Delayed Gastric Emptying Is Associated With Early and Long-term Hyperglycemia in Type 1 Diabetes Mellitus.

BACKGROUND & AIMS: After the Diabetes Control and Complications Trial (DCCT), the Epidemiology of Diabetes Interventions and Complications (EDIC) study continued to show persistent benefit of prior intensive therapy on neuropathy, retinopathy, and nephropathy in type 1 diabetes mellitus (DM). The relationship between control of glycemia and gastric emptying (GE) is unclear. METHODS: We assessed GE with a (13)C-spirulina breath test and symptoms in 78 participants with type 1 diabetes at year 20 of EDIC. The relationship between delayed GE and glycated hemoglobin (HbA1c), complications of DM, and gastrointestinal symptoms were evaluated. RESULTS: GE was normal (37 participants; 50%), delayed (35 participants; 47%), or rapid (2 participants; 3%). The latest mean HbA1c was 7.7%. In univariate analyses, delayed GE was associated with greater DCCT baseline HbA1c and duration of DM before DCCT (P ≤ .04), greater mean HbA1c over an average of 27 years of follow-up evaluation (during DCCT-EDIC, P = .01), lower R-R variability during deep breathing (P = .03) and severe nephropathy (P = .05), and a greater composite upper gastrointestinal symptom score (P < .05). In multivariate models, retinopathy was the only complication of DM associated with delayed GE. Separately, DCCT baseline HbA1c (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.3) and duration of DM (OR, 1.2; 95% CI, 1.01-1.3) before DCCT entry and mean HbA1c during DCCT-EDIC (OR, 2.2; 95% CI, 1.04-4.5) were associated independently with delayed GE. CONCLUSIONS: In the DCCT/EDIC study, delayed GE was remarkably common and associated with gastrointestinal symptoms and with measures of early and long-term hyperglycemia. ClinicalTrials.gov numbers NCT00360815 and NCT00360893.

Determinants of successful glycemic control among participants in the BARI 2D trial: a post-hoc analysis.

OBJECTIVE: The BARI 2D trial compared insulin provision (IP) versus insulin sensitization (IS) for the primary outcome of total mortality in participants with T2DM and cardiovascular disease (CVD). In this analysis we examine baseline characteristics that are associated with successful long-term glycemic control. RESEARCH DESIGN AND METHODS: In a 2×2 factorial design, 2368 participants were randomized to either IP or IS therapy, and to either prompt revascularization with medical therapy or medical therapy alone. Successful long-term glycemic control (success) was defined by simultaneously meeting 1) a mean HbA1c level of <7.0% after each participant's third year of follow-up period, and 2) adherence with medications only from the assigned glycemic treatment arm during >80% of the BARI 2D follow-up. The association between baseline variables and success was determined using unadjusted and adjusted logistic regression models. RESULTS: 1917 participants (962 IP and 955 IS participants) had sufficiently long follow-up and data for this analysis. Among these IP and IS participants, 235 and 335 participants met both criteria of success, respectively (p<0.001). Those not on insulin at entry had higher odds of success (OR 2.25; CI 1.79-2.82) when treated with IS versus IP medications, irrespective of baseline HbA1c levels. Younger age, shorter duration of T2DM, and lower HbA1c at baseline were also each independently associated with higher success when treated with IS versus IP medications. CONCLUSION: Patients similar to those in the BARI 2D trial may have a higher chance of achieving success with IS versus IP medications if they are younger, have shorter duration of T2DM, have lower HbA1c levels, have moderate or strenuous physically activity, and are not on insulin. In contrast, increasing age, longer duration of T2DM, higher HbA1c, and insulin therapy are associated with increased chance of success if treated with IP medications.

Impact of glycemic control strategies on the progression of diabetic peripheral neuropathy in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Cohort.

OBJECTIVE: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial demonstrated similar long-term clinical effectiveness of insulin-sensitizing (IS) versus insulin-providing (IP) treatments for type 2 diabetes on cardiovascular outcomes in a cohort with documented coronary artery disease. We evaluated the effects of randomized glycemic control strategy (IS vs. IP) on the prevalence and incidence of diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS: DPN (defined as Michigan Neuropathy Screening Instrument [MNSI] clinical examination score>2) was assessed at baseline and yearly for 4 years. DPN prevalence and incidence were compared by intention-to-treat modeling by logistic generalized estimating equation models for prevalence and Kaplan-Meier estimates and Cox regression models for incidence rates. RESULTS: Results are reported for 2,159 BARI 2D participants (70% males) with valid baseline and at least one follow-up MNSI score (mean age 62±9 years, mean HbA1c 7.7±1.6%, diabetes duration 10±9 years). There were no differences in the prevalence of DPN between the IS and the IP groups throughout the 4 years of follow-up. In 1,075 BARI 2D participants with no DPN at baseline, the 4-year cumulative incidence rate of DPN was significantly lower in the IS (66%) than in the IP (72%) strategy group (P=0.02), which remained significant after adjusting for the in-trial HbA1c (P=0.04). In subgroup analyses, IS strategy had a greater benefit in men (hazard ratio 0.75 [99% CI 0.58-0.99], P<0.01). CONCLUSIONS: Among patients with type 2 diabetes followed for up to 4 years during BARI 2D, a glycemic control therapy with IS significantly reduced the incidence of DPN compared with IP therapy and may add further benefit for men.

