Exocrine pancreatic insufficiency (EPI) in type 3c diabetes

Pancreatic exocrine insufficiency in diabetes

• pancreatic exocrine insufficiency (EPI) is characterised by a deficiency of three major groups of pancreatic enzymes (amylase, protease, lipase):
  • causes an impairment in digestion and consequent nutrient malabsorption and malnutrition
• patients with type 1 or type 2 DM have been shown to have reductions in fecal elastase levels, with some pathologic changes similar to chronic pancreatitis (CP), and this has been termed "diabetic exocrine pancreatopathy"

• prevalence of EPI has been stated as an average of 40% in type 1 DM and 27% in type 2 DM (3)
  
  
• co-existing EPI in people with either type 1 or type 2 diabetes is likely to be a different clinical entity to pancreatic diabetes (sometimes referred to as type 3c diabetes) (4)
  • type 3c diabetes is diabetes due to pancreatic disease or injury so both endocrine and exocrine hormone production are affected
  • most commonly identified cause of type 3c diabetes is chronic pancreatitis

Clinical features of EPI:

• patients have varying degrees of exocrine and endocrine dysfunction
  • damage to the islet of Langerhans effects the secretion of hormones from the alpha, beta, and pancreatic polypeptide cells; the combination of low insulin, glucagon, and pancreatic polypeptide contributes to rapid fluctuations in glucose levels
    • form of "brittle diabetes" may result in the poorer glycemic control observed in patients with DEP/type 3c diabetes
    • patients are more likely to require early insulin initiation compared with those with T2DM
      • individuals should be advised about the symptoms of decompensated hyperglycemia, although they are less likely to develop ketoacidosis (5,6)
• symptoms of EPI develop when approximately 90% of the exocrine function of the pancreas is lost
  • possible clinical features of EPI include steatorrhea (often without diarrhea), abdominal bloating, weight loss, various vitamin deficiencies, and metabolic bone disease (6)

glycaemic control following pancreatic enzyme replacement therapy (PERT)

• pancreatic enzyme replacement therapy (PERT) can affect glycaemic control pathways via (7)
  • altered action of the hormones leptin and incretins on glucose homeostasis
    • PERT may lead to an improvement of incretin response to food and with consequent lower blood glucose levels
  • leading to improved absorption of oral diabetes medication
• there is a need to frequently check a patient's glycaemic response and blood glucose levels during PERT as the dose of the diabetes medication may need adjustment (especially sulphonylureas and insulin)

Management

• seek expert advice
• is generally managed by starting with metformin, but insulin may eventually be needed
• incretin therapy is avoided considering the risk of pancreatitis (8)
• need consistent treatment of PEI (pancreatic exocrine insufficiency) to ensure nutrient absorption for prevention of hypoglycemia and additional vigilance to prevent hypoglycemia because of potential loss of counter-regulatory glucagon secretion (8)

Reference:

• Mohapatra S, Majumder S, Smyrk TC, et al. : Diabetes Mellitus Is Associated With an Exocrine Pancreatopathy: Conclusions From a Review of Literature. Pancreas. 2016;45(8):1104-10. 10.1097/MPA.0000000000000609
• Struyvenberg MR, Martin CR, Freedman SD: Practical guide to exocrine pancreatic insufficiency - Breaking the myths. BMC Med. 2017;15(1):29. 10.1186/s12916-017-0783-y
• Zsori G, Illes D, Terzin V, et al. : Exocrine pancreatic insufficiency in type 1 and type 2 diabetes mellitus: do we need to treat it? A systematic review. Pancreatology. 2018;18(5):559-65, pii: S1424-3903(18)30111-X. 10.1016/j.pan.2018.05.006
• Hart PA et al. Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer.Lancet Gastroenterol Hepatol. 2016 Nov; 1(3): 226-237.
• Wynne K et al. Diabetes of the exocrine pancreas. J Gastroenterol Hepatol. 2018 Aug 27.
• Ewald N, Kaufmann C, Raspe A, Kloer HU, Bretzel RG, Hardt PD. Prevalence of diabetes mellitus secondary to pancreatic diseases (type 3c). Diabetes Metab Res Rev. 2012; 28:338-42.
• Pham A, Forsmark C: Chronic pancreatitis: review and update of etiology, risk factors, and management. F1000Res. 2018;7: pii: F1000 Faculty Rev-607. 10.12688/f1000research.12852.1
• Hines O J, Pandol S J. Management of chronic pancreatitis BMJ 2024; 384 :e070920 doi:10.1136/bmj-2023-070920