To determine whether women with gestational diabetes (GDM) have an increased risk of cardiovascular disease (CVD) following pregnancy.

All women aged 20 to 49 years with live births between April 1994 and March 1997 in Ontario, Canada were identified. Women with GDM were matched with up to ten women without GDM, and were followed for CVD.

The matched cohorts included 8,191 women with GDM and 81,262 women without. Mean age at entry was 31 years, and median follow up was 11.5 years. The hazard ratio for CVD events was 1.71 (95% confidence interval 1.08–2.69). After adjustment for subsequent type 2 diabetes, the hazard ratio was attenuated (1.13, 95% confidence interval 0.67–1.89).

Young women with GDM had a substantially increased risk for CVD compared to women without GDM. Much of this increased risk was attributable to subsequent development of type 2 diabetes.

High serum uric acid (UA) levels lead to gout and were reported to be associated with an increased risk for hypertension, obesity, metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease. Recently, the putative fructose transporter SLC2A9 was reported to influence UA levels. The aim of the present study was to examine the association of four single nucleotide polymorphisms (SNPs) within this gene with UA levels and whether this association is modified by obesity.

Four SNPs within SLC2A9 (rs6855911, rs7442295, rs6449213 and rs12510549) were genotyped in the population-based prospective Bruneck Study (n=800) and in a case-control study from Utah including 1038 subjects recruited for severe obesity and 831 controls.

We observed highly significant associations between all four polymorphisms with UA levels in all study groups. Each copy of the minor allele decreased age- and gender-adjusted UA levels on average by 0.30-0.35 mg/dl which translates to a relative decrease of 5-6% with p-values ranging from 10^–9 to 10^–11 in the combined analysis. An extended adjustment for BMI, creatinine, gout medication and alcohol intake improved p-values ranging from 10^–14 to 10^–20. The association was more pronounced in women and the population-based Bruneck Study and was significantly modified by BMI with stronger effect sizes in individuals with high BMI.

Genetic variants within SLC2A9 have significant effects on UA levels and are modified by gender and BMI.

To determine whether increased daily physical activity improves mitochondrial function and/or lipid oxidation in Type 2 diabetes.

Volunteers with (n=10) and without (n=10) Type 2 diabetes were matched for habitual physical activity, age, sex and weight. Basal and maximal mitochondrial activity, physical activity and resting substrate oxidation were measured at baseline, and after 2 and 8 weeks of increased physical activity.

Baseline physical activity (6450 ± 851 vs. 7638 ± 741 steps/day), basal ATP use (12 ± 1 vs. 12 ± 1 µmol/ml/min), phosphocreatine recovery from exercise (31 ± 5 vs. 29 ± 3 sec) and basal lipid oxidation (0.57 ± 0.07 vs. 0.65 ± 0.06 mg/kg body weight/min) were similar in people with and without Type 2 diabetes. There was a significant increase in physical activity after 8 weeks (12322 ± 1979 vs. 9187 ± 1159 steps/day respectively). Following increased physical activity there were no changes in basal ATP use or phosphocreatine recovery after exercise in either group. Basal lipid oxidation increased after 8 weeks of increased physical activity in people with Type 2 diabetes (0.79 ± 0.08 mg/kg/min) but not people without (0.68 ± 0.13 mg/kg body weight/min).

Resting and maximal ATP turnover are not impaired in people with well-controlled Type 2 diabetes compared with controls matched for physical activity as well as age and weight. Increased unsupervised daily physical activity is sustainable and improves lipid oxidation independent of change in mitochondrial activity in people with Type 2 diabetes.

Acute hyperglycemia on admission for acute coronary syndrome (ACS) worsens the prognosis in patients with and without known diabetes mellitus. Postulated mechanisms of this observation include prothrombotic effects. The aim of this study was to evaluate the effect of elevated glucose levels on blood clotting in ACS patients.

We studied 60 ACS patients within the first 12 hours after pain onset, including 20 subjects with type 2 diabetes, 20 with no diagnosed diabetes but with glucose levels above 7.0 mmol/L, and 20 with glucose levels below 7.0 mmol/L. We determined generation of thrombin-antithrombin complexes (TAT) and soluble CD40 ligand (sCD40L), a platelet activation marker, at the site of microvascular injury, together with ex vivo plasma fibrin clot permeability and lysis time.

The ACS patients with no prior diabetes but elevated glucose levels had increased maximum rates of formation and total production of TAT (by 42.9%, p<0.0001 and 25%, p<0.0001, respectively) as well as sCD40L release (by 16.2%, p=0.0011 and 16.3%, p<0.0001, respectively) compared with those with normoglycemia, while DM patients had the highest values of the TAT and sCD40L variables (p<0.0001 for all comparisons). Patients with hyperglycemia, with no previously diagnosed diabetes, had longer clot lysis time (by ~18%, p<0.0001) similarly to diabetic subjects, but not lower clot permeability, compared with normoglycemic subjects.

Hyperglycemia in ACS is associated with enhanced local thrombin generation and platelet activation, as well as unfavorably altered clot features in patients with and without a previous history of diabetes.

The rising incidence of type 1 diabetes has been attributed to environment, implying a lesser role for genetic susceptibility. However, the rise could be accounted for either by more cases with classic high risk genes or by cases with other risk genes. Separately, for any degree of genetic susceptibility, age at presentation may decrease in a permissive environment. To examine these possibilities, HLA class II DRB1 genes known to confer risk for type 1 diabetes were analysed in relation to year of birth and age at diagnosis over the last five decades.

Caucasoid subjects (n=462) diagnosed with type 1 diabetes before age 18 between 1950 and 2005 were DRB1 genotyped.

Mean age at diagnosis, 8.5 years (SD 4.5 years), did not differ across decades. Recent diagnosis was associated with a lower proportion but unchanged incidence of the highest risk DRB1 genotype DR3,4 (2000-05: 28% vs 1950-1969: 79%; p<0.0001) and a higher proportion of lower risk genotypes DR4,X and DR3,X (2000-05: 48% vs 1950-1969: 20%; p=0.0002). The frequency of the DRX,X genotype was low (≤ 3%) across decades. Recent birth was associated with a lower age at diagnosis for lower risk DR3,3 and DR4,4 (p<0.0001) and DR4,X (p<0.0001) and DR3,X (p=0.015) genotypes, but not for DR3,4.

The rising incidence and decreasing age at diagnosis of type 1 diabetes is accounted for by the impact of environment on children with lower risk HLA class II genes, who previously would not have developed type 1 diabetes in childhood.

Determine whether development of insulin requirement in patients with latent autoimmune diabetes in adults (LADA) is accompanied with the emergence of a type 1 diabetes-like autoimmune response.

We correlated beta-cell specific autoimmunity reflected in autoantibodies to the 65kDa isoform of GAD (GAD65) with insulin requirement. We determined GAD65Ab epitope specificities in type 1 diabetes patients, LADA patients without insulin requirement (non-progressed), and LADA patients that had developed insulin requirement (progressed).

Recognition of a type 1 diabetes-specific GAD65Ab epitope was more pronounced in type 1 diabetes patients than in non-progressed (p<0.001) or progressed (p<0.01) LADA patients, with no significant differences between the two LADA cohorts. These differences were particularly pronounced in samples with GAD65Ab titers <1000 U/ml, with no differences in epitope specificities in samples with higher GAD65Ab titers. Disease duration (initial diabetes diagnosis until sample collection, or development of insulin requirement) in non-progressed and progressed LADA patients, respectively, was not correlated with epitope specificity, suggesting lack of epitope maturation. This was supported by epitope analyses of longitudinal samples from LADA patients during progression to insulin requirement.

a) the GAD65Ab specific autoimmune reaction in type 1 diabetes patients with low and moderate GAD65Ab titers differs from that in LADA patients, irrespective of insulin requirement, b) the GAD65Ab specific autoimmune response in LADA patients does not change after their initial diabetes diagnosis, and c) LADA patients with high GAD65Ab titers resemble type 1 diabetes patients in their GAD65Ab epitope specificity.

