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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The JCR:LA-cp rat is a unique strain that, if homozygous for the autosomal recessive cp gene, is obese and exhibits the metabolic syndrome of insulin resistance, hyperinsulinemia, and hypertriglyceridemia. Obese male rats spontaneously develop advanced atherosclerosis and ischemic myocardial lesions. The angiotensin-converting enzyme inhibitor, captopril, was administered to obese rats at 30 mg/kg body weight from 6 to 39 weeks of age. There were no significant changes in food consumption or body weights of the treated animals. Insulin sensitivity was not improved. Plasma insulin levels were unaltered, but the volume density of the islets of Langerhans was halved, reflecting both reduced hyperplasia and a more normal islet structure. Triglyceride concentrations were not reduced, but unesterified cholesterol and cholesteryl esters decreased by 50% and 34%, respectively (p < 0.01). The impaired nitric oxide-mediated vascular relaxation of the obese rats was not improved, and the relaxant sensitivity to acetylcholine as indicated by the median effective concentration (EC50) was reduced. In vitro, captopril significantly reduced the basal tension of aortic rings from untreated rats, antagonized the contractile effects of norepinephrine, and induced complete relaxation of the contraction in response to 10(-7) M norepinephrine. The severity of spontaneous, raised atherosclerotic lesions of the aortic arch at age 39 weeks was not significantly decreased by captopril treatment. In contrast, the frequency of ischemic myocardial lesions was reduced by 78% (p < 0.01). The protective effects of captopril on the heart and pancreas in this animal model of type II diabetes and atherosclerosis are probably the result of its bradykinin-enhancing effects.
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PMID:Inhibition of myocardial lesions in the JCR:LA-corpulent rat by captopril. 964 85

We report a study of 10 candidate genes presumably involved in diabetes or insulin resistance or obesity among Pondicherian Tamil Indians, an isolated population with a high prevalence of diabetes. Forty-nine families with at least two affected patients in the sibship (567 individuals) were selected and tested by PCR-RFLP techniques for reported mutations in 10 diabetes or obesity candidate genes: glucagon receptor, insulin receptor substrate 1, insulin receptor, human beta 3 adrenergic receptor, fatty acid binding protein 2, mitochondrial tRNA(Leu(UUR)), sulphonylurea receptor, human uncoupling protein and the glycogen-associated regulatory subunit of protein phosphatase-1. Glucokinase gene was also screened for mutations. No mutations were found in glucokinase, glucagon receptor and mitochondrial genes in any of the 49 probands. Frequencies of polymorphisms at other loci were similar to those reported in Caucasian populations, except for 4 of the loci at which a higher frequency of variants was observed: human beta 3 adrenergic receptor, human uncoupling type 1 protein, fatty acid binding protein 2 and the glycogen-associated regulatory subunit of protein phosphatase-1. However, no evidence of association between any of these gene variants and non-insulin-dependent diabetes mellitus (NIDDM) or quantitative traits related to NIDDM (including body mass index, waist/hip ratio, insulinaemia, glycaemia, triglycerides and total cholesterol) was found in our sample. These results suggest that none of these gene variants commonly found in the Pondicherian Tamil population of South India is a major NIDDM predisposing locus, although it cannot be excluded that they may contribute to the polygenic background of the metabolic syndrome in Pondichery.
Diabetes Metab 1998 Jun
PMID:Genetic studies of polymorphisms in ten non-insulin-dependent diabetes mellitus candidate genes in Tamil Indians from Pondichery. 969 58

Recent studies in Europe, North America, and the developing world have shown that low birth weight and other indices of abnormal fetal growth in babies born at term are linked with a higher prevalence of glucose intolerance and NIDDM in adult life. Reduced fetal growth is also associated with a higher prevalence of the metabolic syndrome (in particular, hypertension and vascular disease) and with insulin resistance in adult life. Because birth size is determined largely by nongenetic factors, these findings have led to the "fetal origins" hypothesis, which proposes that fetal adaptations to an adverse intrauterine environment that reduces fetal growth program lifelong physiological changes. These changes in turn predispose to diabetes and the metabolic syndrome. The mechanisms are unknown, but evidence from animal studies and preliminary human evidence suggests that adverse events in early life may influence the neuroendocrine development of the fetus. This results in long-term alterations in the setpoint of several major hormonal axes, including an increase in adrenal glucocorticoid secretion. These hormonal alterations may contribute to the predisposition to diabetes and the metabolic syndrome in people who were small at birth.
Diabetes Care 1998 Aug
PMID:Birth weight and the future development of diabetes. A review of the evidence. 970 43

