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BMJ Publishing Group, BMJ Open Diabetes Research and Care, 1(10), p. e002643, 2022

DOI: 10.1136/bmjdrc-2021-002643

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Intestinal alkaline phosphatase deficiency increases the risk of diabetes

Journal article published in 2022 by Jagannath Malo, Md Jahangir Alam ORCID, Salequl Islam ORCID, Md Abdul Mottalib, Md Mehedi Hasan Rocki, Ginok Barmon, Shamema Akter Tinni, Swapan K. Barman, Tapas Sarker, Md Nayeemul Islam Khan, Kanakaraju Kaliannan, Muhammad Abul Hasanat, Salimur Rahman, Md Faruque Pathan, A. K. Azad Khan and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

IntroductionOur previous case–control study demonstrated that a high level of intestinal alkaline phosphatase (IAP), an endotoxin-detoxifying anti-inflammatory enzyme secreted by villus-associated enterocytes and excreted with stool, plays a protective role against type 2 diabetes mellitus (T2DM) irrespective of obesity. In the current study, we investigated the long-term effect of IAP deficiency (IAPD) on the pathogenesis of T2DM.Research design and methodsA healthy cohort of participants without diabetes (30–60 years old), comprising 188 without IAPD (IAP level: ≥65 U/g stool) and 386 with IAPD (IAP level: <65 U/g stool), were followed up for 5 years. We measured stool IAP (STAP) and fasting plasma glucose, and calculated the risk ratio (RR) using log-binomial regression model.ResultsT2DM incidence rates were 8.0%, 11.7%, 25.6%, and 33.3% in participants with ‘persistent no IAPD’ (IAP level: always ≥65 U/g stool), ‘remittent IAPD’ (IAP level: increased from <65 U/g stool to ≥65 U/g stool), ‘persistent IAPD’ (IAP level: always <65 U/g stool), and ‘incident IAPD’ (IAP level: decreased from ≥65 U/g stool to <65 U/g stool), respectively. Compared with ‘persistent no IAPD’ the risk of developing T2DM with ‘incident IAPD’ was 270% higher (RR: 3.69 (95% CI 1.76 to 7.71), χ2 p<0.001). With ‘persistent IAPD’ the risk was 230% higher (RR: 3.27 (95% CI 1.64 to 6.50), p<0.001). ‘Remittent IAPD’ showed insignificant risk (RR: 2.24 (95% CI 0.99 to 5.11), p=0.0541). Sensitivity analyses of persistent IAP levels revealed that, compared with participants of the highest persistent IAP pentile (always >115 U/g stool), the rate of increase of fasting glycemia was double and the risk of developing T2DM was 1280% higher (RR: 13.80 (95% CI 1.87 to 101.3), p=0.0099) in participants of the lowest persistent IAP pentile (always <15 U/g stool). A diabetes pathogenesis model is presented.ConclusionsIAPD increases the risk of developing T2DM, and regular STAP tests would predict individual vulnerability to T2DM. Oral IAP supplementation might prevent T2DM.