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. 2025 Aug;39(15):e70075.
doi: 10.1002/jcla.70075. Epub 2025 Jul 23.

Sex-Specific Associations of Serum Alkaline Phosphatase With Metabolic Syndrome and Its Components: Over 15 Years of Follow-Up Among Iranian Adults

Parto Hadaegh  1   2 , Amir Abdi  1   3 , Mitra Hasheminia  1 , Farzad Hadaegh  1 , Fereidoun Azizi  4 , Maryam Tohidi  1
Affiliations

Sex-Specific Associations of Serum Alkaline Phosphatase With Metabolic Syndrome and Its Components: Over 15 Years of Follow-Up Among Iranian Adults

Parto Hadaegh et al. J Clin Lab Anal. 2025 Aug.

Abstract

Background: To investigate the association of serum alkaline phosphatase (ALP) with incident metabolic syndrome (MetS) and its components, as well as the influence of sex on this relationship among Iranian adults.

Methods: The multivariable Cox proportional hazards regression models were applied to assess the associations between ALP both as continuous and categorical variables with incident MetS and its components.

Results: Among 831 subjects (467 women) with a mean age of 44.51 years, during a median follow-up of 15.6 years, 597 MetS cases (336 women) occurred. Interaction was found between ALP quartiles and sex (p-value = 0.006). Among women, increasing levels of ALP across the second to fourth quartiles were associated with hazard ratios (HRs) of 1.269, 1.491, and 2.092 for MetS, respectively (p for trend < 0.001). Among men, no association was found between ALP and incident MetS. Among women, the second and fourth quartiles of ALP were associated with incident high triglycerides (TG), with HRs of 1.793 and 1.815, respectively. Moreover, a 1-SD increase in ALP conferred a 17.9% higher risk of low high-density lipoprotein cholesterol (HDL-C). Among men, a 1-SD increase in ALP was associated with an HR of 1.222 for incident high waist circumference (WC) (All p-values < 0.05).

Conclusion: Sex significantly influenced the impact of serum ALP on the incidence of MetS and its components. In women, ALP was a strong harbinger for incident MetS and its dyslipidemia components. However, among men, the increasing value of ALP was associated with incident central obesity but not MetS.

Keywords: alkaline phosphatase; components; metabolic syndrome; sex differences.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Flowchart of the study population. TLGS, Tehran Lipid and Glucose Study; ALP, alkaline phosphatase; n, number; MetS, metabolic syndrome; WC, waist circumference; BP, blood pressure; FPG, fasting plasma glucose; TG, triglycerides; HDL‐C, high density lipoprotein cholesterol.
FIGURE 2
FIGURE 2
The cumulative incidence of metabolic syndrome (MetS) according to the baseline serum alkaline phosphatase (ALP) quartiles among women, men, and the whole population.
FIGURE 3
FIGURE 3
Risk of incident metabolic syndrome according to serum alkaline phosphatase. (A) as categorical variable (first quartile as reference), (B) as continuous variable (per 1 SD increase); Hazard ratios are adjusted for age, sex (for whole population), body mass index, estimated glomerular filtration rate, smoking, physical activity, education, marital status, history of cardiovascular diseases, and family history of diabetes mellitus.
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