Characterization of Spontaneous Severe Hypertriglyceridemia in Diabetic Nonhuman Primates

Severe hypertriglyceridemia is a condition where serum triglyceride levels increase above 500 mg/dl. Severe hypertriglyceridemia may result from primary (genetic defects in triglyceride metabolism) or may occur secondary to a high fat diet, excess alcohol consumption, obesity or type 2 diabetes. Severe hypertriglyceridemia has serious consequences for the development of coronary artery disease, pancreatitis and glomerulonephritis. In mice, diet‐induced hypertriglyceridemia and transgenic models of hyperlipidemia have been used to investigate the pathophysiology and associated co‐morbidities induced by hypertriglyceridemia. None of these models has, however, reproduced either severe hypertriglyceridemia (triglyceride levels above 1000mg/dl) or the co‐morbidities associated with the human condition. In the present study of 173 adult genetically unrelated nonhuman primates, ingesting only a low fat diet, we have characterized the progression of hypertriglyceridemia using the ATP National Cholesterol Education Program classifications: normal <150 mg/dl; borderline‐high 150–199; high 200–499; very high >500 mg/dl. This progression of hypertriglyceridemia was found to increase in parallel to the progression of metabolic syndrome to prediabetes and overt, then severe diabetes in the nonhuman primates. Ninety‐nine monkeys were normal, and the elevated triglyceride groups had respective means of 176.9 ± 23.6 mg/dl (N=15); 275.4±40.5 mg/dl (N=34); and 643.5 ± 43.4 (N=25). In addition, 8 monkeys had naturally occurring very severe hypertriglyceridemia (1000–4000 mg/dl). Hypertriglyceridemia was significantly correlated with HbA1c% (r 2 =0.2564). Further analysis of serum lipase and amylase levels showed increased levels of lipase in overt diabetes (57.7 ± 3.5 U/L). This is the first report showing the development of spontaneous severe hypertriglyceridemia in prediabetic and diabetic rhesus macaques and associated increased serum lipase levels. Characterization of this nonhuman primate model of naturally‐occurring severe hypertriglyceridemia provides a spontaneously occurring and ideal animal model for understanding the pathophysiology of severe hypertriglyceridemia and for evaluating therapeutic interventions.