The 232 participants randomly assigned to the CGM group (165 with baseline A1C ≥7.0% and 67 with A1C <7.0%) were asked to use CGM on a daily basis. The associations of baseline factors and early CGM use with CGM use ≥6 days/week in the 6th month and with change in A1C from baseline to 6 months were evaluated in regression models.

The only baseline factors found to be associated with greater CGM use in month 6 were age ≥25 years (P < 0.001) and more frequent self-reported prestudy blood glucose meter measurements per day (P < 0.001). CGM use and the percentage of CGM glucose values between 71 and 180 mg/dl during the 1st month were predictive of CGM use in month 6 (P < 0.001 and P = 0.002, respectively). More frequent CGM use was associated with a greater reduction in A1C from baseline to 6 months (P < 0.001), a finding present in all age-groups.

After 6 months, near-daily CGM use is more frequent in intensively treated adults with type 1 diabetes than in children and adolescents, although in all age-groups near-daily CGM use is associated with a similar reduction in A1C. Frequency of blood glucose meter monitoring and initial CGM use may help predict the likelihood of long-term CGM benefit in intensively treated patients with type 1 diabetes of all ages.

We developed a standardized inpatient continuous subcutaneous insulin infusion protocol to produce a progressive fall in plasma glucose concentrations in insulin pump–treated patients. Plasma glucose and counterregulatory hormone concentrations were measured in 14 young children (3 to <8 years, A1C 7.7 ± 0.6%) vs. 14 adolescents (12 to <18 years, A1C 7.6 ± 0.8%).

Plasma glucose decreased to similar nadir concentrations in the two groups. Four young children and four adolescents never had an epinephrine response. In the four young children and five adolescents who had a modest epinephrine response, this only occurred when plasma glucose fell to <60 mg/dl. In evaluating symptom scores, 29% of parents of young children felt that their child looked hypoglycemic, even at the lowest plasma glucose concentrations. Adolescents were better able to detect symptoms of hypoglycemia. In comparison with our data, epinephrine response to hypoglycemia in 14 nondiabetic adolescents studied at the Children's Hospital of Pittsburgh was higher.

These data suggest that even young children and adolescents with type 1 diabetes are prone to develop hypoglycemia-associated autonomic failure regardless of duration. Whether these abnormalities can be reversed using continuous glucose monitoring and closed-loop insulin delivery systems awaits further study.

In 605 Caucasian women with GDM, antenatal obstetrical and glucose data and the glucose data of the ppOGTTs performed 13 weeks (median) after delivery were prospectively collected.

A total of 132 (21.8%) women had an abnormal ppOGTT (2.8% impaired fasting glucose, 13.6% impaired glucose tolerance, and 5.5% diabetes). Independent risk factors were BMI ≥30 kg/m² (prevalence of abnormal ppOGTT 36.0 vs. 17.3%), gestational age at diagnosis <24 weeks (32.4 vs. 18.0%), 1-h antenatal value >200 mg/dl (11.1 mmol/l) (35.2 vs. 14.8%), and insulin therapy (30.3 vs. 14.5%). The prevalence of an abnormal ppOGTT was assessed according to the number of risk factors: 0, 9.2% (14 of 153); 1, 13.4% (25 of 186); 2, 28.5% (43 of 151); 3, 45.6% (26 of 57); and 4, 68.4% (13 of 19). Subjects were divided according to a significant increase of prevalence and risk for a ppOGTT: low risk (59.9% of subjects), <2 risk factors, 11.6%, odds ratio 1.3; intermediate risk, 2 risk factors, 28.5%, 4.0; and high risk, >2 risk factors, 51.3%, 10.5. The intermediate/high-risk group included 86.6% of those with diabetes and 67% of all those with abnormal ppOGTTs.

Women with ≥2 risk factors have a high risk for an abnormal ppOGTT, and 86% of postpartum diabetes is diagnosed within this group. Targeting women for ppOGTTs based on a risk assessment using available antenatal risk factors might reduce the number of missed cases of postpartum diabetes.

A total of 522 individuals (aged 40–64 years) were randomly allocated either to an intensive diet-exercise counseling group or to a control group. Diabetes incidence during follow-up was calculated according to sleep duration at baseline. Sleep duration was obtained for a 24-h period. Physical activity, dietary intakes, body weight, and immune mediators (C-reactive protein and interleukin-6) were measured.

Interaction between sleep duration and treatment group was statistically significant (P = 0.003). In the control group, the adjusted hazard ratios (HRs) (95% CI) for diabetes were 2.29 (1.38–3.80) and 2.74 (1.67–4.50) in the sleep duration groups 9–9.5 h and ≥10 h, respectively, compared with for that of the 7–8.5 h group. In contrast, sleep duration did not influence the incidence of diabetes in the intervention group; for sleep duration groups 9–9.5 h and ≥10 h, the adjusted HRs (95% CI) were 1.10 (0.60–2.01) and 0.73 (0.34–1.56), respectively, compared with that in the reference group (7–8.5 h sleep). Lifestyle intervention resulted in similar improvement in body weight, insulin sensitivity, and immune mediator levels regardless of sleep duration.

