Size and shape of the associations of glucose, HbA1c, insulin and HOMA-IR with incident type 2 diabetes: the Hoorn Study

Carolien Ruijgrok,David J Mela,Martijn W Heymans,Joline W Beulens,Veerle M H Coupé,Jacqueline M Dekker,Marjan Alssema,Peter L Zock,Margreet R Olthof,Femke P C Sijtsma,Ingeborg A Brouwer

doi:10.1007/s00125-017-4452-7

Abstract

Aims/hypothesisGlycaemic markers and fasting insulin are frequently measured outcomes of intervention studies. To extrapolate accurately the impact of interventions on the risk of diabetes incidence, we investigated the size and shape of the associations of fasting plasma glucose (FPG), 2 h post-load glucose (2hPG), HbA1c, fasting insulin and HOMA-IR with incident type 2 diabetes mellitus.MethodsThe study population included 1349 participants aged 50–75 years without diabetes at baseline (1989) from a population-based cohort in Hoorn, the Netherlands. Incident type 2 diabetes was defined by the WHO 2011 criteria or known diabetes at follow-up. Logistic regression models were used to determine the associations of the glycaemic markers, fasting insulin and HOMA-IR with incident type 2 diabetes. Restricted cubic spline logistic regressions were conducted to investigate the shape of the associations.ResultsAfter a mean follow-up duration of 6.4 (SD 0.5) years, 152 participants developed diabetes (11.3%); the majority were screen detected by high FPG. In multivariate adjusted models, ORs (95% CI) for incident type 2 diabetes for the highest quintile in comparison with the lowest quintile were 9.0 (4.4, 18.5) for FPG, 6.1 (2.9, 12.7) for 2hPG, 3.8 (2.0, 7.2) for HbA1c, 1.9 (0.9, 3.6) for fasting insulin and 2.8 (1.4, 5.6) for HOMA-IR. The associations of FPG and HbA1c with incident diabetes were non-linear, rising more steeply at higher values.Conclusions/interpretationFPG was most strongly associated with incident diabetes, followed by 2hPG, HbA1c, HOMA-IR and fasting insulin. The strong association with FPG is probably because FPG is the most frequent marker for diabetes diagnosis. Non-linearity of associations between glycaemic markers and incident type 2 diabetes should be taken into account when estimating future risk of type 2 diabetes based on glycaemic markers.

Highlights

Increased levels of glucose and insulin, in the fasting and postprandial state, and HbA1c are key characteristics of typeDiabetologia (2018) 61:93–1002 diabetes mellitus
For 2 h post-load glucose (2hPG), insulin and HOMA-IR, the increment in probability to develop diabetes is more gradual over the whole range of their corresponding distributions. In this cohort study of a 50–75-year-old Dutch population, fasting plasma glucose (FPG) was most strongly associated with incident type 2 diabetes followed by 2hPG, HbA1c, HOMA-IR and fasting insulin
The key finding of this study was non-linearity of the associations of FPG and HbA1c with incident type 2 diabetes, in contrast to 2hPG, loge fasting insulin and loge HOMA-IR, which were all linearly associated with incident type 2 diabetes

Summary

Introduction

Increased levels of glucose and insulin, in the fasting and postprandial state, and HbA1c are key characteristics of typeDiabetologia (2018) 61:93–1002 diabetes mellitus. When people reach the impaired glucose tolerance (IGT) state, the transition from IGT to type 2 diabetes within populations occurs at a remarkably high rate: an estimated 25% of people with IGT develop type 2 diabetes within 3–5 years and 40– 50% within 10 years [3]. To extrapolate the impact of such interventions on diabetes incidence and to estimate their public health impact, accurate quantification of the association between glycaemic markers and incident type 2 diabetes is needed. Knowledge of these associations may subsequently be used to build health impact models that estimate the effect of different interventions on diabetes incidence

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