Effects of High-Density Lipoprotein Elevation With Cholesteryl Ester Transfer Protein Inhibition on Insulin Secretion

Siebel, Andrew L.; Natoli, A; Yap, Felicia Y. T.; Carey, Andrew L.; Reddy-Luthmoodoo, Medini; Sviridov, Dmitri; Weber, Chek Ing Kiu; Meneses-Lorente, Georgina; Maugeais, Cyrille; Forbes, Josephine M.; Kingwell, Bronwyn A.

doi:10.1161/circresaha.113.300689

Cited by 68 publications

(57 citation statements)

References 49 publications

(74 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These findings suggest that low levels of HDL cholesterol per se do not cause type 2 diabetes and thus that the corresponding observational association may be due to reverse causation. Consequently, this questions plasma HDL cholesterol increasing as a novel therapeutic option for treatment or prevention of type 2 diabetes, as recently suggested (3)(4)(5).…”

Section: Discussionmentioning

confidence: 99%

HDL Cholesterol and Risk of Type 2 Diabetes: A Mendelian Randomization Study

et al. 2015

View full text Add to dashboard Cite

Observationally, low levels of HDL cholesterol are consistently associated with increased risk of type 2 diabetes. Therefore, plasma HDL cholesterol increasing has been suggested as a novel therapeutic option to reduce the risk of type 2 diabetes. Whether levels of HDL cholesterol are causally associated with type 2 diabetes is unknown. In a prospective study of the general population (n = 47,627), we tested whether HDL cholesterol-related genetic variants were associated with low HDL cholesterol levels and, in turn, with an increased risk of type 2 diabetes. HDL cholesterol-decreasing gene scores and allele numbers associated with up to 213 and 220% reductions in HDL cholesterol levels. The corresponding theoretically predicted hazard ratios for type 2 diabetes were 1.44 (95% CI 1.38-1.52) and 1.77 (1.61-1.95), whereas the genetic estimates were nonsignificant. Genetic risk ratios for type 2 diabetes for a 0.2 mmol/L reduction in HDL cholesterol were 0.91 (0.75-1.09) and 0.93 (0.78-1.11) for HDL cholesterol-decreasing gene scores and allele numbers, respectively, compared with the corresponding observational hazard ratio of 1.37 (1.32-1.42). In conclusion, genetically reduced HDL cholesterol does not associate with increased risk of type 2 diabetes, suggesting that the corresponding observational association is due to confounding and/or reverse causation.

show abstract

Section: Discussionmentioning

confidence: 99%

HDL Cholesterol and Risk of Type 2 Diabetes: A Mendelian Randomization Study

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Infusion of reconstituted HDLs in type 2 diabetes patients increased their HOMA-B index, an indirect measurement of pancreatic beta cell function (Drew et al 2009). Also, the increase of HDL cholesterol levels in healthy volunteers treated for 2 weeks with a CETP inhibitor was found to increase postprandial insulin and C-peptide plasma levels (Siebel et al 2013). The plasma of the CETP inhibited volunteers but not the CETP inhibitor itself also showed an increased capacity to enhance glucose-stimulated insulin secretion from MIN6 cells.…”

Section: Beneficial Effects Of Hdl On Insulin Secretionmentioning

confidence: 88%

HDLs, Diabetes, and Metabolic Syndrome

Vollenweider

Eckardstein

Widmann

2014

High Density Lipoproteins

View full text Add to dashboard Cite

The prevalence of type 2 diabetes mellitus and of the metabolic syndrome is rising worldwide and reaching epidemic proportions. These pathologies are associated with significant morbidity and mortality, in particular with an excess of cardiovascular deaths. Type 2 diabetes mellitus and the cluster of pathologies including insulin resistance, central obesity, high blood pressure, and hypertriglyceridemia that constitute the metabolic syndrome are associated with low levels of HDL cholesterol and the presence of dysfunctional HDLs. We here review the epidemiological evidence and the potential underlying mechanisms of this association. We first discuss the well-established association of type 2 diabetes mellitus and insulin resistance with alterations of lipid metabolism and how these alterations may lead to low levels of HDL cholesterol and the occurrence of dysfunctional HDLs. We then present and discuss the evidence showing that HDL modulates insulin sensitivity, insulin-independent glucose uptake, insulin secretion, and beta cell survival. A dysfunction in these actions could play a direct role in the pathogenesis of type 2 diabetes mellitus.

show abstract

“…For this reason, UPC2-lacking mice could serve as a useful model for future investigations into the pathological pathways that cause pulmonary hypertension in humans, say the authors. 42 Inhibiting CETP activity may help diabetes patients as well as those with atherosclerosis, say Siebel et al Cholesterylester transfer protein (CETP) is a plasma protein that decreases plasma HDL levels. Therefore CETP inhibition may be one approach for increasing HDL levels in the plasma.…”

Section: Ucp2 Deficiency Mimics Hypoxia (P 126)mentioning

confidence: 99%

Circulation Research “In This Issue” Anthology

Williams¹

2014

Circulation Research

View full text Add to dashboard Cite

Effects of High-Density Lipoprotein Elevation With Cholesteryl Ester Transfer Protein Inhibition on Insulin Secretion

Cited by 68 publications

References 49 publications

HDL Cholesterol and Risk of Type 2 Diabetes: A Mendelian Randomization Study

HDL Cholesterol and Risk of Type 2 Diabetes: A Mendelian Randomization Study

HDLs, Diabetes, and Metabolic Syndrome

Circulation Research “In This Issue” Anthology

Contact Info

Product

Resources

About