Glycated hemoglobin levels are mostly dependent on nonglycemic parameters in 9398 Finnish men without diabetes

Context: Determinants of the variance in glycated hemoglobin (HbA1c) among individuals without type 2 diabetes remain largely unknown. Objective: We investigated the determinants of HbA1c, fasting plasma glucose, and 2-hour glucose in an oral glucose tolerance test and the associations of these glycemic markers with insulin sensitivity and insulin secretion in Finnish men without type 2 diabetes. Design and Setting: The design and setting were the cross-sectional population-based Metabolic Syndrome in Men study including 10 197 Finnish men, aged 45-70 years, and randomly selected from the population register of Kuopio, Eastern Finland. Participants: Participants were a total of 9398 men without type 2 diabetes or with newly diagnosed type 2 diabetes at baseline (mean age 57 ± 7 y; body mass index 27.0 ± 4.0 kg/m², mean ± SD) in the Metabolic Syndrome in Men study cohort. Interventions: The intervention included an oral glucose tolerance test. Main Outcome Measures: Glycemic and nonglycemic determinants of the variance in HbA1c among participants without type 2 diabetes and the association of HbA1c with insulin secretion and insulin sensitivity were measured. Results: Age, fasting plasma glucose, and high-sensitivity C-reactive protein were the strongest determinants of HbA1c, explaining 12% of the variance in HbA1c levels in participants without type 2 diabetes. Disposition index (insulin secretion) and the Matsuda insulin sensitivity index (insulin sensitivity) explained only less than 2% of the variance in HbA1c in the participants without type 2 diabetes. Conclusions: The variance in HbA1c among men without type 2 diabetes was largely determined by nonglycemic factors and only weakly by impaired insulin sensitivity and insulin secretion.