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)

The mean glomerular volume, glomerular fraction of cortical volume, and percentage of obsolescent glomeruli were calculated in kidney specimens from autopsies on 34 Pima Indians, of whom 15 had non-insulin dependent diabetes mellitus and kidney disease of diabetes mellitus. These values were compared with those of black, white, and non-Pima native American individuals without diabetes mellitus. Glomerular volume in the Pima Indians was similar in the diabetic and nondiabetic subjects and significantly greater than in the white subjects. Black and non-Pima native American individuals had glomerular volumes intermediate between white individuals and Pima Indians. The mean glomerular volume was not affected by the number of obsolescent glomeruli in diabetic Pima Indians. The glomerular volume fraction was greater in the Pimas than in the other groups. These data showed that glomerular volume in the Pima Indians was significantly greater than that in white subjects. There was no difference between diabetic and nondiabetics Pimas, and glomerular size was not correlated with the presence or degree of glomerulosclerosis in this population.
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PMID:Large glomerular size in Pima Indians: lack of change with diabetic nephropathy. 139 22

Four overlapping DNA fragments spanning 32 kb containing the human GLUT4 facilitative glucose-transporter gene were isolated and characterized. The sequence of the GLUT4 gene (approximately 6.3 kb) and 2.0 kb of the promoter region was determined. The sequence of the promoter revealed potential binding sites for transcription factors known to regulate gene expression in muscle cells and adipocytes. However, transfection of constructs including 2 kb of the GLUT4 promoter fused to the bacterial CAT gene into 3T3-L1 adipocytes displayed only weak promoter activity. Because insulin resistance plays a prominent role in the development of NIDDM, genetic variation in the sequence of GLUT4 also was evaluated. Oligonucleotide primer pairs were selected that allowed the protein-coding region of the human GLUT4 gene to be amplified by PCR. The sequence of the protein-coding region of the GLUT4 gene and all intron-exon junctions was determined for a single diabetic Pima Indian and was identical to that of the cloned gene and cDNA. SSCP analysis was used to screen patients with diabetes mellitus and normal, healthy nondiabetic individuals for mutations at the GLUT4 locus. In addition to the silent substitution in the codon for Asn130 (AAC or AAT) and a Val383 (GTC)-->Ile(ATC) replacement described previously, two new variants were identified. One was a T-->A substitution in intron 1 that was found in 1 of 36 NIDDM patients who were typed for this variant. The second was a Ile385(ATT)-->Thr(ACT) replacement that occurred in 1 normal individual and was not found in any of 676 other normal and diabetic subjects. A large and racially diverse group of normal and diabetic individuals also was screened for the Ile383 polymorphism. It occurred in both diabetic and nondiabetic subjects. There is no indication from our data that these polymorphisms are associated with NIDDM.
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PMID:Human GLUT4/muscle-fat glucose-transporter gene. Characterization and genetic variation. 139 19

The prevalence and incidence of CHD, defined by ECG abnormalities according to the Tecumseh criteria for Minnesota Codes, were determined in Pima Indians greater than or equal to 25 yr of age. In a cross-sectional analysis, the age-sex-adjusted prevalence (+/- SE) of ECG abnormalities was higher in 1454 NIDDM patients (6.86 +/- 0.65%) than in 1696 nondiabetic subjects (3.23 +/- 0.63%; prevalence rate ratio = 2.12; 95% CI 1.39-3.25). In a prospective analysis, the age-sex-adjusted incidence (+/- SE) of ECG abnormalities was higher in 824 NIDDM patients (12.77 +/- 1.67) than in 935 nondiabetic subjects (5.93 +/- 1.43 cases/1000 person-yr; incidence rate ratio = 2.15; 95% CI 1.26-3.69). The prevalence of ECG abnormalities in insulin-treated NIDDM patients was significantly higher than in NIDDM patients not treated with insulin (age-sex-adjusted OR = 2.83; 95% CI 1.84-4.33); and this association persisted when adjusted for other factors such as sBP, BMI, duration of diabetes, serum cholesterol concentration, and oral hypoglycemic agents (OR = 2.12; 95% CI 1.34-3.37). In the prospective analysis, the incidence of ECG abnormalities in NIDDM patients treated with insulin was higher than in those NIDDM patients not treated with insulin, but, when controlled for age, sex, duration of diabetes, and oral hypoglycemic agents in a proportional-hazards model, the relationship with insulin treatment was not statistically significant (incidence rate ratio = 1.36; 95% CI 0.80-2.31). This suggests that insulin treatment may be a marker of more severe diabetes, and that factors associated with clinical indications for insulin treatment, rather than insulin treatment per se, are related causally to CHD. On the other hand, endogenous fasting and 2-h postload serum insulin concentrations were not associated with ECG abnormalities among 761 NIDDM patients not treated with insulin nor among 1226 nondiabetic subjects. Furthermore, in the prospective study, neither endogenous fasting nor 2-h postload serum insulin was associated with the subsequent development of ECG abnormalities in NIDDM patients or nondiabetic subjects.
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PMID:Insulin treatment, endogenous insulin concentration, and ECG abnormalities in diabetic Pima Indians. Cross-sectional and prospective analyses. 149 65

