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

Curr Opin Lipidol. 2010 Dec;21(6):530-8. doi: 10.1097/MOL.0b013e32833ea9ec.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Cholesterol, LDL / genetics
  • Cholesterol, LDL / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Discovery
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Genetic Predisposition to Disease
  • Humans
  • Hyperlipidemia, Familial Combined / complications
  • Hyperlipidemia, Familial Combined / drug therapy*
  • Hyperlipidemia, Familial Combined / genetics*
  • Hyperlipidemia, Familial Combined / metabolism
  • Insulin / metabolism
  • Insulin Resistance / genetics*
  • Male
  • Metabolic Syndrome / etiology
  • Metabolic Syndrome / genetics
  • Metabolic Syndrome / metabolism
  • Metformin / administration & dosage
  • Models, Biological
  • Obesity / genetics
  • Obesity / metabolism
  • Pioglitazone
  • Risk Factors
  • Thiazolidinediones / administration & dosage
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Triglycerides / genetics
  • Triglycerides / metabolism

Substances

  • Cholesterol, LDL
  • Insulin
  • Thiazolidinediones
  • Transcription Factors
  • Triglycerides
  • Metformin
  • Pioglitazone