It has been recognised for a long time that pancreatic damage caused by pancreatic surgery, pancreatic inflammation (both acute and chronic pancreatitis) and other diseases that affect the pancreas can lead to diabetes. It has also been widely recognised that this type of diabetes is distinct from both type 1 and type 2 diabetes. It has been given various names; secondary pancreatic diabetes, pancreatogenic diabetes, diabetes of the exocrine pancreas (DEP) and type 3c diabetes. What has not been fully appreciated is how common this type of diabetes is.
First study into type 3c diabetes
We have recently undertaken the first large-scale population study that attempts to quantify the prevalence of type 3c diabetes (Woodmansey et al, 2017). We looked at the primary care records of 2.4 million people in England, using the Royal College of General Practitioner Research and Surveillance Centre Database, to identify cases of new onset diabetes in adults between 1st January, 2005 and 31st March, 2016. We then searched the preceding medical record for any evidence of any diseases of the pancreas.
Within the search period we found 31 789 cases of new adult-onset diabetes. Of these, 559 cases had a history of pancreas disease and therefore were possibly cases of type 3c diabetes. This was more common than adult-onset type 1 diabetes, with 354 cases recorded. This equated to 2.6 cases per 100 000 person-years for type 3c diabetes compared with 1.6 cases per 100 000 person-years for type 1 diabetes (P<0.001).
Diabetes after pancreatic disease had a mean age of onset of 59 years (interquartile range [IQR] 49–70) and a median BMI of 29.2 kg/m2 (IQR 25.7–34.3). Therefore these individuals appeared very similar to people with type 2 diabetes, but when we looked at their outcomes after diagnosis, we found that people with a history of pancreatic disease were much more likely to need insulin and much less likely to achieve good glycaemic control.
In people with a history of acute pancreatitis, 20.9% (95% confidence interval [CI] 14.6–28.9%) were on insulin five years after diagnosis and in those with a history of chronic pancreatic disease (chronic pancreatitis, pancreatic cancer, pancreatic surgery, cystic fibrosis, or haemochromatosis), this rose to 45.8% (95% CI 34.2–57.9%). People with diabetes following pancreatic disease were nearly twice as likely to fail to reach an HbA1c target of 53 mmol/mol (7%) compared to people with type 2 diabetes (Odds ration [OR] 1.7; 95 CI 1.3–2.2).
We also found that people with diabetes and a history of pancreatic disease were almost never considered to have type 3c diabetes. The majority, 87.8%, were classified as type 2 diabetes; 7.7% were classified as type 1 diabetes; and only 2.7% were classified as having secondary diabetes.
Complications
Type 3c diabetes is about more than just glycaemic control and insulin use, however. As the damage to the pancreas is global, not just to beta cells, there is loss of all the functions of the pancreas. This includes damage to alpha cells and the cells that produce the pancreatic digestive enzymes. Lack of alpha cells leads to lack of glucagon, which may produce a more brittle form of diabetes with higher hypoglycaemia risk (although the data on this is limited). Lack of pancreatic enzymes leads to fatty stool (steatorrhoea), abdominal pain and bloating, weight loss, and occasionally vitamin deficiency. Vitamin deficiencies tend to be in the fat-soluble vitamins A, D, E, and K. In particular, vitamin D deficiency can lead to osteoporosis, which is present in around 1 in 4 people with chronic pancreatitis.
Failing to identify type 3c diabetes may result in missing these additional complications. We suggest that a diagnosis of type 3c diabetes should be considered in all people with a history of pancreatic disease.
References
Woodmansey C, McGovern AP, McCullough KA et al (2017) Incidence, demographics, and clinical characteristics of diabetes of the exocrine pancreas (type 3c): A retrospective cohort study. Diabetes Care 40: 1486–93
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