Effects of Sitagliptin on Pancreatic Beta-Cells in Type 2 Diabetes With Sulfonylurea Treatment: A Prospective Randomized Study.

BACKGROUND: This prospective randomized, multicenter, open-label, comparative study was performed to analyze the effects of sitagliptin on glycemic control and maintenance of beta-cell function in patients with poorly controlled type 2 diabetes treated with low-dose glimepiride. METHODS: Forty-one patients with type 2 diabetes mellitus treated with low-dose glimepiride (≤ 2 mg/day) were prospectively enrolled in this study (age: 20 - 75 years; hemoglobin A1c (HbA1c): 7.4- 9.4%). The patients were randomized into two groups: the glimepiride (G) group, in which glimepiride dose was increased gradually to 6 mg/day, and the sitagliptin (S) group, in which sitagliptin was added at a dose of 50 mg/day. RESULTS: HbA1c level was significantly decreased after 24 weeks, but not 12 weeks, in the G group, while a significant decrease was seen after 12 weeks in the S group. Although there were no significant differences in HbA1c level at 24 weeks between the two groups (P = 0.057). The overall trend of changes in HbA1c level suggested that the glucose-lowering effects were superior in the S group. Furthermore, a significant change in fasting glucose was seen in the S group, but not in the G group. Glycemic control target was achieved in 36.7% and 16.7% patients in the S group and the G group, respectively. The proinsulin/insulin (P/I) ratio was significantly increased in the G group, whereas it tended to decrease in the S group. After 24 weeks of treatment, no significant difference was observed in the P/I ratio between the two groups, whereas a significant difference was noted in the ΔP/I (amount of change). Albuminuria tended to increase in the G group compared with the S group. CONCLUSION: The results of the present study suggested that sitagliptin effectively lowered hyperglycemia and that it may have a protective effect on pancreatic beta-cells when combined with a low dose of glimepiride. Therefore, sitagliptin may represent a useful combination therapy with low-dose sulfonylurea, not only for achieving glycemic control but also for protection of pancreatic beta-cells.

Administration of recombinant human growth hormone normalizes GH-IGF1 axis and improves malnutrition-related disorders in patients with anorexia nervosa.

High serum level of GH in the presence of low plasma level of insulin-like growth factor-I (IGF-I) is one of the endocrinological features of anorexia nervosa (AN). Whether the amount of endogenous GH is not enough to increase IGF-I is not certain. We studied the effect of recombinant human growth hormone (rhGH) on the GH-IGF-I axis and on malnutrition-related disorders in this syndrome. Twenty patients with AN were divided into two groups; one (N = 13) was given rhGH (0.33 mg/day), and the other (N = 7) was given placebo for 6 or 12 months, respectively. During each treatment, levels of serum GH, plasma IGF-I, serum thyroid hormones, serum cholesterol, fasting plasma glucose and cardiac function were monitored. Changes in body mass index (BMI) and calorie taken were also evaluated. Plasma IGF-I level increased from 74.4 +/- 41.9 to 269.0 +/- 31.2 microg/L (P<0.001) during administration of rhGH, which associated with a decrease in serum GH level from 17.0 +/- 15.0 to 1.6 +/- 0.8 microg/L (P<0.001). Administration of rhGH increased BMI, body temperature, fasting plasma glucose level, and food intake. Serum level of triiodothyronine, but not thyroxine, increased during treatment with rhGH. The treatment decreased serum levels of both total and HDL-cholesterol. Studies with echocardiography showed an increase in cardiac output during the treatment with rhGH. These improvements were not observed in patients treated with placebo. Administration of rhGH is recommended as one of the methods of managing the patients with AN.

Prospective analysis of mortality, morbidity, and risk factors in elderly diabetic subjects: Nagano study.

OBJECTIVE: To clarify mortality and morbidity of intensively managed elderly diabetic individuals and to explore factors predicting mortality and diabetes-related end points. RESEARCH DESIGN AND METHODS: A total of 390 elderly (>or=65 years of age) outpatients with type 2 diabetes ( 173 men and 217 women, mean age 73.0 years) were analyzed. The mean HbA(1c) upon entry was 6.8% (332 receiving oral hypoglycemics and/or insulin) and blood pressure upon entry was 136/74 mmHg (219 receiving antihypertensive drugs). The patients have been followed-up for 3 years with HbA(1c) <7.0% and blood pressure <145/80 mmHg as targets, with mortality and an aggregate of fatal and nonfatal diabetes-related events as end points. Mortality rate and causes of mortality, as well as risk factors for mortality and morbidity, were determined. RESULTS: The mortality rate, 2.9% per year, was comparable to that of the age- and sex-matched general population. Stroke was a leading cause of mortality after malignancy. By the univariate Cox proportional hazards model, only high serum creatinine and prior stroke were highly significant and strong risks for both end points. In those without prior stroke and receiving antihypertensive agents, the incidence of the diabetes-related end point based on their systolic blood pressure (SBP) quartile was U-shaped, with the nadir at the 3rd (SBP, 137-147 mmHg) and the peak at the 1st (SBP