Dataset Information

Pancreatic Steatosis Associates With Impaired Insulin Secretion in Genetically Predisposed Individuals.

ABSTRACT: CONTEXT:Pancreatic steatosis leading to beta-cell failure might be involved in type 2 diabetes (T2D) pathogenesis. OBJECTIVE:We hypothesized that the genetic background modulates the effect of pancreatic fat on beta-cell function and investigated genotype × pancreatic fat interactions on insulin secretion. DESIGN:Two observational studies. SETTING:University hospital. PATIENTS OR PARTICIPANTS:A total of 360 nondiabetic individuals with elevated risk for T2D (Tuebingen Family Study [TUEF]), and 64 patients undergoing pancreatectomy (Pancreas Biobank [PB], HbA1c <9%, no insulin therapy). MAIN OUTCOME MEASURES:Insulin secretion calculated from 5-point oral glucose tolerance test (TUEF) and fasting blood collection before surgery (PB). A genome-wide polygenic score for T2D was computed from 484,788 genotyped variants. The interaction of magnetic resonance imaging-measured and histologically quantified pancreatic fat with the polygenic score was investigated. Partitioned risk scores using genome-wide significant variants were also computed to gain insight into potential mechanisms. RESULTS:Pancreatic steatosis interacted with genome-wide polygenic score on insulin secretion (P = 0.003), which was similar in the replication cohort with histological measurements (P = 0.03). There was a negative association between pancreatic fat and insulin secretion in participants with high genetic risk, whereas individuals with low genetic risk showed a positive correlation between pancreatic fat and insulin secretion. Consistent interactions were found with insulin resistance-specific and a liver/lipid-specific polygenic scores. CONCLUSIONS:The associations suggest that pancreatic steatosis only impairs beta-cell function in subjects at high genetic risk for diabetes. Genetically determined insulin resistance specifically renders pancreatic fat deleterious for insulin secretion.

SUBMITTER: Wagner R

PROVIDER: S-EPMC7497818 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pancreatic Steatosis Associates With Impaired Insulin Secretion in Genetically Predisposed Individuals.

Wagner Róbert R Jaghutriz Benjamin Assad BA Gerst Felicia F Barroso Oquendo Morgana M Machann Jürgen J Schick Fritz F Löffler Markus W MW Nadalin Silvio S Fend Falko F Königsrainer Alfred A Peter Andreas A Siegel-Axel Dorothea D Ullrich Susanne S Häring Hans-Ulrich HU Fritsche Andreas A Heni Martin M

The Journal of clinical endocrinology and metabolism 20201101 11

<h4>Context</h4>Pancreatic steatosis leading to beta-cell failure might be involved in type 2 diabetes (T2D) pathogenesis.<h4>Objective</h4>We hypothesized that the genetic background modulates the effect of pancreatic fat on beta-cell function and investigated genotype × pancreatic fat interactions on insulin secretion.<h4>Design</h4>Two observational studies.<h4>Setting</h4>University hospital.<h4>Patients or participants</h4>A total of 360 nondiabetic individuals with elevated risk for T2D (T ...[more]

PMID: 32725157

Similar Datasets

Project description:ObjectiveThis study aims to compare the levels of serum pancreatic polypeptide (PP), insulin (INS), C-peptide (C-P), and glucagon (GCG) before and after glucose stimulation in type 2 diabetes mellitus (T2DM) patients with different body mass indexes (BMI), analyze the relevant factors associated with PP secretion, and further investigate the role of PP in the development of obesity and diabetes.MethodsData were collected from 83 patients from the hospital. The subjects were divided into normal-weight group, overweight group, and obese group according to their BMI. All subjects were tested with the standard bread meal test (SBMT). PP and relevant parameters were measured, and the area under the curve (AUC) was calculated after 120 min of SBMT. AUCpp (AUC of PP) was used as the dependent variable, and the potential influencing factors were used as independent variables for multiple linear regression analysis.ResultsThe obese and overweight groups had significantly lower PP secretion than the normal-weight group (485.95 pg·h/ml, 95% CI 76.16-895.74, p = 0.021; 664.61 pg·h/ml, 95% CI 285.46-1043.77, p = 0.001) at 60 min postprandial. PP secretion in the obese and overweight groups was also significantly lower than that in the normal-weight group (520.07 pg·h/ml, 95% CI 186.58-853.56, p = 0.003; 467.62 pg·h/ml, 95% CI 159.06-776.18, p = 0.003) at 120 min postprandial. AUCpp was negatively associated with BMI (r = -0.260, p = 0.017) and positively associated with AUCGCG (r = 0.501, p< 0.001). Multiple linear regression analysis showed that there was a linear correlation between AUCGCG, BMI, and AUCpp (p< 0.001, p = 0.008). The regression equation was calculated as follows: AUCpp = 1772.255-39.65 × BMI + 0.957 × AUCGCG (R2 = 54.1%, p< 0.001).ConclusionCompared with normal-weight subjects, overweight and obese subjects had impaired PP secretion after glucose stimulation. In T2DM patients, PP secretion was mainly affected by BMI and GCG.Clinical trial registryThe Ethics Committee of the Affiliated Hospital of Qingdao University.Clinical trial registrationhttp://www.chictr.org.cn, identifier ChiCTR2100047486.

Dataset Information

Pancreatic Steatosis Associates With Impaired Insulin Secretion in Genetically Predisposed Individuals.

Publications

Pancreatic Steatosis Associates With Impaired Insulin Secretion in Genetically Predisposed Individuals.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets