High normal HbA1c levels were associated with impaired insulin secretion without escalating insulin resistance in Japanese individuals: the Toranomon Hospital Health Management Center Study 8 (TOPICS 8)

Diabet. Med. 29, 12851290 (2012) Abstract Aims We aimed to characterize the association of insulin resistance, impaired insulin secretion and beta-cell dysfunction in relation to HbA1c levels in a non-diabetic range in Japanese individuals without clinically diagnosed diabetes. Methods This cross-sectional study included 1444 individuals without a history of outpatient treatment of diabetes or use of insulin or oral hypoglycaemic agents. The homeostasis model assessment of insulin resistance and beta-cell function, insulinogenic index, Matsuda index and disposition index were calculated using data from 75-g oral glucose tolerance tests and compared across quintile (Q) categories of HbA1c levels. Results Fasting plasma glucose and 30-min and 60-min plasma glucose (PG) levels were significantly higher when HbA1c exceeded 36 mmol/mol (5.4%). A HbA1c concentration of 3637 mmol/mol (5.45.5%) (Q3) was significantly associated with a 15% lower homeostasis model assessment of beta-cell function value and 31% lower insulinogenic index value compared with HbA1c = 32 mmol/mol (= 5.1%) (Q1) (P <0.01). Further, a HbA1c concentration of 3840 mmol/mol (5.65.8%) (Q4) was associated with 17% (P <0.01) and 24% (P <0.05) reductions in those indexes, respectively. However, the homeostasis model assessment of insulin resistance was not significantly elevated and the Matsuda index was not significantly lower unless HbA1c exceeded 41 mmol/mol (5.9%). Individuals with HbA1c = 41 mmol/mol (= 5.9%) (Q5) had a 69% lower disposition index than those with a HbA1c concentration of = 32 mmol/mol (= 5.1%) (Q1). Conclusions Elevated HbA1c levels = 41 mmol/mol (= 5.9%) were associated with substantial reductions in insulin secretion, insulin sensitivity and beta-cell dysfunction in Japanese individuals not treated for diabetes. High normal HbA1c levels of 3640 mmol/mol (5.45.8%) were also associated with impaired insulin secretion without marked insulin resistance in Japanese individuals.