Long sleep duration is associated with increased type 2 diabetes risk. Lifestyle intervention with the aim of weight reduction, healthy diet, and increased physical activity may ameliorate some of this excess risk.

A total of 20,210 adults aged 45–69 years from the 2002 China National Nutrition and Health Survey were included. Information on dietary intake was collected using a validated food frequency questionnaire. Factor analysis and cluster analysis were used to identify the food factors and dietary pattern clusters.

Four dietary pattern clusters were identified ("Green Water," "Yellow Earth," "Western Adopter," and "New Affluence"). The prevalence of glucose tolerance abnormalities ranged from 3.9% in the Green Water to 8.0% in the New Affluence. After adjustment for area, age, sex, current smoking, and physical activity, subjects in the Yellow Earth cluster (prevalence ratio 1.22 [95% CI 1.04–1.43]) and New Affluence cluster (2.05 [1.76–2.37]) had significantly higher prevalence rates compared with those for the Green Water cluster. After further adjustment for BMI and waist-to-height ratio, the elevated risk in the New Affluence remained statistically significant.

Dietary patterns and food factors are associated with the presence of glucose tolerance abnormalities in China, even independent of obesity. A New Affluence diet is an important modifiable risk factor, which needs attention from the prevention point of view.

Serum samples from 415 individuals residing in Florida were cross-sectionally analyzed: 153 control subjects, 46 new-onset type 1 diabetic patients, 110 established type 1 diabetic patients (samples ≥5 months from diagnosis), and 106 first-degree relatives of the diabetic patients.

In this study, 25-OH vitamin D levels (median, range, interquartile range [IQR]) were similar among control subjects (20.1, below detection [bd]–163.5, 13.0–37.4 ng/ml), new-onset type 1 diabetic patients (21.2, bd–48.6, 12.2–30.2 ng/ml), established type 1 diabetic patients (23.2, bd–263.8, 13.8–33.9 ng/ml), and first-degree relatives (22.2, bd–59.9, 12.7–33.1 ng/ml) (P = 0.87). Mean 25-OH vitamin D levels were less than the optimal World Health Organization level of 30 ng/ml in all study groups.

Reduced serum 25-OH vitamin D levels were not specifically associated with type 1 diabetes. The uniform suboptimal 225-OH vitamin D levels, despite residence in a zone with abundant sunshine, support additional dietary vitamin D fortification practices.

A total of 1,741 men and women randomly selected from Central Pennsylvania were studied in the sleep laboratory. Insomnia was defined by a complaint of insomnia with duration of ≥1 year, whereas poor sleep was defined as a complaint of difficulty falling asleep, staying asleep, or early final awakening. Polysomnographic sleep duration was classified into three categories: ≥6 h of sleep (top 50% of the sample); 5–6 h (approximately third quartile of the sample); and ≤5 h (approximately the bottom quartile of the sample). Diabetes was defined either based on a fasting blood glucose >126 mg/dl or use of medication. In the logistic regression model, we simultaneously adjusted for age, race, sex, BMI, smoking, alcohol use, depression, sleep-disordered breathing, and periodic limb movement.

Chronic insomnia but not poor sleep was associated with a higher risk for diabetes. Compared with the normal sleeping and ≥6 h sleep duration group, the highest risk of diabetes was in individuals with insomnia and ≤5 h sleep duration group (odds ratio [95% CI] 2.95 [1.2–7.0]) and in insomniacs who slept 5–6 h (2.07 [0.68–6.4]).

Insomnia with short sleep duration is associated with increased odds of diabetes. Objective sleep duration may predict cardiometabolic morbidity of chronic insomnia, the medical impact of which has been underestimated.

We identified diabetic residents in Torino, Italy, as of 31 July 2003, using multiple independent data sources. We collected data on several laboratory tests and specialist medical examinations registered during the subsequent 12 months and performed regression analyses to identify associations with quality-of-care indicators based on existing guidelines.

After 1 year, only 35.8% of patients had undergone a comprehensive assessment. In the multivariate models, factors independently and significantly associated with lower quality of care were age ≥75 years (prevalence rate ratio [PRR] 0.66 [95% CI 0.61–0.70]) and established cardiovascular disease (0.89 [0.86–0.93]). Disease severity (PRR for insulin-treated patients 1.45 [1.38–1.53]) and diabetologist consultation (PRR 3.34 [3.17–3.53]) were positively associated with high quality of care. No clear association emerged between sex and socioeconomic status. These differences were strongly reduced in patients receiving diabetologist care compared with patients receiving general practitioner care only.

Despite widespread availability of guidelines and simple screening procedures, a nonnegligible portion of the diabetic population, namely elderly individuals and patients with less severe forms of the disease, are not properly cared for. As practitioners in diabetes centers are more likely to adhere to guidelines than general practitioners, quality in the diabetes care process can be improved by increasing the intensity of disease management programs, with greater participation by general practitioners.

