in insulin resistance.

These results identify weight gain as the strongest factor associated with declining β-cell compensation for insulin resistance in Hispanic women at high risk for type 2 diabetes. Such effect may be mediated through at least two effects: alterations in adipokine levels and increasing insulin resistance.

To evaluate whether the administration of metformin exerts any effects on serum homocysteine (Hcy) levels in patients with polycystic ovary syndrome (PCOS), and whether supplementation with folate enhances the positive effects of metformin on the structure and function of the vascular endothelium.

Fifty patients affected by PCOS, without additional metabolic or cardiovascular diseases, were enrolled in a prospective, non-randomised placebo-controlled double-blind clinical study. They were grouped into two treatment arms that were matched for age and body mass index. Patients were treated with a six-month course of metformin (1,700 mg daily) plus folic acid (400 µg daily; experimental group, n=25) or placebo (control group, n=25). Complete hormonal and metabolic patterns, serum Hcy, folate, vitamin B12, endothelin-1 (ET-1) levels, brachial artery diameter at the baseline (BAD-B) and after reactive hyperaemia (BAD-RH), flow-mediated dilation (FMD), and intima--media thickness (IMT) in both common carotid arteries were evaluated.

After treatment, a significant increase in serum Hcy levels was observed in the control group in comparison with the baseline values and the experimental group. A beneficial effect was observed in the concentrations of BAD-B, BAD-RH, FMD, IMT, and serum ET-1 in both groups. However, the results were improved more significantly in the experimental group than in the controls.

Metformin exerts a slight but significant deleterious effect on serum Hcy levels in patients with PCOS, and supplementation with folate is useful to increase the beneficial effect of metformin on the vascular endothelium.

We examined the associations of sitting time and television (TV) viewing time with continuously-measured biomarkers of cardio-metabolic risk in Australian adults.

Waist circumference, BMI, resting blood pressure, triglycerides, HDL-cholesterol, fasting and 2-hr post-load plasma glucose and fasting insulin were measured in 2761 women and 2103 men aged ≥ 30 years (mean age: 54 years) without clinically-diagnosed diabetes from the 2004–2005 Australian Diabetes Obesity and Lifestyle study (AusDiab). Multivariate linear regression analyses examined associations of self-reported sitting time and TV viewing time (hours per day) with these biomarkers, adjusting for potential confounding variables.

For both women and men, sitting time was detrimentally associated with waist circumference, BMI, systolic blood pressure, fasting triglycerides, HDL-cholesterol, 2-hr post load plasma glucose and fasting insulin (all p<0.05), but not with fasting plasma glucose and diastolic blood pressure (men only). With the exception of HDL-cholesterol and systolic blood pressure in women, the associations remained significant after further adjustment for waist circumference. TV viewing time was detrimentally associated with all metabolic measures in women; and all except HDL-cholesterol and blood pressure in men. Only fasting insulin and glucose (men only) remained deleteriously associated with TV viewing time following adjustment for waist circumference.

In women and men, sitting time and TV viewing time were deleteriously associated with cardio-metabolic risk biomarkers, with sitting time having more consistent associations in both genders and being independent of central adiposity. Preventive initiatives aimed at reducing sitting time should focus on both non-leisure and leisure-time domains.

Familial predisposition to hypertension has been associated with the development of diabetic nephropathy in adults, but there are limited data in adolescents. Our aim was to assess whether parental ambulatory blood pressure (ABP) was associated with BP and albumin excretion in young offspring with type 1 diabetes.

24-hour ABP monitoring was performed in 509 young offspring (mean age(±SD) 15.8±2.3yr) with type 1 diabetes, 311 fathers and 444 mothers. Systolic (SBP) and diastolic (DBP) BP during 24h, day (d) and night-time (n) were calculated. 3 early morning urinary albumin-creatinine ratios (ACR), HbA1c and anthropometric parameters were available for the offspring.

All paternal ABP parameters, except for nSBP, were independently related to the offspring's ABP (24h-SBP: β=0.18, 24h-DBP: β=0.22, dSBP β=0.25, dDBP β=0.23; nDBP β=0.18, all p<0.01). Maternal 24h-DBP (β=0.19 p=0.004), day-DBP (β=0.09 p=0.04) and nSBP (β=0.24 p=0.001) were related to the corresponding ABP parameter in the offspring.

Significant associations were found between the offspring logACR and maternal ABP. The association with 24h-DBP (β=0.16 p=0.02), dDBP (β=0.16 p=0.02) and nDBP (β=0.15 p=0.03) persisted even after adjusting for the offspring's ABP. Mothers of offspring with microalbuminuria (MA) had higher ABP than mothers of offspring without MA (all p<0.05).

In this cohort, parental ABP significantly influenced the offspring BP, therefore confirming familial influences on this trait. In addition, maternal ABP, particularly DBP, was closely related to ACR in the offspring, suggesting a dominant effect of maternal genes or an effect of the intrauterine environment on MA risk.

To examine after gastric bypass the effect of peroral vs. gastroduodenal feeding on glucose metabolism.

A type 2 diabetic patient was examined on two consecutive days 5 weeks after gastric bypass. A standard liquid meal was given, on the first day into the bypassed gastric remnant and on the second day perorally. Plasma glucose, insulin, C peptide, glucagon, incretin hormones, peptide YY and free fatty acids were measured.

Peroral feeding reduced 2-h-postprandial plasma glucose (7.8 vs. 11.1 mM) and incremental-area-under-the-glucose-curve (0.33 vs. 0.49 mMxmin) compared with gastroduodenal feeding . β-cell function (iAUC_Cpeptide/Glu) was more than 2-fold improved during peroral feeding and the GLP-1 response increased nearly 5-fold.

Improvement in postprandial glucose metabolism after gastric bypass is an immediate and direct consequence of the gastrointestinal rearrangement, associated with exaggerated GLP-1 release and independent of changes in insulin sensitivity, weight-loss and caloric restriction.

To test the hypothesis that maternal gestational diabetes increases cardiovascular risk markers in Indian children.

Anthropometry, blood pressure (BP) and glucose/insulin concentrations were measured in 514 children at 5 and 9.5 years of age (35 offspring of diabetic mothers/ODM; 39 offspring of diabetic fathers/ODF). Children of non-diabetic parents were controls.

At 9.5 years, female ODM had larger skinfolds (P<0.001), higher glucose (30-minute) and insulin concentrations, HOMA insulin resistance and systolic BP (P<0.05) than controls; males had higher HOMA (P<0.01). Associations were stronger than at 5 years. Female ODF had larger skinfolds and males had higher HOMA (P<0.05) than controls; associations were weaker than for ODM. Associations between outcomes in controls, and parental BMI, glucose and insulin concentrations were similar for mothers and fathers.

The intrauterine environment experienced by ODM increases diabetes and cardiovascular risk, over genetic factors; the effects strengthen during childhood.

To validate a low-cost tool for identifying diabetes patients in rural areas of Latin America.

A regression equation incorporating post-prandial time and a random plasma glucose was used to screen 800 adults in Honduras. Patients with a probability of diabetes of 20% or greater were asked to return for a fasting plasma glucose (FPG). A random fifth of those with a screener-based probability of diabetes < 20% was also asked to return for follow-up. The gold standard was an FPG ≥ 126 mg/dl.

The screener had very good test characteristics (area under the receiver operating characteristic curve = 0.89). Using the screening criterion of ≥ 0.42, the equation had a sensitivity of 74.1% and specificity of 97.2%.

This screener is a valid measure of diabetes risk in Honduras and could be used to identify diabetes patients in poor clinics in Latin America.

To determine if multiparity is associated with type 2 diabetes, independent of visceral adipose tissue (VAT) and adipokines.

Participants were from the UCSD Filipino Women's Health Study with at least one live birth. A two hour 75 gram OGTT was administered; adiponectin, leptin, ghrelin, reproductive history, family history of diabetes, VAT, and lifestyle behaviors were measured between 1995-2002.

Among 152 women, mean age was 59.5 years (range: 48-73), mean parity was 4.3 (range: 1-12 births). Type 2 diabetes prevalence increased by parity group (low:1-2 births,25%; medium: 3-5 births, 30.3%; and grand multiparity: 6-12 births, 50%, p=0.048). Family history of diabetes, exercise, insulin resistance, leptin and ghrelin levels did not differ by parity group. Compared to women in the low parity group, women with ≥6 births were significantly older (62 vs 57 years), had lower college completion (22 vs 58%, p=0.006), more hypertension (72 vs 55%), VAT (74.9 vs 58.4 cm³) and lower adiponectin concentration (5.79 vs 7.61 µg/ml).

In multivariate analysis adjusting for adiponectin, VAT, family history of diabetes, age, education, hypertension and estrogen use, grandmultiparous women had a threefold higher odds of type 2 diabetes (Adjusted OR: 3.40, 95% CI: 1.13-10.2) compared to low parity women. No differences were observed in the odds of diabetes between women in the medium (AOR: 1.10, 95% 0.41 - 2.91) compared to the low parity group

Having ≥6 children was associated with type 2 diabetes, independent of adiponectin, VAT, family history, and other measured diabetes risk factors.

To assess the association of 1-h plasma glucose (1hPG) and inflammation with normal glucose tolerance (NGT) and pre-diabetes (pre-DM).

A cohort of 1062 subjects was enrolled. After oral glucose load (OGTT), we compared NGT and pre-DM subjects above and below the 1hPG cut point (155 mg/dl). Fibrinogen and leucocytes count (WBC) for subclinical inflammation, lipid ratios, insulin sensitivity (Matsuda Index), were determined.

NGT and pre-DM patients 1hPG>155 mg/dl showed a significant increase of inflammatory markers and lipid ratios (for all, p<0.05). In age-sex-BMI-adjusted analysis, 1hPG is associated with a significant higher WBC count and fibrinogen (p<0.05). Patients with elevated 1hPG showed a highly significant lower insulin sensitivity than subjects below 1hPG (p<0.01).

Elevated 1hPG in NGT and pre-DM subjects is associated to subclinical inflammation, high lipid ratios and insulin resistance. Therefore, 1hPG >155 mg/dl could be considered a new "marker" for cardiovascular risk.

Obesity and increases in body weight in adults are considered to be among the most important risk factors for type 2 diabetes. Low birth weight is also associated with a higher diabetes incidence. We aimed to examine to what extent the evolution of body shape, from childhood to adulthood is related to incident diabetes in late adulthood.

E3N is a cohort study of French women born 1925-1950 and followed by questionnaire every 2 years. At baseline, in 1990, women were asked to report their current weight, height and body silhouette at various ages. Birth weight was recorded in 2002. Cases of diabetes were self-reported or obtained by drug reimbursement record linkage, and further validated.

Of the 91,453 women non-diabetic at baseline, 2534 developed diabetes over the 15 years of follow-up. Birth weight, and body silhouette at 8 years, at menarche and in young adulthood (20-25 years) were inversely associated with the risk of diabetes, independently of adult BMI during follow-up (all P trends <0.001). In mid-adulthood (35-40 years), the association was reversed, with an increase in risk related to a larger body silhouette. An increase in body silhouette from childhood to mid-adulthood amplified the risk of diabetes.

Low birth weight and thinness until young adulthood may increase the risk of diabetes, independently of adult BMI during follow-up. Young women who were thin children should be especially warned against weight gain.

Identification of asymptomatic patients with type 2 diabetes at increased risk for coronary artery disease remains a challenge. We evaluated the potential of carotid intima media thickness (CIMT) for prediction of abnormal myocardial perfusion in this population.

CIMT and SPECT myocardial perfusion imaging were assessed in 98 asymptomatic patients with type 2 diabetes. An increased CIMT was defined as ≥75^thpercentile of reference values.

