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)

Insulin resistance contributes to the pathogenesis of NIDDM. We have investigated the molecular mechanisms of insulin resistance in patients with genetic syndromes caused by mutations in the insulin-receptor gene. In general, patients with two mutant alleles of the insulin-receptor gene are more severely insulin-resistant than are patients who are heterozygous for a single mutant allele. These mutations can be put into five classes, depending upon the mechanisms by which they impair receptor function. Some mutations lead to a decrease in the number of insulin receptors on the cell surface. For example, some mutations decrease the level of insulin receptor mRNA or impair receptor biosynthesis by introducing a premature chain termination codon (class 1). Class 2 mutations impair the transport of receptors through the endoplasmic reticulum and Golgi apparatus to the plasma membrane. Mutations that accelerate the rate of receptor degradation (class 5) also decrease the number of receptors on the cell surface. Other mutations cause insulin resistance by impairing receptor function--either by decreasing the affinity to bind insulin (class 3) or by impairing receptor tyrosine kinase activity (class 4). The prevalence of mutations in the insulin receptor gene is not known. However, theoretical calculations suggest that approximately 0.1-1% of the general population are heterozygous for a mutation in the insulin-receptor gene; the prevalence is likely to be higher among people with NIDDM. Accordingly, it is likely that mutations in the insulin-receptor gene may be a contributory cause of insulin resistance in a subpopulation with NIDDM.
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PMID:Lilly Lecture: molecular mechanisms of insulin resistance. Lessons from patients with mutations in the insulin-receptor gene. 132 27

The effects of guar incorporated into a complex spaghetti meal on the glycaemic response in 11 healthy and 6 non-insulin dependent diabetic (NIDDM) subjects was studied. To this end, subjects consumed spaghetti made of either Triticum aestivum or Triticum durum wheat with or without 20 g% guar, as part of a complex meal containing 27% fat, 19% protein and 51% carbohydrate. In both the healthy as well as the NIDDM subjects the incremental integrated postprandial glucose and C-peptide responses after ingestion of a guar spaghetti meal were not different from the values found after a spaghetti meal without guar. In NIDDM subjects the incremental glucose and C-peptide levels were lower at 60 and 90 min and 90 and 150 min respectively after ingestion of guar aestivum spaghetti. Our negative results of effects of guar on postprandial glucose values may be explained by the presence of normal quantities of fat and protein in the meal and imply that addition of dietary fibre to a complex meal is not useful in the dietary management of NIDDM.
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PMID:Absence of guar efficacy in complex spaghetti meals on postprandial glucose and C-peptide levels in healthy control and non-insulin-dependent diabetes mellitus subjects. 133 59

Abdominal obesity is closely associated with risk factors for cardiocerebrovascular disease and NIDDM and the precipitation of these diseases. Together, they seem to constitute a metabolic syndrome where hyperinsulinaemia, insulin resistance, hyperlipidaemia, hypertension, visceral fat accumulation, cardiocerebrovascular disease and NIDDM are the individual constituents. The background to this syndrome might be a primary aberration expressing itself as an increased sensitivity of the hypothalamo-adrenal axis, and subsequent inhibition of sex steroid hormone secretions. This in turn will probably be followed by metabolic derangements, primarily peripheral insulin resistance, as well as by visceral fat accumulation by mechanisms which are partially visualized by recent work in the field. Visceral fat accumulation may then amplify the metabolic aberrations via hepatic effects of excessive concentrations of portal FFA, producing hyperproteinaemia, hyperglycaemia, hyperinsulinaemia and, perhaps, hypertension. The background to the central endocrine aberration remains more speculative, but factors leading to increased cortisol production, including specific stress reactions, tobacco smoking and alcohol may turn out to be important. The tentative conclusion provides a hypothesis for further work, and has recently obtained considerable support from further observations in humans in other than the endocrine and metabolic areas, as well as from studies in experimental animal models, where such factors can be studied under fully controlled conditions, which is not possible in humans for ethical reasons.
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PMID:Regional fat distribution--implications for type II diabetes. 133 83

Fluoxetine is an inhibitor of serotonin re-uptake which has been found to produce weight loss in humans and animals. To test the effects of this drug in obese diabetic subjects, 48 male and female, obese type II non-insulin dependent (NIDDM) diabetics who were being treated with insulin were randomized to receive either fluoxetine 60 mg or a placebo once daily in a randomized double-blind fashion for 24 weeks. A four week single-blind placebo lead-in period preceded and a six week single-blind placebo period followed the double-blind treatment period. Subjects performed daily home glucose monitoring and were given instruction in a 1200kcal American Diabetic Association (ADA) diet. Subjects treated with fluoxetine achieved a maximum 8 kg greater weight loss on average than the placebo-treated subjects. At the end of active treatment, fluoxetine-treated subjects had significantly lower glycohaemoglobin levels than the placebo-treated group (9.72 vs. 10.76%, P < 0.05). In addition, fluoxetine-treated subjects showed a greater decrease in total daily insulin dose than placebo-treated subjects (44.5 vs. 20.1% decrease at the end of active treatment, P < 0.05). These results suggest that fluoxetine may be of benefit in the treatment of obese patients with type II non-insulin dependent diabetes mellitus.
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PMID:A randomized double-blind clinical trial of fluoxetine in obese diabetics. 133 89