More than half the Pima Indians over 35 years of age have non-insulin dependent diabetes mellitus (NIDDM). They have been the focus of prospective epidemiologic and metabolic studies for over two decades and the data collected during these studies are now proving invaluable in efforts to find genetic markers for NIDDM in humans. The Pima Indian model of this disease affords two major advantages. The population is genetically homogeneous compared to Caucasian populations, and therefore the causes of NIDDM are less heterogeneous, simplifying genetic linkage studies. Equally important, based on results from metabolic studies, two pre-diabetic phenotypes have been identified in the Pimas: insulin resistance and a low metabolic rate. Use of these phenotypes in genetic linkage analyses should greatly improve chances of finding genetic markers for NIDDM since these phenotypes may be more closely related to the putative abnormal gene products, and actual disease genes, than is the hyperglycemia of the fully developed phenotype of NIDDM.
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PMID:Pima Indians as a model to study the genetics of NIDDM. 157 73

Type 2, non-insulin-dependent diabetes mellitus accounts for 60% of the end-stage renal disease attributed to diabetes in the United States, yet little is known about glomerular function or the development of renal disease in this type of diabetes. The Diabetic Renal Disease Study (DRDS) is a longitudinal study designed to elucidate the natural history of renal disease and to characterize glomerular function throughout the course of renal disease in type 2, non-insulin-dependent diabetes mellitus. The study is being conducted among the Pima Indians from the Gila River Indian Community in Arizona because they experience a very high rate of type 2 diabetes mellitus, which often develops at a young age and which is frequently associated with the development of renal disease. Glomerular filtration rate, renal plasma flow, albumin and IgG excretion, level of vasoactive hormones, retinal damage, and glomerular capillary permeability to dextrans of different sizes will be assessed at regular intervals over 48 months in six groups of subjects representing a range of glucose tolerance from normal to diabetes, and among the diabetic subjects, a range of proteinuria from normal to overt diabetic nephropathy. The DRDS is designed to provide new information on the functional determinants of renal disease in type 2, non-insulin-dependent diabetes mellitus and will serve as the basis for designing intervention strategies.
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PMID:Renal function in non-insulin-dependent diabetes mellitus: purposes and design of the Diabetic Renal Disease Study. 177 50

In examining the pathophysiology underlying the development of hypertension in diabetes mellitus, it is important to draw clear distinctions between Type I and Type II diabetes. In patients with Type I diabetes, with a peak onset of disease early in the second decade of life, hypertension clearly represents the sequelae to the development of substantial renal lesions, especially in the glomerulus. Thus the prevalence of hypertension in those patients without substantial glomerular lesions approximates the incidence of hypertension in the general population (approximately 4%). In patients with Type II diabetes mellitus and onset generally later in adult life, an increase in blood pressure can often be demonstrated early after or even before diagnosis of the disease (most readily demonstrated in the Pima Indians). Furthermore, clear familial tendencies towards the development of nephropathic complications of diabetes can be shown. In patients with Type I disease, the fall in glomerular filtration rate parallels the fall in glomerular capillary surface available for filtration. This reduction in the peripheral glomerular capillary surface correlates well with the expansion of the mesangium, strongly implicating the mesangial expansion in the demise in renal function. For both Type I and Type II diabetes mellitus, the increase in albuminuria may reflect an opening of large pores in the glomerular basement membrane, thereby allowing serum proteins to cross into the filtration space.
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PMID:Diabetic nephropathy: a disease causing and complicated by hypertension. 191 99

