Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oklahoma Indians with NIDDM (n = 1012) underwent a baseline examination in 1972-1980. The incidence of and risk factors for first lower-extremity amputation were estimated. The mortality rates of amputees using data from 875 patients who had no previous history of amputation and who underwent follow-up examination between 1987 and 1991 are presented. The mean age of the 875 patients was 51.6 +/- 10.8 yr, and the mean duration of diabetes was 6.6 +/- 6.1 yr. After a mean follow-up time of 9.9 +/- 4.3 yr, the incidence rate of first LEA among diabetic Oklahoma Indians was 18.0/1000 person-yr. The incidence rate was two times higher in men than in women. In both sexes, significant risk factors (P < 0.05) were retinopathy and duration of diabetes. Fasting plasma glucose, use of insulin, and systolic blood pressure were significant for men only. For women, plasma cholesterol and diastolic blood pressure were additional risk factors. Compared with the mortality rate of 33.5/1000 person-yr among nonamputees, the rate among amputees was 55.5/1000 person-yr. The 5-yr survival rate after first amputation was 40.4%. For the amputees, the most common causes of death were diabetes (37.3%), cardiovascular disease (29.1%), and renal disease (7.3%). The incidence and mortality rates in diabetic Oklahoma Indians were higher than those reported in Pima Indians and other diabetic populations. To lower the incidence of lower-extremity amputation in this high-risk population, preventive action through education, foot care programs, and early detection of lesions must be intensified.
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PMID:Lower-extremity amputation. Incidence, risk factors, and mortality in the Oklahoma Indian Diabetes Study. 849 11

Expression of phosphoenolpyruvate carboxykinase (PEPCK), a rate-limiting enzyme in gluconeogenesis, is under dominant negative regulation by insulin. In this study, we sought to test the hypothesis that mutations in the PEPCK gene promoter may impair the ability of insulin to suppress hepatic glucose production, thereby contributing to both the insulin resistance and increased rate of gluconeogenesis characteristic of NIDDM. The proximal PEPCK promoter region in 117 patients with noninsulin-dependent diabetes mellitus and 20 obese Pima Indians was amplified by PCR and analyzed with single strand conformation polymorphism techniques. In addition, limited direct DNA sequencing was performed on the insulin response sequence and flanking regions. No DNA sequence polymorphisms were found in any patient. This result suggests that mutations in cis-acting PEPCK gene regulatory elements do not constitute a common cause of noninsulin-dependent diabetes mellitus. The significance of genetic variation in promoter regions to human disease is discussed.
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PMID:Examination of the phosphoenolpyruvate carboxykinase gene promoter in patients with noninsulin-dependent diabetes mellitus. 863 58

Recently, a missense mutation replacing tryptophan with arginine at codon 64 of the beta 3-adrenergic receptor gene was shown to be associated with insulin resistance in nondiabetic subjects and to an earlier onset of NIDDM in Pima Indians. We studied whether the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor gene in a cohort of young healthy Danes was associated with high birth weight, accelerated weight gain during childhood and adolescence, present obesity, or impaired insulin sensitivity. The protocol included 380 unrelated white subjects in whom insulin sensitivity and secretion were measured during a combined intravenous glucose and tolbutamide tolerance test. A number of biochemical and anthropometric characteristics were determined for each subject. The subjects were genotyped for the codon 64 polymorphism by applying polymerase chain reaction restriction fragment-length polymorphism screening with the use of endonuclease BstN1. The allelic frequency of the mutated allele was 7% (95% CI: 5-10%), and it was similar in obese and nonobese subjects. The beta 3-adrenergic receptor gene variant was not related to birth weight or weight gain during childhood or adolescence. In its heterozygous form, the gene variant was not associated with an altered insulin sensitivity index (SI) or other features of the insulin resistance syndrome (BMI, blood pressure, fasting serum lipid levels, or fasting serum fibrinolytic variables). Three homozygous carriers of the polymorphism were identified, and each had a significantly higher BMI (27.4 +/- 1.3 vs. 23.5 +/- 3.7 kg/m2 [mean +/- SD]; P = 0.032), lower SI [4.9 +/- 2.9 vs. 15.4 +/- 9.0 10(-5) x (min x pmol/l)-1; P = 0.013], and higher fasting serum C-peptide (730 +/- 155 vs. 471 +/- 158 pmol/l; P = 0.016) than the wild-type carriers. The homozygous carriers also had significantly higher levels of fasting serum triglyceride (P = 0.042) and serum LDL cholesterol (P = 0.013). When adjustments were made for age, sex, BMI, and VO2max in a multiple regression analysis, a significantly negative association was found between homozygosity for the codon 64 variant and the SI (P = 0.009). We conclude that in young healthy Danes, the homozygous form but not the heterozygous form of the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor may be associated with obesity and, independent of BMI, with a low SI. Since only three homozygous carriers were identified among 380 subjects, the results must be interpreted with caution, and studies of larger population samples are needed.
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PMID:Insulin sensitivity and body weight changes in young white carriers of the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor gene. 869 Jan 60

