Diabetes and gut
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Diabetes and Gut interplay By Dr. Usama Ragab Youssif In Gastro Canal Association Annual Conference Agenda Diabetes as the main player Gut as the main player Diabetes and gut in a separate game Gut as game changer Tips and tricks: diabetes drugs
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Diabetes and gut
- 1. Email: usamaragab@medicine.zu.edu.eg Slideshare: https://www.slideshare.net/dr4spring/ Mobile: 00201000035863
- 2. Agenda • Diabetes as the main player • Gut as the main player • Diabetes and gut in a separate game • Gut as game changer • Tips and tricks: diabetes drugs
- 3. Introduction • 50% suffer from GI symptoms “distressing” • Figures are underestimated: diabetes is known for its CVD legacy • Many has been discussed but the most famous is gastroparesis • GI motor dysfunction may have an impact on glycemic control or at least QoL.
- 4. Bharucha AE, Locke GR, Murray JA. Gastrointestinal Manifestations of Diabetes. In: Cowie CC, Casagrande SS, Menke A, et al., editors. Diabetes in America. 3rd edition. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases (US); 2018 Aug. CHAPTER 27.
- 6. Stats • True incidence & prevalence is underestimated • Figures differ between type 1 and type 2 • Symptoms are more common in women with diabetes, as is the case with functional gastrointestinal disorders Arch Intern Med. 2001;161:1989–1996.
- 7. Esophagus • Less studies than stomach • Share similar pathogenesis • Acute hyperglycemia inhibits esophageal motility and reduces the basal lower esophageal sphincter pressure • Reduction of cholinergic activity and vagal parasympathetic dysfunction. Fraser RJ, et al. Diabetologia. 1990;33:675–680. De Boer SY, et al. Gastroenterology. 1992;103:775–780. Lam WF, et al. Digestion. 1993;54:48–53.
- 8. Esophagus (cont.) • Heart burn “as a part of GERD” Reflux Non erosive GERD • Dysphagia “potentially indicating esophageal motor dysfunction” • Disordered esophageal motility leads to pill induced esophagitis due to pill impaction • Candidiasis sometimes draw our attention to lowered immunity “diabetes impair neutrophil function and opsonization”
- 9. Stomach - Diabetic Gastroparesis • Described by Paul Kassander: 6 cases in 1958 and coined the term “gastroparesis diabetocorum” • He suggested that “gastroparesis could impact adversely on glycemic control”. • Modern definition: abnormally delayed gastric emptying of solid food in the absence of mechanical obstruction • It may occur in T1D or T2D not necessary = poor prognosis
- 10. Epidemiology • The ‘true’ incidence and prevalence of diabetic gastroparesis globally remain uncertain • Diabetes is the leading cause of gastroparesis: 30% • In T1DM from DCCT-EDIC: delayed gastric emptying of a solid meal occurred in 47% • It is not exclusive for T1D, it may occur in both types • Awareness of this condition improves it and decrease its incidence
- 11. Risk Factors Long duration of diabetes Presence of other microvascular complications Female gender Obesity Smoking Camilleri M, Chedid V, Ford AC, et al. Gastroparesis. Nat Rev Dis Primers. 2018;4:41.
- 12. Bidirectional relationship between gastric emptying and glycaemia Phillips LK, et al. Nat Rev Endocrinol. 2015;11:112–128.
- 13. Stomach vs diabetes The rate of gastric emptying = major determinant of postprandial glycemia in both health and diabetes Novel anti-diabetic medications e.g., short acting GLP-1 RA, diminish postprandial glycemic excursions by slowing gastric emptying Gastroparesis is less in well controlled diabetes (even longstanding) Marathe CS et al. Diabetes Care. 2013;36:1396–1405. Watson LE et al. Diabetes Res Clin Pract. 2019;154:27–34. Boronikolos GC et al. Diabetologia. 2015;58:1175–1182.