We examined total body composition with dual-energy X-ray absorptiometry annually for 6 years in 2,675 older adults. We also measured mid-thigh muscle cross-sectional area (CSA) with computed tomography in year 1 and year 6. At baseline, 75-g oral glucose challenge tests were performed. Diagnosed diabetes (n = 402, 15.0%) was identified by self-report or use of hypoglycemic agents. Undiagnosed diabetes (n = 226, 8.4%) was defined by fasting plasma glucose (≥7 mmol/l) or 2-h postchallenge plasma glucose (≥11.1 mmol/l). Longitudinal regression models were fit to examine the effect of diabetes on the changes in body composition variables.

Older adults with either diagnosed or undiagnosed type 2 diabetes showed excessive loss of appendicular lean mass and trunk fat mass compared with nondiabetic subjects. Thigh muscle CSA declined two times faster in older women with diabetes than their nondiabetic counterparts. These findings remained significant after adjusting for age, sex, race, clinic site, baseline BMI, weight change intention, and actual weight changes over time.

Type 2 diabetes is associated with excessive loss of skeletal muscle and trunk fat mass in community-dwelling older adults. Older women with type 2 diabetes are at especially high risk for loss of skeletal muscle mass.

Random digit dialing was used to select a sample of adults with self-reported diabetes aged 18–80 years in Quebec, Canada. Health status was assessed by the World Health Organization Disability Assessment Schedule II. Material and social deprivation was measured using the Pampalon index, which is based on the Canadian Census. Potential risk factors for disability included sociodemographic characteristics, socioeconomic status, social support, lifestyle-related factors (smoking, physical activity, and BMI), health care–related problems, duration of diabetes, insulin use, and diabetes-specific complications.

There was a strong association between disability and material and social deprivation in our sample (n = 1,439): participants living in advantaged neighborhoods had lower levels of disability than participants living in disadvantaged neighborhoods. The means ± SD disability scores for men were 7.8 ± 11.8, 12.0 ± 11.8, and 18.1 ± 19.4 for low, medium, and high deprivation areas, respectively (P < 0.001). The disability scores for women were 13.4 ± 12.4, 14.8 ± 15.9, and 18.9 ± 16.2 for low, medium, and high deprivation areas, respectively (P < 0.01). Neighborhood deprivation was associated with disability even after controlling for education, household income, sociodemographic characteristics, race, lifestyle-related behaviors, social support, diabetes-related variables, and health care access problems.

The inclusion of neighborhood characteristics might be an important step in the identification and interpretation of risk factors for disability in diabetes.

This was a population-based study. Data were obtained from the Medical Birth Registry, covering >98% of all pregnancies in Sweden. A total of 5,089 type 1 diabetic pregnancies and 1,260,207 control pregnancies were included. Odds ratios (ORs) were adjusted for group differences in maternal age, parity, BMI, chronic hypertensive disease, smoking habits, and ethnicity.

In type 1 diabetes, preeclampsia was significantly more frequent (OR 4.47 [3.77–5.31]) as was delivery by cesarean section (5.31 [4.97–5.69]) compared with results for the general population. Stillbirth (3.34 [2.46–4.55]), perinatal mortality (3.29 [2.50–4.33]), and major malformations (2.50 [2.13–2.94]) were more common in type 1 diabetic than in control pregnancies. The risk of very preterm birth (<32 gestational weeks) was also higher among type 1 diabetic women (3.08 [2.45–3.87]). The incidence of fetal macrosomia (birth weight ≥2 SD above the mean) was increased in the diabetic group (11.45 [10.61–12.36]).

Type 1 diabetes in pregnancy is still associated with considerably increased rates of adverse obstetric and perinatal outcomes. The eightfold increased risk for fetal macrosomia in type 1 diabetic pregnancies is unexpected and warrants further investigation.

We compared the distribution of birth months within the SEARCH for Diabetes in Youth Study (SEARCH study) with the monthly distributions in U.S. births tabulated by race for years 1982–2005. SEARCH study participants (9,737 youth with type 1 diabetes and 1,749 with type 2 diabetes) were identified by six collaborating U.S. centers.

Among type 1 diabetic youth, the percentage of observed to expected births differed across the months (P = 0.0092; decreased in October–February and increased in March–July). Their smoothed birth-month estimates demonstrated a deficit in November–February births and an excess in April–July births (smoothed May versus January relative risk [RR] = 1.06 [95% CI 1.02–1.11]). Stratifications by sex or by three racial groups showed similar patterns relating type 1 diabetes to month of birth. Stratification by geographic regions showed a peak-to-nadir RR of 1.10 [1.04–1.16] in study regions from the northern latitudes (Colorado, western Washington State, and southern Ohio) but no birth-month effect (P > 0.9) in study regions from more southern locations. Among type 2 diabetic youth, associations with birth month were inconclusive.

Spring births were associated with increased likelihood of type 1 diabetes but possibly not in all U.S. regions. Causal mechanisms may involve factors dependent on geographic latitude such as solar irradiance, but it is unknown whether they influence prenatal or early postnatal development.

