Background-Circulating adiponectin levels are lower in men than in women and lower in advanced coronary artery disease, obesity, and type 2 but not type 1 diabetes. However, it is not known whether low adiponectin levels predict development of atherosclerosis independently of other cardiovascular risk factors. Methods and Results-Progression of coronary artery calcification (CAC) over an average of 2.6 years (range, 1.6 to 3.3)was assessed in a cohort of patients with type 1 diabetes and nondiabetic subjects 19 to 59 years of age. In this nested case-control substudy, plasma adiponectin levels were measured in 101 cases with significant CAC progression and in 205 controls. Controls were oversampled on the basis of age, gender, diabetes status, and presence of baseline CAC. In conditional logistic regression adjusted for baseline CAC volume and other significant predictors of CAC progression, adiponectin levels were inversely related to progression of CAC in diabetic (OR, 0.47; 95% CI, 0.24 to 0.94) and nondiabetic (OR, 0.15; 95% CI, 0.05 to 0.40 for a doubling in adiponectin levels) subjects. Adjustment for additional cardiovascular risk factors did not change this association. In conditional logistic regression models by quartiles of plasma adiponectin levels, the probability value for trend was statistically significant for all participants (PϽ0.001) and nondiabetic participants (PϽ0.001) and was borderline for type 1 diabetics (Pϭ0.08). Conclusions-Low

OBJECTIVE -To compare the prevalence, awareness, treatment, and control of hypertension in a population-representative sample of adults with type 1 diabetes and comparable nondiabetic control subjects. , the Coronary Artery Calcification in Type 1 Diabetes Study enrolled 1,416 individuals aged 19 -56 years with no known history of coronary artery disease: 652 type 1 diabetic patients (46% male, mean age 37 years) and 764 nondiabetic control subjects (50% male, mean age 39 years). Subjects were asked if they had been told by a physician that they had hypertension or were on a blood pressure medication. Blood pressure was measured using standardized Joint National Committee (JNC) protocol. RESEARCH DESIGN AND METHODSRESULTS -Type 1 diabetic subjects, compared with nondiabetic subjects, had higher rates of hypertension prevalence (43 vs. 15%, P Ͻ 0.001), awareness (53 vs. 45%, P ϭ 0.11), treatment (87 vs. 47%, P Ͻ 0.001), and control (55 vs. 32%, P Ͻ 0.001) for the JNC 6 goal (130/85 mmHg). Only 42% of all type 1 diabetic hypertensive subjects met the new JNC 7 goal (130/80 mmHg). Type 1 diabetic subjects had better blood pressure control (72 vs. 32%, P Ͻ 0.0001), using 140/90 mmHg as a common measure. The majority of treated subjects were on a single antihypertensive agent (75 vs. 64%).CONCLUSIONS -Subjects with type 1 diabetes have higher rates of hypertension prevalence, treatment, and control than nondiabetic subjects. However, hypertension remains largely uncontrolled, even if treated in high-risk populations, such as type 1 diabetic subjects and undiagnosed individuals in the general population. Achieving more stringent blood pressure goals will require increased attention and may necessitate the use of multiple antihypertensive agents. Diabetes Care 28:301-306, 2005N umerous advances in care have led to improved health and longer survival in patients with type 1 diabetes. Hypertension has been estimated to affect ϳ30% of type 1 diabetic patients and usually reflects the development of diabetic nephropathy (1). Effective control of blood pressure is a well-established target to decrease morbidity and mortality in patients with type 1 diabetes and nondiabetic individuals as well (1,2).In type 1 diabetes, hypertension is related to an increased risk of microvascular complications, such as retinopathy (3-5), and is a modifiable risk factor in the progression of nephropathy (6) as well as in the development of the macrovascular complications of cardiovascular disease (7,8). The risk of cardiovascular disease doubles with each increase of 20/10 mm/Hg beginning at 115/75 mm/Hg (2). It has been estimated that 35-75% of diabetes complications are due to hypertension (9). Recently revised guidelines have been published by both the American Diabetes Association (ADA) (1) and the Joint National Committee (JNC) 7 (2) regarding goals for blood pressure treatment.Reports on prevalence, awareness, treatment, and control of hypertension exist for the general population (10,11) and the type 2 diabetic population (12-16), wher...