- 14. Diagnosis • Take care, symptoms may be decieving: more symptoms and no emptying troubles • Exclude mechanical obstruction: I need help my “GI” friend • Scintigraphy, developed in the 1970s, remains the ‘gold standard’ technique. • It is precise but involve radiation exposure and need technical expertise Marathe CS, et al. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553219/
- 15. Methods • Standardized meal criteria “American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine”: intra-gastric retention of >60% of a standardized meal at 2 hours and/or >10% at 4 hours • 13C based breath tests: GEBT “gastric emptying breathing test” • Ultrasonography: operator- dependent • Wireless motility capsule, MRI, and SPECT imaging Camilleri M, et al. Am J Gastroenterol. 2013;108:18–37. Phillips LK, et al. Nat Rev Endocrinol. 2015;11:112–128. Camilleri M, et al. Gastroparesis. Nat Rev Dis Primers. 2018;4:41.
- 16. Diabetologist perspectives • We need to match insulin with CHO to minimize postprandial hypos • Delayed gastric emptying = mismatch = time difference • Lower blood glucose concentrations in the early postprandial period (so-called ‘gastric hypoglycemia’) and subsequent hyperglycemia. • Greater glycemic variability = worse outcomes • Individualize insulin treatment in those patients • Avoid GIT upset antidiabetic drugs Horowitz M, et al. Neurogastroenterol Motil. 2006;18:405–407. Ishii M, et al. Diabetes Care. 1994;17:901–903. Ceriello A, et al. Lancet Diabetes Endocrinol. 2019;7:221–230.
- 17. Gastroparesis management • Management of gastroparesis should be individualized. • Small frequent meals, low fat, more liquid than solid • It is difficult so, involve a dietitian • Optimize glycemic control • Adjust insulin, avoid gastric wise antidiabetics Olausson EA, et al. Am J Gastroenterol. 2014;109:375–385. Tornblom H. Diabetologia. 2016;59:409–413. Calles-Escandon J, et al. PLoS One. 2018;13:e0194759.
- 18. Drug therapy Prokinetic drugs: Metocloperamide: FDA approved for short periods “12 weeks” Domperidone: the famous but cardiac concerns Erythromycin: but tachyphylaxis Novel agents including Ghrelin agonist: relamorelin 5HT4 receptor agonist: velusetrag and prucalopride Tornblom H. Diabetologia. 2016;59:409–413. Patterson D, et al. Am J Gastroenterol. 1999;94:1230–1234. Jones KL, et al. Diabetes Care. 1999;22:339–344. Lembo A, et al. Gastroenterology 151: 87-96 e86. Manini ML, et al. Neurogastroenterol Motil 22: 42-49, e47-48. Carbone F, et al. Am J Gastroenterol. 2019;114:1265–1274.
- 19. Diabetic Gastroparesis Bottom-line Du YT, et al. Diabetes Care. 2018;41:627–637.
- 20. Gall bladder • Gall stones are more frequent in people with diabetes “risk factors for stones, such as intestinal dysmotility, obesity, and hyper TG, are more common in this group (esp. T2D) • Diabetic cholecystoparesis: acute hyperglycemia inhibit GB motility • Delayed gastric emptying = delayed GB emptying • Some drugs may impair GB emptying e.g., GLP1 RA • Dramatic weight loss after metabolic surgery may be contributor Pazzi P, et al. Aliment Pharmacol Ther. 2000;14 Suppl 2:62–65. Gielkens HA, et al. Scand J Gastroenterol. 1998;33:1074–1079. Marso SP, et al. N Engl J Med. 2016;375:311–322. Gether IM, et al. J Clin Endocrinol Metab. 2019;104:2463–2472. Pineda O, et al. Obes Surg. 2017;27:148–153.
- 21. Small intestine • SIBO: 15% – 40% in T1D It is due to altered intestinal motility and partly due to impaired immunity • Diabetic enteropathy with impaired intestinal motility in a way like gastroparesis Diagnosis of exclusion
- 22. Enteropathy workup • Exclude diabetes and gut in same battle e.g., T1D and Celiac • Exclude your fault: your antidiabetic drugs e.g., metformin, GLP1 RA, acarbose… • Small intestinal manometry: limited to specialized centers. • Scintigraphy can quantify small intestinal transit: uncertain. • More recent technologies: ingestible wireless capsules • SIBO: diagnosis by aspiration and culture
- 23. Treatment of enteropathy Prokinetic agents used for gastroparesis, but much less well evaluated. SIBO can be treated with antibiotics, such as rifamixin, amoxicillin- clavulanic acid or metronidazole. SIBO frequently relapses.
