Congenital lipodystrophies and dyslipidemias.

Lipodystrophies are rare acquired and genetic disorders characterized by the selective loss of adipose tissue. One key metabolic feature of patients with congenital inherited lipodystrophy is hypertriglyceridemia. The precise mechanisms by which the lack of adipose tissue causes dyslipidemia remain largely unknown. In recent years, new insights have arisen from data obtained in vitro in adipocytes, yeast, drosophila, and very recently in several genetically modified mouse models of generalized lipodystrophy. A common metabolic pathway involving accelerated lipolysis and defective energy storage seems to contribute to the dyslipidemia associated with congenital generalized lipodystrophy syndromes, although the pathophysiological changes may vary with the nature of the mutation involved. Therapeutic management of dyslipidemia in patients with lipodystrophy is primarily based on specific approaches using recombinant leptin therapy. Preclinical studies suggest a potential efficacy of thiazolidinediones that remains to be assessed in dedicated clinical trials.

Impact of diabetes, high triglycerides and low HDL cholesterol on risk for ischemic cardiovascular disease varies by LDL cholesterol level: a 15-year follow-up of the Chinese Multi-provincial Cohort Study.

AIMS: A large proportion of ischemic cardiovascular disease occur in people without hypercholesterolemia. We aimed to investigate whether risk factors other than low-density lipoprotein cholesterol (LDL-C) have different impacts on cardiovascular risk in people with low verses high LDL-C levels. METHODS: A total of 30,378 participants (35-64 years) were followed for 15 years in the Chinese Multi-provincial Cohort Study. Associations of coronary heart disease (CHD) and ischemic stroke with risk factors other than LDL-C were assessed in participants with low (<130 mg/dL) and high (≥130 mg/dL) LDL-C levels. RESULTS: During the follow-up, 65.5% of CHD and 70.2% of ischemic stroke events occurred in participants with low LDL-C. High triglycerides predicted CHD (HR=1.74, 95% CI 1.25-2.42, P=0.001), and low HDL-C predicted ischemic stroke (HR=1.54, 95% CI 1.18-2.03, P=0.002) only in participants with low LDL-C. Diabetes predicted CHD in participants with high LDL-C (HR=2.38, 95% CI 1.31-4.34, P=0.005), but not in those with low LDL-C. Older age, male, hypertension, central obesity, and smoking had similar effects on the risk in both groups. CONCLUSIONS: Triglycerides and low HDL-C should be addressed in the management of dyslipidemia in people with low LDL-C. When LDL-C is high, tighter management of glycemia and LDL-C is warranted.