Rationale and protocol of a trial for prevention of diabetic atherosclerosis by using antiplatelet drugs: study of Diabetic Atherosclerosis Prevention by Cilostazol (DAPC study)

BACKGROUND: Secondary treatment of arteriosclerosis may be applicable for the primary prevention of atherosclerosis in diabetic patients. This prospective, 2-year follow-up study was designed to determine the efficacy and safety of antiplatelet therapy in the prevention of atherosclerosis of diabetic subjects. METHODS: Patients with type 2 diabetes and arteriosclerosis obliterans from the Eastern Asian countries were registered online and randomly assigned either to the aspirin group (81–100 mg/day) or the cilostazol group (100–200 mg/day) in this international, 2-year, prospective follow-up interventional study. RESULTS: The primary study endpoint was changes in right and left maximum intima-media thickness of the common carotid artery. Secondary endpoints include changes in right and left maximum intima-media thickness of the internal carotid artery; semiquantitative evaluation of cerebral infarction by magnetic resonance imaging; cardiovascular events including sudden death, stroke, transient cerebral ischemic attacks, acute myocardial infarction, angina, and progression of arteriosclerosis obliterans; overall death; withdrawal; and change in ankle-brachial pressure index. CONCLUSION: This is the first study to use an online system that was developed in Asian countries for pooling data from an international clinical trial. These findings are expected to help in the prevention of diabetic atherosclerosis and subsequent cardiovascular and cerebrovascular disease

Brachial-ankle pulse wave velocity and symptomatic cerebral infarction in patients with type 2 diabetes: a cross-sectional study

BACKGROUND: Recently a new automatic device that measures brachial-ankle pulse wave velocity using an oscillometric method has been developed. However, the practical significance of brachial-ankle pulse wave velocity measurement remains uncertain. The purpose of this study was to examine the association between brachial-ankle pulse wave velocity and symptomatic cerebral infarction in patients with type 2 diabetes. METHODS: One thousand sixty six patients with type 2 diabetes were studied cross-sectionally. Measurements of brachial-ankle pulse wave velocity were made using the automatic device. Logistic regression analysis was used to calculate the odds ratio for cerebral infarction. RESULTS: The presence of symptomatic cerebral infarction was confirmed in 86 patients. In these patients brachial-ankle pulse wave velocity was found to be significantly higher than in patients without cerebral infarction (18.94 ± 4.95 versus 16.46 ± 3.62 m/s, p < 0.01). The association between brachial-ankle pulse wave velocity and cerebral infarction remained significant after adjustment for traditional risk factors. There was an increasing odds ratio for each tertile of brachial-ankle pulse wave velocity, from the second tertile (odds ratio, 2.28; 95% confidence interval, 1.05 to 4.94), to the third (odds ratio, 2.53; 95% confidence interval, 1.09 to 5.86). CONCLUSION: Overall, we conclude that an increase in brachial-ankle pulse wave velocity is associated with symptomatic cerebral infarction in patients with type 2 diabetes

primary prevention of cardiovascular disease and type 2 diabetes in patients at metabolic risk an endocrine society clinical practice guideline

Objective: The objective was to develop clinical practice guidelines for the primary prevention of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) in patients at metabolic risk. Conclusions: Healthcare providers should incorporate into their practice concrete measures to reduce the risk of developing CVD and T2DM. These include the regular screening and identification of patients at metabolic risk (at higher risk for both CVD and T2DM) with measurement of blood pressure, waist circumference, fasting lipid profile, and fasting glucose. All patients identified as having metabolic risk should undergo 10-yr global risk assessment for either CVD or coronary heart disease. This scoring will determine the targets of therapy for reduction of apolipoprotein B-containing lipoproteins. Careful attention should be given to the treatment of elevated blood pressure to the targets outlined in this guideline. The prothrombotic state associated with metabolic risk should be treated with lifestyle modification measures and in appropriate individuals with low-dose aspirin prophylaxis. Patients with prediabetes (impaired glucose tolerance or impaired fasting glucose) should be screened at 1- to 2-yr intervals for the development of diabetes with either measurement of fasting plasma glucose or a 2-h oral glucose tolerance test. For the prevention of CVD and T2DM, we recommend that priority be given to lifestyle management.Thisincludesantiatherogenicdietarymodification,aprogramofincreasedphysicalactivity, andweightreduction.Effortstopromotelifestylemodificationshouldbeconsideredanimportant component of the medical management of patients to reduce the risk of both CVD and T2DM. (J Clin Endocrinol Metab 93: 3671–3689, 2008