To assess the efficacy of 1 hour plasma glucose concentration and the metabolic syndrome in predicting future risk of T2DM.

1611 subjects from the San Antonio Heart Study, who were free of T2DM at baseline, who had plasma glucose and insulin concentrations measured at time 0, 30, 60 and 120 minutes during the OGTT, and who had their diabetes status determined with an OGTT after 7-8 years of follow-up, were evaluated. Two models, based on glucose tolerance status, 1-h plasma glucose (1h-PG) concentration and presence of the metabolic syndrome, were tested in predicting the risk for T2DM at 7-8 years of follow-up

A cut off point of 155 mg/dl for the 1h-PG concentration during the OGTT was used to stratify subjects in each glucose tolerance group into low, intermediate and high risk for future T2DM. A model based upon 1h-PG concentration, ATP III criteria for the metabolic syndrome, and FPG, independent of 2-h plasma glucose, performed equally well in stratifying non-diabetic subjects into low, intermediate and high risk for future T2DM and identified a group of NGT subjects who were at very high risk for future T2DM.

The plasma glucose concentration at 1 hour during the OGTT is a strong predictor of future risk for T2DM. A plasma glucose cut off point of 155 mg/dl and the ATP III criteria for the metabolic syndrome can be used to stratify non-diabetic subjects into 3 risk groups: low, intermediate and high risk

To examine whether diabetes is a risk factor for hospitalization with pneumonia and to assess the impact of HbA_1c level on such risk.

In this population-based case-control study we identified patients with a first-time pneumonia-related hospitalization between 1997 and 2005, using health care databases in Northern Denmark. For each case, ten sex- and age-matched population controls were selected from Denmark's Civil Registration System. We used conditional logistic regression to compute relative risk (RR) for pneumonia-related hospitalization among persons with and without diabetes, controlling for potential confounding factors.

The study included 34,239 patients with a pneumonia-related hospitalization and 342,390 population controls. The adjusted RR for pneumonia-related hospitalization among persons with diabetes was 1.26 (95% confidence interval (CI) 1.21-1.31) compared with nondiabetic individuals. The adjusted RR was 4.43 (95% CI 3.40-5.77) for persons with type 1 diabetes and 1.23 (95% CI 1.19-1.28) for persons with type 2 diabetes. Diabetes duration ≥10 years increased the risk of a pneumonia-related hospitalization (adjusted RR 1.37; 95% CI 1.28-1.47). Compared with persons without diabetes, the adjusted RR was 1.22 (95% CI 1.14-1.30) for diabetic persons whose HbA_1c level was <7%, and 1.60 (95% CI 1.44-1.76) for diabetic persons whose HbA_1c level was ≥9%.

Type 1 and type 2 diabetes are risk factors for a pneumonia-related hospitalization. Poor long-term glycemic control among patients with diabetes clearly increases the risk of hospitalization with pneumonia.

To investigate the effects of fenofibrate and Coenzyme Q₁₀ (CoQ) on diastolic function, ambulatory blood pressure (BP) and heart rate (HR) in type 2 diabetic (T2DM) subjects with left ventricular diastolic dysfunction (LVDD).

74 subjects were randomized, double-blind, to fenofibrate 160mg daily, CoQ 200mg daily, fenofibrate 160mg plus CoQ 200mg daily, or matching placebo for six months. Echocardiography (including tissue Doppler imaging) and 24-hour ambulatory BP and HR monitoring were performed pre- and post-intervention.

Neither fenofibrate nor CoQ, alone or in combination, altered early diastolic mitral annular myocardial relaxation velocity (E`), early-to-late mitral inflow velocity ratio (E/A), deceleration time, isovolumic relaxation time or E/E` compared with placebo (p>0.05). Fenofibrate and CoQ interactively (p=0.001) lowered 24-hour systolic BP (–3.4±0.09mmHg, p=0.010), with a prominent nocturnal effect (–5.7±1.5mmHg, p=0.006). Fenofibrate (–1.3±0.5mmHg, p=0.013) and CoQ (–2.2±0.5mmHg, p<0.001) independently lowered 24-hour diastolic BP (DBP). Fenofibrate reduced 24-hour HR (–3.3±0.5 beats/min, p<0.001) but CoQ had no effect on HR.

In T2DM subjects with LVDD, neither fenofibrate nor CoQ, alone or in combination, improved diastolic function significantly. However, fenofibrate and CoQ independently and interactively lowered 24-hour BP, and fenofibrate alone reduced 24-hour HR.

Polychlorinated biphenyls and dibenzofurans (PCBs/PCDFs) are important and persistent organic pollutants (POPs) within humans. Recent cross-sectional studies have detected increased concentrations of serum POPs within diabetic patients. We aimed to examine the association between previous high exposures to PCBs/PCDFs and the cumulative incidence of type 2 diabetes and hypertension.

During the late 70s, the consumption of rice-bran oil laced with PCBs poisoned thousands of Taiwanese people. Between 1993 and 2003, we examined 1,054 Yucheng ("oil-disease") victims against neighborhood references, using a protocol blinded for POP exposure. Here we report the results derived from 378 Yucheng subjects and 370 matched references.

The diabetic risk to members of the Yucheng cohort relative to their references was significantly increased for women (Odds Ratio=2.1, 1.1-4.5) but not for men, after the considerations of age, body mass index, cigarette smoking and alcohol intake. Yucheng women diagnosed with chloracne had an adjusted OR of 5.5 (95% C.I.: 2.3-13.4) for diabetes and 3.5 (1.7-7.2) for hypertension, as compared to those who were chloracne free.

Yucheng women, who had endured previous exposure to PCBs/PCDFs, suffered from increased incidences of diabetes, particularly for those who had retained significant levels of the pollutant, as evident from chloracne. When planning treatments against diabetes, the body burden of PCBs and dioxins should be carefully considered, especially for women.

To assess the association between impaired chronotropic response (CR) and adverse events among patients with diabetes referred for exercise treadmill testing (ETT).

Impaired CR was defined as achievement of less than 80% of a patient's heart rate reserve. Multivariable Cox proportional hazards regression assessed the independent association between impaired CR and adverse outcomes adjusting for demographics, co-morbidities and treadmill variables including the Duke Treadmill score.

Of 1,341 patients with diabetes, 35.7% (n=479) demonstrated impaired CR during ETT. Patients with impaired CR were at increased risk of all-cause mortality, myocardial infarction, or coronary revascularization procedures. In multivariable analyses, impaired CR remained significantly associated with adverse outcomes (HR 1.53; 95% CI 1.10-2.14).

Among patients with diabetes, impaired CR is common during ETT and is associated with adverse outcomes. Impaired CR can be used as another non-invasive tool to risk stratify patients with diabetes following ETT.

Blood Glucose Awareness Training (BGAT), a psycho-educational intervention, trains individuals with type 1 diabetes to: 1) detect/interpret internal cues to better detect extreme BG, e.g. neurogenic and neuroglycopenic symptoms; and 2) interpret external cues to detect current and anticipate future extreme BG, e.g. insulin timing/dose, recent SMBG results. Although outcome studies utilizing BGAT are significant, limitations include requirement of eight weekly meetings, and limited professionals trained to deliver BGAT.

Therefore, BGAT was operationalized for web-based delivery. The Internet allows BGAT delivery to be dynamic, engaging, convenient, and personalized. Using a 2 (BGAThome, N=20 vs. Control, N=20) X 2 (pre-post) design, efficacy was evaluated.

