Insulin resistant diabetes mellitus in SHORT syndrome: case report and literature review

SHORT syndrome is a rare developmental disorder frequently associated with growth failure and insulin resistant diabetes mellitus (IRDM). Since GH has diabetogenic effect, therapy been regarded as contraindication. We observed Brazilian girl who received from 4 6/12 years of age for SGA short stature. dosage was increased 0.23 to 0.36 mg/kg/week, but statural response remained poor. Her blood HbA1c level, though it 5.5–6.0% in childhood, began elevate puberty 9.2% at 10 age, despite the discontinuation 9 11/12 age. Laboratory studies indicated antibody-negative IRDM. She treated metformin canagliflozin (a sodium glucose co-transporter 2 (SGLT2) inhibitor), which ameliorated overt diurnal hyperglycemia mild nocturnal hypoglycemia reduced her around 7%. Whole exome sequencing revealed de novo heterozygous pathogenic variant (c.1945C>T:p.(Arg649Trp)) PIK3R1 known sole causative gene syndrome. Subsequent literature review patients molecularly confirmed development IRDM 15 GH-untreated aged ≥12 none three GH-treated six ≤10 years. These findings imply critical role pubertal and/or advanced rather than IRDM, usefulness SGLT2 inhibitor treatment