title: Inverse association of HbA1c with faecal elastase 1 in people without diabetes.
abstract: OBJECTIVE
  Faecal elastase 1 (FE1) was inversely correlated with diabetes duration and HbA1c in type 2 diabetes. The association of FE1 and HbA1c has not been investigated in people without diabetes.
  
  
  METHODS
  Type 2 diabetes patients (oral antidiabetic drugs or insulin: n = 391; medically untreated: n = 145) and matched (age, sex, practice) people without diabetes (n = 529) from general practices in Cambridgeshire (UK) were included. FE1 measurements (μg/g stool) were performed centrally (ScheBo-Tech Institute, Wettenberg, Germany). Linear regression models were fitted using FE1 as dependent variable and HbA1c, diabetes (no, untreated diabetes, treated diabetes) and interactions as independent variables. Potential confounders were sex, age, BMI, current alcohol consumption, smoking, triglycerides, and amylase.
  
  
  RESULTS
  In univariate linear regression models, HbA1c was significantly inversely related to FE1 in controls (β-coefficient: -108.74, p < 0.0001), whereas no significant associations were found for the diabetes groups. The inverse relationship of HbA1c with FE1 concentrations in people without diabetes persisted after adjusting for potential confounders in multivariate regression (β-coefficient: -109.18, p < 0.0001). In people without diabetes, there were lower FE1 concentrations among those with increased diabetes risk (HbA1c 5.7%-6.4% [38.8-46.4 mmol/mol]: 395 ± 204 μg/g vs. HbA1c ≤ 5.6% [≤37.7 mmol/mol]: 476 ± 219 μg/g; p < 0.0001). The prevalence of FE1<100 μg/g was significantly increased among persons with an HbA1c of 5.7%-6.4% (38.8-46.4 mmol/mol) compared with those with a normal HbA1c ≤ 5.6% (≤37.7 mmol/mol) (6.1% vs. 1.4%; p = 0.004).
  
  
  CONCLUSIONS
  The present study suggests that pancreatic exocrine dysfunction might be an early disturbance that develops in parallel with hyperglycemia.
authors.affiliation: Institute for Biometrics and Epidemiology, German Diabetes Center, Düsseldorf, Germany. Electronic address: rathmann@ddz.uni-duesseldrof.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rathmann
authors.affiliation: MediStatistica, Neuenrade, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Haastert
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Oscarsson
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Berglind
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D005243:Feces / Q000201:enzymology*; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D016014:Linear Models; D008875:Middle Aged; D010196:Pancreatic Elastase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D010196:Pancreatic Elastase; C517652:hemoglobin A1c protein, human
keywords: Exocrine pancreas; Faecal elastase 1; HbA1c; Pancreatic exocrine dysfunction; Prediabetes; Type 2 diabetes