Diabetes mellitus (DM) is frequently associated with hypertension for which an independent pathomechanism has been suggested. We studied 26 patients with insulin-dependent (IDDM) and 18 patients with non-insulin-dependent (NIDDM) uncomplicated DM; all patients were in metabolic balance and none of them had hypertension. Exchangeable body sodium (NaE was estimated by isotope dilution, using appr. 1.1 Mbq 24NA. In a subset of 8 IDDM and 8 NIDDM patients atrial natriuretic peptide (ANP) plasma concentration was determined prior to and after the infusion of 2000 ml physiological saline over 2 hr. NaE was significantly increased both in IDDM and NIDDM patients (104.4 +/- 11.4% and 109.9 +/- 8.0% of the normal value for healthy subjects of identical body surface area; p < 0.05 and < 0.001 resp.). Mean blood pressure (MBP) correlated significantly with NaE in both groups (r = 0.364 and r = 0.520; p < 0.05 and < 0.025, resp.) but not in healthy control subjects (r = 0.112; N.S.). Resting ANP levels were not significantly different in IDDM (34.9 +/- 11.3 pg/ml), NIDDM (42.6 +/- 11.7 pg/ml) or control subjects (40.9 +/- 17.2 pg/ml) however the infusion of saline resulted in a significantly greater increase of plasma ANP in the NIDDM patients (to 82.9 +/- 43.2 pg/ml; P < 0.01) than in the controls (55.6 +/- 23.7 pg/ml; P < 0.01) which was associated with a significantly less increase in sodium excretion (UNAV) in the NIDDM patients (+86% vs. 3170%; P < 0.02) indicating down-regulation of ANP receptors in the kidney of NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Body sodium, atrial natriuretic peptide and blood pressure in diabetes mellitus. 134 Jun 60

Lipoprotein(a) [Lp(a)] has been added to the list of independent risk factors for cardiovascular disease (CVD), whose incidence is greater in obese subjects. There are few data available on the serum Lp(a) concentrations in obese individuals with or without insulin dependent diabetes mellitus (NIDDM). We selected 31 obese men with normal glucose tolerance (NGT) tests, 15 obese diabetic men, 14 non obese diabetic men and 17 healthy men as controls. We measured serum total cholesterol, HDL cholesterol, triglycerides, glucose, insulin and Lp(a). The mean Lp(a) levels in NGT obese men were 70.00 +/- 13.40 mg/l, which were similar to those found in normal controls (75.98 +/- 24.70 mg/l); significantly higher mean Lp(a) levels were found in obese diabetic men (168.84 +/- 56.43 mg/l) and in non obese diabetic men (240.85 +/- 63.35 mg/l). No significant correlation between Lp(a) levels and age, body mass index (BMI), total cholesterol, HDL cholesterol, triglycerides, insulin, was found; only a significant positive correlation between Lp(a) levels and glucose could be revealed (P < 0.05). Since higher levels of Lp(a) were found in NIDDM subjects with or without obesity, we conclude that hyperglycemia may influence the levels of serum Lp(a) facilitating its glycosylation in the liver with the consequence of a decline in its catabolic rate.
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PMID:Serum lipoprotein Lp(a) in obesity. 134 6

78 diabetics and a healthy control group of 100 were evaluated according to their haemorrheological parameters (whole blood viscosity, plasma viscosity, aggregability and rigidity of erythrocytes). Diabetics were divided according to type of diabetes, quality of metabolic control and expression of microangiopathy. Hyperviscosity was noted in both groups of diabetics as compared to the control group. Changes in patients with IDDM were more pronounced in erythrocyte rigidity, while in patients with NIDDM they were more expressed in cell aggregability. These changes were present even before the clinical onset of the late complications of diabetes, although they were more expressed in patients with complications. Changes in patients with good metabolic control, were less expressed in comparison to those with poor metabolic control. The conclusion is that metabolic derangements in diabetes have an important influence on haemorrheological properties. Thus, reducing blood viscosity in these patients, may be a promising approach to improving microcirculation and delaying the progression of microangiopathy.
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PMID:[Hemorheologic changes in diabetes mellitus]. 134 47

