GSD1 is characterized by severe fasting hypoglycemia because of the lack of G6Pase-α, but several studies have indicated that patients could demonstrate glucose production [
3‐
5]. This recovery may be related to the widespread G6Pase-β expression in the body [
6]. GSD-Ia children show hypoglycemia, but with age, their endogenous glucose production rate improves, starting from 50% of the normal in young GSD-Ia patients, reaching 67–100% of the normal in adult GSD-Ia patients [
3‐
5]. Because muscle mass increases with age, forming 20% of the body weight in a newborn, 36% in adolescence, and 40–45% of adulthood [
6], the muscle G6Pase- β/G6PT complex may be the source of some or all of the extra blood glucose. Upon undergoing such an age-related change in the muscle volume as well as visceral fat and due to fatty liver and increased BMI because of frequent feeding, patients show insulin resistance and their blood glucose level dynamics are similar to those in type 2 diabetes. The reason for glucose resistance and hyperglycemia in GSD type Ia is unclear, but seems to be caused by frequent feeding, night time feeding, raw cornstarch, body weight gain, liver dysfunction, and renal dysfunction, all of which could cause insulin resistance and abnormal endogenous glucose production. Frequent hypoglycemia could also induce (1) downregulation of insulin/glucagon ratio leading to the release of free fatty acids, and (2) stimulation of glycogenesis in the liver leading to increased malonyl Co A and inhibition of beta oxidation. Fatty liver in GSD type Ia is also thought to be caused by these mechanisms [
7]. In contrast, excessive carbohydrate, which is needed to prevent hypoglycemia, is stored as glycogen in the liver, causing non-alcoholic fatty liver disease (NAFLD). It is reported that 69.8% of patients with NAFLD presented a glucose intolerance pattern [
8]. In our patient, NAFLD/NASH since teenage and body weight gain were undoubtedly related to insulin resistance. Therefore, she was treated with an SGLT2 inhibitor, which could inhibit glucose reabsorption in the proximal renal tubule, release excessive glucose into urine and correct the plasma glucose levels. In addition, hypoglycemia is not expected because SGLT1 is still active and capable of preventing hypoglycemia. Preclinical studies indicate that the SGLT2 inhibitor could reduce insulin resistance, visceral fat, and body weight. A large clinical study in the UK (DAPA-HF study) indicated that the SGLT2 inhibitor could reduce the risk of cardiovascular death [
9]. Another global clinical trial (DAPA-CKD Study, Phase III) indicated that an SGLT2 inhibitor (dapagliflozin) reduced the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes [
10]. Further, A prospective, single-arm trial (LEAD trial) indicated that Luseogliflozin could be a novel promising agent for treating patients with T2DM and NAFLD [
11].
In our case, the SGLT2 inhibitor showed good performance in suppressing the dumping syndrome-like symptoms mainly by alleviating hyperglycemia after feeding. In hypoglycemia, the SGLT2 inhibitor could reduce episodes of hypoglycemia and decrease between-meal eating, which may cause loss of body weight. Laboratory data related to NAFLD/NASH remained unchanged after intervention, but we consider that these may require a long-term treatment for improving.