Cross-sectional and Longitudinal Analyses of Factors Contributing to the Progressive Loss of the ß-cell Function in Type 2 Diabetes.

OBJECTIVE: Type 2 diabetes is a progressive disease characterized by insulin resistance and insulin secretory dysfunction. In this study, we assessed the factors contributing to an insulin secretory defect in type 2 diabetes patients. METHODS: The subjects consisted of 382 patients with type 2 diabetes, aged 57±13 years. We estimated the ß-cell function using 6-min post-glucagon increments in C-peptide (ΔCPR). RESULTS: A significant inverse correlation was observed between the time since the diagnosis of diabetes and ΔCPR. A simple liner regression analysis showed that ΔCPR decreases at a rate of 0.056 ng/mL/year. According to a multiple regression model, body mass index (BMI) and log (triglyceride) were positively correlated with ΔCPR. Time since the diagnosis of diabetes, diabetes in 1st degree relatives, the presence of diabetic retinopathy, and HbA1c were inversely correlated with ΔCPR. In 50 patients who underwent the glucagon stimulation test twice, the ΔCPR decreased from 2.27±1.47 to 1.72±1.08 ng/mL over a period of 6.5±0.9 years. A multiple regression analysis revealed the BMI and fasting plasma glucose level to be significant contributing factors to the decline in ΔCPR. CONCLUSION: The duration of diabetes, a low BMI, genetic factors, and the presence of microangiopathy may be associated with ß-cell dysfunction in diabetic patients. The observations in this study suggest that obese subjects showed a rapid decline in the ß-cell function despite an initial high CPR response. Environmental factors causing insulin resistance and glucotoxicity may therefore be involved in progressive ß-cell failure.

Prevalence and clinical characteristics of unremembered nocturnal eating in diabetic subjects: Kurume sleep trouble in obesity and metabolic disorders (KUSTOMED) study.

Nighttime food intake is associated with weight gain and higher HbA1c levels. We experienced night eaters who have no memory of their nocturnal eating in the morning. In this study, the curious night eating behavior was designated as "unremembered nocturnal eating syndrome (UNES)". We screened 1,169 patients with diabetes for sleep quality and abnormal eating behavior at night using the Pittsburgh Sleep Quality Index questionnaire with an additional question regarding UNES. When abnormal nocturnal eating behavior was noted, detailed clinical information was extracted from interviews with the patients. We identified 9 patients who experienced UNES. They had a higher BMI compared with subjects who reported no such episodes. Among them, 6 patients who consumed food at night without memory 2-5 times per month or more had significantly higher HbA1c levels. Continuous glucose monitoring in a patient with type 1 diabetes revealed an abrupt elevation of glucose levels from midnight when some foods were consumed. Eight of the 9 patients were taking benzodiazepine and/or non-benzodiazepine hypnotic agents when they experienced the episodes. The prevalence of UNES was 0.8% in all subjects and 4% in those taking hypnotic drugs. The ratio of hypnotic drug use in subjects with UNES was significantly higher than for individuals without UNES (89% vs. 17%, p<0.0001). Although UNES seems to be etiologically heterogeneous, hypnotics-induced parasomnia and/or anterograde amnesia may be associated with the behavior. UNES is not rare in diabetic patients on hypnotic medicine and may be a hidden cause of unexpected morning hyperglycemia.

Classification and characteristics of interferon-related diabetes mellitus in Japan.

AIM: The aim of this study was to assess the classification and clinical characteristics of interferon (IFN)-related diabetes. METHODS: Cases with IFN-related diabetes in Japan were retrieved through web search engines for medical literature until July in 2009, and unreported data were obtained from the authors by letter or e-mail. RESULTS: We collected 143 cases with IFN-related diabetes consisting of 104 type 1 diabetes including 4 own cases, and 39 non-autoimmune type 2-like diabetes. We found a marked increase in IFN-related type 1 diabetes for these 3 years. In contrast, no increase was observed in IFN-related type 2-like diabetes in the literature. Polyethylene glycol (PEG)-IFN and ribavirin had been more frequently used in patients with type 1 diabetes than in patients with type 2-like diabetes. The age of diabetes onset was comparable between type 1 and type 2-like diabetes, while the ratio of male patients was higher and the latency before diabetes was shorter in type 2-like diabetes. Patients with IFN-related type 1 diabetes had HLA types susceptible to Japanese type 1 diabetic patients, and a high positive rate of GAD antibodies. CONCLUSION: Potent combination therapy with PEG-IFN and ribavirin is likely associated with the increase in IFN-related type 1 diabetes. The combined measurement of GAD antibody and HLA-typing could be an effective strategy to predict the onset of type 1 diabetes associated with IFN therapy.

Distinct pharmacodynamics of insulin glargine and insulin detemir: crossover comparison in Type 1 and Type 2 diabetic patients on basal-bolus regimen.

We compared blood glucose profile when glargine or detemir was injected once daily before dinner in combination with pre-meal insulin lispro by a crossover design. Glargine showed lower post-dinner and bedtime glucose levels in Type 1 diabetes, and lower pre-dinner and post-dinner glucose levels in Type 2 diabetes than detemir.

Clinical characteristics of thyroid abnormalities induced by sunitinib treatment in Japanese patients with renal cell carcinoma.

Sunitinib is a multi-targeted tyrosine kinase inhibitor that is effective for advanced renal cell carcinoma. However, sunitinib often causes hypothyroidism. In this study, we report eight cases with thyroid dysfunction that occurred during sunitinib treatment for advanced renal cell carcinoma. In seven cases, mild hypothyroidism developed early in the first treatment cycle, and recovered spontaneously. Transient hyperthyroidism was observed during the second or third treatment cycles and was preceded by a rapid increase in thyroglobulin levels. (99m)Tc scintigraphy in the hyperthyroid state showed decreased thyroidal uptake of (99m)TcO(4)(-), suggesting destructive thyroiditis. Hypothyroidism subsequently developed, requiring levothyroxine replacement therapy. Ultrasonography showed a hypoechogenic pattern of the parenchyma and decreased intrathyroidal blood flow. The thyroid glands ultimately became atrophic, which may progress to permanent hypothyroidism. These findings suggest that sunitinib-induced hypothyroidism may occur frequently and may be a consequence of thyroiditis with transient thyrotoxicosis. The marked decrease in thyroid size due to reduced capillary blood flow induced by VEGF receptor inhibition may cause delayed and/or permanent hypothyroidism. Therefore, thyroid function should be monitored in all patients treated with sunitinib.