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)

To elucidate the metabolism of islet amyloid polypeptide (IAPP) with respect to a possible renal elimination we investigated IAPP levels in 20 lean, nondiabetic patients with renal failure maintained on chronic hemodialysis (HD) and in 20 healthy controls. The basal levels of IAPP were significantly higher in uremic patients than in controls (15.1 +/- 3.2 vs. 3.2 +/- 0.2 pM, P < 0.001) suggesting renal excretion of IAPP. To investigate the impact of chronically elevated levels of endogenous IAPP on insulin secretion and insulin sensitivity, a frequently sampled intravenous glucose tolerance test (FSIGT) was performed in a subset of patients on hemodialysis and in age-matched healthy controls (C) and obese patients with normal (NGT) and with impaired glucose tolerance (IGT). Insulin sensitivity index (SI) was 8.7 +/- 1.5 in C (P < 0.05 vs. NGT, P < 0.01 vs. IGT), 5.4 +/- 0.9 in HD (P < 0.05 vs. IGT), 3.1 +/- 1.0 in NGT, and 2.0 +/- 0.5 in IGT. First phase insulin secretion was increased in patients on HD compared with those of several control groups. The results of this study therefore indicate a renal route of metabolism of IAPP. Increased endogenous circulating IAPP levels over a long period of time do not lead to a decrease in insulin release in patients on HD and do not cause the insulin resistance commonly seen in obesity and diabetes. Increased levels of circulating IAPP therefore are not likely to be a pathogenetic factor in the development of non-insulin-dependent diabetes mellitus (NIDDM).
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PMID:Increased levels of circulating islet amyloid polypeptide in patients with chronic renal failure have no effect on insulin secretion. 796 50

A four-yr prospective study was undertaken to examine the natural history of IGT in 128 South-African Indians classified as such at year 0 of the study, based on WHO criteria. Subjects were reexamined at year 1 and year 4. Of the 113 subjects who completed the study, 50.4% progressed to NIDDM (rate of progression 12.6%/yr), 24.8% persisted with IGT, and 24.8%, reverted to NGT. The majority (72%) who progressed to NIDDM did so in year 1. At year 1, 47 subjects were still classified as IGT; of the 40 subjects completing the study, 16 subjects (40%) progressed to NIDDM, 17 subjects (42.5%) persisted with IGT, and 7 subjects (17.5%) reverted to NGT. Examination of risk factors predictive of subsequent progression to NIDDM was undertaken by analysis of baseline variables in two ways: When year 0 was used as baseline (in 113 IGT0 subjects), significant predictive risk factors were the FPG and 2-h plasma glucose concentrations. All subjects who at year 0 had 2-h plasma glucose > or = 10.2 and < 11.1 mM or FPG > or = 7.3 but < 7.8 mM, subsequently progressed to NIDDM. When year 1 was used as baseline (40 IGT1 subjects), 90-min plasma glucose concentration (midtest level) was found to be a significant risk factor for development of NIDDM. In conclusion, this study has demonstrated that in South-African Indians with IGT, the majority (50.4%) progress to NIDDM within 4 yr; significant predictors of subsequent diabetes are the baseline fasting and 2-h plasma glucose concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1993 Apr
PMID:High risk of progression to NIDDM in South-African Indians with impaired glucose tolerance. 845 6

Cross-sectional associations between carotid artery stenosis (CAS) on the one hand, and parameters of glycaemia and specific insulin levels on the other, were investigated in an age, sex, and glucose tolerance stratified random sample from a 50-74-year-old Caucasian population. Subjects treated with insulin or oral hypoglycaemic agents were classified as having known diabetes mellitus (KDM) (n = 66). Using two oral glucose tolerance tests, and based on the World Health Organisation criteria, all other participants were classified as having a normal (NGT) (n = 287), an impaired (IGT) (n = 169) or a diabetic (NDM) (n = 106) glucose tolerance. CAS was defined haemodynamically using duplex scanning. The crude prevalences of only moderate (16-49%) CAS were 6.6%, 7.1%, 5.7% and 12.1% in NGT, IGT, NDM and KDM subjects, respectively. For any severe (> or = 50%) CAS, crude prevalences were 2.8%, 4.7%, 9.4% and 7.6%. The prevalence of any severe CAS was higher in NDM (p < 0.01) and KDM subjects (p = 0.07) than in NGT subjects. The prevalence of a history of stroke or transient ischaemic attack was 1.7%, 1.8%, 2.8% and 1.5% in NGT, IGT, NDM and KDM, respectively. In univariate logistic regression analysis, HbA1c, serum fructosamine, fasting and 2-h post-load glucose were significantly associated with any severe CAS. In multivariate analyses controlling for other risk factors, only HbA1c and 2-h post-load plasma glucose remained significantly associated (odds ratios: 1.29 per % and 1.09 per mmol/l, respectively) in separate models. No association could be shown between either fasting or 2-h post-load specific insulin and any severe CAS in either univariate or multivariate analyses. In conclusion, HbA1c and 2-h post-load plasma glucose are independently associated with any severe CAS, whereas specific insulin is not.
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PMID:Carotid artery stenosis is related to blood glucose level in an elderly Caucasian population: the Hoorn Study. 908 66

