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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate whether insulin resistance contributes to the increased risk of diabetes in patients with Turner's syndrome, we measured insulin sensitivity (using the euglycemic insulin clamp technique, 40 mU/m2.min) and whole body glucose and lipid oxidation (assessed by indirect calorimetry) in two groups of nondiabetic patients with Turner's syndrome and age-matched normal controls. Group 1 consisted of eight young patients (mean age, 10 +/- 0.8 yr) who had never received hormone therapy, and group 2 consisted of five patients (mean age, 17.6 +/- 1.4 yr) who had been or were on estrogen therapy. In group 2, [3-3H]glucose was also infused during the euglycemic clamp to assess hepatic sensitivity to insulin. During the euglycemic clamp, insulin-stimulated glucose metabolism was decreased in both groups of patients [group 1, 8.4 +/- 1.0 vs. 14.7 +/- 2 mM/m2.min in controls (P less than 0.05); group 2, 9 +/- 0.7 vs. 11.7 +/- 0.9 mM/m2.min in controls (P less than 0.05)]. The impairment of insulin-stimulated glucose metabolism in patients with Turner's syndrome was accounted for by reduced nonoxidative glucose disposal; glucose oxidation rose to a similar extent in Turner patients and normal controls. Insulin-induced suppression of hepatic glucose production (group 2) and plasma FFA and branched chain amino acid levels in Turner patients was also indistinguishable from that in normal controls. Our data suggest that in patients with Turner's syndrome, insulin resistance is a very early metabolic defect that may be restricted to nonoxidative pathways of intracellular glucose metabolism.
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PMID:Insulin resistance: an early metabolic defect of Turner's syndrome. 200 9

Postprandial lipoprotein metabolism may be important in atherogenesis and has not been studied in detail in noninsulin-dependent diabetes mellitus (NIDDM). We used the vitamin A fat-loading test to label triglyceride-rich lipoprotein particles of intestinal origin after ingestion of a high fat mixed meal containing 60 g fat/m2 and 60,000 U vitamin A/m2 in 12 untreated NIDDM subjects with normotriglyceridemia (NTG; triglycerides, less than 1.7 mmol/L), 7 untreated NIDDM subjects with moderate hypertriglyceridemia (HTG; triglycerides, 1.7-4.7 mmol/L), and 8 age- and weight-matched normotriglyceridemic nondiabetic controls. The postprandial triglyceride increment was greater in NIDDM with HTG (P = 0.0001) and correlated strongly in all groups with the fasting triglyceride concentration (r = 0.83; P = 0.0001). Retinyl palmitate measured in whole plasma, an Sf greater than 1000 chylomicron fraction, and an Sf less than 1000 nonchylomicron fraction was also significantly greater in NIDDM with HTG, but did not differ significantly between NIDDM with NTG and controls. In NIDDM with HTG, chylomicrons appeared to be cleared at a slower rate, as evidenced by the significantly later intersection of the chylomicron and nonchylomicron retinyl palmitate response curves (13.7 h in HTG NIDDM vs. 8.5 h in NTG NIDDM vs. 7.3 h in controls; P less than 0.01). Although fasting FFA levels were similar in all three groups, the HTG diabetic subjects had a late postprandial surge in FFAs that lasted for up to 14 h. The postprandial FFA elevation in all groups correlated with the fasting triglyceride concentration (r = 0.57; P less than 0.002) and postprandial triglyceride increment (r = 0.80; P = 0.0001). The fasting core triglyceride content of the HDL particles in NIDDM with HTG was significantly elevated compared to those in NIDDM with NTG and controls (21.0% vs. 14.0% vs. 14.1% respectively; P less than 0.05), and this increased proportionately in all groups after the meal at the expense of cholesteryl ester, the increase correlating with total plasma postprandial triglyceride increment (r = 0.51; P less than 0.01). We conclude that moderate fasting hypertriglyceridemia in NIDDM is predictive of a constellation of postprandial changes in lipids and lipoproteins that may potentiate the already unfavorable atherogenic fasting lipid profile in these subjects.
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PMID:Fasting hypertriglyceridemia in noninsulin-dependent diabetes mellitus is an important predictor of postprandial lipid and lipoprotein abnormalities. 200 21

