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)

Maturity onset diabetes (MOD) is characterized by the fact that the response of insulin secretion to glucose loading is either completely missing or is reduced if compared with that of persons whose metabolism is intact. But insulin secretion can be provoked by other specific stimuli. However, the quantitative IRI response can provide no information as to which of the MO diabetics must be treated by dietetic measures only and which of them are liable to treatment with sulfonylurea. It was, therefore, investigated whether in 109 patients suffering from recently developed overt MOD a differentiation from a therapeutical point of view can be attained by joint evaluation of stimulated IRI secretion, of glucose tolerance, of the dynamics of free fatty acids, of the fasting values of triglycerides and cholesterol and of the body weight. The findings suggest that no better differentiation for the two methods of treatment of MOD stated above is possible by simultaneous evaluation of the parameters of fat metabolism, glucose level and IRI secretion than by IRI secretion and carbohydrate tolerance alone.
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PMID:Insulin secretion, carbohydrate tolerance, fat metabolism and body weight in maturity onset diabetics requiring various methods of therapy. 9 78

Previous work has suggested that impaired islet glucose recognition occurs in patients with adult onset diabetes, as acute insulin release is absent after iv glucose but present after beta adrenergic stimulation with isoproterenol (Iso). However, insulin responses to Iso were variably reduced as compared to normal in the diabetics. In order to evaluate the importance of the Iso dose, dose-response studies were performed in 9 diabetics (fasting plasma glucose greater than 150 mg/dl) and 10 age-matched controls. In both control subjects and diabetics, 0.5 microgram Iso produced no insulin response; 2 micrograms Iso produced an intermediate response; and 8 and 12 micrograms Iso produced a higher response. The insulin responses to the larger doses of Iso were lower in diabetics than control subjects (8 micrograms, 20 +/- 5 vs. 39 +/- 6 (P less than 0.025); 12 micrograms, 21 +/- 6 vs. 37 +/- 4 (P less than 0.05); means +/- SEM, microU/ml). Of 16 diabetics who received 12 micrograms Iso, 5 had insulin responses greater than 2 SD below the control mean, while others had responses that spanned the entire range of normal. Seven diabetics also were given iv secretin (150 U). Their insulin responses to secretin correlated with the responses to Iso (r = 0.83, P less than 0.02). Thus, patients with subnormal responses to Iso also had low secretion responses. The abnormalities of acute insulin secretion in diabetics can be explained by a lesion variably affecting islet membrane receptors; some patients may have glucose receptor damage, but intact responses to other stimuli, and others may have more widespread damage affecting beta-adrenergic and secretin responses as well. Alternatively, there may be heterogeneity in adult onset diabetes, as patients with low responses to all stimuli could have a qualitatively different lesion affecting insulin secretory capacity rather than membrane receptors.
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PMID:Mechanisms of impaired acute insulin release in adult onset diabetes: studies with isoproterenol and secretin. 40 Jul 68

In a family with maturity-onset type of diabetes mellitus inherited as a dominant, autosomal trait (MODY), the HLA genotypes were compared with the glucose tolerance and the plasma insulin response to oral glucose. In the members with impaired glucose tolerance, the plasma insulin response was of the insulino-tardic type, while those with normal or borderline glucose tolerance had a normal plasma insulin response. HLA tissue typing for A, B, C and D series antigens carried out in 19 of the members showed no association between specific HLA antigens and imparied glucose tolerance. Moreover, when analysing the segregation of the disease and the HLA characters, several recombinants between MODY and HLA would have to be postulated if the gene(s) for this form of diabetes mellitus should be closely linked to the HLA locus.
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PMID:HLA antigens in a family with maturity-onset type diabetes mellitus. 58 Aug 33

