Emerging concepts in the pathogenesis of diabetes in fibrocalculous pancreatic diabetes
While definitive criteria for the assessment of the PP response to nutrients have yet to be established, non-diabetic subjects demonstrate a fold increase over basal levels, whereas patients with chronic pancreatitis-associated diabetes demonstrate less than a doubling of their basal values 8. In addition to considering pancreatic endocrine function testing as above, the diagnosis will require evidence of pancreatic exocrine dysfunction, with fecal elastase-1 serving as a noninvasive screening test 25 , and some form of sensitive imaging for detecting pancreatic pathology 2.
When weight loss exists, and especially if out-of-proportion for the severity of the presenting diabetes, pancreatic imaging is essential for possible early detection of pancreatic cancer While limited data exist, patients with T3cDM appear to share a similar risk for the micro- and macro-vascular complications of diabetes as seen in T1DM and T2DM 7, Thus, patients should be monitored for the development of retinopathy, nephropathy, neuropathy, and follow the same cardiovascular disease risk reduction guidelines as for patients with T1DM and T2DM Currently, there are no randomized controlled trial data available to direct the development of guidelines specific to T3cDM.
Therefore, the recommendations detailed below are based on guidelines developed as part of a consensus conference of gastroenterologists, endocrinologists, and surgeons with clinical and research expertise in the management of chronic pancreatitis and its complications Attempts to reduce the toxic and modifiable contributors to chronic pancreatitis such as abstaining from alcohol and smoking cessation are highly recommended as both exacerbate progression of underlying pancreatic inflammation and fibrosis and contribute to pain.
Alcohol abstinence is also helpful for diabetes management, since alcohol acutely inhibits hepatic glucose production and can cause hypoglycemia, especially in the setting of insulin therapy. Medical nutritional therapy should include advice regarding eating meals rich in soluble fiber and low in fat, and in patients with any degree of pancreatic exocrine insufficiency, together with oral enzyme replacement.
Oral pancreatic enzyme replacement is particularly important for fat digestion and absorption, and so helps to control symptoms of steatorrhea and protect against fat soluble vitamin deficiency. Maintaining sufficient levels of vitamin D is essential to prevent the development of metabolic bone disease and osteoporosis As already discussed, treatment with pancreatic enzymes is also important for maintaining incretin hormone secretion in patients with exocrine insufficiency where their use is associated with better glucose tolerance during meal ingestion.
Since the principal endocrine defect is insulin deficiency, insulin therapy is the preferred treatment for most patients, and especially to correct hyperglycemia for CFRD, for acutely ill or hospitalized patients, and for severely malnourished patients wherein the anabolic effects of insulin are particularly beneficial.
When concomitant insulin resistance is suspected or evidenced, therapy with the insulin sensitizer metformin should be considered.
Fibrocalculous pancreatic diabetes in adult
Metformin is recommended as first-line oral therapy for T2DM 31 , a population in which metformin may reduce the risk of pancreatic cancer, and so has a theoretical rationale in chronic pancreatitis if tolerable due to common gastrointestinal adverse effects and weight loss. Therapy with insulin secretagogues sulfonylureas and glinides may also be considered, but because these drugs can cause hypoglycemia, short-acting agents are preferred when meal ingestion is inconsistent.
Incretin-based therapies e. GLP-1 analogues and DPP-IV inhibitors also enhance insulin secretion, but have been associated with cases of drug-induced pancreatitis 2 precluding their use in T3cDM until more data become available. TPIAT is considered as definitive treatment of recurrent acute or chronic pancreatitis for the primary indication of providing pain relief, with hoped for withdrawal of narcotics and amelioration from recurrent hospitalizations to treat pain exacerbations 3.
It is important to appreciate that the objective of the islet autotransplant is prevention or amelioration of surgical diabetes, and while the chances of achieving good glycemic control increase with exclusion of pre-existing T3cDM, this procedure does not prevent nor is a treatment for T3cDM.
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All of the histology slides presented in Figure 2 are a generous contribution from Dr. Skip to main content. Search form Search. Lalitha Gudipaty and Michael R. Gudipaty, Lalitha. Rickels, Michael R. Pancreatogenic Type 3c Diabetes. Attachment Size Pancreatogenic Type 3c Diabetes Definition Pancreatogenic diabetes is a form of secondary diabetes, specifically that associated with disease of the exocrine pancreas.
Epidemiology While diseases of the pancreas are uncommon, diabetes mellitus is common in patients with pancreatic disease and following pancreatic resection. Clinical Presentation Because exocrine insufficiency usually pre-dates endocrine insufficiency in chronic pancreatitis, most patients with T3cDM have a known history of pancreatitis with abdominal pain, steatorrhea or maldigestion with nutritional deficiencies and glucose intolerance.
This imaging modality has a high sensitivity but limited specificity. The most common pancreatic function tests do not detect mild to moderate exocrine pancreatic insufficiency with adequate accuracy. Late in the disease, tests of pancreatic exocrine function more reliably become abnormal.
Direct tests are done to monitor the actual secretion of pancreatic exocrine products bicarbonate and enzymes , whereas indirect tests are done to measure the secondary effects resulting from the lack of pancreatic enzymes eg, fat malabsorption. Direct pancreatic function tests are most useful in patients who have an earlier stage of chronic pancreatitis in whom imaging studies are not diagnostic. Direct tests involve intravenous infusion of the hormone cholecystokinin to measure the production of digestive enzymes or infusion of the hormone secretin to measure the production of bicarbonate.
