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)

A defect in the early phase of insulin secretion has been proposed as a major determinant of the impaired glucose homeostasis of adult onset diabetes. Since the process of aging is also associated with a deterioration of glucose tolerance, we have measured the acute phase of insulin secretion and glucose disposal rate (KG) after a 20 g glucose pulse in 11 normal, healthy men greater than 65 yr and compared it with the response in 11 nondiabetic men 20-31 yr. The mean fasting plasma sugar levels of the aged subjects (107 mg/dl), tended to be higher than that of the young (94 mg/dl). Comparison of Kg provided clear separation (P less than 0.01) of the old (mean Kg = 0.93) from the young population (mean Kg = 1.95). The acute insulin response to the glucose pulse when expressed either as the area above basal for the 10 min post stimulation or as the mean encremental increase above basal at 3, 4 and 5 min (delta 3-5 IRI) was the same in both timing and magnitude for the old and young subjects. Although our aged subjects had clearly abnormal kg's their acute phase of insulin secretion in response to glucose was normal. Seven noninsulin requiring diabetics with fasting plasma glucose levels greater than 140 mg/dl similarly studied had abnormal kg's (mean = 0.55) but markedly attenuated early release of insulin. Therefore, even though in the diabetics a deficiency of acute phase insulin secretion may have contributed to their impaired kg, in our aged subjects the lack of correlation between kg and a deficiency of acute phase insulin release suggests that factors other than an impairment in the early phase of insulin secretion are responsible for their glucose intolerance or, that there is a dissociation between the biologic and immunologic activity of insulin in these aged subjects.
J Clin Endocrinol Metab 1975 Sep
PMID:Acute-phase insulin secretion and glucose tolerance in young and aged normal men and diabetic patients. 115 58

The application of molecular scanning techniques to the detection of potentially pathogenic mutations in candidate genes in patients with non-insulin-dependent diabetes has revealed a number of molecular variants of uncertain pathophysiologic significance. The determination of the significance of such variants requires large-scale population studies of the prevalence of the mutant in affected and control groups. Herein, we describe two adaptations of the technique of single nucleotide primer extension (SNuPE) which allow the simultaneous examination of large numbers of alleles at multiple loci. The usefulness of these adaptations is illustrated by their application to the simultaneous detection of three point mutations, two in the tyrosine kinase domain of the insulin receptor and one in the insulin-responsive glucose transporter (GLUT4) in a highly insulin-resistant NIDDM population. By pooling genomic or amplified DNA and performing the SNuPE reactions with three primers of different length we could readily examine 300 alleles on a single 20 lane gel. Using pooled SNuPE, we also examined a large British Caucasian control population for the prevalence of GLUT4 Ile383, a variant which has previously been reported only in NIDDM. GLUT4 Ile383 was detected in 2/42 of the highly insulin-resistant NIDDM subjects and 4/240 middle-aged blood donors. Family studies and examination of the expressed mutant transporter will be necessary to establish whether this mutation is of functional significance. Pooled and multiplex SNuPE are powerful techniques with wide applicability to population genetic studies of specific mutations.
Hum Mol Genet 1992 Sep
PMID:Rapid and simultaneous detection of multiple mutations by pooled and multiplex single nucleotide primer extension: application to the study of insulin-responsive glucose transporter and insulin receptor mutations in non-insulin-dependent diabetes. 130 12

To examine the release of insulin in response to oral glucose, intravenous glucagon and intravenous arginine, we measured the levels of plasma glucose, immuno-reactive insulin (IRI) and C-peptide levels on fasting and following an oral glucose loading (OGTT), intravenous glucagon (GON) and arginine (ARG) infusion test in nine newly diagnosed non-insulin dependent diabetics. Their ages ranged from 38 to 65. The fasting plasma glucose and hemoglobin A1c levels were 240 +/- 14 mg/dl (Mean +/- SEM) and 10.7 +/- 0.54%, respectively. Mean values of the peak C-peptide/fasting C-peptide ratio and peak IRI/fasting IRI ratio were significantly increased, as compared with the basal level (P < 0.05), but not significantly different from those of the OGTT, GON and ARG test. In conclusion, the effect of arginine-induced insulin secretion in non-insulin dependent diabetes mellitus is as good as those of glucose or glucagon.
Zhonghua Yi Xue Za Zhi (Taipei) 1992 Sep
PMID:Arginine induced insulin release in patients with newly onset non-insulin-dependent diabetes mellitus. 133 Feb 42

