The effect of high-dose simvastatin on free fatty acid metabolism in patients with type 2 diabetes mellitus

Isley, William L.; Harris, William S.; Miles, John M.

doi:10.1016/j.metabol.2006.01.013

Cited by 25 publications

(21 citation statements)

References 37 publications

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“…However, simvastatin did not ameliorate EGP suppression in our patients with type 2 diabetes, a result that is in line with the only previous study on pravastatin treatment in familial hypercholesterolemia (20). Statins not only decrease LDL cholesterol but may also interfere with fasting and postprandial triglyceride-rich lipoprotein metabolism, resulting in altered substrate flux and accumulation of HCLs (11,12,21). Our patients exhibited a tight correlation between excessive HCL storage and M value similar to that in previous reports (2).…”

Section: Effects On Insulin Sensitivitysupporting

confidence: 91%

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Effects of High-Dose Simvastatin Therapy on Glucose Metabolism and Ectopic Lipid Deposition in Nonobese Type 2 Diabetic Patients

Szendroedi

Anderwald²,

Krššák³

et al. 2009

Diabetes Care

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OBJECTIVE -Statins may exert pleiotropic effects on insulin action that are still controversial. We assessed effects of high-dose simvastatin therapy on peripheral and hepatic insulin sensitivity, as well as on ectopic lipid deposition in patients with hypercholesterolemia and type 2 diabetes.RESEARCH DESIGN AND METHODS -We performed a randomized, double-blind, placebo-controlled, single-center study. Twenty patients with type 2 diabetes received 80 mg simvastatin (BMI 29 Ϯ 4 kg/m 2 , age 55 Ϯ 6 years) or placebo (BMI 27 Ϯ 4 kg/m 2 , age 58 Ϯ 8 years) daily for 8 weeks and were compared with 10 healthy humans (control subjects; BMI 27 Ϯ 4 kg/m 2 , age 55 Ϯ 7 years). Euglycemic-hyperinsulinemic clamp tests combined with D-[6,6-d2]glucose infusion were used to assess insulin sensitivity (M) and endogenous glucose production (EGP).1 H magnetic resonance spectroscopy was used to quantify intramyocellular and hepatocellular lipids.RESULTS -High-dose simvastatin treatment lowered plasma total and LDL cholesterol levels by ϳ33 and ϳ48% (P Ͻ 0.005) but did not affect M, intracellular lipid deposition in soleus and tibialis anterior muscles and liver, or basal and insulin-suppressed EGP. In simvastatintreated patients, changes in LDL cholesterol related negatively to changes in M (r ϭ Ϫ0.796, P Ͻ 0.01). Changes in fasting free fatty acids (FFAs) related negatively to changes in M (r ϭ Ϫ0.840, P Ͻ 0.01) and positively to plasma retinol-binding protein-4 (r ϭ 0.782, P ϭ 0.008).CONCLUSIONS -High-dose simvastatin treatment has no direct effects on whole-body or tissue-specific insulin action and ectopic lipid deposition. A reduction in plasma FFAs probably mediates alterations in insulin sensitivity in vivo.

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Section: Effects On Insulin Sensitivitysupporting

confidence: 91%

“…Statins not only decrease LDL cholesterol but may also interfere with fasting and postprandial metabolism of triglyceride-rich lipoproteins, resulting in altered substrate flux and accumulation of HCLs (11,12), which could subsequently affect muscle glucose metabolism and deposition of IMCLs.…”

mentioning

confidence: 99%

Effects of High-Dose Simvastatin Therapy on Glucose Metabolism and Ectopic Lipid Deposition in Nonobese Type 2 Diabetic Patients

Szendroedi

Anderwald²,

Krššák³

et al. 2009

Diabetes Care

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“…Atorvastatin enhances serum LPL levels in type 2 diabetics [83]. Similar clinical observations have been made for simvastatin [84]. This increased serum LPL seen in response to atorvastatin is suggested to occur via increased LPL production in the skeletal muscle in an adenosine-monophosphate-activated protein kinase (AMPK)-dependent mechanism [85].…”

