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

Hypertension in insulin resistance states is generally attributed to hyperinsulinemia, with resulting increases in renal sodium retention and/or sympathetic nervous system activity. However, recent data from our laboratory suggest that cellular insulin resistance, rather than hyperinsulinemia per se, may lead to hypertension. The basic tenet proposed in this review is that the common mechanism involved in the development of hypertension in both type I and type II diabetes mellitus is a deficiency of insulin at the cellular level. Recent observations suggest that impaired cellular response to insulin predisposes to increased vascular smooth muscle (VSM) tone (the hallmark of hypertension in the diabetic state). For example, recently reported studies from our laboratory demonstrate that insulin in physiological doses attenuates the vascular contractile response to phenylephrine, serotonin, and potassium chloride. Thus, insulin appears to normally modulate (attenuate) VSM contractile responses to vasoactive factors, and insulin resistance should accordingly be associated with enhanced vascular reactivity. Abnormal VSM cell calcium [Ca2+]i homeostasis may be the nexus between insulin resistance and increased VSM tone. The genetically obese, hyperinsulinemic, insulin-resistant Zucker rat demonstrates increased vascular reactivity, reduced membrane Ca2(+)-ATPase activity, increased cellular Ca2+ levels, and a marked impairment in vascular smooth muscle Ca2+ efflux compared to lean controls. Insulin stimulates membrane Ca-ATPase, blocks Ca2+ currents, and Ca2(+)-driven action potentials. Thus, an insulin-resistant state as exists in the Zucker rat may be associated with increased Ca2+ influx through voltage-dependent sarcolemmal Ca2+ channels and/or decreased production or activation of the VSM cell Ca-ATPase pump.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of hypertension in diabetes. 202 49

Insulin resistance was evaluated in 807 middle-aged subjects at a health survey, with use of an index measured in 75 g oral glucose tolerance tests. The mean value of insulin resistance was higher in a hypertensive group than among the normotensives, independent of body mass index, physical activity, smoking sex, age, and thiazide treatment. One-third of the hypertensives had a high resistance value. Another third of the hypertensives, and also about one-third of the normotensives, had a slightly increased resistance. The remaining third of the hypertensives had a normal-low resistance. A high resistance was also independently related to obesity, low physical leisure time activity, and a family history of NIDDM, but not to a family history of hypertension. The statistical analysis implied a sequence of events: low physical activity might cause high resistance, which in turn might cause high blood pressure.
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PMID:Insulin resistance in the oral glucose tolerance test--a link with hypertension. 204 30

The attempt has been made to identity the lowest dose of glipizide, a second generation sulphonylurea, capable of improving glucose tolerance in overweight and obese subjects with various degrees of glucose tolerance. Thirty one obese subjects, 12 with non insulin dependent diabetes mellitus (NIDDM), 9 with impaired glucose tolerance (IGT) and 10 with normal glucose tolerance (NGT) each underwent four OGTTS (75 g), at 1 week intervals, after administration in random order of placebo or glipizide 0.5, 1.0 or 2.5 mg 30 min before glucose. Glucose tolerance in all groups was progressively improved by the increasing doses of glipizide and was normalized by 1.0 mg glipizide in impaired glucose tolerance (IGT) and by 2.5 mg glipizide in NIDDM. Insulin release was not significantly affected by glipizide in the three groups of subjects. The data indicate that it is possible, at least in acute experiments, to improve glucose tolerance in overweight and obese subjects with IGT, with NGT and with NIDDM, with doses of glipizide that do not affect insulin release.
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PMID:Acute effect of glipizide on glucose tolerance in obesity and diabetes mellitus (NIDDM). 206 May 41