BGAThome was judged as useful and easy to use, completed by 94% of the participants, and resulted in significant clinical improvements (p<.05).

The Internet may be an efficient and effective means of delivering diabetes interventions like BGAT.

Hemipancreatectomy (HPx) for the purpose of organ donation has been associated with a 25% risk of developing abnormal glucose tolerance or diabetes in the year following surgery. Since 1997, the University of Minnesota has imposed criteria to prevent potential donors with clinical features associated with an increased diabetes risk from undergoing HPx. We recently assessed glucose tolerance in HPx donors selected since the adoption of the new criteria to determine if the risk of developing abnormal glucose tolerance was reduced below the rate of 25% previously demonstrated.

Individuals who underwent HPx for the purpose of pancreas donation between 1997-2003 were contacted and interviewed about their health status. Those not on diabetes medications were invited to undergo an assessment of their glucose tolerance.

Successful contact was made with 15/21 donors who underwent HPx during this period. Two donors reported use of oral diabetic medications and were not studied further. Of the remaining 13, 2 had impaired fasting glucose (FBG 100-125 mg/dl), 1 had impaired glucose tolerance (2 hr post-glucose load BG 140-199 mg/dl), and 3 displayed both. One donor met diagnostic criteria for diabetes. Six donors had normal glucose values.

Despite the use of stringent criteria to exclude those at risk for developing abnormalities in glucose metabolism, 43% of healthy humans who underwent HPx between 1997-2003 have impaired fasting glucose, impaired glucose tolerance, or diabetes on follow-up. The current preoperative criteria are insufficient to predict those that will develop abnormal glucose metabolism following hemipancreatectomy.

In type 1 diabetes, plantar fascia, a collagen-rich tissue, is susceptible to glycation and oxidation. Paraoxonase-1 (PON1) is an HDL-bound anti-oxidant enzyme. PON1 polymorphisms have been associated with macro and microvascular complication susceptibility. We investigated the relationship between plantar fascia thickness (PFT) and PON1 gene variants: p.Leu54Met, p.Gln192Arg and c.-107C>T in type 1 diabetes.

Cross-sectional study of 331 adolescents with type 1 diabetes (162 M; 169 F). PFT was assessed by ultrasound; PON1 genotyping by PCR and restriction fragment length polymorphism (RFLP); serum PON1 activity by rates of hydrolysis of paraoxon and phenylacetate.

Median [interquartile range] age was 15.4 yrs [13.5 – 17.3] and diabetes duration was 7.6 yrs [ 4.9 – 10.6] . The distribution of p.Leu54Met genotypes was LL 135 (40.8%); ML 149 (45%) and MM 47 (14.2%). PFT was abnormal (>1.7mm) in 159 (48%). In multivariate analysis, predictors of abnormal PFT were ML/LL vs MM p.Leu54Met polymorphism (OR, [95% CI] 3.84 [1.49 – 9.82], p=0.005; BMI (percentile) 1.02, [1.01 – 1.03], p=0.007 and SBP (percentile) 1.01, [1.00 – 1.02], p=0.03; male gender 3.29, [1.98 – 5.46], p<0.001.

Thickening of the plantar aponeurosis occurs predominantly in overweight and male adolescents with type 1 diabetes. The MM genotype at PON1 p.Leu54Met is associated with reduced risk of abnormal PFT.

To assess whether psychological constructs of hostility, anger, type A behavior pattern, and depressive symptom severity 1) were associated with concurrent and prospective fasting glucose levels and 2) whether this association was moderated by marital status.

Participants were 485 healthy men (mean age = 59 [SD=7] years) without a history of heart disease, diabetes, or taking related medications in the VA Normative Aging Study. Their fasting glucose levels between 1986 and 1995 were examined. Hierarchical linear regressions were conducted to investigate whether hostility, anger, type A behavior, and depressive symptoms were associated with concurrent fasting glucose levels as well as fasting glucose 9 years later, controlling for standard sociodemographic and biomedical covariates, including baseline fasting glucose, age, education, marital status, BMI, total cholesterol, and systolic blood pressure.

Although none of the psychological variables were associated with concurrent fasting glucose, Cook-Medley hostility (β=0.105), anger (β=0.091), and type A behavior (β=0.152) each were associated with prospective fasting glucose at 9 years later, controlling for standard covariates. Depressive symptom severity was not associated with either concurrent or follow-up glucose levels. Further analysis showed that marital status moderated the effects of these characteristics on follow-up fasting glucose, such that hostility, anger, and type A behavior were significant only among those who were not married (βs=0.348, 0.444, 0.439, respectively; all Ps < 0.001 ).

Hostility, anger, and type A behavior appear to be independent risk factors for impaired glucose metabolism among unmarried older men.

To evaluate the effects of hyperglycemia due to partial insulin deprivation on myocardial triglyceride (TG) content and myocardial function in patients with type 1 diabetes.

Myocardial TG content and left ventricular (LV) function were measured by magnetic resonance (MR) spectroscopy and MR imaging during optimal glucoregulation and after 24 hours of partial insulin deprivation (n=10).

Mean insulin infusion rate was 45 ± 5 units at baseline, whereas it was 27 ± 5 units during hyperglycemia (per 24 hours, P < 0.001). Plasma glucose levels increased from 8.4 ± 0.6 to 15.9 ± 0.8 mmol/l (P < 0.001), and plasma levels of non-esterified fatty acids from 0.31 ± 0.05 to 0.46 ± 0.07 mmol/l (P = 0.015). Hyperglycemia had no effects on myocardial TG content and LV function.

Short-term hyperglycemic dysregulation does not modulate myocardial TG content or myocardial function, despite considerable metabolic adaptations.

To quantify the effects of glycemic index (GI) on the postprandial blood glucose excursion (PPGE) in children with type 1 diabetes on multiple daily injections (MDI). To determine optimal insulin therapy for a low GI meal.

20 subjects consumed test breakfasts, with equal macronutrient contents on four consecutive days; high and low GI meals (GI: 84 vs. 48) were consumed with preprandial ultra short acting insulin, and the low GI meal was also consumed with preprandial regular insulin and postprandial ultra short acting insulin. Each child's insulin dose was standardized. Continuous glucose monitoring was used.

The PPGE was significantly lower for the low GI meal compared to the high GI meal at 30-180 minutes (p<0.02) when preprandial ultra short acting insulin was administered. The maximum difference occurred at 60 minutes (4.2 mmol/l p<0.0001).

Regular insulin produced a 1.1 mmol/l higher PPGE at 30 minutes compared to ultra short acting insulin (p=0.015) when the low GI meal was consumed.

Postprandial ultra short acting insulin produced a higher PPGE at 30 and 60 minutes compared to preprandial administration when the low GI meal was consumed. The maximum difference was 2.5 mmol/l at 60minutes (P<0.0001).

Low GI meals produce a lower PPGE compared to high GI meals. Preprandial ultra short acting insulin is the optimal therapy for a low GI meal.

Observational studies assessing the association of combination therapy of metformin and sulfonylurea on all-cause and/or cardiovascular mortality in type 2 diabetes have shown conflicting results.

To evaluate the effects of combination therapy of sulfonylureas and metformin on risk of all-cause mortality and cardiovascular disease among people with type 2 diabetes.

A MEDLINE search (1966- July 2007) was conducted to identify observational studies that examined the association between combination therapy of sulfonylureas and metformin on risk of cardiovascular disease or all-cause mortality. From 299 relevant reports, nine were included in the meta-analysis. In these studies, combination therapy of metformin and sulfonylurea was assessed, the risk of cardiovascular disease and/or mortality was reported, adjusted relative risk or equivalent (hazard ratio, odds ratio), and corresponding variance or equivalent was reported.

