High normal HbA(1c) levels were associated with impaired insulin secretion without escalating insulin resistance in Japanese individuals: the Toranomon Hospital Health Management Center Study 8 (TOPICS 8)

Abstract

Aims: We aimed to characterize the association of insulin resistance, impaired insulin secretion and β-cell dysfunction in relation to HbA(1c) 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 HbA(1c) levels.

Results: Fasting plasma glucose and 30-min and 60-min plasma glucose (PG) levels were significantly higher when HbA(1c) exceeded 36 mmol/mol (5.4%). A HbA(1c) concentration of 36-37 mmol/mol (5.4-5.5%) (Q3) was significantly associated with a 15% lower homeostasis model assessment of β-cell function value and 31% lower insulinogenic index value compared with HbA(1c) ≤ 32 mmol/mol (≤ 5.1%) (Q1) (P <0.01). Further, a HbA(1c) concentration of 38-40 mmol/mol (5.6-5.8%) (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 HbA(1c) exceeded 41 mmol/mol (5.9%). Individuals with HbA(1c) ≥ 41 mmol/mol (≥ 5.9%) (Q5) had a 69% lower disposition index than those with a HbA(1c) concentration of ≤ 32 mmol/mol (≤ 5.1%) (Q1).

Conclusions: Elevated HbA(1c) levels ≥ 41 mmol/mol (≥ 5.9%) were associated with substantial reductions in insulin secretion, insulin sensitivity and β-cell dysfunction in Japanese individuals not treated for diabetes. High normal HbA(1c) levels of 36-40 mmol/mol (5.4-5.8%) were also associated with impaired insulin secretion without marked insulin resistance in Japanese individuals.