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

Steatosis has emerged as a histologic finding of importance to the progression of hepatitis C virus (HCV)-associated liver disease. However, most studies of HCV-associated steatosis have excluded alcohol drinkers and individuals with diabetes and thus have not addressed the relative contribution of known causes of steatosis to liver injury in HCV-associated disease. To address this issue, we studied 297 consecutive patients with HCV who met inclusion criteria. Alcohol consumption, demographics, and serologic tests were correlated with degrees of steatosis and fibrosis on liver biopsy. Liver biopsy specimens were also examined for evidence of significant alcohol or nonalcoholic steatohepatitis (NASH) injury. In univariate analysis, steatosis correlated with type 2 diabetes mellitus (P =.005) and body mass index (BMI) (P =.0001) but not with the intensity of alcohol intake (in grams per day). In multivariate analysis, BMI (P =.0002) and genotype 3a infection (P =.02) were independent predictors of steatosis. When patients with risk factors for NASH were excluded, genotype 3a infection was the only independent predictor of steatosis. Steatosis (P =.04) and inflammation (P <.0001) scores on liver biopsy were the only independent predictors of fibrosis. Significant alcohol or NASH injury was found in only 6% of biopsy specimens. In conclusion, steatosis in HCV infection is associated with risk factors for NASH, particularly obesity, rather than alcohol consumption.
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PMID:Steatosis in chronic hepatitis C: relative contributions of obesity, diabetes mellitus, and alcohol. 1219 67

High-fat diet and intrauterine growth retardation may predispose to obesity, insulin resistance, and type 2 diabetes. Because prenatal ethanol (ETOH) exposure causes intrauterine growth retardation, we investigated its interactions with postnatal high-fat diet on glucose tolerance and adipocyte-derived hormones in the rat offspring. High-fat-fed offspring had increased adiposity, serum leptin, and muscle uncoupling protein-3, but decreased adiponectin mRNA, compared with corresponding chow-fed groups. ETOH-exposed offspring had normal adiponectin, but increased resistin mRNA and protein, compared with controls, regardless of postnatal diet. Skeletal muscle glucose transporter-4 content was decreased after both ETOH exposure and high-fat feeding. Glycemic and insulin responses to an ip glucose challenge were equally increased in non-ETOH-exposed high-fat-fed offspring and in ETOH-exposed chow-fed offspring, with additive effects of ETOH and high-fat diet. Pancreatic insulin content was elevated only in non-ETOH-exposed high-fat-fed offspring. The data suggest that high-fat diet worsens glucose intolerance in offspring of rats exposed to ETOH. Prenatal ETOH exposure and postnatal high-fat diet might cause insulin resistance through separate mechanisms, involving resistin and adiponectin, respectively.
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PMID:Glucose intolerance and resistin expression in rat offspring exposed to ethanol in utero: modulation by postnatal high-fat diet. 1253 10

The goal of this study was to explore the relationship between alcohol intake and glycemia and type 2 diabetes in American Indians aged 45 to 74 years. Data were obtained from participants in the Strong Heart Study, a longitudinal study of 13 American Indian communities in 3 geographic areas in the United States. Alcohol consumption was determined by self-reported alcohol intake history. Participants previously diagnosed with diabetes were excluded from the analysis. Analysis of covariance (ANCOVA) was used to estimate the adjusted means of blood glucose for alcohol intake categories. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the association between alcohol intake and type 2 diabetes in the cross-sectional analysis and between alcohol intake and glucose intolerance using longitudinal data. Fasting and 2-hour plasma glucose concentrations showed an inverse J-shaped curve across categories of alcohol intake. Using never drinkers as the referent group in cross-sectional analysis, light drinkers had a significantly lower risk of having diabetes (OR, 0.66; 95% CI, 0.44 to 0.99); among drinkers, heavy drinkers had a higher, although not significant, prevalence of diabetes. Longitudinal analysis showed no significant worsening of glucose tolerance across levels of alcohol intake. Subanalyses stratified by body mass index (BMI) did not show differences between obese and non-obese participants in the relationship between alcohol intake and glucose tolerance. Although plasma glucose concentration showed a shallow, inverse J-shaped association across levels of increasing alcohol intake in American Indians aged 45 to 74 years, alcohol intake did not appear to significantly increase the risk for worsening glucose tolerance. Thus, alcohol intake does not appear to be a determinant of diabetes risk in this population.
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PMID:Alcohol intake and glycemia in American Indians: the strong heart study. 1260 20

