ESPE Abstracts

Case report: 14 yrs. old Hispanic girl was referred for evaluation of diabetes (Hb A1c 9.8 %) and morbid obesity BMI 36 kg/m2. She developed acanthosis nigricans, elevated triglycerides (TG) 1162 mg/dl, low HDL 34 mg/dl, fatty liver with elevated AST 84 U/l, ALT 103 U/L. The abdominal sonogram revealed significant hepatomegaly with moderate steatosis. Her islet cell AB were negative, C-peptide 3.11 ng/ml was normal. She has a strong family history of diabetes: mother, maternal aunt, uncle and maternal grandmother. She was treated with Glyburide 10 mg twice a day, metformin 1000 mg twice a day, Victoza 1.8 mg daily, Gemfibrozil 600 mg twice a day, Omega 3 1000 mg daily. After 1 year of treatment BMI decreased to 31.6 3 kg/m2, Hb A1c improved to 6.7 %, TG decreased to 144 mg/dl, HDL 34 mg/dl, LDL 115 mg/d, ALT18 U/l, AST 14 U/L. All medications were discontinued except Metformin. Dexcom sensor readings confirmed glucose level in the normal range on Metformin treatment.

Results: Genetic analysis identified heterozygous polymorphism in Glucokinase gene GCK c.1033C> G (P.Arg345Gly). This sequence change replaces arginine with glycine at codon 345 of the GCK protein (P.Arg345Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GCK-related conditions. ClinVar contains an entry for this variant (Variation ID: 987827).

Discussion: Glucokinase MODY 2 is usually suspected in nonobese patients without signs of insulin resistance, with mild fasting hyperglycemia, normal C-peptide, negative β-cell antibodies, and associated with a positive family history of diabetes. In our case after BMI improved from 36 to 31.6 kg/m2, the severity of diabetes improved and only Metformin was enough to keep glucose level in the normal range. MODY 2 with obesity was described before. But this is the first case when obesity with MODY 2 was complicated with severe diabetes, with dramatic improvement in HB a1c after moderate weight loss.

Conclusion: Genetic analysis in cases of diabetes is important for individualized treatment and understanding of the natural history of diabetes.

References:

1. Hyperglycemia in pediatric age: could it be maturity onset diabetes of the young? Case reports and review of the literature. Mafalda Cascais et al. Ann Pediatr Endocrinol Metab, 2019 Dec;24(4):262-266.