Rosiglitazone taken once daily provides effective glycaemic control in patients with Type 2 diabetes mellitus

Nolan, John J.; Jones, NigelP.; Patwardhan, Rita; Deacon, L F

doi:10.1046/j.1464-5491.2000.00269.x

Cited by 111 publications

(65 citation statements)

References 23 publications

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“…Consistent with previous clinical reports [15,18,19], plasma HDL cholesterol increased significantly during rosiglitazone treatment (Table 1). We did not observe any effect of rosiglitazone on plasma triglyceride or total/LDL cholesterol concentrations with rosiglitazone treatment.…”

Section: Discussionsupporting

confidence: 92%

Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in Type II diabetic patients

Miyazaki¹,

Glass²,

Triplitt³

et al. 2001

Diabetologia

247

177

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The thiazolidinediones represent a new class of insulin sensitizing agents for the treatment of Type II (non-insulin-dependent) diabetes mellitus. The original drug in this class, troglitazone, has been shown to ameliorate insulin resistance and improve glycaemic control and dyslipidaemia in Type II diabetic patients [1±6]. However, all previous studies which employed the insulin clamp technique to examine the effect of troglitazone on insulin sensitivity employed pharmacologic insulin infusion rates (80±300 mU/m 2 min) that produced supraphysiologic plasma insulin con- Results. After 12 weeks, rosiglitazone reduced fasting plasma glucose (195 11 to 150 7 mg/dl, p < 0.01), mean plasma glucose (PG) during OGTT (293 12 to 236 9 mg/dl, p < 0.01), and HbA 1 c (8.7 0.4 to 7.4 0.3 %, p < 0.01) without changes in plasma insulin concentration. Basal endogenous glucose production (EGP) declined (3.3 0.1 to 2.9 0.1 mg/kg FFM´min, p < 0.05) and whole body glucose metabolic clearance rate increased after rosiglitazone (first clamp step: 2.8 0.2 to 3.5 0.2 ml/kg FFM´min, p < 0.01; second clamp step: 6.7 0.6 to 9.2 0.8, p < 0.05) despite increased body weight (86 4 to 90 4 kg, p < 0.01) and fat mass (33 3 to 37 3 kg, p < 0.01). Fasting plasma non-esterified fatty acid (NEFA) (735 52 to 579 49 mEq/l, p < 0.01), mean plasma NEFA during OGTT (561 33 to 424 35, p < 0.01), and basal NEFA turnover (18.3 1.5 to 15.5 1.2 mEq/kg FM´min, p < 0.05) decreased after rosiglitazone. Changes in EPG and mean plasma glucose (PG) during OGTT correlated with changes in basal EGP (r = 0.54; r = 0.58), first EGP (r = 0.36; r = 0.41), first MCR (r = ±0.66; r = ±0.68), second MCR (r = ±0.49; r = ±0.54), fasting plasma NEFA (r = 0.53; r = 0.49), and NEFA during OGTT (r = 0.66; r = 0.66). Conclusion/interpretation. Rosiglitazone increases hepatic and peripheral (muscle) tissue insulin sensitivity and reduces NEFA turnover despite increased total body fat mass. These results suggest that the beneficial effects of rosiglitazone on glycaemic control are mediated, in part, by the drug's effect on NEFA metabolism. [Diabetologia (2001) 44: 2210±2219]Keywords Type II diabetes mellitus, rosiglitazone, glucose and non-esterified fatty acid metabolism, insulin sensitivity.

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Section: Discussionsupporting

confidence: 92%

Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in Type II diabetic patients

Miyazaki¹,

Glass²,

Triplitt³

et al. 2001

Diabetologia

247

177

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“…RGZ, a drug of the class thiazolidinedione (TZD), is a potent agonist of the PPAR␥ (12, 37) and highly effective in lowering blood glucose in type II diabetes (21). PPARs are nuclear receptors that regulate gene transcription affecting a number of pathways involved in energy metabolism, in particular for PPAR␥, pathways involved in adipocyte differentiation and adipogenesis.…”

Section: Discussionmentioning

confidence: 99%

Regulation of the renal thiazide-sensitive Na-Cl cotransporter, blood pressure, and natriuresis in obese Zucker rats treated with rosiglitazone

