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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity and impaired glucose tolerance (IGT) are risk factors for non insulin dependent diabetes mellitus (NIDDM) and for ischemic heart disease. Long term treatment of IGT subjects with diet and tolbutamide prevents progression of IGT to NIDDM. We have evaluated the lowest dose of glipizide, a second-generation sulfonylurea, able to improve glucose tolerance in response to oral glucose in 31 obese subjects, 12 with NIDDM, 9 with IGT and 10 with normal glucose tolerance (NGT). All subjects underwent four OGTTs, preceded by placebo and by different doses of glipizide (0.5, 1.0, 2.5 mg). Glucose tolerance was progressively improved by increasing glipizide doses in all groups, probably by peripheral mechanism and by enhanced insulin release.
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PMID:Improvement of glucose tolerance by minimal doses of glipizide in obese subjects with different degrees of glucose intolerance. 149 Jun 90

Previous studies have suggested that noninsulin dependent diabetes mellitus (NIDDM) could lead to learning and memory deficits. We studied cognitive performance and computed tomography (CT) findings of the brain in elderly subjects with drug treated NIDDM (n = 12), with diet treated NIDDM (n = 13), and in nondiabetic individuals (ND, n = 59). The cognitive performance (orientation and up-to-date knowledge, praxic functions, understanding of speech, expressive speech, memory, general reasoning) did not differ between the groups. The drug treated diabetics had more pronounced central temporal atrophy compared to that in the ND subjects as evidenced by wider right temporal horn (ANCOVA adjusted for age, p = 0.011). The drug treated diabetics (all women) also had wider frontal horns than did the ND women. The CT measures of diet treated diabetics were comparable with those of the ND group. The fasting glucose level was positively correlated with the width of the right temporal horn but not with other CT measures in diabetic subjects. The results suggest that NIDDM and poor glucose control may carry a risk for accelerated brain atrophy in the elderly.
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PMID:Diabetes mellitus and brain atrophy: a computed tomography study in an elderly population. 149 37

60 NIDDM patients, mean age (68 +/- 3 years), BMI (25 +/- 5.1 kg/m2), fasting blood glucose (FG) (170 +/- 10 mg/dl), mean daily blood glucose (MDBG) (180 +/- 10 mg/dl), daily glycosuria (GLU) (15.6 +/- 9 g/24 hours), HbA1c (7.9 +/- 0.6%), basal (1.2 +/- 0.2 ng/ml) and stimulated (3.89 +/- 1.3 mg/ml) C peptide (CP) treated by ASS (7.5 +/- 75 mg), after a strict 4 months follow-up period, were assigned to G + M treatment (7.5 +/- 1.500 mg) during a 4 months period. During G+M treatment FG (171 +/- 13 at t0 to 165 +/- 11 mg/dl: p < 0.01 at t4) varied significantly. MDBG (180 +/- 10 at t0 to 175 +/- 12 mg/dl at t4:p < 0.05), GLU (16 +/- 9 at t0 to 11 + 6 g/24 hours at t4; p < 0.01), HbA1c (8.1 +/- 0.4 at t0 to 7.6 +/- 0.3% at t4; p < 0.01). Basal CP remained unchanged in G+M period and varied significantly during ASS period (1.3 +/- 0.3 ng/ml at t4; p < 0.01) and stimulated CP (unchanged during ASS) was reduced during G+M (4.19 +/- 0.4 to 4.04; p < 0.05). Highly significant variations were observed for LAC (28.4 +/- 2.1 at t0 to 14.9 +/- 0.6 mg/dl: p < 0.01 during G+M treatment). G+M therapy was found to be more effective and safer than ASS therapy in regard to glucose metabolism and lactate production in a selected group of NIDDM patients.
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PMID:[Median-term (4 months) treatment with glibenclamide + metformin substituting for glibenclamide + fenformin lowers the lacticemia levels in type-2 diabetics (NIDDM)]. 149 70

