Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults

Abstract

Background: 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.

Methods: A 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.

Results: Over 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) CONCLUSIONS: In 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.

Keywords: Alkaline phosphatase; Hypertension; New-onset diabetes; New-onset impaired fasting glucose; Total homocysteine.

Conflict of interest statement

XPX reports grants from the National Key Research and Development Program [2016YFE0205400, 2018ZX09739010, 2018ZX09301034003]; the Science and Technology Program of Guangdong [2020B121202010]; the Science and Technology Planning Project of Guangzhou [201707020010]; the Science, Technology and Innovation Committee of Shenzhen [GJHS20170314114526143, JSGG20180703155802047]; the Economic, Trade and Information Commission of Shenzhen Municipality [20170505161556110, 20170505160926390, 201705051617070].

XHQ reports grants from the National Natural Science Foundation of China [81730019, 81973133] and Outstanding Youths Development Scheme of Nanfang Hospital, Southern Medical University [2017J009].

No other disclosures were reported.

Figures

Fig. 1

Flow chart of the participants

Fig. 2

The association between baseline serum alkaline phosphatase (ALP) and new-onset diabetes a and new-onset impaired fasting glucose (IFG) b in hypertensive adults. Adjusted for age, sex, study center, treatment group, body mass index (BMI), smoking, alcohol drinking, family history of diabetes, SBP, fasting glucose (FG), total cholesterol (TC), triglycerides (TG), eGFR, folate, total homocysteine and the use of antihypertensive drugs at baseline, as well as time-averaged SBP during the treatment period. Subjects with baseline FG < 6.1 mmol/L and without new-onset diabetes during follow-up were included in the analysis for new-onset IFG

Fig. 3

The association between baseline serum alkaline phosphatase (ALP) and change in FG levels. Adjusted for age, sex, study center, treatment group, body mass index (BMI), smoking, alcohol drinking, family history of diabetes, SBP, fasting glucose (FG), total cholesterol (TC), triglycerides (TG), eGFR, folate, total homocysteine and the use of antihypertensive drugs at baseline, as well as time-averaged SBP during the treatment period. The analysis was only included subjects without physician-diagnosed diabetes, or use of glucose-lowering drugs during follow-up

Fig. 4

The association between baseline alkaline phosphatase (ALP) and new-onset diabetes in normal ALP levels (20–140 IU/L). Adjusted for age, sex, study center, treatment group, body mass index (BMI), smoking, alcohol drinking, family history of diabetes, SBP, fasting glucose (FG), total cholesterol (TC), triglycerides (TG), eGFR, folate, total homocysteine and the use of antihypertensive drugs at baseline, as well as time-averaged SBP during the treatment period

Fig. 5

The association between baseline serum alkaline phosphatase (ALP, per SD increment) and new-onset diabetes in various groups. Adjusted for age, sex, study center, treatment group, body mass index (BMI), smoking, alcohol drinking, family history of diabetes, SBP, fasting glucose (FG), total cholesterol (TC), triglycerides (TG), eGFR, folate, total homocysteine and the use of antihypertensive drugs at baseline, as well as time-averaged SBP during the treatment period, if not be stratified