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

Peroxisome proliferator-activated receptor (PPAR)-delta regulates fatty acid oxidation and improves insulin sensitivity. We screened six single nucleotide polymorphisms (SNPs) of the PPAR-delta gene (PPARD) for an association with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in 769 subjects participating in the STOP-NIDDM trial. A 2.7-fold increase in the risk of diabetes was observed in female carriers of the C allele of rs6902123 (95% CI 1.44-5.30; adjusted P = 0.002). In the placebo group, subjects possessing both the 482Ser allele of the PPAR-gamma coactivator-1alpha gene (PGC-1A) and the rare allele of two SNPs of PPARD (rs6902123 and rs3734254) had up to 2.5-fold increased risk for diabetes. Furthermore, women carrying the C allele of rs6902123 of PPARD and the Pro12Pro genotype of the PPAR-gamma2 gene (PPARG2) had a 3.9-fold (95% CI 1.79-8.63; P = 0.001)-higher risk for diabetes than women with protective genotypes. Expression levels of PPAR-delta in subcutaneous adipose tissue of 87 offspring of Finnish patients with type 2 diabetes did not differ among the genotype groups of SNPs of PPARD. We conclude that SNPs in PPARD modify the conversion from IGT to type 2 diabetes, particularly in combination with the SNPs of PGC-1A and PPARG2.
Diabetes 2006 Jul
PMID:Single nucleotide polymorphisms of PPARD in combination with the Gly482Ser substitution of PGC-1A and the Pro12Ala substitution of PPARG2 predict the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial. 1680 87

The increasing prevalence of diabetes is reaching epidemic proportion worldwide. Because of the associated morbidity and mortality, it is exerting major pressure on the healthcare system. With a better understanding of the pathophysiology of type-2 diabetes, the concept of primary prevention has emerged. A number of studies have confirmed that intensive lifestyle modification was very effective in the prevention of diabetes in the impaired glucose tolerance (IGT) population. However, maintaining long-term lifestyle modification is a major challenge. It is, therefore, important to have other strategies, either pharmacological or surgical, that can be used as an adjunct or alternative to lifestyle modification. The Chinese study showed that metformin and acarbose could reduce the risk of diabetes by 65 and 83%, respectively, in IGT subjects. The efficacy of metformin was confirmed by the Diabetes Prevention Program (31% risk reduction) and that of acarbose by the STOP-NIDDM trial (36% risk reduction) in a similar high-risk population. The TRIPOD study showed that troglitazone could reduce the risk of diabetes by 55% in Hispanic women with a history of gestational diabetes. And more recently, the XENDOS study showed that orlistat could reduced the risk of diabetes by 37% in obese subjects when used as an adjunct to an intensive lifestyle program. Three studies have suggested that bariatric surgery in morbidly obese subjects could reduce the risk of diabetes to near zero. Furthermore, a number of studies have examined the effect of a renin angiotensin aldosterone system inhibitor, as well as statin and hormone replacement therapy on the prevention of type-2 diabetes in high-risk subjects as secondary outcomes and have suggested that they could be of potential benefit. The accumulating evidence is now overwhelming. Yes, diabetes can be prevented or delayed in high-risk populations. With this new information, we need to design new strategies to screen high-risk populations and to implement the new treatments that have proven effective in the prevention of type-2 diabetes.
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PMID:Pharmacological and surgical intervention for the prevention of diabetes. 1682 Jul 29

