Late Reactive Hypoglycemia (RHG) as a Common Early Sign of Glycemic Dysfunction in Obese Adolescent Girls

Many obese adolescent girls describe symptoms of hypoglycemia, but this has not been systematically assessed. Due to pubertal insulin resistance (IR), hormonal responses to an oral glucose tolerance test (OGTT) may occur beyond the typical 2h sampling interval. We sought to determine how often reactive hypoglycemia (RHG) occurs in these girls. 56 girls aged 12-20 years, BMI percentile ≥ 90th, were enrolled in a study including fasting metabolic labs and a 6h OGTT with frequently sampled glucose, C-peptide, insulin, GLP-1 and glucagon. RHG was defined as a blood glucose (BG) < 70 mg/dL with a ≥ 20 mg/dL drop from the previous sample. Comparisons between those with and without RHG were performed with a Student’s t-test. 50% of girls had BG <70mg/dL (mean nadir was 62 mg/dL); 18% were <65 mg/dL and 12% < 60 mg/dL. The median time for lowest BG was 240 min (range 210-360 min) after the glucose load. Girls with RHG were slightly younger (15.1±1.8 vs. 16.2±1.5 years; p=0.02). The groups had similar BMI percentile (97.8 vs. 96.8) and percent fat mass, but tended to have more visceral fat (10.1% vs. 8.1%; p=0.08). Fasting glucose and insulin were not different between groups, but HOMA-IR tended to be higher in RHG (7.0±5.4 vs. 4.9±2.2, p=0.07). The area under the curve of insulin and glucose for the first 180 min of the OGTT was higher in RHG (p=0.01 and p=0.04, respectively), with impaired glucose tolerance tending to be more frequent in RHG (63% vs. 40%; p=0.08). The mean insulin peak for the RHG was at 150 min, vs. 30 min post-drink in the normal group. At 240 min, glucagon tended to be higher in RHG (81 vs. 67 pg/ml; p=0.06). RHG defined as a BG <70 mg/dL following a rapid drop, is common in girls with obesity in response to liquid sugar, and occurs later than detectable with a standard 2h OGTT. RHG appears to be secondary to an overly robust, late insulin response. This pattern is likely related to IR, may precede further dysglycemia and may be severe enough to cause a counter regulatory response, arguing to avoid consuming liquid sugar in isolation.