The duodenal secretions are collected using double-lumen gastroduodenal collection tubes or an endoscope. Direct tests are cumbersome, are time-consuming, and have not been well standardized. Direct pancreatic function tests have mostly been phased out of clinical practice and are done in only a few specialized centers. Indirect pancreatic function tests are less accurate in diagnosing earlier stages of chronic pancreatitis.
These tests involve blood or stool samples. The serum trypsinogen test is an inexpensive test and is available through commercial laboratories. A hour test for stool fecal fat in patients who are following a high-fat diet is diagnostic for steatorrhea. This test is fairly reliable but cannot establish the cause of malabsorption. In other tests, fecal concentration of chymotrypsin and elastase may be decreased. The indirect tests are widely available, less invasive, inexpensive, and easier to do than the direct tests. Pain control is the most challenging task in the management of patients with chronic pancreatitis.
First, vigorous efforts and appropriate referrals to encourage smoking cessation and alcohol abstinence should be made for patients with chronic pancreatitis in an effort to slow the disease progression as early as possible. Second, treatable complications of chronic pancreatitis that can cause similar symptoms should be sought. Patients with chronic pancreatitis should be educated about healthy lifestyle practices, and this should be reinforced at each visit. Pancreatic enzyme supplementation may reduce chronic pain by suppressing the release of cholecystokinin from the duodenum, thereby reducing the secretion of pancreatic enzymes.
Enzyme therapy is more likely to be successful in patients with less advanced disease, in women, and in patients with idiopathic pancreatitis than in patients with alcoholic pancreatitis.
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Although enzyme therapy is often tried because of its safety and minimal adverse effects, it may not provide substantial benefit in improving pain. Often these measures do not relieve pain, requiring increased amounts of opioids, which increases the risk of addiction. Adjunctive pain drugs, such as tricyclic antidepressants, gabapentin , pregabalin , and selective serotonin reuptake inhibitors, have been used alone or combined with opioids to manage chronic pain; results are variable.
Drug treatment of pain in chronic pancreatitis is often unsatisfactory. Other treatment modalities include endoscopic therapy, lithotripsy, celiac plexus nerve block, and surgery. Endoscopic therapy is aimed at decompressing a pancreatic duct obstructed by stricture, stones, or both and may provide pain relief in carefully selected patients with appropriate ductal anatomy.
If there is significant stricture at the papilla or distal pancreatic duct, endoscopic retrograde cholangiopancreatography ERCP with sphincterotomy, stent placement, or dilation may be effective. Pseudocysts can cause chronic pain.
Fibrocalculous pancreatic diabetes—current scenario in developing countries
Some pseudocysts can be drained endoscopically. Lithotripsy extracorporeal shock wave lithotripsy or intraductal lithotripsy is usually need to treat large or impacted pancreatic stones. Percutaneous or endoscopic ultrasound-guided nerve blockade of the celiac plexus with a corticosteroid and long-acting anesthetic may provide short-term pain relief in some patients with chronic pancreatitis. Surgical treatment may be effective for pain relief. Surgical options should be reserved for patients who have stopped using alcohol and who can manage diabetes that may be intensified by pancreatic resection.
The choice of surgical procedure depends on the anatomy of the pancreatic duct, consideration of local complications, the surgical history of the patient, and local expertise. If the pancreatic duct is not dilated, a variation of the modified Puestow procedure called a V-plasty or Hamburg procedure can be done. Other surgical approaches include a partial resection such as a distal pancreatectomy for extensive disease at the tail of the pancreas , a Whipple procedure for extensive disease at the head of the pancreas , a pylorus-sparing pancreaticoduodenectomy similar to a Whipple procedure , a duodenum-preserving pancreatic head resection Beger procedure , or a total pancreatectomy with autotransplantation of islets.
Overall, surgical drainage is more effective than endoscopic approaches in relieving obstruction and achieving pain relief 1.
In patients with exocrine pancreatic insufficiency, malabsorption of fat is more severe than malabsorption of proteins and carbohydrates. Fat malabsorption also results in a deficit of fat-soluble vitamins A, D, E, and K. Pancreatic enzyme replacement therapy replacement of deficient hormones to treat pancreatic insufficiency is used to treat steatorrhea.
Various preparations are available, and a dose of 75, to , United States Pharmacopeia units 25, to 50, international units lipase per meal and half that amount with snacks is needed for appropriate fat absorption. The treatment should be started at a low dose with subsequent titration based on clinical response. The preparations should be taken with meals. An H2 blocker or proton pump inhibitor should be given to patients taking nonenteric—coated preparations to prevent acid breakdown of the enzymes.
Favorable clinical responses include weight gain, fewer bowel movements, elimination of oil droplet seepage, increases in levels of fat-soluble vitamins, and improved well-being. It is situated in the upper left of the abdomen behind the stomach. Pancreas has two main functions. It helps the body digest food and it helps regulate blood sugar. More than 95 per cent of the pancreas' mass is made up of cells and tissues that produce pancreatic juices containing digestive enzymes such as amylase, lipase, elastase, and nucleases. A cluster of cells called "Islets of Langerhans" releases insulin, glucagon, and other hormones directly into the bloodstream and helps in controlling blood sugar.
Unhealthy or abnormally functioning pancreas results in a number of health conditions depending on its severity and the part affected. In this condition, the pancreatic enzymes secreted by the organ accumulate in the organ and starts digesting the organ itself.
The pancreas becomes inflamed and there is a severe bout of pain sensations that last days. The organ is swollen and the tissue lining gets eroded. This condition also has a tendency to progress over time. The most common causes are gallstones and alcohol.
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It is caused by permanent damage to the gland. Patients will develop recurrent episodes of pain and can have fatty stools steatorrhea. When the insulin-producing cells in the pancreas are affected, the body requires external injections to fulfill its insulin requirement.
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