Hepatocyte nuclear factor 4alpha (HNF4alpha) is a transcription factor, which is necessary for normal function of human liver and pancreatic islets. We investigated whether single nucleotide polymorphisms (SNPs) of HNF4A, encoding HNF4alpha, influenced the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus in subjects of the STOP-NIDDM trial. This trial aimed at evaluating the effect of acarbose compared to placebo in the prevention of type 2 diabetes mellitus. Eight SNPs covering the intragenic and alternate P2 promoter regions of HNF4A were genotyped in study samples using the TaqMan Allelic Discrimination Assays. Three SNPs in the P2 promoter region (rs4810424, rs1884614, and rs2144908) were in almost complete association (D'>0.97, r (2)>0.95) and, therefore, only rs4810424 was included in further analyses. Female carriers of the less frequent C allele of rs4810424 had a 1.7-fold elevated risk [95% confidence interval (CI) 1.09-2.66; P=0.020] for the conversion to diabetes compared to women with the common genotype after the adjustment for age, treatment group (placebo or acarbose), smoking, weight at baseline, and weight change. No association was found in men. Haplotype analysis based on three SNPs (rs4810424, rs2071197, and rs3818247) representing the linkage disequilibrium blocks in our study population indicated that the conversion to type 2 diabetes mellitus was dependent on the number of risk alleles in different haplotypes in women. Our results suggest that SNPs of HNF4A and their haplotypes predispose to type 2 diabetes mellitus in female subjects of the STOP-NIDDM study population.
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PMID:Single nucleotide polymorphisms of the HNF4alpha gene are associated with the conversion to type 2 diabetes mellitus: the STOP-NIDDM trial. 1683 70

Retroviruses-derived elements in the human genome constitute 90% of non-coding mobile sequences. Reverse transcriptase (RT) plays an essential role in their transposition as do long terminal repeats (LTRs), which contain promotors, enhancers, and regulatory sequences. Some retroelements (pseudogens and retrogenes, e.g. SINE) are non-autonomic and do not possess their own RT. These elements are dependent on autonomic elements (retroposons, e.g. LINE, retrotransposons, exo- and endogenous retroviruses). The genome of retroviruses is composed of gag, pol, and env genes flanked by long terminal repeats. Endogenous retroviruses are probably the remnants of ancient germ cell infection by exogenous retroviruses and are transmissible to the next generation in a Mendelian way. Most of them are defective (because of mutation accumulation), but some are still active and their expression is regulated by different factors (UV radiation, inflammatory cytokines, steroid hormones, and exogenous virus products). Retroelements as well as their gene products exert influence on the organism's functions. They influence the plasticity and evolution of genomes, are a source of promotors and regulatory sequences, but they also supply additional signals of transcription initiation, mRNA splicing, and STOP codons. One of the positive aspects of human endogenous retroviruses (HERVs) is the participation of their products in normal syncytiotrophoblast formation. They also block exogenous retrovirus replication by receptor interference or antisense mRNA. Their presence is considered to be connected with a number of autoimmunological diseases (multiple sclerosis, insulin-dependent diabetes mellitus, systemic lupus erythematosus), cancer, or even psychiatric disorders (schizophrenia). There are also other problems connected with the potential role of ERVs in genomic therapy (with retroviruses vectors) and transplantology (xenotransplantation).
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PMID:[Retroviruses-derived sequences in the human genome. Human endogenous retroviruses (HERVs)]. 1719 6

The increased risk of cardiovascular disease associated with type 2 diabetes is well documented. Lesser degrees of abnormal glucose metabolism including impaired fasting glycaemia and impaired glucose tolerance are also associated with increased cardiovascular risk. Studies showing improved cardiovascular outcomes with oral antidiabetic agents are limited, with the UKPDS demonstrating improved macrovascular outcomes only in a subgroup of obese patients with type 2 diabetes treated with metformin, and the heavily criticized STOP NIDDM trial showing a reduction in the number of cardiovascular events with the alpha glucosidase inhibitor acarbose. In recent years there has been an increase in the number of oral antidiabetic drugs available to treat the hyperglycaemia of diabetes. Some of these drugs have complex metabolic properties, additional to their antihyperglycaemic effect, improving endothelial function and markers of atherogenesis, with the potential to reduce cardiovascular morbidity and mortality, as supported by the recently published results of the PROACTIVE study. The results of further long-term cardiovascular outcome studies with these newer agents are awaited.
Diabetes Obes Metab 2007 Jan
PMID:Oral antidiabetic agents as cardiovascular drugs. 1719 15