Type II (non-insulin-dependent) diabetes mellitus is a metabolically heterogeneous condition, and is invariably preceded by impaired glucose tolerance (IGT). We examined whether metabolic heterogeneity is a feature of IGT. Three subject groups were studied: IGT subjects with two or more living non-insulin-dependent diabetic relatives (IGTWF, n = 17), and IGT subjects (IGTWOF, n = 17) and subjects with normal glucose tolerance (NGT, n = 25) without a family history of diabetes. Glucose tolerance, glucose (KITTG) and nonesterified fatty acid (KITTNEF) insulin sensitivity, and first-phase insulin secretion (FPIS) were assessed by oral glucose tolerance (OGTT), insulin tolerance (ITT), and intravenous glucose tolerance (IVGTT) tests, respectively. Comparison of groups was made by ANOVA and t test. The three groups were matched for age, gender, body mass index (BMI), and waist to hip ratio (WHR). IGTWOF and IGTWF subjects had comparable 2-hour plasma glucose levels on OGTT, and insulin secretion and KITTG were decreased to comparable degrees. However, in comparison to IGTWF subjects, IGTWOF subjects had increased fasting serum triglyceride (geometric mean, 1.8 [range, 0.8 to 4.5] v 1.1 [0.4 to 2.5] mmol. L-1, P = .02) and 2-hour plasma nonesterified fatty acid ([NEFA] mean +/- SD, 0.12 +/- 0.07 v 0.08 +/- 0.03 mmol.L-1, P < .02) levels and decreased KITTNEF values (4.0 [1.7 to 8.9] v 6.2 [2.8 to 12.1]%.min-1, P < .02). Thus, the two IGT groups had comparable changes in glucose metabolism, but IGTWOF subjects had additional abnormalities of lipid metabolism. In conclusion, metabolic heterogeneity is a feature of IGT, and this may reflect underlying etiological heterogeneity.
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PMID:Metabolic heterogeneity in impaired glucose tolerance. 925 74

Although an increased plasma non-esterified fatty acid (NEFA) concentration has been shown to increase insulin resistance (Randle cycle), decrease insulin secretion and increase hepatic gluconeogenesis, the effect of NEFA on the deterioration of glucose tolerance has not been studied prospectively in Caucasian subjects. Therefore, we investigated whether plasma NEFA may be regarded as predictors of deterioration of glucose tolerance in subjects with normal (NGT, n = 3671) or impaired (IGT, n = 418) glucose tolerance who were participants in the Paris Prospective study. The subjects were first examined between 1967 and 1972 and underwent two 75-g oral glucose tolerance tests 2 years apart with measurements of plasma glucose, insulin and NEFA concentrations. Glucose tolerance deteriorated from NGT to IGT or non-insulin-dependent diabetes (NIDDM) in 177 subjects and from IGT to NIDDM in 32 subjects. In multivariate analysis, high fasting plasma NEFA in NGT subjects and high 2-h plasma NEFA and low 2-h plasma insulin concentrations in IGT subjects were significant independent predictors of deterioration along with older age, high fasting and 2-h plasma glucose concentrations and high iliac to thigh ratio. When subjects were divided by tertiles of plasma NEFA concentration at baseline, there was an increase in 2-h glucose concentration with increasing NEFA in the subjects who did not deteriorate, but no effect of plasma NEFA in those who deteriorated. In subjects with IGT who deteriorated compared with those who did not 2-h plasma insulin concentration was lower but there was no evidence that this resulted from an effect of plasma NEFA. Our data suggest that a high plasma NEFA concentration is a risk marker for deterioration of glucose tolerance independent of the insulin resistance or the insulin secretion defect that characterize subjects at risk for NIDDM.
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PMID:The role of non-esterified fatty acids in the deterioration of glucose tolerance in Caucasian subjects: results of the Paris Prospective Study. 930 Feb 48