It is clearly recognized that patients with NIDDM have an increased risk for CHD. Recent data indicate that persons with glucose concentrations in the nondiabetic range also may be at higher risk for CHD. These associations may not represent cause and effect, however. Emerging data suggest that hyperglycemia and CHD may both arise from hyperinsulinemia/insulin resistance. In support of this hypothesis are studies showing that NIDDM and CHD have many risk factors in common, including age, elevated blood pressure, dyslipidemia, adiposity, and a central pattern of fat distribution. Moreover, these risk factors are frequent concomitants of hyperinsulinemia, itself a risk factor for CHD and perhaps for NIDDM. Although the duration of NIDDM has been infrequently related to risk of CHD, the authors hypothesize that duration of hyperinsulinemia/insulin resistance would be a more sensitive marker for risk of CHD. The relation of IDDM to CHD is a different situation. The etiological process leading to IDDM, namely the destruction of beta-cells in genetically predisposed persons, is not related to cardiovascular risk. However, IDDM patients still have an excess of CVD, the risk factors for which may vary according to the location of the diseases (e.g., LEAD vs. CHD). There is a strong relationship between proteinuria and CVD, which has led to a general theory of vascular complications in IDDM based on defective heparan sulfate metabolism (Steno hypothesis). Recent evidence challenges parts of this hypothesis, and the possibility is raised that a higher case-fatality rate in a subgroup of patients with both renal and CVD explains part of the renal connection, as does the general worsening of CVD risk factors.
Diabetes Care 1992 Sep
PMID:Diabetes mellitus and macrovascular complications. An epidemiological perspective. 139 12

Not all patients with diabetes develop clinically significant nephropathy and, for this reason, attention has begun to focus on the risk factors for development of this serious complication. These risk factors have not been quantified to the same degree as those factors associated with more common progressive vascular diseases, such as atherosclerosis. However, studies of pathogenesis and clinical and epidemiological surveys of diabetic nephropathy point to numerous risk categories. Glycemic control, genetic and familial predispositions, renal and glomerular enlargement, glomerular hyperfiltration, and capillary and systemic hypertension can be invoked as contributors to this disease process. This review focuses on hemodynamic alterations and their role in the development and progression of diabetic nephropathy. Increases in GFR, largely driven by increases in plasma flow and capillary pressure, appear in early IDDM and NIDDM. This abnormality of renal vascular control probably is derived from alterations in several vasoactive control systems. In addition, the elevations in capillary pressure may be damaging to the glomerular capillaries. Arterial hypertension is not necessarily present before clinical nephropathy appears; however, it is a usual concomitant of progressive diabetic renal disease. The strongest evidences for the roles of altered systemic and renal hemodynamics in the progression of diabetic renal disease are clinical and experimental studies demonstrating attenuation of the disease process by lowering systemic and capillary pressures with antihypertensive agents, and dietary and glycemic modifications. Thus, although multiple factors probably interact to determine risk for the development of diabetic nephropathy, hemodynamic forces are a particularly important contributor and are especially amenable to therapeutic intervention.
Diabetes Care 1992 Sep
PMID:Diabetic nephropathy. Metabolic versus hemodynamic considerations. 139 17

Information concerning cardiovascular disease risk factors in Native American children is limited. In adult Native American populations, cardiovascular disease risk factors of non-insulin dependent diabetes mellitus, obesity, and cigarette smoking are prevalent, and recent reports indicate mortality caused by cardiovascular disease has dramatically increased. In a screening program at the Onondaga Nation School, six cardiovascular disease risk factors were evaluated. Of 95 school children, 55 representing 39 interrelated families, participated. Family histories were positive for diabetes mellitus in 72%, for cardiovascular disease in 54%, and for passive smoking in 90% of families. Physical examinations of the children revealed obesity (weight/height greater than 90th percentile) in 42% and hypertension (systolic or diastolic blood pressure/height greater than 95th percentile) in 22%. Fingerstick cholesterol levels (Reflotron system) were greater than 170 mg/dL in 25%. Overall, 85% of participants had three or more risk factors for cardiovascular disease. The study results indicate that Onondaga Native American children are at significant risk for cardiovascular disease; programs for identification and modification of cardiovascular disease risk factors are urgently needed.
N Y State J Med 1992 Sep
PMID:Cardiovascular risk factors in Native American children. 140 96

The aim of this study was to determine whether exercise training produces a myocardium intrinsically more tolerant to ischemic-reperfusion injury. Male Fischer 344 rats were treadmill trained for 11-16 wk at one of the following intensities: LOW (20 m/min, 0% grade, 60 min/day), moderate (MOD; 30 m/min, 5% grade, 60 min/day) or intensive (INT; 10 bouts of alternating 2-min runs at 16 and 60 m/min, 5% grade). Cardiac function was evaluated both before and after 25 min of global, zero-flow ischemia in the isolated, working heart model. Compared to hearts from sedentary (SED) rats, postischemic cardiac output (CO) and work were significantly higher in all trained groups. Percent recovery of CO (relative to preischemia) was 36.0 +/- 7.1 in SED and 61.2 +/- 6.5, 68.1 +/- 9.3, and 73.2 +/- 5.0 in LOW, MOD, and INT, respectively. Postischemic increases in stroke volume with increased preload and cardiac work at high work load were significantly higher in INT compared with SED. Coronary flow during initial retrograde reperfusion was significantly enhanced with training and correlated with subsequent recovery of CO (R2 = 0.613). Furthermore, trained hearts had higher phosphocreatine (P less than 0.05) and ATP (P less than 0.01) contents after 45 min reperfusion. It is concluded that exercise training results in an intrinsic myocardial adaptation, allowing greater recovery of cardiac pump function after global ischemia in the isolated rat heart.
Am J Physiol 1992 Sep
PMID:Exercise training improves cardiac function after ischemia in the isolated, working rat heart. 141 6