Khan¹,

Riazi²,

Hu³

et al. 2005

American Journal of Physiology-Renal Physiology

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. Regulation of the renal thiazidesensitive Na-Cl cotransporter, blood pressure, and natriuresis in obese Zucker rats treated with rosiglitazone. Am J Physiol Renal Physiol 289: F442-F450, 2005. First published April 5, 2005; doi:10.1152/ajprenal.00335.2004.-Previously, we showed an increase in protein abundance of the renal thiazide-sensitive Na-Cl cotransporter (NCC) in young, prediabetic, obese Zucker rats relative to lean age mates (Bickel CA, Verbalis JF, Knepper MA, and Ecelbarger CA. Am J Physiol Renal Physiol 281: F639 -F648, 2001). To test whether this increase correlated with increased thiazide sensitivity (NCC activity) and blood pressure, and could be modified by insulinsensitizing agents, we treated lean and obese Zucker rats (9 wk old) with either a control diet or this diet supplemented with 3 mg/kg body wt rosiglitazone (RGZ), a peroxisomal proliferator-activated receptor subtype ␥ agonist and potent insulin-sensitizing agent, for 12 wk (n ϭ 9/group). The rise in blood pressure, measured continuously by radiotelemetry, was significantly blunted in the RGZ-treated obese rats. Similarly, blood glucose and urinary albumin were markedly decreased in these rats. RGZ-treated rats whether lean or obese excreted a NaCl load faster but excreted less sodium in response to hydrochlorothiazide, applied as a novel in vivo measure of NCC activity. Obese rats had increased renal protein abundance and urinary excretion of NCC; however, this was not significantly reduced by RGZ (densitometry in cortex homogenate Ϫ %lean control): 100 Ϯ 9, 93 Ϯ 4, 124 Ϯ 9, and 141 Ϯ 14 for lean control, lean RGZ, obese control, and obese RGZ, respectively. Subcellular localization, as evaluated by confocal microscopy and immunoblotting following differential centrifugation, of NCC was not different between rat groups. Overall, RGZ reduced blood pressure and thiazide sensitivity; however, the mechanism(s) did not seem to involve a decrease in NCC protein abundance or cellular location. Decreased NCC activity may have contributed to the maintenance of normotension in RGZ-treated obese rats. insulin resistance; type II diabetes; TSC THE OBESE ZUCKER RAT is a model of gross obesity with marked insulin resistance coupled to mild hypertension. Dysregulation of sodium balance and pressure-natriuresis as a result of insulin resistance likely are major contributors to the rise in blood pressure. Previously, we (4) showed increased renal abundances of three major sodium transport proteins in the kidney of the obese Zucker rat relative to lean age mates at both 2 and 4 mo of age, i.e., the thiazide-sensitive Na-Cl cotransporter (NCC or TSC), the ␤-subunit of the epithelial sodium channel (ENaC), and the ␣ 1 -subunit of Na-K-ATPase. These relative differences in protein abundance in the kidney seemed to be attenuated some in 6-mo-old rats, as the rats became fully diabetic and the kidneys hypertrophied (3). The mechanisms underlying these changes in abundance, i.e., transcriptional vs. changes in protein turnover rate, were not determined.T...

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“…For example, in rodents, rosiglitazone and troglitazone decrease fasting NEFA concentrations by 40 to 90% [9,10]. In contrast, in human studies, fasting NEFA concentrations increase, or fall by up to 30% [11][12][13][14], and these changes are often not statistically significant.…”

Section: Introductionmentioning

confidence: 99%

The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes

et al. 2004

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Aims/hypothesis: We investigated the effects of rosiglitazone on NEFA and triglyceride metabolism in type 2 diabetes. Methods: In a double-blind, placebo-controlled, cross-over study of rosiglitazone in diet-treated type 2 diabetic subjects, we measured arteriovenous differences and tissue blood flow in forearm muscle and subcutaneous abdominal adipose tissue, used stable isotope techniques, and analysed gene expression. Responses to a mixed meal containing [1,1,1-13 C]tripalmitin were assessed. Results: Rosiglitazone induced insulin sensitisation without altering fasting NEFA concentrations (−6.6%, p=0.16). Postprandial NEFA concentrations were lowered by rosiglitazone compared with placebo (−21%, p=0.04). Adipose tissue NEFA release was not decreased in the fasting state by rosiglitazone treatment (+24%, p=0.17) and was associated with an increased fasting hormone-sensitive lipase rate of action (+118%, p=0.01). Postprandial triglyceride concentrations were decreased by rosiglitazone treatment (−26%, p<0.01) despite unchanged fasting concentrations. Rosiglitazone did not change concentrations of triglyceride-rich lipoprotein remnants. Adipose tissue blood flow increased with rosiglitazone (+32%, p=0.03).

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Rosiglitazone taken once daily provides effective glycaemic control in patients with Type 2 diabetes mellitus

Abstract: Rosiglitazone improves glycaemic control when given once daily to treat Type 2 diabetes mellitus and is well tolerated at doses up to and including 12 mg.

Cited by 111 publications

References 23 publications

Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in Type II diabetic patients

Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in Type II diabetic patients

Regulation of the renal thiazide-sensitive Na-Cl cotransporter, blood pressure, and natriuresis in obese Zucker rats treated with rosiglitazone

The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes

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