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Novel drugs in familial combined hyperlipidemia: lessons from type 2 diabetes mellitus

Brouwers, Martijn CGJa; de Graaf, Jacquelineb; van Greevenbroek, Marleen MJa; Schaper, Nicolaasa; Stehouwer, Coen DAa; Stalenhoef, Anton FHb

doi: 10.1097/MOL.0b013e32833ea9ec
Therapy and clinical trials: Edited by Anton F. Stalenhoef and John J.P. Kastelein

Purpose of review Familial combined hyperlipidemia (FCHL) and type 2 diabetes mellitus (T2DM) are prevalent entities that share many features of the metabolic syndrome. Recent findings suggest that FCHL and T2DM are less distinct than initially anticipated, which could offer new insights for their therapeutic approach.

Recent findings Genetic association studies have provided evidence for a common genetic background (upstream transcription factor 1, activating transcription factor 6, transcription factor 7-like 2 and hepatocyte nuclear factor 4 alpha) between FCHL and T2DM. The metabolic overlap can be illustrated by the presence of ectopic fat accumulation and insulin resistance (muscle, adipose tissue and liver). We have shown that FCHL patients are at increased risk to develop T2DM. This indicates that both entities are not static, but instead the former is able to migrate to the latter as insulin resistance progresses. Given these new findings, it can be anticipated that FCHL patients could also benefit from insulin-sensitizing therapy such as pioglitazone and metformin. Indeed, pilot studies have demonstrated that pioglitazone might be advantageous in FCHL patients.

Summary Recent studies suggest that FCHL patients have an increased risk to develop T2DM, which has important clinical implications. Further studies are necessary to evaluate whether FCHL patients can be protected from new-onset T2DM and premature cardiovascular events with insulin-sensitizing therapy.

aLaboratory of Vascular Medicine and Metabolism, Department of Internal Medicine, Divisions of General Internal Medicine and Endocrinology, Cardiovascular Research Institute Maastricht, Maastricht University Centre of Health, Maastricht

bDepartment of Internal Medicine, Division of Vascular Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Correspondence to Dr Martijn C.G.J. Brouwers, Laboratory of Vascular Medicine and Metabolism, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands Tel: +31 43 3882129; fax: +31 43 3670916; e-mail:

© 2010 Lippincott Williams & Wilkins, Inc.