Increased CIMT was an independent predictor of the extent of abnormal perfusion (P<0.001). In patients with increased CIMT as compared to patients with normal CIMT, abnormal perfusion (75%vs9%) and severely abnormal perfusion (28%vs3%) were observed more frequently.

Increased CIMT was significantly related to the presence and extent of abnormal myocardial perfusion. Assessment of CIMT may be useful to identify asymptomatic patients with type 2 diabetes at higher risk for coronary artery disease.

Diabetes is increasingly common in cystic fibrosis (CF), but little exists describing its influence on mortality. Using national UK data, this study documents diabetes-specific mortality rates, estimates the impact of diabetes on survival, and estimates population attributable fractions.

This retrospective cohort study identified 8,029 individuals aged 0–65 years from the UK CF Registry (1996–2005). 5,892 patients were included in analyses of mortality rates and 4,234 in analyses of risk factors. We calculated age-adjusted mortality rates using Poisson regression, standardized mortality ratios using the population of England and Wales, and relative risks using proportional hazards modeling.

During 17,672 person-years of follow-up, 393 subjects died. The age-adjusted mortality rate was 1.8/100 person-years (95% CI 1.6 to 2.0). The age-adjusted mortality rates per 100 person-years were 2.0 (CI 1.8 to 2.4) in women and 1.6 (95% CI 1.4 to 1.9) in males, and 4.2 (95% CI 3.4–5.1) in individuals with diabetes vs 1.5 (95% CI 1.3 to 1.7) in those without diabetes. Independent risk factors for death included diabetes (hazard ratio, 95% confidence interval, 1.31 (1.03 to 1.67), female sex (1.71, 1.36 to 2.14) plus poorer pulmonary function, lower body mass index, B. cepacia infection, absence of S. aureus infection, allergic bronchopulmonary aspergillosis, liver disease, prior organ transplantation, and corticosteroid use.

Individuals with CF die earlier with diabetes, which, if delayed or better treated, might reasonably extend survival, and merits testing.

Several studies have suggested an association between specific diabetes treatment and cancer mortality. We studied the association between metformin use and cancer mortality in a prospectively followed cohort.

In 1998 and 1999, 1353 patients with type 2 diabetes mellitus were enrolled in the ZODIAC-study in the Netherlands. Vital status was assessed in January 2009. Cancer mortality rate was evaluated using standardized mortality ratios (SMR), and the association between metformin use and cancer mortality was evaluated with a Cox proportional hazard model, taking possible confounders into account.

Median follow-up time was 9.6 years, average age at baseline was 68 years, and average HbA1c was 7.5%. Five hundred seventy patients died, of which 122 from malignancies. SMR for cancer mortality was 1.47 (95%CI 1.22-1.76). In patients taking metformin compared to patients not taking metformin at baseline, the adjusted hazard ratio (HR) for cancer mortality was 0.43 (95%CI 0.23-0.80), and the HR with every increase of 1 gram of metformin was 0.58 (95%CI 0.36-0.93).

In general, patients with type 2 diabetes are at increased risk for cancer mortality. In our group, metformin use was associated with lower cancer mortality when compared to non-metformin use. Although the design cannot be conclusive about causality, our results suggest a protective effect of metformin on cancer mortality.

To determine whether regular aspirin use (≥75 mg/day) is independently associated with cardiovascular disease (CVD) and all-cause mortality in community-based patients with type 2 diabetes and no history of CVD.

Of the type 2 diabetes patients recruited to the longitudinal observational Fremantle Diabetes Study, 651 (50.3%) with no prior CVD history at entry between 1993 and 1996 were followed until death or end-June 2007, representing a total of 7,537 patient-years (mean±SD 11.6±2.9 years). Cox proportional hazards modeling was used to determine independent baseline predictors of CVD and all-cause mortality including regular aspirin use.

There were 160 deaths (24.6%) during follow-up, with 70 (43.8%) due to CVD. In Kaplan-Meier survival analysis, there was no difference in either CVD or all-cause mortality in aspirin users vs non-users (P=0.52 and 0.94, respectively, by logrank test). After adjusting for significant variables in the most parsimonious Cox models, regular aspirin use at baseline independently predicted reduced CVD and all-cause mortality (hazard ratio (95% CI) 0.30 (0.09-0.95) and 0.53 (0.28-0.98), respectively; P≤0.044). In subgroup analyses, aspirin use was independently associated with reduced all-cause mortality in those aged ≥65 years and men.

Regular low-dose aspirin may reduce all-cause and CVD mortality in a primary prevention setting in type 2 diabetes. All-cause mortality reductions appear greatest in men and those aged ≥65 years. The present observational data support recommendations that aspirin should be used in primary CVD prevention in all but the lowest risk patients.

The epidemiological association between coffee drinking and decreased risk of type 2 diabetes is strong. However, caffeinated coffee acutely impairs glucose metabolism. We assessed acute effects of decaffeinated coffee on glucose and insulin levels.

Randomized cross-over placebo-controlled trial of the effects of decaffeinated coffee, caffeinated coffee and caffeine on glucose, insulin and glucose-dependent insulinotropic polypeptide (GIP) levels during a two-hour oral glucose tolerance test (OGTT) in eleven young men.

Within the first hour of the OGTT, glucose and insulin were higher for decaffeinated coffee than for placebo (p<0.05). During the whole OGTT decaffeinated coffee yielded higher insulin than placebo, and lower glucose and a higher insulin sensitivity index than caffeine. Changes in GIP could not explain any beverage effects on glucose and insulin.

Some types of decaffeinated coffee may acutely impair glucose metabolism, but less than caffeine.

We hypothesized that labile HbA1c (LHbA1c), is directly correlated with stable HbA1c (SHbA1c) and between-patient differences in SHbA1c which are independent of mean blood glucose (MBG).

We measured SHbA1c, LHbA1c, MBG and a single clinic capillary glucose (CCG) from 152 pediatric patients with type 1 diabetes. Patients were grouped as High, Moderate, or Low glycators by Hemoglobin Glycation Index.

LHbA1c and SHbA1c were correlated with CCG and MBG. LHbA1c was not correlated with SHbA1c (r=0.06, p=0.453). LHbA1c level was significantly associated with glycator group status (p<0.0019) and CCG (p<0.0001). Adjusted LHbA1c levels were highest in the Low HGI patients and lowest in the High HGI group.

A conventional model of SHbA1c being directly correlated with LHbA1c concentration was not confirmed. Between patient differences in SHbA1c at the same MBG may be due to complex intracellular factors influencing formation of SHbA1c from LHbA1c.

This randomized controlled trial evaluated the effect of a registered dietitian (RD)-led management of diabetes on glycemic control and macronutrient intake in type 2 diabetic patients in primary care clinics in Taiwan and studied the association between changes in macronutrient intake and glycemic measures.

We recruited 154 adult patients with type 2 diabetes and randomly assigned them to a routine care control group (n=79) or an RD-led intervention group (n=75) who received on-site diabetic self-management education every three months over 12 months.

Over the one year period, neither the intervention group (n=75) nor the control group (n=79) had significant changes in HbA1c, while the intervention patients with poorly controlled baseline HbA1c(>7%) (n=56) had significantly greater improvements in HbA1c and fasting plasma glucose than the controls (n=60) (–0.7 vs. –0.2%, p=0.034; –13.4 vs. 16.9mg/dl, p=0.007) during the same period. We also found significant net intervention-control group differences in overall energy intake (–229.06+309.16 vs. 56.10+309.41kcal/day) and carbohydrate intake (–31.24+61.53 vs. 7.15+54.09 g/day) (p<0.001) in patients with poorly controlled HbA1c. Multivariable adjusted modeling revealed an independent association between changes in carbohydrate intake and HbA1c in the intervention group (n=56, beta=0.10; SE=0.033; p=0.004).

On-site RD-led management of diabetes can improve glycemic control in patients with poorly managed type 2 diabetes in primary care clinics in Taiwan. A reduction in carbohydrate intake may improve glycemic status.

To describe the clinical experience and the pharmacokinetics of U-500 regular insulin in severely insulin resistant obese type 2 diabetic patients.

Patients requiring >200 units of insulin with A1C levels >8.0% were switched to U-500 regular insulin. For the pharmacokinetic study, fasting subjects received 100 units of U-500 regular insulin subcutaneously and samples drawn before and every 30-60 minutes for glucose, insulin and C-peptides until glucose fell below 100 mg/dl.

U-500 regular insulin doses were adjusted using the same approach as for adjusting NPH insulin doses. Mean values at baseline and at minimum A1C levels, respectively, were, respectively: A1C (%) — 9.9, 7.1; units/kg — 3.2, 3.3; weight (kg) — 98.6, 102.8. Pharmacokinetically, insulin concentrations rose briskly by 30 minutes and remained elevated for at least 7 hours.

Uncontrolled severely insulin resistant obese type 2 diabetic patients can be satisfactorily controlled with U-500 regular insulin.

Fetuin-A is an inhibitor of vascular calcification and a mediator of insulin resistance. This study evaluated the association of low plasma fetuin-A and peripheral arterial disease (PAD).

A total of 738 individuals with type-2 diabetes (mean age 58.7 years, 37.1% female) without known cardiovascular or kidney disease were included in this cross-sectional analysis.

Subjects with PAD had a significantly lower fetuin-A (264.3 vs. 293.4 ng/dl, P<0.001). In multivariable analysis, a one standard deviation decrease in fetuin-A increased the odds of PAD (OR 1.6, p=0.02). Subgroup analysis revealed an increased odds even in subjects with eGFR >80 (OR 1.9, p=0.05) or hsCRP <3 mg/dl (OR=2.7, p=0.002).

Lower circulating fetuin-A is associated with PAD in type-2 diabetes beyond traditional and novel cardiovascular risk factors. Our findings suggest a potentially unique role for fetuin-A deficiency as a biomarker of PAD in patients with type-2 diabetes.

Progressive Beta-cell loss causes catabolism in Cystic Fibrosis (CF). Existing diagnostic criteria for diabetes were based on microvascular complications rather than CF-specific outcomes.

We aimed to relate glycemic status in CF to weight and lung-function changes.

We determined peak blood glucose (BG_max) during Oral Glucose Tolerance Tests (OGTT) with samples every 30 minutes on 33 consecutive children (aged 10.2–18 years). Twenty-five also agreed to Continuous Glucose Monitoring (CGM, Medtronic).

Outcome Measures were change in weight Standard Deviation Score (wtSDS), %Forced Expiratory Volume in 1 second (%FEV1), and %Forced Vital Capacity (%FVC) in the year preceding OGTT.

Declining wtSDS and %FVC were associated with higher BG_max (both p=0.02) and with CGM-time above 7.8mmol/l (p=0.006 and p=0.02 respectively), but not with BG_120mins. Decline in %FEV1 was related to CGM-time above 7.8mmol/l (p=0.02). Using Receiver Operating Characteristic (ROC) analysis to determine optimal glycemic cut-offs, CGM-time above 7.8mmol/l ≥4.5% detected declining wtSDS with 89% sensitivity and 86% specificity (AUC 0.89, p=0.003). BG_max ≥8.2 mmol/l gave 87% sensitivity and 70% specificity (AUC 0.76, p=0.02). BG_120mins did not detect declining wtSDS (AUC 0.59, p=0.41). After excluding 2 patients with BG_120mins ≥11.1 mmol/L, decline in wtSDS was worse if peak BG was ≥8.2mmol/l (–0.3±0.4 vs 0.0±0.4 for BG <8.2, p=0.04) or if CGM-time above 7.8mmol/l was ≥4.5% (–0.3±0.4 vs +0.1±0.2 for time <4.5%, p=0.01).

