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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Background. Latent autoimmune diabetes in adults (LADA) is characterized by islet beta-cell loss and absolute insulin deficiency, however, studies in recent years have shown some extent of insulin resistance in LADA patients. In view of insulin resistance being the central pathogenesis of metabolic syndrome (MS), we hypothesized that MS could be found in LADA patients. Methods. A total of 60 glutamic acid decarboxylase antibody (GAD-Ab)-positive LADA patients and 120 patients with type 2 diabetes (T2DM) were enrolled for the study. MS and its components were diagnosed according to the working definitions proposed by World Health Organization and National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATP III]). Insulin resistance and high sensitive C reactive protein (hsCRP) levels were also evaluated in patients with or without MS. Serum insulin and hsCRP levels were determined with radioimmune and immunoturbidimetric assays, respectively. Results. MS was found in 50% of LADA patients by WHO criteria and in 40% by ATP III criteria. The proportions of MS and its metabolic components were all comparable between LADA and T2DM patients except that a lower proportion of hypertension was seen in LADA. LADA patients with MS had significantly higher HOMA-IR index (0.85 +/- 0.33 vs. 0.60 +/- 0.26, p = 0.001 for WHO criteria; 0.89 +/- 0.34 vs. 0.62 +/- 0.26, p = 0.000 for ATP III criteria) and hsCRP levels (0.86 vs. 0.41, p = 0.019 for WHO criteria; 0.96 vs. 0.66, p = 0.018 for ATP III criteria) than LADA without MS patients. Conclusions. Our findings indicate that MS does exist in LADA patients, suggesting that the a diagnosis of MS could not exclude one of LADA and that insulin sensitizers may be beneficial in therapeutic strategies for treating these conditions.
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PMID:Metabolic syndrome in adult-onset latent autoimmune diabetes. 1837 Jul 24

Inappropriate adaptation of beta-cell mass is a primary cause of the development of diabetic hyperglycemia. However, the mechanisms underlying regulation of the beta-cell mass in response to insulin resistance or in the development of type 2 diabetes remain unclear. We determined the insulin signaling in the beta-cells and the adaptation of the beta-cell mass in response to the progression of insulin resistance in OLETF rats. By 25 weeks of age, at the onset of diabetes, compared to control LETO rats, OLETF rats developed obesity (Body weight: LETO vs OLETF = 474.0+/-9.5 vs 581.3+/-21.8 g, P < 0.001, n=6), hyperlipidemia (Cholesterol: LETO vs OLETF = 1.67+/-0.07 vs 2.19+/-0.20 mM, P < 0.05, n=6; triglyceride: LETO vs OLETF = 0.36+/-0.05 vs 1.36+/-0.12 mM, P < 0.001, n=6), and impaired glucose tolerance (AUC: LETO vs OLETF = 10.3+/-3.4 vs 29.6+/-7.8 mM, P < 0.001, n=6). Insulin sensitivities as assessed by the insulin sensitivity index (ISI) and the homeostasis model assessment (HOMA) indicated that OLETF rats developed severe insulin resistance. The measurement of plasma insulin levels by ELISA demonstrated, at the onset of diabetes, that fasting insulin levels were increased by 1.2-fold, and 2 hr postprandial insulin levels were increased by 3-fold (P < 0.05, n=6) in OLETF rats compared to age-matched LETO mates which is suggestive of hyperinsulinemia. Immunostaining detected a significant reduction in the insulin receptor substrate 1 (IRS1) (by 54%, P < 0.001) and IRS2 (by 55%, P < 0.001) in the beta-cells of the OLETF rats. Interestingly, while the beta-cell mass was found to be increased (by 2.2-fold; P < 0.001), the beta-cell insulin content as determined by immunostaining was significantly reduced by 32% (P < 0.001) in the OLETF rats when compared to the controls. Our findings suggest that despite increasing beta-cell mass the impaired beta-cell insulin signaling and reduced beta-cell insulin content may contribute to the onset of overt diabetes in OLETF rats.
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PMID:Increased beta-cell apoptosis and impaired insulin signaling pathway contributes to the onset of diabetes in OLETF rats. 1845 52

