Exocrine pancreatic function in hepatocyte nuclear factor 1β‐maturity‐onset diabetes of the young ( HNF 1B‐ MODY ) is only moderately reduced: compensatory hypersecretion from a hypoplastic pancreas

Abstract Objectives To examine the exocrine pancreatic function in carriers of the hepatocyte nuclear factor 1β gene ( HNF 1B ) mutation by direct testing. Methods Patients with HNF 1B mutations and control subjects were assessed using rapid endoscopic secretin tests and secretin‐stimulated magnetic resonance imaging. Seven patients and 25 controls underwent endoscopy, while eight patients and 20 controls had magnetic resonance imaging. Ductal function was assessed according to peak bicarbonate concentrations and acinar function was assessed according to peak digestive enzyme activities in secretin‐stimulated duodenal juice. The association of pancreatic exocrine function and diabetes status with pancreatic gland volume was examined. Results The mean increase in secretin‐stimulated duodenal fluid was smaller in patients than controls (4.0 vs 6.4 ml/min; P  =   0.003). We found lower ductal function in patients than controls (median peak bicarbonate concentration: 73 vs 116 mE q/L; P  <   0.001) and lower acinar function (median peak lipase activity: 6.4 vs 33.5 kU /ml; P  =   0.01; median peak elastase activity: 0.056 vs 0.130 U/ml; P  =   0.01). Pancreatic fluid volume outputs correlated significantly with pancreatic gland volumes ( r 2   =   0.71, P  =   0.008) in patients. The total fluid output to pancreatic gland volume ratios were higher in patients than controls (4.5 vs 1.3 ml/cm 3 ; P  =   0.03), suggesting compensatory hypersecretion in the remaining gland. Conclusion Carriers of the HNF 1B mutation have lower exocrine pancreatic function involving both ductal and acinar cells. Compensatory hypersecretion suggests that the small pancreas of HNF 1B mutation carriers is attributable to hypoplasia, not atrophy.