BG_max on OGTT ≥ 8.2 mmol/L and CGM-time above 7.8mmol/l ≥4.5% are associated with declining wtSDS and lung-function in the preceding 12 months.

To assess the relationship between habitual sleep disturbances and the incidence of type 2 diabetes, and to obtain an estimate of the risk.

Systematic search of publications using MEDLINE (1955-April 2009), EMBASE, the Cochrane Library and manual searches without language restrictions. We included studies if they were prospective, with follow-up >3 years, had an assessment of sleep disturbances at baseline and incidence of type 2 diabetes. We recorded several characteristics for each study. We extracted quantity and quality of sleep, how they were assessed, and incident cases defined with different validated methods. We extracted relative risks (RR) and 95% C.I. and pooled them using random effects models. We performed sensitivity analysis, and assessed heterogeneity and publication bias.

We included ten studies (13 independent cohort samples; 107,756 male and female participants, follow-up range 4.2 to 32 years, 3,586 incident cases of type 2 diabetes). In pooled analyses, quantity and quality of sleep predicted the risk of developing type-2 diabetes. For short duration of sleep (≤5-to-6h per night) the RR was 1.28; 95% CI 1.03 to 1.60; p=0.024 (heterogeneity p=0.015); for long duration of sleep (>8-to-9h per night) 1.48 (1.13 to 1.96; p=0.005); for difficulty in initiating sleep 1.57 (1.25 to 1.97; p<0.0001) and for difficulty in maintaining sleep 1.84 (1.39 to 2.43; p<0.0001).

Quantity and quality of sleep consistently and significantly predict the risk of the development of type 2 diabetes. The mechanisms underlying such relation may differ between short and long sleepers.

We aimed at characterizing familial risks for type 2 diabetes by the type and number of affected family members, including half siblings, adoptees and spouses in order to quantify risks and estimate the contribution of environmental effect.

Families were identified from the Multigeneration Register and type 2 diabetes patients were obtained from the Hospital Discharge Register. Standardize incidence ratios (SIR) were calculated for offspring type 2 diabetes whose family members were hospitalized for type 2 diabetes at ages over 39 years compared to those lacking affected family members.

The number of hospitalized type 2 diabetes patients was 157,549. Among 27,895 offspring, 27.9% had a parent or sibling also hospitalized for type 2 diabetes. The familial relative risk ranged from 2.0 to over 30, depending on the number and type of probands. The highest relative risks of type 2 diabetes were found in individuals who had at least two siblings affected by type 2 diabetes, irrespective of the parental disease. Adoptees showed no risk from adopted parents.

The study, the largest yet published, showed that familial relative risks varied by the number and type of affected family member. Assumably, much of the familial clustering remains yet to be genetically explained. The high risk should be recognized in clinical genetic counseling. The data from adoptees confirmed the genetics basis of the familial associations but those from half siblings and spouses suggested that a smaller part of familial clustering may be accounted for by environmental factors.

To determine glycosylated hemoglobin (HbA1c) cut-points for glucose intolerance in Asian Indians.

2188 participants without known diabetes were randomly selected from the Chennai Urban Rural Epidemiology Study. All had fasting plasma glucose [FPG] and 2hr post glucose [2hr PG] measurements after 75g load and were classified as impaired fasting glucose [IFG] (ADA criteria: FPG ≥5.5 mmol/L and < 7 mmol/L and WHO criteria: FPG ≥6.1mmol/L and <7 mmol/L; impaired glucose tolerance [IGT]: 2hr PG ≥ 7.8 mmol/L and < 11.1 mmol/L, or diabetes: FPG ≥7mmol/L and/or 2hr PG ≥ 11.1 mmol/L. HbA1c was measured using the Biorad Variant machine. Based on Receiver Operating Characteristic curves, optimum sensitivity and specificity were derived for defining HbA1c cut points for diabetes, IGT and IFG.

Mean values of HbA1c among NGT, IGT and diabetes subjects were 5.5±0.4%, 5.9±0.6% and 8.3±2.0% respectively [p for trend <0.001] with considerable overlap. To identify diabetes based on 2hr PG, HbA1c cut point of 6.1% had area under the curve (AUC) of 0.941 with 88.0% sensitivity and 87.9% specificity. When diabetes was defined as FPG ≥ 7.0mmol/L, the HbA1c cut point was 6.4% (AUC=0.966, sensitivity 93.3%, specificity 92.3%). For IGT, AUC = 0.708; IFG – WHO, AUC = 0.632 and IFG – ADA, AUC=0.708, the HbA1c cut point was 5.6%.

In Asian Indians, HbA1c cut point of 6.1% and 6.4% defined diabetes by 2hr PG or FPG criteria respectively. A value of 5.6% optimally identified IGT or IFG, but was less than 70% accurate.

To predict the frequency of type 1 diabetes in childhood and adolescence (<15 years of age) in Germany for the next 20 years.

Data on diabetes onset has been collected by means of a registry in the Federal German state of Baden-Wuerttemberg (documentation period, 1987-2006; n=5,108; completeness of data 98.1%).

The current incidence rate (2000-2006) is 19.4/100,000/year (95% CI 18.6-20.2). The annual incidence rate can be expressed as a square of a linear function of the calendar year x (y = (3.05+0.0778*(x-1986))², r² = 0.90). The highest increase per year was observed in the age groups comprising 2- and 3-year-olds (12% and 13% per year, respectively). The incidence rate for the year 2026 is estimated to be 37.9/100,000/year (95% CI 33.3-42.9).

The increase that we found in younger children is characteristic of a left shift towards an earlier age.

To evaluate the heterogeneity in the clinical expression in a family with GCK-MODY.

Members (three generations) of the same family presented either with overt neonatal hyperglycemia, marked postprandial hyperglycemia or glucosuria. HOMA_IR, insulinogenic and disposition indices were calculated. OGTT results in the glucokinase(GCK)-mutation carriers from this family were compared with those from other subjects with GCK mutations in the same codon (GCK₂₆₁), with other missense and other types of GCK mutations in different codons from the European-MODY-Consortium database (GCK_m).

Mutation G261R was found in the glucokinase gene. During OGTT, glucose (p=0.02) and insulin (p=0.009) response at 2-hours as well as 2h glucose increment (GCK₂₆₁ vs. other missense GCK-mutations, p=0.003) were significantly higher in GCK₂₆₁ than in GCK_m carriers.

Differing from other GCK_m carriers, the glucose and insulin response to oral glucose was significantly higher in GCK₂₆₁ carriers indicating clinical heterogeneity in GCK-MODY.

Although magnesium (Mg) may favorably affect metabolic outcomes, few studies have investigated the role of Mg intake in systemic inflammation and endothelial dysfunction in humans.

Among 3,713 postmenopausal women aged 50-79 y in the Women's Health Initiative Observational Study and free of cardiovascular disease, cancer, and diabetes at baseline, we measured plasma concentrations of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumor necrosis factor receptor 2 (TNF--R2), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin. Mg intake was assessed using a semi-quantitative food frequency questionnaire.

After adjusting for age, ethnicity, clinical center, time of blood draw, smoking, alcohol, physical activity, energy intake, BMI, and diabetes status, Mg intake was inversely associated with hs-CRP (p-for-trend=0.003), IL-6 (p<.0001), TNF--R2 (p=0.0006), and sVCAM-1 (p=0.06). Similar findings remained after further adjustment for dietary fiber, fruit, vegetables, folate, and saturated and trans-fat intake. Multivariable-adjusted geometric means across increasing quintiles of Mg intake were 3.08, 2.63, 2.31, 2.53, 2.16 mg/L for hs-CRP (p=0.005), 2.91, 2.63, 2.45, 2.27, 2.26 pg/mL for IL-6 (p=0.0005), and 707, 681, 673, 671, 656 ng/mL for sVCAM-1 (p=0.04). An increase of 100 mg/d Mg was inversely associated with hs-CRP (-0.23 mg/L ± 0.07; p=0.002), IL-6 (-0.14 pg/mL± 0.05; p=0.004), TNF--R2 (-0.04 pg/mL ± 0.02; p=0.06), and sVCAM-1 (-0.04 ng/mL ± 0.02; p=0.07). No significant ethnic differences were observed.

High Mg intake is associated with lower concentrations of certain markers of systemic inflammation and endothelial dysfunction in postmenopausal women.

Blockade of the renin angiotensin system (RAS) plays an important role in preventing end-organ injury associated with diabetes mellitus (DM). The recent development of direct renin inhibitors (DRI) provides a new approach to block the RAS, but the effect of DRIs on renal and systemic vascular function in uncomplicated type 1 DM have not been elucidated.

Renal hemodynamic function (inulin, paraaminohippurate clearance), augmentation index and pulse wave velocity, endothelial dependent vasodilatation (FMD) and endothelial independent vasodilatation (response to sublingual nitroglycerin) were evaluated before and after taking aliskiren (300 mg daily for 30 days) in 10 adult subjects with uncomplicated type 1 DM during clamped euglycemia (4-6 mmol/L) and hyperglycemia (9-11 mmol/L).

In response to DRI, plasma renin activity decreased (0.40 to 0.13 ng/mL/h, p<0.05) and plasma renin increased (5.2 to 75.0 ng/L, p<0.05). Peripheral and central blood pressures decreased and effective renal plasma flow and glomerular filtration rate increased during clamped euglycemia and hyperglycemia (p<0.05). Carotid augmentation index during clamped euglycemia decreased (26±6% to 20±5%, p<0.05) as did pulse wave velocity during clamped hyperglycemia (7.8±0.6 m/s to 6.8±0.5 m/s, p<0.05). In response to DRI, FMD increased during both clamped euglycemia (1.92±1.13% to 5.55±0.81%) and hyperglycemia (1.86±0.98% to 5.63±0.62) as did the vasodilatory response to sublingual nitroglycerin.

DRI exerts a renal vasodilatory effect and improves parameters of systemic vascular function, suggesting that blockade of the RAS with this new class of agents has important functional effects in subjects with uncomplicated type 1 DM.

We evaluated the efficacy of malabsorptive bariatric surgery on daily blood glucose fluctuations and oxidative stress in type 2 diabetic obese patients.

48-h continuous subcutaneous glucose monitoring (CSGM) were assessed in type 2 patients before and 1 month after biliopancreatic diversion (BPD) (n=36), or after diet-induced equivalent weight loss (n=20). The mean amplitude of glycemic excursions (MAGE) and oxidative stress (nitrotyrosine) were evaluated during CSGM. During a standardized meal, glucagon-like peptide-1 (GLP-1), glucagon, and insulin were measured.

Fasting and postprandial glucose decreased equally in surgical and diet groups. A marked increase in GLP-1 occurred during interprandial period in surgical patients toward diet group (P<0.01). Glucagon was more suppressed during interprandial period in surgical patients compared to diet group (P<0.01). MAGE and nitrotyrosine levels decreased more after GBP than after diet (P<0.01).

Oxidative stress reduction after BPD seem to be related to the regulation of glucose fluctuations resulting from intestinal bypass.

We investigated whether palmitoleate, which prevents from insulin resistance in mice, predicts insulin sensitivity (IS) in humans.

The fasting fatty acid pattern in the plasma FFA fraction was determined in 100 subjects at increased risk for type 2 diabetes. IS was estimated during an oral glucose tolerance test (OGTT) at baseline and after 9 months of lifestyle intervention and measured during the euglycemic, hyperinsulinemic clamp (n=79).

Circulating palmitoleate (OGTT:F-Ratio=8.2, p=0.005; clamp:F-Ratio=7.8, p=0.007) but not total FFAs (OGTT:F-Ratio=0.6, p=0.42; clamp:F-Ratio=0.7, p=0.40) correlated positively with IS, independently of age, gender and adiposity. High baseline palmitoleate predicted larger increase in IS. For 1 standard deviation increase in palmitoleate the odds ratio for being in the highest vs the lowest tertile of adjusted change in IS was 2.35 (95%-CI, 1.16-5.35).