The prevalence of the metabolic syndrome is rising, particularly in developed countries, and this is largely driven by increasing obesity and sedentarity rates. Regardless of the definition, the prevalence found in France was lower than in North America and in other European countries; it varied from 11.7 p. cent in men and 7.5 p. cent in women according to the National Cholesterol Education Program (NCEP) definition to 26 p. cent in men and 18.4 p. cent in women according to the International Diabetes Federation (IDF) definition. The presence of the metabolic syndrome promotes the occurrence of type 2 diabetes and clinical atherosclerosis. Relative risk of cardiovascular morbidity and mortality is close to 2 in subjects with metabolic syndrome. The informative value of identifying metabolic syndrome has been demonstrated in the general population as well as in hypertensive subjects. However, it could provide only limited clinical value for cardiovascular disease risk stratification in type 2 diabetes mellitus.
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PMID:[Metabolic syndrome: epidemiology and its risks]. 1846 92

We investigated the relationship between serum dehydroepiandrosterone-sulfate (DHEA-S) and insulin-like growth factor-I (IGF-I) to various parameters for atherosclerosis in type 2 diabetes. The levels of DHEA-S and IGF-I are known to decrease with aging and thereby might be associated with an increased risk of cardiovascular disease. One hundred forty-eight men and 106 postmenopausal women with type 2 diabetes were assessed in a cross-sectional study. Serum DHEA-S and IGF-I concentrations were measured and brachial-ankle pulse wave velocity (baPWV) and ultrasonographically-evaluated intima-media thickness (IMT) were assessed. Although simple regression analysis showed that log(DHEA-S) and IGF-I in men and log(DHEA-S) in women were significantly and inversely correlated with baPWV and IMT, only log(DHEA-S) in women was still significantly and inversely correlated with these atherosclerotic parameters after multiple regression analysis was adjusted for age, duration of diabetes, BMI, HbA(1C), systolic blood pressure, LDL-Cholesterol (C), serum creatinine, and smoking (Brinkman index). Serum DHEA-S level seemed to be associated with atherosclerosis in diabetic postmenopausal women independent of age, body stature, diabetic status, and other atherosclerotic risk factors, and might be a useful addition to other parameters for assessing the risk of atherosclerosis in this population.
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PMID:Serum DHEA-S level is associated with the presence of atherosclerosis in postmenopausal women with type 2 diabetes mellitus. 1849 2

Risk reduction in patients with clinically manifest vascular disease focuses on preventing new vascular events and not on prevention of type 2 diabetes. However, given the common pathophysiological pathways involved in the development of atherosclerosis and type 2 diabetes, it is probable that people with atherosclerotic vascular disease have an elevated risk of type 2 diabetes. The present prospective cohort study investigated the incidence of type 2 diabetes and the effect of the presence of metabolic syndrome on the incidence of type 2 diabetes in 4,022 patients with clinically manifest atherosclerosis, included in the study from September 1996 to June 2006. Patients who died (n=456), who were lost to follow-up (n=84) and those with diabetes at baseline (n=558) were excluded, leaving 2,924 patients for analysis. The incidence of diabetes was assessed by questionnaire (self-reported diabetes). During 13,726 person-years of follow-up (median follow-up 4.3 years, range 2.4-7.0 years), there were 152 type 2 diabetes cases (5.2%), corresponding to an incidence rate of 11.1 (95% CI 9.4-13.0) per 1,000 person-years. Patients with metabolic syndrome were at increased risk of incident type 2 diabetes compared to those without metabolic syndrome, with an adjusted hazard ratio of 5.7 (95% CI 3.7-8.9) for Revised National Cholesterol Education Program, 6.0 (4.1-9.0) for National Cholesterol Education Program and 4.0 (2.7-6.1) for International Diabetes Federation definitions of metabolic syndrome. Of all metabolic syndrome components, abdominal obesity was most strongly associated with incident type 2 diabetes (94% higher risk of type 2 diabetes for 1 standard deviation (11.3 cm) increase in waist circumference). In conclusion, patients with manifest atherosclerosis are at high risk of developing type 2 diabetes. Metabolic syndrome identifies those at the highest risk and is an easy to use clinical tool. Abdominal obesity is a strong individual predictor of type 2 diabetes. Patients with manifest atherosclerosis and metabolic syndrome may derive particular benefit from lifestyle interventions focusing on weight reduction.
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PMID:Metabolic syndrome and incidence of type 2 diabetes in patients with manifest vascular disease. 1853 99

