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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the long-term effect of pravastatin, a new potent inhibitor of endogenous cholesterol biosynthesis, on glucose and lipid metabolism in hyperlipidemic NIDDM. Ten patients (5 on sulfonylurea, 5 on diet) were studied over 12 months. Five were WHO type IIa and 5 were type IIb. Blood was taken before and then 1, 6 and 12 months after initiating 10 or 20 mg daily of pravastatin. The cholesterol concentration in whole plasma and very low density lipoprotein (VLDL), plasma triglyceride and apolipoprotein (apo) B were all significantly decreased within the first month. These changes lasted for 1 year. High density lipoprotein (HDL)-cholesterol increased in the first month but returned to base line thereafter. Low density lipoprotein (LDL)-cholesterol tended to decrease in the first month, and was suppressed significantly from the 6th month (11%) to the 12th month (16%). The effect of pravastatin on LDL-cholesterol in NIDDM was slower and weaker than that published for non-diabetic hypercholesterolemia. Therefore, the mechanism by which pravastatin suppresses plasma cholesterol levels in these two conditions may differ. After 1 year, no adverse effects were noted on hematopoietic, hepatic or renal function. Blood glucose level, hemoglobin A1c and the insulin response to oral glucose were unchanged. In addition, serum creatine phosphokinase showed no abnormal increase. Careful ophthalmological examinations before and after pravastatin treatment revealed no development of new lenticular opacities. Thus, pravastatin appears to be a safe and effective drug for the long-term treatment of NIDDM with hypercholesterolemia.
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PMID:Long-term treatment of hypercholesterolemic non-insulin dependent diabetics (NIDDM) with pravastatin (CS-514). 249 12

The paper provides representative data on the indices of lipid metabolism and the activity of cardiospecific (lactate dehydrogenase--LDH, creatine phosphokinase--CPK) in patients with diabetes mellitus, Type I and II, (male inhabitants of Kaunas aged 40 to 59) which were compared with similar data on control persons randomly selected from the population during epidemiological surveys. They covered 85.3% of all detected and followed-up patients of this age with diabetes mellitus. Total and HDL cholesterol and triglycerides were determined by the enzymatic methods, LDH by the spectrophotometric method and CPK by the fluorometric method. It was shown that patients with Type II diabetes mellitus (insulin-independent) in addition to a raised concentration of glucose on an empty stomach were characterized by an increase in the level of cholesterol up to 6.34-0.51 mmol/l and especially triglycerides up to 5.98-1.78 mmol/l as compared to the control values (5.39-0.11 and 1.48-0.12 mmol, respectively). The concentration of HDL cholesterol and CPK and LDH activity in the patients did not differ from the control level.
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PMID:[Lipid metabolism and the activity of cardiospecific enzymes in diabetes mellitus]. 378 99

In untrained subjects, strenuous exercise provokes the appearance of oxidant stress markers in blood and muscle. On the other hand, trained muscle is resistant to oxidant stress unless exercise challenges the muscle glycogen supply. It is not known whether chronic high-intensity exercise alters the susceptibility of skeletal muscle to oxidant stress, whether there are gender-related differences in markers of oxidant stress, or whether elevating muscle glycogen stores by increasing dietary carbohydrate can minimize any exercise-related oxidant stress. To address these issues, collegiate rowers (12 men, 11 women) were randomly assigned to a moderate-(MOD, 5 g/kg body wt) or high-carbohydrate (HI, 10 g/kg) diet in a double-blind design and underwent strenuous training for 4 wk. Training in the A.M. was 40 min at 70% maximal O2 consumption (VO2); in the P.M. it was either three 2,500-m time trials (to assess power output) or aerobic and lactate tolerance training. Total daily training time was 65 min at 70% maximal VO2 and 38 min at > or = 90% maximal VO2. Thrice-weekly morning blood samples were assayed for serum creatine kinase (CK), plasma thiobarbituric acid-reactive substances (TBARS), and serum beta-glucuronidase (beta-Gluc). Weekly muscle biopsies were obtained for analysis of glycogen and, when tissue sample quantity allowed, TBARS. HI rowers produced more power and improved power more (10.7 +/- 1.0 vs. 1.6 +/- 1.6%) over the 4 wk than did the MOD rowers. Preexercise muscle glycogen concentration was maintained at 119 mmol/kg in MOD but increased 65% in HI rowers (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:No evidence of oxidant stress during high-intensity rowing training. 833 41