Background. One in three adolescents and young adults with type 1 diabetes have at least one early diabetes-related complication/comorbidity. However, the prevalence, patterning, and risk factors for co-occurring complications in this population are not well understood. Methods. The SEARCH for Diabetes in Youth observational cohort study includes 1327 individuals diagnosed with type 1 diabetes before 20 years of age from 5 United States locations. Sociodemographic and metabolic risk factors were assessed at baseline (mean diabetes duration = 0·8 years, mean age = 10·9 years) and follow-up (mean diabetes duration = 7.8 years, mean age = 18·0 years). Early diabetes complications (diabetic kidney disease, diabetic retinopathy, peripheral neuropathy, cardiovascular autonomic neuropathy, and arterial stiffness) were assessed at follow-up. We aimed to describe co-occurrence of complications and examine differences in co-occurrence within demographic and metabolic risk factor clusters identified using cluster analysis. Findings. Overall, co-occurrence of any ≥2 complications was observed in 5·9% of all participants, more frequently than expected by chance alone (4·4%, p=0·015). Specifically, retinopathy and diabetic kidney disease, retinopathy and arterial stiffness, and arterial stiffness and cardiac autonomic neuropathy all co-occurred more frequently than expected (all p<0·05). The cluster analysis produced four unique clusters characterized by progressively worsening metabolic risk factor profiles (longer duration; higher A1c, non-HDL cholesterol, and waist to height ratio) and differences in sociodemographic characteristics (race/ethnicity, household income, type of health insurance). Prevalence of ≥2 complications progressively increased with worsening metabolic profiles (from 2·3% to 20·8%, p<0·001). Interpretation. We report that early complications co-occur in adolescents and young adults with type 1 diabetes more frequently than expected after an average of less than eight years of diabetes duration. A cluster of high risk factors identifies groups that may benefit most from interventions to reduce complications.

To evaluate the contemporary prevalence of diabetic peripheral neuropathy (DPN) in participants with type 1 diabetes in the T1D Exchange Clinic Registry throughout the U.S. RESEARCH DESIGN AND METHODSDPN was assessed with the Michigan Neuropathy Screening Instrument Questionnaire (MNSIQ) in adults with ‡5 years of type 1 diabetes duration. A score of ‡4 defined DPN. Associations of demographic, clinical, and laboratory factors with DPN were assessed. RESULTSAmong 5,936 T1D Exchange participants (mean 6 SD age 39 6 18 years, median type 1 diabetes duration 18 years [interquartile range 11, 31], 55% female, 88% non-Hispanic white, mean glycated hemoglobin [HbA 1c ] 8.1 6 1.6% [65.3 6 17.5 mmol/mol]), DPN prevalence was 11%. Compared with those without DPN, DPN participants were older, had higher HbA 1c , had longer duration of diabetes, were more likely to be female, and were less likely to have a college education and private insurance (all P < 0.001). DPN participants also were more likely to have cardiovascular disease (CVD) (P < 0.001), worse CVD risk factors of smoking (P 5 0.008), hypertriglyceridemia (P 5 0.002), higher BMI (P 5 0.009), retinopathy (P 5 0.004), reduced estimated glomerular filtration rate (P 5 0.02), and Charcot neuroarthropathy (P 5 0.002). There were no differences in insulin pump or continuous glucose monitor use, although DPN participants were more likely to have had severe hypoglycemia (P 5 0.04) and/or diabetic ketoacidosis (P < 0.001) in the past 3 months. CONCLUSIONSThe prevalence of DPN in this national cohort with type 1 diabetes is lower than in prior published reports but is reflective of current clinical care practices. These data also highlight that nonglycemic risk factors, such as CVD risk factors, severe hypoglycemia, diabetic ketoacidosis, and lower socioeconomic status, may also play a role in DPN development.Diabetic neuropathy is a prevalent complication in patients with diabetes and a major cause of morbidity and mortality (1). Among the various forms of diabetic neuropathy, distal symmetric polyneuropathy (DPN) and diabetic autonomic neuropathies are by far the most studied (1).