Comparison of a novel insulin bolus-patch with pen/syringe injection to deliver mealtime insulin for efficacy, preference, and quality of life in adults with diabetes: a randomized, crossover, multicenter study.

OBJECTIVE: This study compared the efficacy, safety, device satisfaction, and quality of life (QOL) in people with diabetes using an insulin bolus-patch versus current devices (pen/syringe) to deliver mealtime insulin. RESEARCH DESIGN AND METHODS: Thirty-eight subjects with diabetes (26 with type 1 and 12 with type 2) were randomized to bolus-patch or current injection device (55% pen and 45% syringe) to deliver mealtime insulin in a multicenter, 6-week crossover study. Efficacy was assessed by equivalence in mean daily seven-point blood glucose (MDBG). Safety assessments included severe hypoglycemia episodes, adverse device effects (ADEs), and adverse events (AEs). Device satisfaction was determined by the validated Insulin Delivery System Rating Questionnaire (IDSRQ) and QOL by the validated Diabetes Specific QOL Scale (DSQOLS). RESULTS: Using bolus-patch, MDBG (mean±SE) was equivalent to that using pen/syringe (8.61±0.28 vs. 9.02±0.26 mmol/L; P=0.098). SD of the seven-point blood glucose measurements was lower using bolus-patch (3.18±0.18 vs. 3.63±0.17 mmol/L; P=0.004), as was the coefficient of variation (CV) (37.2±1.7 vs. 40.3±1.7%; P=0.046). Hemoglobin A1c, 1,5-anhydroglucitol, fructosamine, and insulin use were similar between groups. There were no severe hypoglycemia episodes or serious ADEs. Between-device AEs were comparable. Subjects scored better on six of seven subscales on the DSQOLS and five of six subscales on the IDSRQ while using bolus-patch versus pen/syringe. At study completion, 76% of subjects would choose to switch to bolus-patch (P=0.001). CONCLUSIONS: Delivery of mealtime insulin with bolus-patch compared with pen/syringe resulted in equivalent MDBG, lower SD and CV of seven-point blood glucose measurements, good safety, significant device satisfaction, and improved QOL.

Relation of chronic and acute glycemic control on mortality in acute myocardial infarction with diabetes mellitus.

Acute hyperglycemia during myocardial infarction predicts adverse short-term outcomes and mortality in diabetic patients. Conversely, chronic hyperglycemia is associated with an increased incidence of long-term cardiovascular complications, although its effect on acute hyperglycemic response and mortality after acute myocardial infarction is unknown. We investigated the prognostic relation of the glucose concentration at admission and the baseline average glycohemoglobin on acute myocardial infarction mortality. Of 808 consecutive diabetic patients with acute myocardial infarction, the most significant independent predictor of in-hospital mortality was the glucose concentration at admission. Baseline glycohemoglobin strongly correlated with admission hyperglycemia but did not predict mortality independently.

A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes.

OBJECTIVE: To assess the effect of mealtime amylin replacement with pramlintide on long-term glycemic and weight control in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: In a 52-week, double-blind, placebo-controlled, multicenter study, 480 patients with type 1 diabetes were randomized to receive preprandial injections of placebo or 30 microg pramlintide q.i.d., in addition to existing insulin regimens. At week 20, pramlintide-treated patients were re-randomized to 30 or 60 microg pramlintide q.i.d. if decreases from baseline in HbA(1c) were <1% at week 13. Of the 342 patients who completed the 52-week study, 236 individuals ( approximately 70%) elected to participate in a 1-year open-label extension in which all patients received 30 or 60 microg pramlintide q.i.d. RESULTS: Treatment with pramlintide led to a mean reduction in HbA(1c) of 0.67% from baseline to week 13 that was significantly (P < 0.0001) greater than the placebo reduction (0.16%), and a significant placebo-corrected treatment difference was sustained through week 52 (P = 0.0071). The greater HbA(1c) reduction was associated with an average weight loss, rather than weight gain, and was not accompanied by an increased overall event rate of severe hypoglycemia. In the open-label extension, mean HbA(1c) levels decreased rapidly in patients receiving pramlintide for the first time and remained at reduced levels in patients who continued pramlintide treatment. The most common adverse events reported by the pramlintide group were mild nausea and anorexia, which both occurred during the initial weeks of treatment and dissipated over time. CONCLUSIONS: Mealtime pramlintide treatment as an adjunct to insulin improved long-term glycemic control without inducing weight gain or increasing the overall risk of severe hypoglycemia in patients with type 1 diabetes.