After the symposium "Beyond Cholesterol: Prevention and Treatment of Coronary Heart Disease with n-3 Fatty Acids," faculty who presented at the conference submitted manuscripts relating to their conference topics, and these are presented in this supplement. The content of these manuscripts was reviewed, and 2 conference calls were convened. The objective was to summarize existing evidence, gaps in evidence, and future research needed to strengthen recommendations for specific intakes of n-3 fatty acids for different conditions relating to cardiovascular disease. The following 2 questions were the main items discussed. What are the roles of n-3 fatty acids in primary versus secondary prevention of coronary heart disease? What are the roles of n-3 fatty acids in hypertriglyceridemia, in the metabolic syndrome and type 2 diabetes, and in sudden cardiac death, cardiac arrhythmias, and vulnerable plaque? Each area was summarized by using 2 general categories: 1) current knowledge for which general consensus exists, and 2) recommendations for research and policy. Additional references for these conclusions can be found in the articles included in the supplement.
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PMID:Conclusions and recommendations from the symposium, Beyond Cholesterol: Prevention and Treatment of Coronary Heart Disease with n-3 Fatty Acids. 1854 3

Insulin secretion from pancreatic beta-cells is mediated by the opening of voltage-gated Ca2+ channels (CaV) and exocytosis of insulin dense core vesicles facilitated by the secretory soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein machinery. We previously observed that beta-cell exocytosis is sensitive to the acute removal of membrane cholesterol. However, less is known about the chronic changes in endogenous cholesterol and its biosynthesis in regulating beta-cell stimulus-secretion coupling. We examined the effects of inhibiting endogenous beta-cell cholesterol biosynthesis by using the squalene epoxidase inhibitor, NB598. The expression of squalene epoxidase in primary and clonal beta-cells was confirmed by RT-PCR. Cholesterol reduction of 36-52% was observed in MIN6 cells, mouse and human pancreatic islets after a 48-h incubation with 10 mum NB598. A similar reduction in cholesterol was observed in the subcellular compartments of MIN6 cells. We found NB598 significantly inhibited both basal and glucose-stimulated insulin secretion from mouse pancreatic islets. CaV channels were markedly inhibited by NB598. Rapid photolytic release of intracellular caged Ca2+ and simultaneous measurements of the changes in membrane capacitance revealed that NB598 also inhibited exocytosis independently from CaV channels. These effects were reversed by cholesterol repletion. Our results indicate that endogenous cholesterol in pancreatic beta-cells plays a critical role in regulating insulin secretion. Moreover, chronic inhibition of cholesterol biosynthesis regulates the functional activity of CaV channels and insulin secretory granule mobilization and membrane fusion. Dysregulation of cellular cholesterol may cause impairment of beta-cell function, a possible pathogenesis leading to the development of type 2 diabetes.
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PMID:Inhibition of cholesterol biosynthesis impairs insulin secretion and voltage-gated calcium channel function in pancreatic beta-cells. 1859 49

Cellular cholesterol efflux is regulated by cholesterol transporters including adenosine triphosphate-binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor class B type I (SR-BI). We have investigated whether the expression of these transporters is affected by type 2 diabetes mellitus and the association with glycemic indexes and oxidized low-density lipoprotein (oxLDL). Messenger RNA of ABCA1, ABCG1, and SR-BI in peripheral monocytes was measured in 30 diabetic patients and 30 matched controls. Plasma oxLDL and advanced glycation end products (AGEs) were assayed by enzyme-linked immunosorbent assay. Cellular cholesterol efflux from monocytes to serum was determined in a subgroup chosen randomly. The expression of ABCG1 was decreased in diabetic patients (P < .05), whereas the levels of ABCA1 and SR-BI were comparable between the 2 groups. Fasting glucose, hemoglobin A(1c), AGEs, and oxLDL were all significantly increased in diabetic patients. There was an inverse correlation between serum AGEs and ABCG1 (r = -0.44, P < .05) that remained significant after adjusting for potential confounding factors. No associations between fasting glucose, hemoglobin A(1c), plasma lipids, or oxLDL and the expression of ABCG1, ABCA1, or SR-BI were found. Cholesterol efflux from monocytes to standard serum or autologous serum was significantly impaired in diabetic patients, and the reduction in efflux to autologous serum correlated with the expression of ABCG1 (r = 0.60, P < .05). The expression of ABCG1 in monocytes is reduced in type 2 diabetes mellitus and is partly related to serum AGEs concentration. The reduction in ABCG1 is associated with impairment in cholesterol efflux and may contribute to accelerated foam cell formation in diabetic patients.
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PMID:Determinants of leukocyte adenosine triphosphate-binding cassette transporter G1 gene expression in type 2 diabetes mellitus. 1864 Mar 93

