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

Nerve ischemia/hypoxia has been linked to the pathogenesis of diabetic complications. Red blood cell 2,3-diphosphoglycerate is an important regulator of peripheral tissue oxygenation; however, the relationship between 2,3-diphosphoglycerate concentration and diabetic complications has not been studied in detail. This investigation focused on the relationship between red blood cell 2,3-diphosphoglycerate and diabetic neuropathy, by measuring motor nerve conduction velocity and sciatic nerve blood flow in streptozotocin-induced diabetic rats. The effect of treatment with niceritrol, a nicotinic acid derivative that acts as a vasodilator and reduces serum lipid concentrations, on 2,3-diphosphoglycerate concentration and diabetic neuropathy was also examined. Untreated diabetic rats had significantly lower concentrations of red blood cell 2,3-diphosphoglycerate, higher concentrations of serum total cholesterol and triglyceride, as well as reduced motor nerve conduction velocity and sciatic nerve blood flow, compared to untreated normal rats. Niceritrol prevented these abnormalities without correcting hyperglycemia in diabetic rats, but had no effect on these parameters in normal rats. Red blood cell 2,3-diphosphoglycerate concentration and motor nerve conduction velocity showed a positive correlation with sciatic nerve blood flow and 2,3-diphosphoglycerate, respectively. These observations suggest that ischemia/hypoxia plays an important role in the development of diabetic neuropathy, and that niceritrol has a therapeutic effect on this condition by improving endoneurial ischemia/hypoxia.
J Diabetes Complications
PMID:Niceritrol prevents the decrease in red blood cell 2,3-diphosphoglycerate and neuropathy in streptozotocin-induced diabetic rats. 754 76

Patients with non-insulin-dependent diabetes mellitus (NIDDM) are at high risk of cardiovascular disease for many reasons and especially due to the fact that dyslipidemias are more frequent in this group of patients. Fibrate derivatives are the drugs of choice when hypertriglyceridemia is the main lipid anomaly. When hypercholesterolemia is predominant, the use of resins and nicotinic acid has been advocated but these drugs are poorly tolerated on a long-term basis. We assessed the effect of simvastatin, a recent HMG-CoA reductase inhibitor in 12 NIDDM patients with hypercholesterolemia. After 4 weeks of placebo, which did not significantly modify the lipid values, patients were given simvastatin at increasing dosages (from 10 to a maximum of 40 mg daily) during 24 weeks. Compliance and clinical tolerance were excellent. There was no major biological side effect, but a significant deterioration of glucose control was noted at the end of the study. Simvastatin reduced total cholesterol by 28%, LDL-cholesterol by 36% and apo B by 31%. Concomitantly, there was an increase of HDL-cholesterol by 15%. This improvement of lipid profile persisted during the 24 weeks of treatment. Comparing the patients with pure hypercholesterolemia to those presenting combined hyperlipidemia, it was evident that the hypolipidemic effect was more marked in the diabetic subjects with combined hyperlipidemia.
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PMID:Efficacy of simvastatin for lowering cholesterol in non-insulin dependent diabetic patients with hypercholesterolemia. 806 75

Acute administration of the antilipolytic nicotinic acid analog acipimox to patients with noninsulin-dependent diabetes mellitus (NIDDM) is associated with increased peripheral and hepatic insulin sensitivity. However, long term acipimox treatment (250 mg, 3 times/24 h) of NIDDM patients does not improve blood glucose control, possibly due to rebound lipolysis. The current study assessed the influence of intensified acipimox administration (125 mg, 12 times/24 h) on diurnal plasma profiles of glucose, insulin, nonesterified FFA (NEFA), and triglycerides during a 3-day period. Eight NIDDM patients [mean age, 58.9 yr (range, 46-68); mean body mass index, 31.4 kg/m2 (range, 24.9-39.6)] were included in a randomized, double blind, placebo-controlled, cross-over study. Blood samples were collected every second hour during the study. The acipimox and placebo treatments were separated by a 2-week washout period. Acipimox treatment was associated with reduced diurnal mean plasma concentrations of NEFA [0.26 +/- 0.03 (+/- SEM) vs. 0.63 +/- 0.06 mmol/L; P < 0.001], triglycerides (1.74 +/- 0.21 vs. 2.10 +/- 0.18 mmol/L; P < 0.03), glucose (12.7 +/- 1.0 vs. 15.8 +/- 1.2 mmol/L; P < 0.002), and insulin (157 +/- 21 vs. 207 +/- 27 pmol/L; P < 0.05). However, despite the overall reduction in mean NEFA, during acipimox treatment NEFA increased from days 1-3 (0.18 +/- 0.03 vs. 0.34 +/- 0.04 mmol/L; P < 0.001), whereas plasma glucose (13.4 +/- 1.2 vs. 12.3 +/- 0.9 mmol/L; P < 0.03) and plasma insulin (168 +/- 23 vs. 148 +/- 17 pmol/L; P < 0.04) decreased steadily from days 1-3 during active treatment. In conclusion, inhibition of lipolysis using the intensified acipimox treatment regiment was associated with a pronounced blood glucose- and plasma insulin-lowering effect. However, minor rebound effects of lipolysis occurred in some patients despite the presence of allegedly effective acipimox levels. This suggests that caution should be employed concerning long term use of acipimox as a hypoglycemic agent in NIDDM patients.
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PMID:Pronounced blood glucose-lowering effect of the antilipolytic drug acipimox in noninsulin-dependent diabetes mellitus patients during a 3-day intensified treatment period. 812 47