Circulating palmitoleate strongly and independently predicts IS, suggesting that it plays an important role in the pathophysiology of insulin resistance in humans.

Stress may play a role in the pathogenesis of the metabolic syndrome (MetS). However, the scant evidence available is not population-based, restricting external validity of the findings. Our aim was to test associations between stressful life events, their accumulation and the MetS in a large population-based cohort. We also tested associations between stress and the individuals components related to the MetS.

A population-based, random sample of 3,407 women and men aged 18--78 years residing in the Western Finland. Metabolic syndrome was defined according to the ATP III and IDF criteria. Severity of 15 stressful life events pertaining to finance, work, social relationships, health and housing was self-rated.

In comparison to subjects not reporting any extremely stressful life events, those reporting work- or finance-related events had an increased odds for having the MetS. The risk was further increased according to accumulation of stressful finance-related events and to having at least three stressful life events in any of the life domains assessed. Accumulation of stressful life events was associated with insulin resistance, obesity and triglycerides. The associations were not confounded by sex, age, lifestyle or family history of diabetes.

Life events perceived as stressful, particularly those related to finance and work, may signal for poor metabolic health.

The goal of this study was to examine whether metabolic abnormalities are responsible for the histological changes observed in Japanese patients with nonalcoholic fatty liver disease (NAFLD) who have undergone serial liver biopsies.

In total, 39 patients had undergone consecutive liver biopsies. Changes in their clinical data were analyzed, and biopsy specimens were scored histologically for stage.

The median follow-up time was 2.4 years (range, 1.0–8.5 years). Liver fibrosis had improved in 12 patients (30.7%), progressed in 11 patients (28.2%), and remained unchanged in 16 patients (41%). In a Cox proportional hazard model, decrease in A1C and use of insulin were associated with improvement of liver fibrosis independent of age, gender and BMI. However, A1C was more strongly associated with the improvement of liver fibrosis than use of insulin after adjusted for each other (chi-square; 7.97 vs. 4.58, respectively).

Tight glycemic control may prevent histological progression in Japanese patients with NAFLD.

To determine maternal hormonal and metabolic factors associated with insulin sensitivity in human pregnancy

Prospective observational cross sectional study of one hundred and eighty normal pregnant women, using samples collected at the time of blinded oral glucose tolerance testing between 24 and 32 weeks gestation as an ancillary to the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Setting - two public university teaching hospitals — Cleveland, Ohio, USA and Brisbane, Australia. Methods of assessment - Fasting maternal serum cholesterol, triglycerides, free fatty acids, insulin, leptin, tumour necrosis factor alpha, placental growth hormone (PGH), insulin like growth factors (IGFs) 1 and 2 and insulin like growth factor binding proteins (IGFBPs) 1 and 3 were assayed. Correlation and multiple regression analyses were used to determine factors associated with maternal insulin sensitivity estimated using both OGTT derived (IS _OGTT) and fasting (IS _HOMA) insulin and glucose concentrations.

Insulin sensitivity correlated (r = x, y for IS _OGTT, IS _HOMA respectively) with fasting maternal serum leptin (–0.44, –0.52 ), IGFBP1 ( 0.42, 0.39) and triglycerides (–0.31, –0.27 ). These factors were significantly associated with insulin sensitivity in multiple regression analyses (adjusted R² 0.44 for IS _OGTT and IS _HOMA). These variables explained more than 40% of the variance in estimates of insulin sensitivity.

Maternal hormonal and metabolic factors related to the placenta, adipose tissue and the growth hormone axis are associated with the variation in insulin sensitivity seen during normal human pregnancy.

Despite increased information on the importance of an inappropriate inflammatory response in the acute Charcot process, there has been no previous attempt to define the specific pathways that mediate its pathogenesis. Here, the role played by monocytes was analyzed.

The immune phenotype of peripheral monocytes was studied by FACS analysis comparing patients with acute Charcot (n=10), in both the active and recovered phase, diabetic patients with neuropathy, with or without osteomyelitis and normal controls.

As compared to diabetic controls and healthy subjects, monocytes from acute Charcot patients showed a proinflammatory immune phenotype characterized by increased production of proinflammatory cytokines, reduced secretion of antiinflammatory cytokines, increased expression of surface costimulatory molecules, and increased resistance to serum withdrawal-induced apoptosis. In addition, the pattern of circulating cytokines confirmed activation of proinflammatory cytokines. No modulation of the monocyte phenotype was documented in diabetic controls and healthy subjects, thus indicating that the proinflammatory alterations of monocytes are specific and causative of acute Charcot.

Together, these data provide evidence for the role of proinflammatory changes in the immune phenotype of monocytes in the pathogenesis of acute Charcot. These alterations may explain the abnormally intense and prolonged inflammatory response that characterizes this disorder and may represent a potential therapeutic target for specific pharmacological interventions.

Hemoglobin A1c (A1C) ≥6.5% has been recently proposed as the defining criterion for diabetes. However, performance characteristics of this definition have not been described.

We compared new to previous definitions of diabetes, 1999 World Health Organization (DM_1999WHO) and 2003 American Diabetes Association based on fasting glucose alone (DM_FPG126), in the Insulin Resistance Atherosclerosis Study.

Participants with A1C ≥6.5%, DM_1999WHO, and DM_FPG126 were 44 (5.2%), 132 (15.4%), and 61 (7.1%), respectively. In individuals with DM_1999WHO, mean, median, and interquartile range of A1C were 6.3%, 5.9%, and 5.5 – 6.6%, respectively; in those with DM_FPG126, 7.0%, 6.6%, and 6.0 – 7.1%.

A1C ≥6.5% identifies fewer individuals than DM_1999WHO or DM_FPG126. Studies are needed to determine that A1C ≥6.5% compromises neither blood pressure and lipid management in early diabetes nor the implementation of lifestyle interventions for diabetes prevention.

To determine the effects of daily walnut consumption on endothelial function, cardiovascular biomarkers, and anthropometric measures in type 2 diabetics.

This study was a randomized, controlled, single-blind, cross-over trial. Twenty-four participants with type 2 diabetes (mean age 58 years; 14 women, 10 men) were randomly assigned to one of the two possible sequence permutations to receive an ad libitum diet enriched with 56 g (366 kcal) of walnuts per day and an ad libitum diet without walnuts for 8 weeks. Subjects underwent endothelial function testing (measured as flow-mediated dilatation or FMD) and assessment of cardiovascular biomarkers before and after each 8-week treatment phase. The primary outcome measure was the change in FMD after 8 weeks. Secondary outcome measures included changes in plasma lipids, HbA1c, fasting glucose, insulin sensitivity, and anthropometric measures.

Endothelial function significantly improved after consumption of a walnut-enriched ad libitum diet compared to an ad libitum diet without walnuts (2.2 ± 1.7 % vs. 1.2 ± 1.6 %; p=0.04). The walnut-enriched diet increased fasting serum glucose, lowered serum total cholesterol and low-density lipoprotein cholesterol from baseline (10.0 ± 20.5 mg/dL; p=0.04, –9.7 ± 14.5 mg/dL; p<0.01; and –7.7 ± 10 mg/dL; p<0.01 respectively), though these changes were not significant when compared to an ad libitum diet without walnuts. There were no significant changes in anthropometric measures, plasma HbA1c, and insulin sensitivity.

A walnut-enriched ad libitum diet improves endothelium-dependent vasodilatation in type 2 diabetics, suggesting a potential reduction in overall cardiac risk.

To determine how glucose control in women with GDM treated with metformin and/or insulin influenced pregnancy outcomes.

Women randomized to metformin or insulin treatment in the Metformin in Gestational diabetes (MiG) trial had baseline glucose tolerance test (OGTT) results and HbA1c documented, together with all capillary glucose measurements during treatment. In the 724 women who had glucose data for analysis, tertiles of baseline glucose values and HbA1c, and of mean capillary glucose values during treatment, were calculated. The relationships between maternal factors, glucose values and outcomes (including a composite of neonatal complications, preeclampsia and large and small for gestational age (LGA, SGA) infants) were examined with bivariable and multivariate models.

Baseline OGTT did not predict outcomes, but HbA1c predicted LGA (p=0.003). During treatment, fasting capillary glucose predicted neonatal complications (p<0.001) and postprandial glucose predicted preeclampsia (p=0.016) and LGA (p=0.001). Obesity did not influence outcomes and there was no interaction between glycemic control, randomized treatment or maternal BMI in predicting outcomes. The lowest risk of complications was seen in the lowest tertile when fasting capillary glucose was <4.9mmol/l (mean(SD)=4.6(0.3)mmol/l) compared with 4.9-5.3mmol/l or higher and when postprandial glucose was <6.5mmol/l (mean(SD)=6.2(0.2)mmol/l)

Glucose control in women with GDM treated with metformin and/or insulin is strongly related to outcomes. Obesity is not related to outcomes in this group. Targets for fasting and postprandial capillary glucose may need to be lower than currently recommended.

Glycated albumin (GA) relative to glycated hemoglobin (HbA_1C) is a useful marker of short-term glycemic control. We investigated whether endogenous insulin secretion in type 2 diabetes mellitus (T2DM) has different effects on GA and HbA_1C levels.

HbA_1C, GA and GA/HbA_1C ratio were compared in 202 T2DM patients by type of treatment. Effect of beta-cell function determined by homeostasis model assessment (HOMA-%β) on GA/HbA_1C ratio was examined. In addition, GA/HbA_1C ratio was compared between T2DM patients and 16 patients with type 1 diabetes mellitus (T1DM).

In T2DM patients, GA/HbA_1C ratio was significantly higher in those treated with insulin than in those treated with diet or oral hypoglycemic agents. HOMA-%β showed a significant inverse correlation with GA/HbA_1C ratio. This ratio was higher in T1DM patients than in T2DM patients.

In diabetic patients with decreased insulin secretion, serum GA levels are higher relative to HbA_1C.

The peroxisome proliferator-activated receptor gamma 2 (PPARG2) Pro12Ala polymorphism has been associated with a higher body mass index (BMI) and a lower risk of type 2 diabetes in adulthood. The association between adiposity and PPARG variants can be influenced by environmental factors like early growth, dietary fat and (as recently shown) breastfeeding. The study objectives were to assess (i) the influence of the PPARG2 Pro12Ala polymorphism on adiposity markers in adolescents and (ii) a possible modulating effect of breastfeeding on these associations.

Data on breastfeeding duration, BMI and genotypes for the Pro12Ala polymorphism were available for 945 adolescents (mean age 14.7 y). The breastfeeding duration was obtained from parental records. We measured weight, height, waist circumference and 6 skinfold thicknesses.

No significant associations between the Pro12Ala polymorphism and any of the above-mentioned anthropometric parameters were found. There were significant interactions between the PPARG2 Pro12Ala polymorphism and breastfeeding with regard to adiposity measurements (all adjusted p<0.05). Indeed, in children who had not been breastfed, Ala12 allele carriers had higher adiposity parameters (e.g. delta BMI: +1.88 kg/m², adjusted -for age, gender and center- p=0.007) than Pro12Pro adolescents. In contrast, in breastfed subjects, there was no significant difference between Ala12 allele carriers and Pro12Pro children in terms of adiposity measurements, whatever the duration of breastfeeding.

Breastfeeding appears to counter the deleterious effect of the PPARG2Pro12Ala polymorphism on anthropometric parameters in adolescents.