Section: Pharmacological Targeting Of Lplmentioning

confidence: 69%

Emerging strategies of targeting lipoprotein lipase for metabolic and cardiovascular diseases

Geldenhuys

Darvesh

et al. 2017

Drug Discovery Today

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Although statins and other pharmacological approaches have improved the management of lipid abnormalities, there exists a need for newer treatment modalities especially for the management of hypertriglyceridemia. Lipoprotein lipase (LPL), by promoting hydrolytic cleavage of the triglyceride core of lipoproteins, is a crucial node in the management of plasma lipid levels. Although LPL expression and activity modulation is observed as a pleiotropic action of some the commonly used lipid lowering drugs, the deliberate development of drugs targeting LPL has not occurred yet. In this review, we present the biology of LPL, highlight the LPL modulation property of currently used drugs and review the novel emerging approaches to target LPL.

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“…Candidate mechanisms include a statin-mediated reduction in superoxide-induced cell damage [26], statinmediated reduction of low-grade inflammation [27] or a reduction in non-esterified fatty acid flux and hepatic fat storage [28] resulting in improved hepatic insulin sensitivity. The present study does not allow conclusions on the putative effects of statins on superoxide production or superoxide-mediated cell damage.…”

Section: Putative Mechanisms Of Statin-mediated Potentiation Of the Bmentioning

confidence: 99%

The use of statins potentiates the insulin-sensitizing effect of exercise training in obese males with and without Type 2 diabetes

et al. 2010

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Exercise training is advocated in insulin resistance and statins are used to treat hyperlipidaemia, two cardiometabolic risk factors often presenting concurrently. Statin intake may blunt mitochondrial function and the adaptive response to exercise training. Thus combining exercise training with statin administration may have adverse effects. We examined whether improvements in cardiometabolic risk factors, insulin sensitivity and mitochondrial function mediated by progressive exercise training are affected by statin use. A group of 14 obese elderly males on statins (ST) and 22 matched control subjects (C) were examined. Results on in vivo mitochondrial function [MRS (magnetic resonance spectroscopy)], mitochondrial density (Western blotting), insulin sensitivity (clamp) and metabolic flexibility (indirect calorimetry) were compared before and after a 12-week combined progressive exercise training programme (3 x per week; 45 min per session). Except for LDL (low-density lipoprotein) cholesterol, all pre-training values were comparable between statin users and control subjects. In vivo mitochondrial function and mitochondrial density improved by training in both groups. Interestingly, blood-lipid profile, insulin sensitivity (+72%), non-oxidative and oxidative glucose disposal (+38% and +112%) and insulin-mediated suppression of fat oxidation (-62%) improved only in the ST group. We conclude that statin treatment did not impede exercise performance or tolerance, mitochondrial function or mass. In addition, training-induced improvements in glucose homoeostasis were preserved in the ST group. Strikingly, the insulin-sensitizing effect of training was more prominent in the ST group than in the C group. The combined prescription of statins along with exercise training is safe and should be considered for subjects prone to develop insulin resistance.

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The effect of high-dose simvastatin on free fatty acid metabolism in patients with type 2 diabetes mellitus

Cited by 25 publications

References 37 publications

Effects of High-Dose Simvastatin Therapy on Glucose Metabolism and Ectopic Lipid Deposition in Nonobese Type 2 Diabetic Patients

Effects of High-Dose Simvastatin Therapy on Glucose Metabolism and Ectopic Lipid Deposition in Nonobese Type 2 Diabetic Patients

Emerging strategies of targeting lipoprotein lipase for metabolic and cardiovascular diseases

The use of statins potentiates the insulin-sensitizing effect of exercise training in obese males with and without Type 2 diabetes

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