Severe Insulin-resistant Diabetes due to Insulin Antibodies Associated with Eosinophilia.

A 66-year-old man with type 2 diabetes on hemodialysis treatment was admitted due to poor glycemic control. His serum insulin level and the (125)I-insulin binding rate were extremely high with an increased eosinophil count, although he did not have an allergic reaction to insulin or an elevation of specific IgE for human insulin. A Scatchard analysis revealed that the patient's insulin antibodies had a low affinity constant and a high binding capacity. Prednisolone administration decreased the eosinophil count and (125)I-insulin binding rate; accordingly, the glycemic control improved. Corticosteroid therapy may be a potent therapeutic strategy for insulin antibody-induced severe insulin resistance with eosinophilia.

Association of glycated albumin with the presence of carotid plaque in patients with type 2 diabetes.

AIMS/INTRODUCTION: Postprandial hyperglycemia is a potent risk factor for cardiovascular disease. Serum glycated albumin (GA) has been reported to reflect postprandial blood glucose fluctuations. In the present study, we assessed the possible correlation of GA with the presence of carotid plaque to evaluate the potential clinical usefulness of GA for predicting atherosclerotic cardiovascular complications in patients with type 2 diabetes. MATERIALS AND METHODS: Patients with type 2 diabetes (n = 236) admitted to Nippon Medical School Hospital (Tokyo, Japan) for glycemic control (aged 19-86 years, 81 females and 155 males) were examined. Clinical measurements were taken on admission. The presence of carotid plaque was assessed by ultrasonography. RESULTS: In patients with carotid plaque (n = 154), GA (P = 0.023) was higher than those without carotid plaque (n = 82). In contrast, neither fasting plasma glucose (P = 0.48) nor glycated hemoglobin (P = 0.41) was significantly different between the groups. The results of logistic regression analysis showed that GA (age- and sex-adjusted odds ratio [95% confidence interval], 1.05 [1.01-1.09]; P = 0.017) and glycated hemoglobin (1.17 [1.01-1.37]; P = 0.036) were significantly associated with the presence of carotid plaque. CONCLUSIONS: The positive correlation of serum GA with the presence of carotid plaque in type 2 diabetes suggests that GA will serve as a useful clinical marker for predicting diabetic cardiovascular complications.

Selective breeding of mice for different susceptibilities to high fat diet-induced glucose intolerance: Development of two novel mouse lines, Selectively bred Diet-induced Glucose intolerance-Prone and -Resistant.

UNLABELLED: Aims/Introduction: The development of type 2 diabetes is primarily due to lifestyle and environmental factors, as well as genetics, as shown by familial clustering. To establish mouse lines for evaluating heritable factors determining susceptibility to diet-induced diabetes, we performed selective breeding for differences in high fat diet (HFD)-induced glucose intolerance. MATERIALS AND METHODS: Selective breeding was performed using hybrid mice of C57BL/6J, C3H/HeJ and AKR/N backgrounds. After 5-week HFD feeding, mice showing high and low 2-h blood glucose levels in an oral glucose tolerance test (OGTT) were selected and bred over 14 generations to produce lines prone and resistant to diet-induced glucose intolerance (designated Selectively bred Diet-induced Glucose intolerance-Prone [SDG-P] and -Resistant [SDG-R]). RESULTS: At 5 weeks of age (pre HFD feeding), SDG-P mice showed higher blood glucose levels both in the OGTT and insulin tolerance test as compared to SDG-R mice. After receiving HFD, the glucose intolerance of SDG-P mice became more evident without hyper insulin secretion. In addition, SDG-P mice had greater body weight gain and lower HDL-cholesterol levels as compared to SDG-R mice. In comparison with C57BL/6J, a well-known strain prone to HFD-induced glucose intolerance, SDG-P mice showed significantly higher glucose levels in OGTT after the 5-week HFD feeding. CONCLUSIONS: Susceptibility to HFD-induced glucose intolerance was transmitted over generations and was intensified by selective breeding. The newly established mouse lines, SDG-P and SDG-R, may be useful in investigating the pathophysiology of type 2 diabetes through elucidating the crucial factors for determining the susceptibility to HFD-induced glucose intolerance. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00175.x, 2011).