Diabetes of the exocrine pancreas (DEP)

Diabetes due to diseases of the exocrine pancreas (DEP) was previously described as pancreatogenic or pancreatogenous diabetes mellitus - however recent literature refers to it as type 3c diabetes

• is far more common than has been previously considered, with a recent study showing 1.8% of adults with new-onset diabetes should have been classified as DEP
  • majority is misdiagnosed as type 2 diabetes mellitus (T2DM)
  • 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 (1,2)
          
          
• DEP/type 3c diabetes is not a single entity
  • occurs because of a variety of exocrine pancreatic diseases with varying mechanisms of hyperglycaemia
  • most commonly identified causes of type 3c diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma, haemochromatosis, cystic fibrosis, and previous pancreatic surgery
    • distribution of causes for type 3c diabetes consisted of
      • chronic pancreatitis (79%),
      • pancreatic ductal adenocarcinoma (8%),
      • haemochromatosis (7%),
      • cystic fibrosis (4%), and previous pancreatic surgery (2%)
        
        
• two major causative factors in the pathogenesis of diabetes are inadequate pancreatic beta-cell function (type 1 diabetes) and insulin resistance (type 2 diabetes)
  • two factors appear to contribute differentially to the hyperglycaemia observed in patients with type 3c diabetes
    
    
• no universally accepted diagnostic criteria for type 3c diabetes (DEP)
  • diagnosis can be made in patients who meet the three following criteria (2):
    • those who fulfil the diagnostic criteria for diabetes,
    • those who have a disease of the exocrine pancreas, and
    • those whose diabetes is reasonably certain to be secondary to their exocrine pancreatic disease
      
      
• management of DEP/Type 3c diabetes
  • patients with DEP can benefit from specific lifestyle advice, pancreatic enzyme replacement therapy, metformin treatment, appropriate insulin dosing, and monitoring (1)

Notes:

• should screen for DEP/Type 3 c diabetes in patients with acute or chronic pancreatitis, following pancreatic resection, or with co-existing cystic fibrosis or hemochromatosis
  • incident diabetes may herald the onset of pancreatic ductal carcinoma in a small subset of patients (1)

Reference:

• 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.
• Hart PA et al. Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer. Lancet Gastroenterol Hepatol . 2016 November ; 1(3): 226-237.