The Korea National Health and Nutrition Examination Survey (KNHANES), a nationwide survey examining the general health and nutrition status of the Korean people, was conducted in 1998, 2001, and 2005. Using the first (1998; n = 5,645), second (2001; n = 4,154), and third (2005; n = 4,628) KNHANES datasets, in the present study, we estimated the prevalence of diabetes among Korean adults (aged ≥30 years), the proportions of known cases of diabetes, and the proportions of well-controlled cases of diabetes, as defined by either the American Diabetes Association (A1C <7%) or the International Diabetes Federation guidelines (A1C <6.5%).

In 2005, the prevalence of diabetes was estimated to be 9.1% (~2.58 million people: 10.2% of men and 7.9% of women), including 6.2% with known diabetes and 2.9% with newly diagnosed diabetes. The prevalence of impaired fasting glucose was 17.4% (~4.94 million people). The proportion of known cases of diabetes drastically increased from 23.2% in 1998 to 41.2% in 2001 and 68.0% in 2005 (P < 0.0001). Among known diabetic patients in 2005, 43.5 and 22.9% had A1C levels <7.0 and <6.5%, respectively.

The overall prevalence of diabetes in Korea has not changed significantly between 1998 and 2005. Physician diagnosis and treatment rates of diabetes have significantly improved during this period, but glycemic control was still poorer than that in other developed countries.

The analysis included 4,472 Dutch participants aged ≥55 years without diabetes at baseline. Dietary intake was assessed with a semiquantitative food frequency questionnaire. Hazard ratios (relative risk [RR]) with 95% CIs were used to examine risk associations adjusted for age, sex, lifestyle, and nutritional factors.

After 15 years of follow-up, 463 participants developed type 2 diabetes. Median fish intake, mainly lean fish (81%), was 10 g/day. Total fish intake was associated positively with risk of type 2 diabetes; the RR was 1.32 (95% CI 1.02–1.70) in the highest total fish group (≥28 g/day) compared with that for non–fish eaters (P_trend = 0.04). Correspondingly, lean fish intake tended to be associated positively with type 2 diabetes (RR highest group ]≥23 g/day] 1.30 [95% CI 1.01–1.68]; P_trend = 0.06), but fatty fish was not. No association was observed between EPA and DHA intake and type 2 diabetes (RR highest group [≥149.4 mg/day] 1.22 [0.97–1.53]). With additional adjustment for intake of selenium, cholesterol, and vitamin D, this RR decreased to 1.05 (0.80–1.38; P_trend = 0.77).

The findings do not support a beneficial effect of total fish, type of fish, or EPA and DHA intake on the risk of type 2 diabetes. Alternatively, other dietary components, such as selenium, and unmeasured contaminants present in fish might explain our results.

This study included 1,066 individuals aged ≥40 years from the 2005–2006 National Health and Nutrition Examination Survey. A1C, FPG, and 45° color digital retinal images were assessed. Retinopathy was defined as a level ≥14 on the Early Treatment Diabetic Retinopathy Study severity scale. We used joinpoint regression to identify linear inflections of prevalence of retinopathy in the association between A1C and FPG.

The overall prevalence of retinopathy was 11%, which is appreciably lower than the prevalence in people with diagnosed diabetes (36%). There was a sharp increase in retinopathy prevalence in those with A1C ≥5.5% or FPG ≥5.8 mmol/l. After excluding 144 people using hypoglycemic medication, the change points for the greatest increase in retinopathy prevalence were A1C 5.5% and FPG 7.0 mmol/l. The coefficients of variation were 15.6 for A1C and 28.8 for FPG. Based on the areas under the receiver operating characteristic curves, A1C was a stronger discriminator of retinopathy (0.71 [95% CI 0.66–0.76]) than FPG (0.65 [0.60 – 0.70], P for difference = 0.009).

The steepest increase in retinopathy prevalence occurs among individuals with A1C ≥5.5% and FPG ≥5.8 mmol/l. A1C discriminates prevalence of retinopathy better than FPG.

The case-control study was conducted with 537 ischemic stroke patients and 537 control subjects. A structured questionnaire was used to collect information on conventional cardiovascular risk factors and laboratory results. The genetic polymorphisms of PPAR were determined by PCR–restriction fragment–length polymorphism.

A significant interaction was seen between the –2821C allele and diabetes but not between this allele and hypertension. A markedly elevated risk of ischemic stroke (odds ratio 9.7) was found in the subjects with diabetes and the –2821C allele compared with that in those without these two risk factors.

The –2821C allele of PPAR was a strong predictor of ischemic stroke for diabetic patients.

A total of 188 patients, aged 10–35 years, with recently diagnosed type 1 diabetes were randomly assigned for a treatment consisting of the subcutaneous administration of placebo or 1, 0.5, or 0.1 mg NBI-6024 at baseline, weeks 2 and 4, and then monthly until month 24. Fasting, peak, and area under the curve (AUC) C-peptide concentrations during a 2-h mixed-meal tolerance test were measured at 3-month intervals during treatment. Immune function parameters (islet antibodies and CD4 and CD8 T-cells) were also studied.

