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  • 1
    ISSN: 1432-0428
    Keywords: Insulin-mediated glucose uptake ; glucose oxidation ; non-oxidative glucose disposal ; lipid oxidation ; insulin resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin resistance is a common feature of Type 2 (non-insulin-dependent) diabetes mellitus. This defect in insulin-mediated glucose metabolism could result from a defect in either glucose oxidation or non-oxidative glucose disposal. To examine this question, euglycaemic insulin clamp studies were performed in 16 normal weight Type 2 and 11 age-matched control subjects. In Type 2 diabetic patients the fasting plasma glucose concentration, 8.39±0.50 mmol/l, was allowed to decline (over 54±6 min) to 5.33±0.11 mmol/l before starting the insulin clamp. Total body glucose uptake was significantly decreased in Type 2 diabetic patients vs control subjects (148±15 vs 264±25 mg/min · m2, p〈0.001). Both total glucose oxidation (59±6 vs 89±6 mg/min·m2, p〈0.005) and non-oxidative glucose disposal (89±15 vs 179±24 mg/min · m2, p〈0.005) were significantly reduced in the Type 2 diabetic patients. Basal glucose oxidation was also reduced in the Type 2 diabetic patients (22±3 vs 38±5 mg/min·m2, p〈0.01). In conclusion, during the postabsorptive state and under conditions of euglycaemic hyperinsulinaemia, impairment of glucose oxidation and non-oxidative glucose disposal both contribute to the insulin resistance observed in normal weight Type 2 diabetic patients. Since lipid oxidation was normal in this group of diabetic patients, excessive non-esterified fatty acid oxidation cannot explain the defects in glucose disposal.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Free fatty acid ; Type 2 (non-insulin-dependent) diabetes ; insulin suppression ; insulin dose-response curve
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to define the effect of Type 2 (non-insulin-dependent) diabetes mellitus on the ability of insulin to regulate plasma-free fatty acid (FFA) concentrations, we determined the plasma FFA response to the intravenous infusion of various amounts of insulin. Plasma FFA concentrations were higher in patients with Type 2 diabetes (two way analysis of variance, p〈0.001) over a plasma insulin concentration which ranged from approximately 5 to 55 mU/l of insulin. Although plasma FFA concentrations were higher in patients with Type 2 diabetes at any given insulin concentration, the relative ability of insulin to suppress plasma FFA concentration to half the initial value was comparable in normal individuals and patients with Type 2 diabetes, occurring at a plasma insulin concentration of approximately 20 mU/l. These data demonstrate that plasma FFA levels are regulated over a narrow range of plasma insulin concentrations in humans, and that plasma concentrations are higher than normal in patients with Type 2 diabetes throughout this range.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: Hyperlipidaemia ; Orlistat ; lipase inhibitor ; fat malabsorption ; LDL cholesterol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of orlistat, a nonabsorbed inhibitor of gastric and pancreatic lipases, was examined in patients with primary hyperlipidaemia (serum cholesterol ≥6.2 mmol·l−1 and triglycerides ≤5.0 mmol·l−1) not responsive to dietary change alone. In a multicentre, randomised, double-blind study, 103 men and 70 women received 30, 90, 180, or 360 mg of orlistat or placebo for 8 weeks. Total and low-density lipoprotein cholesterol levels were reduced by 4% and 5% with 30 mg orlistat, by 7% and 8% with 90 mg orlistat, by 7% and 7% with 180 mg orlistat and by 11% and 10% with 360 mg orlistat compared to placebo. High density lipoprotein cholesterol levels significantly decreased in the 360 mg orlistat group. Triglyceride levels significantly increased in the placebo group but not in the drug groups. Body weight decreased by 1.2 kg with 360 mg orlistat, despite a weight maintenance diet. Decreases in vitamin E and D levels occurred, although both vitamins remained within the normal range. Adverse effects from the gastrointestinal tract were frequent, but led to discontinuation of therapy in only seven patients. Orlistat is a new therapeutic drug for the treatment of hyperlipidaemia that may be particularly useful among overweight patients. Its potential place in therapy will await long-term studies. Vitamin supplementation should be considered during treatment.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-5233
    Keywords: Obesity ; Free fatty acids ; Lipid oxidation ; Glucose oxidation ; Glucose storage ; Glucose uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of changes in lipid oxidation on glucose utilization (storage and oxidation) was studied in seven nondiabetic obese patients. They participated in three protocols in which: (1) Intralipid (to raise plasma FFA concentrations), (2) β-pyridylcarbinol [a precursor of nicotinic acid, to lower plasma free fatty acids (FFA) concentrations], or (3) isotonic saline were infused over 2 h. Thereafter, these infusions were discontinued, and a 2-h cuglycemic, hyperinsulinemic clamp was performed to measure glucose uptake. All studies were carried out in combination with indirect calorimetry to measure oxidative and nonoxidative glucose disposal (glucose storage). The high plasma FFA concentrations (1024±57 μmol/l) and lipid oxidation rates (1.1±0.1 mg/kg·min) found at the end of the Intralipid infusion and the low plasma FFA concentrations (264±26 μmol/l and lipid oxidation rates 0.7±0.1 mg/kg·min) found at the end of the β-pyridylcarbinol infusions resulted in significantly different rates of total and nonoxidative glucose disposal during the insulin clamp. The values were 2.6±0.6 mg/kg·min after Intralipid and 4.1±1.0 mg/kg·min after β-pyridylcarbinol for total glucose disposal, and 0.4±0.4 and 1.6±0.8, respectively for nonoxidative glucose disposal. In conclusion, these observations show that changes in lipid oxidation rates preceding a glucose load influence glucose disposal and glycogen storage in obese subjects.
    Type of Medium: Electronic Resource
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