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

Increased nonesterified fatty acid (NEFA) levels may be important in causing insulin resistance in skeletal muscles in patients with non-insulin-dependent diabetes mellitus (NIDDM). The acute effect of the antilipolytic nicotinic acid analogue Acipimox (2 X 250 mg) on basal and insulin-stimulated (3 h, 40 mU/m2 per min) glucose metabolism was therefore studied in 12 patients with NIDDM. Whole-body glucose metabolism was assessed using [3-3H]glucose and indirect calorimetry. Biopsies were taken from the vastus lateralis muscle during basal and insulin-stimulated steady-state periods. Acipimox reduced NEFA in the basal state and during insulin stimulation. Lipid oxidation was inhibited by Acipimox in all patients in the basal state (20 +/- 2 vs. 33 +/- 3 mg/m2 per min, P less than 0.01) and during insulin infusion (8 +/- 2 vs. 17 +/- 2 mg/m2 per min, P less than 0.01). Acipimox increased the insulin-stimulated glucose disposal rate (369 +/- 49 vs. 262 +/- 31 mg/m2 per min, P less than 0.01), whereas the glucose disposal rate was unaffected by Acipimox in the basal state. Acipimox increased glucose oxidation in the basal state (76 +/- 4 vs. 50 +/- 4 mg/m2 per min, P less than 0.01). During insulin infusion Acipimox increased both glucose oxidation (121 +/- 7 vs. 95 +/- 4 mg/m2 per min, P less than 0.01) and nonoxidative glucose disposal (248 +/- 47 vs. 167 +/- 29 mg/m2 per min, P less than 0.01). Acipimox enhanced basal and insulin-stimulated muscle fractional glycogen synthase activities (32 +/- 2 vs. 25 +/- 3%, P less than 0.05, and 50 +/- 5 vs. 41 +/- 4%, P less than 0.05). Activities of muscle pyruvate dehydrogenase and phosphofructokinase were unaffected by Acipimox. In conclusion, Acipimox acutely improved insulin action in patients with NIDDM by increasing both glucose oxidation and nonoxidative glucose disposal. This supports the hypothesis that elevated NEFA concentrations may be important for the insulin resistance in NIDDM. The mechanism responsible for the increased insulin-stimulated nonoxidative glucose disposal may be a stimulatory effect of Acipimox on glycogen synthase activity in skeletal muscles.
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PMID:Effect of the antilipolytic nicotinic acid analogue acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus. 191 78

Whether insulin secretion from transplanted islets is normally regulated has not been established. We have studied the effects of either alpha-adrenoceptor antagonism or induction of insulin resistance on glucose-stimulated insulin secretion in streptozotocin (70 mg/kg)-diabetic rats transplanted with 1000 freshly isolated islets to the left kidney subcapsular space. The alpha 2-adrenoceptor antagonist yohimbine (15 micrograms/min) increased basal and potentiated glucose-stimulated insulin secretion in control rats. In contrast, yohimbine did not affect basal or glucose-stimulated insulin secretion in transplanted rats. This suggests that the alpha-adrenoceptor islet tonus is lost following islet transplantation. Induction of insulin resistance by nicotinic acid (6 mg orally twice daily for 10 days) was followed by increased basal insulin levels without any effect on basal plasma glucose levels, both in control and islet transplanted rats, as an adaptation to insulin resistance. Furthermore, after nicotinic acid, the plasma insulin response during glucose infusion was adequate to maintain the normal hyperglycemic response, both in controls and in islet transplanted rats. This suggests that transplanted islets retain the capability to adapt to insulin resistance.
Diabetes Res Clin Pract 1991 Feb
PMID:Effects of yohimbine and nicotinic acid on insulin secretion in islet transplanted streptozotocin-diabetic rats. 202 79

The short-term effect of the lipid lowering agent nicotinic acid on circulating concentrations of insulin, glucose, lactate, pyruvate, non-esterified fatty acids (NEFA), glycerol, total ketone bodies and triglycerides was examined in six insulin-dependent diabetic patients. On two occasions a week apart 24h metabolic profiles were performed. Three patients received nicotinic acid (800 mg/day) for 1 week prior to the first study and three patients between studies. Using this dose of nicotinic acid in patients with insulin-dependent diabetes no lipid lowering effect was demonstrated, nor did we observe an impairment of glycaemic control. During treatment with nicotinic acid circulating free insulin concentrations were higher and blood glucose concentrations were lower. Despite the higher insulin concentrations, circulating levels of NEFA, ketone bodies, and glycerol were all significantly elevated during treatment with nicotinic acid. These results suggest that any extrapolation of findings with regard to the use of nicotinic acid and its derivatives in non-insulin-dependent diabetes to insulin-dependent diabetes should be considered with caution.
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PMID:The short-term effect of nicotinic acid on intermediary metabolism in insulin-dependent diabetes mellitus. 202 32