The mean peak C-peptide concentration at 24 months after study entry showed no significant difference between the groups treated with 0.1 mg (0.59 pmol/ml), 0.5 mg (0.57 pmol/ml), and 1.0 mg NBI-6024 (0.48 pmol/ml) and the placebo group (0.54 pmol/ml). Fasting, stimulated peak, and AUC C-peptide concentrations declined linearly in all groups by ~60% over the 24-month treatment period. The average daily insulin needs at month 24 were also comparable between the four groups. No treatment-related changes in islet antibodies and T cell numbers were observed.

Treatment with altered peptide ligand NBI-6024 at repeated doses of 0.1, 0.5, or 1.0 mg did not improve or maintain β-cell function.

Fifteen patients diagnosed with type 1 diabetes and for whom autologous umbilical cord blood was stored underwent a single intravenous infusion of autologous cells and completed 1 year of postinfusion follow-up. Intensive insulin regimens were used to optimize glycemic control. Metabolic and immunologic assessments were performed before infusion and at established time periods thereafter.

Median (interquartile range [IQR]) age at infusion was 5.25 (3.1–7.3) years, with a median postdiagnosis time to infusion of 17.7 (10.9–26.5) weeks. No infusion-related adverse events were observed. Metabolic indexes 1 year postinfusion were peak C-peptide median 0.50 ng/ml (IQR 0.26–1.30), P = 0.002; A1C 7.0% (IQR 6.5–7.7), P = 0.97; and insulin dose 0.67 units · kg^–1 · day^–1 (IQR 0.55–0.77), P = 0.009. One year postinfusion, no changes were observed in autoantibody titers, regulatory T-cell numbers, CD4-to-CD8 ratio, or other T-cell phenotypes.

Autologous umbilical cord blood transfusion in children with type 1 diabetes is safe but has yet to demonstrate efficacy in preserving C-peptide. Larger randomized studies as well as 2-year postinfusion follow-up of this cohort are needed to determine whether autologous cord blood–based approaches can be used to slow the decline of endogenous insulin production in children with type 1 diabetes.

We studied 83 of 86 individuals ≥25 years of age with type 1 diabetes who used CGM as part of a 6-month randomized clinical trial in a subsequent 6-month extension study.

After 12 months, median CGM use was 6.8 days per week. Mean change in A1C level from baseline to 12 months was –0.4 ± 0.6% (P < 0.001) in subjects with baseline A1C ≥7.0%. A1C remained stable at 6.4% in those with baseline A1C <7.0%. The incidence rate of severe hypoglycemia was 21.8 and 7.1 events per 100 person-years in the first and last 6 months, respectively. Time per day with glucose levels in the range of 71–180 mg/dl increased significantly (P = 0.02) from baseline to 12 months.

In intensively treated adults with type 1 diabetes, CGM use and benefit can be sustained for 12 months.

This was a prospective observational study of 45 type 1 diabetic pregnancies and 39 normal pregnancies. All participants had concentrations of fetal pro–B-type natriuretic peptide (proBNP) and troponin-T (TnT) measured at the time of delivery. All patients with type 1 diabetes had Doppler evaluation of the umbilical artery, middle cerebral artery, and ductus venosus in the third trimester, and a subset (n = 21) had detailed fetal echocardiograms performed in each trimester.

Fetal proBNP and TnT concentrations were higher in the diabetic cohort than in the normal cohort (P < 0.05). ProBNP correlated positively with interventricular septum thickness (P < 0.05) but not with cardiac function indexes in the third trimester. In patients with poor glycemic control, there was a significant positive correlation (P < 0.05) between fetal TnT and the third trimester umbilical artery pulsatility index. There were also increased levels of fetal TnT in infants with poor perinatal outcome (P < 0.05).

Biochemical markers of cardiac dysfunction are elevated in infants of diabetic mothers, especially those with cardiomyopathy or poor perinatal outcome. Hyperglycemia in early pregnancy may affect myocardial and placental development, thus contributing to the susceptibility to hypoxia seen in these infants.

A prospective single-arm blinded study was completed in which 66 patients with type 1 and type 2 diabetes were enrolled and followed over a 24-week period. Clinical, medical, and diabetes histories were collected. Transcutaneous oxygen tension was measured at the ankles. Superficial tissue oxyhemoglobin (oxy) and deoxyhemoglobin (deoxy) were measured with hyperspectral imaging from intact tissue bordering the ulcer. A healing index derived from oxy and deoxy values was used to assess the potential for healing.

Fifty-four patients with 73 ulcers completed the study; at 24 weeks, 54 ulcers healed while 19 ulcers did not heal. When using the healing index to predict healing, the sensitivity was 80% (43 of 54), the specificity was 74% (14 of 19), and the positive predictive value was 90% (43 of 48). The sensitivity, specificity, and positive predictive values increased to 86, 88, and 96%, respectively, when removing three false-positive osteomyelitis cases and four false-negative cases due to measurements on a callus. The results indicate that cutaneous tissue oxygenation correlates with wound healing in diabetic patients.

