Exocrine pancreatic function in hepatocyte nuclear factor 1β-maturity-onset diabetes of the young (HNF1B-MODY) is only moderately reduced: compensatory hypersecretion from a hypoplastic pancreas

• Published in: Diabetic medicine Vol. 30; no. 8; pp. 946 - 955
• Main Authors: Tjora, E., Wathle, G., Erchinger, F., Engjom, T., Molven, A., Aksnes, L., Haldorsen, I. S., Dimcevski, G., Ræder, H., Njølstad, P. R.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01.08.2013; Blackwell
• Subjects: Acinar Cells - pathology; Acinar Cells - secretion; Adolescent; Adult; Aged; Biological and medical sciences; Central Nervous System Diseases - genetics; Central Nervous System Diseases - pathology; Central Nervous System Diseases - physiopathology; Child; Dental Enamel - abnormalities; Dental Enamel - pathology; Dental Enamel - physiopathology; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - pathology; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Exocrine Pancreatic Insufficiency - etiology; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Hepatocyte Nuclear Factor 1-beta - genetics; Humans; Kidney Diseases, Cystic - genetics; Kidney Diseases, Cystic - pathology; Kidney Diseases, Cystic - physiopathology; Male; Medical sciences; Middle Aged; Mutation; Organ Size; Pancreas, Exocrine - pathology; Pancreas, Exocrine - physiopathology; Pancreas, Exocrine - secretion; Pancreatic Ducts - pathology; Pancreatic Ducts - physiopathology; Pancreatic Ducts - secretion; Pancreatic Juice - chemistry; Pancreatic Juice - secretion; Pedigree; Secretin; Up-Regulation; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Hypoplasia; Maturity onset diabetes young; Obesity; Nutrition; Digestive system; Liver; Nutrition disorder; Metabolic diseases; Hypersecretion; Genetic disease; Reduction; Hepatocyte; Malformation; Pancreas; Endocrinology; Nutritional status
• ISSN: 0742-3071; 1464-5491; 1464-5491
• DOI: 10.1111/dme.12190

Objectives To examine the exocrine pancreatic function in carriers of the hepatocyte nuclear factor 1β gene (HNF1B) mutation by direct testing. Methods Patients with HNF1B 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 mEq/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 (r2 = 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/cm3; P = 0.03), suggesting compensatory hypersecretion in the remaining gland. Conclusion Carriers of the HNF1B mutation have lower exocrine pancreatic function involving both ductal and acinar cells. Compensatory hypersecretion suggests that the small pancreas of HNF1B mutation carriers is attributable to hypoplasia, not atrophy. What's new? The exocrine pancreatic function in HNF1B‐MODY is moderately reduced. Both ductal and acinar pancreatic function are affected in HNF1B‐MODY. Ductal function in HNF1B‐MODY is dependent on the pancreatic gland size. There is a compensatory hypersecretion in HNF1B‐MODY as a response to secretin. The small pancreas in HNF1B‐MODY is probably attributable to hypoplasia, and not atrophy.