The prevalence rates of NIDDM in this study population are the highest reported to date in a Canadian native population and among the highest reported in the world. Females appear to be at much higher risk of developing obesity, IGT, and NIDDM and at a younger age. Due to the high prevalence rates of IGT and NIDDM in this young population, there is urgent need to develop culturally appropriate community-based public health intervention programs before the long-term complications of diabetes have a devastating effect on the residents.

OBJECTIVEThe development of periarticular thickening of skin on the hands and limited joint mobility (cheiroarthropathy) is associated with diabetes and can lead to significant disability. The objective of this study was to describe the prevalence of cheiroarthropathy in the well-characterized Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort and examine associated risk factors, microvascular complications, and the effect of former DCCT therapy (intensive [INT] vs. conventional [CONV]) on its development.RESEARCH DESIGN AND METHODSThis cross-sectional analysis was performed in 1,217 participants (95% of the active cohort) in EDIC years 18/19 after an average of 24 years of follow-up. Cheiroarthropathy—defined as the presence of any one of the following: adhesive capsulitis, carpal tunnel syndrome, flexor tenosynovitis, Dupuytren's contracture, or a positive prayer sign—was assessed using a targeted medical history and standardized physical examination. A self-administered questionnaire (Disabilities of the Arm, Shoulder and Hand [DASH]) assessed functional disability.RESULTSCheiroarthropathy was present in 66% of subjects (64% of the INT group and 68% of the CONV group; P = 0.1640) and was associated with age, sex, diabetes duration, skin intrinsic fluorescence, HbA1c, neuropathy, and retinopathy (P < 0.005 for each). DASH functional disability scores were worse among subjects with cheiroarthropathy (P < 0.0001).CONCLUSIONSCheiroarthropathy is common in people with type 1 diabetes of long duration (∼30 years) and is related to longer duration and higher levels of glycemia. Clinicians should include cheiroarthropathy in their routine history and physical examination of patients with type 1 diabetes because it causes clinically significant functional disability.

OBJECTIVEGLP-1 receptor (GLP-1R) agonists induce natriuresis and reduce blood pressure (BP) through incompletely understood mechanisms. We examined the effects of acute and 21-day administration of liraglutide on plasma atrial natriuretic peptide (ANP), urinary sodium excretion, office and 24-h BP, and heart rate (HR). RESEARCH DESIGN AND METHODSLiraglutide or placebo was administered for 3 weeks to hypertensive subjects with type 2 diabetes in a double-blinded, randomized, placebo-controlled crossover clinical trial in the ambulatory setting. End points included within-subject change from baseline in plasma ANP, Nt-proBNP, office BP, and HR at baseline and over 4 h following a single dose of liraglutide (0.6 mg) and after 21 days of liraglutide (titrated to 1.8 mg) versus placebo administration. Simultaneous 24-h ambulatory BP and HR monitoring and 24-h urine collections were measured at baseline and following 21 days of treatment. RESULTSPlasma ANP levels did not change significantly after acute (+16.72 pg/mL, P = 0.24, 95% CI [212.1, +45.5] at 2 h) or chronic (217.42 pg/mL, 95% CI [236.0, +1.21] at 2 h) liraglutide administration. Liraglutide significantly increased 24-h and nighttime urinary sodium excretion; however, 24-h systolic BP was not significantly different. Small but significant increases in 24-h and nighttime diastolic BP and HR were observed with liraglutide. Body weight, HbA 1c , and cholesterol were lower, and office-measured HR was transiently increased (for up to 4 h) with liraglutide administration. CONCLUSIONSSustained liraglutide administration for 3 weeks increases urinary sodium excretion independent of changes in ANP or BP in overweight and obese hypertensive patients with type 2 diabetes.Patients with type 2 diabetes experience a greater than twofold excess risk for the development of cardiovascular disease (1,2), with coexistent hypertension further increasing the risk of cardiovascular complications (3). Even modest reductions in blood pressure (BP) reduce the risk of stroke and myocardial infarction (4).

Objective: To examine the persistence of the original treatment effects 10 years after the Diabetes Control and Complications Trial (DCCT) in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. In the DCCT, intensive therapy aimed at nearnormal glycemia reduced the risk of microvascular complications of type 1 diabetes mellitus compared with conventional therapy.Methods: Retinopathy was evaluated by fundus photography in 1211 subjects at EDIC year 10. Further 3-step progression on the Early Treatment Diabetic Retinopathy Study scale from DCCT closeout was the primary outcome.Results: After 10 years of EDIC follow-up, there was no significant difference in mean glycated hemoglobin levels (8.07% vs 7.98%) between the original treatment groups. Nevertheless, compared with the former conven-tional treatment group, the former intensive group had significantly lower incidences from DCCT close of further retinopathy progression and proliferative retinopathy or worse (hazard reductions, 53%-56%; PϽ.001). The risk (hazard) reductions at 10 years of EDIC were attenuated compared with the 70% to 71% over the first 4 years of EDIC (PϽ.001). The persistent beneficial effects of former intensive therapy were largely explained by the difference in glycated hemoglobin levels during DCCT. Conclusion:The persistent difference in diabetic retinopathy between former intensive and conventional therapy ("metabolic memory") continues for at least 10 years but may be waning.