Hyperspectral imaging of tissue oxy and deoxy may predict the healing of DFUs with high sensitivity and specificity based on information obtained from a single visit.

The study subjects were 401 type 2 diabetic individuals (252 with normoalbuminuria and 149 with albuminuria) who were examined for SMAP under conditions of shear stress only (no agonist stimulation) and the reversibility of platelet microaggregation after stimulation with 1 µmol/l ADP, measured by a laser light-cattering method. Active glycoprotein IIb/IIIa (GPIIb/IIIa) and P-selectin expression levels on platelets as an index of platelet activation were measured by whole-blood flow cytometry.

SMAP formation was noted in 53% of diabetic patients. All patients with SMAP showed an irreversible pattern of platelet microaggregates by a low dose of ADP. SMAP was observed in 75% of diabetic subjects with albuminuria and in 39% of those with normoalbuminuria. Multivariate logistic regression analysis identified urinary albumin excretion rate and brachial-ankle pulse-wave velocity as independent factors associated with SMAP. The degree of SMAP correlated with active GPIIb/IIIa ( = 0.59, P < 0.001) and P-selectin ( = 0.55, P < 0.001) expression levels. These early-activated platelet profiles were significantly inhibited in albuminuric patients with aspirin intake, although the effect was incomplete.

Our study demonstrated an independent association between albuminuria and early changes in activated platelet profiles of type 2 diabetic patients. Further follow-up and intervention studies are needed to establish whether the inhibition of SMAP affects the course of cardiovascular disease in type 2 diabetic patients.

This was a multicenter, factorial randomized trial of perindopril-indapamide versus placebo (double-blind comparison) and intensive glucose control with a gliclazide MR–based regimen (target A1C ≤6.5%) versus standard glucose control (open comparison) in 11,140 participants with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial. Annual event rates and risks of major macrovascular and microvascular events considered jointly and separately, renal events, and death during an average 4.3 years of follow-up were assessed, using Cox proportional hazards models.

There was no interaction between the effects of routine blood pressure lowering and intensive glucose control for any of the prespecified clinical outcomes (all P > 0.1): the separate effects of the two interventions for the renal outcomes and death appeared to be additive on the log scale. Compared with neither intervention, combination treatment reduced the risk of new or worsening nephropathy by 33% (95% CI 12–50%, P = 0.005), new onset of macroalbuminuria by 54% (35–68%, P < 0.0001), and new onset of microalbuminuria by 26% (17–34%). Combination treatment was associated with an 18% reduction in the risk of all-cause death (1–32%, P = 0.04).

The effects of routine blood pressure lowering and intensive glucose control were independent of one another. When combined, they produced additional reductions in clinically relevant outcomes.

Participants consisted of 224 individuals with diabetes and 103 nondiabetic control subjects. Flicker light–induced retinal vasodilation (percentage increase over baseline diameter) was measured using the Dynamic Vessel Analyzer. Diabetic retinopathy was graded from retinal photographs.

Mean ± SD age was 56.5 ± 11.8 years for those with diabetes and 48.0 ± 16.3 years for control subjects. Mean arteriolar and venular dilation after flicker light stimulation were reduced in participants with diabetes compared with those in control subjects (1.43 ± 2.10 vs. 3.46 ± 2.36%, P < 0.001 for arteriolar and 2.83 ± 2.10 vs. 3.98 ± 1.84%, P < 0.001 for venular dilation). After adjustment for age, sex, diabetes duration, fasting glucose, cholesterol and triglyceride levels, current smoking status, systolic blood pressure, and use of antihypertensive and lipid-lowering medications, participants with reduced flicker light–induced vasodilation were more likely to have diabetes (odds ratio 19.7 [95% CI 6.5–59.1], P < 0.001 and 8.14 [3.1–21.4], P < 0.001, comparing lowest vs. highest tertile of arteriolar and venular dilation, respectively). Diabetic participants with reduced flicker light–induced vasodilation were more likely to have diabetic retinopathy (2.2 [1.2–4.0], P = 0.01 for arteriolar dilation and 2.5 [1.3–4.5], P = 0.004 for venular dilation).

Reduced retinal vasodilation after flicker light stimulation is independently associated with diabetes status and, in individuals with diabetes, with diabetic retinopathy. Our findings may therefore support endothelial dysfunction as a pathophysiological mechanism underlying diabetes and its microvascular manifestations.

This was a hospital-based prospective study of 590 patients aged 12–20 years with type 1 diabetes free of retinopathy at baseline. All patients had seven-field retinal photographs taken of both eyes. Incident retinopathy was ascertained from retinal photographs taken at follow-up visits. Fractal dimension was measured from baseline photographs using a computer-based program following a standardized protocol.