In one third of patients who suffered an infarction NIDDM and arterial hypertension are present. In the absolute majority of patients with IHD, as apparent from the IRI and C-peptide response after a glucose load, hyperinsulinism is present. The blood sugar response can have the character of diabetes or of impaired glucose tolerance, the curve may be very flat or normal while the IRI and C-peptide response are excessive. Hyperinsulinism has a hypersecretory origin as suggested by the concurrently elevated C-peptide level but also reduced insulin utilization in the liver and peripheral target organs. Hyperinsulinism is thus a regular associated phenomenon of IHD and is a special risk factor independent on hyperglycaemia and associates with the other main risk factors of IHD such as arterial hypertension, HPLP (android obesity), hyperglycaemia (NIDDM) and hirsutism as a manifestation of a hyperandrogenic state in the female organism with the syndrome of polycystic ovaries. Hyperinsulinism plays an indirect role in the pathogenesis of coronary syndrome via the main risk factors (5H syndrome--hyperinsulinism, hypertension, HPLP, hyperglycaemia, hirsutism) and also directly by its action on endothelial paracrine mechanism of the coronary circulation where in the early stage vasoconstrictor factors predominate (endothelin-1, PGF2-alpha) over physiological vasodilatating factors (EDRF-NO, PGE2, PGI2) and this leads then to functional spasms. It seems that also the coronary X syndrome develops very frequently on the background of the hormonal metabolic X syndrome or the 5H syndrome.
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PMID:[Hyperinsulinism and the coronary syndrome]. 149 68

The pancreatic beta cell presents functional abnormalities in the early stages of development of non-insulin dependent diabetes mellitus (NIDDM). The disappearance of the first phase of insulin secretion induced by a glucose load is a early marker of NIDDM. This abnormality could be secondary to the low expression of the pancreatic glucose transporter GLUT2. Together with the glucokinase enzyme, GLUT2 is responsible for proper beta cell sensing of the extracellular glucose levels. In NIDDM, the GLUT2 mRNA levels are low, a fact which suggests a transcriptional defect of the GLUT2 gene. The first phase of glucose-induced insulin secretion by the beta pancreatic cell can be partly restored by the administration of a peptide discovered by a molecular approach, the glucagon-like peptide 1 (GLP-1). The gene encoding for the glucagon is expressed in a cell-specific manner in the A cells of the pancreatic islet and the L cells of the intestinal tract. The maturation process of the propeptide encoded by the glucagon gene is different in the two cells: the glucagon is the main hormone produced by the A cells whereas the glucagon-like peptide 1 (GLP-1) is the major peptide synthesized by the L cells of the intestine. GLP-1 is an incretin hormone and is at present the most potent insulinotropic peptide. The first results of the administration of GLP-1 to normal volunteers and diabetic patients are promising and may be a new therapeutic approach to treating diabetic patients.
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PMID:[Various molecular mechanisms involved in the pathogenesis of type II diabetes and their potential therapeutic importance]. 149 38