Physiologically, a postprandial glucose rise induces metabolic signal sequences that use several steps in common in both the pancreas and peripheral tissues but result in different events due to specialized tissue functions. Glucose transport performed by tissue-specific glucose transporters is, in general, not rate limiting. The next step is phosphorylation of glucose by cell-specific hexokinases. In the beta-cell, glucokinase (or hexokinase IV) is activated upon binding to a pore protein in the outer mitochondrial membrane at contact sites between outer and inner membranes. The same mechanism applies for hexokinase II in skeletal muscle and adipose tissue. The activation of hexokinases depends on a contact site-specific structure of the pore, which is voltage-dependent and influenced by the electric potential of the inner mitochondrial membrane. Mitochondria lacking a membrane potential because of defects in the respiratory chain would thus not be able to increase the glucose-phosphorylating enzyme activity over basal state. Binding and activation of hexokinases to mitochondrial contact sites lead to an acceleration of the formation of both ADP and glucose-6-phosphate (G-6-P). ADP directly enters the mitochondrion and stimulates mitochondrial oxidative phosphorylation. G-6-P is an important intermediate of energy metabolism at the switch position between glycolysis, glycogen synthesis, and the pentose-phosphate shunt. Initiated by blood glucose elevation, mitochondrial oxidative phosphorylation is accelerated in a concerted action coupling glycolysis to mitochondrial metabolism at three different points: first, through NADH transfer to the respiratory chain complex I via the malate/aspartate shuttle; second, by providing FADH2 to complex II through the glycerol-phosphate/dihydroxy-acetone-phosphate cycle; and third, by the action of hexo(gluco)kinases providing ADP for complex V, the ATP synthetase. As cytosolic and mitochondrial isozymes of creatine kinase (CK) are observed in insulinoma cells, the phosphocreatine (CrP) shuttle, working in brain and muscle, may also be involved in signaling glucose-induced insulin secretion in beta-cells. An interplay between the plasma membrane-bound CK and the mitochondrial CK could provide a mechanism to increase ATP locally at the KATP channels, coordinated to the activity of mitochondrial CrP production. Closure of the KATP channels by ATP would lead to an increase of cytosolic and, even more, mitochondrial calcium and finally to insulin secretion. Thus in beta-cells, glucose, via bound glucokinase, stimulates mitochondrial CrP synthesis. The same signaling sequence is used in the opposite direction in muscle during exercise when high ATP turnover increases the creatine level that stimulates mitochondrial ATP synthesis and glucose phosphorylation via hexokinase. Furthermore, this cytosolic/mitochondrial cross-talk is also involved in activation of muscle glycogen synthesis by glucose. The activity of mitochondrially bound hexokinase provides G-6-P and stimulates UTP production through mitochondrial nucleoside diphosphate kinase. Pathophysiologically, there are at least two genetically different forms of diabetes linked to energy metabolism: the first example is one form of maturity-onset diabetes of the young (MODY2), an autosomal dominant disorder caused by point mutations of the glucokinase gene; the second example is several forms of mitochondrial diabetes caused by point and length mutations of the mitochondrial DNA (mtDNA) that encodes several subunits of the respiratory chain complexes. Because the mtDNA is vulnerable and accumulates point and length mutations during aging, it is likely to contribute to the manifestation of some forms of NIDDM.(ABSTRACT TRUNCATED)
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PMID:Mitochondria and diabetes. Genetic, biochemical, and clinical implications of the cellular energy circuit. 854 53

