Is Hypoglycemia Caused by G6PD Deficiency?

Background: Individuals with G6PD deficiency are mostly asymptomatic but develop hemolytic anemia with the use of certain medications, chemicals, or food. Hemolytic anemia episodes in patients with G6PD deficiency have been observed to occur following hypoglycemia. Case: An 18-year-old, vigorously exercising African American male was referred to the endocrine clinic for post-prandial hypoglycemia (Blood glucose (BG) of 47 mg/dl) accompanied by palpitations, lightheadedness, dyspnea, diaphoresis, and tremulousness. He admitted to having short symptomatic episodes, almost daily over four years. His mother has sickle cell trait, and due to the need for blood typing, a qualitative direct fluoroscopic screening test was positive for G6PD deficiency. Physical examination revealed a height of 5’2” with a weight of 126 lbs. (BMI: 22.7 kg/m2), blood pressure of 97/55 mmHg, and heart rate of 62/minute. The patient was a normal male with low set ears, and no other abnormalities, except for questionable non-genetic short stature. Fingerstick BG was 62 mg/dl. Lab tests showed a fasting BG of 90 mg with concomitant proinsulin of 8.2 pmol/l (≤ 18.8 pmol/l), fasting insulin of 8.98 mIU/l (≤ 25 mIU/l), 2-hour post-prandial insulin of 33.4 µIU/ml (5.0–55.0 µIU/ml), and a c-peptide 1.24 ng/ml (0.81–3.85 ng/ml). Uric acid, TSH, Free T4, LH, FSH, Prolactin, IGF-1, PTH, free and total testosterone were all normal. Fasting cortisol level was normal with an elevated ACTH of 72 pg/ml (0–47 pg/ml), low 25-hydroxyvitamin D at 18.5 ng/ml (30–100 ng/ml), and a flat oral glucose tolerance test. A continuous glucose monitor revealed average daily glucose of 85 mg/dl with 34% of the time spent < 80 mg/dl. A high carbohydrate diet with frequent meals improved symptoms with normal fingerstick BG. However, due to the concern that hypoglycemia can be related to G6PD deficiency, hemoglobin electrophoresis, and gene testing for G6PD were done to confirm this diagnosis, and they were both normal. In addition, a bone density scan was done, which revealed osteopenia. He was started on vitamin D supplementation. Conclusion: Case reports exist of G6PD deficient hospitalized patients with type 1 diabetes mellitus and DKA in recovery, who have had new onset hemolytic anemia, proposing that relative hypoglycemia can be responsible for this effect. Multiple screening tests have been developed for the detection of G6PD deficiency, which assay the normal function of the enzyme and reduction of NADP to NADPH. However, confirmatory testing needs to be conducted if the screening test is positive. Although this adds to the burden of testing, screening tests can result in false positives and lead to a misdiagnosis, as in our case. References: Messina MF et al. Hemolytic crisis in a non-ketotic and euglycemic child with glucose-6-phosphate dehydrogenase deficiency and onset of type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2004 Dec;17(12):1671–3