Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis of type 2 diabetes involves abnormalities in insulin action, insulin secretion, and endogenous glucose output (EGO). However, the sequence with which these abnormalities develop and their relative contributions to the deterioration in glucose tolerance remain unclear in the absence of a detailed longitudinal study. We measured insulin action, insulin secretion, and EGO longitudinally in 17 Pima Indians, in whom glucose tolerance deteriorated from normal (NGT) to impaired (IGT) to diabetic over 5.1 +/- 1.4 years. Transition from NGT to IGT was associated with an increase in body weight, a decline in insulin-stimulated glucose disposal, and a decline in the acute insulin secretory response (AIR) to intravenous glucose, but no change in EGO. Progression from IGT to diabetes was accompanied by a further increase in body weight, further decreases in insulin-stimulated glucose disposal and AIR, and an increase in basal EGO. Thirty-one subjects who retained NGT over a similar period also gained weight, but their AIR increased with decreasing insulin-stimulated glucose disposal. Thus, defects in insulin secretion and insulin action occur early in the pathogenesis of diabetes. Intervention to prevent diabetes should target both abnormalities.
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PMID:The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. 1049 14

With the release of the new 1997 American Diabetes Association diagnostic criteria, a new category was introduced, termed "impaired fasting glucose" (IFG). The metabolic abnormalities of individuals with IFG, compared with those with impaired glucose tolerance (IGT) (World Health Organization criteria), remain to be elucidated. We assessed insulin action (hyperinsulinemic clamp), insulin secretion (25-g intravenous glucose tolerance test), and endogenous glucose output (EGO) (3-(3)H-glucose) in 434 nondiabetic Pima Indians with either normal (NFG; <6.1 mmol/l) or impaired (IFG; 6.1-7.0 mmol/l) fasting glucose and with either normal (NGT; 2-h glucose <7.8 mmol/l) or impaired (IGT; 2-h glucose 7.8-11.1 mmol/l) glucose tolerance: NFG/NGT (n = 307), IFG/NGT (n = 11), NFG/IGT (n = 98), and IFG/IGT (n = 18). Compared with the NFG/NGT group, individuals with IFG/NGT had lower maximal insulin-stimulated glucose disposal (M; -20%, P < 0.01), a lower acute insulin response (AIR) to intravenous glucose (-33%, P < 0.05), and higher EGO (8%, P = 0.055). Individuals with NFG/IGT also had lower M (-21%, P < 0.001) and lower AIR (-8%, P < 0.05), but normal EGO (-1%, NS). Individuals with IFG/IGT showed the most severe abnormalities in M (-27%), AIR (-51%), and EGO (+13%) (all P < 0.001 compared with NFG/NGT). These group differences could be explained by the observation that AIR and EGO, but not M, were more strongly related to the fasting than to the 2-h glucose concentration. Thus, Pima Indians with isolated IFG and isolated IGT show similar impairments in insulin action, but those with isolated IFG have a more pronounced defect in early insulin secretion and, in addition, increased EGO. More severe metabolic abnormalities are present in Pima Indians with combined IFG and IGT.
Diabetes 1999 Nov
PMID:Metabolic characteristics of individuals with impaired fasting glucose and/or impaired glucose tolerance. 1053 54

We evaluated dietary habits as risk factor for glucose intolerance in a high risk population of Japanese-Brazilians enrolled in a study on the prevalence of diabetes (DM). Based on oral glucose tolerance test and WHO criteria, 331 had normal tolerance (NGT), 88 impaired tolerance (IGT) and 83 had type 2 DM (51 self-reported, 32 newly diagnosed diabetics). Clinical, laboratory and dietary data, assessed by food frequency questionnaire (FFQ), were compared between the NGT group and another composed of IGT and newly diagnosed DM (disturbed glucose tolerance or DGT group). Associations of total energy intake and nutrient intakes with glucose intolerance were analyzed by logistic regression. Also, subjects with NGT and DGT entered into separate models of multiple linear regression including BMI as the dependent variable, and total energy intake or each nutrient as independent variables. DGT group showed higher waist-to-hip ratio, blood pressure, plasma glucose and insulin levels and worse lipid profile. Total energy intake, macronutrients, fibers, alcohol and saturated fat intakes did not differ between groups; DGT was not associated with any nutrient intake in multivariate analyses. BMI of the subjects with DGT but not with NGT was associated with protein and cholesterol intakes in linear regression analysis. Our findings did not support an association between nutritional factors and glucose intolerance even in subjects who are unaware of their DGT, using FFQ to reflect current habits. However, we suggest that protein and cholesterol intakes may be markers of increased BMI. Despite assuming that obesity and insulin resistance precedes DM, FFQ may not be useful in the assessment of unfavorable dietary patterns among subjects at risk for glucose intolerance, such as Japanese-Brazilians with elevated BMI.
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PMID:Dietary patterns in a high-risk population for glucose intolerance. Japanese-Brazilian Diabetes Study Group. 1077 35