Over a mean ± SD follow-up period of 2.9 ± 2.0 years, 262 participants developed mild nonproliferative diabetic retinopathy (15.0 per 100 person-years). After adjusting for age, sex, diabetes duration, A1C, and other risk factors, we found no association between retinal vascular fractal dimension and incident retinopathy.

Retinal vascular fractal dimension was not associated with incident early diabetic retinopathy in this sample of children and adolescents with type 1 diabetes.

A total of 162 subjects with type 1 diabetes and 343 with type 2 diabetes, of whom 329 subjects had no diabetic retinopathy, 27 had nonproliferative diabetic retinopathy (NPDR), 101 had proliferative diabetic retinopathy (PDR), and 107 had clinically significant macular edema (CSME), were recruited. Blinding diabetic retinopathy was defined as severe NPDR, PDR, or CSME. Serum ADMA, SDMA, and l-arginine concentrations were determined by mass spectroscopy.

In multivariate analysis, blinding diabetic retinopathy, PDR, and nephropathy were associated with significantly increased serum levels of ADMA (P < 0.001), SDMA (P < 0.001), and l-arginine (P = 0.001). Elevated ADMA (P < 0.001) and SDMA (P < 0.001) were also significantly associated with CSME.

Severe forms of diabetic retinopathy are associated with elevated serum ADMA, SDMA, and l-arginine. Further investigation is required to determine whether these findings are of clinical relevance.

Fasting lipoprotein particle size and concentration and visceral adipose tissue (VAT) were determined in 226 children (117 black, 101 male) aged 8 to <18 years. The relationship between lipoproteins and insulin sensitivity was evaluated in a subset of 194 children (100 black, 88 male) who underwent a hyperinsulinemic-euglycemic clamp.

Black male children had smaller VLDL and black female children had larger HDL size than their white counterparts. Overall, blacks had larger LDL size with no sex-specific race differences. After adjusting for VAT and sex, only VLDL size and concentrations remained significantly favorable in blacks. Analysis of lipoprotein particle size and concentration across insulin sensitivity quartiles revealed that in both racial groups, the most insulin-resistant children had higher concentrations of small dense LDL, small HDL, and large VLDL and smaller LDL and HDL sizes than their more insulin-sensitive counterparts.

The previously reported favorable lipoprotein profiles in black versus white children is partly due to race differences in VAT. In both groups, however, the most insulin-resistant youths have a high-risk atherogenic profile of small dense LDL, small HDL, and large VLDL, akin to the atherogenic lipoprotein pattern in adults with coronary artery disease.

Calibration and discrimination of the three prediction models were tested using prospective data for 1,482 Caucasian men and women, 50–75 years of age, who participated in the Hoorn Study. All analyses were stratified by glucose status.

During 10 years of follow-up, a total of 197 CHD events, of which 43 were fatal, were observed in this population, with the highest percentage of first CHD events in the diabetic group. The Framingham and UKPDS prediction models overestimated the risk of first CHD event in all glucose tolerance groups. Overall, the prediction models had a low to moderate discriminatory capacity. The SCORE risk function was the best predictor of fatal CHD events in the group with NGT (area under the receiver operating characteristic curve 0.79 [95% CI 0.70–0.87]), whereas the UKPDS performed better in the intermediate hyperglycemia group (0.84 [0.74–0.94]) in the estimation of fatal CHD risk. After exclusion of known diabetic patients, all prediction models had a higher discriminatory ability in the group with diabetes.

The use of the Framingham function for prediction of the first CHD event is likely to overestimate an individual's absolute CHD risk. In CHD prevention, application of the SCORE and UKPDS functions might be useful in the absence of a more valid tool.

Anthropometric measurements were performed at 6–8 years of age in 213 offspring of type 1 diabetic mothers who participated in a previous nationwide study. Homeostasis model assessment of insulin resistance (HOMA-IR) was determined from a fasting blood sample in 155 of these children. In addition, we studied BMI standard deviation score (SDS) growth trajectories. Results were compared with national reference data.

The prevalence of overweight in the study population was not different from that in the reference population. However, children who were born macrosomic showed twice as much overweight as nonmacrosomic children. Macrosomia and maternal overweight were independent predictors of childhood overweight. Overweight children showed an increase in BMI SDS starting already after 6 months of age and had a significantly increased HOMA-IR.

In type 1 diabetic women with adequate glycemic control during pregnancy, long-term effects on body composition and overweight in their offspring at school age are limited and related mainly to macrosomia at birth. Possible targets for prevention of childhood overweight are fetal macrosomia, maternal overweight, and an increase in BMI SDS during the first years of life.

MCP-1/CCL2 concentration was measured in plasma fractions of 363 middle-aged overweight/obese individuals (aged 61 ± 12 years, BMI 30.1 ± 6.6 kg/m², 15% with type 2 diabetes, and 12% with impaired glucose tolerance) of a population survey carried out in 1990–1991 in Lombardy, Italy (Cremona Study), and cardiovascular disease (CVD) mortality was assessed in 2006 through Regional Health Registry files.