We determined whether overnight inhibition of lipolysis by a long-acting nicotinic acid derivative (acipimox) decreases gluconeogenesis from lactate in NIDDM patients. For this purpose, 250 mg of acipimox or placebo was administered in a double-blind crossover study at 2400, 0400, and 0800 to 8 NIDDM patients (54 +/- 4 yr of age, body mass index 29.5 +/- 1.3 kg/m2, fasting plasma glucose 11 +/- 1 mM). The next morning, total hepatic glucose production (glucose Ra) and gluconeogenesis from lactate were determined using primed, continuous infusions of [3-3H]glucose and [U-14C]acetate. Glucose and lipid oxidation rates were measured using indirect calorimetry. Mean overnight serum free fatty acid concentrations averaged 242 +/- 8 microM after acipimox and 721 +/- 30 microM after placebo (P < 0.001). Inhibition of lipolysis decreased lipid oxidation from 33 +/- 3 to 22 +/- 2 J.kg-1 x min-1 (P < 0.001) and increased carbohydrate oxidation from 15 +/- 3 to 23 +/- 2 mumol.kg-1.min-1 (P < 0.005). Gluconeogenesis from lactate decreased by approximately 40%, from 6.2 +/- 0.6 to 3.8 +/- 0.5 mumol.kg-1 x min-1 (P < 0.005); lactate oxidation increased from 5.6 +/- 0.8 to 7.9 +/- 1.1 mumol.kg-1 x min-1 (P < 0.005), with no change in plasma lactate concentrations or total lactate Rd. Fasting plasma glucose concentrations were comparable at 2400 (10.0 +/- 1.1 vs. 10.6 +/- 1.3 mM, acipimox vs. placebo) and between 0900 and 1000 (10.6 +/- 1.3 and 11.3 +/- 1.3 mM, respectively). Also, total glucose production rates remained unchanged (14.0 +/- 1.2 vs. 14.9 +/- 1.3 mol.kg-1 x min-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1993 Dec
PMID:Inhibition of lipolysis decreases lipid oxidation and gluconeogenesis from lactate but not fasting hyperglycemia or total hepatic glucose production in NIDDM. 824 14

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

Plasma nonesterified fatty acid (NEFA) levels are increased in the insulin-stimulated state in non-insulin-dependent diabetes mellitus (NIDDM) and may contribute to the decrease in peripheral and hepatic insulin sensitivity. To test this hypothesis and to avoid the confounding effect of obesity, we examined the effect of decreasing plasma NEFA levels on peripheral and total glucose metabolism in eight non-obese, NIDDM patients. Each received 250 mg Acipimox (a nicotinic acid analogue) or placebo at 0 and 120 minutes on separate occasions. [6,6-2H2]-glucose (0 to 300 minutes) and insulin (120 to 300 minutes) were infused in each study, and isoglycemia was maintained. Plasma NEFA levels (140 +/- 30 v 600 +/- 70 mumol/L [SEM]; P < .001) and forearm NEFA uptake measured with [1-14C]-palmitate (+93 +/- 21 v +313 +/- 42 nmol x 100 mL forearm-1; P < .001) were decreased with acipimox during the basal period (90 to 120 minutes), with no change in forearm glucose uptake (+334 +/- 80 and +330 +/- 60 nmol x 100 mL forearm-1 x min-1) and hepatic glucose output ([HGO] 13.6 +/- 0.9 and 13.4 +/- 0.7 mumol.kg-1 x min-1). Serum insulin (256 +/- 12 and 266 +/- 18 pmol/L) and plasma glucose (9.5 +/- 0.6 and 9.4 +/- 0.5 mmol/L) levels were comparable during the clamp period (270 to 300 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Peripheral and hepatic insulin sensitivity in non-insulin-dependent diabetes mellitus: effect of nonesterified fatty acids. 849 15