To determine quantitative and qualitative differences in insulin secretion equimolar amounts of glucose and arginine were infused in 9 healthy subjects, in 8 individuals each with obesity without and with impaired glucose tolerance, and in non-obese and obese non-insulin-dependent diabetic patients (NIDDM). Insulin secretion was calculated after individual determination of metabolic clearance rate of C-peptide (MCRcp) both as the area under the C-peptide concentration curve times MCRcp, and by a mono-compartment mathematical model, both yielding identical results. MCRcp fell consistently with increasing C-peptide infusion rate (e.g.: healthy subjects: C-peptide, 10 nmol/h, 4.2 +/- 0.4; 20 nmol/h, 3.3 +/- 0.3; 30 nmol/h, 3.1 +/- 0.2 ml/kg.min; p less than 0.05 to p less than 0.01). Basal insulin secretion was 2.1-fold greater in the obese with impaired glucose tolerance than in healthy subjects, but was unchanged in non-obese NIDDM. Glucose and arginine triggered insulin release was greater than in healthy subjects at almost identical area under the respective substrate concentration curve (AUC/kg body weight) in obese subjects without (2-fold) and with impaired glucose tolerance (4-fold), and in NIDDMs following i.v. arginine (2-fold). The mean ratio of incremental insulin release to i.v. glucose and arginine was smaller in NIDDM (normal weight, 1.3 +/- 0.4; obese, 1.0 +/- 0.2) than in healthy (2.0 +/- 0.3), or obese subjects with impaired glucose tolerance (2.8 +/- 0.7). Stimulated C-peptide/insulin ratio was reduced in all patients vs that in healthy subjects (p less than 0.05). We conclude that (a) MCR of C-peptide is in part a saturable process; (b) insulin clearance may be impaired in obesity and NIDDM; and (c) insulin secretion differs in obese states and NIDDM both quantitatively and qualitatively, and thereby separates the two disorders as different entities. In addition, quantitation of insulin release in obese states may also help (d) to better define primary algorithms for insulin replacement in normal- and overweight insulin-dependent diabetic patients.
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PMID:Quantitative and qualitative differences in basal and glucose- and arginine-stimulated insulin secretion in healthy subjects and different stages of NIDDM. 207 83

The borderline between diabetes and intolerance to carbohydrates has been drawn on the basis of prospective studies which determined a glycaemic threshold marking the risk for microangiopathy. On the other hand, the borderline between intolerance to carbohydrates and normal glucose tolerance remains arbitrary: 25% for subjects who are intolerant to carbohydrates return to normal glucose tolerance within 10 years. This is due to the fact that intolerance to carbohydrates is a heterogeneous entity which should be dismembered according to the severity of insulin deficiency and to the degree of insulin resistance. Alteration of insulin secretion is perhaps the most specific marker of susceptibility to non insulin dependent diabetes, but insulin resistance is certainly the principal factor exhausting insulin secretion and leading to non insulin dependent diabetes. Insulin resistance and the hyperinsulinism it creates seem to facilitate atherogenesis, even when glucose tolerance is still normal, so that the oral glucose tolerance test is not only poorly reproducible but loses a great deal of its value in the early detection of vascular risk. Measurements of fasting and post-prandial glucose levels and of A1C haemoglobin, cholesterol, triglyceride, and HDL cholesterol levels usually make it possible to classify subjects into one of the three following categories: (1) no risk of macro- or microangiopathy; (2) diabetes with a risk of macro- or microangiopathy; (3) intolerance to glucose with risk of atherogenesis but no risk of microangiopathy. The oral glucose tolerance test probably remains useful within a small set of values that are either very slightly above normal or dissociated. Measuring blood insulin levels might be a better way of assessing the risk of atherogenesis, but the clinical use of this test requires evaluation.
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PMID:[Intolerance to carbohydrates: the seven questions]. 209 35

Assessment of peripheral insulin sensitivity using artificial endocrine pancreas was done in 15 diabetics (6 with insulin dependent diabetes mellitus and 9 with non-insulin dependent diabetes mellitus) and in 10 healthy controls, matched for sex, age and body mass index. Insulin sensitivity-RC was expressed in mg of utilised glucose/kg body weight in minute. Significantly lower insulin sensitivity was found in non-insulin dependent diabetes mellitus (RC = 2.30 +/- 1.37) compared to insulin dependent group (RC = 5.88 +/- 2.89) and control group (RC = 4.93 +/- 1.96). There was no significant change in insulin sensitivity between insulin dependent diabetics and controls (p greater than 0.05). It is concluded that investigations of this kind could be used in search for pathogenetic mechanism of insulin resistance in some types of diabetes mellitus on one side, and on the other side that euglycemic clamp technique could be used for the assessment of the effects of some therapeutical measures on peripheral insulin sensitivity.
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PMID:[Evaluation of insulin sensitivity in diabetes using the euglycemic hyperinsulinemic clamp method]. 210 55