Attempts to build an artificial pancreas by using subcutaneous (SC) insulin delivery from a portable pump guided by an SC glucose sensor have confronted delays and variability of insulin absorption. We tested closed-loop intra-peritoneal (IP) insulin infusion from an implanted pump driven by an SC glucose sensor via a proportional-integral-derivative (PID) algorithm.

Two-day closed-loop therapy (except for a 15-minute pre-meal manual bolus) was compared with a one-day control phase with intra-peritoneal open-loop insulin delivery, according to randomized order, in a hospital setting in eight type 1 diabetic patients treated by implanted pumps. Percentage of time spent with blood glucose in the 4.4–6.6 mmol/L range was the primary endpoint.

During the closed-loop phases, the percentage of time spent with blood glucose in the 4.4–6.6 mmol/L range was significantly higher: 39.1±4.5 vs. 27.7±6.2% (mean ± SEM, p=0.05), and overall dispersion of blood glucose values was reduced between patients. Better closed-loop glucose control came from the time periods excluding the two early postprandial hours with higher % time within 4.4–6.6 mmol/L: 46.3±5.3 vs. 28.6±7.4 (p=0.025) and lower mean blood glucose levels: 6.9±0.3 vs. 7.9±0.6 mmol/L (p=0.036). Time spent with blood glucose below 3.3 mmol/L was low and similar for both investigational phases.

Our results demonstrate the feasibility of IP insulin delivery for an artificial β-cell and support the need for further study. Moreover, according to a semi-automated mode, the features of the pre-meal bolus in terms of timing and amount warrant further research.

The severity of peripheral neuropathy in diabetic patients varies for unclear reasons. Long-term use of metformin is associated with malabsorption of vitamin B₁₂ (cobalamin; Cbl) and elevated homocysteine (Hcy) and methylmalonic acid (MMA) levels, which may have deleterious effects on peripheral nerves. This study intends to clarify the relationship between metformin exposure, levels of Cbl, Hcy and MMA, and severity of peripheral neuropathy in diabetic patients. We hypothesized that metformin exposure would be associated with lower Cbl levels, elevated Hcy and MMA levels, and more severe peripheral neuropathy.

A prospective case-control study of patients with type 2 diabetes and concurrent symptomatic peripheral neuropathy comparing those who had received more than 6 months of metformin therapy (N=59) to those without metformin exposure (N=63). Comparisons were made using clinical (Toronto Clinical Scoring System, Neuropathy Impairment Score), laboratory (serum Cbl, fasting Hcy, fasting MMA), and electrophysiological measures (nerve conduction studies).

Metformin-treated patients had depressed Cbl levels and elevated fasting MMA and Hcy levels. Clinical and electrophysiological measures identified more severe peripheral neuropathy in these patients; cumulative metformin dose correlated strongly with these clinical and paraclinical group differences.

Metformin exposure may be an iatrogenic cause for exacerbation of peripheral neuropathy in patients with type 2 diabetes. Interval screening for Cbl deficiency and systemic Cbl therapy should be considered upon initiation of, as well as during, metformin therapy to detect potential secondary causes of worsening peripheral neuropathy.

Although fenofibrate was associated with less progression of albuminuria in the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study, it is unknown if it has any effect on renal function. We explored if there were changes in commonly available markers of renal function during fenofibrate treatment in the FIELD Helsinki cohort excluding statin users.

170 subjects with type 2 diabetes were randomly assigned to micronised fenofibrate 200 mg/day or placebo for 5 years. In this substudy, we measured several markers of albumin excretion and renal function.

Following intensified treatment, blood pressure and fasting glucose decreased in both groups while HbA_1c remained at 7.2%. Plasma creatinine increased with fenofibrate while urine creatinine remained comparable between the groups, resulting in significant decreases in both creatinine clearance and estimated glomerular filtration rates (eGFR) by the MDRD-4 and Cockroft-Gault equations in the fenofibrate group. Cystatin C increased during fenofibrate treatment. Urinary albumin/creatinine ratio and diurnal urine protein remained unchanged, whereas overnight urinary albumin excretion rate showed minor decreases in both groups.

We report concomitant decreases in creatinine clearance and eGFR by fenofibrate. These changes complicate the clinical surveillance during fenofibrate treatment. We could not demonstrate beneficial effects of fenofibrate on albumin excretion. A novel finding is increase of cystatin C in type 2 diabetic patients during fenofibrate treatment. The clinical relevance of the changes needs to be assessed in a long-term outcome study of renal function.

To examine whether concentrations of serum 25-hydroxyvitamin D (25[OH]D) and parathyroid hormone (PTH) are associated with surrogate markers of insulin resistance (IR) in U.S. adults without physician-diagnosed diabetes.

Cross-sectional data (n=3,206) from the 2003-2006 National Health and Nutrition Examination Survey were analyzed.

The age-adjusted prevalence of hyperinsulinemia, high homeostatic model assessment-IR, high glycohemoglobin, and fasting and 2-hour hyperglycemia decreased linearly across quintiles of 25(OH)D but increased linearly across quintiles of PTH (except for a quadratic trend for fasting hyperglycemia). After extensive adjustment for potential confounders, the relationships between 25(OH)D and the markers of IR and 2-hour hyperglycemia persisted. Only hyperinsulinemia was positively associated with PTH (P<0.05).

Among U.S. adults without physician-diagnosed diabetes, low concentrations of serum 25(OH)D were associated with markers of IR. The role of PTH in IR deserves further investigation.

To study the association between microalbuminuria and development of preeclampsia and preterm delivery in pregnant women with type 1 diabetes.

Population-based prospective study in 846 normo- or microalbuminuric women with type 1 diabetes without antihypertensive treatment in early pregnancy. Data were collected prospectively by 1-3 caregivers in each center and reported to a central registry.

The prevalence of microalbuminuria in the first trimester was 10%, median diabetes duration 11 years and 3^rd trimester HbA1c 6.6 %. The frequency of preeclampsia and preterm delivery before 34 weeks in the microalbuminuric group was 40% and 13%, both significantly higher than in the normoalbuminuric group where the figures were 12% and 6% respectively (p<0.001). After adjustments for possible confounders, significant predictors for development of preeclampsia were: Microalbuminuria 4.0 (2.2-7.2) (odds ratio, 95% confidence interval), nulliparity 3.1 (1.9-5.1) and 3^rd trimester HbA1c 1.3 (1.1-1.5) per 1 % increase.

Delivery before 34 weeks was associated with early microalbuminuria in univariate analyses, but in multiavariate analyses Hba1c was the only significant predictor of this outcome. Preeclampsia was associated with a threefold higher risk of delivery before 34 weeks.

Presence of microalbuminuria in early pregnancy is associated with a four-fold increased risk of developing preeclampsia. Hba1c values during pregnancy are highly predictive of both preeclampsia and preterm delivery. Future research with antihypertensive treatment in normotensive, microalbuminuric pregnant women to prevent preeclampsia is proposed.

To examine usual marine omega-3 fatty acid (mO-3FA) intake in persons with diabetes, its association with adiposity, lipid and glucose control and its changes with behavioral lifestyle intervention for weight loss.

Cross-sectional and one-year longitudinal analyses were performed on 2397 Look AHEAD (LA) participants. LA is a cardiovascular-outcome trial evaluating the effects of intensive lifestyle intervention (ILI) for weight loss in overweight/obese subjects with type 2 diabetes.

Baseline mO-3FA intake was 162 ± 138 mg/day. It was inversely associated with triglycerides (B = –0.41, p <0.001) and weakly with HDL (B = 4.14, p = 0.050), after multiple covariate adjustment. One-year mO-3FA and fried/sandwich fish intake decreased with ILI (p <0.001).

mO-3FA intake in LA participants was low but associated favorably with lipids. These results encourage investigation on the potential benefits of increasing mO-3FA intake in lifestyle interventions for weight loss in individuals with diabetes.

To determine the concurrent, prospective and time concordant relationships between major depressive disorder (MDD), depressive symptoms (DS), and diabetes distress (DD) with glycemic control.

In a non-interventional study, we assessed 506 type 2 patients for MDD (Composite International Diagnostic Interview), for DS (Center for Epidemiological Studies-Depression) and for DD (Diabetes Distress Scale), along with self-management, stress, demographics, and diabetes status, at baseline, 9 and 18 months later. Using multilevel modeling (MLM), we explored the cross-sectional relationships of the three affective variables with HbA1C; the prospective relationships of baseline variables with change in HbA1C over time; and the time-concordant relationships with HbA1C.

All three affective variables were moderately inter-correlated, although the relationship between DS and DD was higher than either was with MDD. In the cross-sectional MLM, only DD and not MDD or DS was significantly associated with HbA1C. None of the three affective variables were linked with HbA1C in prospective analyses. Only DD displayed significant time-concordant relationships with HbA1C.

We found no concurrent or longitudinal association between MDD or DS with HbA1C, whereas both concurrent and time-concordant relationships were found between DD and HbA1C. What has been called "depression" among type 2 patients may really be two conditions – MDD and DD – with only the latter displaying significant associations with HbA1C. Ongoing evaluation of both DD and MDD may be helpful in clinical settings.

Oxidative stress is a major contributing factor in the development of diabetic nephropathy. Peroxisome proliferator-activated receptor gamma (PPAR-) heterozygous mice and Pro12Ala polymorphism in PPARG exhibited increased resistance to oxidative stress. Smoking increases the production of reactive oxygen species, which accelerates oxidative stress under hyperglycemia. To determine whether the Pro12Ala polymorphism, alone or in combination with smoking, contributes to the development of diabetic nephropathy, a case-control study was performed in 760 Chinese patients with type 2 diabetes.

Among patients, 532 had diabetic nephropathy with micro-albuminuria (n=245) or overt-albuminuria (n=287), and 228 did not show either of these symptoms but had been suffering from diabetes for ≥ 10 years and were not undergoing antihypertensive treatment.

After adjusting for confounders, the Pro/Pro genotype significantly associated with diabetic nephropathy, odds ratio (OR) 2.30 (95% CI 1.18-4.45), p=0.014; smoking was also an independent risk factor for diabetic nephropathy with OR 1.99 (1.08-3.68), p=0.029. In addition, we identified possible synergistic effects, i.e., the high-risk group (smokers with the Pro/Pro genotype) showed 4.52 times higher risk (95% CI, 1.78-11.48; p=0.002) of diabetic nephropathy than the low-risk group (nonsmokers with Pro/Ala genotype) in a multiple-logistic-regression analysis controlled for the confounders.

Our results indicated that the Pro/Pro genotype and smoking were significant independent risk factors for diabetic nephropathy. The possible synergistic effects of genotype and smoking may aggravate oxidative stress and contribute to the development of diabetic nephropathy.

To identify type 1 diabetes-susceptible HLA DR-DQ haplotypes using tag single nucleotide polymorphisms (SNPs), and to estimate the disease risk using these tag SNPs.

Five tag SNPs were typed in a total of 211 Japanese subjects including 201 patients with type 1 diabetes who had already typed for HLA-DRB1, -DQA1, and -DQB1 alleles and 300 control subjects.

Tag SNP rs2395185 captured haplotypes involving all DR4 specificities and DR9 specificity with a sensitivity of 98.5% and specificity of 94.9%. Using the T allele of rs2395185, we obtained odds ratio (95% confidence interval) of 2.87 (2.21–3.74) for type 1 diabetes. In addition, rs3129888 captured haplotypes involving HLA-DRB1*0802 with a sensitivity of 92.3% and specificity of 98.9%.

Typing of two tag SNPs (rs2395185 and rs3129888) may be useful for screening of Japanese subjects at genetic risk of type 1 diabetes.

To investigate serum levels of the adipokine chemerin in patients on chronic hemodialysis (CD) as compared to controls with a glomerular filtration rate (GFR) above 50 ml/min.