Hyperinsulinemia and hyperglycemia per se both stimulate glucose uptake and the disposal of glucose by oxidative (Gox) and nonoxidative (Nox) metabolism. However, the intracellular metabolic fate of glucose may not be the same when glucose uptake is stimulated predominantly by either of these mechanisms due to different effects on fat oxidation (Fox). To address this issue, 11 healthy subjects each had four glucose-clamp studies performed in combination with indirect calorimetry to compare Gox, Nox, and Fox at two different rates of glucose uptake (approximately 7 and 10 mg.kg-1 fat-free mass [FFM].min-1) matched at each level by either hyperglycemia or hyperinsulinemia. When glucose uptake was matched at the lower rate (7 mg.kg-1 FFM.min-1), there was less suppression of both FFA (33 vs. 43%, P less than 0.05) and Fox (73 vs. 90%, P less than 0.05) and less stimulation of incremental (above basal) Gox (1.95 vs. 2.49 mg.kg-1 FFM.min-1, P less than 0.025) at low insulin (72 pM) and hyperglycemia (21.8 mM) compared with high insulin (280 pM) and euglycemia (5.1 mM). Matching glucose uptake at the higher rates (10 mg.kg-1 FFM.min-1) required greater than 300 pM of insulin (309 and 632 pM) in both studies and resulted in maximal suppression of FFA (49 vs. 46%, NS) and Fox (both greater than 90%, NS) and similar incremental Gox (2.89 vs. 2.73 mg.kg-1 FFM.min-1, NS) whether at hyperglycemia (15.7 mM) or euglycemia (5.2 mM). Therefore, both hyperinsulinemia and hyperglycemia stimulate glucose uptake and increase intracellular glucose availability, but insulin also regulates Gox by suppression of FFA and Fox. However, when FFA and Fox are maximally suppressed, the rate of glucose uptake, rather than the prevailing insulin level, determines the distribution of intracellular glucose metabolism.
Diabetes 1990 Jan
PMID:Effect of hyperinsulinemia and hyperglycemia on intracellular glucose and fat metabolism in healthy subjects. 221 57

It has been proposed that central obesity, by virtue of the enhanced lipolytic activity of abdominal adipose tissue, leads to higher plasma FFA concentrations, which, in turn, decrease both hepatic removal of insulin and insulin-stimulated glucose uptake by peripheral tissues. In short, the predicted consequences of abdominal obesity are elevations in circulating FFA and insulin levels as well as insulin resistance. The goal of this study was to evaluate the relationships predicted by the overall hypothesis; this study was carried out in 31 obese females, defined as having normal glucose tolerance (n = 12), impaired glucose tolerance (n = 8), or noninsulin-dependent diabetes mellitus (n = 11). Abdominal obesity was estimated by determining the ratio of waist to hip girth, fasting and postprandial plasma FFA and insulin concentrations were measured at hourly intervals from 0800-1600 h, and insulin-stimulated glucose disposal was quantified by the euglycemic hyperinsulinemic clamp technique. The first step in the postulated sequence of events to be tested was that the greater the WHR, the higher the total integrated plasma FFA response. The correlation coefficient between these two variables was 0.29, indicating that the results did not support the prediction. Furthermore, we could not demonstrate any relationship between the magnitude of the plasma FFA and insulin responses (r = 0.20; P = NS). However, there was a modest inverse relationship between height of circulating plasma insulin concentration and a decrease in insulin-stimulated glucose uptake (r = -0.43; P less than 0.03) in the group as a whole. On the other hand, when the three groups were analyzed individually, a significant inverse relationship was only seen in the control group (r = -0.67), and a direct relationship was actually seen in patients with impaired glucose tolerance (r = 0.88). Furthermore, when the mean responses for the variables in each of the three groups were compared, it was apparent that the postulated relationships between abdominal obesity, plasma FFA concentration, and insulin secretion and action were not present. Thus, the data presented do not support the hypothesis that differences in the degree of central obesity play an important role in regulation of plasma concentrations of either FFA or insulin or in modulation of insulin-stimulated glucose uptake in the patients we studied.
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PMID:Effect of central obesity on regulation of carbohydrate metabolism in obese patients with varying degrees of glucose tolerance. 222 87