In type 2 diabetes, it is not uncommon to find an elevated serum triglyceride and/or reduced high-density lipoprotein (HDL) cholesterol levels; elevated total cholesterol levels often occur as well. To evaluate the short-term efficacy and tolerability of combination therapy with lovastatin and acipimox in Chinese patients with type 2 diabetes who have mixed dyslipidemia, an open-label 6-month trial was conducted. All patients had type 2 diabetes (n = 33) with total cholesterol > or = 6.2 mmol/L and fasting triglyceride > or = 2.8 mmol/L, which had been confirmed twice and persisted for at least 12 weeks after introduction of diet control. After a 4-week run-in period, they were given lovastatin 40 mg daily at night for 12 weeks. Acipimox 250 mg three times a day was then added for a further 12 weeks. After 12 weeks of treatment with lovastatin alone, improvement was observed in total cholesterol (21% reduction), triglyceride (32% reduction), low-density lipoprotein (LDL) cholesterol (5.5% reduction), HDL cholesterol (11.6% elevation), apolipoprotein A-I (4.6% elevation), and apolipoprotein B (20.5% reduction). The addition of acipimox to lovastatin for an additional 12 weeks further reduced serum total cholesterol, triglyceride, LDL cholesterol, and apolipoprotein B, but this additional decrease was not statistically significant. However, HDL cholesterol and apolipoprotein A-I levels were significantly increased by the addition of acipimox (a 14.2% and 9.0% elevation, respectively). Serum creatine phosphokinase increased slightly after 12 weeks of lovastatin but decreased to a concentration similar to baseline after 12 weeks of combination treatment. No patients reported muscle pain or weakness or other side effects. Combination treatment with lovastatin and acipimox appears to be a safe and effective therapy in patients with type 2 diabetes and mixed dyslipidemia, and has particular benefit in elevating serum HDL cholesterol and apolipoprotein A-I levels.
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PMID:Short-term efficacy and tolerability of combination therapy with lovastatin and acipimox in Chinese patients with type 2 diabetes mellitus and mixed dyslipidemia. 980 71

This randomized, double-blind study was undertaken to compare the efficacy and tolerability of policosanol (10 mg/day) and lovastatin (20 mg/day) in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus. After 6 weeks on a lipid lowering diet, 53 patients were randomized to receive either policosanol or lovastatin tablets that were taken o.i.d. for 12 weeks under double-blind conditions. Both groups were similar at randomization. Policosanol significantly (p < 0.001) lowered low-density lipoprotein (LDL)-cholesterol (20.4%), total cholesterol (14.2%) and the ratio of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol (23.7%). Lovastatin significantly (p < 0.01) lowered LDL-cholesterol (16.8%), total cholesterol (14.0%) and the ratio (p < 0.05) of LDL-cholesterol to HDL-cholesterol (14.9%). Triglyceride levels did not significantly change after therapy. Policosanol, but not lovastatin, significantly increased (p < 0.01) levels of HDL-cholesterol (7.5%). Comparison between groups showed that changes in HDL-cholesterol induced by policosanol were significantly greater (p < 0.01) than those induced by lovastatin. Both treatments were safe and well tolerated. Lovastatin moderately but significantly (p < 0.05) increased levels of aspartate aminotransferase, creatine phosphokinase and alkaline phosphatase. Adverse reactions were more frequent in the lovastatin group (p < 0.01) than in the policosanol group. In conclusion, policosanol administered at 10 mg/day produces more advantageous changes in HDL-cholesterol and has a better safety and tolerability profile than lovastatin 20 mg/day.
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PMID:Comparative study of the efficacy and tolerability of policosanol and lovastatin in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus. 1093 29

