Background: Severe hypertriglyceridaemia (triglycerides >22.4mmol/L) in diabetic ketoacidosis (DKA), known as diabetic lipaemia is associated with increased morbidity and mortality. The hydrolysis of triglycerides to free fatty acids is catalysed by lipoprotein lipase (LPL), which is regulated by insulin. We previously reported a case of extreme diabetic lipaemia associated with a mutation in the LPL gene (1). We hypothesized that combined LPL and insulin deficiency causes most cases of diabetic lipaemia.
Aims: To determine if patients with diabetic lipaemia have reduced LPL concentrations and/or mutations in LPL or its cofactor APOC2.
Methods: We conducted a case-control study involving two tertiary care hospitals in Adelaide, SA. 6 cases admitted to hospital with diabetic lipaemia and 12 age- and sex-matched controls with DKA (glucose >15mmol/L, bicarbonate <15mmol/L and ketosis) and peak triglyceride concentrations <2.4mmol/L were recruited. Subjects were well at the time of study investigations. Plasma LPL concentrations were measured post-heparin. The coding regions of LPL and APOC2 genes were sequenced.
Results: The mean LPL concentration post-heparin was lower in patients with diabetic lipaemia than controls (306 vs 484μg/L, P=0.04). One case had a loss of function mutation in LPL and no functional mutations in APOC2  were identified. The mean fasting C-peptide concentration was higher in cases than in controls (771 vs 50 mmol/L, P=0.001).
Conclusions: Severe hypertriglyceridemia in DKA is associated with LPL deficiency. LPL deficiency is usually quantitative, rather than secondary to mutations in LPL or its cofactors. The majority of patients with diabetic lipaemia may have ketosis prone Type 2, rather than Type 1 Diabetes.

Reference
1. McLean AG et al. Extreme diabetic lipaemia associated with a novel lipoprotein lipase gene mutation. ClinChimActa.2009;406:167-9.