The epidemiologic evidence on the association between moderate alcohol intake and risk of coronary heart disease (CHD), biological mechanisms for this association, and potential hazards of alcohol intake in individuals with type 2 diabetes is reviewed here. Three prospective cohort studies have examined the association between alcohol consumption and risk of CHD among diabetics. The results indicated significant risk reductions, ranging from 34% to 79%, associated with light to moderate alcohol intake. Potential mechanisms include increased high-density lipoprotein cholesterol, decreased coagulation, and enhanced insulin sensitivity. Alcohol intake is also associated with certain risks among diabetics. However, for moderate alcohol consumption, the benefits would likely outweigh the risks.
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PMID:Alcohol consumption and risk of coronary heart disease among individuals with type 2 diabetes. 1264 15

Low birth weight in humans predisposes to obesity, cardiovascular diseases, and type 2 diabetes in adult life. Alcohol exposure during pregnancy has been associated with fetal growth restriction. We investigated the effects of prenatal exposure to alcohol on glucose metabolism later in the offspring. Female Sprague Dawley rats were given ethanol (ETOH), 4 g/kg/day by gavage throughout pregnancy. Compared with controls, newborn ETOH rats had decreased body size (5.1 +/- 0.1 v 6.3 +/- 0.1 g, P <.001), plasma insulin (0.44 +/- 0.4 v 0.67 +/- 0.1 ng/mL, P <.05), and leptin mRNA (P <.05), but they had normal beta-cell mass and elevated adipose resistin mRNA and plasma glucose (5.0 +/- 0.5 v 3.6 +/- 0.3 mmol/L, P <.01). Food intake was decreased in ETOH rats during the fourth week of life, and body weight remained decreased compared with controls until a catch-up growth occurred by 7 weeks of life. At 13 weeks of age, body weight and beta-cell mass of ETOH offspring were normal, but plasma glucose and insulin after a glucose challenge were increased compared with controls (P <.05). Adipose leptin and hypothalamic Ob-R mRNA were not different from controls, but resistin was increased (P <.05), and muscle GLUT4 content was decreased (P <.05) in ETOH offspring compared with controls. The data suggest that prenatal alcohol exposure impairs glucose tolerance in the offspring by both inducing insulin resistance and beta-cell dysfunction. The prevailing mechanism in 3-month-old rat offspring appears to be insulin resistance, manifested by glucose intolerance and decreased GLUT4 despite hyperinsulinemia.
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PMID:Effects of prenatal alcohol exposure on glucose tolerance in the rat offspring. 1270 Oct 58

Insulin resistance and hyperinsulinemia are the critical characteristics of the metabolic syndrome that is associated with abdominal obesity and are the early manifestations of its progression to type 2 diabetes. These metabolic abnormalities are becoming recognized as a major contributor to cardiovascular disease. The experimental studies required to elucidate the underlying mechanisms and to develop effective preventative strategies will require the use of appropriate animal models and these are available. The evidence from such research indicates that a wide range of interventions (including peroxisome proliferator activator receptor agonists, insulin-sensitizing agents, statins, fibrates, angiotensin-converting enzyme inhibitors, estrogen receptor modulators, lipid-based nutriceuticals, and ethanol) can markedly reduce or prevent vasculopathy and ischemic cardiac lesions in animal models. Overall, the results suggest that early damage to the vascular wall, both in function and presenting as atherosclerotic lesions, is secondary to long-term hyperinsulinemia and, especially, to postprandial peaks in plasma insulin levels, and is exacerbated by the accompanying hyperlipidemia. Effective treatment will, of necessity, be preventative and will necessitate diagnostic approaches that can identify asymptomatic individuals at high risk for vascular damage and eventual progression to type 2 diabetes. Therapeutic targets in this population include insulin sensitivity and the associated signal transduction pathways, the peroxisome proliferator activator receptor-alpha and -gamma systems, and the complex pathways leading from acetyl CoA and the citric acid cycle to the synthesis of fatty acid and the storage of triglyceride. These pharmacological approaches offer the prospect of preventing a significant proportion of cardiovascular disease.
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PMID:Reduction and prevention of the cardiovascular sequelae of the insulin resistance syndrome. 1276 60