Chemerin was quantified by ELISA in control (n=60) and CD (n=60) patients and correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation, in both groups.

Median serum chemerin levels were more than 2-fold higher in CD patients (542.2 µg/l) as compared to subjects with a GFR above 50 ml/min (254.3 µg/l) (p < 0.001). Furthermore, glomerular filtration rate as assessed by the original Modification of Diet in Renal Disease formula independently predicted circulating chemerin concentrations in multiple regression analyses in both control subjects (p < 0.05) and patients on CD (p < 0.01).

We demonstrate that markers of renal function are independently related to circulating chemerin levels.

To compare recent US and United Kingdom (UK) guidelines on gestational diabetes (GDM)

The guidelines from the American Diabetes Association, American College of Obstetrics and Gynecology and the National Institute of Health and Clinical Excellence (NICE) in the UK were collated and compared using a general inductive approach

There are substantial differences in recommendations between the UK and US guidelines. Of particular note are the reduced sensitivity of the early and later antenatal and postnatal screening and diagnostic criteria. NICE undertook a cost effectiveness analysis using lower prevalence estimates and limited outcomes and still showed screening for GDM to be cost-effective.

The latest NICE recommendations appear to reduce access to proven, cost-effective management of GDM, an issue relevant in the current US health policy debate.

To determine whether continuous glucose monitoring (CGM) is effective in the management of type 1 diabetes (T1D) when implemented in a manner that more closely approximates clinical practice.

After completion of a 6-month randomized clinical trial (RCT) evaluating CGM in children, adolescents, and adults with T1D, CGM was initiated in the trial's control group with less intensive training and follow up than was included in the RCT. Subjects had an outpatient training session, two follow-up phone calls, and outpatient visits at 1, 4, 13, and 26 weeks. For subjects with baseline A1c ≥7.0%, the primary outcome was change in A1c at 6 months.

CGM use decreased from median of 7.0 days/week in the first month in the ≥ 25 year old group, 6.3 days/week in the 15-24 year olds, and 6.8 days/week in the 8-14 year olds to 6.5, 3.3, and 3.7 days/week in the sixth month, respectively (P<0.001 for each age group). Among subjects with baseline A1c ≥7.0% CGM use was associated with A1c reduction after 6 months (P=0.02 adjusted for age group). Severe hypoglycemia decreased from 27.7 events per 100 person-years in the 6-month control phase of the RCT to 15.0 events per 100 person-years in the 6 month follow-up CGM phase (P=0.08).

Frequent use of CGM in a clinical care setting may improve A1c and reduce episodes of hypoglycemia. However, sustained frequent use of CGM is less likely in children and adolescents than in adults.

To examine the sensitivity and specificity of hemoglobin A1c (HbA1c) as a diagnostic test for type 2 diabetes mellitus (T2DM) in older adults.

Cross-sectional study of community-dwelling adults without known diabetes who had an oral glucose tolerance test and HbA1c measured on the same day.

Mean age of the 2107 participants was 69.4±11.1 yrs; 43% were men. Based on ADA criteria, 198 had previously undiagnosed T2DM. The sensitivity/specificity of HbA1c cut point of 6.5% was 44/79%. Results were similar in age and sex-stratified analyses. Given the HbA1c cut point of 6.5%, 85% of participants were classified as non-diabetic by ADA criteria.

The limited sensitivity of the HbA1c test may result in delayed diagnosis of T2DM, while the strict use of ADA criteria may fail to identify a high proportion of individuals with diabetes by HbA1c ≥6.5% or retinopathy.

Although abdominal obesity and related metabolic abnormalities are hypothesized to promote colorectal carcinogenesis, direct confirmation of this effect is required. Here, we examined the relation of early-stage colorectal neoplasia to visceral fat area and markers of insulin resistance.

Subjects were participants in a comprehensive health screening conducted at the Hitachi Health Care Center, Ibaraki, Japan. During a 3-year period (2004 to 2007), a total of 108 patients with early-stage colorectal neoplasia, including 22 with early cancer, were identified among persons who received both colorectal cancer screening and abdominal computed tomography scanning. Three controls matched to each case were randomly selected from those whose screening results were negative. Conditional logistic regression analysis was used to examine the association of measures of obesity and markers of insulin resistance with colorectal neoplasia, with adjustment for smoking and alcohol drinking.

Visceral fat area, but not subcutaneous fat area, was significantly positively associated with colorectal cancer, with odds ratio (95% CI) for the lowest to highest tertile of visceral fat area of 1 (reference), 2.17 (0.45, 10.46), and 5.92 (1.22, 28.65), respectively (P for trend = 0.02). Markers of insulin resistance, particularly fasting glucose, were also positively associated with colorectal cancer risk. In contrast, no associations were observed for colorectal adenomas.

These results suggest that visceral adipose accumulation and insulin resistance may promote the development of early-stage cancer but not adenoma in the colorectum.

Evidence that the metabolic syndrome is a risk factor for poor cognition is mixed, is mainly focused on elderly population, and it is a rare occurrence that socio-economic factors are adjusted for. We examined this association in late mid life, with particular focus on cumulative effects and the role of socioeconomic circumstances.

Analyses were carried on 4150 white participants from the Whitehall II study. Metabolic syndrome, using the National Cholesterol Education Program Adult treatment Panel III (ATP III) criteria, was assessed three times over the 10-years follow-up (1991-2001). Cognitive function was assessed using a battery of 6 tests at the end of the follow-up.

After adjusting for demographic variables, health behaviours and health status, participants with persistent metabolic syndrome (at least 2 out of the 3 screenings) over the 10-year follow-up had lower cognitive performance than participants who never had metabolic syndrome. No significant differences in cognitive function were observed between participants with non-persistent metabolic syndrome (1 out of the 3 screenings) and those who never had metabolic syndrome during the follow-up. Adjustment for adult occupational position attenuated this association by between 41% and 86%, depending on the measure of cognitive function. Adjustment for education had little effect.

Only persistent metabolic syndrome was associated with lower cognitive performance in late mid life. Adult occupational position, but not education, had a substantial impact on this association; these results highlight the importance of adult socioeconomic circumstances in identifying and targeting risk factors for cognitive ageing.

C-reactive protein (CRP) is closely associated with obesity and cardiovascular disease in both diabetic and non-diabetic populations. In short term, commonly prescribed anti-diabetic agents have different effects on CRP; however, the long-term effects of those agents are unknown.

In ADOPT (A Diabetes Outcome Progression Trial), we examined long-term effects of rosiglitazone, glyburide, and metformin on CRP and the relationship between CRP, weight and glycemic variables in 904 subjects over 4 years.

Baseline CRP was significantly correlated with HOMA IR, HbA1c, BMI, waist circumference, and waist/hip ratio. CRP reduction was greater in the rosiglitazone group by –47.6% relative to glyburide and –30.5% to metformin at 48 months. Mean weight gain from baseline (at 48 month) was 5.6 kg with rosiglitazone, 1.8 kg with glyburide and –2.8 kg with metformin. The change in CRP from baseline to 12 months was correlated positively with change in BMI in glyburide (r=0.18) and metformin (r=0.20) groups but not the rosiglitazone (r=–0.05, p=NS) group. However, there was no longer a significant correlation between change in CRP and change in HOMA IR, HbA1c or waist-hip ratio in any of the three treatment groups.

Rosiglitazone treatment was associated with durable reductions in CRP independent of changes in insulin sensitivity, HbA1c, and weight gain. CRP in the glyburide and metformin groups was positively associated with changes in weight, but this was not the case with rosiglitazone.

Zinc Transporter 8 (ZnT8) is an islet beta-cell secretory granule membrane protein recently identified as an autoantibody antigen in type 1 diabetes. The aim of this study was to determine prevalence and role of antibodies to ZnT8 (ZnT8A) in adult-onset diabetes.

ZnT8A were measured by a radio immunoprecipitation assay using recombinant ZnT8 COOH-terminal or NH₂-terminal proteins in 193 patients with adult onset autoimmune diabetes as having antibodies to either GAD (GADA) or IA-2 (IA-2A) and in 1056 antibody-negative patients with type 2 diabetes from the NIRAD study.

ZnT8A-COOH were detected in 18.6% patients with autoimmune diabetes and 1.4% with type 2 diabetes. ZnT8A-NH₂ were rare. ZnT8A were associated with younger age and high GADA titre. The use of GADA, IA-2A and ZnT8A in combination allowed a stratification of clinical phenotype, with younger age of onset and characteristics of more severe insulin deficiency (higher fasting glucose and HbA1c, lower Body Mass Index, total cholesterol, triglycerides) in patients with all three markers, with progressive attenuation in patients with two, one and no antibodies (all P for trend <0.001). Autoantibody titres, association with high risk HLA genotypes and prevalence of thyroid peroxidase antibodies followed the same trend (all P<0.001).

ZnT8A are detectable in a proportion of adult-onset autoimmune diabetes and appear as a valuable marker to differentiate clinical phenotypes.

Dietary recommendations are mainly focused on relative dietary fat and carbohydrate content in relation to diabetes risk. Meanwhile, high protein diets may contribute to disturbance of glucose metabolism, but evidence from prospective studies is scarce. We examined the association between dietary total, vegetable, and animal protein intake and diabetes incidence and whether consuming 5 energy% from protein at the expense of 5 energy% from either carbohydrates or fat was associated with diabetes risk.

A prospective cohort study was conducted among 38,094 participants of the EPIC-NL study. Dietary protein intake was measured with a validated food-frequency questionnaire. Incident diabetes was verified against medical records.

During 10 years follow-up, 918 incident diabetes cases were documented. Diabetes risk increased with higher total protein (HR (95%CI) highest vs. lowest quartile: 2.15 (1.77-2.60)) and animal protein (2.18 (1.80-2.63)) intake. Adjustment for confounders did not materially change these results. Further adjustment for adiposity measures attenuated the associations. Vegetable protein was not related to diabetes. Consuming 5 energy% from total or animal protein at the expense of 5 energy% from carbohydrates or fat increased diabetes risk.

Diets high in animal protein are associated with an increased diabetes risk. Our findings also suggest a similar association for total protein itself instead of only animal sources. Consumption of energy from protein at the expense of energy from either carbohydrates or fat may similarly increase diabetes risk. This indicates that accounting for protein content in dietary recommendations for diabetes prevention may be useful.

To examine self-rated health and healthcare utilization among women with histories of gestational diabetes (hGDM)

A cross-sectional analysis of the 2006 National Health Interview Survey of parous women with (n=370) and without (n=6695) hGDM.

Women with hGDM reported fair or poor health status and ≥ 10 office visits in the past year more frequently than women without hGDM. The higher prevalence of obesity in hGDM women accounted for their poorer self-rated health after adjustment for other demographic factors. While the association between hGDM and more frequent office visits was reduced after adjustment for demographic factors including health insurance, hGDM was still associated with a lower odds of contact with a mental health professional.

Due to obesity, women with hGDM have poorer self-rated health than women without hGDM. Contact with mental health providers was reduced compared to women without hGDM.

To compare risks of lower-extremity amputation between patients with Charcot arthropathy and those with diabetic foot ulcers.

A retrospective cohort of patients with incident Charcot arthropathy or diabetic foot ulcers in 2003 was followed for five years for any major and minor amputations in the lower extremities.

After a mean follow-up of 37±20 and 43±18 months, the Charcot and ulcer groups had 4.1 and 4.7 amputations per 100 person-years, respectively. Among patients < 65 years old at the end of follow-up, amputation risk relative to patients with Charcot alone was seven times higher for patients with ulcer alone and twelve times higher for patients with Charcot and ulcer.

