PMID- 35082135
OWN - NLM
STAT- MEDLINE
DCOM- 20220323
LR  - 20220531
IS  - 2052-4897 (Electronic)
IS  - 2052-4897 (Linking)
VI  - 10
IP  - 1
DP  - 2022 Jan
TI  - Intestinal alkaline phosphatase deficiency increases the risk of diabetes.
LID - 10.1136/bmjdrc-2021-002643 [doi]
LID - e002643
AB  - INTRODUCTION: Our 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 METHODS: A 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. RESULTS: 
      T2DM 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), chi(2) 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. 
      CONCLUSIONS: IAPD increases the risk of developing T2DM, and regular STAP tests 
      would predict individual vulnerability to T2DM. Oral IAP supplementation might 
      prevent T2DM.
CI  - (c) Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Malo, Jagannath
AU  - Malo J
AD  - Diabetic Association of Bangladesh, Dhaka, Bangladesh.
FAU - Alam, Md Jahangir
AU  - Alam MJ
AUID- ORCID: 0000-0002-5372-8789
AD  - Department of Statistics, University of Rajshahi, Rajshahi, Bangladesh.
FAU - Islam, Salequl
AU  - Islam S
AUID- ORCID: 0000-0001-6131-4132
AD  - Department of Microbiology, Jahangirnagar University, Savar, Bangladesh.
FAU - Mottalib, Md Abdul
AU  - Mottalib MA
AD  - Department of Biochemistry and Molecular Biology, BIRDEM, Dhaka, Bangladesh.
FAU - Rocki, Md Mehedi Hasan
AU  - Rocki MMH
AD  - Diabetic Association of Bangladesh, Dhaka, Bangladesh.
FAU - Barmon, Ginok
AU  - Barmon G
AD  - Diabetic Association of Bangladesh, Dhaka, Bangladesh.
FAU - Tinni, Shamema Akter
AU  - Tinni SA
AD  - Diabetic Association of Bangladesh, Dhaka, Bangladesh.
FAU - Barman, Swapan K
AU  - Barman SK
AD  - Diabetic Association of Bangladesh, Dhaka, Bangladesh.
FAU - Sarker, Tapas
AU  - Sarker T
AD  - Diabetic Association of Bangladesh, Dhaka, Bangladesh.
FAU - Khan, Md Nayeemul Islam
AU  - Khan MNI
AD  - Department of Biochemistry and Molecular Biology, BIRDEM, Dhaka, Bangladesh.
FAU - Kaliannan, Kanakaraju
AU  - Kaliannan K
AD  - Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 
      Boston, Massachusetts, USA.
FAU - Hasanat, Muhammad Abul
AU  - Hasanat MA
AD  - Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka, 
      Bangladesh.
FAU - Rahman, Salimur
AU  - Rahman S
AD  - Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, 
      Bangladesh.
FAU - Pathan, Md Faruque
AU  - Pathan MF
AD  - Department of Endocrinology, BIRDEM, Dhaka, Bangladesh.
FAU - Khan, A K Azad
AU  - Khan AKA
AD  - Diabetic Association of Bangladesh, Dhaka, Bangladesh.
FAU - Malo, Madhu S
AU  - Malo MS
AUID- ORCID: 0000-0002-2629-687X
AD  - Diabetic Association of Bangladesh, Dhaka, Bangladesh madhumalo@hotmail.com.
AD  - Department of Biochemistry and Molecular Biology, BIRDEM, Dhaka, Bangladesh.
AD  - Centre for Global Health Research, Diabetic Association of Bangladesh, Dhaka, 
      Bangladesh.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - BMJ Open Diabetes Res Care
JT  - BMJ open diabetes research & care
JID - 101641391
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - Adult
MH  - *Alkaline Phosphatase
MH  - *Diabetes Mellitus, Type 2/epidemiology/etiology
MH  - Fasting
MH  - Humans
MH  - Incidence
MH  - Middle Aged
MH  - Obesity/complications
PMC - PMC8796214
OTO - NOTNLM
OT  - diabetes mellitus
OT  - type 2
COIS- Competing interests: None declared.
EDAT- 2022/01/28 06:00
MHDA- 2022/03/24 06:00
PMCR- 2022/01/26
CRDT- 2022/01/27 05:46
PHST- 2021/10/22 00:00 [received]
PHST- 2021/12/06 00:00 [accepted]
PHST- 2022/01/27 05:46 [entrez]
PHST- 2022/01/28 06:00 [pubmed]
PHST- 2022/03/24 06:00 [medline]
PHST- 2022/01/26 00:00 [pmc-release]
AID - 10/1/e002643 [pii]
AID - bmjdrc-2021-002643 [pii]
AID - 10.1136/bmjdrc-2021-002643 [doi]
PST - ppublish
SO  - BMJ Open Diabetes Res Care. 2022 Jan;10(1):e002643. doi: 
      10.1136/bmjdrc-2021-002643.