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

Genetic factors influence the development of type II diabetes mellitus, but genetic loci for the most common forms of diabetes have not been identified. A genomic scan was conducted to identify loci linked to diabetes and body-mass index (BMI) in Pima Indians, a Native American population with a high prevalence of type II diabetes. Among 264 nuclear families containing 966 siblings, 516 autosomal markers with a median distance between adjacent markers of 6.4 cM were genotyped. Variance-components methods were used to test for linkage with an age-adjusted diabetes score and with BMI. In multipoint analyses, the strongest evidence for linkage with age-adjusted diabetes (LOD = 1.7) was on chromosome 11q, in the region that was also linked most strongly with BMI (LOD = 3.6). Bivariate linkage analyses strongly rejected both the null hypothesis of no linkage with either trait and the null hypothesis of no contribution of the locus to the covariation among the two traits. Sib-pair analyses suggest additional potential diabetes-susceptibility loci on chromosomes 1q and 7q.
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PMID:An autosomal genomic scan for loci linked to type II diabetes mellitus and body-mass index in Pima Indians. 975 19

Congenital retardation of renal development may increase the risk of renal disease, and this risk may be enhanced by diseases, such as diabetes, that damage the kidney. In this study, the prevalence of urinary albumin excretion, determined in 308 Pima Indians with type 2 diabetes, was 63% in subjects with low birth weight (<2,500 g), 41% in those with normal birth weight (2,500-4,499 g), and 64% in those with high birth weight (> or =4,500 g). When examined as a continuous variable by generalized additive logistic regression, birth weight had a U-shaped association with the prevalence of elevated urinary albuminuria (p = 0.04) after adjustment for age, sex, duration of diabetes, glycosylated hemoglobin, and blood pressure. The odds of elevated albuminuria in subjects of low birth weight was 2.3 times (95% confidence interval 0.72-7.2) that in subjects of normal birth weight, and the odds in subjects of high birth weight was 3.2 times (95% confidence interval 0.75-13.4) as high. Sixty-four percent of the subjects with high birth weight and none of those with low birth weight were offspring of diabetic mothers. After maternal diabetes during pregnancy was controlled for, the odds of elevated albuminuria in subjects of high birth weight was no longer higher (odds ratio = 1.0, 95% confidence interval 0.22-4.9). The higher prevalence of elevated albuminuria in diabetic Pima Indians with high birth weight may be due to intrauterine diabetes exposure, whereas the higher prevalence in those with low birth weight may be due to the effects of intrauterine growth retardation.
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PMID:Birth weight and renal disease in Pima Indians with type 2 diabetes mellitus. 977 71

Evidence suggests that impaired lipolysis may contribute to fat accumulation. To test whether the lipolytic response to adrenergic stimulation is lower in Pima Indians, a population prone to obesity and type 2 diabetes mellitus, than in Caucasians, 48 healthy, non-diabetic subjects were studied: 27 Pima Indians (12 males and 15 females, 30 +/- 7 yr, 85 +/- 18 kg, 36 +/- 10% body fat; mean +/- SD) and 21 Caucasians (11 males and 10 females, 34 +/- 7 yr, 105 +/- 26 kg, 39 +/- 11% body fat). Lipolysis in the abdominal s.c. adipose tissue was assessed in situ by glycerol concentration in microdialysis samples at baseline and during local infusion of the nonselective beta-adrenergic agonist isoproterenol (10(-6) mol/L), mental stress, and submaximal exercise. The baseline dialysate glycerol concentrations were similar in Pima Indians and Caucasians. Lipolytic response (relative increment in dialysate glycerol concentration, percentage above the baseline) was similar in Pima Indians and Caucasians in response to local isoproterenol infusion (77 +/- 36% and 76 +/- 40%) and exercise (38 +/- 38% and 41 +/- 41%). During mental stress, the dialysate concentration did not change significantly from baseline in either group. Changes in local blood flow, determined by ethanol dilution, did not differ between the two groups. In conclusion, the high propensity for obesity in Pima Indians does not seem to be due to an impaired lipolytic response to stimuli.
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PMID:In situ lipolytic responses to isoproterenol and physiological stressors are similar in obese Pima Indians and Caucasians. 981 91

