PMID- 35897035
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231103
IS  - 1758-5996 (Print)
IS  - 1758-5996 (Electronic)
IS  - 1758-5996 (Linking)
VI  - 14
IP  - 1
DP  - 2022 Jul 27
TI  - Combined effect of pancreatic lipid content and gene variants (TCF7L2, WFS1 and 
      11BHSD1) on B-cell function in Middle Aged Women in a Post Hoc Analysis.
PG  - 106
LID - 10.1186/s13098-022-00876-z [doi]
LID - 106
AB  - BACKGROUND: TCF7L2 rs7903146 and PNPLA3 rs738409 gene variants confer the 
      strongest risk for type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver 
      disease (NAFLD), respectively. Pancreatic triacylglycerol content (PTGC) was 
      reported to have a role in T2DM development. We aimed to assess the correlation 
      between PTGC and hepatic triacylglycerol content (HTGC) stratified by PNPLA3 
      rs738409 genotype and subsequently interactions between PTGC and gene variants 
      associated with beta-cell dysfunction (TCF7L2, WFS1) and visceral adiposity 
      (11BetaHSD1) on beta-cell function were also tested. METHODS: PTGC and HTGC were 
      assessed using MR in a post-hoc analysis of a genotype-based (PNPLA3 rs738409) 
      recall study of 39 (lipid- and glucose lowering) drug-naive women. Oral glucose 
      tolerance test, HbA1c, insulin indices, anthropometric data were evaluated. The 
      effect of minor allele carrying of TCF7L2 (rs7903146); WFS1 (rs1801214) and 
      11BetaHSD1 (rs4844880) variants in combination with PTGC was studied on surrogate 
      markers of beta-cell function. We used Spearman's rank-order, Mann-Whitney-U tests, 
      and linear regression models. RESULTS: PTGC and HTGC values were correlated after 
      stratification by the rs738409 variant (only in CC genotype group R = 0.67, 
      p = 10(- 4)). PTGC and HbA1c values correlated in the entire study population 
      (R = 0.58, p = 10(- 4)). Insulin resistance, sensitivity and disposition indices 
      were correlated with PTGC (HOMA2-IR: R = 0.42, p = 0.008; TyG: R = 0.38, 
      p = 0.018; Matsuda: R= - 0.48, p = 0.002; DI(basal): R=-0.33, p = 0.039; ISSI-2: 
      R=-0.35, p = 0.028). Surrogate markers of beta-cell function (HOMA2-B, 
      AUC(insulin)/AUC(glucose)) correlated significantly with PTGC in subjects with 
      the following genotypes rs7903146: CC R = 0.51, p = 0.022; rs18001214: CT + CC 
      R = 0.55, p = 0.013; rs4844880: TA + AA R = 0.56, p = 0.016. The strongest 
      interactions were found between PTGC and TCF7L2 rs7903146 effect on HOMA2-B 
      (p = 0.001) and AUC(insulin)/AUC(glucose) (p = 0.013). CONCLUSIONS: The PNPLA3 
      rs738409 genotype has a major effect on the correlation between PTGC and HTGC. 
      Furthermore we first report the combined effect of PTGC and individual risk gene 
      variants of TCF7L2, WFS1 and 11BetaHSD1 on beta-cell dysfunction. The correlation 
      between pancreatic lipid accumulation and HbA1c also indicates an important role 
      for the latter pathology.
CI  - (c) 2022. The Author(s).
FAU - Nadasdi, Akos
AU  - Nadasdi A
AUID- ORCID: 0000-0002-7016-6474
AD  - Department of Internal Medicine and Haematology, Faculty of Medicine, Semmelweis 
      University, Szentkiralyi St 46, 1088, Budapest, Hungary.
FAU - Gal, Viktor
AU  - Gal V
AD  - Brain Imaging Centre, Research Centre for Natural Sciences, Eotvos Lorand 
      Research Network, Budapest, Hungary.
FAU - Masszi, Tamas
AU  - Masszi T
AD  - Department of Internal Medicine and Haematology, Faculty of Medicine, Semmelweis 
      University, Szentkiralyi St 46, 1088, Budapest, Hungary.
FAU - Patocs, Attila
AU  - Patocs A
AD  - MTA-SE Hereditary Tumors Research Group, Eotvos Lorand Research Network, 
      Budapest, Hungary.
AD  - Department of Laboratory Medicine, Faculty of Medicine, Semmelweis University, 
      Budapest, Hungary.
FAU - Igaz, Peter
AU  - Igaz P
AD  - MTA-SE Molecular Medicine Research Group, Eotvos Lorand Research Network, 
      Budapest, Hungary.
AD  - Department of Endocrinology, Faculty of Medicine, Semmelweis University, 
      Budapest, Hungary.
AD  - Department of Internal Medicine and Oncology, Faculty of Medicine, Semmelweis 
      University, Budapest, Hungary.
FAU - Somogyi, Aniko
AU  - Somogyi A
AD  - Department of Internal Medicine and Haematology, Faculty of Medicine, Semmelweis 
      University, Szentkiralyi St 46, 1088, Budapest, Hungary.
FAU - Firneisz, Gabor
AU  - Firneisz G
AUID- ORCID: 0000-0002-9123-8131
AD  - Department of Internal Medicine and Haematology, Faculty of Medicine, Semmelweis 
      University, Szentkiralyi St 46, 1088, Budapest, Hungary. 
      firneisz.gabor@med.semmelweis-univ.hu.
AD  - MTA-SE Molecular Medicine Research Group, Eotvos Lorand Research Network, 
      Budapest, Hungary. firneisz.gabor@med.semmelweis-univ.hu.
LA  - eng
GR  - Doctoral Fellowship Award/Worwag Pharma/
GR  - Higher Education Institutional Excellence Program/Ministry of Human Capacities in 
      Hungary/
GR  - Higher Education Institutional Excellence Program/Ministry of Human Capacities in 
      Hungary/
GR  - New Horizons/European Foundation for the Study of Diabetes/
PT  - Journal Article
DEP - 20220727
PL  - England
TA  - Diabetol Metab Syndr
JT  - Diabetology & metabolic syndrome
JID - 101488958
PMC - PMC9331183
OTO - NOTNLM
OT  - 11BetaHSD1
OT  - HbA1c
OT  - Liver fat
OT  - PNPLA3
OT  - Pancreatic fat
OT  - TCF7L2
OT  - WFS1
COIS- The authors declare that they have no competing interests.
EDAT- 2022/07/28 06:00
MHDA- 2022/07/28 06:01
PMCR- 2022/07/27
CRDT- 2022/07/27 23:51
PHST- 2022/03/04 00:00 [received]
PHST- 2022/07/11 00:00 [accepted]
PHST- 2022/07/27 23:51 [entrez]
PHST- 2022/07/28 06:00 [pubmed]
PHST- 2022/07/28 06:01 [medline]
PHST- 2022/07/27 00:00 [pmc-release]
AID - 10.1186/s13098-022-00876-z [pii]
AID - 876 [pii]
AID - 10.1186/s13098-022-00876-z [doi]
PST - epublish
SO  - Diabetol Metab Syndr. 2022 Jul 27;14(1):106. doi: 10.1186/s13098-022-00876-z.