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

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

Long-term dietary restriction to maintain constant body weight in adult rhesus monkeys prevents the development of impaired glucose tolerance, hyperglycemia, and noninsulin-dependent diabetes mellitus. We sought to determine whether these positive antidiabetogenic effects of reduced calorie intake with maintenance of normal lean body weight might be mediated through prevention of the development of insulin resistance. Insulin-stimulated glucose uptake was assessed by the euglycemic hyperinsulinemic clamp technique in seven older-aged rhesus monkeys (20.7 +/- 0.6 years) who had been dietary restricted for 9 +/- 2 years. Results were compared to seven ad libitum-fed nondiabetic monkeys of similar age (21.0 +/- 1.3 years). Results showed that the dietary restricted monkeys had significantly higher in vivo insulin action compared to the ad libitum-fed group (14.06 +/- 2.4 vs 7.75 +/- 0.9 mg/kg FFM/min, respectively; p < .03). We conclude that long-term dietary restriction is an effective means of mitigating the development of significant insulin resistance in older-aged rhesus monkeys, and may be the mechanism underlying the prevention of Type II diabetes in this model.
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PMID:Long-term dietary restriction in older-aged rhesus monkeys: effects on insulin resistance. 774 93

The aim of our study was to compare plicometry and bioelectrical impedance analysis as methods for body composition assessment (fat mass-FM%, fat-free mass-FFM) and to extrapolate population-specific equations in order to predict the plicometrically-derived FM and FFM on the basis of body resistance. A cross-sectional study was carried out at the Diabetes Out-Patient Clinic, Department of Internal Medicine, University of Palermo, Italy. We examined 102 subjects (45 men, 57 women, age range 30-45 years) divided into three groups: Group N (36 normal weight subjects, body mass index-BMI = weight/height2 = 24.5 +/- 0.8), Group O (35 obese subjects, BMI = 35.1 +/- 0.4), and Group GO (morbid obese subjects, BMI = 49.2 +/- 1.2) as well as a control group of 30 subjects (12 men, 18 women, age range 30-45 years, BMI = 20.9-63.1). We measured the following parameters: bioelectrical impedance analysis (body resistance: R), plicometry (triceps, biceps, subscapular, and suprailiac skinfolds), height (Ht), weight (W). The two methods were comparable in Groups N and O. In Group GO, however, especially in men and for FM%, measurements were significantly different. Plicometrically-determined FM% and FFM-Kg were significantly correlated to R.W/Ht2 (r = 0.821, p < 0.0001) and to Ht2/R (r = 0.867, p < 0.0001) respectively. The following prediction formulas for plicometric FM and FFM from body resistance and anthropometric variables were obtained: 1) FM% = 22.3 (R.W/Ht2)-2.2, and 2) FFM-Kg = 1.1 (Ht2/R)-3.1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Assessment of body composition in groups of subjects with different body size. Comparison of skinfold thickness and impedance methods]. 789 71

In vivo resistance to the action of insulin on glucose uptake has been documented during puberty. To test the hypothesis that the glucose-fatty acid cycle, as proposed by Randle et al. (Randle PJ, Garland PB, Hales CN, Newsholme EA: The glucose fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785-789, 1963), may be responsible for this phenomenon, we studied nine prepubertal (Tanner I), nine pubertal (Tanner II-IV), and five young adult healthy subjects. The rate of lipolysis was measured with [d-5]glycerol tracer during basal state and during a stepwise hyperinsulinemic (10 and 40 mU.m-2.min-1)-euglycemic clamp. The rates of insulin-stimulated glucose disposal (Rd) were measured during the clamp, whereas glucose and fat oxidation were measured by using indirect respiratory calorimetry. Basal glycerol rate of appearance (Ra; lipolysis) and fat oxidation were similar between prepubertal and pubertal subjects but higher than adults when the data were expressed per kilogram body weight or per kilogram fat-free mass (FFM; glycerol Ra: 2.5 +/- 0.2, 2.6 +/- 0.2 vs. 1.6 +/- 0.2 mumol.min-1.kg FFM-1, P < 0.05; fat oxidation: 4.4 +/- 0.6, 4.8 +/- 0.3 vs. 3.2 +/- 0.6 mumol.min-1.kg FFM-1, P < 0.05). However, when expressed for total body, glycerol Ra and fat oxidation were higher in pubertal versus prepubertal and adult subjects. Insulin-like growth factor I (IGF-I) levels correlated with total-body lipolysis (r = 0.52, P = 0.006) and with total lipid oxidation (r = 0.44, P = 0.016) at baseline.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1994 Jul
PMID:Correlations between fatty acid and glucose metabolism. Potential explanation of insulin resistance of puberty. 801 56