A number of cross-sectional and prospective studies that compared the insulin sensitivity of various national and ethnic populations within the U.S. to the total U.S. population were analyzed to find possible risk factors for the development of type 2 diabetes. It was found that the risks for diabetes in African-Americans, Hispanics, and Native Americans are approximately 2, 2.5, and 5 times greater, respectively, than in Caucasians. Studies of the prevalence of type 2 diabetes in Mexican Americans and non-Hispanic whites in San Antonio showed that there is an inverse relationship between socioeconomic status and the prevalence of diabetes. It also appears that cultural effects lead to an increased incidence of obesity in these populations, which may lead to insulin resistance. Genetic factors may also be a contributing factor. A 5-year, prospective study of insulin resistance in Pima Indians showed a relationship between impaired glucose tolerance and subsequent development of type 2 diabetes. In a 7-year study in Mexican Americans, those subjects who had both high insulin secretion and impaired insulin sensitivity had a 14-fold increased risk of developing type 2 diabetes. Regardless of cultural and ethnic factors, the San Antonio Heart Study, which compared Mexican Americans and non-Hispanic whites, showed that in both groups, the strongest predictors of developing type 2 diabetes are elevated fasting insulin concentrations and low insulin secretion.
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PMID:Epidemiology of type 2 diabetes: risk factors. 985 Apr 78

In rodents, administration of leptin promotes beta3-adrenergic stimulation of thermogenesis in brown adipose tissue. Conversely, administration of a beta3-adrenoceptor (beta3-AR) agonist decreases leptin mRNA expression and secretion, suggesting that leptin and sympathetic nervous system activity mediated through the beta3-AR comprise a negative-feedback loop. It has recently been proposed that a defect in the beta3-AR in humans may contribute to a resistance to the sympathetically mediated effects of leptin on thermogenesis and lipolysis, thus leading to obesity and type 2 diabetes mellitus. We thus hypothesized that the Trp64Arg variant in the human beta3-AR would be associated with elevated plasma leptin concentrations. We studied 101 healthy nondiabetic Pima Indians: 11 Arg64 homozygotes, 35 Trp64 homozygotes, and 55 heterozygotes. The fasting plasma leptin concentration as an absolute value or after adjustment for percent body fat and sex was not associated with the beta3-AR genotype. Thus, the data do not support an influence of the Trp64Arg variant on the plasma leptin concentration.
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PMID:No effect of Trp64Arg beta3-adrenoceptor polymorphism on the plasma leptin concentration in Pima Indians. 986 85

Insulin-dependent diabetes mellitus (IDDM) develops predominantly in children and young adults, but may appear in all age groups. The incidence of IDDM differs greatly among populations, with Finland and Sardinia showing the greatest incidence rates (approximately 30-35% of cases annually per 100000 children up to age 14 years) and oriental populations showing the lowest rates. IDDM is diagnosed more frequently in the winter months. The major genetic susceptibility to IDDM is linked to the HLA complex on chromosome 6. These genetic backgrounds interact with environmental factors (possibly certain viruses, foods and climate) to initiate the immune-mediated process that leads to beta-cell destruction. Non-insulin dependent diabetes (NIDDM) is the most common form of diabetes. The prevalence of NIDDM varies enormously from population to population. The greatest rates have been found in Pima Indians. The major environmental factors identified as contributing to this form of diabetes are obesity and reduced physical activity. NIDDM shows strong familial aggregation in all populations and is clearly the result of an interaction between genetic susceptibility and environmental factors. Before NIDDM develops, insulin concentrations are high for the degree of glycaemia and of obesity, reflecting the presence of insulin resistance. As insulin resistance worsens, glucose levels increase, with the appearance of glucose intolerance and, finally, of NIDDM, when insulin response cannot compensate for insulin resistance.
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PMID:The epidemiology of diabetes mellitus. 987 Apr 17

The expansion of polymorphic CAG/CTG repeats in specific genes causes several neurodegenerative disorders and in many instances the length of the disease-causing repeat correlates with the onset age and/or severity of symptoms. Type 2 diabetes mellitus has features in common with diseases resulting from trinucleotide repeat expansion, including a variable age of disease onset and penetrance. We have investigated whether CAG/CTG repeat expansion contributes to the genetic etiology of type 2 diabetes in the Pima Indians, a population with the highest reported prevalence of this disease. Using the Repeat Expansion Detection (RED) method, we determined the size range in nondiabetic Pimas to be between (CAG)20 and (CAG)130 (mean repeat length = 195 bp), which is significantly larger than the mean size reported in Caucasians (150 bp). We compared the distribution of CAG/CTG repeat lengths among 40 Pimas with an early onset of type 2 diabetes (<22 years) and 38 nondiabetic subjects (>55 years). A 240-bp CAG/CTG RED product was found more frequently in early onset diabetics relative to nondiabetic controls (26% vs 11%), whereas a 210-bp band was more prominent in unaffected subjects (29% vs 13%); however, these differences were not statistically significant. In one Pima kindred, we also identified large RED products (>/=360 bp) that displayed intergenerational instability among family members. However, these expansions were not associated with diabetes or any other clinical abnormalities in the carriers. We conclude that this unstable CAG/CTG repeat may represent a novel locus, consisting of large, but apparently nonpathogenic, unstable sequences.
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PMID:Genome-wide scan for CAG/CTG repeat expansions in Pimas with early onset of type 2 diabetes mellitus. 997 49