1. We have investigated the effects of the sulphonylurea, glimepiride, currently used to treat type 2 diabetes, on ATP-sensitive K(+) (K(ATP)) currents of rat cardiac myocytes and on their cloned constituents Kir6.2 and SUR2A expressed in HEK 293 cells. 2. Glimepiride blocked pinacidil-activated whole-cell K(ATP) currents of cardiac myocytes with an IC(50) of 6.8 nM, comparable to the potency of glibenclamide in these cells. Glimepiride blocked K(ATP) channels formed by co-expression of Kir6.2/SUR2A subunits in HEK 293 cells in outside-out excised patches with a similar IC(50) of 6.2 nM. 3. Glimepiride was much less effective at blocking K(ATP) currents activated by either metabolic inhibition (MI) with CN(-) and iodoacetate or by the K(ATP) channel opener diazoxide in the presence of inhibitors of F(0)/F(1)-ATPase (oligomycin) and creatine kinase (DNFB). Thus 10 microM glimepiride blocked pinacidil-activated currents by >99%, MI-activated currents by 70% and diazoxide-activated currents by 82%. 4. In inside-out patches from HEK 293 cells expressing the cloned K(ATP) channel subunits Kir6.2/SUR2A, increasing the concentration of ADP (1 - 100 microM), in the presence of 100 nM glimepiride, lead to significant increases in Kir6.2/SUR2A channel activity. However, over the range tested, ADP did not affect cloned K(ATP) channel activity in the presence of 100 nM glibenclamide. These results are consistent with the suggestion that ADP reduces glimepiride block of K(ATP) channels. 5. Our results show that glimepiride is a potent blocker of native cardiac K(ATP) channels activated by pinacidil and blocks cloned Kir6.2/SUR2A channels activated by ATP depletion with similar potency. However, glimepiride is much less effective when K(ATP) channels are activated by MI and this may reflect a reduction in glimepiride block by increased intracellular ADP.
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PMID:Effect of metabolic inhibition on glimepiride block of native and cloned cardiac sarcolemmal K(ATP) channels. 1208 84

Micronised fenofibrate is a synthetic phenoxy-isobutyric acid derivative (fibric acid derivative) indicated for the treatment of dyslipidaemia. Recently, a new tablet formulation of micronised fenofibrate has become available with greater bioavailability than the older capsule formulation. The micronised fenofibrate 160mg tablet is bioequivalent to the 200mg capsule. The lipid-modifying profile of micronised fenofibrate 160mg (tablet) or 200mg (capsule) once daily is characterised by a decrease in low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels, a marked reduction in plasma triglyceride (TG) levels and an increase in high-density lipoprotein cholesterol (HDL-C) levels. Micronised fenofibrate 200mg (capsule) once daily produced greater improvements in TG and, generally, in HDL-C levels than the hydroxymethylglutaryl coenzyme A reductase inhibitors simvastatin 10 or 20 mg/day, pravastatin 20 mg/day or atorvastatin 10 or 40 mg/day. Combination therapy with micronised fenofibrate 200mg (capsule) once daily plus fluvastatin 20 or 40 mg/day or atorvastatin 40 mg/day was associated with greater reductions from baseline than micronised fenofibrate alone in TC and LDL-C levels. Similar or greater changes in HDL-C and TG levels were seen in combination therapy, compared with monotherapy, recipients. Micronised fenofibrate 200mg (capsule) once daily was associated with significantly greater improvements from baseline in TC, LDL-C, HDL-C and TG levels than placebo in patients with type 2 diabetes mellitus enrolled in the double-blind, randomised Diabetes Atherosclerosis Intervention Study (DAIS) [> or =3 years follow-up]. Moreover, angiography showed micronised fenofibrate was associated with significantly less progression of coronary atherosclerosis than placebo. Micronised fenofibrate has also shown efficacy in patients with metabolic syndrome, patients with HIV infection and protease inhibitor-induced hypertriglyceridaemia and patients with dyslipidaemia secondary to heart transplantation. Micronised fenofibrate was generally well tolerated in clinical trials. The results of a large (n = 9884) 12-week study indicated that gastrointestinal disorders are the most frequent adverse events associated with micronised fenofibrate therapy. Elevations in serum transaminase and creatine phosphokinase levels have been reported rarely with micronised fenofibrate. In conclusion, micronised fenofibrate improves lipid levels in patients with primary dyslipidaemia; the drug has particular efficacy with regards to reducing TG levels and raising HDL-C levels. Micronised fenofibrate is also effective in diabetic dyslipidaemia; as well as improving lipid levels, the drug reduced progression of coronary atherosclerosis in patients with type 2 diabetes mellitus. The results of large ongoing studies (e.g. FIELD with approximately 10 000 patients) will clarify whether the beneficial lipid-modifying effects of micronised fenofibrate result in a reduction in cardiovascular morbidity and mortality.
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PMID:Micronised fenofibrate: an updated review of its clinical efficacy in the management of dyslipidaemia. 1221 67