Glucose turnover was assessed from [6,6-2H]glucose and [U-13C]glucose dilution analysis in six lean nondiabetic subjects, six obese patients with normal glucose tolerance, and six obese patients with non-insulin-dependent diabetes mellitus (NIDDM) during sequential infusions of glucose (13.9 mumol/kg fat-free mass [FFM]/min) and glucose+amino acid (4.2 mg/kg FFM/min). Cori cycle activity was assessed from the difference between glucose turnover obtained from [6,6-2H]glucose and [U-13C]glucose. During infusion of glucose alone, total glucose turnover was increased by 70% in obese NIDDM patients. Amino acid infusion decreased glucose concentrations by 0.8, 0.5, and 1.8 mmol/L in controls, obese patients, and NIDDM patients, respectively. This decrease in glycemia occurred despite an increase in glucose turnover in lean and obese nondiabetic subjects, and was due to an increased metabolic clearance rate (MCR) of glucose. In NIDDM patients the MCR of glucose was unchanged, and the decrease in glycemia was explained by a diminution in hepatic glucose output. Glucose turnover obtained by [6.6-2H] dilution analysis exceeded significantly the values obtained by dilution analysis in obese subjects and obese NIDDM patients, but not in controls. This indicates an increased Cori cycle activity in these patients.
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PMID:Effects of glucose and amino acid infusion on glucose turnover in insulin-resistant obese and type II diabetic patients. 815 98

To determine the effect of inhibition of gluconeogenesis on liver glycogen stores in patients with non-insulin-dependent diabetes mellitus (NIDDM) after a 3-day fast, 10% ethanol (EtOH) was administered intravenously to nine obese patients with NIDDM and six obese nondiabetic subjects. Rates of glucose appearance (3-[3H]glucose) and [U-14C]alanine incorporation into glucose (alanine gluconeogenesis [Ala-GNG]) were determined before and during EtOH administration, and residual glycogen stores were assessed by the incremental glucose response to glucagon (glucoseAUC). Hepatic glucose output (HGO) was closely correlated with plasma glucose levels (r = 0.71, P < 0.001) after the 3-day fast and was significantly greater in the diabetic compared with the nondiabetic subjects (13.8 +/- 1.4 vs. 7.6 +/- 0.6 mumol.kg-1 FFM.min-1, P < 0.01). During the 120-min EtOH infusion, Ala-GNG fell by more than 50% in both groups and did not increase after intravenous glucagon administration. HGO fell modestly in both the diabetic and nondiabetic subjects during the first 30 min of EtOH infusion and stabilized thereafter. In contrast to Ala-GNG, HGO increased significantly after intravenous glucagon administration in both the diabetic and nondiabetic subjects, but the increase was significantly greater in the patients with NIDDM (P < 0.01). The glucose area under the curve in response to glucagon (glucoseAUC) was lower in the presence of EtOH than in its absence (14.9 +/- 7 vs. 68 +/- 15.6 mM/min, P < 0.01) in the obese nondiabetic subjects, which suggests a decrease in liver glycogen stores.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1994 Feb
PMID:Suppression of gluconeogenesis after a 3-day fast does not deplete liver glycogen in patients with NIDDM. 828 50

Studies have shown that insulin resistance increases with age, independent of changes in total adiposity. However, there is growing evidence that the development of insulin resistance may be more closely related to abdominal adiposity. To evaluate the independent effects of aging and regional and total adiposity on insulin resistance, we performed hyperinsulinemic euglycemic clamps on 17 young (21-33 yr) and 67 older (60-72 yr) men and women. We assessed FFM and total and regional adiposity by hydrodensitometry and anthropometry. Insulin-stimulated GDRs at a plasma insulin concentration of approximately 450 pM averaged 45.6 +/- 3.3 mumol.kg FFM-1 x min-1 (mean +/- SE) in the young subjects, 45.6 +/- 10.0 mumol.kg FFM-1 x min-1 in 24 older subjects who were insulin sensitive, and 23.9 +/- 11.7 mumol.kg FFM-1 x min-1 in 43 older subjects who were insulin resistant. Few significant differences were apparent in skin-fold and circumference measurements between young and insulin-sensitive older subjects, but measurements at most central body sites were significantly larger in the insulin-resistant older subjects. Waist girth accounted for > 40% of the variance in insulin action, whereas age explained only 10-20% of the total variance and < 2% of the variance when the effects of waist circumference were statistically controlled. These results suggest that insulin resistance is more closely associated with abdominal adiposity than with age.
Diabetes 1993 Feb
PMID:Insulin resistance in aging is related to abdominal obesity. 842 63

The short-term administration of a nicotinic acid analogue (acipimox) increases insulin sensitivity and consequently glucose disposal, both in patients with non-insulin-dependent diabetes mellitus (NIDDM) and in patients with cirrhosis. This effect has been attributed to a decrease in plasma nonesterified fatty acid (NEFA) levels and fatty acid oxidation rates, and a corresponding increase in carbohydrate oxidation. The aim of the present study was to determine whether acipimox influenced glucose disposal independent of changes in lipid metabolism. Seven normal men (age, 31 +/- 4 years; body mass index, 23.2 +/- 1.8 kg.m-2; fat-free mass [FFM], 66.8 +/- 4.2 kg) were studied on two separate occasions with hyperinsulinemic (0.06 U.kg FFM-1.h-1) euglycemic clamps (duration, 150 minutes). A primed (150 U), continuous (0.4 U.kg-1.min-1) infusion of heparin together with 10% intralipid (25 mL.h-1) was infused in both studies from -90 to 150 minutes to maintain comparable levels of plasma NEFA and lipid oxidation rates. Acipimox (500-mg capsules) or placebo were administered orally in a double-blind random fashion at t = -90 and t = 0 minutes. Whole-body lipid and carbohydrate oxidation were measured in the last 30 minutes of both the basal (preclamp) period (-30 to 0 minutes) and the clamp period (120 to 150 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acipimox increases glucose disposal in normal man independent of changes in plasma nonesterified fatty acid concentration and whole-body lipid oxidation rate. 848 48