Physical training is useful as a therapeutic means to obtain a decrease in body fat. The success in terms of lost fat is dependent on the ability to adhere to the programme, and probably also on regulatory factors associated with the degree of filling of adipose tissue (adipocyte volume). The rate of weight loss is usually slower than with dietary treatment but physical exercise may be more successful and less uncomfortable in the long run as a means to lose weight and prevent regaining it. Physical training is also effective against the metabolic complications associated with obesity such as decreased glucose tolerance, hyperinsulinemia and hypertriglyceridemia and should therefore be a method of choice to prevent or treat adult onset diabetes mellitus and endogenous hypertriglyceridemia in obesity. The feasibility of training in different groups of subjects seems to be dependent on, among other factors, selection of subjects and design of the training programme.
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PMID:Physical training in the treatment of obesity. 71 62

We have used a continuous intravenous infusion of glucose (6 mg/kg/min), insulin (80 mU/min), epinephrine (6 mug/min), and propranolol (0.08 mg/min) to directly assess insulin resistance in 14 untreated adult onset diabetics with a mean (plus or minus SE) fasting plasma glucose level of 217 plus or minus 17 mg/100 ml. During the infusion endogenous insulin secretion is inhibited and steady-state plasma glucose and insulin levels are achieved after 90 min. Since similar steady-state levels of plasma insulin are achieved in all subjects, the plasma glucose concentration observed during the steady-state period is a measure of an individual's insulin resistance. Under these conditions, the mean (plus or minus SE) steady-state plasma glucose level of the 14 diabetic patients was 350 plus or minus 16 mg/100 ml, while that of 12 normal subjects was 121 plus or minus 4 mg/100 ml. Additional studies were performed in which control subjects and patients with diabetes had their fasting plasma glucose levels acutely raised or lowered to comparable levels before receiving the basic infusion mixture of glucose, insulin, epinephrine, and propranolol. The results of these studies indicated that differences in initial plasma glucose levels could not account for the different glucose responses of the two groups to the basic infusion. Finally, the mean (plus or minus SE) steady-state plasma glucose level of 104 plus or minus 17 mg/100 ml observed during the same basic infusion in five patients with fasting hyperglycemia (mean plus or minus SE, 142 plus or minus 12 mg/100 ml) secondary to chronic pancreatitis suggested that neither chronic hyperglycemia nor hypoinsulinemia per se necessarily lead to insulin resistance. These results demonstrate that marked insulin resistance exists in adult onset diabetics with fasting hyperglycemia. Since previous studies have documented the presence of insulin resistance in patients with chemical diabetes, the possibility exists that insulin resistance may be characteristic of adult onset diabetes mellitus.
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PMID:Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia. 111 64

1. In 161 consecutive cases of fluctuant hearing loss and 13 control cases of other causes of deafness, patients were examined for their ability to metabolize a 100 gm. oral dose of glucose. 2. The plasma glucose level in response to the oral dose of glucose was measured at hourly intervals for three hours. 3. Insulin and proinsulin levels were measured in 46 cases of fluctuant hearing loss and in 13 control cases. 4. None of the control group showed borderline or diabetic tolerance curves. 5. Fourteen per cent of the patients with fluctuant hearing loss had borderline glucose intolerance curves and 19 per cent showed diabetic glucose tolerance curves. 6. In patients whose insulin and proinsulin levels were determined, the insulin response to an oral glucose load was typical of adult onset diabetes, i.e., delayed hyperinsulinemia with concomitant hyperglycemia. The hyperinsulinemia was not associated with hyperproinsulinemia. 7. We conclude that in patients with fluctuant hearing loss there is a significantly higher incidence of borderline or diabetic glucose tolerance than in the "control deafness" or "normal population" group.
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PMID:Diabetes mellitus in fluctuant hearing loss. 115 1

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.
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PMID:Acute-phase insulin secretion and glucose tolerance in young and aged normal men and diabetic patients. 115 58

Diabetes mellitus is commonly associated with systolic and diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive controls, a heightened plasma insulin response to a glucose challenge is found consistently. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. Using the insulin/glucose clamp technique in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: sodium retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth-muscle cells. Physiological maneuvers, such as caloric restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; good evidence indicates that these maneuvers also can lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia also are associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate density and low-density lipoproteins, both of which are atherogenic. Last, insulin per se, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth-muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth-muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of a variety of growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including type II diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.
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PMID:Insulin resistance, hyperinsulinemia, and coronary artery disease: a complex metabolic web. 128 37

