title: 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: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, University of Tsukuba Institute of Clinical Medicine, Ibaraki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Heianza
authors.forename: Y
authors.initials: Y
authors.lastname: Arase
authors.forename: K
authors.initials: K
authors.lastname: Fujihara
authors.forename: H
authors.initials: H
authors.lastname: Tsuji
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.forename: S D
authors.initials: SD
authors.lastname: Hsieh
authors.forename: S
authors.initials: S
authors.lastname: Kodama
authors.forename: H
authors.initials: H
authors.lastname: Shimano
authors.forename: N
authors.initials: N
authors.lastname: Yamada
authors.forename: S
authors.initials: S
authors.lastname: Hara
authors.forename: H
authors.initials: H
authors.lastname: Sone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D044466:Asian People; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005215:Fasting / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007564:Japan; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; C517652:hemoglobin A1c protein, human