The term metabolic syndrome (MS) refers to a clustering of risk factors of metabolic origin that promote the development of cardiovascular disease and type 2 diabetes. Metabolic syndrome includes such pathological factors as insulin resistance, hyperinsulinemia, abdominal obesity, impaired glucose tolerance, type 2 diabetes, microalbuminuria, high level of triglycerides, low level of HDL cholesterol, elevated blood pressure, and proinflammatory and prothrombotic state. Several organizations have recommended clinical criteria for the diagnosis of metabolic syndrome. The most widely accepted were the worked out by the World Health Organization (WHO), the European Group for the Study of Insulin Resistance (EGIR), and the National Cholesterol Education Program--Third Adult Treatment Panel (NCEP-ATP III). In 2005, IDF experts proposed a universally accepted diagnostic tool that is easy to use in clinical practice and does not rely on measurements available only in research settings. All groups agreed on the core components of the metabolic syndrome: obesity, insulin resistance, dyslipidemia, and hypertension. Their criteria are similar in many aspects, but they also reveal fundamental differences in their positioning of the predominant causes of the syndrome. This study provides a brief overview of current definitions of metabolic syndrome, with particular reference to the differences between them, and presents critical remarks on the concept of metabolic syndrome and its usefulness. It also presents epidemiological data which consider metabolic syndrome and its association with increased risk of cardiovascular disease and type 2 diabetes.
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PMID:[The metabolic syndrome. Part I: definitions and diagnostic criteria for its identification. Epidemiology and relationship with cardiovascular and type 2 diabetes risk]. 1893 29

Excess glycated hemoglobin (HbA(1c)), an indicator of long-term glucose homeostasis, is recognized as a risk factor for cardiovascular (CV) disease and mortality even among persons without diabetes. However, information is scant regarding its distribution and correlates of CV risk in nondiabetic younger adults. This aspect was examined in a biracial (black-white) community-based sample of 1111 younger adults (mean age: 36.2 years; 71% white, 43% male) enrolled in the Bogalusa Heart Study. Blacks vs whites and women vs men had higher HbA(1c) values (P < .0001). In bivariate analysis adjusted for age, race, sex, and smoking status, significant adverse trends were noted for body mass index, waist circumference, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), total cholesterol to HDL-C ratio, insulin, glucose, and homeostasis model assessment of insulin resistance across HbA(1c) quartiles; trends were not significant for mean arterial blood pressure, triglycerides, C-reactive protein, adiponectin, and estimated glomerular filtration rate. In multivariate analysis, besides race and sex, total cholesterol to HDL-C ratio and waist circumference were independent correlates of HbA(1c). Furthermore, the prevalence of excess (top decile) HbA(1c) was 1.6-fold (P < .05) higher among those with metabolic syndrome defined by the National Cholesterol Education Program Adult Treatment Panel III and 2.1-fold (P < .01) and 1.5-fold (P < .05) higher, respectively, among those with positive parental history of CV disease and type 2 diabetes mellitus. These findings underscore the potential value of HbA(1c) in risk assessments of CV disease and type 2 diabetes mellitus in nondiabetic, apparently "healthy" younger adults.
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PMID:Distribution and cardiovascular risk correlates of hemoglobin A(1c) in nondiabetic younger adults: the Bogalusa Heart Study. 1894 Mar 83


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