1. To determine the effects of gene dilution on development of IGT, NIDDM and in vitro glucose oxidation, heterozygous lean LA/N-cp female and SHR/N-cp male rats were mated, and F1 offspring studied at periodic intervals to determine the prevalence of obese and diabetic traits. 2. Obesity occurred in 25% of offspring by 5 weeks of age, consistent with inheritance of the autosomal recessive cp trait. 3. IGT occurred in all obese male F1, 67% of obese female F1, and 18% of the lean male F1 rats by 5 months of age, and diabetes occurred in 80% of male obese and 17% of female obese rats from 6 months of age. Glycosuria occurred with glucose intolerance, and was more severe in rats with NIDDM than IGT. 4. Rates of in vitro glucose oxidation were greater in diaphragm and adipose tissue, and were greater in the presence of insulin (100 mu Units/ml) in obese female but not obese male F1 rats. 5. These results indicate that the development of glucose intolerance is more prominent in male than in female F1 rats, that the progression of IGT to NIDDM occurs later in life in the F1 hybrid than in the SHR/N-cp strain from which the diabetic trait was transmitted, and that genetic dilution of the diabetic trait via hybrid breeding results in a delay in the expression of NIDDM which is chronologically more similar to that which occurs in man.
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PMID:Effect of genetic dilution on development of diabetes, impaired glucose tolerance and in vitro glucose oxidation in LA/N-cp x SHR/N-cp F1 hybrid rats. 134 69

Diets with a high-fiber content have been shown to produce some beneficial effects on metabolic factors in subjects with NIDDM. However, some controversies still exist. In this report, the long-term effect of guar gum (Guarina) on both glycemic and blood lipid profiles was assessed in a randomized, double-blind and cross-over study on 16 (seven male and nine female) subjects with NIDDM. Each subject received placebo (P) and Guarina (G) treatment for two eight-week periods separated by a four-week period to facilitate wash-out. Fasting plasma glucose levels showed significant improvement during G treatment but not during P treatment (151.7 +/- 7.9 vs 168.6 +/- 12.2 mg/dl, p less than 0.01 by paired Student's t test). Hemoglobin Alc levels decreased significantly during G treatment but not during P treatment (6.9 +/- 0.2 vs 7.2 +/- 0.8%, p less than 0.001). Fasting insulin concentrations also showed significant lowering during G treatment but not during P treatment (18.3 +/- 2.1 vs 23.1 +/- 2.9 U/ml, p less than 0.005). Other variables, including serum total cholesterol, triglyceride, HDLc, LDLc, sodium, potassium, chloride, magnesium and calcium levels showed no significant changes during G or P treatment. Ten out of the 16 patients (62.5%) suffered from side effects; these included abdominal cramps (one case), diarrhea (seven cases) and skin itching (one case). In conclusion, guar gum effectively lowers fasting plasma glucose and HbAlc levels in subjects with NIDDM. Hyperinsulinemia could also be ameliorated. The effectiveness and side effects of guar gum treatment should be cautiously evaluated in each NIDDM subject.
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PMID:Therapeutic effect of guar gum in patients with non-insulin-dependent diabetes mellitus. 135 28

Familial NIDDM probably results from combined inherited defects of insulin secretion and action. Members of the facilitative glucose transporter family are strong candidates for both defects, and RFLPs for both GLUT1 (erythrocyte) and GLUT2 (liver/islet) genes have been associated with NIDDM in some populations. To test the hypothesis that GLUT1 and GLUT2 mutations contribute to the inherited predisposition to NIDDM, we examined linkage of these loci with NIDDM in 18 large Utah white pedigrees (two and three generation) ascertained for > or = 2 NIDDM siblings. We used two RFLPs detected with Xba1 and Stu1 for the GLUT1 transporter. For the GLUT2 (liver/beta-cell) transporter gene, we used an RFLP detected with EcoR1 and a highly polymorphic (6-allele) dinucleotide (microsatellite) repeat. Analysis was performed with the MLINK program of the LINKAGE package. We tested four models for each locus: dominant and recessive, with IGT alternately considered as unknown affection status, or affected if IGT was diagnosed < or = 45 yr of age and unknown if > 45 yr. Disease gene frequencies were chosen to give approximate disease prevalence in American whites (q = 0.03, dominant; q = 0.25, recessive). Linkage of GLUT1 and NIDDM was strongly and significantly rejected under all models, with total (pooled) LOD scores of -5.7 to -8.9, indicating > 500,000:1 odds against linkage. Pooled LOD scores were significantly negative (< -2.0, or 100:1 odds against linkage) to a recombination fraction of > 5%. No heterogeneity was apparent. Analysis of GLUT2 gave similar results, with LOD scores of < -4.0 under each model, indicating at least 10,000:1 odds against linkage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Linkage analysis of GLUT1 (HepG2) and GLUT2 (liver/islet) genes in familial NIDDM. 135 87


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