The pooled relative risks (95% confidence intervals) of outcomes for individuals with type 2 diabetes prescribed combination therapy of sulfonylureas and metformin were 1.19 (0.88-1.62) for all-cause mortality, 1.29 (0.73-2.27) for cardiovascular disease mortality, and 1.43 (1.10-1.85) for a composite endpoint of cardiovascular disease hospitalizations or mortality (fatal or non-fatal events).

The combination therapy of metformin and sulfonylurea significantly increased the relative risk of the composite endpoint of cardiovascular hospitalization or mortality (fatal and nonfatal events) irrespective of the reference group (diet therapy, metformin monotherapy or sulfonylurea monotherapy); however, there were no significant effects of this combination therapy on either cardiovascular disease mortality or all-cause mortality alone.

To estimate the prevalence of female sexual dysfunction (FSD) in diabetic and non diabetic Jordanian women.

Data were collected from 1137 married females using the Arabic translation of the Female Sexual Function Index ( FSFI ) Questionnaire .

Prevalence of sexual dysfunction in diabetic females 50 years or older was 59.6% versus 45.6% in non diabetics ( P=0.003). Diabetic women had more dysfunction of desire, arousal, lubrication and orgasm than non diabetics. Glycemic control, smoking, dyslipidemia, hypertension, autonomic neuropathy and peripheral neuropathy did not have significant effect on FSD .Age, BMI, duration of diabetes, the presence of CAD, nephropathy and retinopathy had a negative effect on FSD .

Prevalence of FSD among Jordanian females was found to be significantly higher in diabetic women compared to non diabetic women.

To determine whether elective use a health plan-sponsored health club membership impacted health care use and costs among older adults with diabetes.

Administrative claims for 2031 older adults with diabetes enrolled in a Medicare Advantage plan were obtained for this retrospective cohort study. Participants (n=618) in the plan-sponsored health club benefit (Silver Sneakers^®, SS) and controls (n=1413) matched on SS enrollment index date were enrolled in the plan for at least one year prior to the index date. Two year health care use and costs of SS participants and controls were estimated in regressions adjusting for baseline differences.

SS participants were more likely to be male, had a lower chronic disease burden, used more preventive services, and had a lower prevalence of arthritis (p≤05). SS participants had lower adjusted total health care costs than controls in the first year after enrollment [–$1633, (95% Confidence Interval, CI, –2620, –646), p=.001] and adjusted total costs in year two trended lower [–$1230, (95% CI, –2494, 33), p=.06]. Participants who made on average ≥2 SS visits/week in year one had lower total costs in year two [$2141 (95%CI, –$3877, –$405; p=.02)] compared participants who made <2 visits/week.

Use of a health club benefit by older adults with diabetes was associated with slower growth in total health care costs over two years; greater use of the benefit was actually associated with declines in total costs.

To identify reproductive risk factors associated with dysglycemia (diabetes, impaired glucose tolerance, and impaired fasting glucose) in a contemporary, multiethnic population.

We studied 14,661 women screened with an OGTT for the DREAM Trial. Reproductive risk factors were compared in normoglycemic and dysglycemic women.

Dysglycemia was significantly associated with the number of children born (OR 1.03 per child, 95% CI 1.01-1.05), age (OR 1.05 per year, 1.04-1.05), non-European ancestry (OR 1.09, 1.01-1.17), pre-eclampsia/eclampsia (OR 1.14, 1.02-1.27), irregular periods (OR 1.21, 1.07-1.36), and GDM (OR 1.53, 1.35-1.74). The relationship between GDM and dysglycemia did not differ across BMI tertiles (p=0.84), nor did the relationships of other risk factors.

Reproductive factors, particularly GDM, are associated with dysglycemia in middle-aged women from many ethnicities. Reproductive factors can be used to counsel young women about their future risk of dysglycemia, while in middle age they may help screen for dysglycemia.

Hyperglycemia is a risk factor for microvascular complications and may increase the risk of cardiovascular disease in patients with type 2 diabetes. This study tested the LDL-cholesterol–lowering agent colesevelam HCl (colesevelam) as a potential novel treatment for improving glycemic control in patients with type 2 diabetes on sulfonylurea-based therapy.

A 26-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study was carried out between August 2004 and August 2006 to evaluate the efficacy and safety of colesevelam for reducing A1C in adults with type 2 diabetes whose glycemic control was inadequate (A1C 7.5%–9.5%) with existing sulfonylurea monotherapy or sulfonylurea in combination with additional oral antidiabetic agents. In total, 461 patients were randomized (230 [colesevelam 3.75 g/day] and 231 [placebo]). The primary efficacy measurement was mean placebo-corrected change in A1C from baseline to Week 26 in the intent-to-treat population (last observation carried forward).

The LS mean change in A1C from baseline to Week 26 was –0.32% in the colesevelam group and +0.23% in the placebo group, resulting in a treatment difference of –0.54% (P<0.001). The LS mean percent change in LDL-cholesterol from baseline to Week 26 was –16.1% in the colesevelam group and +0.6% in the placebo group, resulting in a treatment difference of –16.7% (P<0.001). Furthermore, significant reductions in fasting plasma glucose, fructosamine, total cholesterol, non–HDL-cholesterol, and apolipoprotein B were demonstrated in the colesevelam group relative to placebo at Week 26.

Colesevelam improved glycemic control and reduced LDL-cholesterol levels in patients with type 2 diabetes receiving sulfonylurea-based therapy.

We assessed the lifetime risk of CVD among individuals with and without obesity and diabetes.

Participants were drawn from the Original and Offspring Cohorts of the Framingham Heart Study. Lifetime (30 year) risk of CVD was assessed using a modified Kaplan-Meier approach adjusting for the competing risk of death, beginning from age 50 years.

Over 30 years, the lifetime risk of CVD among women with diabetes was 54.8% among normal weight women, but 78.8% among obese women. Among normal weight men with diabetes, the lifetime risk of CVD was 78.6%, whereas it was 86.9% among obese men.

The lifetime risk of CVD among individuals with diabetes is high, and this relationship is further accentuated with increasing adiposity.

To determine if a systems navigator service, called the Maestro Project, could increase medical surveillance for young adults with type 1 diabetes who transfer from pediatric to adult care.

There were two cohorts of participants: 1) a younger group (age 18) who had the assistance of the navigator as they graduated from pediatric care (n=84) and 2) an older group (age 19–25 years) who were transferred to adult care without this initial support, but later enrolled in the program.

40% of the older group (who did not have initial access to the navigator) dropped out of adult medical care, compared to a drop-out rate of 11% of the younger group, who had access to the navigator at the time of transfer from pediatric care.

The systems navigator helped improve medical surveillance for both groups although there was no evidence of improved short term medical outcomes.

The prevalence of type 2 diabetes mellitus (DM) among Hispanic and Asian Americans is increasing. These groups are largely comprised of immigrants who may be undergoing behavioral and lifestyle changes associated with development of DM. We studied the association between acculturation and DM in a population sample of 708 Mexican-origin Hispanics, 547 non-Mexican-origin Hispanics, and 737 Chinese participants in the Multi-ethnic Study of Atherosclerosis.

DM was defined as fasting glucose ≥126 mg/dl and/or use of anti-diabetic medications. An acculturation score was calculated for all participants using nativity, years living in the U.S., and language spoken at home. The score ranged from 0-5; 0=least acculturated and 5=most acculturated. Relative risk regression was used to estimate the association between acculturation and DM.