More than 50% of Pima Indians develop NIDDM. This disorder is preceded by impaired glucose tolerance (IGT) and we tested the hypothesis that the elevated glucose levels in IGT must be due to reduced beta-cell function. We first determined the plasma glucose/plasma insulin and plasma insulin/insulin resistance relationships in individuals with NGT, relationships which by definition must be normal, and determined if these relationships were intact in individuals with IGT. We also compared Pimas and Caucasians with NGT or IGT. Subjects were assessed with an OGTT, an IVGTT, underwater weighing (for body composition), and a euglycaemic clamp. The results showed that insulin concentrations in Pimas with IGT were not lower than the levels predicted by the relationships found in subjects with NGT. Compared to Caucasians, Pima Indians had elevated insulin concentrations at the same degree of insulin resistance. These studies indicate that insulin resistance, and not beta-cell failure, is the principal lesion determining IGT in Pimas. NIDDM occurs when beta-cell failure develops in the presence of insulin resistance. In some individuals of other races, beta-cell function may be less able to withstand insulin resistance, and presumably in these individuals beta-cell failure assumes a greater importance in the evolution to NIDDM.
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PMID:Impaired glucose tolerance in Pima Indians. 889 96

The prevalence of both NIDDM and IGT vary considerably within and between developing island populations of the Pacific and Indian Ocean regions. Longitudinal data have been collected recently in a number of these populations, allowing incidence rates to be compared. The incidence of NIDDM in adults ranged from a low of 1.2/1000 person-years (p.y.) in peri-urban and rural Papua New Guinea (PNG) Highlanders to 22.5/1000 p.y. in Micronesian Nauruans and 24.0/1000 p.y. in the rural Wanigelas of coastal PNG. Intermediate rates were observed in Polynesian Western Samoans (16.6 and 5.7/1000 p.y. in urban and rural areas, respectively) and ethnically diverse Mauritians: Asian Indians (15.8), African-origin Creoles (12.2), and Chinese (10.4/1000 p.y.). When stratified by age and body mass index (BMI), incidence in Wanigelas exceeded rates observed in Pima Indians, and rates in Mauritians were higher than those of Nauruans. For subjects with IGT at baseline, rates of conversion to NIDDM ranged from 19.0 to 102.6/1000 p.y. Particularly after stratifying for age and body mass index, it was apparent that there was less variation between populations in rates of decompensation from IGT than was observed for total incidence. The relative risk of conversion to NIDDM for IGT versus normal subjects ranged from 2.1 in urban Samoans to 7.6 in Nauruans, but most estimates exceeded 5.
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PMID:Incidence of NIDDM and the natural history of IGT in Pacific and Indian Ocean populations. 901 69

Risk factors associated with the progression from impaired glucose tolerance (IGT) to NIDDM were examined in data from six prospective studies. IGT and NIDDM were defined in all studies by World Health Organization (WHO) criteria, and baseline risk factors were measured at the time of first recognition of IGT. The studies varied in size from 177 to 693 participants with IGT, and included men and women followed from 2 to 27 years after the recognition of IGT. Across the six studies, the incidence rate of NIDDM was 57.2/1,000 person-years and ranged from 35.8/1,000 to 87.3/1,000 person-years. Although baseline measures of fasting and 2-h postchallenge glucose levels were both positively associated with NIDDM incidence, incidence rates were sharply higher for those in the top quartile of fasting plasma glucose levels, but increased linearly with increasing 2-h postchallenge glucose quartiles. Incidence rates were higher among the Hispanic, Mexican-American, Pima, and Nauruan populations than among Caucasians. The effect of baseline age on NIDDM incidence rates differed among the studies; the rates did not increase or rose only slightly with increasing baseline age in three of the studies and formed an inverted U in three studies. In all studies, estimates of obesity (including BMI, waist-to-hip ratio, and waist circumference) were positively associated with NIDDM incidence. BMI was associated with NIDDM incidence independently of fasting and 2-h post challenge glucose levels in the combined analysis of all six studies and in three cohorts separately, but not in the three studies with the highest NIDDM incidence rates. Sex and family history of diabetes were generally not related to NIDDM progression. This analysis indicates that persons with IGT are at high risk and that further refinement of risk can be made by other simple measurements. The ability to identify persons at high risk of NIDDM should facilitate clinical trials in diabetes prevention.
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PMID:Predictors of progression from impaired glucose tolerance to NIDDM: an analysis of six prospective studies. 907 14

