Abstract Introduction Atypical forms of diabetes, encompassing entities beyond type 1 and type 2, remain underrecognized. In younger individuals, timely identification and individualized treatment are particularly crucial, as they can significantly alter clinical trajectories and long-term outcomes. Clinical Case We present a 30-year-old Asian woman who developed diabetes at age 16 and was referred for evaluation 10 months postpartum. She has multigenerational history of diabetes, BMI 25.9 kg/m²; height 155cm, weight 62.2 kg, and no autoimmune disease history. There were no known history of maternal hearing loss nor familial renal cysts. She tolerated metformin for 5 years after initial diagnosis but later discontinued due to diarrhoea. During pregnancy, glycaemic control was achieved with isophane and rapid-acting insulin; however, post-natally she was transitioned to basal-bolus insulin (glargine 40 units and aspart 20–28 units) alongside oral agents including gliclazide, linagliptin, and dapagliflozin. Despite this, glycaemic control was suboptimal (HbA1c 63 mmol/mol). On clinical review, lipodystrophy was noted at injection sites. She denied having hearing problems. She tested negative for diabetes antibodies and had a preserved C-peptide level (1.06 ng/ml). Her MODY probability (Exeter score) was 75.5%. Genetic testing confirmed m.3243AG mitochondrial diabetes with 34% heteroplasmy. Following diagnosis, targeted therapy with empagliflozin and semaglutide led to significant improvement in glycaemic control and reduced insulin requirements (Figure) While the genetic diabetes diagnosis explained her diabetes atypical presentation, systemic investigations were done as the clinical course remains unpredictable due to phenotypic variability, which is likely influenced by the degree of heteroplasmy in specific target tissues. Her audiology assessment revealed mild sensorineural hearing loss. Cardiac screening (ECG and echocardiogram), renal function and retinal examination were normal. She also reported symptoms of polyarthropathy and peripheral neuropathy. Rheumatology and neurology assessments showed normal autoimmune markers and unremarkable lumbar puncture, CT head, and MRI head studies. Nerve conduction studies and EMG confirmed mild distal sensory axonal neuropathy with small fibre involvement, restricted to the lower limbs. She is currently awaiting further neurology assessment at a tertiary centre. Genetic counselling was offered to the patient and family. Conclusion This case highlights the precision diabetes diagnosis allows for tailored treatment and improves the patient’s outcomes. As research into atypical forms of diabetes advances, this individualized approach holds the potential to revolutionize diabetes management on a larger scale, paving the way for the integration of genomic medicine into routine clinical practice.Figure 1:Continuous freestyle Libre glucose monitoring
Aung et al. (Thu,) studied this question.