This article is divided into two parts. A retrospective overview summarizes some of the work that provided the framework and tools of the more recent studies. The five novel areas of research are related to the indirect effects of insulin. Regulation of plasma glucose is of central importance in health and diabetes. Understanding this precise regulation requires sensitive isotope dilution methods that can measure the rates at which glucose is produced by the liver and used by the tissues on a minute-to-minute basis. Validation studies indicated that the non-steady-state tracer method yields reasonable results when the specific activity of plasma glucose does not change abruptly. During hyperinsulinemic glucose clamps, the decrease in specific activity of glucose can be prevented by the MSTI. During exercise, the decrease of specific activity can be only in part ameliorated by step-tracer infusion. Depancreatized dogs are used extensively as a model of selective insulin deficiency, because dog stomach secretes physiological amounts of glucagon. This strategy can avoid injections of somatostatin, which can have other affects in addition to the suppression of insulin and glucagon. In human diabetes, in addition to an increase of glucose production, there is also an increase in glucose cycling in the liver. In animal models of diabetes, mild NIDDM, and in glucose intolerance, the percentage of increments of glucose cycling are much larger than those of glucose production. We hypothesize, therefore, that measurements of glucose cycling can be used as an early marker of glucose intolerance. Application of different tracer strategies and use of the depancreatized dog as a model of diabetes, we investigated the importance of the indirect effects of insulin in the pathogenesis of diabetes. 1) Because, in the treatment of IDDM, insulin is administered by the peripheral routes we compared the relative importance of hepatic and peripheral effects of insulin in regulating the rate of glucose production. Experiments were performed in depancreatized dogs that were initially maintained at moderate hyperglycemia (10 mM) with subbasal portal insulin infusion. During the experimental period, insulin was infused either peripherally or portally at 0.9 mU.kg-1.min-1. In addition, peripheral infusions were also given at 0.45 mU.kg-1.min-1. We concluded that when suprabasal insulin levels are provided to moderately hyperglycemic depancreatized dogs, the suppression of glucose production is more dependent on peripheral than portal insulin concentrations. This indirect effect of insulin may be mediated by limitation of the flow of precursors and energy substrates for gluconeogenesis and/or by suppressive effect of insulin on glucagon secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Banting Lecture: glucose turnover. A key to understanding the pathogenesis of diabetes (indirect effects of insulin). 149 70

The effect of the calcium antagonist nicardipine on insulin secretion and glucose homoeostasis was investigated in elderly hypertensives with and without diabetes mellitus; 15 patients with essential hypertension for at least 10 years and normal glucose tolerance according to standard criteria (Group I) and 15 elderly hypertensive patients affected by Type 2 diabetes mellitus and on treatment with diet or oral drugs (Group 2). In the basal state, all patients were submitted to an oral glucose tolerance test (OGTT, 75 g) and an iv arginine test (30 g), on two different days and in random order. The same tests were repeated after one month of treatment with nicardipine 60 mg/day, in three spaced doses, the last being given 1 h before the post-treatment test. Nicardipine did not change overall glucose homoestasis, as assessed by haemoglobin Alc and fructosamine, nor did it significantly affect the plasma insulin response either to glucose or arginine in Groups 1 and 2. Only the glucagon response to arginine was significantly reduced in diabetic hypertensives. Small, non-significant variations in the metabolic and hormonal parameters were seen in additional two groups of patients (Groups 3 and 4), matched with Groups 1 and 2 for age, sex and diseases, who took capsules containing placebo. Thus, nicardipine did not produce any significant overall alteration in glucose homoestasis when given to elderly diabetic or nondiabetic hypertensive subjects.
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PMID:Nicardipine does not cause deterioration of glucose homoeostasis in man: a placebo controlled study in elderly hypertensives with and without diabetes mellitus. 150 7

To clarify the problem in the measurement of renal plasma flow and glomerular filtration rates in diabetes, the effect of glucose on the determination of para-aminohippuric acid (PAH) and inulin was examined. The concentration of urinary PAH in glucosuric diabetic subjects decreased after the storage of urine samples because of the glycation of PAH. Therefore, glucose must be removed by the acid treatment before the determination of the concentrations of urinary PAH. Since glucose can interfere with the assay of inulin, the sample must be treated with NaOH prior to the determination of the inulin concentration. GFR of the subjects with type 2 diabetes was next examined. GFR in the subjects with a duration of diabetes less than 10 years was significantly higher than that in the subjects with a duration of diabetes more than 10 years. Thus, the subjects with short-term type 2 diabetes may present with hyperfiltration similar to the subjects with short-term type 1 diabetes.
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PMID:[Measurement of renal plasma flow and glomerular filtration rates in diabetic subjects]. 150 86