At baseline MCP-1/CCL2 was increased in individuals with type 2 diabetes (P < 0.05) and showed significant correlations with biochemical risk markers of atherosclerosis. After 15 years, among the 363 subjects, there were 82 deaths due to CVD. In univariate analysis age, sex, fasting glucose and insulin, fibrinogen, glucose tolerance status, smoking habit, and MCP-1/CCL2 were associated with CVD mortality. Age, sex, fasting serum glucose, MCP-1/CCL2, and smoking habit maintained an independent association with CVD mortality in multiple regression analysis. In a subgroup of 113 subjects in whom data for C-reactive protein (CRP) were available, its level was not predictive of CVD mortality.

In middle-aged overweight/obese individuals MCP-1/CCL2 was independently associated with CVD mortality. Further studies will be necessary to establish its role as a surrogate biomarker and as a potential therapeutic target.

Eleven men with metabolic syndrome were studied in a randomized, double-blind, crossover trial of 5-week intervention periods with placebo, fenofibrate (200 mg/day), and atorvastatin (40 mg/day). LpA-I and LpA-I:A-II kinetics were examined using stable isotopic techniques and compartmental modeling.

Compared with placebo, fenofibrate significantly increased the production of both LpA-I:A-II (30% increase; P < 0.001) and apoA-II (43% increase; P < 0.001), accounting for significant increases of their corresponding plasma concentrations (10 and 23% increases, respectively), but it did not alter LpA-I kinetics or concentration. Atorvastatin did not significantly alter HDL concentration or the kinetics of HDL particles.

In the metabolic syndrome, fenofibrate, but not atorvastatin, influences HDL metabolism by increasing the transport of LpA-I:A-II particles.

In a longitudinal research design, insulin sensitivity (S_i) of 96 research participants was determined at baseline and 1 year later. Body adiposity was assessed at four assessments.

The change in S_i during the first year of the study was a significant predictor of further fat mass development (P < 0.05). Considering different directions of S_i change, S_i was a strong predictor for further fat mass development only in the group that decreased their S_i (P < 0.05).

The results show that the direction of change in insulin sensitivity at an early age is an important independent predictor for further fat mass development and emphasize the importance of insulin sensitivity as a primary target for long-term obesity prevention, as well as the significance of early age intervention.

A case-cohort study within a prospective study was designed. We randomly selected a subcohort (n = 2,500) from 26,444 participants, of whom 1,962 were diabetes free at baseline. Of the 801 incident type 2 diabetes cases identified in the cohort during 7 years of follow-up, 579 remained for analyses after exclusions. Prediction models were compared by receiver operatoring characteristic (ROC) curve and integrated discrimination improvement.

Case-control discrimination by the lifestyle characteristics (ROC-AUC: 0.8465) improved with plasma glucose (ROC-AUC: 0.8672, P < 0.001) and A1C (ROC-AUC: 0.8859, P < 0.001). ROC-AUC further improved with HDL cholesterol, triglycerides, -glutamyltransferase, and alanine aminotransferase (0.9000, P = 0.002). Twenty SNPs did not improve discrimination beyond these characteristics (P = 0.69).

Metabolic markers, but not genotyping for 20 diabetogenic SNPs, improve discrimination of incident type 2 diabetes beyond lifestyle risk factors.

A total of 284 adolescents (49.3% of whom were female) aged 14.9 ± 1.2 years were included in the study. Birth weight and gestational age were obtained from parental records. Abdominal adiposity (in three regions: R1, R2, and R3) and trunk and total body fat mass were measured by dual-energy X-ray absorptiometry. Regional fat mass indexes (FMIs) were thereafter calculated as fat mass divided by the square of height (Trunk FMI and abdominal FMI R1, R2, and R3).

Birth weight was negatively associated with abdominal FMI R1, R2, and R3 independently of total fat mass, gestational age, sex, breast-feeding duration, pubertal stage, physical activity, and socioeconomic status (all P < 0.01).

Our study shows an inverse association between birth weight and abdominal adiposity in adolescents independently of total fat mass and other potential confounders. These findings suggest that fetal nutrition, as reflected by birth weight, may have a programming effect on abdominal adiposity later in life.

A systematic computer-assisted and hand search was conducted to identify relevant articles with longitudinal design and quantitative measurement of alcohol consumption. Adjustment was made for the sick-quitter effect. We used fractional polynomials in a meta-regression to determine the dose-response relationships by sex and end point using lifetime abstainers as the reference group.

The search revealed 20 cohort studies that met our inclusion criteria. A U-shaped relationship was found for both sexes. Compared with lifetime abstainers, the relative risk (RR) for type 2 diabetes among men was most protective when consuming 22 g/day alcohol (RR 0.87 [95% CI 0.76–1.00]) and became deleterious at just over 60 g/day alcohol (1.01 [0.71–1.44]). Among women, consumption of 24 g/day alcohol was most protective (0.60 [0.52–0.69]) and became deleterious at about 50 g/day alcohol (1.02 [0.83–1.26]).

Our analysis confirms previous research findings that moderate alcohol consumption is protective for type 2 diabetes in men and women.