The role of insulin in the therapy of NIDDM is still under discussion. To clarify the problem we performed a randomized double-blind placebo controlled crossover study of insulin treatment for 4 weeks in diabetic patients (n = 18, age 52-74 years) who were unsatisfactorily controlled by oral antidiabetic agents. The patients continued to use these agents during the study. Special attention was given to informing the patients about the trial and, in particular, about self-monitoring the blood glucose by the use of a reflectance meter. Insulin treatment produced the following significant changes: decreases in blood glucose (at 7.00, 10.00, 16.00), mean daily blood glucose, HbA1, urinary glucose and low density lipoprotein (LDL) cholesterol and increased postglucose immunoreactive insulin (IRI) levels. Significant changes were also observed during the placebo periods: decreases in HbA1 urinary glucose and LDL cholesterol (but not in blood glucose). Therapy with insulin increased the body weight, whereas the placebo insulin had the opposite effect. The finding emphasizes the importance of using not only a run-in period but also a placebo design when the metabolic effects of antidiabetes therapy are to be evaluated. The study indicates that insulin therapy for patients with type 2 diabetes can be initiated at home.
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PMID:Insulin and sulphonylurea in the therapy of type 2 diabetes. 211 Dec 39

Staub Effect or improved glucose disposal after repetitive glucose loads does not occur in untreated diabetes. In non-insulin dependent diabetes (NIDDM) there is impaired insulin response to intravenous (i.v.) glucose injection, especially in early insulin release (EIR) and the lesser known post EIR suppression of insulin levels below basal, or acute insulin decrement (AID). To test the ability of a second generation sulfonylurea, glyburide, to affect glucose primed glucose disposal and insulin secretory patterns, sixteen NIDDM male subjects received three hourly intravenous glucose loads while untreated and again after six months of glyburide therapy. After treatment there was a fall of fasting glycemia from 204 +/- 11 to 147 +/- 8 mg/dl (p less than 0.001), of all glucose levels during the i.v. glucose tolerance tests (p less than 0.025) and glycosylated hemoglobin from 8 +/- 0.3% to 7.6 +/- 0.3% (p less than 0.005). Before treatment i.v. glucose disposal (K value) changed very little after successive glucose challenges, but after glyburide all mean K values were higher, and glucose primed glucose disposals were faster after the second (K2) and third (K3) glucose injection than after the first (K1) (p less than 0.025 and p less than 0.01 respectively). In the untreated state, there was higher and significant EIR by the third glucose load, (p less than 0.025) while AID was clearly more pronounced after the second load (p less than 0.001). After glyburide treatment EIR was significantly higher than before in all loads, and mean AID was no longer demonstrable. Insulin summation (S) after successive i.v. loads maintained a stepwise increase both before and after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recovery of Staub Effect and amelioration of insulin secretion defects after glyburide treatment in non-insulin-dependent diabetes. 213 1

Two matched groups of insulin requiring non-insulin dependent diabetic (NIDDM) patients with mild proteinuria (200 to 999 mg/day), one on mono component (MC) insulin therapy and the other on conventional insulins were studied for a 3 year period to evaluate the course of nephropathy in these two groups. Twenty-seven and 35 patients were followed-up in the MC insulin and conventional insulin groups respectively. In the MC insulin treated group, the percentage of patients showing deterioration in proteinuria was lower (11% vs 34%, P less than 0.05) and the percentage showing improvement was higher (48% vs 29%) compared to the conventional insulin treated group. Insulin antibody titres decreased significantly in the MC insulin group and serum C-peptide values decreased in both groups on follow-up.
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PMID:Comparative study of monocomponent insulins and conventional insulins on the course of diabetic nephropathy. A follow-up study. 184 13

In vivo studies indicate that patients with NIDDM have defects in both insulin secretion and insulin action. The decrease in insulin action is due to both hepatic and extrahepatic insulin resistance. The impairment in glucose uptake is associated with alterations in both oxidative and nonoxidative disposal. Defective glucose transport may limit both of these processes. NIDDM also is associated with increased concentrations and rates of oxidation of plasma free fatty acids. Insulin resistance appears to be familial and in at least some individuals antedates glucose intolerance. In vitro studies indicate that insulin resistance can involve a variety of insulin sensitive tissues including adipocytes, muscle and liver. While most studies note that insulin binding and insulin receptor kinase activity are decreased in insulin sensitive tissues in obese patients with NIDDM, further delineation of the contribution of obesity and diabetes is required. Alterations in glucose transporter number and function likely account at least in part for impaired glucose transport. The cause of the alterations in other insulin responsive pathways and the role of an abnormal metabolic milieu versus intrinsic cellular defects remain to be established.
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PMID:Insulin resistance in type II diabetes mellitus. 216 26


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