The metabolic syndrome, including type 2 diabetes, insulin resistance, obesity/abdominal obesity, hypertension and dyslipidemia, is a major public health problem. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands such as thiazolidinediones are effective against this syndrome. In this study, we showed that nonaqueous fractions of licorice (Glycyrrhiza uralensis Fisher) extracted with ethanol, ethyl acetate and acetone, but not an aqueous extract, had PPAR-gamma ligand-binding activity with a GAL4-PPAR-gamma chimera assay. Some prenylflavonoids including glycycoumarin, glycyrin, dehydroglyasperin C and dehydroglyasperin D, a newly found compound, were identified as active compounds with PPAR-gamma ligand-binding activity in the nonaqueous fraction of licorice. A licorice ethanolic extract contained these four active compounds at a total concentration of 16.7 g/100 g extract. Feeding the licorice ethanolic extract at 0.1-0.3 g/100 g diet [approximately 100 to 300 mg/(kg body x d)] for 4 wk decreased (P < 0.05) blood glucose level in younger (6 wk old) and older (13 wk old) diabetic KK-Ay mice and reduced (P < 0.05) weights of intra-abdominal adipose tissues in high fat diet-induced obese C57BL mice. An increase in blood pressure in spontaneously hypertensive rats was suppressed (P < 0.01) by 3 wk of oral administration of the licorice ethanolic extract at 300 mg/(kg body x d). These findings indicate that licorice ethanolic extract is effective in preventing and ameliorating diabetes, ameliorating abdominal obesity and preventing hypertension, and suggest that licorice ethanolic extract would be effective in preventing and/or ameliorating the metabolic syndrome.
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PMID:A licorice ethanolic extract with peroxisome proliferator-activated receptor-gamma ligand-binding activity affects diabetes in KK-Ay mice, abdominal obesity in diet-induced obese C57BL mice and hypertension in spontaneously hypertensive rats. 1460 46