Osteopontin Mediates Obesity-Induced Adipose Tissue Macrophage Infiltration and Insulin Resistance in Mice

Obesity is associated with a state of chronic, low-grade inflammation characterized by abnormal cytokine production and macrophage infiltration into adipose tissue, which may contribute to the development of insulin resistance. During immune responses, tissue infiltration by macrophages is dependent on the expression of osteopontin, an extracellular matrix protein and proinflammatory cytokine that promotes monocyte chemotaxis and cell motility. In the present study, we used a murine model of diet-induced obesity to examine the role of osteopontin in the accumulation of adipose tissue macrophages and the development of insulin resistance during obesity. Mice exposed to a high-fat diet exhibited increased plasma osteopontin levels, with elevated expression in macrophages recruited into adipose tissue. Obese mice lacking osteopontin displayed improved insulin sensitivity in the absence of an effect on diet-induced obesity, body composition, or energy expenditure. These mice further demonstrated decreased macrophage infiltration into adipose tissue, which may reflect both impaired macrophage motility and attenuated monocyte recruitment by stromal vascular cells. Finally, obese osteopontin-deficient mice exhibited decreased markers of inflammation, both in adipose tissue and systemically. Taken together, these results suggest that osteopontin may play a key role in linking obesity to the development of insulin resistance by promoting inflammation and the accumulation of macrophages in adipose tissue

Cardiovascular events in Japanese asymptomatic patients with type 2 diabetes: a 1-year interim report of a J-ACCESS 2 investigation using myocardial perfusion imaging

金沢大学医薬保健研究域医学系Purpose Diabetic patients have a high risk for cardiovascular events. The role of myocardial perfusion imaging was investigated in asymptomatic diabetic patients to evaluate short-term prognosis in a Japanese population. Methods A total of 506 asymptomatic patients ≥50 years of age who had carotid artery maximum intima-media thickness ≥1.1 mm, urinary albumin excretion of ≥30 mg/g creatinine, with additional criteria of abdominal obesity, low HDL cholesterol, high triglyceride level, and hypertension were enrolled and followed up over a 3-year period. Gated SPECT with stress-rest protocol was performed and analyzed by summed defect scores and QGS software. One-year cardiovascular events were analyzed. Results Myocardial ischemia was observed in 17% of patients, and abnormal perfusion findings of ischemia and/or scar were observed in 32% of patients. By the end of the 1-year follow-up, 33 (6.5%) cardiovascular events occurred including 6 all-cause deaths. Patients with summed stress score (SSS) >8 had a higher incidence of either death or cardiovascular events. Event-free survival rates for SSS 0–3, 4–8, 9–13, and ≥14 were 0.96, 0.95, 0.82, and 0.76, respectively. Multivariate Cox regression analysis showed that significant variables were SSS, history of cerebrovascular accident, and electrocardiographic abnormality at rest. Conclusion The 1-year interim summary showed that cardiovascular events were significantly higher in patients with SPECT abnormality, although hard cardiac event rate was relatively low. Targeted treatment strategy is required for asymptomatic but potentially high-risk diabetic patients

Association of New Loci Identified in European Genome-Wide Association Studies with Susceptibility to Type 2 Diabetes in the Japanese

Several novel susceptibility loci for type 2 diabetes have been identified through genome-wide association studies (GWAS) for type 2 diabetes or quantitative traits related to glucose metabolism in European populations. To investigate the association of the 13 new European GWAS-derived susceptibility loci with type 2 diabetes in the Japanese population, we conducted a replication study using 3 independent Japanese case-control studies. locus, had nominal association with type 2 diabetes in the present Japanese samples (P<0.05). locus may be common locus for type 2 diabetes across different ethnicities