Lack of effect of simvastatin on insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia: results from a double-blind, randomized, placebo-controlled crossover study

Hwu, Chii‐Min; Kwok, Ching-Yee; Chen, H. S.; Shih, KC; Lee, S. H.; Hsiao, Li Chuan; Lin, S. H.; Ho, L T

doi:10.1046/j.1464-5491.1999.00113.x

Cited by 20 publications

(14 citation statements)

References 21 publications

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“…Similarly, we tested only a single statin. There are controversies regarding the effect of statins on the insulin sensitivity (37,38) and on the endothelial function in DM patients among the statins (39 -41). Therefore, further studies comparing different agents, especially hydrophilic and hydrophobic agents, may be necessary in the future.…”

Section: Discussionmentioning

confidence: 99%

Effects of pravastatin on progression of glucose intolerance and cardiovascular remodeling in a type II diabetes model

Yu¹,

Ohmori²,

Chen³

et al. 2004

Journal of the American College of Cardiology

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Section: Discussionmentioning

confidence: 99%

Effects of pravastatin on progression of glucose intolerance and cardiovascular remodeling in a type II diabetes model

Yu¹,

Ohmori²,

Chen³

et al. 2004

Journal of the American College of Cardiology

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“…Recent data suggest an early direct effect of intracellular FFA content on insulin stimulation GLUT4 transporter activity (31,32). Contrasting results in a few experimental studies regarding the effect of statins in glucose metabolism of patients with diabetes have been published (33)(34)(35). The nonhomogeneous selection of patients together with the low doses of statins and short times of EHC used could have limited some of these results.…”

Section: Discussionmentioning

confidence: 99%

Cerivastatin Improves Insulin Sensitivity and Insulin Secretion in Early-State Obese Type 2 Diabetes

et al. 2002

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In a double-blind, placebo-controlled, randomized crossover study, 15 stable mild hyperglycemic patients without treatment and with features of metabolic syndrome were treated with cerivastatin (0.4 mg/day) or placebo for 3 months. The insulin sensitivity index during the euglycemic-hyperinsulinemic clamp (EHC; 5.4 mmol/l; 80 mU ⅐ m ؊2 ⅐ min ؊1 ) was increased by cerivastatin treatment (66.39 ؎ 3.9 nmol ⅐ lean body , 0.91 ؎ 0.01; P < 0.01 and P < 0.05, respectively). During statin treatment, the first-phase insulin response increased from 2.07 ؎ 0.28 to 2.82 ؎ 0.38 pmol ⅐ l ؊1 ⅐ pmol ؊1 (P < 0.05). The second phase of insulin responses examined by C-peptide and insulin levels averaged during the hyperglycemic clamp (20 mmol/l) was unchanged. In conclusion, this study demonstrates that 0.4 mg cerivastatin therapy improves first-phase insulin secretion and increases insulin-mediated glucose uptake and respiratory quotient in the early state of obese type 2 diabetes. Diabetes 51:2596 -2603, 2002 T ype 2 diabetes represents the final stage of a progressive syndrome characterized by targettissue resistance to insulin that cannot be overcome by ␤-cell hypersecretion (1). In the initial period, some subjects accumulate a constellation of major risk factors such as central (intra-abdominal) obesity, hypertriglyceridemia, low HDL cholesterol, raised blood pressure, and insulin resistance associated with proinflammatory states (2). In this state, patients receive primary care from their physicians with a recommendation for lifestyle changes (3). However, most people do not adequately maintain weight loss after participating in weightcontrol programs (4), and some subjects develop late micro-and macrovascular complications of diabetes. Approaches to reduce coronary heart disease have been focused on statins therapy (5,6). Several pleiotropic effects of statins could represent a potential means for controlling multifactorial atherosclerosis observed in diabetes. A post hoc analysis in the West of Scotland Coronary Prevention Study database provided evidence for the protective treatment effect of Pravastatin on the development of diabetes (7). However, whether statin treatment is beneficial in glucose metabolism of diabetes still remains to be seen. Suppression with high doses of statins on VLDL production of patients with type 2 diabetic hypertriglyceridemia could effect the release of fatty acids (FAs) from the liver (8). It is now recognized that plasma FA concentrations have profound effects on insulin action and glucose metabolism (9,10). Finally, cholesterol is a key component in the regulation of signal transduction through membrane lipid-ordered microdomains and in the regulation of gene expression through cholesterol-activated transcription factors (11). Intracellular cholesterol might serve as a link between fat cell size, glucose metabolism, and adipocyte metabolic activity (12). Sterol regulatory element-binding protein is implicated as a major mediator of insulin action (13). The major aim of the present study w...

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“…pravastatin, rosuvastation, fluvastatin) reproducibly improve insulin sensitivity independent of lipid lowering in obese subjects with and without diabetes (112–116), while others (e.g. simvastatin) consistently fail to do so despite similarly improvements in inflammatory markers (112; 115; 117). Interestingly, pravastatin therapy had no effect in lean, insulin sensitive patients, a population where previous studies have shown the alternative macrophage phenotype to be dominant (118).…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Alternative Macrophage Activation and Metabolism

Odegaard

Chawla

2011

Annu. Rev. Pathol. Mech. Dis.

546

502

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Obesity and its attendant metabolic disorders represent the great public health challenge of our time. Recent evidence suggests that onset of inflammation in metabolic tissues pathogenically links obesity to insulin resistance and type 2 diabetes. In this review, we briefly summarize the extant literature with special attention to the central role of the tissue-associated macrophage in the initiation of metabolic inflammation. We argue that rather than simple inflammatory disease, obesity and metabolic syndrome represent derangements in macrophage activation with concomitant loss of metabolic coordination. As such, the sequelae of obesity are as much products of the loss of positive macrophage influences as the presence of deleterious inflammation. The therapeutic implications of this conclusion are profound because they suggest that pharmacologic targeting of macrophage activation, rather than purely inflammation, might be efficacious in treating this global epidemic.

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Lack of effect of simvastatin on insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia: results from a double-blind, randomized, placebo-controlled crossover study

Abstract: Simvastatin significantly reduced the serum TC and LDL-C levels without alteration of insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia.

Cited by 20 publications

References 21 publications

Effects of pravastatin on progression of glucose intolerance and cardiovascular remodeling in a type II diabetes model

Effects of pravastatin on progression of glucose intolerance and cardiovascular remodeling in a type II diabetes model

Cerivastatin Improves Insulin Sensitivity and Insulin Secretion in Early-State Obese Type 2 Diabetes

Alternative Macrophage Activation and Metabolism

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