OBJECTIVE-The Diabetes Control and ComplicationsTrial (DCCT) demonstrated the powerful impact of glycemic control on the early manifestations of microvascular complications. Contemporary prospective data on the evolution of macrovascular and late microvascular complications of type 1 diabetes are limited. The Epidemiology of Diabetes Interventions and Complications (EDIC) study is a multicenter, longitudinal, observational study designed to use the well-characterized DCCT cohort of >1,400 patients to determine the long-term effects of prior separation of glycemic levels on micro-and macrovascular outcomes.RESEARCH DESIGN AND METHODS-Using a standardized annual history and physical examination, 28 EDIC clinical centers that were DCCT clinics will follow the EDIC cohort for 10 years. Annual evaluation also includes resting electrocardiogram, Doppler ultrasound measurements of ankle/arm blood pressure, and screening for nephropathy. At regular intervals, a timed 4-h urine is collected, lipid profiles are obtained, and stereoscopic fundus photographs are taken. In addition, dual B-mode Doppler ultrasound scans of the common and internal carotid arteries will be performed at years 1 and 6 and at study end.RESULTS-Written informed consent was obtained from 96% of the DCCT subjects. The participants, compared with nonparticipants, tended to have better glycemic control at the completion of the DCCT and were more likely to have their diabetes care provided by DCCT personnel. The EDIC baseline measurement stratified by sex delineates multiple cardiovascular disease risk factor differences such as age (older in men), waist-to-hip ratio (higher in men), HDL cholesterol (lower in men), hypertension (more prevalent in men), and maximum intimal-medial thickness of common and internal carotid arteries (thicker in men). Of the original conventional treatment group, 69% have changed to continuous subcutaneous insulin infusion or multiple daily injections. Although the mean HbA 1c difference between the intensive and conventional treatment groups narrowed at EDIC years 1 and 2, HbA 1c remained significantly lower in the intensive group. Of all expected clinic visits, 95% were completed, and the quality of EDIC data is very similar to that observed in the DCCT.CONCLUSIONS-Although obvious problems exist in extended follow-up studies of completed clinical trials, these are balanced by the value of continued systematic observation of the DCCT cohort. In contrast to other epidemiologic studies, EDIC will provide 1) definitive data on type 1 as distinct from type 2 diabetes; 2) reliance on prospective rather than on cross-sectional analysis; 3) long-term follow-up in a large population; 4) consistent use of objective, reliable measures of outcomes and glycemia; and 5) observation of patients from before the onset of complications. [3][4][5]. While the reduction of the earlier stages of diabetic complications could reasonably be expected to slow the evolution to end-stage complications, such as loss of vision or renal failure...

OBJECTIVE -To evaluate glycemic control, hypoglycemic events, and quality of life in patients treated with continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injection (MDI), with insulin lispro as the principal insulin. RESEARCH DESIGN AND METHODS-This clinical trial enrolled 27 patients with type 1 diabetes. They were randomly assigned to CSII (n ϭ 13) or MDI (n ϭ 14) treatment regimens. Glycemic control (HbA 1c level) was the primary outcome and was measured monthly for 9 months. Secondary outcomes were patient reports of hypoglycemic events (recorded monthly for 9 months) and quality of life assessed at 9 months using the Diabetes Quality of Life (DQOL) questionnaire.RESULTS -A significant decrease in HbA 1c from baseline was shown for both groups. However, the overall treatment effect (CSII Ϫ MDI) for HbA 1c was ϩ0.08% (95% CI Ϫ0.23 to ϩ0.39, P Ͼ 0.10). This was significantly less than the a priori limit of Ϯ0.5% (P ϭ 0.004). The relative treatment effect ([CSII Ϫ MDI]/MDI) for the overall number of hypoglycemic events was ϩ9% (95% CI Ϫ37 to ϩ87, P Ͼ 0.10). There were no statistically significant differences between treatment groups for any of the DQOL subscales.CONCLUSIONS -No statistically significant differences in glycemic control, reported hypoglycemic events, or quality of life were found in this study. Furthermore, a clinically significant difference of more than Ϯ0.5% HbA 1c between the two regimens can be confidently ruled out. We conclude that the choice of intensive insulin therapy should be a matter of patient preference, consistent with lifestyle.

OBJECTIVETo determine whether skin intrinsic fluorescence (SIF) is associated with long-term complications of type 1 diabetes (T1D) and, if so, whether it is independent of chronic glycemic exposure and previous intensive therapy.RESEARCH DESIGN AND METHODSWe studied 1,185 (92%) of 1,289 active Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) participants from 2010 to 2011. SIF was determined using a fluorescence spectrometer and related cross-sectionally to recently determined measures of retinopathy (stereo fundus photography), cardiac autonomic neuropathy (CAN; R-R interval), confirmed clinical neuropathy, nephropathy (albumin excretion rate [AER]), and coronary artery calcification (CAC).RESULTSOverall, moderately strong associations were seen with all complications, before adjustment for mean HbA1c over time, which rendered these associations nonsignificant with the exception of sustained AER >30 mg/24 h and CAC, which were largely unaffected by adjustment. However, when examined within the former DCCT treatment group, associations were generally weaker in the intensive group and nonsignificant after adjustment, while in the conventional group, associations remained significant for CAN, sustained AER >30 mg/24 h, and CAC even after mean HbA1c adjustment.CONCLUSIONSSIF is associated with T1D complications in DCCT\EDIC. Much of this association appears to be related to historical glycemic exposure, particularly in the previously intensively treated participants, in whom adjustment for HbA1c eliminates statistical significance.

SIF reflects age, mean HbA1c over time, smoking, and renal damage, which are known risk factors for diabetes complications.