IntroductionClosed-loop systems titrate insulin based on sensor glucose levels, providing novel means to reduce the risk of hypoglycaemia while improving glycaemic control. We will assess effectiveness of 6-month day-and-night closed-loop insulin delivery compared with usual care (conventional or sensor-augmented pump therapy) in children and adolescents with type 1 diabetes.Methods and analysisThe trial adopts an open-label, multicentre, multinational (UK and USA), randomised, single-period, parallel design. Participants (n=130) are children and adolescents (aged ≥6 and <19 years) with type 1 diabetes for at least 1 year, and insulin pump use for at least 3 months with suboptimal glycaemic control (glycated haemoglobin ≥58 mmol/mol (7.5%) and ≤86 mmol/mol (10%)). After a 2–3 week run-in period, participants will be randomised to 6-month use of hybrid closed-loop insulin delivery, or to usual care. Analyses will be conducted on an intention-to-treat basis. The primary outcome is glycated haemoglobin at 6 months. Other key endpoints include time in the target glucose range (3.9–10 mmol/L, 70–180 mg/dL), mean sensor glucose and time spent above and below target. Secondary outcomes include SD and coefficient of variation of sensor glucose levels, time with sensor glucose levels <3.5 mmol/L (63 mg/dL) and <3.0 mmol/L (54 mg/dL), area under the curve of glucose <3.5 mmol/L (63 mg/dL), time with glucose levels >16.7 mmol/L (300 mg/dL), area under the curve of glucose >10.0 mmol/L (180 mg/dL), total, basal and bolus insulin dose, body mass index z-score and blood pressure. Cognitive, emotional and behavioural characteristics of participants and caregivers and their responses to the closed-loop and clinical trial will be assessed. An incremental cost-effectiveness ratio for closed-loop will be estimated.Ethics and disseminationCambridge South Research Ethics Committee and Jaeb Center for Health Research Institutional Review Office approved the study. The findings will be disseminated by peer-review publications and conference presentations.Trial registration numberNCT02925299; Pre-results.

Objective Incidence of youth‐onset diabetes in India has not been well described. Comparison of incidence, across diabetes registries, has the potential to inform hypotheses for risk factors. We sought to compare the incidence of diabetes in the U.S.‐based registry of youth onset diabetes (SEARCH) to the Registry of Diabetes with Young Age at Onset (YDR—Chennai and New Delhi regions) in India. Methods We harmonized data from both SEARCH and YDR to the Observational Medical Outcomes Partnership (OMOP) Common Data Model. Data were from youth registered with incident diabetes (2006‐2012). Denominators were from census and membership data. We calculated diabetes incidence by averaging the total cases across the entire follow‐up period and dividing this by the estimated census population corresponding to the source population for case ascertainment. Incidence was calculated for each of the registries and compared by type and within age and sex categories using a 2‐sided, skew‐corrected inverted score test. Results Incidence of type 1 was higher in SEARCH (21.2 cases/100 000 [95% CI: 19.9, 22.5]) than YDR (4.9 cases/100 000 [95% CI: 4.3, 5.6]). Incidence of type 2 diabetes was also higher in SEARCH (5.9 cases/100 000 [95% CI: 5.3, 6.6] in SEARCH vs 0.5/cases/100 000 [95% CI: 0.3, 0.7] in YDR). The age distribution of incident type 1 diabetes cases was similar across registries, whereas type 2 diabetes incidence was higher at an earlier age in SEARCH. Sex differences existed in SEARCH only, with a higher rate of type 2 diabetes among females. Conclusion The incidence of youth‐onset type 1 and 2 diabetes was significantly different between registries. Additional data are needed to elucidate whether the differences observed represent diagnostic delay, differences in genetic susceptibility, or differences in distribution of risk factors.

The objective of this study was to compare tobacco smoke exposure in mothers and their healthy children less than 3 years old using hair cotinine (HC) levels as an objective long-term measure of exposure. Hair samples were obtained from mother/child pairs recruited from the Columbus Children's Hospital Primary Care Center, and were analyzed by radioimmunoassay to compare HC levels. Mothers were both self-reported smokers and nonsmokers. Contributing and confounding variables were assessed based on questionnaires completed by participants. Exclusion criteria for children were prematurity and presence of chronic cardiopulmonary disease. Hair samples and questionnaires were obtained from 104 mother/child pairs. Child and maternal HC levels were correlated for both self-reported maternal smokers (R2 = .13, p < .013) and self-reported maternal nonsmokers (R2 = .54, p < 001). Child HC levels were higher than maternal HC levels (1.18 ng/mg vs. .78 ng/mg, p < .001). Children of nonsmokers had higher HC levels than their mothers (.77 ng/mg vs. .35 ng/mg, p < .001), while HC levels of smokers and their children were no different (1.91 ng/mg vs. 1.92 ng/mg, p = .978). The relationship between child and maternal HC did not differ by child age, gender, or race. In conclusion, environmental tobacco smoke exposure in young children as reflected by HC is higher than expected based on prior studies of biomarkers and passive tobacco smoke exposure in adult nonsmokers.

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