The present study was undertaken to compare the effect of hyperglycemia and euglycemia during identical hyperinsulinemic conditions on glucose metabolism in NIDDM subjects. Eight NIDDM subjects participated in a 4 h hyperglycemic (12.1 +/- 0.7 mmol/l), hyperinsulinemic (475 +/- 43 pmol/l) and in a 4 h euglycemic (5.5 +/- 0.5 mmol/l), hyperinsulinemic (468 +/- 36 pmol/l) insulin clamp in combination with indirect calorimetry and [3H]-3-glucose. Six non-diabetic subjects were studied during euglycemia (5.1 +/- 0.2 mmol/l) and hyperinsulinemia (474 +/- 35 pmol/l) and served as controls. In NIDDM patients the rate of insulin-stimulated glucose disposal was 57% greater during hyperglycemia compared with euglycemia throughout the 4 h clamp (p less than 0.01). The major part of the increase in glucose metabolism during hyperglycemia was due to an increase in the non-oxidative glucose metabolism (89%). Whereas glucose metabolism could not be normalized during the prolonged euglycemic hyperinsulinemic clamp in NIDDM patients (49.9 +/- 6.8 vs 57.5 +/- 5.4 mumol.(kgLBM)-1.min-1 in controls) the addition of hyperglycemia resulted in complete normalization of the glucose disposal rates (78.3 +/- 5.8 mumol.(kgLBM)-1.min-1). The effect of hyperglycemia was apparent already at 60 min of the clamp. The data thus suggest that glucose metabolism in NIDDM is insulin resistant, but that the defect in insulin-stimulated glucose uptake can be overcome by increasing the glucose concentration.
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PMID:Time-dependent effect of hyperglycemia and hyperinsulinemia on oxidative and non-oxidative glucose metabolism in patients with NIDDM. 152 56

Non-insulin-dependent diabetes mellitus (NIDDM) results from an imbalance between insulin sensitivity and insulin secretion. Both longitudinal and cross-sectional studies have demonstrated that the earliest detectable abnormality in NIDDM is an impairment in the body's ability to respond to insulin. Because the pancreas is able to appropriately augment its secretion of insulin to offset the insulin resistance, glucose tolerance remains normal. With time, however, the beta-cell fails to maintain its high rate of insulin secretion and the relative insulinopenia (i.e., relative to the degree of insulin resistance) leads to the development of impaired glucose tolerance and eventually overt diabetes mellitus. The cause of pancreatic "exhaustion" remains unknown but may be related to the effect of glucose toxicity in a genetically predisposed beta-cell. Information concerning the loss of first-phase insulin secretion, altered pulsatility of insulin release, and enhanced proinsulin-insulin secretory ratio is discussed as it pertains to altered beta-cell function in NIDDM. Insulin resistance in NIDDM involves both hepatic and peripheral, muscle, tissues. In the postabsorptive state hepatic glucose output is normal or increased, despite the presence of fasting hyperinsulinemia, whereas the efficiency of tissue glucose uptake is reduced. In response to both endogenously secreted or exogenously administered insulin, hepatic glucose production fails to suppress normally and muscle glucose uptake is diminished. The accelerated rate of hepatic glucose output is due entirely to augmented gluconeogenesis. In muscle many cellular defects in insulin action have been described including impaired insulin-receptor tyrosine kinase activity, diminished glucose transport, and reduced glycogen synthase and pyruvate dehydrogenase. The abnormalities account for disturbances in the two major intracellular pathways of glucose disposal, glycogen synthesis, and glucose oxidation. In the earliest stages of NIDDM, the major defect involves the inability of insulin to promote glucose uptake and storage as glycogen. Other potential mechanisms that have been put forward to explain the insulin resistance, include increased lipid oxidation, altered skeletal muscle capillary density/fiber type/blood flow, impaired insulin transport across the vascular endothelium, increased amylin, calcitonin gene-related peptide levels, and glucose toxicity.
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PMID:Pathogenesis of NIDDM. A balanced overview. 153 77


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