For non-Mexican-origin Hispanics, the prevalence of DM was positively associated with acculturation score, after adjusting for socio-demographics. The prevalence of DM was significantly higher among the most acculturated vs. the least acculturated non-Mexican-origin Hispanics (Prevalence ratio= 2.49; 95% CI=1.14 –5.44); the higher the acculturation score, the higher the prevalence of DM (P-value for trend=0.059). This relationship between acculturation and DM was partly attenuated after adjusting for BMI or diet. Diabetes prevalence was not related to acculturation among Chinese or Mexican-origin Hispanics.

Among non-Mexican-origin Hispanics in MESA, greater acculturation is associated with higher DM prevalence. The relation is at least partly mediated by BMI and diet. Acculturation is a factor that should be considered when examining predictors of DM in racial/ethnic groups.

To evaluate the effect of supervised progressive resistance exercise training (PRT) protocol on insulin sensitivity, glycemia [blood glucose and glycosylated hemoglobin (HbA1c) levels], lipids and body composition in Asian Indians with type 2 diabetes mellitus (T2DM).

Thirty patients with T2DM underwent 12 w PRT of six muscle groups (2 sets, 10 repetitions). The subjects were evaluated with Short Insulin Tolerance Test (for assessment of insulin sensitivity, K_ITT), fasting blood glucose, HbA1c, lipids, high-sensitivity C-reactive protein (hsCRP), detailed anthropometry, total body fat, regional fat and lean body mass by Dual energy x-ray absorptiometry, cross-sectional skeletal muscle area of upper arm and thigh by computed tomography scan.

Insulin sensitivity improved significantly from K_ITT 1.22 ± 0.73to K_ITT 2.13 ± 0.75 (p<0.0001), after the intervention. Significant decline (mean difference ± SD) from the baseline was recorded in the levels of following parameters; HbA1c (0.54 ± 0.4%, p<0.001), fasting blood glucose (2.7 ± 2.2 mmol/L, p<0.001), total cholesterol (0.39 ± 0.7 mmol/L, p=0.003), serum triglycerides (0.39 ± 0.5 mmol/L, p<0.001), truncal and peripheral subcutaneous adipose tissue compartments (SCAT) (p<0.001). However, no significant changes were noticed in body mass index, total body fat, truncal fat, lean body mass and cross-sectional skeletal muscle area of the extremities and hsCRP levels.

Moderate-intensity PRT for 3 m resulted in significant improvement in insulin sensitivity, glycemia, lipids and truncal and peripheral SCAT in patients with T2DM. Resistance training should be an integral part of exercise regimen in Asian Indians with T2DM.

In patients with type 2 diabetes left ventricular hypertrophy (LVH) predicts cardiovascular events and its prevention is cardioprotective.

This pre-specified study compared the incidence of electrocardiographic (ECG) LVH by Sokolow-Lyon and Cornell voltage criteria in 816 hypertensive type 2 diabetic patients of the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) randomized to at least 3-year blinded angiotensin-converting-enzyme (ACE) inhibition with trandolapril (2 mg/day) or non-ACE inhibitor therapy, who had no ECG-LVH at baseline. Treatment was titrated to systolic/diastolic blood pressure (BP) <130/80 mmHg. ECG readings were centralized and blinded to treatment.

Baseline characteristics of the two groups were similar. Over a median (interquartile range) follow-up of 36 (24 to 48) months, 13 of the 423 patients (3.1%) on trandolapril compared to 31 of the 376 (8.2%) on non-ACE inhibitor therapy developed ECG-LVH. [Hazard Ratio (95% CI): 0.34 (0.18 to 0.65), P=0.0012 (unadjusted); 0.35 (0.18 to 0.68), P=0.0018 (adjusted for pre-define baseline covariates)]. The Hazard Ratio was significant even after adjustment for follow-up BP and BP reduction vs baseline. Compared to baseline, both Sokolow-Lyon and Cornell voltages significantly decreased on trandolapril, but did not change on non-ACE inhibitor therapy.

ACE inhibition has a specific protective effect against the development of ECG-LVH that is additional to that of BP lowering. Since ECG-LVH is a strong cardiovascular risk factor in people with hypertension and diabetes, early ACE inhibition may be cardioprotective in this population.

To estimate the risks of non-traumatic lower extremity amputations (LEAs) in patients with type 1 diabetes mellitus (T1DM).

We identified 31,354 patients with T1DM (15,001 women and 16,353 men) in the Swedish Inpatient Register between 1975 and 2004. The incidence of non-traumatic LEAs was followed up until December 31, 2004, by cross-linkage in the Inpatient Register and linkage to the Death and Migration registers. Poisson regression modeling was used to compare the risks of non-traumatic LEAs during different calendar periods of follow-up, with adjustment both for gender and attained age at follow-up. Standardized incidence ratios (SIRs) was used to estimate the relative risks with the age-, sex-, and calendar-period-matched general Swedish population as reference. The cumulative probability of non-traumatic LEAs was calculated by the Kaplan-Meier method.

In total, 465 patients with T1DM underwent non-traumatic LEAs. The risk was lower during the most recent calendar period (2000-2004) than the period prior to 2000 (relative risk = 0.6, 95% confidence interval [CI] 0.5-0.8). However, even in this most recent period, the risk for non-traumatic LEAs among these relatively young patients was 86-fold higher than that in the matched general population (SIR =85.8, 95% CI 72.9-100.3). By the age of 65, the cumulative probability of having a non-traumatic LEA was 11.0% for women with T1DM, and 20.7% for men with T1DM.

Although the risks appeared to have declined in recent years, patients with type 1 diabetes still run a very high risk for non-traumatic LEAs.

Dietary patterns in Western populations have been linked to type 2 diabetes, but the role of diet in Japanese remains unclear. We investigated the association between major dietary patterns and glucose tolerance status as measured by glycated hemoglobin (HbA_1c) in Japanese adults.

Subjects were 3,243 men and 4,667 women who participated in the baseline survey of an on-going cohort study on lifestyle-related diseases in Fukuoka, Japan. Dietary patterns were derived by using principal component analysis of the consumption of 49 food items ascertained by a food frequency questionnaire. Logistic regression analysis was used to estimate sex-specific odds ratios of elevated HbA_1c (≥ 5.5%) with adjustment for potential confounding variables.

The westernized breakfast pattern characterized by frequent intake of bread but infrequent intake of rice was inversely related to HbA_1c concentrations (P for trend = 0.02 in each men and women); the multivariate-adjusted odds ratios (95% CI) for the highest versus lowest quintiles were 0.60 (0.43-0.84) and 0.64 (0.46-0.90) for men and women, respectively. The seafood dietary pattern was positively associated with HbA_1c concentrations in men only (P for trend = 0.01). Neither the healthy nor high-fat dietary pattern was related to HbA_1c.

A dietary pattern featured by frequent intake of white rice may deteriorate glucose metabolism in Japanese men and women, and the salty seafood dietary pattern may have similar effect in men.

We examined the contribution of the CTLA4 gene in the susceptibility to fulminant type 1 diabetes (T1D), and compared them with "classic" type 1A diabetes (T1AD).

We genotyped the +49G>A and CT60 G>A of the CTLA4 in fulminant T1D (n=55), "classic" T1AD (n=91), and healthy control subjects (n=369). We also assessed serum levels of soluble form of CTLA4.

The +49GG and CT60GG genotypes were associated with T1AD (P<0.001). In contrast, the CT60AA genotype, but not +49G>A, was associated with fulminant T1D (P<0.05), especially in patients carrying HLA-DR4 (P<0.001). Serum levels of sCTLA4 were significantly decreased in patients with fulminant T1D (P<0.05).

