Insulin action and glucose metabolism are improved by gemfibrozil treatment in hypertriglyceridemic patients

Avogaro, Angelo; Beltramello, Piero; Marin, Raffaella; Bonanome, A; Biffanti, S.; Confortin, Loris; Manzato, Enzo; Crepaldi, Gaetano; Tiengo, Antonio

doi:10.1016/0021-9150(94)05437-n

Cited by 31 publications

(24 citation statements)

References 28 publications

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“…Axelsen et al (45) found that feeding cornstarch at bedtime lowered fasting FFA concentrations and reduced postbreakfast hyperglycemia in subjects with type 2 diabetes; however, overall glycemic control was not affected. In type 2 diabetic subjects, gemfibrozil lowered fasting plasma FFA and glucose concentrations, but did not affect HbA 1c (46). A recent study reported improvement in fasting hyperglycemia, glucose tolerance, and insulin sensitivity when acipimox was administered to subjects with type 2 diabetes (47).…”

Section: Discussionmentioning

confidence: 93%

Nocturnal and Postprandial Free Fatty Acid Kinetics in Normal and Type 2 Diabetic Subjects

et al. 2003

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Whether free fatty acid (FFA) rate of appearance (R a ) is increased in type 2 diabetes is controversial. To characterize nocturnal and postprandial abnormalities in FFA kinetics and to determine the effects of treatment with insulin sensitizers on lipolysis, we measured palmitate R a in control subjects (n ‫؍‬ 6) and individuals with poorly controlled, sulfonylurea-treated type 2 diabetes (HbA 1c ‫؍‬ 8.7 ؎ 0.2%, n ‫؍‬ 20), the latter before and at the end of 12 weeks of treatment with troglitazone (600 mg/day, n ‫؍‬ 4), metformin (ϳ2,000 mg/day, n ‫؍‬ 8), or placebo (n ‫؍‬ 8). Subjects consumed a standard breakfast at 0800 h. Results in control subjects and type 2 diabetic subjects were compared at baseline. Integrated nocturnal FFA R a (AUC 1:00 -8:00 A.M. ) was ϳ50% higher in type 2 diabetic subjects than in control subjects (29.4 ؎ 3.0 vs. 19.4 ؎ 3.9 mmol ⅐ m ؊2 ⅐ 7 h ؊1 , respectively, P < 0.05), whereas postprandial palmitate R a (AUC 0 -240 min ) was almost threefold higher in type 2 diabetic subjects than in control subjects (14.2 ؎ 1.7 vs. 5.3 ؎ 1.0 mmol ⅐ m ؊2 ⅐ 4 h ؊1 , respectively, P < 0.01). After troglitazone treatment, nocturnal palmitate R a did not change, but postprandial palmitate R a decreased by ϳ30% (P < 0.05). Palmitate kinetics did not change with metformin or placebo treatment. In summary, nocturnal and postprandial FFA R a is increased in type 2 diabetes. Postprandial lipolysis appears to be preferentially improved by thiazolidinediones compared with nocturnal lipolysis. Diabetes 52:675-681, 2003 P atients with type 2 diabetes have resistance to the antilipolytic effects of insulin on adipose tissue (1,2). This dysregulation of adipose tissue lipolysis has been implicated as a major cause of the abnormalities in lipoprotein and glucose metabolism that are characteristic of type 2 diabetes (3). However, plasma free fatty acid (FFA) turnover has been reported to be both increased (4) and normal (5-8) in type 2 diabetes.FFA tracer studies in patients with type 2 diabetes have generally been performed under postabsorptive conditions (4,5,7) or during a hyperinsulinemic-euglycemic clamp (1,2); little information is available regarding nocturnal and postprandial FFA metabolism. In fact, patients with poorly controlled type 2 diabetes exhibit an increase in plasma FFA concentrations during the night (9), but it is not known whether this is the result of increased release of FFA into the systemic circulation or decreased plasma FFA clearance. An understanding of fatty acid metabolism during nocturnal and absorptive conditions is important because postabsorptive measurements may not necessarily reflect conditions at other times of the day.The treatment of type 2 diabetes has been revolutionized by the availability of medications, including biguanides and thiazolidinediones, which improve insulin action on glucose metabolism. In addition, some (10,11) but not all (12) studies suggest that these agents may improve abnormalities in FFA metabolism in the postabsorptive state and during hyperinsulin...

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Section: Discussionmentioning

confidence: 93%

Nocturnal and Postprandial Free Fatty Acid Kinetics in Normal and Type 2 Diabetic Subjects

et al. 2003

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“…Despite the widespread use of PPAR-α agonists (i.e. FENO and gemfibrozil) for the treatment of hypertriacylglycerolaemia in type 2 diabetic patients, their effect on insulin sensitivity in humans has not been rigorously examined and conflicting results have been reported [9][10][11][12][13][14]. Studies in rodents conclusively demonstrate that PPAR-α activation with FENO and other more potent PPAR-α agents enhances peripheral (muscle) and hepatic insulin sensitivity [4][5][6][7][8].…”

