Participant characteristics and study features associated with high retention rates in a longitudinal investigation of type 1 diabetes mellitus.

BACKGROUND: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study has sustained an extraordinarily high level of participant involvement for over two decades. PURPOSE: In order to identify specific characteristics of EDIC that contributed most strongly to retention, study-designed questionnaires were distributed to 1334 participants. METHODS: Confidential questionnaires were completed during EDIC Years 15-17. Participants were classified as Completely Adherent (completed all visits), Partly Adherent (missed >1 visit or major portion of a visit), or Inactive (did not participate for >5 years). Questionnaire items addressed specific aspects of clinic visits, evaluation procedures, staff-participant relationships, and medical/health-care support provided by EDIC. RESULTS: The most commonly cited reasons for continuing participation were Cutting Edge Tests to assess diabetes complications (79.3%), Annual Evaluations (67.7%), a desire to Help Others (65.2%), and Better Care for Diabetes (61.6%). Women chose Cutting Edge Tests as their first or second most important reason significantly more often than men, whereas men chose Better Care for Diabetes more frequently. Individuals with at least three diabetes-related complications were more likely than those with fewer complications to choose Annual Evaluations as their first or second reason for continued involvement. LIMITATIONS: The small proportion of individuals who discontinued participation restricted our ability to identify factors associated with suspended involvement. In addition, our analysis is limited to a cohort with type 1 diabetes followed in an observational study after an average participation time of 6.5 years in a randomized trial. CONCLUSIONS: The primary reasons identified by respondents for their long-term commitment are consistent with shorter-term studies and underscore the importance of expert medical care, supportive staff-participant relationships, and involvement with clinically and scientifically meaningful research.

Obesity impairs vascular relaxation in human subjects: hyperglycemia exaggerates adrenergic vasoconstriction arterial dysfunction in obesity and diabetes.

OBJECTIVES: Arterial dysfunction occurs in obesity and diabetes. However, there is uncertainty about the relative contribution of endothelial dysfunction, smooth muscle dysfunction, or adrenergic hyperresponsiveness. METHODS AND RESULTS: We examined forearm resistance vessel responses to intra-arterial vasoactive agents in matched subjects on no antihyperglycemic medications classified as (1) Type 2 diabetes, (2) impaired fasting glucose (IFG), (3) obese, and (4) nonobese. Responses to both acetylcholine and nitroprusside were impaired in obese, IFG, and diabetic subjects compared to nonobese. However, diabetic and IFG subjects had no further impairment than normoglycemic obese subjects. Gender-specific data revealed that obese, IFG, and diabetic males compared to nonobese males demonstrated impaired responses to nitroprusside. However, among females, obese, IFG, and diabetic subjects demonstrated impaired acetylcholine-mediated responses. Multivariate analyses revealed that gender and adiposity, but not glycemia, were strongly related to acetylcholine and nitroprusside responses. Vasoconstriction to norepinephrine was greater in subjects with diabetes and IFG compared to nondiabetic obese controls. CONCLUSIONS: Microvascular vasodilator function is impaired in obesity, with little further impairment in IFG and Type 2 diabetes. Females appear more sensitive to the deleterious effect of obesity on endothelium-mediated resistance vessel function, and males to smooth muscle-mediated function. There is a specific increase in adrenergic vasoconstrictor responses in IFG and Type 2 diabetes independent of obesity.

Leptin and body fat in type 2 diabetes and monodrug therapy.

To better understand the relations among leptin, insulin, and body fat during the metabolic progression to diabetes and during drug monotherapy, metabolic parameters were examined in subjects classified as 1) type 2 diabetes; 2) impaired fasting glucose or mild diabetes mellitus; 3) nondiabetic, matched for body mass index (BMI); and 4) nonobese, nondiabetic. Diabetic subjects were also studied during no pharmacological treatment, after 3 months of randomization to metformin or glyburide, and after 3 months of cross-over to the opposite drug. Log leptin correlated more with percent body fat (slope, 0.042; confidence interval, 0.036-0.047; r(2) = 0.826; P < 0.0001) than with total fat mass, percent truncal or nontruncal fat, or BMI. When normalized to percent fat, leptin did not differ by gender. Leptin normalized to percent fat was 35% less in untreated diabetes than that in BMI-matched controls (P < 0.001). Leptin normalized to percent fat was increased by 25% (P < 0.01) as a result of glyburide therapy compared with pretreatment values, but was unchanged by therapy with metformin. Across a spectrum of subjects with diabetes, impaired fasting glucose/mild diabetes, or BMI-matched nondiabetic controls, normalized leptin significantly correlated with glucose-induced insulin release, but not with insulin sensitivity. Our data suggest that plasma leptin is reduced in untreated type 2 diabetes probably as a consequence of reduced insulin secretion and that circulating leptin concentrations are differentially affected by monodrug therapy.

Antecedent caloric intake and glucose excursion following a subsequent meal in Type 1 diabetes.

BACKGROUND: In the present study, we tested the hypothesis that calories consumed at a prior meal (lunch) may impair glycemic control after a subsequent meal (supper) even if the pre-supper glucose did not differ regardless of the size of the lunch meal. METHODS: Nine subjects with Type 1 diabetes using continuous subcutaneous (s.c.) insulin infusion (CSII) therapy were studied on two separate days. Lunch (1200 h) was randomly assigned as 25% or 50% of the usual daily intake on alternate study days. The CSII was stopped at 1000 h on the day of the study and glucose was controlled until supper by adjusting the rate of intravenous (i.v.) insulin based on glucose measurements every 15 min. The CSII was restarted 1 h before supper and i.v. insulin discontinued 15 min before the first bite of supper. An identical supper meal and pre-supper s.c. bolus of short-acting insulin were administered on both visits. RESULTS: Pre-supper glycemia was nearly identical on each of the two study days. However, the post-supper glucose area under the curve was 27.5% greater on the day of the antecedent large lunch compared with the small lunch (P = 0.0039). CONCLUSIONS: For optimal postprandial glucose control, people with Type 1 diabetes may need to consider not only anticipated meal calories, but also prior food intake, a practice not commonly recommended based on currently used insulin dosing algorithms.