Charcot arthropathy by itself does not pose a serious amputation risk, but ulcer complication multiplicatively increased the risk. Early surgical intervention for Charcot patients in the absence of deformity or ulceration may not be advisable.

To examine whether day napping or short night sleeping is associated with higher risk of diabetes.

A prospective study of hours of daytime napping and night sleeping assessed in 1996-1997 in relation to diabetes diagnosed between 2000 and 2006 (n = 10,143) among 174,542 participants of the NIH-AARP Diet and Health Study. Odds ratios (OR) and 95% confidence intervals (CI) were derived from multivariate logistic regression models.

Longer day napping was associated with higher risk of diabetes. After adjusting for potential confounders, compared with individuals who did not nap, the OR was 1.23 (95%CI: 1.18-1.29) for those reporting < 1 hour and 1.55 (95%CI: 1.45-1.66) for ≥ 1 hour of napping (P for trend < 0.0001). For night sleeping, with 7-8 hours as the referent, the OR was 1.46 (95%CI: 1.31-1.63) for < 5 hours, 1.11 (1.06-1.16) for 5-6 hours, and 1.11 (0.99-1.24) for ≥ 9 hours. In both analyses, additional adjustment for BMI only modestly attenuated the associations. Further analysis showed a statistically significant interaction between hours of napping and sleeping on diabetes (P for interaction < 0.0001). Among participants with no napping, only short night sleeping was associated with higher occurrence of diabetes, whereas among those with ≥ 1 hour of napping, both long and short sleeping was associated with higher risk.

Day napping and short night sleeping are associated with higher risk of diabetes. The association between sleep duration and diabetes may be modified by napping habit.

Despite higher rates of nephropathy, calcified atherosclerotic plaque (CP) is less prevalent in African Americans (AA) with diabetes relative to European Americans (EA). We explored ethnic-specific relationships between albuminuria and CP involving the infra-renal aorta, coronary and carotid artery in 835 EA and 393 AA subjects with type 2 diabetes.

Generalized estimating equations with exchangeable correlation and the sandwich estimator of the variance were used to test for association between the principal component of CP in the 3 vascular beds and urine albumin:creatinine ratio (ACR).

Mean (SD) age of AA and EA participants was 56.7 (9.6) and 61.7 (9.1) years, respectively, diabetes duration 10.4 (7.4) and 10.0 (7.3) years, and median urine ACR 17.5 and 13.4 mg/g. In AA and EA participants, respectively, median CP mass scores were 53.5 and 291 for coronary artery, 3 and 35.5 for carotid artery, and 761 and 3237 for aorta. Adjusting for age, gender, glomerular filtration rate and body mass index, albuminuria was significantly associated with CP in EA (p=3.4 x 10^–8), not in AA (p=0.33), with significant ethnic interaction (p=0.01). Ethnic differences in this relationship persisted after adjustment for blood pressure, smoking, lipids and use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers.

Albuminuria is strongly associated with severity of CP in EA with diabetes, but not in AA. Disparities in this relationship may contribute to ethnic differences in the rates of cardiovascular disease that are observed in subjects with type 2 diabetes.

To assess the efficacy of Sativex, a cannabis based medicinal extract, as adjuvant treatment in painful-DPN.

In this randomized controlled trial, 30 subjects with painful-DPN received daily Sativex or placebo. Primary outcome measure was change in mean daily pain scores and secondary outcome measures included quality of life assessments.

There was significant improvement in pain scores in both groups but mean change between groups was not significant. There were no significant differences in secondary outcome measures. Patients with depression had significantly greater baseline pain scores that improved regardless of intervention.

This first ever, trial assessing the efficacy of cannabis has shown it to be no more efficacious than placebo in painful-DPN. Depression was a major confounder and may have important implications for future painful-DPN trials.

Recent studies suggested an impact of prandial insulin delivery on postprandial (pp) regulation of tissue blood flow. This study compared the effect of Viaject^TM with human regular insulin and insulin lispro on postprandial oxidative stress and endothelial function in patients with type 2 diabetes mellitus.

Fourteen patients (7 male; age 61.5±1.8 years; duration of diabetes 6.6±4.6 years; HbA1c 7.2±0.5 %; mean±SEM) received a prandial injection of Viaject^TM, human regular insulin and insulin lispro. At baseline and after a standardised liquid meal test (Ensure Plus^TM) the pp increase in asymmetric dimethylarginine (ADMA) and nitrotyrosine levels were investigated. In addition, the pp effects on microvascular blood flow, skin oxygenation, and vascular elasticity were measured.

Treatment with Viaject^TM (VJ) resulted in a significant reduction in the peak pp generation of ADMA compared with human insulin (HI) and insulin lispro (LI) (VJ: –27.3±22.6; HI: 97.7±24.4; LI: 66.9±33.9 nmol/L; p<0.05 respectively). The pp increase in nitrotyrosine levels were significant less after Viaject^TM compared with human regular insulin (VJ: –0.22±0.17, HI: 0.25±0.15 µg/ml; p<0.05), while nitrotyrosine after insulin lispro was in between (LI: 0.09±0.07 µg/ml; n.s.). In parallel, earlier and more pronounced increases in microvascular blood flow and skin oxygenation were obtained after Viaject^TM compared to HI or insulin lispro (p<0.05 respectively). All insulin formulations resulted in comparable improvements in central arterial elasticity.

Treatment with Viaject^TM reduced pp oxidative stress and improved endothelial function compared to human regular insulin or insulin lispro.

Insulin glargine (Lantus, Aventis Pharmaceuticals) is an extended-action insulin analogue with greater stability and duration of action compared to regular human insulin. The long duration of action and decreased incidence of hypoglycemia provide potential advantages for its use in pregnancy. However, the placental pharmacokinetics of insulin glargine have not been studied. Therefore, the objective of this study is to determine whether insulin glargine crosses the human placenta using the human perfused placental lobule technique.

Placentae were obtained with informed consent following elective cesarean section delivery of non-complicated term pregnancies. Insulin glargine, at a therapeutic concentration of 150 pmol/L (20µU/ml) was added to the maternal circulation. Additional experiments were carried out at insulin glargine concentrations 1000-fold higher than therapeutic levels (150, 225, 300 nmol/L). A subsequent perfusion was completed for further confirmation of findings where the maternal circuit remained open and insulin glargine was continuously infused at 150pmol/L. The appearance of insulin glargine in the fetal circulation was analyzed by a chemiluminescence immunoassay.

Results from perfusions carried out at therapeutic concentrations (150pmol/L) of insulin glargine showed no detectable insulin glargine in the fetal circuit. Following perfusion with very high insulin glargine concentrations of 150, 225, and 300 nmol/L, the rate of transfer remained low, 0.079 ± 0.01, 0.14 and 0.064 pmol/min/g tissue respectively.

Insulin glargine, when used at therapeutic concentrations, is not likely to cross the placenta.

We examined the relationship between intima-media thickness of common carotid artery (CCA-IMT) and silent cerebral infarction (SCI) with the magnetic resonance (MR) imaging study in Japanese subjects with type 2 diabetes.

The brain MR imaging study and the carotid ultrasonography were performed in a total of 217 consecutive Japanese subjects with type 2 diabetes. Various risk factors for SCI were examined using multiple logistic analyses.

The SCI was found in 60.4% of the diabetic subjects. In the diabetic subjects, age, systolic blood pressure (SBP), pulse wave velocity (PWV) and CCA-IMT were significantly higher in the subjects with SCI than those without it. Multiple logistic analyses indicated that age, SBP and CCA-IMT were significant and independent risk factors of SCI in the diabetic subjects.

CCA-IMT, but not PWV, was independently associated with SCI in Japanese subjects with type 2 diabetes.

Few validated measures exist to evaluate self-management of diabetes in families with limited English proficiency. The present study evaluated the psychometric properties and the factorial equivalence of a Spanish translation of the parent report version of the Diabetes Self-Management Profile (DSMP-Parent-Sp).

Hispanic families of youth (M = 13.7 years old) with type 1 diabetes were recruited from three clinics in South Florida and represented a wide range of nationalities and acculturation levels. One hundred and twenty-seven parents reported on their child's self-management behaviors using either the original DSMP-Parent (59.8%) or the DSMP-Parent-Sp (40.2%). In addition, youth reported their self-management using the original DSMP in English, and physicians rated their perceptions of the youth's self-management. Glycemic control was indexed by HbA1c in the past 3 months, and collected from medical chart review.

Item analysis confirmed that the DSMP-Parent-Sp items related to the overall composite score in expected ways, and internal consistency estimates were adequate. Paired correlations demonstrated strong parent-child concordance and a significant relationship with physician perceptions of self-management. Evidence of concurrent and convergent validity, as well as "strict factorial invariance" was demonstrated.

These preliminary findings indicate that the DSMP-Parent-Sp is a reliable and valid parent-report measure of Hispanic youths' diabetes self-management behaviors. In addition, there is preliminary evidence that the translated measure may be considered equivalent to the original English measure when used to measure self-management in Hispanic youth with diabetes.

1h-glucose during an oral glucose tolerance test (oGTT) was recently proposed as a valuable marker to identify normal glucose tolerant individuals (NGT) with increased intima media thickness (IMT). However, central markers of glycemic control were not considered, thus it is still unclear, which marker of glycemic control is most informative with respect to the variation of IMT in individuals with NGT.

Cardiovascular risk factors, glucose metabolism (oGTT) and IMT were determined in 1219 non-diabetic individuals (f=851, m=368; 558 NGT).

1h-glucose and HbA1c were significantly correlated to carotid IMT in individuals with NGT, while fasting and 2h-glucose were not informative. Only HbA1c was associated with IMT independent of other confounders, while 1h-glucose was not informative. Comparable results were found in the total cohort including individuals with IFG and IGT.

HbA1c was the most informative glycemic marker with respect to IMT in individuals with NGT.

There are limited data on the risk of pulmonary disease in patients with diabetes. The aim of this study is to evaluate and compare the incidence of asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pneumonia and lung cancer in patients with and without a diagnosis of diabetes.

We conducted a retrospective, longitudinal cohort study using the electronic records of a large health plan in Northern California. Age and sex data were available for all cohort members (n= 1,811,228). Data on confounders were available for a sub-cohort that responded to surveys (n= 121,886), among whom Cox proportional hazards regression models were fit.

Age- and sex-adjusted incidence rates and 95% confidence intervals were calculated for members with and without diabetes in the full cohort and the sub-cohort. No difference was observed for lung cancer, but the incidence of asthma, COPD, fibrosis, and pneumonia was significantly higher in those members with a diagnosis of diabetes. These differences remained significant in regression models adjusted for age, gender, race-ethnicity, smoking, BMI, education, alcohol consumption, and outpatient visits [asthma HR= 1.08 (95% CI 1.03-1.12), COPD HR= 1.22 (95% CI 1.15-1.28), pulmonary fibrosis HR=1.54 (95% CI 1.31-1.81), pneumonia HR= 1.92 (95% CI 1.84-1.99)]. The risk of pneumonia and COPD significantly increased with increasing HbAlc.

Individuals with diabetes are at increased risk of several pulmonary conditions: asthma, COPD, fibrosis, and pneumonia, but not lung cancer. This increased risk may be a consequence of declining lung function in patients with diabetes.

Insulin resistance and β-cell function are major predictors of type 2 diabetes, but studies using direct methods of insulin resistance and secretion are few and relatively small. Furthermore, the strength of these associations has not been tested in different ethnic groups and varying states of glucose tolerance, family history of diabetes, and obesity.