Impaired glucose tolerance (IGT) was standardized in 1979 by the National Diabetes Data Group and the World Health Organization as a risk factor for type 2 diabetes, replacing groups such as 'borderline' and 'chemical' diabetes. IGT was defined by a blood/plasma glucose value 2 h after a 75 g glucose load that was clearly abnormal but did not convey a risk of microangiopathy in those with non-diabetic fasting blood/plasma glucose levels. IGT is not uncommon, having a prevalence of 2-25% in adults. Determinants include age, obesity (total and central), family history of type 2 diabetes, physical inactivity and triglyceride levels. The main clinical significance of IGT is: (1) as a risk factor for type 2 diabetes, with 20-50% of individuals developing type 2 diabetes over 10 years; (2) as a risk factor for cardiovascular disease (CVD); and (3) as a component of the metabolic syndrome. IGT can be treated and this may prevent or delay progression to type 2 diabetes, though the effect of treatment on the risk of CVD is unknown.
Diabetes Res Clin Pract 1998 Jul
PMID:Impaired glucose tolerance: what are the clinical implications? 974 Apr 95

Impaired lipolysis has been proposed as a pathogenic factor contributing to clustering of abdominal obesity and dyslipidaemia in Type II (non-insulin-dependent) diabetes mellitus--that is, the metabolic syndrome (MSDR). As this syndrome clusters in families, alterations in the hormone-sensitive lipase (HSL) gene could contribute to the genetic predisposition to MSDR. To test this hypothesis we carried out population and intrafamily association studies in individuals with MSDR, using a polymorphic marker (LIPE) in the HSL gene. There was a significant difference in allele frequency distribution between 235 Type II diabetic patients and 146 control subjects (p = 0.002), particularly between 78 abdominally obese Type II diabetic patients with MSDR and the control group (p = 0.010). An extended transmission disequilibrium test (TDT) showed transmission disequilibrium of 66 alleles to 42 nondiabetic, abdominally obese offspring in families with Type II diabetes (p < 0.05). A slight difference in allele frequency distribution was seen between 71 individuals from the lowest and 71 from the highest tertile of isoprenaline-induced lipolysis in fat tissue (p = 0.07). No missense mutations were found with single-strand conformational polymorphism (SSCP) in 20 abdominally obese subjects with MSDR. In conclusion, our population and intrafamily association studies suggest that the LIPE marker in the HSL gene is in linkage disequilibrium with an allele and/or gene which increases susceptibility to abdominal obesity and thereby possibly to Type II diabetes.
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PMID:The putative role of the hormone-sensitive lipase gene in the pathogenesis of Type II diabetes mellitus and abdominal obesity. 986 20

Adipose tissue is considered as the body's largest storage organ for energy in the form of triglycerides, which are mobilised through the lipolysis process to provide fuel to other organs and to deliver substrates to liver for gluconeogenesis (glycerol) and lipoprotein synthesis (free fatty acids). The release of glycerol and free fatty acids is intensively regulated by hormones and agents. In man, the major hormones are insulin (inhibition of lipolysis) and catecholamines (stimulation of lipolysis). Physiological factors such as dieting, physical exercise and ageing also regulate lipolysis. The lipolytic process is modified in pathological conditions, e.g. obesity (both upper and lower obesity), diabetes (non- and insulin-dependent diabetes mellitus), and dyslipidaemia (in particular, familial combined hyperlipidaemia). The regulation of lipolysis is complex because of the heterogeneity of fat depots (visceral versus subcutaneous), which may contribute to the well-known gender differences in accumulation of fat. Since visceral fat depot is directly drained into the liver and has a high turnover of visceral triglycerides, "portal" free fatty acids seem to be an important pathophysiological factor in common complications of obesity (in particular, metabolic syndrome). New advances in genetic studies indicate that polymorphisms in several genes encoding for proteins that regulate the lipolysis process are important for the development of obesity and its complications.
Diabetes Metab 1998 Nov
PMID:Regulation of lipolysis in humans. Pathophysiological modulation in obesity, diabetes, and hyperlipidaemia. 988 Dec 38

The aim of the study was 1) to establish the prevalence of GAD antibodies (GADab) in a population-based study of type 2 diabetes in western Finland, 2) to genetically and phenotypically characterize this subgroup, and 3) to provide a definition for latent autoimmune diabetes in adults (LADA). The prevalence of GADab was 9.3% among 1,122 type 2 diabetic patients, 3.6% among 558 impaired glucose tolerance (IGT) subjects, and 4.4% among 383 nondiabetic control subjects. Islet antigen 2 antibodies (IA2ab) or islet cell antibodies were detected in only 0.5% of the GADab- patients. The GADab+ patients had lower fasting C-peptide concentrations (median [interquartile range]: 0.46 [0.45] vs. 0.62 [0.44] nmol/l, P = 0.0002) and lower insulin response to oral glucose compared with GADab- patients. With respect to features of the metabolic syndrome, the GADab+ patients had lower systolic (140 [29.1] vs. 148 [26.0] mmHg, P = 0.009) and diastolic (79.2 [17.6] vs. 81.0 [13.1] mmHg, P = 0.030) blood pressure values, as well as lower triglyceride concentrations (1.40 [1.18] vs. 1.75 [1.25] mmol/l, P = 0.003). GADab+ men had a lower waist-to-hip ratio compared with GADab- patients. Compared with GADab- patients and control subjects, the GADab+ patients had an increased frequency HLA-DQB1*0201/0302 (13 vs. 4%; P = 0.002) and other genotypes containing the *0302 allele (22 vs. 12%; P = 0.010). However, the frequency of these high-risk genotypes was significantly lower in GADab+ type 2 patients than in type 1 diabetes of young or adult onset (0201/0302 or 0302/X: 36 vs. 66 vs. 64%, P < 0.001). The GADab+ type 2 group did not differ from control subjects with respect to genotypes containing the protective DQB1-alleles *0602 or *0603, nor with respect to the type 1 high-risk genotype in the IDDM1 (Hph1 +/+). We conclude that GADab+ patients differ from both GADab- type 2 diabetic patients and type 1 diabetic patients with respect to beta-cell function, features of the metabolic syndrome, and type 1 diabetes susceptibility genes. Further, we propose that LADA be defined as GADab positivity (>5 relative units) in patients older than 35 years at onset of type 2 diabetes.
Diabetes 1999 Jan
PMID:Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies. 989 37