GH has been implicated in the pathophysiology of various acute and chronic complications of diabetes mellitus. As a consequence, there has been a great deal of interest in developing methods for suppressing GH secretion in diabetes. SMS 201-995 is a long-acting somatostatin analog which inhibits the secretion of numerous hormones, including GH. To determine the metabolic and hormonal responses to SMS 201-995 independent of endogenous insulin suppression, we studied six patients with insulin-dependent diabetes mellitus while they received 150 micrograms SMS 201-995, sc, daily for an 8-week period. This treatment resulted in no change in 24-h glucose profiles, although the mean insulin dose decreased by 19%, while hemoglobin A1c decreased significantly (0.084 +/- 0.023 to 0.067 +/- 0.011, P = 0.04). The 24-h profiles of blood lactate, plasma free insulin, glucagon, FFA, blood glycerol, and beta-hydroxybutyrate were unchanged, whereas that of blood alanine increased significantly (7.8 +/- 0.4 to 10.6 +/- 0.9 mmol/L.h; P = 0.01). GH secretion declined in five of the six patients; the mean values before and during SMS 201-995 treatment were 102 +/- 23 and 68 +/- 12 micrograms/L.h, respectively (P = NS), for the six patients. [In the five patients in whom GH secretion declined, the mean values before and during SMS 201-995 treatment were 115 +/- 23 and 63 +/- 14 micrograms/L.h, respectively (P = 0.01).] These results suggest that SMS 201-995 may be administered to patients with insulin-dependent diabetes mellitus without a deleterious effect on metabolic control.
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PMID:The effects of SMS 201-995 (sandostatin) on metabolic profiles in insulin-dependent diabetes mellitus. 264 88

Plasma glucose, FFA, and insulin responses to an oral glucose challenge, plasma lipid and lipoprotein concentrations, and the ability of insulin to stimulate glucose disposal were measured in 35 nondiabetic sedentary and overweight subjects. The subjects were divided into 2 groups on the basis of the presence (n = 19) or absence (n = 16) of a history of a first degree relative with noninsulin-dependent diabetes. The 2 groups were similar in age, body mass index, waist to hip ratio, and maximal aerobic capacity. The results demonstrated that the ability of insulin to stimulate disposal of a glucose load was significantly reduced in the subjects with a positive family history of noninsulin-dependent diabetes. In addition, these individuals had significantly higher plasma triglyceride and very low density lipoprotein cholesterol concentrations. Since all environmental factors known to modify insulin action and very low density lipoprotein metabolism were equal in the 2 groups, these data suggest that the metabolic differences noted are likely to be genetic in origin.
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PMID:Insulin resistance and hypertriglyceridemia in nondiabetic relatives of patients with noninsulin-dependent diabetes mellitus. 266 29

To characterize the effects of artificial beta-cell directed insulin therapy on carbohydrate, lipid and amino acid metabolism, five insulin-dependent diabetic patients were challenged with a 100-g glucose meal while on conventional (single or split mixed insulin injections) therapy and again after 72 hr on an artificial beta-cell unit. It was verified that the high levels of blood glucose of the conventionally treated diabetics were marked reduced toward normal by the artificial beta-cell therapy, while the blood lactate and pyruvate concentrations increased significantly to levels higher than in normal controls. The elevated levels of FFA, glycerol, and ketones in the diabetics under conventional therapy were entirely normalized during the artificial beta-cell regulation. Furthermore, the artificial beta-cell insulin therapy showed capable to restore the abnormalities in the blood profiles of alanine, glutamine and branched-chain amino acids, exceeding in some points the normal response. It was also detected hyperinsulinemia in the diabetics treated with the artificial beta-cell unit and no change in the pancreatic beta-cell function during this period of regulation, evidenced by low and unchanged blood levels of C-peptide. Marked suppression of pancreatic alpha-cell secretion was detected by the significant decrease of the hyperglucagonemia in the conventionally treated diabetics by the artificial beta-cell therapy. These studies reveal that the artificial beta-cell insulin therapy is capable of restoring to normal not only the abnormal glucose metabolism of conventionally treated diabetics, but also other substrate metabolism related to the lipid and protein homeostasis of the organism.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1989 May
PMID:Carbohydrate, lipid and amino acid metabolism of insulin-dependent diabetic patients regulated by an artificial beta-cell unit. 269 78

