Importance of early insulin secretion: comparison of nateglinide and glyburide in previously diet-treated patients with type 2 diabetes.

OBJECTIVE: This study compared the effects of nateglinide, glyburide, and placebo on postmeal glucose excursions and insulin secretion in previously diet-treated patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This randomized, double-blind, placebo-controlled multicenter study was conducted in 152 patients who received either nateglinide (120 mg before three meals daily, n = 51), glyburide (5 mg q.d. titrated to 10 mg q.d. after 2 weeks, n = 50), or placebo (n = 51) for 8 weeks. Glucose, insulin, and C-peptide profiles during liquid meal challenges were measured at weeks 0 and 8. At weeks -1 and 7, 19-point daytime glucose and insulin profiles, comprising three solid meals, were measured. RESULTS: During the liquid-meal challenge, nateglinide reduced the incremental glucose area under the curve (AUC) more effectively than glyburide ( = -4.94 vs. -2.71 mmol. h/l, P < 0.05), whereas glyburide reduced fasting plasma glucose more effectively than nateglinide ( = -2.9 vs. -1.0 mmol/l, respectively, P < 0.001). In contrast, C-peptide induced by glyburide was greater than that induced by nateglinide ( = +1.83 vs. +0.95 nmol. h/l, P < 0.01), and only glyburide increased fasting insulin levels. During the solid meal challenges, nateglinide and glyburide elicited similar overall glucose control ( 12-h incremental AUC = -13.2 vs. -15.3 mmol. h/l), but the insulin AUC induced by nateglinide was significantly less than that induced by glyburide ( 12-h AUC = +866 vs. +1,702 pmol. h/l, P = 0.01). CONCLUSIONS: This study demonstrated that nateglinide selectively enhanced early insulin release and provided better mealtime glucose control with less total insulin exposure than glyburide.

Current trends in treating type 2 diabetes.

Recent advances in understanding the mechanisms of diabetes and its microvascular and macrovascular complications have mandated a much more aggressive approach to treatment. Parallel progress in developing new therapeutic agents has made that approach possible. Current recommendations underscore the importance of early management of prediabetic stages (such as impaired glucose tolerance), early diagnosis and early pharmacologic intervention, achievement of target plasma glucose levels, and use of a regimen designed for the individual patient.

Physical performance in persons with spinal cord injuries after discharge from rehabilitation.

PURPOSE: The purpose of this study was to investigate changes in physical capacity and performance of activities of daily living (ADL) during the postrehabilitation period of persons with spinal cord injuries and to determine the factors explaining the changes in physical capacity. METHODS: Nine subjects with tetraplegia and 11 subjects with paraplegia were measured at time of discharge from rehabilitation (t1) and on average 1.2 yr later (t2). Physical capacity was measured as maximal isometric strength (F(iso)), sprint power output (P30), maximal power output (POmax), and peak oxygen uptake (VO2peak). Physical strain and performance time were measured during standardized ADL (ascending ramp, passing door, making transfer, washing hands). RESULTS: P30 and POmax showed a significant increase at t2, whereas F(iso) and VO2peak remained unchanged. Sport activity was the most important independent variable explaining relative changes in P30 and POmax, showing on average larger values in active subjects. Other independent variables that were significantly related to changes in physical capacity were the occurrence of illness and having a tetraplegia (negatively associated with changes in P30 and VO2peak), and incompleteness of the lesion and an increased body mass (positively associated with changes in F(iso)). Increase in physical capacity was found to coincide with decrease of the physical strain and performance time of ADL, reflected in significant negative correlation coefficients for some tasks. CONCLUSIONS: It is concluded that physical capacity and performance of ADL improved or remained constant during the first year after rehabilitation and that sport participation is associated with improvements in physical capacity. Results of this study underline the importance of being physically active during the period after rehabilitation of persons with spinal cord injuries.

Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study.

OBJECTIVE: Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications. RESEARCH DESIGN AND METHODS: In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28-40 kg/m2, and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured. RESULTS: After 1 year of treatment, the orlistat group lost 6.2 +/- 0.45% (mean +/- SEM) of initial body weight vs. 4.3 +/- 0.49% in the placebo group (P < 0.001). Twice as many patients receiving orlistat (49 vs. 23%) lost > or = 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA1c (P < 0.001) and fasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P < 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients. CONCLUSIONS: Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile.

New oral agents for type II diabetes. Taking a more aggressive approach to therapy.

Status quo obviously is not optimal in the management of patients with non-insulin-dependent diabetes, given the fact that the average hemoglobin A1c value in this diabetic population is between 9% and 10%. There is an impetus, therefore, to move up the treatment ladder more quickly than at present. The availability of new oral hypoglycemic agents provides the potential for expanding the role of this category of agents and for improving overall glycemic control in these patients.