The effect of changes in plasma non-esterified fatty acid concentration (NEFA) on plasma glucose concentration, hepatic glucose production (Ra), and glucose disposal (Rd) rates was determined in 14 patients with Type 2 diabetes. Seven patients had relatively mild fasting hyperglycaemia (less than 10.0 mmol l-1), whereas the remaining seven had relatively severe fasting hyperglycaemia (greater than 14.0 mmol l-1). Each patient was infused from 2000 to 0800 h with 3-3H-glucose on two occasions, with or without neutral fat emulsion and heparin (mild hyperglycaemia group), or with or without nicotinic acid (severe hyperglycaemia group). Plasma NEFA concentration increased from 0.33 +/- 0.06 (+/- SE) to 4.78 +/- 0.42 mmol l-1 in response to the lipid and heparin infusion, but plasma glucose concentration (7.8 +/- 0.7 vs 7.4 +/- 0.8 mmol l-1), Ra (0.44 +/- 0.02 vs 0.46 +/- 0.02 mmol m-2 min-1), and Rd (0.42 +/- 0.02 vs 0.46 +/- 0.02 mmol m-2 min-1) were unchanged. Nicotinic acid decreased plasma NEFA concentration from 0.54 +/- 0.15 to 0.23 +/- 0.08 mmol l-1, but plasma glucose (15.0 +/- 1.0 vs 15.5 +/- 1.4 mmol l-1), Ra (0.74 +/- 0.07 vs 0.68 +/- 0.07 mmol m-2 min-1), and Rd (0.73 +/- 0.07 vs 0.68 +/- 0.07 mmol m-2 min-1) were unchanged. The results indicate that acute changes in plasma NEFA concentration did not lead to any change in overnight glucose production or disposal rates.
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PMID:Acute changes in plasma non-esterified fatty acid concentration do not change hepatic glucose production in people with type 2 diabetes. 214 83

Coronary heart disease is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM). NIDDM patients have a high frequency of dyslipidemia, which along with obesity, hypertension, and hyperglycemia may contribute significantly to accelerated coronary atherosclerosis. Because risk factors for coronary heart disease are additive and perhaps multiplicative, even mild degrees of dyslipidemia may enhance coronary heart disease risk. Therefore, therapeutic strategies for management of NIDDM should give equal emphasis to controlling hyperglycemia and dyslipidemia. The National Cholesterol Education Program recently issued guidelines for treatment of hyperlipidemia in adults including diabetic patients. Because of the unique features of diabetic dyslipidemia, however, we suggest that certain modifications in these guidelines be made to meet specific needs of diabetic patients. For example, therapeutic goals for serum cholesterol reduction should be lower in diabetic patients than in nondiabetic subjects. Particular emphasis should be given to weight reduction in NIDDM patients. In some diabetic patients, monounsaturated fatty acids may be a better replacement for saturated fatty acids than carbohydrates. The target for cholesterol lowering should include both very-low-density lipoprotein and low-density lipoprotein (LDL) (non-high-density lipoprotein) rather than LDL alone. To obtain a substantial reduction of cholesterol levels, drug therapy may be required in many patients. However, first-line drugs for nondiabetic patients (nicotinic acid and bile acid sequestrants) may be less desirable in NIDDM patients than hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors and even fibric acids. In fact, HMG CoA reductase inhibitors may be the drugs of choice for NIDDM patients with elevated LDL cholesterol and borderline hypertriglyceridemia, whereas gemfibrozil appears preferable for NIDDM patients with severe hypertriglyceridemia.
Diabetes Care 1990 Feb
PMID:Management of dyslipidemia in NIDDM. 219 Jul 70

In a large percentage of cases, diabetes mellitus leads to hyperlipidemia. In addition to the diabetes-related secondary hyperlipidemias, all types of primary disturbances of lipid metabolism can also be observed in diabetics. Depending upon the degree of severity and type of metabolic disorder presenting, not only suitable dietetic treatment, but also the various lipid-lowering drugs, fibrates, nicotinic acid, probucol, cholestyramine and the HMG-CoA reductase inhibitors should be introduced into therapy. As in all groups with an elevated coronary risk, strict management of the lipid levels is mandatory in diabetics, too.
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PMID:[Treatment of hyperlipoproteinemia in patients with diabetes mellitus]. 220 98

The prevalence of mild and moderate hypercholesterolemia among the middle-aged population of the G.D.R. is about 30%. Thus, this is the most important risk factor for coronary heart diseases. Primary therapeutic techniques are elimination of overweight, low-fat diet, rich in monoenic and polyenic acids, and increase of physical activity. When by these measures a decrease of cholesterol to 5.2-5.5 mmol/l is not achieved the introduction of lipid drugs is to be considered in dependence on the individual risk (associated risk factors like smoking, hypertension, diabetes, low HDL-cholesterol). In case of mild to moderate polygenic hypercholesterolemia cholestyramine, nicotinic acid and modern fibrates have the priority. Familial hypercholesterolemia demands as a rule the introduction of statins (e.g. lovastatin) or combinations of the above mentioned lipid drugs or the combination of cholestyramine and lovastatin, resp. In this way the prognosis even of patients with severe familial hypercholesterolemia can be improved decisively. Considering the fact that this would be a life-accompanying therapy a thorough consideration of the risk/benefit ratio and an adequate medical supervision are necessary.
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PMID:[Guidelines for the treatment of hypercholesterolemia]. 224 95