Skeletal muscle is strongly dependent on oxidative phosphorylation for energy production. Because the insulin resistance of skeletal muscle in type 2 diabetes and obesity entails dysregulation of the oxidation of both carbohydrate and lipid fuels, the current study was undertaken to examine the potential contribution of perturbation of mitochondrial function. Vastus lateralis muscle was obtained by percutaneous biopsy during fasting conditions from lean (n = 10) and obese (n = 10) nondiabetic volunteers and from volunteers with type 2 diabetes (n = 10). The activity of rotenone-sensitive NADH:O(2) oxidoreductase, reflecting the overall activity of the respiratory chain, was measured in a mitochondrial fraction by a novel method based on providing access for NADH to intact mitochondria via alamethicin, a channel-forming antibiotic. Creatine kinase and citrate synthase activities were measured as markers of myocyte and mitochondria content, respectively. Activity of rotenone-sensitive NADH:O(2) oxidoreductase was normalized to creatine kinase activity, as was citrate synthase activity. NADH:O(2) oxidoreductase activity was lowest in type 2 diabetic subjects and highest in the lean volunteers (lean 0.95 +/- 0.17, obese 0.76 +/- 0.30, type 2 diabetes 0.56 +/- 0.14 units/mU creatine kinase; P < 0.005). Also, citrate synthase activity was reduced in type 2 diabetic patients (lean 3.10 +/- 0.74, obese 3.24 +/- 0.82, type 2 diabetes 2.48 +/- 0.47 units/mU creatine kinase; P < 0.005). As measured by electron microscopy, skeletal muscle mitochondria were smaller in type 2 diabetic and obese subjects than in muscle from lean volunteers (P < 0.01). We conclude that there is an impaired bioenergetic capacity of skeletal muscle mitochondria in type 2 diabetes, with some impairment also present in obesity.
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PMID:Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. 1235 31

This study evaluated the efficacy of adding pioglitazone 30 mg to the therapy of patients with type 2 diabetes mellitus whose glycaemic control was poor on an alpha-glucosidase inhibitor (alpha-GI) alone or in combination with a sulphonylurea (SU). The patients (n = 20) had a HbA(1c) level between 7.0 and 12.0% and the fasting plasma glucose was 7.8 mmol/l or higher. They were treated with 30 mg pioglitazone once daily for 16 weeks. The decrease in HbA(1c) at week 16 of treatment was 0.8% (7.8% at baseline dropping to 7.1% at week 16; p < or = 0.01). An increase in leptin was observed 4 weeks after starting the post-study period (p < or = 0.05). Tumour necrosis factor-alpha (TNF-alpha) and body fat percentage did not show any significant alterations. Correlations between the decrease in HbA1c at week 16 and characteristic variables of patients were examined. A correlation with leptin (p = -0.5632, p < or = 0.05) levels was found. Five patients experienced adverse drug reactions, such as oedema, hypoglycaemia and increased creatine phosphokinase (CK), all of which were mild in severity. The addition of pioglitazone in diabetics whose glycaemic control was poor on a alpha-GI alone or with a alpha-GI and SU combination resulted in a significant decrease in HbA1c, and the treatment was well-tolerated. Our findings also suggest that leptin levels could be useful for assessing responders to pioglitazone.
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PMID:Clinical effect of combination therapy of pioglitazone and an alpha-glucosidase inhibitor. 1468 36


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