Acanthosis nigricans is a reaction pattern to over a dozen different causes. The skin, most classic in the axilla, is dark, soft, velvet-like with fine folding and papillae. The mechanism of this skin change is decreased viscosity of extracellular matrix (ECM) combined with mechanical extrusion of ECM into papillae extending out from the upper dermis. It occurs in obesity (increased mechanical pressure on ECM), diabetes (decreased quality of glycosaminoglycans) (GAG), excess corticosteroids (decreased quality of GAG), pineal tumors (increased ECM and edema), other endocrine disorders (alterations in the quality of GAG), multiple genetic variants (structural and chemical change), from drugs such as nicotinic acid, estrogens, corticosteroids (weakened or altered GAG) and adenocarcinoma (fractions of depolymerized or altered GAG released from the tumor area are incorporated into and weaken the skin GAG). Acanthosis nigricans was first reported in 1890 as a cutaneous sign of internal malignancy. Acanthosis nigricans presents an opportunity to better understand what is occurring in the ECM in many disorders. The understanding of the association of AN and internal malignancy will expand our understanding of how a neoplasm decreases generalized ECM viscosity.
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PMID:Acanthosis nigricans--decreased extracellular matrix viscosity: cancer, obesity, diabetes, corticosteroids, somatotrophin. 850 93

The distal enzymatic step in the process of glucose output is catalyzed by the glucose-6-phosphatase (Glc-6-Pase) complex. The recently cloned catalytic unit of this complex has been shown to be regulated by insulin, dexamethasone, cAMP, and glucose. Using a combination of intralipid and/or nicotinic acid infusions and a pancreatic clamp technique, we maintained plasma free fatty acids (FFAs) at three different levels (0.26 +/- 0.07, 0.56 +/- 0.09, and 1.59 +/- 0.12 mmol/l) in the presence of well-controlled hormonal and metabolic conditions. An increase in the plasma FFA concentration within the physiological range caused a rapid, greater than threefold increase in the mRNA and protein levels of the catalytic subunit of Glc-6-Pase in the liver. These data indicate that the in vivo gene expression of Glc-6-Pase in the liver is regulated by circulating lipids independent of insulin and thus that prolonged hyperlipidemia may contribute to the increased production of glucose via increased expression of this protein.
Diabetes 1997 Jan
PMID:Induction of hepatic glucose-6-phosphatase gene expression by lipid infusion. 897 Oct 97

A hypothesis is advanced, according to which substances containing an amino group can compete with glucose in binding with protein groups and inhibiting in this way glycosylation. Screening in vitro experiments with nicotinic acid, nicotinamide, piracetam, panangin, ascorbic acid, bucarban, betanase, and adebit in a concentration of 10(-3) M were performed. Bucarban, betanase, and adebit were found to be capable of inhibiting glycosylation. Daily oral administration of bucarban and adebit in therapeutic doses for one month reduced the blood fructosamine level in rats with alloxan diabetes without changing the level of glycemia.
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PMID:[The pharmacological blockade of protein glycosylation in diabetes mellitus using sulfonylurea derivatives and biguanides]. 902 9

The effects of daily supplemental chromium (200 micrograms) complexed with 1.8 mg nicotinic acid on plasma glucose and lipids, including total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides, were assessed in 14 healthy adults and 5 adults with noninsulin-dependent diabetes mellitus (NIDDM) using a double-blind crossover study with 8-wk experimental periods. Eight of the 14 healthy subjects and all 5 subjects with NIDDM also underwent an oral glucose tolerance test with assessment of 90 min postprandial plasma glucose and insulin concentrations. No statistically significant effects of chromium nicotinic acid supplementation were found on plasma insulin, glucose, or lipid concentrations, although chromium nicotinic acid supplementation slightly lowered fasting plasma total and LDL cholesterol, triglycerides, and glucose concentrations, and 90-min postprandial glucose concentrations in individuals with NIDDM.
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PMID:Effect of chromium nicotinic acid supplementation on selected cardiovascular disease risk factors. 909 56


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