SGLT2 inhibition alleviated hyperglycemia, glucose intolerance, and dumping syndrome-like symptoms in a patient with glycogen storage disease type Ia: a case report

Abstract

Background Glycogen storage disease (GSD) type Ia is a glycogenesis disorder with long-term complications such as hepatomegaly and renal dysfunction and is caused by congenital loss of glucose-6-phosphatase (G6Pase) expression. G6Pase is essential for the final step of gluconeogenesis and glycogenolysis, and its deficiency causes clinical hypoglycemia in the fasting state during infancy. Contrastingly, patients also show blood glucose trends and glucose intolerance similar to those in type II diabetes. Owing to the contrasting presentation of hypoglycemia with glucose intolerance, glucose control in patients remains a challenge, requiring management of both fasting hypoglycemia and post-prandial hyperglycemia. Case presentation The patient was a 45-year old Asian (Japanese) woman who showed disease onset at 3 years of age, when hypoglycemia and hepatomegaly were observed, and GDS type Ia was diagnosed by the lack of G6Pase activity. Over the past 45 years, she presented hyperglycemia and dumping syndrome like symptoms (a feeling of fullness, even after eating just a small amount, abdominal cramping, nausea, sweating, flushing, or light-headedness and rapid heartbeat) at 2 hours after food intake. Her liver and kidney dysfunction also worsened over time. Treatment with exercise combined with a sodium-glucose co-transporter 2 inhibitor and an alpha glucosidase inhibitor alleviated her glucose intolerance and dumping syndrome-like symptoms, without increasing hypoglycemic events. Conclusion This case suggests SGLT2 inhibitor as a promising candidate for treating glucose intolerance in GSD type Ia without worsening of hypoglycemia.

Diabetes in a Patient with Glycogen Storage Disease Type 1a

“…Previously, GSD-1a was reported to cause insulin resistance owing to the accumulation of G6P in the liver, which causes de novo lipid production, leading to fatty liver (7). In previous reports of GSD-1a combined with impaired glucose tolerance, obesity and hyperinsulinemia have been associated (3,8). However, obesity was not observed in the present case.…”

Dumping Syndrome in Children: A Narrative Review

“…However, the main accepted mechanism for lowering blood glucose is by suppressing the renal SGLT-2 and, thus, increasing the urinary glucose excretion. It holds back glucose reabsorption in the proximal renal tubule, releases excessive glucose into the urine, and corrects the plasma glucose levels alleviating hypoglycemic symptoms [19,20]. On top of that, they work on reducing episodes of hypoglycemia by activating SGLT-1.…”