- 24. Diabetic constipation Maleki D, et al. Arch Intern Med. 2000;160:2808–2816. Prasad VG, et al. Indian J Gastroenterol. 2017;36:11–22. Rao SS, et al. Neurogastroenterol Motil. 2011;23:8–23.
- 25. Chronic constipation in diabetes Marathe CS, et al. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK55321 9/
- 26. Diabetic diarrhea Autonomic neuropathy Large volume, painless, nocturnal, diarrhea with or without fecal incontinence. It is a diagnosis of exclusion Diabetic diarrhea vs just incontinence Remember antidiabetic drugs that may cause diarrhea: metformin (malabsorptive), acarbose (osmotic), and GLP-1 receptor agonists Celik AF, et al. Am J Gastroenterol. 2001;96:1314–1316. Marathe CS, et al. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553219/
- 27. Chronic Diarrhea in Diabetes Marathe CS, et al. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK55321 9/
- 28. Fecal incontinence It is more in diabetes Longer duration +/- the control Presence of microvascular complication may predict it Exclude organic causes e.g., malignancies, IBS, other neuropathies… Anorectal manometry (conventional, 3D or HRM) Barium defecography is useful to detect structural abnormalities Epanomeritakis E, et al. Dis Colon Rectum. 1999;42:1394–1400. Sun WM, et al. Eur J Gastroenterol Hepatol. 1996;8:1007–1012. Schiller LR, et al. N Engl J Med. 1982;307:1666–1671. Norton C, et al. BMJ. 2007;334:1370–1371. Carrington EV, et al. Nat Rev Gastroenterol Hepatol. 2018;15:309–323.
- 29. Treatment of fecal incontinence Rarely curative We focus to improve QoL Fecal impaction with overflow: manual removal then increase fibers and toilet training Biofeedback training Engel BT, et al. N Engl J Med. 1974;290:646–649. Narayanan SP, et al. Curr Gastroenterol Rep. 2019;21:21.
- 30. Drugs that affect gut Metformin GLP1 RA Glucosidase inhibitors Imeglimin
- 31. Acute abdomen as a presentation of diabetes DKA Herpes zoster
- 32. Agenda • Diabetes as the main player • Gut as the main player • Diabetes and gut in a separate game • Gut as game changer • Tips and tricks: diabetes drugs
- 33. Gut as the main player Secondary diabetes e.g., cystic fibrosis and pancreatitis
- 34. Pancreatic diabetes • Commonly misdiagnosed as T2D • Has been called “type 3c diabetes” or pancreoprivic diabetes • Easily use pancreatic diabetes as umbrella term • Due to loss of structural and functional insulin secretion in context of exocrine pancreatic dysfunction • It includes: Pancreatitis (acute and chronic), trauma or pancreatectomy, neoplasia, fibrocalculous pancreatopathy idiopathic forms
- 35. Post Pancreatitis Diabetes Mellitus (PPDM) Even single but may lead to PPDM Both acute and chronic pancreatitis can lead to PPDM Risk is highest with recurrent bouts. PPDM versus T1DM: pancreatic exocrine insufficiency Risk of microvascular complication is the same
- 36. Cystic fibrosis– related diabetes (CFRD) CFRD is the most common comorbidity in people with cystic fibrosis CFRD occur in about 20% of adolescents and 40–50% of adults. Worse nutritional status, more severe inflammatory lung disease, and greater mortality. Insulin insufficiency is the primary defect in CFRD. Moran A, et al. Pediatr Diabetes 2018;19(Suppl. 27):64–74
- 38. Agenda • Diabetes as the main player • Gut as the main player • Diabetes and gut in a separate game • Gut as game changer • Tips and tricks: diabetes drugs
- 39. Gut and diabetes in a separate game Celiac disease. Hemochromatosis Autoimmune gastritis Somatostatinoma and other PNETs
- 40. Type 1 Diabetes and Celiac disease Gut malabsorption and upset There is a genetic link between both 6% of T1DM patients have CD Symptoms of CD may be overlooked More T1D members in 1 family increases risk of CD
- 42. Autoimmune gastritis and diabetes De Block CE, et al. The Journal of Clinical Endocrinology & Metabolism. 1999 Nov 1;84(11):4062-7.