These results suggest that CTLA4 CT60 affects the genetic susceptibility to fulminant T1D. Furthermore, the contribution of the CTLA4 to the disease susceptibility is distinct between fulminant T1D and "classic" T1AD.

To assess the cost-effectiveness of intensive versus conventional therapy for 8 years as applied in the Steno-2 study in patients with type 2 diabetes and microalbuminuria.

A Markov model was developed to incorporate event and risk data from Steno-2 and account Danish-specific costs to project life expectancy, quality-adjusted life expectancy (QALE) and lifetime direct medical costs expressed in year 2005 Euro values. Clinical and cost outcomes were projected over patient lifetimes and discounted at 3% annually. Sensitivity analyses were performed.

Intensive treatment was associated with increased life expectancy and QALE, and increased lifetime costs, compared to conventional treatment. Mean undiscounted life expectancy was 18.1±7.9 years with intensive treatment and 16.2±7.3 years with conventional treatment (difference 1.9 years). Discounted life expectancy values were 13.4±4.8 (intensive) versus 12.4±4.5 years (conventional). Lifetime costs (discounted) for intensive and conventional treatment were 45,521±19,697 and 41,319±27,500, respectively (difference 4,202). Increased costs with intensive treatment were due to increased pharmacy and consultation costs. Discounted QALE was 1.66 quality-adjusted life years (QALYs) higher on intensive (10.2±3.6 QALYs) versus conventional (8.6±2.7 QALYs) treatment, resulting in an incremental cost-effectiveness ratio of 2,538 per QALY gained. This is considered a conservative estimate since prescription of generic drugs and capturing indirect costs would further favor intensified therapy.

Intensive therapy was cost-effective versus conventional treatment from a healthcare payer perspective in Denmark. Assuming that patients in both arms were treated in a primary care setting, intensive therapy became dominant (cost-and life saving).

To assess the effect of normoglycemia following simultaneous pancreas/kidney transplantation (SPK) on neurological function and intraepidermal nerve fiber density (IENFD) in patients with type 1 (DM).

We performed vibration perception threshold (VPT) and autonomic function testing (AFT) and assessed IENFD in skin biopsies from the lower thigh and upper calf in 14 healthy controls and 18 patients with DM at the time of and at 21–40 (median 29) months post-SPK.

At baseline, significantly increased VPTs, pathological AFT results and severe reduction in IENFD were present in SPK recipients. After SPK, an increase of IENFD in the thigh of more than 1 ENF/mm was noted in 3 patients (median 4.1; range 1.9-10.2), but changes were not significant for the group as a whole.

We conclude that irreversible nerve damage might be present in some SPK recipients, or that longer periods of normoglycemia might be needed to allow nerve regeneration.

Heme oxygenase (HO) leads to the generation of free iron, carbon monoxide, and bilirubin. A length polymorphism of GT repeat in the promoter of human HO-1 gene has been shown to modulate gene transcription. This study aims to assess the association of the length of (GT)n repeats in HO-1 gene promoter with serum bilirubin, markers of iron status, and the development of coronary artery disease (CAD).

We screened the allelic frequencies of (GT)ⁿ repeats in the HO-1 gene promoter in 986 unrelated individuals that underwent coronary angiography. Serum bilirubin and markers of iron status were evaluated.

The distribution of numbers of (GT)_n repeats was divided into 2 subclasses: class S included shorter (<27) repeats, and class L included longer (≥27) repeats. Among those with diabetes, subjects with L/L genotype had significantly lower bilirubin levels than those with S/S and S/L genotypes (0.70±0.22 vs. 0.81±0.24 mg/dL, P=0.001) and higher serum ferritin values (4.76±0.72 vs. 4.28±1.05 µg/L for log-ferritin, P=0.001). Compared with those carrying S allele, diabetic subjects with L/L genotype had an almost three-fold increase in CAD risk after controlling for conventional risk factors (odds ratio 2.81, 95% confidence interval [CI] 1.22 to 6.47, P=0.015). Adjusting for both serum bilirubin and ferritin, the effect of HO-1 promoter polymorphism on susceptibility to CAD disappeared.

Length polymorphism in the HO-1 gene promoter is correlated with susceptibility to CAD in diabetic patients and such effect might be conveyed through its influence on serum bilirubin and ferritin.

The prevalence of chronic kidney disease (CKD) increased among US adults from 1988-1994 through 1999-2004. We sought to explore the importance of trends in risk factors for CKD over time.

The prevalence of cigarette smoking, obesity, hypertension, high cholesterol, and diabetes among US adults with stage-3 CKD (estimated GFR <60 ml/min/1.73m²) and albuminuria (urinary albumin to creatinine ratio ≥30 mg/g), separately, were determined for 1988-1994 and 1999-2004 using data from serial National Health and Nutrition Examination Surveys. The prevalence ratio (PR) for stage-3 CKD and albuminuria by the presence of these risk factors were compared across survey periods.

The PR for CKD declined between 1988-1994 and 1999-2004 for obesity (PR=1.51 and 1.14 for 1988-1994 and 1999-2004, respectively; p-value for change=0.010), hypertension (PR=2.60 and 1.70; p-value for change=0.005) and high cholesterol (PR=1.58 and 1.20; p-value for change=0.028). However, for diagnosed diabetes, the prevalence ratio remained unchanged (1.64 in NHANES III and 1.62 in NHANES 1999-2004; p-value for change=0.898). Similar results were observed for undiagnosed diabetes: the prevalence ratio of CKD was 1.38 and 1.50 in NHANES III and NHANES 1999-2004; p=0.373). The association of cigarette smoking was similar in each time period. Besides obesity, for which the association remained stable over time, similar patterns were observed for the PR of albuminuria.

In terms of CKD, improvements in hypertension and high cholesterol management have been offset by both diagnosed and undiagnosed diabetes. Further increases in CKD may occur if diabetes continues to increase.

To assess the association of 1,5-anhydroglucitol (1,5-AG) with 2-hour postprandial glucose values in type 2 diabetic patients followed over 12 months in an outpatient setting.

In 55 patients, self-measured postprandial blood glucose values were correlated with 1,5-AG values over pre-specified preceding time periods (3 days, 1 week, weekly up to 12 weeks).

The correlation coefficients were –0.34 (p<0.05) for postprandial glucose values in the preceding three days, –0.38 (p<0.001) for values during the week before a visit, and –0.40 (p<0.001) for the values obtained two weeks preceding the measurement of 1,5-AG. Correlations declined for time periods of ≥ 2 weeks before measurement of 1,5-AG. The correlation was lower with fasting/preprandial plasma glucose levels. There was no time-dependency of the correlation of HbA_1c and fasting or postprandial glucose.

1,5-AG best reflected the 2-hour postprandial glucose values of the two previous weeks.

African American (AA) children are hyperinsulinemic and insulin resistant compared with American White (AW) children. Previously, we demonstrated that insulin secretion relative to insulin sensitivity was ~75% higher in AA compared with AW children, suggesting that hyperinsulinemia in AA children is not merely a compensatory response to lower insulin sensitivity. The aim of the present investigation was to assess if glucose-stimulated insulin response is higher in AA vs AW adolescents who have comparable in vivo insulin sensitivity.

The hyperinsulinemic-euglycemic and hyperglycemic clamp techniques were utilized to assess first and second phase insulin secretion. Insulin secretion relative to insulin sensitivity was calculated as the glucose disposition index.

AA adolescents compared with their AW peers with comparable insulin sensitivity and body composition had higher first-phase insulin concentrations.

The quantitative relationship between insulin sensitivity and first phase insulin appears to differ among AA and AW adolescents.

To develop and assess the feasibility of an early preconception counseling program for adolescents called READY-Girls..