We compared the effects of oral vanadyl sulfate (100 mg/day) in moderately obese NIDDM and nondiabetic subjects. Three-hour euglycemic-hyperinsulinemic (insulin infusion 30 mU / m / min) clamps were performed after 2 weeks of placebo and 3 weeks of vanadyl sulfate treatment in six nondiabetic control subjects (age 37 +/- 3 years; BMI 29.5 +/- 2.4 kg/m2 ) and seven NIDDM subjects (age 53 +/- 2 years; BMI 28.7 +/-1.8 kg/m2). Glucose turnover ([3-3 H]glucose), glycolysis from plasma glucose, glycogen synthesis, and whole-body carbohydrate and lipid oxidation were evaluated. Decreases in fasting plasma glucose (by approximately 1.7 mmol/l) and HbAlc (both P < 0.05) were observed in NIDDM subjects during treatment; plasma glucose was unchanged in control subjects. In the latter, the glucose infusion rate (GIR) required to maintain euglycemia (40.1 +/- 5.7 and 38.1 +/- 4.8 micromol / kg fat-free mass FFM / min) and glucose disposal (Rd) (41.7 +/- 5.7 and 38.9 +/-4.7 micromol / kg FFM / min were similar during placebo and vanadyl sulfate administration, respectively. Hepatic glucose output (HGO) was completely suppressed in both studies. In contrast, in NIDDM subjects, vanadyl sulfate increased GIR approximately 82% (17.3 +/- 4.7 to 30.9 +/- 2.7 micromol / kg FFM / min, P < 0.05); this improvement in insulin sensitivity was due to both augmented stimulation of Rd (26.0 +/-4.0 vs. 33.6 +/- 2.22 micromol / kg FFM / min, P < 0.05) and enhanced suppression of HGO (7.7 +/- 3.1 vs. 1.3 +/- 0.9 micromol / kg FFM / min, P < 0.05). Increased insulin-stimulated glycogen synthesis accounted for >80% of the increased Rd with vanadyl sulfate (P < 0.005), but plasma glucose flux via glycolysis was unchanged. In NIDDM subjects, vanadyl sulfate was also associated with greater suppression of plasma free fatty acids (FFAs) (P < 0.01) and lipid oxidation (P < 0.05) during clamps. The reduction in HGO and increase in Rd were both highly correlated with the decline in plasma FFA concentrations during the clamp period (P < 0.001). In conclusion, small oral doses of vanadyl sulfate do not alter insulin sensitivity in nondiabetic subjects, but it does improve both hepatic and skeletal muscle insulin sensitivity in NIDDM subjects in part by enhancing insulin's inhibitory effect on lipolysis. These data suggest that vanadyl sulfate may improve a defect in insulin signaling specific to NIDDM.
Diabetes 1996 May
PMID:Oral vanadyl sulfate improves insulin sensitivity in NIDDM but not in obese nondiabetic subjects. 862 Oct 19

Insulin resistance and insulin hypersecretion are established features of obesity. Their prevalence, however, has only been inferred from plasma insulin concentrations. We measured insulin sensitivity (as the whole-body insulin-mediated glucose uptake) and fasting posthepatic insulin delivery rate (IDR) with the use of the euglycemic insulin clamp technique in a large group of obese subjects in the database of the European Group for the Study of Insulin Resistance (1,146 nondiabetic, normotensive Caucasian men and women aged 18-85 yr, with a body mass index (BMI) ranging from 15 to 55 kg.m-2). Insulin resistance, defined as the lowest decile of insulin sensitivity in the lean subgroup (608 subjects with a mean BMI of 29 kg.m-2). Insulin sensitivity declined linearly with BMI at an age- and sex-adjusted rate of 1.2 micromol.min-1.kg FFM-1 per BMI unit (95% confidence intervals = 1.0-1.4). Insulin hypersecretion, defined as the upper decile of IDR, was significantly (P<0.0001) more prevalent (38%) than insulin resistance in the obese group. In the whole dataset, IDR rose as a function of both BMI and insulin resistance in a nonlinear fashion. Neither the waist circumference nor the waist-to-hip ratio, indices of body fat distribution, was related to insulin sensitivity after adjustment for age, gender, and BMI; both, however, were positively associated (P<0.001) with insulin hypersecretion, particularly in women. In nondiabetic, normotensive obese subjects, the prevalence of insulin resistance is relatively low, and is exceeded by the prevalence of insulin hypersecretion, particularly in women with central obesity. In the obese with preserved insulin sensitivity, risk for diabetes, cardiovascular risk, and response to treatment may be different than in insulin resistant obesity.
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PMID:Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR). 930 23


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