- Credits - Section Writer: [[Dr. Om J Lakhani]] - Section Editor: [[Dr. Om J Lakhani]] - Q. What is the definition of Fibrocalculous pancreatic diabetes (FCPD)? - Diabetes associated with non-alcoholic calcific pancreatitis seen in developing countries - Q. What is the prediabetic form of FCPD? - It is called tropical calcific pancreatitis (TCP) - Q. Give the difference between TCP and Alcoholic pancreatitis? -  - Q. Who is the father of FCPD? - Geeverghese - Q. Which are the two types of malnutrition-related DM (MRDM)? - Fibrocalculous pancreatic diabetes - Protein deficient diabetes mellitus - Q. What is the typical triad of FCPD? - Abdominal pain- the first symptom- in childhood - Pancreatic calculi- In adolescent - Diabetes – in adulthood - Q. Where is the calcification seen in Plain Xray in FCPD? - Close to L1/L2 vertebra - Q. Ketosis is present in FCPD. True or false? - False - Patients with FCPD do not develop ketosis - Q. Intake of which food substance is implicated in causing FCPD? - Cassava - Q. Which cancer risk is increased in FCPD ? - Pancreatic cancer - Q. There are no microvascular complications in FCPD, True or false? - False - It was believed earlier but no so anymore - Microvascular complications are very much present in patients with FCPD - Q. What are the diagnostic criteria for FCPD? - As given by Mohan et al - Essential criteria - Diabetes present - Patient from a tropical country - Absence of any other cause of pancreatitis - Any 3 of the following - Abnormal morphology of pancreas on imaging - Abnormal pancreatic function test - Abdominal pain –recurrent since childhood - Steatorrhea - Q. Which is the tumor marker for pancreatic cancer? - CA 19-9 - Q. What is the classical clinical description of a patient with FCPD? - Cyanotic hue - emaciated - Parotidomegaly - Abdominal distention - Q. Why is there no ketosis in FCPD? - Some of the theories for absence of ketosis in FCPD are as follows - No non-esterified fatty acid hence less substrate for ketosis - Also there is reduced glucagon along with insulin - High glucagon and reduced insulin is required for ketosis to develop - The fat present is resistant to lipolysis - There is some eesidual beta-cell function - Carnitine deficiency – prevents Fatty acid entering the mitochondria for beta-oxidation - Q. Is the calcification present in the parenchyma or in the duct ? - FCPD- in the duct - Alcoholic pancreatitis – in the parenchyma - Q. What is the composition of the calculi ? - It is composed of calcium carbonate - Q. Can ERCP and EUS be used to define pancreatic morphology in FCPD ? - Yes - Q. Which is the invasive test for detecting pancreatic function ? - Injection of secretin and Pancreozymin - Collection of pancreatic juice - Juice contains less of lipase, bicarbonate and trypsin compared to normal - Q. Which are non-invasive (tubeless tests for pancreatic function) ? - BT-PABA (Bentriomide para aminobenzyoic acid) - Urine / plasma - Fecal elastase - Fecal chymotrypsin - Q. Which is the gold standard Tubeless test ? - Fecal elastase - Q. How Is endocrine pancreatic function tested for in FCPD ? - Using C-peptide - The value is intermediate between type 1 and type 2 – suggestive of residual pancreatic function - Q. What is done for abdominal pain in FCPD ? - It occurs earlier - Non-opiod / opiod analgesisc are used - It resolves once the endocrine dysfunction occurs - Pancreatic enzyme supplementation does not reduce the pain - Q. What is done for non resolving pain ? - ESWL + ERCP - Celiac plexus block - Surgery drainage procedures – ductal decompression or pancreaticojejunostomy - Surgery ablative procedures – partial or subtotal pancreatectomy - Q. What is done for the management of steatorrhea? - Pancreatic enzyme supplementation - Reduce diet fat - Give vitamins - Q. What is the dose of pancreatic enzyme supplementation in these patients? - Typical brand name is "Creon" 10,000 units before each meal #Clinicalpearl - In clinical practice is is observed that giving pancreatic enzyme supplement also has some beneficial effect on glycemic control. Some experts have suggested a link between the exocrine and endocrine dysfunctions. - Q. What is the best treatment of diabetes in these patients? - 85% require insulin - Some may do well with OAD because of residual pancreatic function - However, incretin-based therapies are best avoided - They often have brittle diabetes and prone to hypoglycemia - Q. What is done for nutrition ? - Diet rich in proteins and carbs are given to combat the malnutrition - Fat-soluble vitamins - Avoid fat – to reduce steatorrhea - Q. Enlist the pathogenic factors for FCPD? - Malnutrition - Protein deficiency - Cassava toxicity - Oxidative stress - Genetic and familial causes - Q. Which are the cyanogenic glycosides present in cassava? - Linamarin - Lotaustralin - Q. What are the investigations done to diagnose FCPD ? - Tests to detect pancreatic function- - Test to detect pancreatic morphology - Xray, USG , EUS, ERCP, etc - Q. Which are the tests to detect pancreatic function? - Fecal elastase - Fecal chymotrypsin - Fecal immunoreactive lipase - Q. Enlist the complications associated with FCPD? - Pancreatic cancer- 100 times increased risk - Retinopathy and other microvascular complications - Pancreatic osteodystrophy – malnutrition + malabsorption + diabetes = severe osteoporosis - Pancreatic exocrine deficiency - Q. Enlist the treatment options for FCPD? - Diabetes management - Exocrine pancreatic enzyme replacement - Fat-soluble vitamin replacement- intramuscularly - Pain management - Endotherapy- ESWL + ERCP - Early cancer detection - Surgical therapy- mainly for the pain - #Updates - Date: Monday, 19 April 2021 - Source: Review article: Emerging concepts in the pathogenesis of diabetes in fibrocalculous pancreatic diabetes ^[Dasgupta R, Naik D, Thomas N. Emerging concepts in the pathogenesis of diabetes in fibrocalculous pancreatic diabetes. J Diabetes. 