A new study from Bangladesh, which examined the association of deficiency of IAP and incident type 2 diabetes has found that deficiency of intestinal alkaline phosphatase (IAPD) increases the risk of type 2 diabetes.¹

The 5-year prospective cohort study selected 671 healthy participants without diabetes, aged between 30 and 60 years. Of these, 97 were lost to follow up. Hence, 574 patients constituted the final analysis group. Based on IAP levels measured at the time of the first visit, the participants were categorized into IAP deficiency group (<65 U/g stool) and high IAP group (≥65 U/g stool). Stool alkaline phosphatase (STAP) was measured and was taken to be representative of IAP for this study since 80% of STAP is IAP. Glycemic status was determined by fasting plasma glucose (≥126 mg/dL) and/or HbA1c (≥6.5%). Other laboratory parameters including lipids, alanine aminotransferase (ALT) and body mass index (BMI) were also measured and the risk ratios were calculated.

After adjusting for variables like age, gender, BMI, blood pressure, lipid profile, creatinine, ALT, and fasting plasma glucose, results show that the incidence of type 2 diabetes amongst the “incident IAPD” patients (decrease in IAP from ≥65 U/g stool to <65 U/g stool) was 33.3%. In the “persistent IAPD” group (IAP always <65 U/g) stool, the incidence rate of type 2 diabetes was 25.6%; in the “remittent IAPD” group (increase in IAP from <65 U/g stool to ≥65 U/g stool), it was 11.7%, while in the “persistent no IAPD” group (IAP always ≥65 U/g stool), the incidence of diabetes was just 8%.

Individuals with “incident IAPD” were at 3.69 times higher risk of developing type 2 diabetes compared to the “persistent no IAPD” group. Similarly, those in the “persistent IAPD” group were 3.27 times more likely to develop type 2 diabetes. Conversely, the risk ratio for type 2 diabetes in the “remittent IAPD” was just 2.24, which did not hold statistical significance.

Participants in the lowest persistent IAP pentile (always <15 U/g stool) were 14-folds higher risk of developing type 2 diabetes as opposed to those with the highest persistent IAP pentile (always >115 U/g stool). In this study, obese subjects (BMI ≥25.0 kg/m2) with normal or high IAP levels did not develop type 2 diabetes.

IAP is an anti-inflammatory enzyme secreted by the gastrointestinal tract and is excreted with stool. This study published in BMJ Open Diabetes Research & Care has demonstrated the protective effect of high IAP against type 2 diabetes, despite the presence of obesity.

Compared to healthy non-diabetic controls, those with IAP deficiency, both “incident” and “persistent”, were at a significantly higher risk of developing type 2 diabetes. The risk was lower in “persistent no IAPD” and “remittent IAPD” groups. The authors further suggest that oral supplementation of IAP may prevent the development of diabetes. Hence, deficiency of IAP may be regarded as an independent risk factor for type 2 diabetes. Regular tests for IAP in stool may aid identification of the at-risk persons for early initiation of preventive measures.

Reference

1. Malo J, et al. Intestinal alkaline phosphatase deficiency increases the risk of diabetes. BMJ Open Diabetes Res Care. 2022 Jan;10(1):e002643. doi: 10.1136/bmjdrc-2021-002643.