Plasma levels of high-density lipoprotein-cholesterol (HDL-C) are a powerful independent cardiovascular risk factor, bearing an inverse relationship with atherosclerotic cardiovascular disease (with risk rising sharply when levels are <1.04 mmol/L). Apart from its protective role in atherosclerosis, HDL-C increases fibrinolysis, is an antioxidant to low density lipoprotein-cholesterol (LDL-C), and decreases platelet aggregability. Up to a third of patients with atherosclerotic cardiovascular disease have 'desirable' plasma levels of total cholesterol but low HDL-C levels. Benefits of treating low plasma HDL-C levels were clearly demonstrated in the Veterans Affairs HDL Intervention Trial (VA-HIT) where gemfibrozil reduced nonfatal infarcts and coronary deaths by 22%. This was achieved by a 6% increase in plasma HDL-C levels, and a 24.5% decrease in plasma levels of triglycerides, without any significant decrease in LDL-C levels. Multivariate analyses revealed the rise in plasma HDL-C levels after treatment, but not decreases in plasma levels of triglycerides or LDL-C, predicted coronary artery disease events. The typical patient under consideration in this article is one with plasma levels of HDL-C <1 mmol/L, LDL-C <3.37 mmol/L [either receiving therapeutic lifestyle changes or or LDL-C-lowering therapy comprising a hydroxymethylglutaryl coenzyme-A (HMG-CoA) reductase inhibitor or bile acid sequestrant] and fasting triglycerides <2.26 mmol/L. We propose this dyslipidemia be classified as Type VI phenotype following the Frederickson and Lees classification. High-risk patients (with >/=2 risk factors for atherosclerotic cardiovascular disease, or 10-year cardiovascular risk >20%), patients with established atherosclerotic cardiovascular disease, or type 2 diabetes mellitus, or metabolic syndrome should receive pharmacotherapy. Plasma HDL-C levels >1.16 mmol/L may be considered optimal and between 1 and 1.16 mmol/L as desirable. Fibric acid derivatives, nicotinic acid, HMG-CoA reductase inhibitors, estrogens, and ethanol (not recommended as therapy) increase plasma HDL-C levels. Nicotinic acid is the most potent agent and recent reports indicate that, in contrast to gemfibrozil, it selectively increases antiatherogenic HDL subfraction, lipoprotein (Lp) AI (without apolipoprotein AII), in patients with low plasma HDL-C levels. An extended-release formulation, administered once daily, has improved the tolerability of nicotinic acid. Recent evidence also indicates that nicotinic acid may effectively correct dyslipidemia in patients with diabetes mellitus without significantly compromising glycemic control. Fibric acid derivatives and estrogen raise plasma HDL-C levels by different mechanisms of action, and these agents may be used with nicotinic acid. Combination therapy (especially HMG-CoA reductase inhibitor and nicotinic acid) should be considered in patients with atherosclerotic cardiovascular disease and low plasma HDL-C levels.
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PMID:Optimal therapy of low levels of high density lipoprotein-cholesterol. 1472 46

Recent epidemiological studies suggest that alcohol consumption is one of the risk factors leading to type 2 diabetes, but the direct effect of ethanol on beta-cell gene expression is not known. Here, using cDNA RDA method, we isolated 43 ethanol-induced genes in pancreatic beta-cells, and confirmed their differential expression by Northern blot or semi-quantitative RT-PCR. These genes were further categorized by the functional criteria based on the published data; Translation, Transcription, Metabolism, Signal transduction, Transport, Structure, Cytoskeleton, Regulation, or Putative/Unknown genes. The effects of each gene on beta-cell function need to be further investigated, however, the present data strongly suggest that these genes might be related to the metabolic alterations caused by ethanol as indicated in earlier study. In particular, RPS3 gene expression was increased by ethanol, glucosamine, and cytokines, implying that ethanol might decrease the metabolic activity by oxidative stress in beta-cells. Therefore, cloning of these genes in full-length and the detailed studies of each gene on beta-cell functions might provide clues on the pathophysiology of type 2 diabetes caused by alcohol.
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PMID:Isolation of ethanol-induced genes in pancreatic beta-cells by representational difference analysis (RDA). 1503 69

Gastric ulcers were induced in normal/NIDDM rats by various physical (2 hr cold restraint stress and 4 hr pylorus ligation) and chemical agents (ethanol, 1 ml/200 g, oral, 1 hr before; aspirin, 200 mg/kg, oral, 4 hr) and duodenal ulcers were induced by cysteamine (40 mg/200 g). Ulcer healing activity was studied in gastric ulcers induced by acetic acid (50%) and HCI (0.6 M). The result indicated that in both, normal and NIDDM rats, B. monniera extract (BME, 20-100 mg/kg) did not show any significant effect on blood glucose level, while A. indica (AIE, 250-1000 mg/kg) significantly decreased it. However, both BME (50 mg/kg) and AIE (500 mg/kg) showed significant anti-ulcer and ulcer-healing activities in normal and NIDDM rats. Further, the present results also indicated that the ulcer protective effects of BME was more pronounced in non-diabetic, while that of AIE was more in NIDDM rats. The anti-ulcer and ulcer-healing activities of BME and AIE may be due to their effects on various mucosal offensive and defensive factors, and correction of blood sugar level by AIE may help to have more ulcer protective effect in NIDDM rats.
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PMID:Effect of Bacopa monniera and Azadirachta indica on gastric ulceration and healing in experimental NIDDM rats. 1508 89


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