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)

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.
Int J Obes Relat Metab Disord 1992 Dec
PMID:A randomized double-blind clinical trial of fluoxetine in obese diabetics. 133 89

We designed this study to elucidate a possible involvement of genetic factors which influence the progression of renal dysfunction in patients with non-insulin dependent diabetes mellitus (NIDDM). A total of 328 patients was randomly selected in the Tokai University Hospital. They had been cared for in our hospital as NIDDM for the past five years, until April, 1989. Fifty-six patients with persistent albuminuria, and an equal number of patients without persistent albuminuria were included in this study. No significant differences were observed between the two groups in terms of age, estimated period of illness, blood pressure, body-mass index, HbAlc, blood glucose, total cholesterol, triglyceride level and mean blood pressure. The family histories obtained by questionnaires revealed that there might be some genetic predisposing factors leading to the onset of nephropathy in patients with NIDDM, especially in cases with paternal high blood pressure. It is suggested that paternal hypertension might be related to the development of nephropathy in patients with NIDDM.
Tokai J Exp Clin Med 1992 Dec
PMID:Genetic predisposing factors in non-insulin dependent diabetes with persistent albuminuria. 134 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)
Diabetes 1992 Dec
PMID:Linkage analysis of GLUT1 (HepG2) and GLUT2 (liver/islet) genes in familial NIDDM. 135 87

Weight reduction in non-insulin dependent diabetes mellitus (NIDDM) patients improves metabolic control, reduces cardiovascular risk factors, has blood pressure lowering effects and improves the well-being of the patient. This paper describes the role of very low calorie diets (VLCD), exercise, beta-adrenergic drugs and serotoninergic agents in the treatment of overweight in NIDDM. VLCD reduce body weight and improve glucose metabolism. Physical exercise programmes in addition to dietary restriction substantially contribute to weight loss and metabolic control in NIDDM. New specific beta-adrenergic agents, exhibiting virtually no beta 1 or beta 2 activity, increase energy expenditure and weight loss probably by enhancement of the basal metabolic rate. The target tissue in humans of this beta-adrenergic effect is as yet unknown. These drugs seem to enhance weight loss when used in combination with (very) low calorie diets compared to dietary restriction alone. Serotoninergic drugs reduce body weight by decreasing appetite, in particular for carbohydrates. Furthermore these drugs seem to improve insulin receptor sensitivity.
Int J Obes Relat Metab Disord 1992 Dec
PMID:Very low calorie diets and recently developed anti-obesity drugs for treating overweight in non-insulin dependent diabetics. 136 97

To define the pathogenic factors responsible for glucose intolerance in NIDDM, we estimated insulin secretory capacity, SI, and SG in 11 healthy, nondiabetic subjects and 9 NIDDM patients who had no SI impairment. All subjects studied were nonobese and normotensive. Each underwent a 75-g OGTT and a modified FSIGT: glucose was administered (300 mg/kg body weight), and insulin was infused (20 mU/kg over 5 min) from 20 to 25 min after the administration of glucose. SI and SG were estimated by Bergman's minimal-model method. The insulin response to oral glucose was significantly lower in NIDDM patients than in normal control subjects. First-phase insulin secretion expressed as the integrated area of plasma insulin above the basal level during the first 20 min was much smaller in NIDDM subjects (214 +/- 112 pM.min) than in control subjects (4643 +/- 885 pM.min, P < 0.01). SI was not statistically different in normal control subjects (1.27 +/- 0.18 x 10(-4) min-1.pM-1) versus diabetic patients (1.62 +/- 0.33 x 10(-4) min-1.pM-1). However, SG was significantly lower in diabetic subjects (1.11 +/- 0.17 x 10(-2) min-1) than in control subjects (2.35 +/- 0.26 x 10(-2) min-1, P < 0.01). These results suggest that impaired insulin secretion and decreased SG are the factors responsible for glucose intolerance of Japanese NIDDM patients with normal insulin sensitivity. Because SI and SG are the factors responsible for glucose intolerance of NIDDM patients with insulin resistance, it is conceivable that decreased SG is common in NIDDM patients regardless of their SI index.
Diabetes 1992 Dec
PMID:Pathogenic factors responsible for glucose intolerance in patients with NIDDM. 144 94

This study was initiated to explore the possibility that an increase in the supply of gluconeogenic precursors contributes to the overproduction of glucose by the liver in NIDDM patients. To address this issue, a form of experimental NIDDM was produced in rats by injecting a low dose (38 mg/kg) of STZ and comparing lactate and alanine production and PDH activity in skeletal muscle and isolated adipocytes from normal and diabetic rats. Skeletal muscle lactate production was measured by using a hindlimb perfusion technique and was significantly greater (P < 0.01) in the diabetic rats compared with two groups of control rats: one perfused at normal glucose levels and the other perfused at glucose concentrations comparable with those observed in diabetic rats. Alanine production by hindlimb from diabetic rats was 46% greater than hindlimbs from control rats perfused at normal glucose levels (P < 0.01) but was not significantly greater than control rats perfused at diabetic glucose levels. The percentage of glucose converted to lactate by muscle from both control groups was 4-5%, significantly lower than the 18% conversion rate observed in diabetic animals (P < 0.001). An increase in the ratio of lactate produced/glucose transport by isolated adipocytes from diabetic rats also was observed when measured in both the basal state (0.65 +/- 0.12 vs. 0.15 +/- 0.03, P < 0.01) and in the presence of maximal amounts of insulin (0.15 +/- 0.02 vs. 0.04 +/- 0.01, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Dec
PMID:Lactate production and pyruvate dehydrogenase activity in fat and skeletal muscle from diabetic rats. 144 95

