Endocrine Abstracts

Case history: A 25 year old primigravid woman was referred through to the Joint Antenatal clinic with a 15-year history of Diabetes Mellitus Type 2 treated with metformin. Her past medical history included polycystic ovarian syndrome, (causing significant hirsutism and amenorrhoea), non-alcoholic fatty liver disease, dyslipidaemia and hypertension (previously investigated for secondary causes). Her HbA1c was well controlled at 30 mmol/mol, and her Metformin had been discontinued. Due to her lack of adipose tissue, muscular appearance and diabetes-onset at a young age, a differential diagnosis of a lipodystrophy syndrome was considered.

Investigations: Initial investigations demonstrated raised triglycerides of 9.06 mmol/l, insulin level 109 pmol/l, a C-peptide level of 949 pmol/l and a random glucose 3.9 mmol/l. She was referred to the National Insulin Resistance team.

Results and treatment: Further investigations showed Leptin levels returned as 5.7 ug/l (normal as her BMI was below 25), however she was found to have a heterozygous missense mutation of her PPARG gene, giving a diagnosis of familial partial lipodystrophy. This diagnosis not only explains the early-onset of her diabetes but also her co-morbidities of PCOS, hypertension and dyslipidaemia. Due to this diagnosis she was referred through to the National Severe Insulin Resistance Service at Addenbrooke’s Hospital for further specialised treatment and family genetic counselling.

Conclusions and points for discussion: There are a number of interesting aspects to this lady’s case. Her diagnosis of Diabetes Mellitus Type 2 was made at a very young age, and she had this diagnosis for 15 years before further investigation was triggered. Phenotypical lack of adipose tissue in heterozygous individuals is partial and may only become evident following puberty. A diagnosis of familial partial lipodystrophy may therefore elude clinicians, often for many years. This highlights the importance of considering differentials when meeting a patient for the first time, irrespective of the duration of prior diagnosis, especially in atypical cases which do not fit typical cases of Diabetes Mellitus Type 1 or Type 2 or MODY and of young onset. In spite of a borderline leptin level, her genetic tests confirmed a result of partial lipodystrophy, which has unified all her pre-existing conditions under one signal diagnosis. This will now allow her to go on and have more targeted treatment and genetic counselling for her wider family and her new born child, who has a 50% chance of having the condition also.