Pioglitazone Reduces Atherogenic Dense LDL Particles in Nondiabetic Patients With Arterial Hypertension

Winkler, Karl; Konrad, Thomas R.; Fullert, S; Friedrich, I.; Destani, Ramadan; Baumstark, Manfred W.; Krebs, Kristin; Wieland, Heinrich; März, Winfried

doi:10.2337/diacare.26.9.2588

Cited by 103 publications

(77 citation statements)

References 50 publications

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“…Pioglitazone compared to placebo has been studied in 54 patients with type 2 diabetes for 16 weeks. An increase in LDL particle diameter, together with a decrease of LDL density, was observed, without any changes in the classic lipid parameters (triglycerides, total, LDL, and HDL cholesterol) [92]. This finding was confirmed in subsequent studies [93,94].…”

Section: Antihyperglycemic Treatments With Effects On Ldl Particle DIsupporting

confidence: 76%

Small dense low-density lipoprotein particles: priority as a treatment target in Type 2 diabetes?

Gerber¹,

Spinas²,

Berneis³

2012

Diabetes Management

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During the past two decades, the importance of the quality of low-density lipoprotein (LDL) particles -in addition to its quantity -has become of increasing interest. The risk of cardiovascular events was recognized to be closely linked to a predominance of small, dense LDL particles. In addition, in patients with Type 2 diabetes mellitus, the disease itself and its severity (in particular the degree of insulin resistance) is associated with this subclass of LDL particles. Lipid lowering as well as antihyperglycemic drugs have been evaluated in many studies concerning their effect on LDL particle size. It has increasingly been recognized that a reduction of LDL quantity is not necessarily associated with a beneficial effect on LDL quality. Advances in the understanding of alterations in LDL quality may therefore influence the choice of the therapeutic regimen in patients with diabetes in the future. SummaryDuring the last two decades, the importance of the quality of low-density lipoprotein (LDL) particles -in addition to its quantity -has become of increasing interest. The risk of cardiovascular events was recognized to be closely linked to a predominance of small, dense LDL particles. In addition, in patients with type 2 diabetes mellitus, the disease itself and its severity (in particular the degree of insulin resistance) is associated with this subclass of LDL particles. Lipid lowering as well as antihyperglycemic drugs have been evaluated in many studies concerning their effect on LDL particle size. It has increasingly been recognized that a reduction of LDL quantity is not necessarily associated with a beneficial effect on LDL quality. Advances in the understanding of alterations in LDL quality may therefore influence the choice of the therapeutic regimen in patients with diabetes in the future.

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Section: Antihyperglycemic Treatments With Effects On Ldl Particle DIsupporting

confidence: 76%

Small dense low-density lipoprotein particles: priority as a treatment target in Type 2 diabetes?

Gerber¹,

Spinas²,

Berneis³

2012

Diabetes Management

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“…Since there appears to be an inverse correlation between AIP and LDL particle size, we believe that pioglitazone treatment may cause a favourable change in LDL cholesterol from small, dense to large, more buoyant LDL particles. Such a reduction in the number of small dense LDL particles has been reported previously with pioglitazone [10,11].…”

Section: Resultsmentioning

confidence: 67%

Long-term effects on lipids and lipoproteins of pioglitazone versus gliclazide addition to metformin and pioglitazone versus metformin addition to sulphonylurea in the treatment of type 2 diabetes