According to data from prevalence study on population from Pingdingshan coal mining districts in Henan province, we analysed 174 patients with diabetes mellitus(DM) and 3,066 control subjects with normal blood glucose(NGT) by a population-based case-control study. After the adjustment of other factors and controlled on confounding factors, the results of unconditional logistic multivariate regression analysis demonstrated that age, DM history of mother and sib, highest BMI through one's life, higher concurrent WHR, higher systolic blood pressure, frequently eating Chinese sorghum and legume may serve as independent risk factors of DM, their odds ratios(OR) were 2.04, 6.04, 2.24, 1.85, 2.57, 1.51, 2.22, 1.25 and their population attribution rates (PAR%) were 80.04%, 7.19%, 3.18%, 37.35%, 48.80%, 8.15%, 3.20%, 10.63% respectively. Higher occupational physical activity and frequently eating vegetables of light colour might serve as independent protective factors of DM, with ORs 0.89 and 0.50 and PAR% of -19.20% and -269.5% respectively. Confounding analysis showed that age was both a positive and negative confounding factor to other factors in the logistic regression model.
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PMID:[Analysis on the risk factors in patients with diabetes mellitus from population in mining districts--a population-based case-control study]. 1092 Nov 20

Age, female sex, and obesity are well-known risk factors for gallstones; in contrast the possible role of type 2 diabetes mellitus (type-2 DM) is controversial. One reason for this discrepancy might be that type 2 DM is often accompanied by obesity. Therefore, the aim of this study was to evaluate the importance of obesity and of type 2 DM, separately and together, as risk factors for gallstones. In all, 203 obese patients with normal glucose tolerance (obese NGT), 446 obese patients with type 2 DM (obese type 2 DM), 269 lean patients with type 2 DM (lean type 2 DM) and 250 lean subjects with a normal glucose tolerance (lean NGT) were evaluated by ultrasonography for the presence of gallstones. At univariate analysis patients with gallstones (177) were older and were more frequently affected by both obesity and type 2 DM, and had higher triglycerides and fasting blood glucose levels. At multiple logistic regression analysis, only age and obesity, both in the presence or in absence of type 2 DM, were strongly associated with gallstones (P < 0.001); diabetes alone had a lower level of statistical significance (P = 0.07). These data suggest that obesity is a stronger risk factor for gallstones than type 2 DM.
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PMID:Association of obesity and type II diabetes mellitus as a risk factor for gallstones. 1111 74

Although insulin resistance has been shown to be a primary defect causing type 2 (non insulin-dependent) diabetes mellitus in Pima Indians and Caucasians, insulin secretory defect has also been known to be an important factor in the development of type 2 diabetes. We undertook a study to investigate the initial abnormality of glucose intolerance in Koreans. A total of 370 Korean subjects were classified into 5 groups according to their degree of glucose intolerance (normal fasting glucose [NFG]/normal glucose tolerance [NGT], n = 95; impaired fasting glucose [IFG]/NGT, n = 29; NFG/impaired glucose tolerance [IGT], n = 60; IFG/IGT, n = 68; diabetes, n = 118). Insulinogenic index was used as an index of early-phase insulin secretion. Insulin resistance was assessed by the R value of the homeostasis model assessment [HOMA(R)]. Insulinogenic index significantly decreased in subjects with IFG/NGT and NFG/IGT compared with those with NFG/NGT. However, there was no significant difference in HOMA(R) between subjects with NFG/NGT and those with IFG/NGT or NFG/IGT. Insulinogenic index decreased significantly with the increase of plasma glucose 120-minute value at the earlier stage of glucose intolerance compared with HOMA(R). These results suggest that early-phase insulin secretory defect may be the initial abnormality in the development of type 2 diabetes in Korean subjects.
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PMID:Insulin secretory dysfunction and insulin resistance in the pathogenesis of korean type 2 diabetes mellitus. 1131 22

We tried to characterize the clinical features associated with glucose metabolism in the development of diabetes. Study subjects were glucose-tolerant subjects without a family history of diabetes (normal glucose tolerance [NGT]1 group, n = 15) and with a first-degree diabetes relative (NGT2, n = 9), 12 subjects with impaired glucose tolerance (IGT), and 13 subjects with type 2 diabetes mellitus (DM). The first phase C-peptide secretion (CS1), insulin sensitivity (Si), and glucose effectiveness (Sg) were assessed by the combination of C-peptide 2-compartment model and minimal model analyses. Using these parameters, each group was characterized: CS1 was decreased in NGT2 and IGT compared with NGT1 and further decreased in DM; Si was not different among NGT1, NGT2, and IGT, whereas Si was decreased in DM; CS1 x Si value was decreased in NGT2 compared with NGT1 and decreased in IGT, DM, progressively; Sg was decreased in IGT and DM compared with NGT1 and NGT2. CS1 x Si and Sg values could segregate each group distinctively, although it had a large variety of phenotypes. CS1 x Si value and Sg are assumed to represent the contributions of insulin-dependent and independent mechanisms to glucose tolerance, respectively, and thus, both mechanisms should play an important role in the characterization of pathophysiologic phenotypes of the subjects with various degrees of glucose tolerance.
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PMID:Pathophysiologic phenotypes of Japanese subjects with varying degrees of glucose tolerance: using the combination of C-peptide secretion rate and minimal model analysis. 1143 87