Section: Discussionmentioning

confidence: 99%

“…Studies in rodents clearly demonstrate that PPAR-α agonists improve hepatic and muscle insulin resistance, decrease hepatic and intramuscular fat content, reduce plasma NEFA and enhance adiponectin (AD) expression [4][5][6][7][8]. Some [9][10][11], but not all [12][13][14], studies in humans with hypertriacylglycerolaemia and/or type 2 diabetes suggest that PPAR-α agonists, i.e. fibrates, enhance insulin sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Effects of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ agonists on glucose and lipid metabolism in patients with type 2 diabetes mellitus

et al. 2007

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Aims/hypothesis The aim of the study was to examine the effects of pioglitazone (PIO), a peroxisome proliferatoractivated receptor (PPAR)-γ agonist, and fenofibrate (FENO), a PPAR-α agonist, as monotherapy and in combination on glucose and lipid metabolism. Subjects and methods Fifteen type 2 diabetic patients received FENO (n=8) or PIO (n=7) for 3 months, followed by the addition of the other agent for 3 months in an openlabel study. Subjects received a 4 h hyperinsulinaemiceuglycaemic clamp and a hepatic fat content measurement at 0, 3 and 6 months. Results Following PIO, fasting plasma glucose (FPG) (p<0.05) and HbA 1c (p<0.01) decreased, while plasma adiponectin (AD) (5.5±0.9 to 13.8±3.5 μg/ml [SEM], p<0.03) and the rate of insulin-stimulated total-body glucose disposal (R d ) (23.8 ± 3.8 to 40.5 ± 4.4 μmol kg −1 min −1 , p < 0.005) increased. After FENO, FPG, HbA 1c , AD and R d did not change. PIO reduced fasting NEFA (784±53 to 546± 43 μmol/l, p<0.05), triacylglycerol (2.12±0.28 to 1.61± 0.22 mmol/l, p<0.05) and hepatic fat content (20.4±4.8 to 10.2±2.5%, p<0.02). Following FENO, fasting NEFA and hepatic fat content did not change, while triacylglycerol decreased (2.20± 0.14 to 1.59± 0.13 mmol/l, p<0.01).Addition of FENO to PIO had no effect on R d , FPG, HbA 1c , NEFA, hepatic fat content or AD, but triacylglycerol decreased (1.61±0.22 to 1.00±0.15 mmol/l, p<0.05). Addition of PIO to FENO increased R d (24.9±4.4 to 36.1± 2.2 μmol kg −1 min −1 , p<0.005) and AD (4.1±0.8 to 13.1± 2.5 μg/ml, p<0.005) and reduced FPG (p<0.05), HbA 1c (p<0.05), NEFA (p<0.01), hepatic fat content (18.3±3.1 to 13.5±2.1%, p<0.03) and triacylglycerol (1.59±0.13 to 0.96±0.9 mmol/l, p<0.01). Muscle adenosine 5′-monophosphate-activated protein kinase (AMPK) activity did not change following FENO; following the addition of PIO, muscle AMPK activity increased significantly (phosphorylated AMPK:total AMPK ratio 1.2±0.2 to 2.2±0.3, p<0.01). Conclusions/interpretation We conclude that PPAR-α therapy has no effect on NEFA or glucose metabolism and that addition of a PPAR-α agonist to a PPAR-γ agent causes a further decrease in plasma triacylglycerol, but has no effect on NEFA or glucose metabolism.

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“…Indeed, to the best of our knowledge, only a few studies which were conducted on a limited number of subjects have reported some controversial ®ndings related to this issue. 22,23 Therefore, it appears relevant to hypothesize that gem®-brozil may represent a valuable therapeutic approach for the management of metabolic alterations associated with an excess of visceral adipose tissue, especially when combined with dietary recommendations. Therefore, the objective of the present study was to investigate the effects of a 6 month gem®brozil treatment (1200 mgaday) combined with dietary recommendations on both anthropometric and metabolic risk variables in a sample of 64 dyslipidemic visceral obese men.…”

Section: Introductionmentioning

confidence: 99%

Effect of a six month gemfibrozil treatment and dietary recommendations on the metabolic risk profile of visceral obese men

et al. 2001

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OBJECTIVE:The aim of the present study was to investigate the effects of a 6 month gem®brozil treatment. SUBJECTS: A sample of 64 visceral obese men (age 46 AE 6 y; body mass index 31 AE 3 kgam 2 ; waist circumference 104 AE 7 cm; mean AE s.d.) who received dietary recommendations. METHODS: Subjects were randomly assigned to receive a placebo (n 32) or gem®brozil (1200 mgaday) (n 32). RESULTS: In both placebo and gem®brozil treated groups, signi®cant reductions were noted in body weight, fat mass, waist circumference and visceral adipose tissue area measured by computed tomography (0.0001`P`0.05). Plasma cholesterol (CHOL) and apolipoprotein B (apo B) levels were also decreased in both groups (P`0.01) whereas plasma high density lipoprotein (HDL) and HDL-3-CHOL levels were only signi®cantly (P`0.01) increased in the gem®brozil-treated group. After the 6 month treatment period, gem®brozil-treated men displayed signi®cantly lower plasma triglycerides (TG) levels, compared to those who received the placebo (P`0.01). Finally, both fasting plasma insulin concentration and insulin area measured during an oral glucose load were signi®cantly decreased only in the placebo group (P`0.05). Taken together, these results suggest that the improvement in plasma lipidalipoprotein pro®le observed in gem®brozil treated visceral obese men seems to be independent from changes in adipose tissue mass and in visceral fat accumulation. Furthermore, improvements in the plasma lipoprotein pro®le produced by gem®brozil therapy appear to be independent from changes in indices of plasma glucose ± insulin homeostasis.

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Insulin action and glucose metabolism are improved by gemfibrozil treatment in hypertriglyceridemic patients

Cited by 31 publications

References 28 publications

Nocturnal and Postprandial Free Fatty Acid Kinetics in Normal and Type 2 Diabetic Subjects

Nocturnal and Postprandial Free Fatty Acid Kinetics in Normal and Type 2 Diabetic Subjects

Effects of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ agonists on glucose and lipid metabolism in patients with type 2 diabetes mellitus

Effect of a six month gemfibrozil treatment and dietary recommendations on the metabolic risk profile of visceral obese men

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