Variation in hypoglycemia ascertainment and report in type 2 diabetes observational studies: a meta-epidemiological study

INTRODUCTION: Observational studies constitute an important evidence base for hypoglycemia in diabetes management. This requires consistent and reliable ascertainment and reporting methodology, particularly in studies of type 2 diabetes where hypoglycemia risk is heterogeneous. Therefore, we aimed to examine the definitions of hypoglycemia used by observational studies of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a meta-epidemiological review of observational studies reporting on hypoglycemia or evaluating glucose-lowering medications in adults with type 2 diabetes. MEDLINE and Google Scholar were searched from January 1970 to May 2018. The definitions of non-severe, severe and nocturnal hypoglycemia were examined. RESULTS: We reviewed 243 studies: 47.7% reported on non-severe hypoglycemia, 77.8% on severe hypoglycemia and 16.9% on nocturnal hypoglycemia; 5.8% did not specify. Among 116 studies reporting non-severe hypoglycemia, 18.1% provided no definition, 23.3% used glucose values, 38.8% relied on patient-reported symptoms, 17.2% accepted either glucose values or patient-reported symptoms and 2.6% relied on International Classification of Disease (ICD) codes. Among 189 studies reporting severe hypoglycemia, 11.1% provided no definition, 53.4% required symptoms needing assistance, 3.7% relied on glucose values, 14.8% relied on ICD codes, 2.6% relied on ICD codes or glucose values and 15.9% required both symptoms needing assistance and glucose values. Overall, 38.2% of non-severe and 67.7% of severe hypoglycemia definitions were consistent with the International Hypoglycemia Study Group. CONCLUSIONS: The marked heterogeneity in how hypoglycemia is defined in observational studies may contribute to the inadequate understanding and correction of hypoglycemia risk factors among patients with type 2 diabetes.