While the hyperleptinemia of obesity is likely to be associated with the metabolic complications of obesity/hyperinsulinemia/insulin resistance, it is not associated with diabetes, with the relative hypercortisolism of upper body obesity, with hypertension in women, (it is in men), or with dyslipidemia. Overall, the correlations between leptin and the metabolic diseases associated with obesity are weak. The equivocal results of an association of leptin with components of the metabolic syndrome make it unlikely that leptin affects these directly. (On the other hand, these correlations, when found, preclude any causal relationship between leptin and metabolic diseases.) There are experimental data showing a definite role for insulin and glucocorticoids in the regulation of leptin, and of leptin in the regulation of insulin. More data are required on the effects of leptin, but it is likely that leptin will not be a major link between obesity and the metabolic syndrome. Certainly, however, when leptin is available for clinical use, its effect on different aspects of the metabolic syndrome will be worth studying.
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PMID:Therapeutic controversy: Obesity--a modern-day epidemic. 992 54

BM 17.0744 (2,2-dichloro-12-(p-chlorophenyl)-dodecanoic acid) is a substance from a group of omega-substituted alkyl carboxylic acids with the general formula, ring-spacer-carboxylic acid. With BM 17.0744-a compound structurally unrelated to thiazolidinediones--antihyperglycemic and antihyperinsulinemic potency has been demonstrated in various animal models of type II diabetes. The antidiabetic effect is independent of the genetic background of the disease, gender, and animal species. The 24-hour blood glucose profile was dose- and time-dependently improved in ob/ob mice after a single and fourth oral administration of 0.3, 1, and 3 mg/kg/d. A dose-dependent reduction of hyperglycemia (10%, 15%, 28%, and 66%) was found in db/db mice after the fifth oral administration of 3, 10, 30, and 100 mg/kg/d. Hyperinsulinemia was reduced dose-dependently in yellow KK mice by 1%, 24%, 34%, and 66% after the fifth oral administration of 0.3, 1, 3, and 10 mg/kg/d. Overall glucose metabolism was predominantly higher in euglycemic-hyperinsulinemic clamp studies in obese fa/fa rats pretreated for 14 days with 10 mg/kg/d BM 17.0744. The data in diabetic and insulin-resistant animals suggest an improvement of insulin action that is supported by enhancement of insulin effects in vitro. There is no evidence of a risk for hypoglycemia in diabetic and metabolically healthy animals. Triglyceride (TG) and cholesterol were reduced in the serum of metabolically healthy rats, as well as serum lipids in db/db mice, which suggests this effect is independent of amelioration of the diabetic status. Lipid-lowering effects in diabetic and healthy animals show an additional property of BM 17.0744. Because of its antidiabetic and lipid-lowering potency, the substance is of great interest in treating the metabolic syndrome. Lipid decreases in rats are associated with a dose-dependent increase in carnitine acetyltransferase activity in the liver to about 100-fold (12.5 mg/kg/d). This together with hepatomegaly in small rodents may indicate peroxisomal proliferation, a phenomenon considered species-specific. Its relevance for humans is well documented for other classes of compounds including fibrates. Specific side effects of insulin sensitizers of the thiazolidinedione type, such as an increase in body weight and heart weight, could not be observed after 4-week oral application of BM 17.0744 in rats. In general, BM 17.0744 was well tolerated in the pharmacological dose range in all species tested.
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PMID:BM 17.0744: a structurally new antidiabetic compound with insulin-sensitizing and lipid-lowering activity. 992 Jan 42

Kuzmak's adjustable gastric banding procedure is well established and has proven to be efficacious in obese patients. After gastric banding we observed a good weight loss and an improvement in metabolic syndrome diseases. Therefore we were able to reduce the dosage of preoperative medication in patients with diabetes or hypertension.
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PMID:[Reducing concomitant illnesses of morbid obesity after gastric banding]. 993 77


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