Relationship of hyperinsulinaemia, insulin resistance and β‐cell dysfunction with incident diabetes and pre‐diabetes: the Tehran Lipid and Glucose Study

AIMS: To examine the association of fasting insulin, insulin resistance and reduced β-cell function with incident Type 2 diabetes and pre-diabetes (isolated impaired fasting glucose/isolated impaired glucose tolerance and combined impaired fasting glucose/impaired glucose tolerance). METHODS: An Iranian population comprising 1532 men and 2221 women, aged ≥ 20 years, with normal fasting glucose and normal glucose tolerance at baseline, were enrolled in the study. Multivariable Cox proportional hazard models were used to calculate the hazard ratios and 95% CIs of fasting insulin, updated homeostasis model assessments of insulin resistance and β-cell function for incident Type 2 diabetes, isolated impaired fasting glucose, isolated impaired glucose tolerance and combined impaired fasting glucose/impaired glucose tolerance. RESULTS: During a median follow-up of 9.2 years, the annual incidence rates (95% CI) of diabetes were 3.73 (2.74-4.94) and 4.06 (3.21-5.06) per 1000 person-years in men and women, respectively. In both men and women, fasting insulin and homeostasis model assessment of insulin resistance (≥ 75th percentile) were significantly associated with incident diabetes and combined impaired fasting glucose/impaired glucose tolerance; however, reduced β-cell function as measured by homeostasis model assessment of β-cell function (< 25th percentile) was associated with incident isolated impaired fasting glucose solely in men [hazard ratio 1.35 (95% CI 1.02-1.78)] in multivariable analysis including waist-hip ratio). Hyperinsulinaemia, insulin resistance and β-cell dysfunction were not related to the incidence of isolated impaired glucose tolerance in either gender. CONCLUSIONS: Fasting hyperinsulinaemia and insulin resistance were strong risk factors for progression to diabetes and combined impaired fasting glucose/impaired glucose tolerance in a population with normal fasting glucose/normal glucose tolerance. In addition, impaired β-cell function at baseline was related to the development of isolated impaired fasting glucose only in men and, in both men and women, neither insulin resistance nor β-cell dysfunction were associated with incident isolated impaired glucose tolerance.