Postprandial Cardiometabolic risk in Autoimmune Thyroid Disease and Type 1 Diabetes Mellitus

Abstract

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Atherosclerosis is implicated in the development of CVD. Postprandial lipaemia is independently predictive of atherogenesis and of future cardiovascular events. Postprandial studies can unmask lipoprotein abnormalities not present in the fasting state. The overall CVD risk is increased in overt hypothyroidism (OH) and possibly in subclinical hypothyroidism (SCH). LDL-Cholesterol (LDL-C) is increased in OH but not SCH, which may partly explain the increased CVD risk in OH, but likely does not entirely explain it. It is not consistently clear what happens to triglyceride and HDL-Cholesterol (HDL-C) in OH and is even less clear in SCH. Hence, our hypothesis for the Thyroid study: Postprandial dyslipidaemia is associated with lipoprotein derangements that may contribute to the increased cardiovascular risk observed in hypothyroidism in addition to that conferred by fasting LDL-C concentrations ? To examine fasting and postprandial HDL-C metabolism in both OH and SCH in an effort to elucidate the differences observed between OH and SCH. In order to test these hypotheses, a clinical study was undertaken. The thyroid study was a cross-sectional study with 21 OH, 28 SCH and 44 controls. Plasma lipids with particular emphasis on intestinally derived lipoproteins (ApoB48), HDL cholesterol (HDL-C) and endothelial function, as assessed by flow-mediated dilatation (FMD) of the forearm were measured fasting and postprandially. The original findings of these studies are that ApoB48 was increased postprandially in OH and to a lesser degree in SCH compared to a matched control group. FMD was decreased in OH only. In addition, HDL-C was significantly lower postprandially in SCH only and CETP associated HDL-C was decreased in OH, which may account for the preserved HDL-C observed in this cohort. In conclusion, postprandial lipoprotein and vascular abnormalities differ between OH and SCH. Although both are characterized by increased intestinally derived lipoprotein particles, HDL is reduced only in SCH. Maintained HDL in OH probably reflects reduced CETP activity, which was not observed in SCH. Postprandial endothelial dysfunction is abnormal only in OH and this effect does not appear to reflect increased inflammation. These findings give additional insight into the pathophysiology of CVD associated with hypothyroidism. The overall CVD risk is increased in type 1 diabetes mellitus (T1DM) and individuals with T1DM have accelerated atherosclerosis. Endothelial dysfunction precedes the development of atherosclerosis. Yet, in the presence of good glycaemic control, individuals with T1DM have a relatively preserved fasting and even favourable lipid profile. It is not known to what extent postprandial lipoprotein changes contribute to the increased CVD risk. Hence, our hypothesis for the T1DM study: Postprandial dyslipidaemia is associated with lipoprotein derangements and endothelial dysfunction that may contribute to the increased cardiovascular risk observed in T1DM. Elucidate what glucometabolic and lipoprotein factors affect endothelial dysfunction in T1DM. In order to test these hypotheses, a clinical study was undertaken. The T1DM study was a cross-sectional study with 20 T1DM and 24 controls. Additional controls subjects (n=98) were studied to further explore variables associated with endothelial function. Plasma glucose and lipids with particular emphasis on intestinally derived lipoproteins (ApoB48) and endothelial function, as assessed by flow-mediated dilatation (FMD) of the forearm were measured fasting and postprandially. The original findings of these studies are that ApoB48 was increased fasting and postprandially in T1DM only. Fasting FMD did not differ between groups but decreased significantly postprandially in T1DM subjects only. Analysis of the matched group (n=44) and the pooled data (n=142) revealed a positive correlation between peak glucose concentration and overall percentage FMD change and an inverse correlation between AUC HDL-C and percentage postprandial FMD change. To conclude, postprandial lipoprotein and vascular abnormalities differ in T1DM compared to matched controls, resulting in endothelial dysfunction. These changes are possibly mediated through postprandial glucose excursions and maybe attenuated by HDL-C.