Peroxisome proliferator-activated receptor (PPAR) alpha, a transcription factor of the nuclear receptor superfamily, regulates fatty acid oxidation. We evaluated the association of single nucleotide polymorphisms (SNPs) of the PPAR-alpha gene (PPARA) with the conversion from impaired glucose tolerance to type 2 diabetes in 767 subjects of the STOP-NIDDM trial in order to investigate the effect of acarbose in comparison with placebo on the prevention of diabetes. In the placebo group, the G (162V) allele of rs1800206 increased the risk for diabetes by 1.9-fold (95% CI 1.05-3.58) and was associated with elevated levels of plasma glucose and insulin. The effect of this allele on the risk of diabetes in the placebo group was enhanced by the simultaneous presence of the risk alleles of the PPAR-gamma2, PPAR-gamma coactivator 1alpha, and hepatic nuclear factor 4alpha genes (odds ratios 2.2, 2.5, and 3.4, respectively). In the acarbose group, subjects carrying the minor G allele of rs4253776 and the CC genotype of rs4253778 of PPARA had a 1.7- and 2.7-fold increased risk for diabetes. Our data indicate that SNPs of PPARA increase the risk of type 2 diabetes alone and in combination with the SNPs of other genes acting closely with PPAR-alpha.
Diabetes 2007 Apr
PMID:Single nucleotide polymorphisms of the peroxisome proliferator-activated receptor-alpha gene (PPARA) influence the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial. 1731 62

There are few studies on the effects of postprandial hyperglycaemia, and usually it is assumed that its effects are the same as those of post-glucose-load hyperglycaemia, following a standard 75 g oral glucose tolerance test. There is some evidence from a study with blood drawn following ingestion of a standardised "diabetes screening product" or a 75 g oral glucose load, that the glucose concentrations during the 2-hour period of these two tests are highly correlated. There is epidemiological evidence that the 2-hour post-load-glucose is more predictive of cardiovascular mortality than fasting glucose, but it would appear that they are equally predictive of retinopathy. While hyperglycaemia is related with cardiovascular mortality, clinical trials lowering glucose levels in type 2 diabetic patients, have not succeeded in reducing cardiovascular disease rates, in contrast to the beneficial effects on micro-vascular disease. STOP-NIDDM, a clinical trial testing the prevention of type 2 diabetes, used the glucose lowering agent acarbose, a drug which lowers postprandial glucose. There was a beneficial effect on cardiovascular outcomes, however, the number of events was extremely small and the study was not designed to test this effect. Confirmatory studies are required before it is possible to conclude that acarbose is effective in cardiovascular prevention, and that indeed it is the treatment of postprandial glucose which is beneficial. The cardiovascular disease in diabetic patients may be due to the presence of other cardiovascular risk factors associated with diabetes.
Diabetes Metab 2006 Sep
PMID:Epidemiological data on postprandial glycaemia. 1737

The growing prevalence of Type 2 diabetes with its high morbidity and excess mortality is imposing a heavy burden on healthcare systems. Because of the magnitude of the problem, obviating diabetes has been a long-standing dream. In the last decade, a number of intervention strategies have been shown to be effective for the prevention of diabetes in high-risk populations with prediabetes. Seven studies have now confirmed that lifestyle modifications, including weight-reducing diets and exercise programs, are very effective in precluding or delaying Type 2 diabetes in high-risk populations with impaired glucose tolerance (IGT). Two major trials are the Diabetes Prevention Study (n = 522) from Finland and the Diabetes Prevention Program (n = 3234) from the US. Both studies have shown that intensive lifestyle intervention could reduce the progression of IGT to diabetes by 58%. Furthermore, four currently-available drugs have been established as being effective in preventing diabetes in subjects with prediabetes. The Diabetes Prevention Program revealed that metformin 850 mg b.i.d. reduced the risk of diabetes by 31%. The STOP-NIDDM (Study To Prevent Non-Insulin-Dependent Diabetes Mellitus) trial (n = 1429) showed that acarbose 100 mg t.i.d. with meals decreased the incidence of diabetes by 36% when the diagnosis was based on 2 oral glucose tolerance tests. The XENDOS (Xenical in the Prevention of Diabetes in Obese Subjects) study examined the use of orlistat, an antiobesity drug, as an adjunct to an intensive lifestyle modification program in obese non-diabetic subjects. Orlistat treatment resulted in a 37% decline in the development of diabetes. More recently, the DREAM (Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication) study (n = 5269) demonstrated that rosiglitazone at 8 mg once/day in subjects with prediabetes (IGT and/or impaired fasting glucose) was effective in reducing the risk of diabetes by 60%. It can be concluded that Type 2 diabetes can be prevented or delayed through lifestyle modifications and/or pharmacologic interventions. This is a fact.
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PMID:Prevention of Type 2 diabetes: fact or fiction? 1803 59