Impaired glucose tolerance (IGT) and type 2 diabetes including undiagnosed isolated postchallenge hyperglycemia (IPH) are common in the elderly. The aim of this study was to investigate the insulin secretion and sensitivity in Korean elderly lean diabetic women. Forty-one lean women aged 65-88 years took 2 hr oral glucose tolerance test (OGTT) and were stratified according to the WHO criteria (normal glucose tolerance [NGT], n=20; IGT, n=6; and type 2 diabetics, n=15 including seven IPH). HbA1c and fructosamine progressively increased from the NGT to the diabetic subjects (p=0.006 and p=0.001, respectively). Compared with subjects with NGT, the insulinogenic index, a marker of early insulin secretion and the AUC(ins), a marker of total insulin secretion, decreased significantly in diabetic group [0.53 (-0.44 -1.45) vs. 0.18 (0.00 -1.11), p=0.03 and 306+/-165 vs. 199+/-78 pmol/L, p=0.02 respectively]. A significant difference was found in the AUC(c-peptide) among each group (221+/-59 vs. 206+/-34 vs. 149+/-51 pmol/L, p=0.001 for each). The homeostasis model assessment of insulin resistance (HOMA-IR), a marker of insulin resistance, was not different among the groups. We conclude that compared with NGT subjects, elderly lean women with diabetes have impaired oral glucose-induced insulin secretion but have relatively preserved insulin sensitivity. This suggests that insulin resistance is not necessarily an essential component of Korean elderly lean diabetic women.
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PMID:Insulin secretion and sensitivity during oral glucose tolerance test in Korean lean elderly women. 1164 28

The aim of the study was to describe 5-year changes in meal-stimulated pancreatic insulin reserve in adults with normal and impaired glucose tolerance (NGT, IGT) and diabetes, with or without islet-related antibodies. This was a 5-year follow-up of 270 residents of Wadena, MN, of northern European origin, with good kidney function, defined as creatinine clearance greater than 60 mL/min/1.73 m(2). The subjects comprised a population-based sample originally studied in 1986 to 1987. Urine C-peptide (CP), in a 260-minute collection, was the integrated measure of insulin secretion; Ensure-Plus (Ross, Columbus, OH) was the liquid meal. Islet cytoplasmic antibodies (ICA), insulin autoantibodies (IAA), and glutamate decarboxylase antibodies (GAD65ab) were measured. In 182 subjects with NGT, there was no mean within-subject change in urine CP over 5 years (P =.34). In 41 subjects with impaired GT (IGT), there was a moderate, but nonsignificant, increase in mean CP, and 6 (15%) subjects increased. In 37 type 2 diabetic subjects not taking insulin (type 2-No Ins), who had a mean diabetes duration at the 5-year examination of 9.6 +/- 6.3 years, there was a 21% decrease in mean urine CP (P =.012), attributable mostly to a major drop in 8 of the 37 subjects (22%). Islet-related antibody tests were mostly negative; GAD65ab positivity was related to CP decline only among insulin-taking subjects. In summary, in Wadena adults, meal-stimulated urine CP was stable or increased over 5 years in subjects with NGT and IGT, but CP decreased significantly in about one fifth of type 2-No Ins subjects, with no relation to antibody test results.
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PMID:Declining beta-cell function in type 2 diabetes: 5-year follow-up and immunologic studies of the population of Wadena, MN. 1183 39

A G-to-A (UCSNP-43) polymorphism of the calpain-10 gene was significantly associated with type 2 diabetes (DM) in Mexican-American, and was postulated, together with a T-to-C (UCSNP-44) polymorphism, as a risk factor for DM. We examined the association of these genotypes with DM in Japanese. Eighty-one subjects with DM and 81 non-diabetic subjects (NGT) were recruited. The number of subjects with genotypes UCSNP-43 G/G, G/A and A/A were 76, 5 and 0, respectively, for the DM and NGT groups. The number of subjects with genotypes UCSNP-44 T/T, T/C and C/C were 66, 14 and 1 for the DM group and 64, 17 and 0 for the NGT group. There was no difference between the groups in terms of frequency of any genotype combinations. No association between the genotypes and DM was observed. We next examined the differences between the genotypes or genotype combinations in terms of the traits related to DM, obesity, hypertension and dyslipidemia. No differences were observed between the genotypes UCSNP43 G/G and G/A, between UCSNP-44 T/T and the others, or between the genotype combination UCSNP-43 G/G and UCSNP-44 T/T and the others, except that the individuals with the genotype combination had significantly increased serum cholesterol levels (212.6 +/- 34.3 vs. 198.5 +/- 29.9, P=0.020). The genotype combination might be a risk factor, not for DM, obesity and hypertension, but for increased serum cholesterol.
Diabetes Res Clin Pract 2002 May
PMID:Calpain 10 gene polymorphisms are related, not to type 2 diabetes, but to increased serum cholesterol in Japanese. 1189 Oct 23


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