Abstract

BackgroundThe association between alkaline phosphatase (ALP) and incident diabetes remains uncertain. Our study aimed to investigate the prospective relation of serum ALP with the risk of new-onset diabetes, and explore possible effect modifiers, in hypertensive adults.MethodsA total 14,393 hypertensive patients with available ALP measurements and without diabetes and liver disease at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 7.0 mmol/L at the exit visit. The secondary study outcome was new-onset impaired fasting glucose (IFG), defined as FG < 6.1 mmol/L at baseline and ≥ 6.1 but < 7.0 mmol/L at the exit visit.ResultsOver a median of 4.5 years follow-up, 1549 (10.8%) participants developed diabetes. Overall, there was a positive relation of serum ALP and the risk of new-onset diabetes (per SD increment, adjusted OR, 1.07; 95% CI: 1.01, 1.14) and new-onset IFG (per SD increment, adjusted OR, 1.07; 95% CI: 1.02, 1.14). Moreover, a stronger positive association between baseline ALP (per SD increment) with new-onset diabetes was found in participants with total homocysteine (tHcy) < 10 μmol/L (adjusted OR, 1.24; 95% CI: 1.10, 1.40 vs. ≥ 10 μmol/L: adjusted OR, 1.03; 95% CI: 0.96, 1.10; P-interaction = 0.007) or FG ≥ 5.9 mmol/L (adjusted OR, 1.16; 95% CI: 1.07, 1.27 vs. < 5.9 mmol/L: adjusted OR, 1.00; 95% CI: 0.93, 1.08; P-interaction = 0.009)ConclusionsIn this non-diabetic, hypertensive population, higher serum ALP was significantly associated with the increased risk of new-onset diabetes, especially in those with lower tHcy or higher FG levels.Clinical Trial Registration-URL Trial registration: NCT00794885 (clinicaltrials.gov). Retrospectively registered November 20, 2008.

Highlights

  • The association between alkaline phosphatase (ALP) and incident diabetes remains uncertain

  • There was a positive relation of serum ALP and the risk of new-onset diabetes (Fig. 2a), and newonset impaired fasting glucose (IFG) (Fig. 2b)

  • Association between change in serum ALP and new‐onset diabetes In order to further examine the association between serum ALP and new-onset diabetes, we investigated the relation of change in ALP with new-onset diabetes

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Summary

Introduction

The association between alkaline phosphatase (ALP) and incident diabetes remains uncertain. Our study aimed to investigate the prospective relation of serum ALP with the risk of new-onset diabetes, and explore possible effect modifiers, in hypertensive adults. Diabetes result in many complications, including cardiovascular disease (CVD). The identification of more modifiable risk factors may possibly reduce the huge burden of diabetes and its associated complications by leading to early detection and prevention. In a nest case–control study, ALP in type 2 diabetes seemed to be associated with CVD risk and stroke incidence in men, but with borderline significance [10]. Only a few previous prospective studies [11,12,13,14] have been carried out to evaluate the relation of ALP and incident diabetes, and reported inconsistent results. Potential modifiers on the association between ALP and incident diabetes have not been comprehensively examined in previous studies

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