We report a 69 year old female diagnosed, age 33 years, with type 2 diabetes following delivery of a macrosomic baby. Whilst initially managed by diet alone, she was subsequently prescribed anti-diabetic therapy (metformin, gliclazide and pioglitazone). She has no microvascular or macrovascular complications, a normal BMI and a persistently stable, but suboptimal HbA1c of 6.9 - 7.6%. She has a strong family history of diabetes with both parents and 4/6 siblings affected. She had 5 daughters, the eldest of whom was diagnosed with gestational diabetes aged 28 years. The youngest two daughters were diagnosed with type 2 diabetes (ages 29 and 30 years). Her fourth daughter’s diabetes was usually metformin treated, but she required insulin in her two pregnancies. Screening tests for latent autoimmune diabetes of adults (LADA) were negative. Her original OGTT demonstrated a low increment with mild fasting hyperglycaemia (7.1 mmol/L) and 8.8mmol/L at 2hr. Due to this and the strong family history, she underwent genetic testing in pregnancy for maturity-onset diabetes of the young (MODY). This demonstrated a heterozygous GCK (glucokinase) gene mutation (c.1019+1G>A). Cascade testing of her youngest sister and the index patient (their mother) demonstrated the same mutation, confirming the diagnosis of MODY-2, subtype glucokinase not type 2 diabetes.
MODY-2 results in insensitivity of the beta cell to plasma glucose resulting in a mild defect in insulin secretion and a higher glycaemic ‘set-point’. This leads to lifelong, mild and stable hyperglycaemia with minimal risk for complications and generally no requirement for pharmacotherapy. Therefore, the index patient was able to reduce her oral anti-diabetic agents without deterioration in her blood glucose levels. This change in treatment resulted in significant cost savings for the patient and protection from unnecessary treatment-related adverse events (hypoglycaemia, weight gain).
The diagnosis also has significant implications for her daughters’ management including management throughout pregnancy.