NIDDM patients with overt fasting hyperglycemia are characterized by multiple defects involving both insulin secretion and insulin action. At this point of the natural history of NIDDM, however, it is difficult to establish which defects are primary and which are acquired secondary to insulinopenia and chronic hyperglycemia. To address this question, we have studied the glucose-tolerant offspring (probands) of two Mexican-American NIDDM parents. Such individuals are at high risk for developing NIDDM later in life. The probands are characterized by hyperinsulinemia in the fasting state and in response to both oral and intravenous glucose. Insulin-mediated glucose disposal (insulin clamp technique), measured at two physiological levels of hyperinsulinemia (approximately 240 and 450 pM [approximately 40 and 75 microU/ml]), was reduced by 43 and 33%, respectively. During both the low- and high-dose insulin clamp steps, impaired nonoxidative glucose disposal, which primarily represents glycogen synthesis, was the major defect responsible for the insulin resistance. During the lower dose insulin clamp step only, a small decrease in glucose oxidation was observed. No defect in suppression of HGP by insulin was demonstrable. The ability of insulin to inhibit lipid oxidation (measured by indirect calorimetry) and plasma FFA concentration was impaired at both levels of hyperinsulinemia. These results indicate that the glucose-tolerant offspring of two NIDDM parents are characterized by hyperinsulinemia and manifest all of the metabolic abnormalities that characterize the fully established diabetic state, including insulin resistance, a major impairment in nonoxidative glucose disposal, a quantitatively less important defect in glucose oxidation, and a diminished insulin-mediated suppression of lipid oxidation and plasma FFA concentration.
Diabetes 1992 Dec
PMID:The metabolic profile of NIDDM is fully established in glucose-tolerant offspring of two Mexican-American NIDDM parents. 144 99

Recently, linkage between the ADA gene locus and MODY, a subtype of NIDDM, has been reported. The possibility that the region of chromosome 20q containing the ADA locus also may play a role in susceptibility to NIDDM needs to be investigated. Therefore, we examined the linkage between the ADA locus and NIDDM in affected siblings of 50 European white diabetic pedigrees--21 Italian and 29 British. Departure from independent segregation of the disease and an Alu VpA polymorphism within the 5' flanking region of the ADA locus was tested in the affected sib-pairs with the APM statistical method. After DNA amplification by the PCR and PAGE, five alleles were identified in the ALU VpA tract at the ADA locus in the two populations. Allele frequencies did not differ significantly between the two populations (chi 2 = 2.426, P > 0.05 [NS]). Analysis of the 50 diabetic sib sets, and independently of the Italian and British groups of affected sib pairs, revealed no segregation distortion between the marker locus and NIDDM. We conclude that mutations within or around the ADA locus are unlikely to play a major role in the etiology of NIDDM.
Diabetes 1992 Dec
PMID:Sib-pair analysis of adenosine deaminase locus in NIDDM. 144 5

Glucokinase is thought to play a glucose-sensor role in the pancreas, and abnormalities in its structure, function, and regulation can induce diabetes. We isolated the human glucokinase gene, and determined its genomic structure including exon-intron boundaries. Structure of the glucokinase gene in human was very similar to that in rat. Then, by screening Japanese diabetic patients using polymerase chain reaction--single strand conformation polymorphism (PCR-SSCP) and direct-sequencing strategies, we identified a missense mutation substituting arginine (AGG) for glycine (GGG) at position 261 in exon 7 of the glucokinase gene in a patient with early-onset non-insulin-dependent diabetes (NIDDM).
J Clin Endocrinol Metab 1992 Dec
PMID:Structure of the human glucokinase gene and identification of a missense mutation in a Japanese patient with early-onset non-insulin-dependent diabetes mellitus. 146 39

A total of 439 individuals with diabetes mellitus were examined for carriage of yeasts by the oral rinse and palatal swab techniques. Eighteen genetic or environment variables were assessed for their contribution to carriage of yeasts. The factor contributing to palatal and oral carriage of yeasts among individuals with insulin dependent diabetes mellitus (IDDM) was age (P < 0.01). The factor contributing to palatal carriage of yeasts among individuals with non-insulin dependent diabetes mellitus (NIDDM) was poor glycaemic control (glycosuria P < 0.01); carriage in the oral cavity as a whole was influenced additionally by non-secretion of ABH blood group antigens (P < 0.05). Introduction of a denture altered the above risk factors. For individuals with IDDM, oral carriage was associated with the presence of retinopathy (P < 0.05); palatal carriage was influenced by poor glycaemic control (HbA1P < 0.01, plasma glucose levels P < 0.05) and age (P < 0.05). For those with NIDDM, palatal carriage was associated with continuous presence of the denture in the mouth (P < 0.01); oral carriage was associated with plasma glucose levels (P < 0.05).
Epidemiol Infect 1992 Dec
PMID:Factors influencing oral carriage of yeasts among individuals with diabetes mellitus. 146 35


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