Endocrine Abstracts

Background: Severe hypertriglyceridemia (HT) increases the risk of pancreatitis, whereas mild HT may be a risk factor for cardiovascular disease. The variety of hypertriglyceridemia origins often makes the etiological diagnosis complex.

Case report: A 24-year-old female G3P0Ab2 with type 1 diabetes mellitus (T1DM) was referred at 27th week of gestation to the Endocrinology Department in July 2017 for glycemic instability and severe hypertriglyceridemia. Type 1 diabetes was diagnosed at the age of 9 on initial diabetic ketoacidosis. AntiGAD antibodies remained 4 UI/l (N<1 UI/l) during follow-up, C-peptide and insulin undetectable. After puberty the patient developed progressive lipoatrophy of the trunk, abdomen and limbs together with moderate cervico-facial fat accumulation and axillary acanthosis nigricans. BMI prior to pregnancy was 21 kg/m². Long term glycemic control was insufficient (HbA1c 10–14%) under multiple daily injection despite high total daily insulin dose (TDI) 188 u/d (2.9 U/kg/d). Patient refused continuous subcutaneous insulin infusion (CSII). Medical history included humeral artery thrombosis under estrogen containing contraceptives in 2010 and embolic myocardial infarction in 2011. Oncological, rheumatic, thrombophilia markers were negative. Long term anticoagulant medication combined with rosuvastatine 10mg per day were introduced as LDL-cholesterol (LDLc) was 153 mg/dl, HDL-cholesterol (HDLc) 28mg/dl, triglyceride (TG) 192 mg/dl. Statin was stopped during pregnancy. At presentation, TG level was 810 mg/dl, LDLc 109 mg/l, HDLc 36 mg/dl, urinary protein-to-creatinine ratio 123 mg/mmol, haemoglobin 7.2 g/dl requiring a blood transfusion. Diabetic retinopathy evolved during pregnancy from moderate to severe. Despite a very low-fat diet (<10–15% of energy intake), TG level reached up to 1200 mg/dl at 30 week of gestation. CSII was introduced allowing tight glycemic control and the reduction of the TDI from 136 U/d (2 U/kg/d) to 90 u/d (1.3 u/kg/d). TG were stabilized at 1080mg/dl. At 38 weeks caesarean delivery was performed and a healthy girl was delivered. Face to the complex presentation, a genetic analysis was performed. LMNA sequencing revealed heterozygous prelamin-A mutation (p.T655fsX49). The search for a HT predisposing mutation showed heterozygous APOC2 variant (c.122A>C, p.K41T) and heterozygous GP1HBP1 variant (c.41G>T, p.C14F) that increase HT. A heterozygous LPL variant known to increase its activity (c.1421C>G, p S474X) was also found.

Conclusion: Severe hypertriglyceridemia can develop in poorly controlled T1DM during pregnancy; however atypical presentation should encourage further investigation including genetic analysis. In our case T1DM was associated with Dunningan’s syndrome and genetic predisposition to HT, leading to specific therapeutic and care implications.