APOH is Increased in the Plasma and Liver of Type 2 Diabetic Patients with Metabolic Syndrome

Objective: To assess the association of APOH with metabolic and cardiovascular risk markers in type 2 diabetic patients.

Methods: In a cohort of 169 type 2 diabetic subjects, plasma levels of APOH, antibodies anti-APOH, lipoprotein subfractions, oxidation, inflammatory and insulin resistance markers and the Trp316Ser and Val247Leu variations in the APOH gene were analyzed. Apo H mRNA levels and protein content were measured in hepatic and adipose tissue (subcutaneous and visceral) samples obtained during bariatric surgery from three diabetics who fulfilled metabolic syndrome (MS) criteria and three non-diabetic, non-MS.

Results: APOH plasma levels were significantly associated with triglycerides (p<0.001), all the components of triglyceride-rich lipoproteins (p<0.001) and RBP4 (p<0.001) levels. APOH was higher in type 2 diabetic patients with MS (p=0.003) and with clinical evidence of macrovascular disease (p=0.012). The Trp316Ser and Val247Leu APOH gene variants did not modulate APOH plasma values. Neither Apo H mRNA nor protein was detected in the adipose tissue. Liver from patients with diabetes and MS showed a significant increase of both Apo H mRNA and protein respect to the non-diabetic, non-MS patients.

Conclusion: APOH plasma concentrations are strongly associated to MS alterations and vascular disease in type 2 diabetic patients and could be considered as a clinical marker of cardiovascular risk. The enhanced APOH levels in these patients are due to an increased liver synthesis. If APOH plays a major causal role in macrovascular lesions associated to diabetes and MS need further studies.