Fifty-three adolescent females with T1D between 16-19.9yrs were randomized into: CD, book, or control/standard care, and given one comprehensive session. Outcomes were assessed at baseline, immediately-after, and at 3-months.

Teens that received the CD and book significantly (p≤.05) improved in knowledge, perceived benefits of PC and of using effective family planning, and perceived more support with reproductive health issues which were sustained over three months.

Clinical feasibility of the program was demonstrated. Both the CD and book appeared to be efficacious formats for short term. Future studies should examine repeated boosters of both CD and book. They are not to replace, but reinforce and supplement health professional education.

We investigated the natural history of MODY2, notably the factors associated with deterioration of hyperglycemia over time.

We report an 11-year follow-up of glucose tolerance and of indices of insulin secretion and insulin sensitivity derived from oral glucose tolerance tests in 33 MODY2 subjects.

The variation between tests of glucose tolerance (expressed as the area under the glucose curve) was 6.9±3.2% (m±SEM), but individual results ranged from –20% to 61%. Deterioration of glucose tolerance between tests was associated with decreased insulin sensitivity, while insulin secretion remained stable.

Glucose tolerance can remain stable over many years in subjects with MODY2, due to the relative stability of the glucokinase-related beta-cell defect. However, the development of insulin resistance may have an important role in the deterioration of the glucose tolerance and in the long-term evolution of the disorder.

We determined the longitudinal association of glucose metabolism with retinopathy in a representative sample of the Australian population.

The Australian Diabetes Obesity and Lifestyle study (AusDiab), is a national, longitudinal study of adults aged ≥25 years from 42 randomly selected areas of Australia. Retinopathy was assessed at baseline in 1999-2000 and 5-years later in 2004-2005 in participants identified as having diabetes (based on self report and oral glucose tolerance test), impaired glucose metabolism and in a random sample with normal glucose tolerance. Complete retinal data were available for 1192 participants. Photographs were graded at two time points according to a simplified version of the Wisconsin grading system.

The five-year incidence of retinopathy was 13.9% and 3.0% among those with known and newly diagnosed diabetes mellitus at baseline, respectively. Of those who developed incident newly diagnosed diabetes (NDM) at follow-up, 11.9% had retinopathy at baseline as compared with 5.6% of those who did not progress to incident NDM (p=0.037). After adjustment for factors identified as risk factors for diabetes, persons with retinopathy signs at baseline were twice as likely to develop incident NDM compared to those who did not have retinopathy signs at baseline.

The 5-year incidence of retinopathy was 13.9% among persons with known diabetes. Non-diabetic persons with retinopathy signs at baseline had a two-fold higher risk of developing incident NDM 5 years later. This provides further evidence that mild retinopathy signs may be a pre-clinical marker of underlying microvascular disease and future diabetes risk.

The influence of lipid and glucose metabolism in the metabolic syndrome (MS) on aortic pulse wave velocity (PWV) and left ventricular (LV) diastolic function was evaluated using magnetic resonance imaging (MRI).

Aortic PWV and LV diastolic function were assessed using MRI in 32 subjects with (n=16) and without the MS (n=16), matched for age, waist circumference and blood pressure. The groups were compared with the unpaired t-test or Mann-Whitney U-test and linear regression analysis was applied.

Aortic PWV was increased and LV diastolic function was decreased in subjects with compared to subjects without the MS. HDL-cholesterol was independently associated with aortic PWV (R=–0.470, p<0.01) and LV diastolic function (R=–0.421, p=0.02).

Increased aortic PWV and decreased LV diastolic function is observed in subjects with the MS, regardless of blood pressure. Moreover, HDL-cholesterol is independently associated with aortic PWV and LV diastolic function.

Obesity is associated with chronic inflammation due to overproduction of proinflammatory cytokines, including TNF-. We assessed the effects of TNF- neutralization by infliximab on vascular reactivity during hyperinsulinemia in obesity-related metabolic syndrome (MetS).

Vascular responses to intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in patients with MetS, before and after administration of infliximab.

Patients had blunted vasodilator responses to ACh and SNP during hyperinsulinemia compared with controls; a potentiation of the responsiveness to both ACh and SNP, however, was observed in patients following infliximab. The antioxidant vitamin C improved the vasodilator response to ACh in patients with MetS, but its effect was not further enhanced by concurrent administration of infliximab.

TNF- neutralization ameliorates vascular reactivity in MetS during hyperinsulinemia, likely in relation to decreased oxidative stress, thereby suggesting an involvement of inflammatory cytokines in vascular dysfunction of these patients.

To examine the association between fruit, vegetable, and fruit juice intake and development of type 2 diabetes mellitus (DM).

A total of 71,346 female nurses ages 38-63 years, who were free of cardiovascular disease, cancer, and DM in 1984 were followed for 18 years and dietary information was collected using a semi-quantitative food frequency questionnaire every 4 years. Diagnosis of DM was self-reported.

During follow-up, 4,529 cases of DM were documented and cumulative incidence of DM was 7.4%. An increase of 3 servings/day in total fruit and vegetable consumption was not associated with development of DM (multivariate-adjusted hazard ratio [HR], 0.99; 95% Confidence Interval [CI], 0.94 to 1.05) while the same increase in whole fruit consumption was associated with a lower hazard of DM (HR, 0.82; 95% CI, 0.72 to 0.94). An increase of 1 serving/day in green leafy vegetable consumption was associated with a modestly lower hazard of DM (HR, 0.91; 95% CI, 0.84 to 0.98), whereas the same change in fruit juice intake was associated with an increased hazard of DM (HR, 1.18; 95% CI, 1.10 to 1.26).

Consumption of green leafy vegetables and fruit was associated with a lower hazard of DM, whereas consumption of fruit juices may be associated with an increased hazard among women.

Type 2 Diabetes Mellitus (diabetes) and periodontal disease are known to be associated but the temporality of this relationship has not been firmly established. We investigated whether baseline periodontal disease independently predicts incident diabetes over two decades of follow-up.

9,296 nondiabetic male and female National Health and Nutrition Examination Survey (NHANES I) participants aged 25-74 years who completed a baseline dental examination (1971–1976) and at least one follow-up evaluation (1982–1992) were studied. We defined 6 categories of baseline periodontal disease using the periodontal index (PI). Of 7,168 dentate participants, 47% had PI=0 ("periodontally health"); the remaining were classified into PI quintiles. Incident diabetes was defined by: i) death certificate (ICD-9 code 250); ii) self-report diabetes requiring pharmacological treatment; or iii) healthcare facility stay with diabetes discharge code. Multivariable logistic regression models assessed incident diabetes odds across increasing levels of PI in comparison to periodontally healthy participants.

The adjusted odds ratios (OR) for incident diabetes in periodontal index categories 1 and 2 were not elevated while the OR in periodontal index categories 3 through 5 were: 2.26 (95%CI:1.56,3.27), 1.71 (95%CI:1.09,2.69) and 1.50 (95%CI:0.99,2.27), respectively. OR in edentulous was 1.30(95%CI:1.00, 1.70). Dentate participants with advanced tooth loss realized an OR=1.70(p<0.05) relative to those with minimal tooth loss.

Baseline periodontal disease is an independent predictor of incident diabetes in the nationally representative sample of NHANES I.

Carbohydrate counting is an effective approach to mealtime insulin adjustment in type 1 diabetes, but has not been rigorously assessed in type 2 diabetes.

This 24-week, multicenter, randomized, controlled study compared two algorithms for adjusting mealtime (glulisine) insulin along with a standard algorithm for adjusting background (glargine) insulin in 273 intent-to-treat patients with type 2 diabetes. Glulisine and glargine were adjusted weekly in both groups based on previous week's self monitored blood glucose (SMBG) results. The Simple Algorithm group was provided set doses of glulisine to take before each meal. The Carbohydrate Counting group was provided an insulin to carbohydrate ratio to use for each meal and adjusted their glulisine dose based on amount of carbohydrate consumed.