The skeletal muscle activity of protein tyrosine phosphates 1B (PTP1B), a modulator of insulin and IGF-1 signaling, is reduced in obese nondiabetic subjects and in subjects with type 2 diabetes in comparison with leaner, nondiabetic controls. PTP1B mRNA, like many other signaling molecules, including the insulin receptor, is alternatively spliced. Since we have shown that the ratio of the insulin receptor splice variants is modulated by insulin in vitro and is related to insulin levels in vivo, we hypothesized that the relative ratios of the alternatively spliced PTP1B mRNA might also vary in humans in proportion to the degree of hyperinsulinemia. This was tested in 21 nondiabetic Pima Indians, a population at increased risk for obesity and type 2 diabetes. The relative ratio of the PTP1B splice variants was quantified using RT-PCR of total RNA extracted from fractionated monocytes. The ratio of the splice variants was positively correlated with fasting plasma insulin concentration (r = 0.757; P = 0.0001), 2-h plasma insulin concentration following an oral glucose tolerance test (r = 0.614; P = 0.01, n = 16), and percentage of body fat (r = 0.746; P = 0.0001). These data indicate that variability in the ratio of the two splice variants is due, in part, to in vivo levels of chronic hyperinsulinemia. This simple, noninvasive assay is therefore a potential biomarker for chronic hyperinsulinemia, similar to the HbAlc assay in use to monitor glucose management in diabetic patients.
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PMID:Insulin-inducible changes in the relative ratio of PTP1B splice variants. 1006 87

The effect of plasma glucose concentration on overall and cause-specific mortality was examined in 1,745 Pima Indians (725 men, 1,020 women) > or = 15 years old with type 2 diabetes. During a median follow-up of 10.6 years (range 0.1-24.8), 533 subjects (275 men, 258 women) died; 113 of the deaths were attributable to cardiovascular disease, 96 to diabetes-related diseases (diabetic nephropathy for 92 of these), 249 to other natural causes, and 75 to external causes. After adjusting for age, sex, duration of diabetes, and BMI in a generalized additive proportional hazards model, higher baseline 2-h postload plasma glucose concentration predicted deaths from cardiovascular disease (P = 0.007) and diabetes-related diseases (P = 0.003), but not from other natural causes (P = 0.73). An increment of 5.6 mmol/l (100 mg/dl) in the 2-h plasma glucose concentration was associated with 1.2 times (95% CI 1.1-1.4) the death rate from cardiovascular disease, 1.3 times (95% CI 1.1-1.5) the death rate from diabetes-related diseases, and almost no change in the death rate from other natural causes (rate ratio = 1.0; 95% CI 0.94-1.1). In Pima Indians with type 2 diabetes, higher plasma glucose concentration predicts deaths from cardiovascular and diabetes-related diseases but has little or no effect on deaths from other natural or external causes.
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PMID:Effect of glycemia on mortality in Pima Indians with type 2 diabetes. 1010 9

Diabetic nephropathy was first described in patients with non-insulin-dependent diabetes mellitus (NIDDM, type II diabetes) by Kimmelstiel and Wilson in 1936. It is a classical, late diabetic complication, diagnosed by measurement of the urinary albumin or total protein excretion, and typically develops after more than 15 years of diabetes. As most studies of patients with type II diabetes have been performed in White, European or North American populations in which the highest incidence of this disease is recorded in individuals aged over 70 years, a low prevalence has generally been found in these patients. Nephropathy has been considered a rare complication in type II diabetes patients. Other ethnic groups such as Pima Indians in the USA or Pacific Islanders have totally different incidence patterns of type II diabetes, with a high incidence in the 20- to 50-year age group. These patients live long enough to develop nephropathy, and they do so at the same rate as insulin-dependent diabetes mellitus (IDDM, type I diabetes) patients. Since the prevalence of type II diabetes is increasing worldwide, particularly in the developing world, diabetic nephropathy will be a growing problem in patients with this disease. From our experience in the treatment of type I diabetes patients, we know that prevention of end-stage renal failure is possible in most patients, but that treatment of end-stage renal disease is very expensive. In this paper, some of the major risk factors for the development of nephropathy are discussed together with the potential for treatment. It is shown that, in type I diabetes patients, early detection by screening for microalbuminuria and immediate recourse to antihypertensive treatment are likely to increase life-expectancy significantly while at the same time reducing the total costs to healthcare. Whether this is also the case in patients with type II diabetes is less clear, as most of the controlled clinical trials of the effect of strict metabolic control or antihypertensive treatment have been performed in patients with type I diabetes. Thus, clinical trials in patients with type II diabetes should be performed, and further epidemiological data relating to these patients are needed.
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PMID:The costs of nephropathy in type II diabetes. 1015 2


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