Elsevier

The Lancet

Volume 353, Issue 9165, 15 May 1999, Pages 1649-1652
The Lancet

Articles
Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study

https://doi.org/10.1016/S0140-6736(99)01046-6Get rights and content

Summary

Background

Type 2 diabetes mellitus and atherosclerotic cardiovascular disease have common antecedents. Since markers of inflammation predict coronary heart disease and are raised in patients with type 2 diabetes, we investigated whether they predict whether people will develop type 2 diabetes.

Methods

12 330 men and women, aged 45–64 years, were followed up for a mean of 7 years. We analysed the association between different markers of acute inflammation and subsequent diagnosis of diabetes. In a subgroup of 610 individuals selected originally for an unrelated atherosclerosis case-control study, we also investigated diabetes associations with total sialic acid and orosomucoid, haptoglobin, and α1-antitrypsin.

Findings

1335 individuals had a new diagnosis of diabetes. Adjusted odds ratios for developing diabetes for quartile extremes were 1·9 (95% CI 1·6–2·3) for raised white-cell count, 1·3 (1·0–1·5) for low serum albumin, and 1·2 (1·0–1·5) for raised fibrinogen. In the subgroup analysis, individuals with concentrations of orosomucoid and sialic acid of more than the median had odds ratios of 7·9 (2·6–23·7) and 3·7 (1·4–9·8), respectively. Adjustment for body-mass index and waist-to-hip ratio lessened the associations; those for white-cell count (1·5 [1·3–1·8]), orosomucoid (7·1 [2·1–23·7]), and sialic acid (2·8 [1·0–8·1]) remained significant.

Interpretation

Markers of inflammation are associated with the development of diabetes in middle-aged adults. Although autoimmunity may partly explain these associations, they probably reflect the pathogenesis of type 2 diabetes.

Introduction

Type 2 diabetes mellitus and atherosclerotic cardiovascular disease share many antecedent factors that frequently coexist, which has given rise to the concept of common “soil”.1, 2, 3 This cluster of risk factors, such as uric acid, and dyslipidaemia, are strongly related to fasting insulin concentrations and central obesity,2 and are also associated with raised concentrations of inflammatory markers in people with and without diabetes.4, 5, 6

Inflammatory processes play a part in the cause of atherosclerotic cardiovascular disease.7 Concentrations of acute-phase response markers and mediators of inflammation–cytokines such as tumour necrosis factor α (TNFα) and interleukin-6–are raised in people with type 2 diabetes.5, 6 This finding has led to the suggestion that raised concentrations of proinflammatory cytokines and the resultant acute-phase response may underlie much of the metabolic clustering, including glucose intolerance.8 We investigated, in the Artherosclerosis Risk in Communities study, whether inflammatory markers predict the development of type 2 diabetes.

Section snippets

Participants

We selected 15 792 men and women, aged 45–64 years, by probability sampling from four US communities in 1987–89,9 after we obtained ethics-committee approval. We excluded eight individuals for age older than 64 years, 409 individuals with missing information on the covariates we studied, and, because of small numbers, 48 native American and Asian individuals, and 55 black people not at the Jackson or Forsyth centres. We also excluded 2008 individuals who had prevalent diabetes or who had no

Results

We studied 4492 white men, 5163 white women, 1008 black men, and 1667 black women. Of these, 2760 (22%) reported a positive family history of diabetes; 3709 (30%) were hypertensive; and 5257 (43%) had never smoked, 3074 (25%) were current smokers, and 3999 (32%) were previous smokers. Median age was 54 (IQR 49–59) years. The distribution of potential risk factors are shown in table 1.

During a mean follow-up of 7 years, we detected 1335 new cases of diabetes: 127 (9%) through reported use of

Discussion

Associations were seen for a range of inflammatory markers at concentrations lower than that characteristic of acute inflammation.16 Since all models were adjusted for baseline glycaemia and associations were not stronger in individuals with higher baseline fasting glycaemia, undetected diabetes at baseline cannot explain these findings. Some associations were stronger for individuals with diabetes detected at first follow-up and might, therefore, be better explained by the fact that

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