Diabetes mellitus in SHORT syndrome managed with multi-agent oral therapies: a case report and literature review

ABSTRACT

SHORT syndrome is a rare genetic multisystemic disorder caused by a loss-of-function mutation in the phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) gene. The disease's acronym represents its key features: short stature, hyperextensibility, ocular depression, Rieger anomaly, and teeth delay. Insulin resistance, hyperglycemia, and diabetes mellitus are common endocrinological manifestations of this condition. Currently, there are no established guidelines for the treatment of diabetes in SHORT syndrome patients. In this report, we describe a young adult male patient of Chinese descent with atypical diabetes mellitus associated with SHORT syndrome. This case was challenging due to the patient's young-onset diabetes and poor diabetes control, complicated by insulin resistance from lipodystrophy, and a strong aversion to insulin injections. By utilizing a combination of oral anti-glycemic agents with complementary mechanisms of action (metformin, sodium-glucose co-transporter 2 (SGLT-2) inhibitors, sulfonylureas, thiazolidinediones, and GLP-1 agonists), insulin therapy was delayed. The patient's blood glucose levels improved significantly, with HbA1c decreased from 14% to 8.8% within 6 months of starting the multi-agent regimen, and further improved to 7.4% with a fasting plasma glucose of 4.8 mmol/L. With an oral medication regimen that the patient found acceptable, both his quality of life and adherence to treatment improved. These findings provide useful insights into tailoring an individualized diabetes treatment plan.