Predictors of incident diabetes were evaluated in Hispanic, non-Hispanic white, and African American participants in the Insulin Resistance Atherosclerosis Study (age, 40 - 69 years). In 557 participants with normal glucose tolerance and 267 with IGT, insulin sensitivity (insulin sensitivity index [S_I]) and first-phase insulin secretion (acute insulin response [AIR]) were directly measured using the frequently sampled intravenous glucose tolerance test.

At the 5-year follow-up examination, 128 (15.5%) individuals had developed diabetes. Both S_I (OR x 1 SD, 0.50 [0.37 – 0.68]) and AIR (OR x 1 SD, 0.51 [0.40 – 0.65]) were independent predictors of incident diabetes even after adjusting for age, sex, ethnicity, center, IGT, family history of diabetes, and BMI. The strength of the relation of S_I and AIR to incident diabetes was not significantly affected by potential interactions of age, sex, ethnicity, glucose tolerance, BMI, or family history of diabetes (p ≥0.15).

Both insulin sensitivity and β-cell function predict conversion to diabetes in different ethnic groups and varying states of glucose tolerance, family history of diabetes, and obesity. The prevention of type 2 diabetes should focus on interventions that improve both insulin resistance and insulin secretion.

To compare glycosylated hemoglobin (A1C) and fasting glucose for the diagnosis of diabetes among U.S. adults.

This study included 6890 adults (≥20 years) from the 1999-2006 National Health and Nutrition Examination Survey without a self-reported history of diabetes who had fasted ≥9 hours. A1C ≥6.5% and fasting glucose ≥126 mg/dl were used, separately, to define diabetes.

Overall, 1.8% of U.S. adults had A1C ≥6.5% and fasting glucose ≥126 mg/dl, 0.5% had A1C ≥6.5% and fasting glucose <126 mg/dl, and 1.8% had A1C <6.5% and fasting glucose ≥126 mg/dl. Compared to those with A1C <6.5% and fasting glucose ≥126 mg/dl, individuals with A1C ≥6.5% and fasting glucose <126 mg/dl were younger, more likely to be non-Hispanic black, had lower hemoglobin levels, and higher C-reactive protein.

A1C ≥6.5% demonstrates reasonable agreement with fasting glucose for diagnosing diabetes among U.S. adults.

To examine the psychometric properties of a Chinese version of the Problem Areas In Diabetes (PAID-C) scale.

The reliability and validity of the PAID-C were evaluated in a convenience sample of 205 outpatients with type 2 diabetes. Confirmatory factor analysis, Bland-Altman analysis, and Spearman's correlations facilitated the psychometric evaluation.

Confirmatory factor analysis confirmed a one-factor structure of the PAID-C (²/df ratio = 1.894, GFI = 0.901, CFI = 0.905, RMSEA = 0.066). The PAID-C was associated with HbA1c (r_s = 0.15; p < 0.05) and diabetes self-care behaviors in general diet (r_s = –0.17; p < 0.05) and exercise (r_s = –0.17; p < 0.05). The 4-week test-retest reliability demonstrated satisfactory stability (r_s = 0.83; p < 0.01).

The PAID-C is a reliable and valid measure to determine diabetes-related emotional distress in Chinese people with type 2 diabetes.

There is growing evidence that osteocalcin, an osteoblast derived protein locally acting on bone formation, can increase insulin secretion as well as insulin sensitivity and thus prevent the development of obesity and diabetes in experimental animals. In humans, osteocalcin has been reported to be decreased in patients with type 2 diabetes. Since gestational diabetes mellitus (GDM) can serve as a model of pre-type 2 diabetes, the aim of this study was to investigate osteocalcin in gestational diabetes.

Osteocalcin measurement and an oral glucose tolerance test were performed in 78 pregnant women (26 women were diagnosed with gestational diabetes (GDM) and 52 women had normal glucose tolerance during pregnancy (NGT); matched for age and BMI) and in 34 women postpartum.

During pregnancy osteocalcin was significantly higher in GDM compared to NGT (15.6±6.4 vs.12.6±4.0 ng/ml; p<0.015), while no difference was observed between the 2 groups 12 weeks postpartum (36.2±10.2 vs. 36.2±13.0 ng/ml), when osteocalcin was found to be increased compared to the pregnant state in all women (+145±102% in GDM; +187±119% in NGT; p<0.0001). Moreover, osteocalcin showed a significant correlation with basal and total insulin secretion in the whole study group (R=0.3, p<0.01).

In gestational diabetes osteocalcin was higher and thus less curbed than in women with NGT during pregnancy and furthermore correlated with insulin secretion parameters. Therefore, it could be hypothesized that osteocalcin can enhance insulin secretion in insulin resistant states, alternatively an effect of hyperinsulinemia on osteocalcin secretion can not be excluded.

A widespread use of carbohydrate (CHO) counting is limited by its complex education. This study compares a Diabetes Interactive Diary (DID) with standard CHO counting in terms of metabolic and weight control, time required for education, quality of life, and treatment satisfaction.

Adults with T1DM were randomized to DID (Group A, N=67) or standard education (Group B, N=63), and followed-up for 6 months. A subgroup also completed SF-36 and WHO-DTSQ questionnaires at each visit.

Of 130 patients (age 35.7±9.4 years; diabetes duration 16.5±10.5 years), 11 dropped out. Time for education was of 6 hours (range 2-15) in group A and 12 hours (2.5-25) in group B (p=0.07). HbA1c reduction was similar in both groups (Group A: from 8.2±0.8 to 7.8±0.8; Group B: from 8.4±0.7 to 7.9±1.1; p=0.68). Non-significant differences in favor of Group A were documented for FBG and body weight. No severe hypoglycemic episode occurred.

WHO-DTSQ scores increased significantly more in group A (from 26.7±4.4 to 30.3±4.5) than in group B (from 27.5±4.8 to 28.6±5.1) (p=0.04). Role physical, general health, vitality, and role emotional SF-36 scores improved significantly more in group A than in group B.

DID is at least as effective as traditional CHO counting education, allowing dietary freedom to a larger proportion of T1DM patients. DID is safe, requires less time for education, and is associated with lower weight gain. DID significantly improved treatment satisfaction and several quality of life dimensions.

It is unclear how well HOMA-β predicts diabetes development beyond its components, especially glucose.

We identified 12,924 nondiabetic Koreans who had fasting plasma glucose and insulin concentrations measured in 2003 and again in 2008. To minimize the impact of differences in baseline glucose concentration, individuals were divided into 3 glucose categories: Normal fasting glucose (NFG, glucose <5.6 mmoll/L); Impaired Fasting Glucose (IFG-100) (5.6-6.0 mmol/L); and IFG-110 (6.1-6.9 mmol/L).

Diabetes developed in 29% of those in the IFG-110 group, compared with 5% in IFG-100 and 0.3% in NFG groups. Within each glucose category, those who progressed to diabetes had higher baseline glucose concentrations (p ≤ 0.04). Baseline HOMA-β, however, was not lower, but higher in individuals who developed diabetes in NFG group (p=0.009) and similar in IFG-100 and IFG-110 groups.

These data question the utility of using HOMA-β to predict the development of diabetes.

To investigate the relationship between HbA1c, fasting plasma glucose (FPG) and 2 hour postload plasma glucose (2hrPG) in the Dutch general population and to evaluate the results of using HbA1c for screening and diagnosis of diabetes.

In 2006/7, 2753 participants of the New Hoorn Study, 40-65 years old who were randomly selected from the population of Hoorn, The Netherlands, underwent an oral glucose tolerance test (OGTT). Glucose status (normal glucose metabolism (NGM), intermediate hyperglycemia (IH), newly diagnosed diabetes (NDM) and known diabetes (KDM)) was defined by the WHO'06 criteria. Spearman correlations were used to investigate the agreement between markers of hyperglycemia and a receiver operating characteristic (ROC) curve was calculated to evaluate the use of HbA1c to identify NDM.

In the total population, the correlation between FPG and HbA1c and between 2hrPG and HbA1c were 0.46 and 0.33 respectively. In patients with KDM, these correlations were 0.71 and 0.79. An HbA1c level of ≥ 5.8%, representing 12% of the population, had the highest combination of sensitivity (72%) and specificity (91%) for identifying NDM. This cut-off point would identify 72% of the patients with NDM and include 30% of the individuals with IH.

In patients with KDM correlations between glucose and HbA1c are strong, however, moderate correlations were found in the general population. In addition, based on the diagnostic properties of HbA1c defined by ROC curve analysis, the advantage of HbA1c compared to OGTT for the diagnosis of diabetes is limited.

To determine the proportion of the American population who would merit metformin treatment, according to recent ADA consensus panel recommendations, to prevent or delay the development of diabetes.

Risk factors were evaluated in 1581 SIGT, 2014 NHANES III, and 1111 NHANES 2005-2006 subjects, who were non-Hispanic white and black, without known diabetes. Criteria for consideration of metformin included the presence of both IFG and IGT, with ≥1 additional diabetes risk factor: age <60 years, BMI ≥35 kg/m², family history of diabetes, elevated triglycerides, reduced HDL-cholesterol, hypertension, or A1c >6.0%.

Isolated IFG, isolated IGT, and IFG+IGT were found in 18.0%, 7.2%, and 8.2% of SIGT, 22.3%, 6.4%, and 9.4% of NHANES III, and 21.8%, 5.0%, and 9.0% of NHANES 2005-2006 subjects, respectively. In SIGT, NHANES III, and NHANES 2005-2006, criteria for metformin consideration were met in 99%, 96%, and 96% with IFG+IGT, 31%, 29%, 28% of all IFG, and 53%, 57%, and 62% of all IGT – 8.1%, 9.1%, and 8.7% of all subjects, respectively.

Over 96% of individuals with both IFG and IGT are likely to meet ADA consensus criteria for consideration of metformin. Since over 28% of all of those with IFG met criteria, providers should perform OGTTs to find concomitant IGT in all patients with IFG. To the extent that our findings are representative of the U.S. population, approximately 1 in 12 adults has a combination of prediabetes and risk factors which may justify consideration of metformin treatment for diabetes prevention.

To describe the impact of abdominal obesity and hepatic insulin resistance on phase-specific glycemic responses in older women.

We studied 23 healthy older (60-88 y) women. Abdominal obesity was defined by an abdominal circumference ≥95 cm. Plasma glucose and insulin were measured in response to a 3-h OGTT. Insulin suppression of hepatic glucose production (HGP) was determined using in vivo clamp techniques.

Despite identical prevailing insulin concentrations, glucose excursions 30-min post-challenge (but not later) were greater in women having abdominal obesity, compared with those who did not (162±19 vs. 132±16 mg·dL^–1; p<0.01). There was a strong correlation between HGP suppression under low-dose insulin infusion and early-phase glucose excursions from the OGTT (r=–0.83; p<0.001) in women with abdominal obesity, but not in those without (r=0.44; p<0.11).

Abdominal obesity relates specifically to early-phase hyperglycemia via hepatic insulin resistance even in healthy older women.

Prospective evaluation of pregnancy outcomes in pre-gestational diabetes along the Atlantic seaboard 2006/2007.

The Atlantic Diabetes in Pregnancy group representing 5 antenatal centres in a wide geographical location was established in 2005. All women with diabetes for at > 6 months prior to the index pregnancy were included. Results were collected electronically via DIAMOND Diabetes Information System. Pregnancy outcome was compared with background rates.

There were 104 singleton pregnancies. The stillbirth rate (SBR) (25/1000) was 5 times, perinatal mortality rate (PMR) (25/1000) 3.5 times, and congenital malformation rate (CMR) (24/1000) twice that of the background population. 28% of women received pre pregnancy care (PPC), 43% pre pregnancy folic acid and 51% achieved an HbA1C <=7% at first antenatal visit.

Women are not well prepared for pregnancy and outcomes are suboptimal. A regional PPC programme and centralised glucose management are urgently needed.