PurposeActivation of the innate immune system and chronic low-grade inflammation are thought to be involved in the pathogenesis of atherosclerosis and also thought to be associated with type 2 diabetes and its complications. As a receptor for bacterial lipopolysaccharide and heat-shock proteins, Toll-like receptor 4 (TLR4) is one of the central regulators of the immune response. Recent studies have reported an association between TLR4 polymorphisms and diabetes and its complications in Caucasian populations.Materials and MethodsIn this study, we analyzed the association between TLR4 gene polymorphisms in patients with features of type 2 diabetes and healthy controls in Korea. Two polymorphisms of the TLR4 gene (Asp299Gly and Thr399Ile) were examined in 225 diabetic patients and 153 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and single-strand conformation polymorphism (SSCP).ResultsNo Asp299Gly or Thr399Ile mutations were detected in any of the 378 subjects. Seven subjects from each group who had slightly different SSCP patterns were selected for sequencing, but we found no TLR4 polymorphisms on Exon3. The Asp299Gly and Thr399Ile TLR4 gene polymorphisms were absent in both groups, which was similar to the results for Japanese and Chinese Han subjects.ConclusionOur data and other Asian data suggest that a racial difference can be found in the frequency of the TLR4 polymorphism.

Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model.

Background:The aim of this study was to assess the psychological well-being and treatment satisfaction in patients with type 2 diabetes mellitus in a general hospital in Korea. Methods: This study included 440 type 2 diabetes patients above 20 years of age. Well-Being Questionnaire-12 (WBQ-12) and Diabetes Treatment Satisfaction Questionnaire were used to survey well-being and treatment satisfaction, respectively. WBQ-12 consists of 4 categories: negative well-being (NWB), energy (ENE), positive well-being (PWB), and general well-being (GWB). Results: There were significant associations between NWB scores and women, low education, low-income, and number of hospital admissions. Significant associations were also identified between ENE scores and men, higher education, insulin nonusers, high-income, compliance with recommended exercise, number of medications, satisfaction with treatment time, and poor glycemic control. PWB scores were significantly associated with high-income, satisfaction with waiting and treatment times, compliance with recommended diet and exercise, and number of medications. GWB scores were significantly associated with men, higher education, high-income, satisfaction with waiting and treatment times, compliance with recommended exercise, and number of medications. Treatment satisfaction was significantly associated with age, satisfaction with waiting and treatment times, compliance with recommended diet and exercise, and duration of diabetes.

Excessive production of cortisol by abnormal adrenocortical tissue causes clinical manifestations of Cushing' s syndrome and is associated with metabolic abnormalities including abdominal obesity, hyperglycemia, dyslipidemia, and hypertension, which increase the risk for type 2 diabetes mellitus as well as vascular morbidity and mortality. Removing the cause of hypercortisolism is initially required to resolve metabolic disorders in patients with adrenal Cushing' s syndrome. A 38-year-old woman with diabetes mellitus and hypertension, which were not well controlled by medications, complained of abdominal obesity, rounded face, thin limbs, and bruising. Based on clinical manifestations and laboratory findings, she was diagnosed with Cushing' s syndrome due to unilateral cortisol-producing adrenal adenoma. After left adrenalectomy, the patient' s blood glucose improved to a satisfactory level, and she rapidly discontinued insulin and oral glucose-lowering agent therapy. Her body mass index decreased to the normal range, and her other metabolic symptoms, dyslipidemia and hypertension, also improved significantly. She has maintained resolution of metabolic disorders and overweight for eight years since surgery without recurrence of Cushing' s syndrome.