- 43. PNETs and diabetes Lewis A, Li D, Williams J, Singh G. Pancreatic Neuroendocrine Tumors: State-of-the-Art Diagnosis and Management. Oncology (Williston Park, NY). 2017 Oct 15;31(10):e1-2.
- 44. Agenda • Diabetes as the main player • Gut as the main player • Diabetes and gut in a separate game • Gut as game changer • Tips and tricks: diabetes drugs
- 45. Gut share a lot in octet
- 46. Gut as cure for diabetes • Incretin therapy • Acarbose • SGLT1 inhibitors • Metabolic surgery
- 47. Incretin effect
- 48. GLP1 and GIP Diakogiannaki E, et al. Physiology & behavior. 2012 Jun 6;106(3):387-93. DPP4 DPP4
- 50. Acarbose
- 51. SGLT1
- 53. Metabolic surgery Madsbad S, et al. The lancet Diabetes & endocrinology. 2014 Feb 1;2(2):152-64.
- 54. Copyright ADA/EASD 2022 Mingrone et al. The Lancet. 2021 23;397:293-304 Weight Management: Metabolic Surgery
- 55. Agenda • Diabetes as the main player • Gut as the main player • Diabetes and gut in a separate game • Gut as game changer • Tips and tricks: diabetes drugs
- 56. Metformin the GI upset If tolerated not contraindicated Start low go slow Give with main meals Give with dinner to sleep after Use lower dose if higher one is distressing Use XR formulas rather than conventional one
- 57. GLP1 RA and GI upset • Tell the patient that it is the mechanism • It is mild, non distressing, it will help you stop eating!!! • Avoid in gastroparesis • Start low go slow • It will go • Eat small frequent meal • Avoiding eating when not hungry • Avoid fatty meals • Avoid concurrent metformin in high doses • Use prokinetic therapy together at initiation
Notes de l'éditeur
- Predominant among them, and most extensively studied, is abnormally delayed gastric emptying or diabetic gastroparesis. It has been suggested that more than 50% of individuals attending outpatient diabetic clinics will at some stage experience a distressing gastrointestinal symptom. Gastrointestinal motor dysfunction is also common in diabetes and may have an impact on glycemic control. Of the motor dysfunctions, gastroparesis, or delayed gastric emptying, is the most important reported inconsistencies likely reflect discrepancies in the methodology used and the patient populations studied. It should be appreciated that gastrointestinal symptoms are often not volunteered, particularly those considered embarrassing (such as fecal incontinence) and it would not be surprising if current estimates are less than is really the case. Symptoms are more common in women with diabetes, as is the case with functional gastrointestinal disorders (2). While it is unclear whether symptom prevalence varies between type 1 and type 2 diabetes there is no doubt that gastrointestinal symptoms have a substantial negative impact on quality of life in people with diabetes (3).
- Humble explanation -------------- While the esophagus has been less well studied than the stomach, it is clear that disordered esophageal function occurs frequently and that disordered motility in both the esophagus and stomach may share a similar pathogenesis. Acute hyperglycemia inhibits esophageal motility (6), and reduces the basal lower esophageal sphincter pressure (7). It has been postulated that the major mechanism underlying esophageal dysmotility is a reduction of cholinergic activity and vagal parasympathetic dysfunction (8).