Recently, nicotinic acid has been recommended as a first-line hypolipidemic drug. To determine the effectiveness of nicotinic acid in dyslipidemic patients with non-insulin-dependent diabetes mellitus, 13 patients were treated in a randomized crossover trial. Patients received either nicotinic acid (1.5 g three times daily) or no therapy (control period) for 8 weeks each. Compared with the control period, nicotinic acid therapy reduced the plasma total cholesterol level by 24%, plasma triglyceride level by 45%, very-low-density lipoprotein cholesterol level by 58%, and low-density lipoprotein cholesterol level by 15%, and it increased the high-density lipoprotein cholesterol level by 34%. However, nicotinic acid therapy resulted in the deterioration of glycemic control, as evidenced by a 16% increase in mean plasma glucose concentrations, a 21% increase in glycosylated hemoglobin levels, and the induction of marked glycosuria in some patients. Furthermore, a consistent increase in plasma uric acid levels was observed. Therefore, despite improvement in lipid and lipoprotein concentrations, because of worsening hyperglycemia and the development of hyperuricemia, nicotinic acid must be used with caution in patients with non-insulin-dependent diabetes mellitus with dyslipidemia. We suggest that the drug not be used as a first-line hypolipidemic drug in patients with non-insulin-dependent diabetes mellitus.
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PMID:Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. 228 21

To determine whether prolonged nicotinic acid (NA) administration produces insulin resistance and, if so, how the normal pancreatic islet adapts to prolonged insulin resistance, we administered incremental doses of NA to 11 normal men for 2 wk, ending at 2 g/day. Insulin sensitivity was measured with Bergman's minimal model. Islet function was evaluated by measurement of acute insulin (AIR) and glucagon (AGR) responses to arginine at three glucose levels. Insulin resistance was demonstrated and quantified by a marked drop in the insulin sensitivity index (Sl) from 6.72 +/- 0.77 to 2.47 +/- 0.36 x 10(-5) min-1/pM (P less than .0001) and resulted in a doubling of basal immunoreactive insulin levels (from 75 +/- 7 to 157 +/- 21 pM, P less than .001) with no change in fasting glucose (5.5 +/- 0.1 vs. 5.7 +/- 0.1 mM). Proinsulin levels also increased (from 9 +/- 1 to 15 +/- 2 pM, P less than .005), but the ratio of proinsulin to immunoreactive insulin did not change (12.7 +/- 1.9 vs. 10.3 +/- 1.9%). beta-Cell changes were characterized by increases in the AIR to glucose (from 548 +/- 157 to 829 +/- 157 pM, P less than .005) and in the AIR to arginine at the fasting glucose level (from 431 +/- 54 to 788 +/- 164 pM, P less than .05). At the maximal hyperglycemia level the AIR to arginine represents beta-cell secretory capacity, and this increased with administration of NA (from 2062 +/- 267 to 2630 +/- 363 pM, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 May
PMID:Increased beta-cell secretory capacity as mechanism for islet adaptation to nicotinic acid-induced insulin resistance. 265 28

Forty patients with chronic destructive tuberculosis of the lung and concomitant diabetes mellitus treated with the routine chemotherapeutic agents without any effect were subjected to intermittent polychemotherapy. Combinations of 4, 5 and 6 drugs were used. Some of them were administered intermittently. The period of the polychemotherapy ranged from 4 to 8 months and was followed by less intensive regimens. It was shown that the polychemotherapy allowed one to increase the treatment efficacy in the patients with chronic destructive tuberculosis of the lung and concomitant diabetes mellitus. Discontinuation of tubercle bacilli isolation, cavern healing and partial cavern regression were observed in 25 (63 per cent), 11 (26 per cent) and 27 (54 per cent) patients, respectively. The clinical picture did not change in 6 patients (15 per cent). Adverse reactions to the polychemotherapy developed in 17 patients (42.5 per cent). Markedly pronounced adverse reactions requiring discontinuation of the drug use in 7 (17.5 per cent) of them were recorded. Lowering a dose of the drug, applying corticosteroids, pyridoxine, nicotinic acid, cerucal, lipamide, carsyl and unithiol allowed one to eliminate the adverse reactions developed.
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PMID:[Intermittent polychemotherapy of patients with chronic destructive pulmonary tuberculosis with associated diabetes mellitus]. 281 13


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