Background Type 2 diabetes is associated with cognitive dysfunction and increases the risk of dementia in the elderly. The aim of this study was to explore, by means of magnetic resonance (MR) imaging, possible relationships among clinical profiles of diabetes, cognitive function, white matter hyperintensities (WMHs) and subcortical brain atrophy.
These results suggest an association between chronic, life-threatening stress and the worsening of metabolic control in patients with diabetes mellitus.
Aim:To evaluate long-term, multiple risk factor intervention on physical, psychological and mental prognosis, and development of complications and cardiovascular disease in elderly type 2 diabetes patients.
Methods:Our randomized, controlled, multicenter, prospective intervention trial included 1173 elderly type 2 diabetes patients who were enrolled from 39 Japanese institutions and randomized to an intensive or conservative treatment group. Glycemic control, dyslipidemia, hypertension, obesity, diabetic complications and atherosclerotic disease were measured annually. Instrumental activity of daily living, cognitive impairment, depressive symptoms and diabetes burden were assessed at baseline and 3 years. Results: There was no significant difference in clinical or cognitive parameters at baseline between the two groups. The prevalence of low activities of daily living, depressive symptoms and cognitive impairment was 13%, 28% and 4%, respectively, and was similar in the two groups. A small, but significant difference in HbA1c between the two groups was observed at 1 year after the start of intervention (7.9% vs 8.1%, P < 0.05), although this significant difference was not observed after the second year. With the exception of coronary revascularization, there was no significant difference in fatal or non-fatal events between the two groups. Composite events were also similar in the two groups.Conclusions: This study showed no significant differences in fatal or non-fatal events between intensive and conventional treatment. The present study might clarify whether treatment of risk factors influences function and quality of life in elderly diabetic patients.
OBJECTIVE-Components of insulin/IGF-1 receptor-mediated signaling pathways in pancreatic -cells have been implicated in the development of diabetes, in part through the regulation of -cell mass in vivo. Studies in vitro have shown that the protein Ras homolog enriched in brain (Rheb) plays a key role as a positive upstream regulator of the mammalian target of rapamycin complex 1 (mTORC1) pathway in integrating inputs from nutrients and growth factors for cell growth. Our objective was to investigate the role of the mTORC1 pathway in the regulation of -cell mass in vivo.RESEARCH DESIGN AND METHODS-We generated transgenic mice that overexpress Rheb in -cells. We examined the activation of the mTORC1 pathway and its effects on -cell mass, on glucose metabolism, and on protection against hyperglycemia.RESULTS-Immunoblots of islet extracts revealed that the phosphorylation levels of ribosomal protein S6 and eukaryotic initiation factor 4E binding protein 1, downstream effectors for mTORC1, were upregulated in transgenic -cells. Immunostaining of the pancreatic sections with anti-phospho-S6 antibody confirmed upregulation of the mTORC1 pathway in -cells in vivo. The mice showed improved glucose tolerance with higher insulin secretion. This arose from increased -cell mass accompanied by increased cell size. The mice also exhibited resistance to hyperglycemia induced by streptozotocin and obesity.CONCLUSIONS-Activation of the mTORC1 pathway by Rheb led to increased -cell mass in this mouse model without producing obvious unfavorable effects, giving a potential approach for the treatment of -cell failure and diabetes. Diabetes
Background: Management of metabolic syndrome (MetS) seems to constitute an efficient strategy to attain successful ageing. Although the clinical entity of MetS in patients with diabetes mellitus has been discussed, there is very little information on MetS-type cardiometabolic risk factor clustering in diabetic elderly. Objective: To determine the relationship among age-associated changes in obesity, insulin resistance, and clustering of MetS-type risk factors, in association with vascular complications, in Japanese elderly with type 2 diabetes. Methods: A cross-sectional study was conducted of 812 diabetic elderly enrolled in the Japanese Elderly Diabetes Intervention Trial. Information on diabetes, blood examinations and complications was obtained. Abdominal obesity, insulin resistance and prevalence of MetS risk factor clustering, defined by three sets of criteria from the International Diabetes Federation (IDF), the Japanese Society of Internal Medicine (JSIM), and the American Heart Association and the National Heart, Lung, and Blood Institute (AHA/NHLBI), were analyzed. Results: Waist circumference and insulin resistance estimated by homeostasis model assessment insulin resistance (HOMA-IR) increased with age, followed by a partial decrease at age 80 and over. Prevalence of IDF-MetS and JSIM-MetS also increased with age at least until the age of 80, whereas the incidence of AHA/NHLBI-MetS did not show any apparent age changes. There was a significant crude linear association between waist circumference and HOMA-IR, which was highly elevated in IDF and AHA/NHLBI overlapping with MetS, and also elevated in AHA/NHLBI without abdominal obesity. Although IDF-MetS and JSIM-MetS, which specify abdominal obesity, did not always appear to be associated with cardiovascular diseases, AHA/NHLBI-MetS, comprising both abdominal obesity and non-abdominal obesity, independently correlated with coronary heart disease and stroke after adjustment for other risk factors of atherosclerotic diseases. Conclusion: There was an age-associated increase in the prevalence of abdominal obesity and insulin resistance in elderly diabetic Japanese subjects, with a clear relationship between waist circumference and insulin resistance. However, insulin resistance was elevated not only in cases with but also in those without abdominal obesity if accompanied by clustering of metabolic disorders. The AHA/NHLBI definition of MetS proved to be the most useful to predict cardiovascular disease in the diabetic elderly.
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