Pulsatile intermittent intravenous insulin therapy for attenuation of retinopathy and nephropathy in type 1 diabetes mellitus.

Many hormones are secreted in a pulsatile fashion that is more efficient than continuous secretion when tested in vivo. A trial of multiple daily insulin doses with or without the addition of weekly pulsatile insulin infusion therapy was designed to determine if deterioration of renal and retinal function could be blunted. Sixty-five study subjects were evaluated prospectively in 7 centers. Thirty-six patients were randomly allocated to the infusion group and 29 to the standard therapy group. Mean serum creatinine was 1.6 mg/dL in both groups. Subjects were excluded if clearance was less than 30 mL/min. There were no significant differences between the groups with respect to age, duration of diabetes, sex distribution, glycohemoglobin, blood pressure, angiotensin-converting enzyme inhibitor use, proteinuria, or baseline diabetic retinopathy (DR) severity level (all eyes exhibited DR; 8 were deemed technically not amenable to evaluation). Progression of DR was noted in 31.6% of 57 patients (32.3% treated, 30.8% control; P = 1.0) with both eyes evaluable. For patients with 12 or more months of follow-up, 27.9% of 43 patients demonstrated progression of DR (32.0% treated, 22.2% control; P = .57). There were no significant differences between study groups with respect to progression or marked progression, nor was there any influence of duration of follow-up. Progression of DR was noted in 18.8% of 122 eyes that could be adequately evaluated (17.9% of 67 treated, 20% of 55 controls; P = .39). Serum creatinine increased to 1.7 mg/dL in the treatment group and to 1.9 mg/dL in the control group (P = .03). Statistically significant preservation of renal function by pulsatile insulin infusion was not matched by a statistically significant prevention of DR progression compared with standard diabetes care. Inadequate statistical power or duration of the study, or lack of further benefit of pulsatile insulin infusion on the retina in the presence of angiotensin-converting enzyme inhibition may be responsible.

Association between albuminuria and duration of diabetes and myocardial dysfunction and peripheral arterial disease among patients with stable coronary artery disease in the BARI 2D study.

OBJECTIVE: To evaluate the effect of prior duration of diabetes, glycated hemoglobin level at study entry, and microalbuminuria or macroalbuminuria on the extent and severity of coronary artery disease (CAD) and peripheral arterial disease. PATIENTS AND METHODS: We studied baseline characteristics of the 2368 participants of the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) study, a randomized clinical trial that evaluates treatment efficacy for patients with type 2 diabetes and angiographically documented stable CAD. Patients were enrolled from January 1, 2001, through March 31, 2005. Peripheral arterial disease was ascertained by an ankle-brachial index (ABI) of 0.9 or less, and extent of CAD was measured by presence of multivessel disease, a left ventricular ejection fraction (LVEF) of less than 50%, and myocardial jeopardy index. RESULTS: Duration of diabetes of 20 or more years was associated with increased risk of ABI of 0.9 or less (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.04-2.26), intermittent claudication (OR, 1.61; 95% CI, 1.10-2.35), and LVEF of less than 50% (OR, 2.03; 95% CI, 1.37-3.02). Microalbuminuria was associated with intermittent claudication (OR, 1.53; 95% CI, 1.16-2.02) and ABI of 0.9 or less (OR, 1.31; 95% CI, 0.98-1.75), whereas macroalbuminuria was associated with abnormal ABI, claudication, and LVEF of less than 50%. There was a significant association between diabetes duration and extent of CAD as manifested by number of coronary lesions, but no other significant associations were observed between duration of disease, glycated hemoglobin levels, or albumin-to-creatinine ratio and other manifestations of CAD. CONCLUSION: Duration of diabetes and microalbuminuria or macroalbuminuria are important predictors of severity of peripheral arterial disease and left ventricular dysfunction in a cohort of patients selected for the presence of CAD.

Efficacy and safety of ursodeoxycholic acid in primary, type IIa or IIb hypercholesterolemia: a multicenter, randomized, double-blind clinical trial.

BACKGROUND: Ursodeoxycholic acid (UDCA) is a therapeutic bile acid used in dissolution of gallstones and treatment of several cholestatic liver diseases. Results obtained from primary biliary cirrhosis patients treated with UDCA suggested that this agent exerts significant cholesterol-lowering effects and justifies evaluation in primary hypercholesterolemic patients without liver disease. Purpose of this study was to determine whether UDCA had potential to be an effective, safe cholesterol-lowering agent in primary type IIa or IIb hypercholesterolemia. METHODS: This was a multicenter randomized, double blind, placebo-controlled trial. After a 6-week placebo lead-in period during which two qualifying lipid profiles were obtained, patients with a mean serum LDL-cholesterol (LDL-C) between 130 and 190mg/dL, triglycerides <400mg/dL and HDL-cholesterol >30mg/dL were randomized to UDCA or matching placebo for 24 weeks. RESULTS: Seven sites screened 200 patients with 134 patients meeting the entry criteria who were randomized to the two treatments. There were 125 patients meeting the efficacy evaluation criteria, 57 on UDCA and 68 on placebo. LDL-C change from weeks 0 to 24 showed no significant difference between groups. No significant differences in changes for total cholesterol, HDL-cholesterol and triglycerides were observed. Both groups had similar adverse event profiles. CONCLUSIONS: UDCA did not show intrinsic cholesterol-lowering properties and therefore is not a useful therapy in treating type IIa or type IIb hypercholesterolemic patients. UDCA was confirmed as a well tolerated and safe drug in this population.