Pentasomy X mosaic in two adult sisters with non-insulin dependent diabetes mellitus is described. The younger sister had schizophrenia, and both were mentally retarded, but no apparent somatic abnormalities were found. Chromosome analyses revealed karyotype 45,X/46,XX/47,XXX/48,XXXX/49,XXXXX mosaic with a low frequency of aneuploidy on cultured peripheral lymphocytes and 46,XX on cultured skin fibroblasts in both sisters. The low frequency of X chromosome aberration may be responsible for the lack of somatic abnormalities and the long life in both sisters. The association of pentasomy X mosaicism and diabetes mellitus however appears to be coincidental.
Intern Med 1992 Sep
PMID:Pentasomy X mosaic in two adult sisters with diabetes mellitus. 142 17

First-degree relatives of patients with NIDDM manifest severe insulin resistance despite normal glucose tolerance test. To examine the mechanisms underlying the normal glucose tolerance, we evaluated the serum glucose/C-peptide/insulin dynamics and free fatty acid (FFA) as well as substrate oxidation rates and energy expenditure (EE) (indirect calorimetry) in nine young offspring of NIDDM patients (mean +/- SEM age 30 +/- 2.3 years, body mass index 24.2 +/- 1.2 kg/m2). Nine age-, sex- and weight-matched, normal subjects with no family history of diabetes served as the controls. Metabolic parameters were measured before, during and after a two-step glucose infusion (2 and 4 mg/kg.min) for 120 min. Mean basal serum glucose, insulin and C-peptide levels were similar in both groups. During 2 mg/kg.min glucose infusion, mean serum insulin and C-peptide rose to significantly (P less than 0.05-0.02) greater levels in the offspring vs. controls, while serum glucose levels were similar. With the 4 mg/kg.min glucose infusion, mean serum glucose, insulin and C-peptide levels were significantly (P less than 0.02-0.001) greater in the offspring at 100-120 min. Isotopically-derived (D[3-3H]glucose), basal hepatic glucose output (HGO) was not significantly different between the offspring vs. controls (1.86 +/- 0.30 vs. 1.78 +/- 0.06 mg/kg.min). During glucose infusion, basal HGO was partially suppressed by 66% at 60 min and by 100% at 120 min in the offspring. In contrast, HGO was completely (100%) suppressed at both times in the controls. Following cessation of glucose infusion, HGO rose to 1.64 +/- 0.12 mg/kg.min in the offspring and 1.46 +/- 0.05 mg/kg.min in the controls (P less than 0.05) between 200 and 240 min. These were 88% and 82% of the respective basal HGO values. At low glucose infusion (t = 0-60 min), the mean absolute, non-oxidative glucose disposal remained 1.5-fold greater in the offspring while at higher glucose infusion, nonoxidative glucose metabolism was not different in both groups. Throughout the study period, oxidative glucose disposal rate was not significantly different in both groups. The mean basal FFA was significantly greater in the offspring vs. controls (865 +/- 57 vs. 642 +/- 45 microEq/l). It was appropriately suppressed during glucose infusion to a similar nadir in both groups (395 +/- 24 vs. 375 +/- 33 microEq/l). The mean basal lipid oxidation was also significantly greater in the offspring than controls (1.06 +/- 0.05 vs. 0.75 +/- 0.04 mg/kg.min, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes Res Clin Pract 1992 Sep
PMID:The effects of superphysiologic hyperinsulinemia on glucose and lipid metabolism in glucose-tolerant offspring of patients with non-insulin-dependent diabetes mellitus (NIDDM). 142 56

The aim of the present study was to identify in young, diabetes-prone subjects the early abnormalities which may predispose to the development of type 2 diabetes. We studied 10 full-blood Australian Aborigines all of whom had a family history of diabetes and who were from an urbanised community with a high prevalence of this disorder. They were compared to 10 age- and body-mass-index-matched Caucasian controls with no family history of diabetes. Glucose kinetics were measured basally and following an oral glucose load. Fasting plasma glucose was equal in the two groups, but 2 h following the 75 g glucose load, the Aboriginal subjects had higher glycaemia than the controls (P less than 0.01). Insulinaemia was higher in the Aborigines both basally and following the glucose drink (P less than 0.05). Despite the hyperinsulinaemia, hepatic glucose production was higher in the Aboriginal subjects (P less than 0.01), while metabolic clearance rate was lower. It is concluded that in young Australian Aborigines with a strong family history of type 2 diabetes, both hepatic and peripheral insulin resistance are early abnormalities.
Diabetes Res Clin Pract 1992 Sep
PMID:Identification of early metabolic defects in diabetes-prone Australian aborigines. 142 61


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