The rate of the small intestine amylolytic digestion appears to be a major determinant of the glycemic response. Foods such as legumes appear to be digested less rapidly than many cereal foods although even amongst these large differences in rates of in vitro digestion exist. Studies of diabetes using high fibre, high legume diets have almost uniformly noted improvements in glycemic control and blood lipid profile. However, diets where changes in fibre content have been relatively small, but where the foods were selected on the basis of their slow rates of digestion and flatter glycemic response, have also produced similar beneficial effects. The reasons for the altered rates of digestion include fibre, food form, the nature of the starch, antinutrients etc. Through reducing the rate of digestion of starchy foods post prandially "slow release" starchy foods blunt many gut hormone responses, and prolong FFA and ketone body suppression. In addition increased starch losses to the colon may enhance production of SCFA. All these events may modify carbohydrate and lipid metabolism. Many foods which produce these effects are traditional starchy foods and so strengthen current recommendations of the diabetes association, heart foundations and cancer institutes to increase the use of starchy foods through reducing fat intake. Recognition of the nutritional value of these foods is however not new, but was well accepted in the ancient world and is still preserved in traditional cultures where freedom from many of the major non-infective Western diseases is a notable phenomenon.
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PMID:Starchy foods and fiber: reduced rate of digestion and improved carbohydrate metabolism. 282 27

Fructose raises blood glucose and lactate levels in normal as well as diabetic man, but the tissue origin (liver and/or kidney) of these responses and the role of insulin in determining the end products of fructose metabolism have not been fully established. Splanchnic and renal substrate exchange was therefore examined during intravenous infusion of fructose or saline in six insulin-deficient type I diabetics who fasted overnight and in five healthy controls. Fructose infusion resulted in similar arterial concentrations and regional uptake of fructose in the two groups. Splanchnic glucose output increased threefold in the diabetics but remained unchanged in controls in response to fructose infusion, and the arterial glucose concentration rose more in diabetics (+5.5 mmol/liter) than in controls (+0.5 mmol/liter). Splanchnic uptake of both lactate and pyruvate increased twofold in response to fructose infusion in the diabetics. In contrast, a consistent splanchnic release of both lactate and pyruvate was seen during fructose infusion in controls. In diabetics fructose-induced hyperglycemia was associated with no net renal glucose exchange, while there was a significant renal glucose production during fructose infusion in the controls. In both groups fructose infusion resulted in renal output of lactate and pyruvate. In the diabetics this release corresponded to the augmented uptake by splanchnic tissues. In two diabetic patients given insulin infusion, all responses to fructose infusion were normalized. Fructose infusion in diabetics did not influence either splanchnic ketone body production or its relationship to splanchnic FFA inflow. We conclude that in insulin-deficient, mildly ketotic type I diabetes, (a) both the liver, by virtue of lactate, pyruvate, and fructose-derived gluconeogenesis, and the kidneys , by virtue of fructose-derived lactate and pyruvate production, contribute to fructose-induced hyperglycemia; (b) outcome of hepatic fructose metabolism; and (c) fructose does not exert an antiketogenic effect. These data suggest that while total fructose metabolism is not altered in diabetics, intermediary hepatic fructose metabolism is dependent on the presence of insulin.
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PMID:Splanchnic and renal exchange of infused fructose in insulin-deficient type 1 diabetic patients and healthy controls. 291 Sep 19

Successive epinephrine infusions were used as a partial model to examine hormonal and metabolic responses to repeated stress stimuli. As both the endogenous opiates and epinephrine are released in response to stress, we have also studied interactions between epinephrine and B-endorphin. Epinephrine (0.1 microgram/kg . min) was infused for 60 min, followed by a 60-min recovery, in nine normal, conscious dogs. In a similar study, B-endorphin (0.06 microgram/kg . min) was given 30 min before epinephrine, then continuously infused throughout the study (N = 4 dogs). When epinephrine was infused, levels rose to 600-800 pg/ml. The changes in glucagon, B-endorphin, FFA, and hepatic glucose production were similar during both epinephrine infusions, but there was a diminished insulin response, a greater decrease in glucose metabolic clearance, and a greater increase in plasma glucose with the second epinephrine infusion. When B-endorphin was given, plasma levels increased to 5.3 ng/ml. Compared with the infusion of epinephrine alone, there was a much greater rise in plasma glucose due to greater suppression of glucose metabolic clearance. With the second epinephrine infusion, however, the changes in glucose concentration were not substantially different from those seen during the second infusion of epinephrine alone, as both hepatic glucose production and glucose metabolic clearance were suppressed. B-endorphin diminished the insulin and glucagon responses during the first epinephrine infusion and abolished them during the second, but did not alter the FFA, ACTH, or cortisol responses to epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Dec
PMID:Beta-endorphin modulation of the glucoregulatory effects of repeated epinephrine infusion in normal dogs. 299 13


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