Poster Presentation International Association of the Diabetes and Pregnancy Study Groups 2022 - Hosted by ADIPS

Pre-pregnancy planning in a woman with diabetes mellitus secondary to familial partial lipodystrophy type 3 (#88)

Joanna Y Gong 1 , Rahul Barmanray 1 , Alison Nankervis 2 , Sarah Price 2 , Alison Trainer 3 , Jennifer Conn 2
  1. Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Parkville, Victoria, Australia
  2. Diabetes Service, Royal Women's Hospital, Parkville, Victoria, Australia
  3. Adult Genetic Service, Royal Melbourne Hospital, Parkville, Victoria, Australia

Case

A 30-year old former elite gymnast was referred to a tertiary maternity hospital for pre-pregnancy planning with “complex type 1 diabetes mellitus (DM)” of 10 years duration. 

At presentation, the patient’s HbA1c was 6.5%. She was taking gliclazide MR 60mg and empagliflozin 25mg daily with dulaglutide 1.5mg weekly. Metformin had been used but was ceased due to limited efficacy. She was injecting pre-mixed insulin 20 units bd but had previously been administering up to 400 units of insulin daily at a time when her HbA1c was 10.3%. There was dramatic improvement in glycaemic control when dulaglutide was introduced with concurrent reduction in insulin dosage. Further improvement occurred after transitioning to semaglutide as a GLP-1 agonist.  

Notably, the patient was diagnosed with non-alcoholic fatty liver disease (NAFLD) at age 15. She had no diabetes complications but had a number of co-morbidities including hypothyroidism and chronic back pain. On examination, her body mass index (BMI) was 27.3kg/m2.  On investigation, the C-peptide level was elevated at 2.52 nmol/L paired with a glucose level of 6.5 mmol/L.

The presentation was not consistent with type 1 DM nor was it typical of type 2 DM. A monogenic cause of DM associated with severe insulin resistance was hypothesised. On genetic testing, the patient was heterozygous for a pathogenic PPAR gamma gene variant. This correlates with a clinical diagnosis of familial partial lipodystrophy (FPLD) type 3.

 

Discussion

FPLD type 3 due to a PPAR gamma gene variant is extremely rare. It is one of a group of familial partial lipodystrophies that lead to altered body fat distribution, sometimes resulting in a Cushingoid appearance. FPLD type 3 is associated with multi-system complications including DM, NAFLD, hypertriglyceridemia and atherosclerotic cardiac disease.1 A BMI ≤27 kg/m2 with >100 units of insulin/day increases the likelihood of identifying lipodystrophy.2

We identified only two case reports of pregnancy in women with FPLD type 3. Both described poor obstetric outcomes.3,4 For our patient, optimising management for pregnancy presents a significant challenge. Semaglutide has been highly effective for glucose lowering but is not approved for use in pregnancy. There are reports of three women conceiving on semaglutide in the SUSTAIN 1-6 trials. No congenital abnormalities were reported, although fetal exposure likely occurred for <9 weeks. Our current challenge is how to manage pregnancy when prescribing metformin and insulin would create a suboptimal glycaemic response thus exposing the fetus to the known effects of hyperglycaemia.

  1. Akinci B, Onay H, Demir T, et al. Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy. Metabolism 2017;72:109-119.
  2. Visser ME, Kropman E, Kranendonk ME, et al. Characterisation of non-obese diabetic patients with marked insulin resistance identifies a novel familial partial lipodystrophy-associated PPARγ mutation (Y151C). Diabetologia 2011;54:1639-1644.
  3. Castell AL, Hieronimus S, Lascols O, et al. Vascular placental abnormalities and newborn death in a pregnant diabetic woman with familial partial lipodystrophy type 3: A possible role for peroxisome proliferator-activated receptor γ. Diabetes Metab J 2012;38:367-369.
  4. Madhra M, Noh RM, Zammitt NN, et al. A complicated pregnancy in a patient with lipodystrophic diabetes attributable to a peroxisome proliferator‐activated receptor gamma (PPARG) mutation. Diabet Med 2012;29;e398-e401.