2015 Nov;7(6):754-61. doi: 10.1111/1753-0407.12280. Epub 2015 May 6. PMID: 25707547.] - Q. Is malnutrition a cause or effect of FCPD? - Recent studies suggest malnutrition is an effect rather than the cause of FCPD - Q. Enlist the various theories for FCPD over time? - Cassava theory – Geerverghese and McMillin - Increase oxidative stress theory - Genetic theory – recent theory - Q. Which genetic mutation has been associated with FCPD ? - SPINK1 - PRSS1 and PRSS2 - Chymotrypsinogen C - Q. Diabetes onset is at what age ? - Generally age 20-30 years - About 1-2 decade after first episode of abdominal pain - Q. Is insulin secretory defect established in FCPD? - Yes - Q. Is the exocrine and endocrine deficiency linked? - It seems from some of the studies done by Yajnik et al - Q. What is the newer paradigm in the etiology of diabetes in FCPD? - New interest in FCPD is directed to insulin resistance as a cause of diabetes in FCPD - Q. What is the link between insulin resistance and chronic pancreatitis? - Some studies have shown that patient with pancreatic diabetes have hepatic insulin resistance due to internalization of hepatic insulin receptors and GLUT2 - The role of the pancreatic polypeptide has also been proposed - Q. What is the role of a pancreatic polypeptide? - Studies have shown that pancreatic polypeptide regulates the expression of the IR gene in the liver - Thus impairment of PP will impair glucose homeostasis via IR gene expression in liver - Q. Do patients with FCPD have insulin resistance similar to Type 2 diabetes patients? - Yes - This is according to a study by Mohan et al - So FCPD patients have insulin resistance similar to type 2 diabetics! - Q. Is the BMI in these patients showing something else? - Singla et al. showed that these patients have higher body fat percentage despite low BMI - This could contribute to the insulin resistance - Q. What is the vicious cycle of glucagon and insulin? - As far as 35 years ago, it was proposed that diabetes is not just an insulin problem but also a problem with glucagon - Insulin resistance increases insulin production and secretion → higher intra-islet insulin concentration → increase glucagon production → further increase insulin secretion → vicious circle - Q. Is glucagon indeed depleted in patients with FCPD? - This theory is questioned now - Some studies by Mohan and Yajnik have shown that FCPD may have preserved glucagon response and selective damage to beta cells - Q. What is the role of incretin hormones in the pathogenesis of diabetes in chronic pancreatitis - Knop et al. suggested that CP without diabetes had an intact incretin response compared to CP with diabetes - This may be the missing link in FCPD - Also, he showed that pancreatic enzyme replacement might augment incretin response- a theory that could have an impact on the management of FCPD - Q. What is the role of body composition causing diabetes in FCPD? - There is a theory that the lack of fat tissue may be to lipodystrophy like effect, which can lead to insulin resistance in FCPD patients - Deficiency fat stores increase hepatic triglyceride stores → increase circulating fatty acids → improve insulin resistance #Real-life-cases Date - Monday, 19 April 2021 - A 30 year old male presented with history of unintentional weight loss - His weight reduced from 100 kg to 70 kg over a period of 3 months - During this process the patient was found to have hyperglycemia - The patient was started on insulin, some weight was regained but over a few weeks he started developing hypoglycemia - Insulin was stopped and the patient was started on Oral antidiabetics by his physician - At age of 25, he had recurrent episodes of abdominal pain which were never investigated - When he came to us he had an HbA1c of 10% - Looking at the unusual history, we decided to perform a CT scan of the abdomen - True to what we suspected, we found the pancreas studded with calcification -  -  - There was no evidence of malignancy - however the risk and screening for the same has been explained to the patient - The patient was restarted on insulin and pancreatic enzyme supplementation along with nutritional replenishment - Currently he has regained some weight and maintain good glycemic control Things to learn from the case: - Sometimes a diagnosis of FCPD can be made retrospectively ! - In patients with acute symptomatic hyperglycemia- if the [[Glucose Toxicity (Glucotoxicity)]] breaks- the patient can start developing hypoglycemia. The risk of hypoglycemia is higher in patients with FCPD - Abdominal pain can disappear over a period of time. At later age the patient may present with just exocrine and endocrine insufficiency - This patient is from Rajasthan. FCPD is not restricted to some regions of the country and can be considered a pan-Indian issue #Updates ; Date: Friday, 9 July 2021 - Q. Can you give a map of regions in the world in which [[Fibrocalculous pancreatic diabetes]] is seen ? -  ---- Please consider donating to *"Notes in Endocrinology"* to keep us going. Please visit our [[DONATION]] page to know more