Pancreatitis Often Leads to Rarer Form of Diabetes, Often Misdiagnosed

It is well known that people suffering from chronic pancreatitis (“CP”) are at high risk of developing diabetes.  Much less well know, however, is that CP leads to its own specific type of diabetes, Type 3C.  An article in this month’s World Journal of Gastroenterology (available in full for free here) focuses on this phenomenon and the risks and challenges it poses.

Much less is understood about type 3c diabetes than the more common types 1 and 2.  It is a disease very closely related to chronic pancreatitis — according to the authors, over 80% of cases are caused by CP, as over time CP destroys pancreatic islet cells and reduces insulin production.  They report that up to 70% of patients with a confirmed diagnosis of chronic pancreatitis will develop type 3c diabetes…and the prevalence rises to 90% where there is calcification.  Essentially this form of diabetes is a companion condition and should always be considered when a patient has CP.

The authors explain that type 3c is often misdiagnosed, for several reasons. First, when people present with diabetes but have not yet been diagnosed with CP, doctors often assume that it is the more common forms and don’t go on to test for CP (which, as we know, is not easy to detect).  Second, since diabetes can itself lead to pancreatitis, finding the two together may prompt doctors to assume that diabetes came first.  Third, there are not clear diagnostic criteria for type 3c, though the authors go on to propose a high-level list (see Table 2).

This is problematic because type 3c diabetes requires specific treatments that are different than those for types 1 and 2.  And missing the diagnosis of CP means that the condition itself may go untreated.  There are apparently no established guidelines for treatment of type 3c, though the topic was addressed at the 2012 PancreasFest conference.  In general, the authors explain that for type 3c “treating exocrine pancreatic insufficiency, preventing or treating a lack of fat-soluble vitamins (especially vitamin D) and restoring impaired fat hydrolysis and incretin secretion are key-features of medical therapy.” The authors review the current evidence on appropriate therapies, though clearly more research is required.

Interestingly, the authors conclude that chronic pancreatitis may be considerably more common than we think.  The reach this conclusion after finding that type 3c accounts for a much larger proportion of diabetes cases than originally thought — 5-10% of cases rather than traditional estimates of around 1%. Since CP accounts for 80% of those cases, there must be a lot of people with undiagnosed CP.  This is apparently confirmed in autopsies; like some slow growth cancers, many people in the general population may develop CP and never know it.

One other noteworthy point in the article:  In discussing the prevalence of CP, they observe that “chronic pancreatitis has previously been considered a disease of alcoholism until the discovery that it is a multifactorial disease with an impact of complex genetic genotypes, smoking, special anatomic conditions, toxic agents and autoimmunity.”  As CP patients know well, many medical professionals are slow to come to this realization, attributing CP mainly to alcohol abuse.

Fortunately, there seems to be a lot of new research on pancreatitis in the last few years.  This month’s issue of the World Journal of Gastroenterology alone had several insightful articles, including one on pain management discussed here.  We need to make sure that doctors on the front lines are aware of these developments and treat their patients accordingly.

Pain in Chronic Pancreatitis: Traditional Methods Are Ineffective

The most vexing aspect of chronic pancreatitis is recurring pain.  Pain can be overwhelming, can occur daily or last for days or weeks at a time.  And treatment is a challenge, often involving strong opioids such as oxycodone.  These medications are highly addictive and come with their own gastrointestinal side effects (such as “opioid-induced bowel disfunction“), making them problematic for the long term.

A new article published this month in the World Journal of Gastroenterology examines the nature of pain in CP and offers some interesting observations.  Most fundamentally, the authors argue that much of the pain in CP is not “nociceptive,” meaning (in simple terms) that it is not directly caused by an immediate injury.  Instead, repeated inflammation and injury cause damage to the pancreatic nerves, which alters the pain processing system itself.  Because of this, “management of pain by traditional methods… (e.g., surgery and visceral nerve blockade) becomes difficult and ineffective.”

So if traditional methods of pain management are ineffective and opioids are problematic, what do the authors suggest?  For starters, they note that “adjuvant analgesics” — medications commonly used for other purposes such as antidepressants — have proven relatively effective for CP pain.  They cite their own study that pregabalin, an anticonvulsant, had a significant reduction in self-reported pain.  They also highlight ketamine, historically used as an anesthetic, as shown to be helpful.  They review the current science on pancreatic enzymes and antioxidants, which at best offer conflicting evidence when it comes to pain. They then surmise that some emerging treatments for other maladies, such as nerve growth factor (“NGF” — used for knee pain) may hold promise for CP, though these drugs  have yet to be tested for the condition.

Overall, the authors recommend a multidisciplinary approach to pain management that examines the mechanisms at work for the specific patient and apply the treatments thought to be most promising for each.  (They provide a flow chart for approaching the issue, available here.)  They also stress that a stable doctor-patient relationship is a key success factor…something patients can certainly attest to.

The article offers a rigorous look at the source of pain for CP and the most effective approaches.  Well worth sharing with your doctor.