Abnormalities in lymphocyte subpopulations in patients with type 1 diabetes have been reported previously. To evaluate the effect of blood glucose levels on peripheral lymphocyte concentrations we studied the proportion and phenotypic composition of the T-cell population in 7 patients with type 1 and in 12 patients with type 2 diabetes at hospitalization because of metabolic dysregulation and in a period of restored control. Both the number of CD-4 and CD-8 positive cells increased significantly (p < 0.05), although no change in the CD-4:CD-8 ratio was observed. After restoring metabolic control there was a significant rise in the mean number of total lymphocytes (1760 +/- 759 x 10(6)/ml vs 2385 +/- 889 x 10(6)/ml, p < 0.05). The number of total lymphocytes increased in all patients but one. It is concluded that metabolic control can influence immunological parameters such as numbers of peripheral lymphocytes of various phenotypes.
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PMID:Influence of blood glucose levels on peripheral lymphocytes in patients with diabetes mellitus. 128 42

Several methods of varying complexity are available for the measurement of in vivo insulin secretion in man. No study has previously compared these in the same subjects to establish which is the most appropriate for routine use. We have, therefore, compared four methods for measuring insulin secretion in man: Hyperglycaemic clamp (Hy), Minimal model (MIN), shortened intravenous glucose tolerance test (IVGTT) and continuous infusion of glucose with model assessment (C.I.G.M.A.). Seventeen subjects with varying degrees of insulin sensitivity were studied. Seven normal (BMI 22.5 +/- 1.5 kg/m2), five obese (BMI 38 +/- 5 kg/m2) and five NIDDM subjects (BMI 27 +/- 3 kg/m2) were investigated, in a randomised fashion, on separate days. First (PSI) and second phase (PSII) rate constants (MIN); incremental insulin secretion 0-10 mins (Hy delta I) and steady state insulin levels from the last 30 minutes (Hy120-150) from the hyperglycaemic clamp; 3 minute insulin concentration and incremental area under insulin secretion curve 0-10 min (IVGTT) and beta-cell function (%) from C.I.G.M.A. were used as indicators of insulin secretion. Each index of insulin secretion could detect an overall difference between the groups. Insulin secretion in normals and obese was similar but significantly increased compared to NIDDM. In normals PSI correlated with C.I.G.M.A. (Rs = 0.92, p < 0.02) and Hy120-150 (Rs = 0.82, p < 0.05). IVGTT0-10 correlated with PSII (Rs = 0.83, p < 0.05), HY delta I (Rs = 0.84, p < 0.05) and IVGTT3 min (Rs = 1.0, p < 0.001). In obese PSII correlated with C.I.G.M.A. (Rs = 0.91, p < 0.05), Hy delta I (Rs = 1.0, p < 0.02) Hy120-150 (Rs = 0.92, p < 0.05) and IVGTT3 min Rs = 1.0, p < 0.02). In addition Hy delta I also correlated with C.I.G.M.A. (Rs = 0.92, p < 0.05) and IVGTT3 min (Rs = 1.0, p < 0.02). In NIDDM Hy delta I correlated with C.I.G.M.A. (Rs = 0.91, p < 0.005). When all subjects from the three groups were combined, significant positive correlations were obtained between each index of insulin secretion. In conclusion we have demonstrated that: (a) C.I.G.M.A., IVGTT, Minimal model and hyperglycaemic clamp can provide similar overall results for, in vivo, beta-cell function in man. (b) Significant positive correlations were obtained between each index of insulin secretion when all subjects were combined. (c) Using the above methodologies insulin secretion in normal and obese appears similar but significantly increased compared to NIDDM subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A comparison of four methods for assessing in vivo beta-cell function in normal, obese and non-insulin-dependent diabetic man. 128 45


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