Non-insulin-dependent diabetes mellitus (NIDDM) constitutes about 85% of all cases of diabetes in developed countries and it has now reached epidemic proportions in many developing nations, as well as disadvantaged groups in developed countries, e.g., Mexican- and African-Americans and Australian Aborigines and Torres Strait Islanders. The diagnosis of NIDDM is usually made after the age of 50 years in Europids, but it is seen at much younger age in these high prevalence populations, which also include Pacific Islanders, Native Americans, and migrant Asian Indians and Chinese. There is enormous variation in NIDDM prevalence between populations, and exceptionally high rates have been documented in populations who have changed from a traditional to a modern lifestyle, e.g., American Pima Indians, Micronesians, and other Pacific Islanders, Australian Aborigines, migrant Asian Indians, and Mexican-Americans. Over the next decade, following the initial phase of the NIDDM epidemic, macro- and microvascular complications will emerge as a major threat to future public health throughout the world with huge economic and social costs. The major cause of death in NIDDM is macrovascular disease (coronary artery, peripheral vascular, and cerebrovascular), which accounts for at least two-thirds of NIDDM mortality. A key strategy in reducing macrovascular disease lies in the better understanding of the Deadly Quartet or Metabolic Syndrome. New data suggest that hyperleptinemia rather than hyperinsulinemia may play an important and central role in the genesis of the cardiovascular disease risk factor cluster that constitutes the Metabolic Syndrome.
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PMID:The global epidemiology of non-insulin-dependent diabetes mellitus and the metabolic syndrome. 910 89

Non-insulin-dependent diabetes mellitus (NIDDM) and the renal disease attributable to it have been characterized extensively in the Pima Indians, a group of American Indians who form the Gila River Indian Community in Arizona. Both of these diseases are common in this community, and their onset and duration are known with greater certainty than in other populations because research examinations, which include oral glucose tolerance tests and measures of urinary protein excretion, have been performed frequently on most members of the population for the past 30 years. Studies of glomerular structure and hemodynamic function in diabetic Pima Indians indicate that glomerular hyperfiltration often develops at the onset of NIDDM and remains elevated until after overt nephropathy appears. Structurally, the glomeruli in subjects with microalbuminuria are not clearly distinguishable from those in subjects with normoalbuminuria, but macroalbuminuria is characterized by extensive glomerular sclerosis, mesangial expansion, and widening of epithelial cell foot processes that together lead to a rapid decline in the glomerular filtration rate. The decline in glomerular function in subjects with macroalbuminuria is due both to a loss of ultrafiltration surface area and to reduction in glomerular hydraulic permeability.
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PMID:Clinical and pathological course of renal disease in non-insulin-dependent diabetes mellitus: the Pima Indian experience. 914 78

In a population-based epidemiological study, 991 Pima Indians with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and 288 without diabetes aged > or =15 years were examined for retinopathy by fundus photography with a 45 degrees fundus camera after mydriasis. The photographs were graded using a modified Airlie-House classification scheme. The associations of several factors with retinopathy were studied by logistic regression. Non-proliferative retinopathy was present in 11.2 % (19/169) subjects at the time of diagnosis of diabetes and in 8.3% (4/48) in newly diagnosed subjects who had a documented non-diabetic oral glucose tolerance test within 4 years prior to diagnosis of diabetes. The prevalence of retinopathy in subjects with impaired glucose tolerance was 12% (8/68). Retinopathy at the time of diagnosis of diabetes was significantly associated with lower body mass index and higher systolic blood pressure but not glycaemia. Retinopathy was present in 375 (37.8 %) diabetic subjects and 14 (5.2 %) non-diabetic subjects. Among all subjects with diabetes (duration 0-37 years), stepwise multivariate analysis showed non-proliferative retinopathy to be associated with duration of diabetes, mean blood pressure, fasting plasma glucose, treatment with insulin and albuminuria. Proliferative retinopathy was seen in 34 (2.7%) of diabetic and none of the non-diabetic subjects, and was associated with 2 h post-load glucose concentrations, as well as albuminuria, insulin treatment, younger age, and diastolic blood pressure. These data confirm the need for fundus examination at the time of diagnosis of diabetes and during long-term follow-up. Albuminuria and blood pressure are potentially modifiable risk factors and the impact of treating these on incidence and progression of diabetic retinopathy need to be assessed.
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PMID:Diabetic retinopathy assessed by fundus photography in Pima Indians with impaired glucose tolerance and NIDDM. 921 9

Hyperinsulinemia is commonly associated with obesity, but it has not been determined which defect comes first. Some have proposed that hyperinsulinemia may precede obesity in populations prone to NIDDM, such as Pima Indians or Pacific Islanders. In contrast, longitudinal studies in adults show that insulin sensitivity and low fasting insulin concentrations are associated with increased weight gain, whereas insulin resistance seems to protect against weight gain. The present study examined whether fasting plasma hyperinsulinemia is a risk factor for weight gain in prepubertal children in the Pima Indian population-a population that is prone to obesity. Fasting plasma insulin concentration was measured in 328 5- to 9-year-old Pima Indian children (147 boys and 181 girls) with normal glucose tolerance. Follow-up weight was obtained an average of 9.3 +/- 1.9 years (means +/- SD) later at age 15-19 years. Fasting plasma insulin concentration correlated with the rate of weight gain per year in both boys (r = 0.42; P < 0.0001) and girls (r = 0.20; P < 0.01) and was associated with the rate of weight gain, independent of known determinants of weight change, i.e., initial relative weight, change in height, age, and sex. Similar relationships were found between fasting plasma insulin concentration and the change in relative weight and in triceps skinfold thickness-two indicators of obesity. In conclusion, fasting hyperinsulinemia may be a risk factor for the development of obesity in young children.
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PMID:Fasting hyperinsulinemia is a predictor of increased body weight gain and obesity in Pima Indian children. 923 60


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