- Acute hyperglycemia inhibits esophageal motility (6), and reduces the basal lower esophageal sphincter pressure (7). While the esophagus has been less well studied than the stomach, it is clear that disordered esophageal function occurs frequently and that disordered motility in both the esophagus and stomach may share a similar pathogenesis. It has been postulated that the major mechanism underlying esophageal dysmotility is a reduction of cholinergic activity and vagal parasympathetic dysfunction (8).
- Delayed gastric emptying in diabetes was first reported almost a century ago, but it was Kassander who, in 1958, documented asymptomatic increased gastric retention of barium in diabetes and coined the descriptive term ‘gastroparesis diabeticorum’ (15). Interestingly, Kassander also suggested in this paper that gastroparesis could impact adversely on glycemic control. Some sixty years on, diabetic gastroparesis, traditionally defined as abnormally delayed gastric emptying of solid food in the absence of mechanical obstruction, remains a diagnostic and management challenge (16). Gastroparesis occurs in both type 1 and 2 diabetes and may not, necessarily, be indicative of a poor prognosis (17, 18).
- The ‘true’ incidence and prevalence of diabetic gastroparesis globally remain uncertain largely due to inconsistencies in the definition of gastroparesis, study populations, and methodology. It is, however, clear that diabetes is a leading cause of gastroparesis, accounting for about 30% of cases in tertiary referral studies (16). A recent analysis of data from the follow-up arm of the landmark prospective study in type 1 diabetes, called DCCT-EDIC (Diabetes Control and Complications –Epidemiology of Diabetes Interventions and Complications) found that delayed gastric emptying of a solid meal occurred in 47% of this population, consistent with the prevalence reported in other cross-sectional studies (20). Previously believed to be essentially a complication of advanced type 1 diabetes (T1D), it is now apparent that gastroparesis also occurs frequently in type 2 diabetes (T2D) (15, 21).
- Bidirectional relationship between gastric emptying and glycaemia. Abbreviations: CCK, cholecystokinin; GIP, gastric inhibitory polypeptide; GLP-1, glucagon-like peptide 1; PYY, peptide YY. Reproduced with permission from Philips et al (21)
- The rate of gastric emptying is now appreciated as a major determinant of postprandial glycemia in both health and diabetes, and novel anti-diabetic medications, such as short acting GLP-1 receptor agonists, diminish postprandial glycemic excursions predominantly by slowing gastric emptying, are used widely. It should, however, also be noted that the awareness of the central importance of glycemic control to the development and progression of microvascular complications, and the consequent increased priority in management to improve it, may have led to a reduction in the incidence of gastroparesis. Consistent with this, it has recently been shown that in well-controlled T2D, even when longstanding, the prevalence of gastroparesis is low and, not infrequently, gastric emptying is modestly accelerated (18, 24)
- As alluded to, the presence of gastrointestinal symptoms is poorly predictive of delayed gastric emptying. It is well established that patients with debilitating upper GI symptoms may have normal, or even rapid emptying, while others with unequivocally markedly delayed emptying may report few, or no symptoms. Measurement of gastric emptying, after exclusion of mechanical obstruction at the gastric outlet or proximal small intestine is, accordingly, mandatory for a formal diagnosis of gastroparesis, for which scintigraphy, developed in the 1970s, remains the ‘gold standard’ technique.
- The test meal advocated in the consensus statement comprises two egg-whites, two slices of bread and jam (30 g) with water (120 ml), providing 255 kcal with little fat (72% carbohydrate, 24% protein, 2% fat and 2% fiber) (25). While a useful exercise, the probability of universal adoption of a specific meal, especially outside Western cultures, is intuitively low.
- In people with insulin-treated diabetes (type 1 or type 2), it is important to match exogenous insulin delivery with the availability of carbohydrate to minimize the risk of postprandial hypoglycemia. It is, therefore, intuitively likely that delayed gastric emptying predisposes to lower blood glucose concentrations in the early postprandial period (so-called ‘gastric hypoglycemia’) (38) and subsequent hyperglycemia. A study in type 1 patients reported that insulin requirements were lower in those with gastroparesis during the first 120 min post-meal, but greater during 180-240 min, compared to patients with normal gastric emptying(39). It is increasingly appreciated that greater glycemic variability is associated with worse outcomes (40). Knowledge of the rate of emptying may potentially assist the clinician in developing strategies to reduce postprandial glycemic variability in individual patients, although this needs to be evaluated formally.