A1C levels at week 24 were 6.70% (Simple Algorithm) and 6.54% (Carb Count). The respective mean A1C changes from baseline to 24 weeks were –1.46% and –1.59% (P=.24). A1C <7.0% was achieved by 73.2% (Simple Algorithm) and 69.2% (Carb Count) (P=.70); respective values for A1C <6.5% were 44.3% and 49.5% (P=.28). The total daily dose of insulin was lower and there was a trend toward less weight gain in Carb Count patients. Severe hypoglycemia rates were low and equal in the two groups.

Weekly basal:bolus insulin adjustments based on premeal and bedtime glucose patterns resulted in significant reductions in A1C. Having two effective approaches to delivering and adjusting rapid-acting mealtime insulin may increase physicians' and patients' willingness to advance therapy to a basal:bolus insulin regimen.

While metabolic syndrome (MetS) is related to an increased risk of coronary heart disease (CHD) events, persons with MetS encompass a wide range of CHD risk levels. This study describes the distribution of 10-year CHD risk among U.S. adults with MetS.

MetS was defined by the modified National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP III) definition among 4293 U.S. adults aged 20-79 in the U.S. National Health and Nutrition Examination Survey 2003-2004. Low, moderate, moderately high, and high risk status were defined as <6%, 6-10%, 10-20%, and >20% probability of CHD in 10 years (based on NCEP/ATP III Framingham risk score algorithms), respectively; those with diabetes or pre-existing cardiovascular disease were assigned to high risk status.

The weighted prevalence of MetS by NCEP criteria in our study was 29.0% overall (30.0% in men (M) and 27.9% in women (F), p=0.28). 38.5% (M: 30.7%, F: 46.9%) were classified as low risk, 8.5% (M: 7.9%, F: 9.1%) moderate risk, 15.8% (M: 23.4%, F: 7.6%) moderately high risk, and 37.3% (M: 38.0%, F: 36.5%) high risk. The proportion at high risk increased with age but was similar between Hispanics, non-Hispanic whites, and non-Hispanic blacks.

While many MetS subjects are at low calculated risk for CHD, about half are at moderately high or high risk, reinforcing the need for global risk assessment in persons with MetS to appropriately target intensity of treatment for underlying CHD risk factors.

To investigate the association between dietary adherence and glycemic control among youth with type 1 diabetes.

We conducted a cross-sectional analysis of 119 youth ages 9-14 years (12.1± 1.6) with diabetes duration ≥1 year (5.4± 3.1). Dietary adherence was assessed using the Diabetes Self-Management Profile (DSMP) diet domain. Higher score defined greater dietary adherence. Glycemic control was determined by A1C.

Dietary adherence score was inversely correlated with A1C (r=-.36, p<.0001). In a multivariate model (R²=.34, p<.0001), dietary adherence (p=.004), pump use (p=.03), and caregiver education (p=.01) were associated with A1C. A1C of youth in the lowest (9.0%) tertile of diet score was higher than the A1C of youth in the middle (8.1%, p=.004) and upper (8.4%, p=.06) tertiles. Dietary adherence uniquely explained 8% of the variance in A1C in the model.

Greater dietary adherence was associated with lower A1C among youth with type 1 diabetes.

Polycystic ovary syndrome (PCOS) is an insulin resistant (IR) state with IR an established therapeutic target, however measurement of IR remains challenging. We aimed to determine a) serum retinol-binding Protein 4 (RBP4) levels (purported to reflect IR) in PCOS women and controls, b) examine relationship of RBP4 to conventional IR markers and c) examine RBP4 changes with interventions modulating IR, in overweight PCOS women.

38 overweight women (BMI >27 kg/m2) with PCOS and 17 weight-matched controls were compared at baseline. PCOS women were then randomized to 6 months of higher dose oral contraceptive pill (OCP) (35mcg ethinyl estradiol/2mg cyproterone acetate) or metformin (1g bd). Outcome measures were IR [area under curve insulin] on oral glucose tolerance test, RBP4 and metabolic/inflammatory markers.

Overweight women with PCOS were more IR than controls, yet RBP4 levels were not different in PCOS women vs. controls (35.4±4.3 vs. 28.9±3.1µg/ml, P=0.36). RBP4 correlated with cholesterol and triglycerides but not IR. Metformin improved IR by 35%, whilst the OCP worsened IR by 33%. However, RBP4 increased non-significantly in both groups (43.7±6.3 vs 42.6±5.5µg/ml, P=0.92).

Overweight women with PCOS were more IR than controls but this was not reflected by RBP4 levels. RBP4 correlated with lipid levels but not with IR markers. RBP4 levels did not change when IR was reduced by metformin or increased by the OCP. This data suggests that RBP4 is not a useful marker of IR in PCOS but may reflect other metabolic features of this condition.

The objective of this study was to evaluate in those with diabetes the association between foot ulcer (DFU) and lower extremity amputation (LEA) and chronic kidney disease (CKD).

A retrospective cohort study of individuals enrolled between 2002 and 2006.

Individuals cared for in general practice who were between 35 years of age and older with a history of diabetes mellitus.

Physicians who participate in The Health Information Network of the United Kingdom.

The presence of DFU or LEA and estimated glomerular filtration rate (eGFR).

90,617 individuals were fully evaluated with a median time of observation of 2.4 years. 378 individuals had LEA and 2619 had DFU. CKD (eGFR<60 ml/min/1.73m²) was noted in 23,350 (26%) of our cohort. For the development of DFU as compared to our reference group (group 1 (eGFR ≥ 60 ml/min/1.73m²)) the hazard ratios were for group 2 (eGFR ≥30 and <60 ml/min/1.73m²) of 1.85 (1.71, 2.01) and for group 3 (eGFR <30 ml/min/1.73m²) of 3.92 (3.23, 4.75) (all p-values <0.001). For LEA the hazard ratios for group 2 was 2.08 (1.68, 2.58) and for group 3 was 7.71 (5.29, 11.26) (all p-values <0.001).

This was an observational study.

There is a strong association between stage of CKD and DFU or LEA, which is likely not just related to presence of peripheral arterial disease. Individuals with even moderate CKD (eGFR <60 ml/min/1.73m²) are at increased risk for DFU and LEA.

The long-term outcome and functional status of subjects hospitalised for diabetic foot ulcers have been poorly studied and thus are the topics of this study.

Ninety-four consecutive diabetic subjects hospitalized for diabetic foot ulcers between January 1998 and December 2000 were prospectively followed for 79.5±13.3 months. We calculated rates of primary healing, new ulcers, amputations, mortality, and disability and evaluated the global therapeutic success (GTS) of foot care management as defined by the association of primary healing without recurrence or disability at the end of follow-up.

Follow-up was successful in 89/94 subjects (63 men/31 women, mean age 63.7±10.8 years). Of these, 69 (77.5%) experienced primary healing without major amputation, 39 (43.8%) underwent amputation (24 minor/15 major) and 46 died (51.7%), including 23 from cardiovascular events. Forty-two out of 69 patients who experienced primary healing (60.9%) had ulcer recurrence. At the end of the follow-up period, 25 patients (28.1%) were dependent and 40 subjects (44.9%) had achieved GTS. Multivariate analysis showed the independent role of age as a predictor of GTS (p<0.05) and of impaired renal function/albuminuria as independent predictors of healing failure, 1^st amputation and mortality (p<0.01).

Despite a satisfactory initial healing rate, the global long-term outcome of patients hospitalised for diabetic foot ulcers was poor. Nephropathy