The relationship between diabetes mellitus and oral health status was determined in Pima Indians from the Gila River Indian Community in Arizona. This tribe of native Americans has the world's highest reported incidence and prevalence of non-insulin-dependent (type 2) diabetes mellitus. The probing attachment level, alveolar bone loss, age, sex, Calculus Index, Plaque Index, Gingival Index, fluorosis, and DMFT as well as the diabetic status was assessed in 1,342 Pima Indians who were at least partially dentate. The prevalence and severity of destructive periodontal disease was determined by measuring probing attachment loss and radiographically apparent interproximal crestal alveolar bone loss, two independent but correlated indicators of periodontal destruction. Only diabetic status, age, and the presence of subgingival calculus were significantly associated with both increased prevalence and greater severity of destructive periodontal disease in this population. Diabetic status was significantly and strongly related to both the prevalence and severity of disease after adjusting for the effects of demographic variables and several indices of oral health including the Plaque Index. Subjects with type 2 diabetes have an increased risk of destructive periodontitis with an odds ratio of 2.81 (95% confidence interval 1.91 to 4.13) when attachment loss is used to measure the disease. The odds ratio for diabetic subjects was 3.43 (95% confidence interval 2.28 to 5.16) where bone loss was used to measure periodontal destruction. These findings demonstrate tht diabetes increases the risk of developing destructive periodontal disease about threefold. Furthermore, diabetes increases the risk of developing periodontal disease in a manner which cannot be explained on the basis of age, sex, and hygiene or other dental measures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Periodontal disease in non-insulin-dependent diabetes mellitus. 202 65

The mechanisms by which high-carbohydrate, low-saturated-fat diets lower LDL cholesterol (LDLC) concentrations are unknown. In this study, kinetics of VLDL, intermediate density lipoprotein (IDL), and LDL apoprotein B and VLDL triglyceride were determined in seven nondiabetic (ND) and seven non-insulin-dependent diabetic (NIDDM) Pima Indian subjects on high-fat and high-carbohydrate (HICHO) diets. Metabolic changes were similar in ND and NIDDM. On the HICHO diet, LDLC decreased (131 +/- 8 vs. 110 +/- 7 mg/dl, P less than 0.0001) in all subjects. Mean fasting and 24-h triglyceride (TG) concentrations were unchanged, as were mean production rates and fractional clearance rates (FCR) of VLDL apoB and VLDL TG. The mean VLDL apoB pool size (303 +/- 20 vs. 371 +/- 38 mg, P = 0.01) increased owing to a decrease in the mean transport rate (10.7 +/- 1.1 vs. 8.4 +/- 0.9 mg/kg fat-free mass (ffm) per day, P less than 0.0001) and the mean rate constant (2.3 +/- 0.2 vs. 1.5 +/- 0.2, P less than 0.001) for the VLDL apoB to IDL apoB conversion pathway. The mean transport rate of VLDL apoB to LDL apoB via IDL (10.2 +/- 0.9 vs. 8.0 +/- 0.8 mg/kg ffm per day, P less than 0.001) decreased. Mean LDL apoB concentrations decreased (70 +/- 5 vs. 61 +/- 5 mg/dl, P less than 0.001) on the HICHO diet. Means for total LDL apoB transport rate, LDL apoB FCR, and LDLC/apoB ratios were unchanged. In summary, the HICHO diet decreased the activity of mechanisms that convert VLDL to LDL, which contributed to the decrease in LDLC in all subjects. There was also evidence in some subjects for increased activity of LDL apoB clearance mechanisms, and a decrease in the LDLC to apoB ratio.
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PMID:Effect of a high-carbohydrate, low-saturated-fat diet on apolipoprotein B and triglyceride metabolism in Pima Indians. 220 Aug 8

The relationship between type 2 diabetes mellitus and periodontal disease was evaluated in 2,878 Pima Indians of the southwestern United States. Two independent measures of periodontal disease, probing attachment loss and radiographic bone loss, were used to compare prevalence and severity of periodontal disease in diabetic and nondiabetic subjects. In all age groups studied, subjects with diabetes had a higher prevalence of periodontal disease, indicating that diabetes may be a risk factor for periodontal disease.
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PMID:Type 2 diabetes mellitus and periodontal disease. 221 46

Renal failure among elderly individuals with diabetes is a substantial clinical and public health problem. These individuals account for the majority of renal failure among people with diabetes mellitus in the United States. Although limited population-based data directly provide evidence regarding the incidence of and risk factors for ESRD, extant data suggest that blacks and Pima Indians have a markedly increased risk of ESRD compared with whites in the United States. Proteinuria and microalbuminuria appear to be extremely common in elderly individuals with NIDDM and are strongly associated with overall survival, cardiovascular morbidity and mortality, and the development of ESRD. Although randomized clinical trials are needed to test intervention strategies to reduce morbidity and mortality associated with renal disease among individuals with NIDDM, extant data suggest that management efforts directed at hypertension control and, possibly, moderate restriction of protein intake may be important therapeutic modalities for prevention of renal disease and its associated sequelae among elderly individuals with diabetes.
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PMID:Renal complications in non-insulin-dependent diabetes mellitus. 222 48


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