Plasma leptin concentrations were measured in 144 non-diabetic men and women (age 21-73 years, BMI 14.8-37.7 kg m(-2)), in fasting samples collected during a population survey for diabetes mellitus. Leptin, fasting and 2-h post-glucose load plasma concentrations of glucose and immunoreactive insulin were measured. In a subset of 50 normoglycaemic individuals, subcutaneous fat (SF) and visceral fat (VF) areas at L4-L5 level were also measured by CT. As in other populations, women had significantly higher plasma leptin concentrations than men (p < 0.001) but the values were similar in normal (NGT) and impaired glucose tolerance (IGT). Geometric mean concentrations of leptin in men and women with NGT were 4.8 and 17.7 ng ml(-1), respectively, and the corresponding values in IGT were 6.2 and 19.0 ng ml(-1). Multiple regression analysis in the total group showed that the leptin concentration (log-transformed) was strongly dependent on sex (R2 = 53.4%), BMI (R2 = 17.4%), and to a lesser degree on the 2-h plasma insulin (R2 = 2.4%) and the WHR (R2 = 0.8%). In men, the total abdominal fat showed a strong association with leptin (R2 = 49.3%) and in women the subcutaneous fat area showed a similar effect (R2 = 39.5%). It is likely that subcutaneous and not visceral fat may be a determinant of plasma leptin in Asian Indians, and the correlation between leptin and insulin resistance may be less strong than in other ethnic groups.
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PMID:Plasma leptin in non-diabetic Asian Indians: association with abdominal adiposity. 940 Sep 17

The study was performed to determine plasma levels of proinsulin (PI) and specific insulin (SI) in normoglycemic (NGT) Asian Indians and to assess the effect of obesity and impaired glucose tolerance (IGT) on these concentrations. Blood samples from 151 adult nondiabetic South Indian subjects were collected during an epidemiological survey of diabetes. Plasma SI and PI levels were measured in fasting and 30-minute and 120-minute samples of a glucose tolerance test (World Health Organization criteria) using monospecific antibodies. The total insulin (TI) level was also measured by the nonspecific assay. The molar ratio of PI to SI (PI/SI) was calculated. Correlations of the peptides with anthropometry, serum lipids, and blood pressure (BP) were studied by univariate and multivariate analyses. Comparisons were also made in NGT versus IGT groups. As expected, TI values were higher than SI values, but the patterns of response were similar for both. SI and PI responses in NGT were similar to the values found in Mexican-Americans who had a higher body mass index (BMI). Asian Indians were thus found to have a high SI response despite a low BMI. Obesity and IGT produced an increased response of both PI and SI, with normal PI/SI ratios thus showing an absence of hyperproinsulinemia in either condition. Fasting PI showed a strong association with serum triglycerides, and proinsulin at 120 minutes was associated with cholesterol. None of the peptides showed a correlation with BP. Using specific assays for insulin and PI, it is shown that Asian Indians with NGT have a hyperinsulinemic response despite a low BMI. Obesity and mild hyperglycemia in IGT produce a simultaneous increase in PI and SI with no alteration in the PI/SI ratio.
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PMID:Specific insulin and proinsulin concentrations in nondiabetic South Indians. 947 76

Islet amyloid is a characteristic feature of type 2 diabetes. Its major component is the normal beta-cell secretory product amylin, or islet amyloid polypeptide (IAPP). To determine whether increased or disproportionate release of amylin may explain the propensity for amyloid deposition in type 2 diabetes, we measured plasma amylin-like immunoreactivity (ALI) and immunoreactive insulin (IRI) release in response to an oral glucose load in 94 Japanese-American subjects with normal glucose tolerance (NGT; n=56), impaired glucose tolerance (IGT; n=10), and type 2 diabetes (n=28) as defined by World Health Organization criteria. The incremental increase in ALI, IRI, and glucose (G) at 30 min after oral glucose ingestion was used to calculate deltaALI/deltaG and deltaIRI/deltaG as measures of beta-cell function. Overall glucose metabolism was assessed as the incremental glucose area (glucose AUC) during the 2 h of the oral glucose tolerance test. As expected, plasma glucose concentrations at both fasting (NGT, 5.0+/-0.4; IGT, 5.5+/-0.1; type 2 diabetes, 6.2+/-0.3 mmol/l; P < 0.0001) and 2 h (NGT, 6.7+/-0.1; IGT, 9.4+/-0.3; type 2 diabetes, 13.2 +/-0.5 mmol/l; P < 0.0001) were elevated in individuals with IGT and type 2 diabetes. In response to glucose ingestion, plasma IRI and ALI increased in all subjects, but these increments were lower in individuals with reduced glucose tolerance, as reflected in the deltaIRI/deltaG (NGT, 119+/-10.3; IGT, 60.7+/-7.1; type 2 diabetes, 49.7 +/-5.4 pmol/l; P < 0.0001) and deltaALI/deltaG (NGT, 2.6+/-0.2; IGT, 1.8+/-0.3; type 2 diabetes, 1.2+/-0.1 pmol/l; P < 0.0001). Moreover, these reductions in the 30-min incremental ALI and IRI responses were proportionate such that the molar ratio of ALI to IRI was not different among the three groups (NGT, 2.6+/-0.2; IGT, 2.9 +/-0.3; type 2 diabetes, 2.9+/-0.3%; NS). Further, the relationship between beta-cell function, measured as either deltaIRI/deltaG or deltaALI/deltaG, and glucose metabolism, assessed as glucose AUC, was nonlinear and inverse in nature, with r2 values of 0.38 (P < 0.0001) and 0.33 (P < 0.0001), respectively. We conclude that the reduced beta-cell function of IGT and type 2 diabetes includes proportionate reductions in both IRI and ALI release. Thus, it is unlikely that the development of islet amyloid in type 2 diabetes is the result of increased release of ALI.
Diabetes 1998 Apr
PMID:Reduced amylin release is a characteristic of impaired glucose tolerance and type 2 diabetes in Japanese Americans. 956 98