Cardiovascular disease accounts for a great majority of deaths in patients with type 2 diabetes. According to the World Health Organization, the prevalence of cardiovascular disease in diabetic patients ranges from 26 to 36%. Fatality rate after myocardial infarction is greater in diabetic patients, and overall prognosis after coronary heart disease is worse. Based on these observations, it has been proposed that diabetes should be considered as a coronary heart disease risk equivalent. If that is the case, prevention of diabetes and early intervention should be pursued. This view is supported by the notion that cardiovascular risk is already increased in people with impaired glucose tolerance. Moreover, higher-than-optimum blood glucose is a major cause of cardiovascular mortality in most world regions of the world. Whether dysglycemia is a marker for a more complex metabolic condition or may directly contribute to excess cardiovascular risk is still a matter of debate. However, experimental work has shown how increased glucose level can trigger multiple mechanisms of susceptibility to atherosclerosis, and diabetes prevention trials have indicated that along with reduction of the rate of conversion toward diabetes, significant improvement in cardiovascular risk factors occurs. Moreover, in the STOP-NIDDM trial, targeting postprandial glucose was associated with reduction in new cases of hypertension, myocardial infarction, and any cardiovascular events. In conclusion, dysglycemia should be included in the list of established cardiovascular risk factors and early treatment introduced in the attempt to improve cardiovascular morbidity and mortality.
Diabetes Care 2008 Feb
PMID:Primary prevention of cardiovascular disease in people with dysglycemia. 1822 87

The state of prediabetes comprises two types of impairment of carbohydrate metabolism: impaired fasting glycemia and impaired glucose tolerance. According to International Diabetes Federation at present number of patients with prediabtes is almost 2 times greater than that of patients with diabetes. Risk of development of diabetes and cardiovascular complications in patients with prediabtes is 2 times higher than in persons with normal blood glucose level. Impaired glucose tolerance is also one of main components of metabolic syndrome. For prevention of risk of development of diabetes and cardiovascular complications besides life style changes it is necessary to influence insulin resistance and normalize carbohydrate metabolism. When life style changes are ineffective the use of antihyperglycemic drugs is essential. Antihyperglycemic preparations metformin, acarbose, thiazolidinediones do not affect function of pancreatic beta-cells and do not cause hypoglycaemia. This allows to use these drugs in patients without diabetes but having insulin resistance and prediabetes. Therapeutic effect of metformin and rosiglitazone is related to improvement of sensitivity to insulin in insulin dependent tissues, suppression of glyconeogenesis in the liver, and enhancement of pancreatic beta-cells function. Action of acarbose is based on local inhibition of intestinal enzyme alpha-glycosidase, what leads to diminishment of postprandial hyperglycemia peak. Results of DPP, STOP-NIDDM and DREAM trials have demonstrated high efficacy of antihyperglycemic preparations in prevention of type 2 diabetes.
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PMID:[Perspectives of the use of antihyperglycemic preparations in patients with metabolic syndrome and prediabetes]. 1826 Aug 85


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