- Management of gastroparesis should be individualized. In clinical practice, patients are generally advised to consume small, frequent meals that are low in fat and fiber, with more calories as liquids than solids; ingested solids should be those that fragment readily into small particles (41). It should, however, be noted that this advice has not been rigorously evaluated and may be difficult to adhere to, so that the involvement of a dietitian is recommended (42). While optimizing glycemic control is intuitively important, given the inhibitory effect of acute hyperglycemia on gastric emptying, this has not been clearly established to be the case in the chronic setting, although the use of continuous subcutaneous glucose infusion and continuous glucose monitoring has recently been advocated (43). Concurrent medications should be reviewed and, if possible, those which may slow gastric emptying (e.g. opiates, anticholinergics) ceased. In this regard, it should be appreciated that short-acting GLP-1 receptor agonists (e.g. exenatide BD and lixisenatide) and the amylin analogue, pramlintide (44), improve chronic glycemic control primarily by slowing gastric emptying. Olausson EA, et al. Am J Gastroenterol. 2014;109:375–385. Tornblom H. Diabetologia. 2016;59:409–413. Calles-Escandon J, et al. PLoS One. 2018;13:e0194759.
- Lembo A, et al. Gastroenterology 151: 87-96 e86. Manini ML, et al. Neurogastroenterol Motil 22: 42-49, e47-48. Carbone F, et al. Am J Gastroenterol. 2019;114:1265–1274.
- Treatment Algorithm for Diabetic Gastroparesis. PRN, as needed. Reproduced with permission from Du et al (1)
- Gall stones are encountered more frequently in people with diabetes, which is not surprising given that risk factors for the development of stones, such as intestinal dysmotility, obesity, and hypertriglyceridemia, are more common in this group (particularly type 2 diabetes) (57). In addition, impairment of gall bladder motility and autonomic neuropathy, as well as factors such as cholesterol supersaturation and crystal nucleation promoting factors, are considered important. Common techniques used to measure gall bladder motor function include ultrasound and scintigraphy. Some studies have found increased fasting gall bladder volume, while in others, there was no difference, or even a reduction, in people with diabetes. It is possible that differences in the techniques employed (ultrasound or scintigraphy), and the presence of autonomic neuropathy may account for these discrepancies. Many studies, however, have reported impairment in postprandial gall bladder emptying in diabetes, sometimes termed ‘diabetic cholecystoparesis’ (57). It is also possible that delayed gastric emptying contributes to delayed emptying from the gall bladder. In health, acute hyperglycemia inhibits gall bladder motility in a dose-dependent manner (58). An increased prevalence of gall bladder-related disorders (including cholecystitis and cholelithiasis) is associated with the use of GLP-1 receptor agonists (59) and may potentially relate to a drug-induced prolongation of gall bladder refilling time (60). Similarly, an increase in gall-bladder disease has been reported post-bariatric surgery in obese individuals (including those with diabetes) with the implication that dramatic weight loss may predispose (61).
- Diabetic diarrhea” has been traditionally considered a manifestation of autonomic neuropathy (73). The typical symptom is large volume, painless, nocturnal, diarrhea with or without fecal incontinence. Again the diagnosis essentially represents one of exclusion and it is important to distinguish diarrhea from fecal incontinence. It should be remembered that widely used glucose-lowering therapies, including metformin (malabsorptive), acarbose (osmotic), and GLP-1 receptor agonists, not infrequently cause diarrhea. It is likely that optimizing glycemic control is important in the management of diabetic diarrhea (74), but again, this has not been rigorously evaluated.
- Dietary strategies include a low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols) diet under guidance of a qualified dietitian, although this has not been evaluated specifically for the diabetes population in clinical trials. Loperamide, an over-the-counter mu opioid receptor agonist, is used widely. Bile acid sequestrants, such as cholestyramine and colesevelam, are used when bile salt malabsorption is suspected, and have the added advantage of reducing LDL cholesterol and glycated hemoglobin. Other agents include clonidine, diphenoxylate, octreotide, and ondansetron (figure 5).
