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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).
Heianza, Y. 1,2; Arase, Y. 2,3; Fujihara, K. 1; Tsuji, H. 2,3; Saito, K. 1,2; Hsieh, S. D. 2,3; Kodama, S. 1,2; Shimano, H. 1; Yamada, N. 1; Hara, S. 2,3; Sone, H. 1,2
[Article] Diabetic Medicine. 29(10):1285-1290, October 2012.

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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 36-37 mmol/mol (5.4-5.5%) (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 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 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 36-40 mmol/mol (5.4-5.8%) were also associated with impaired insulin secretion without marked insulin resistance in Japanese individuals.