This study was done to analyse the dietary profile of urban south Indian adults. It was also aimed to study, if the dietary profile influenced the glycaemic and anthropometric data. Dietary details were collected in a representative urban sample of 900 study subjects in the epidemiological survey for diabetes conducted in 1995 in the city of Madras. The details were collected by a 24-h recall method. All the dietary factors were similar in the non-diabetic (NGT) and newly diagnosed diabetic cases, but the values were lower in known diabetic cases due to dietary modifications (P < 0.001 for all compared to NGT and new diabetic cases). For further analysis, known diabetic cases were deleted and the rest were combined as one group. Men consumed higher calories (2066+/-437, range 1028-3662 kcal) than women (1745+/-343, range 870-3260 kcal) (P < 0.01). Older persons consumed lower calories and percentages of the proximate principles in diet were proportionately lower. Higher calorie consumption was due to consumption of higher quantities of food and not any specific dietary factor. BMI, WHR, plasma glucose, serum cholesterol and triglycerides were not significantly influenced by the total calorie consumption. Calorie consumption was higher in persons engaged in strenuous physical activity. Total calories and proportionately the proximate principles of diet were less in the high income group. The similarity in diet in the non-diabetic and the newly diagnosed diabetic persons showed that the development of diabetes was probably not related to changes in dietary habits. Lower consumption of calories and carbohydrates by the known cases of diabetes was due to the dietary modifications introduced in the management of the disease. Lower calorie consumption in women and older people could be related to lower physical activity. This study shows a uniform dietary pattern among the different strata of society with minor variations based on age, gender and physical activity. No difference has been noted in dietary habits of the newly diagnosed diabetic subjects and the non-diabetic adults.
Diabetes Res Clin Pract 1998 Dec
PMID:Dietary profile of urban south Indians and its relations with glycaemic status. 992 49

High levels of plasminogen activator inhibitor-1 (PAI-1) and preponderance of small dense low-density lipoproteins (LDL) have both been associated with atherosclerotic disease and with the insulin resistance syndrome (IRS). In vitro studies have shown a stimulatory effect of various lipoproteins on PAI-1 release from different cells, including endothelial cells and adipocytes. The authors sought to investigate the relation of PAI-1 to LDL particle size in a large tri-ethnic population (n=1549) across different states of glucose tolerance. LDL size was determined by gradient gel electrophoresis, and PAI-1 was measured by a 2-site immunoassay, sensitive to free PAI-1. PAI-1 was inversely related to LDL size in the overall population (r=-0.21, P<0.0001), independent of gender and ethnicity. However, the authors found a significant interaction with glucose tolerance status (P=0.035). In univariate analysis, the association between PAI-1 and LDL size was most pronounced in subjects with normal glucose tolerance (NGT, r=-0.22, P<0.0001) and weaker in impaired glucose tolerance (IGT, r=-0.12, P=0.03) and type-2 diabetes (r=-0.10, P=0.02). After adjustment for demographic variables and metabolic variables known to influence PAI-1 levels (triglyceride and insulin sensitivity), a significant inverse relation of LDL size to PAI-1 levels was only present in NGT (P=0. 023). In subjects with IGT or overt diabetes, who usually have elevated PAI-1 levels, additional factors other than LDL size seem to contribute more importantly to PAI-1 levels. The demonstrated inverse relation of LDL size and PAI-1 levels provides one possible explanation for the atherogeneity of small dense LDL particles.
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PMID:Low-density lipoprotein particle size is inversely related to plasminogen activator inhibitor-1 levels. The Insulin Resistance Atherosclerosis Study. 1007 63


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