- HRM= high resolution manometry
- Treatment of fecal incontinence is rarely curative and the focus of management is to improve symptoms and quality of life. Fecal impaction with overflow can be managed by initial manual removal of stool from the rectum and enemas (promoting evacuation) and the subsequent prescription of bulk laxatives, increasing fiber intake, and toilet training. Operant reconditioning of rectosphincteric responses, called ‘biofeedback’ training, was first described by Engel et al in 1974 (83) and can be useful in treating fecal, as well as urinary, incontinence. The technique involves visual demonstration of voluntary contraction of external anal sphincter (EAS) contraction to the patient and training to improve the quality of the response (both strength and duration). Biofeedback training is effective in the longer term in only about 60% of patients in clinical trials; those with a low bowel satisfaction score and having digital evacuations fare better (84).
- Pancreatic diabetes includes both structural and functional loss of glucosenormalizing insulin secretion in the context of exocrine pancreatic dysfunction and is commonly misdiagnosed as type 2 diabetes. Hyperglycemia due to general pancreatic dysfunction has been called “type 3c diabetes,” and, more recently, diabetes in the context of disease of the exocrine pancreas has been termed pancreoprivic diabetes (1). The diverse set of etiologies includes pancreatitis (acute and chronic), trauma or pancreatectomy, neoplasia, cystic fibrosis, hemochromatosis, fibrocalculous pancreatopathy, rare genetic disorders (193), and idiopathic forms (1); as such, pancreatic diabetes is the preferred umbrella terminology. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2014;37(Suppl. 1):S81–S90
- There is loss of both insulin and glucagon secretion and often higher-than-expected insulin requirements. Risk for microvascular complications appears to be similar to that of other forms of diabetes. In the context of pancreatectomy, islet autotransplantation can be done to retain insulin secretion (200,201). In some cases, autotransplant can lead to insulin independence. In others, it may decrease insulin requirements (202).
- CFRD is the most common comorbidity in people with cystic fibrosis, occurring in about 20% of adolescents and 40–50% of adults. Diabetes in this population, compared with individuals with type 1 or type 2 diabetes, is associated with worse nutritional status, more severe inflammatory lung disease, and greater mortality. Insulin insufficiency is the primary defect in CFRD.
- Cystic fibrosis is a genetic condition. It's caused by a faulty gene that affects the movement of salt and water in and out of cells. This, along with recurrent infections, can result in a build-up of thick, sticky mucus in the body's tubes and passageways – particularly the lungs and digestive system. The primary rationale for the use of insulin in people with CFRD isto induce an anabolic state while promoting macronutrient retention and weight gain.
- De Block CE, et al. The Journal of Clinical Endocrinology & Metabolism. 1999 Nov 1;84(11):4062-7.
- There is a much greater release of insulin in response to oral glucose administration as compared with administering the same amount of glucose by intravenous (IV) infusion. Subjects were given oral glucose on day 1 with plasma insulin levels recorded. The same volunteers returned on a second day and an IV glucose infusion was titrated to match the plasma glucose excursion achieved with the oral load. The difference in the measured plasma insulin is the incretin effect, mediated by the hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide.
- Acarbose is a complex oligosaccharide that acts as an inhibitor of several enzymes responsible for the breakdown of complex carbohydrates in the intestines. It inhibits both pancreatic alpha-amylase and membrane-bound alpha-glucosidases - including intestinal glucoamylase, sucrase, maltase, and isomaltase - which are responsible for the metabolism of complex starches and oligo-, tri-, and disaccharides into absorbable simple sugars. By inhibiting the activity of these enzymes, acarbose limits the absorption of dietary carbohydrates and the subsequent postprandial increase in blood glucose and insulin levels. Acarbose is therefore used in conjunction with diet, exercise, and other pharmacotherapies for the management of blood sugar levels in patients with type 2 diabetes.