Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes: a longitudinal analysis from the Whitehall II cohort study - PubMed (original) (raw)

Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes: a longitudinal analysis from the Whitehall II cohort study

Adam Hulman et al. Diabetologia. 2017 Jul.

Abstract

Aims/hypothesis: South Asian individuals have reduced insulin sensitivity and increased risk of type 2 diabetes compared with white individuals. Temporal changes in glycaemic traits during middle age suggest that impaired insulin secretion is a particular feature of diabetes development among South Asians. We therefore aimed to examine ethnic differences in early changes in glucose metabolism prior to incident type 2 diabetes.

Methods: In a prospective British occupational cohort, subject to 5 yearly clinical examinations, we examined ethnic differences in trajectories of fasting plasma glucose (FPG), 2 h post-load plasma glucose (2hPG), fasting serum insulin (FSI), 2 h post-load serum insulin (2hSI), HOMA of insulin sensitivity (HOMA2-S) and secretion (HOMA2-B), and the Gutt insulin sensitivity index (ISI0,120) among 120 South Asian and 867 white participants who developed diabetes during follow-up (1991-2013). We fitted cubic mixed-effects models to longitudinal data with adjustment for a wide range of covariates.

Results: Compared with white individuals, South Asians had a faster increase in FPG before diagnosis (slope difference 0.22 mmol/l per decade; 95% CI 0.02, 0.42; p = 0.03) and a higher FPG level at diagnosis (0.27 mmol/l; 95% CI 0.06, 0.48; p = 0.01). They also had higher FSI and 2hSI levels before and at diabetes diagnosis. South Asians had a faster decline and lower HOMA2-S (log e -transformed) at diagnosis compared with white individuals (0.33; 95% CI 0.21, 0.46; p < 0.001). HOMA2-B increased in both ethnic groups until 7 years before diagnosis and then declined; the initial increase was faster in white individuals. ISI0,120 declined steeply in both groups before diagnosis; levels were lower among South Asians before and at diagnosis. There were no ethnic differences in 2hPG trajectories.

Conclusions/interpretation: We observed different trajectories of plasma glucose, insulin sensitivity and secretion prior to diabetes diagnosis in South Asian and white individuals. This might be due to ethnic differences in the natural history of diabetes. South Asian individuals experienced a more rapid decrease in insulin sensitivity and faster increases in FPG compared with white individuals. These findings suggest more marked disturbance in beta cell compensation prior to diabetes diagnosis in South Asian individuals.

Keywords: Cohort study; Ethnicity; Glucose; Glycaemic trajectory; Insulin; South Asia.

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Conflict of interest statement

Data availability

Whitehall II data are available to bona fide researchers for research purposes. Please refer to the Whitehall II data sharing policy at http://www.ucl.ac.uk/whitehallII/data-sharing.

Funding

AH, RKS and DRW are supported by the Danish Diabetes Academy. The Danish Diabetes Academy is funded by the Novo Nordisk Foundation. RKS is further supported by the Aarhus Institute of Advanced Studies. KF is supported by the Novo Nordisk Foundation. EJB is supported by the British Heart Foundation (RG/13/2/30098).

The UK Medical Research Council (MR/K013351/1; G0902037), the British Heart Foundation (RG/13/2/30098) and the US National Institutes of Health (R01HL36310, R01AG013196) have supported collection of data in the Whitehall II study.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

AH was responsible for the data analysis. RKS and AH wrote the first draft of the manuscript with major contributions from AGT. EJB had the original idea for the study. AGT, MK and EJB contributed to the conception and design of the study and the data acquisition. All authors contributed to the interpretation of the data and critical revision of the manuscript, and approved the final version. AH is the guarantor of this work and, as such, had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Figures

Fig. 1

Trajectories of (a) FPG, (b) 2hPG, (c) FSI and (d) 2hSI, with 95% CIs, by ethnic group (red circles, South Asians; blue squares, whites). All models were adjusted for age, sex, BMI, employment grade, diet and physical activity. Insulin values were log_e_-transformed before fitting the models and then transformed back to the original scale

Fig. 2

Log_e_-transformed (a) HOMA2-B, (b) HOMA2-S and (c) ISI0,120 trajectories with 95% CIs, by ethnic group (red circles, South Asians; blue squares, whites). All models were adjusted for age, sex, BMI, employment grade, diet and physical activity

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Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes: a longitudinal analysis from the Whitehall II cohort study - PubMed (original) (raw)