Betteridge

Vergès

2005

Diabetologia

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Aims/hypothesis: The aim of this study was to determine the long-term effects of pioglitazone add-on to metformin or sulphonylurea on plasma lipids and lipoproteins. Materials and methods: The effects of pioglitazone were studied in two clinical trials in patients with inadequately controlled type 2 diabetes (HbA 1 c ≥7.5 and ≤11%). In the first trial, patients currently receiving metformin were randomised to pioglitazone (15-45 mg/day, n=317) or gliclazide (80-320 mg/day, n=313) add-on therapy. In the second study, pioglitazone (15-45 mg/day, n=319) or metformin (850-2,550 mg/day, n=320) was added to sulphonylurea therapy. Patients were forcetitrated to the maximum tolerated dose of add-on therapy, which was maintained to the 2-year endpoint. Results: There were no statistically significant differences between the groups with respect to HbA 1 c reduction from baseline to week 104. Whether added to metformin or sulphonylurea, pioglitazone caused highly significant greater decreases in triglycerides and increases in HDL cholesterol from baseline to week 104 than treatments with gliclazide or metformin add-on therapies (p≤0.001). The triglyceride reductions noted with pioglitazone were maintained over time, with decreases of 16-18% at 1 year and 17-23% at 2 years. In the pioglitazone groups, the improvement in HDL cholesterol at 1 year was maintained, with 21-22% augmentations at 2 years (p<0.001 between-group difference). Small but statistically significant greater reductions in LDL cholesterol were observed with gliclazide vs pioglitazone add-on to metformin and metformin vs pioglitazone add-on to sulphonylurea (p<0.001 for betweengroup difference). In the pioglitazone groups, mean LDL cholesterol at 2 years was similar to mean baseline LDL cholesterol. Conclusions/interpretation: After 2 years, highly significant decreases in triglycerides and increases in HDL cholesterol that were sustained over time or even improved were observed when pioglitazone was added to metformin or sulphonylurea therapy. These effects of pioglitazone on lipids may be potentially beneficial in reducing cardiovascular risk in type 2 diabetes.

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“…29,30 Improvement of IR reduced small dense LDL particles. 31 To date, no data are available on whether the improvement of LDL size can affect IR. Interestingly, the state of insulin resistance in familial combined hyperlipidemia (FCHL) is associated with the lipid phenotype.…”

Section: Obesementioning

confidence: 99%

Relationship Between Lipid Abnormalities and Insulin Resistance in Japanese School Children

Asato

Katsuren

Ohshiro

et al. 2006

ATVB

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Objective-Dyslipidemia and insulin resistance (IR) are risk factors for coronary heart disease (CHD) in adults. To help prevent the development of CHD, it may be useful to understand the relationship between lipid abnormalities and IR during childhood. Methods and Results-IR was assessed by the homeostasis model approximation index. We studied 1175 Japanese school children (642 boys and 533 girls), aged between 7 and 12 years. Obesity was defined by the body mass index standard deviation score (BMISD) (obese: BMISD Ն2.0). BMISD was most significantly associated with IR in nonobese children (Pϭ0.000). Associations of IR with lipid-related parameters were affected by BMISD. After being corrected by BMISD, in nonobese children, log triglycerides (TG), apoB and low-density lipoprotein (LDL) size in boys and log TG, LDL size, and high-density lipoprotein (HDL) cholesterol in girls were still significantly associated with IR (Pϭ0.000 to 0.017). In obese children, all parameters except for LDL cholesterol in boys and LDL size in girls were significantly associated with IR (Pϭ0.000 to 0.030). Multiple regression analysis showed that log TG and LDL size in nonobese children, log TG in obese boys and LDL size in obese girls were independently associated with IR. Children with IIb and IV hyperlipidemia had significantly higher IR than those with normolipidemia and IIa, even after correcting for BMISD and age. Conclusion-Our results suggest that in addition to controlling body weight, it may be important for school children to characterize lipid phenotypes to prevent progression to CHD and/or type 2 diabetes and to identify subjects who are at high risk for these disorders.

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Pioglitazone Reduces Atherogenic Dense LDL Particles in Nondiabetic Patients With Arterial Hypertension

Cited by 103 publications

References 50 publications

Small dense low-density lipoprotein particles: priority as a treatment target in Type 2 diabetes?

Small dense low-density lipoprotein particles: priority as a treatment target in Type 2 diabetes?

Long-term effects on lipids and lipoproteins of pioglitazone versus gliclazide addition to metformin and pioglitazone versus metformin addition to sulphonylurea in the treatment of type 2 diabetes

Relationship Between Lipid Abnormalities and Insulin Resistance in Japanese School Children

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