1. Dr : Reem Murad

2. The risk of chronic complications increases as a function of the duration of hyperglycemia ; they usually become apparent in the second decade of hyperglycemia. Since type 2 DM often has a long asymptomatic period of hyperglycemia, many individuals with type 2 DM have complications at the time of diagnosis.

3. Risks for Complications in Diabetes  Abnormal blood sugar  Abnormal cholesterol  Abnormal blood pressure  Sedentary lifestyle  Smoking

4.  Blood glucose control A1C <7%  Treat cholesterol profiles to targets  Total cholesterol <200  Triglycerides <150  HDL (“good”) >40 men, >50 women  LDL (“bad”) <100, <70 high risk  Treat blood pressure to target <140/<80

5.  (GI) disorders are common among all people, including diabetics.  75% of patients visiting diabetes clinics will report significant GI symptoms  The entire GI tract can be affected by diabetes  Common complaints may include dysphagia, early satiety, reflux, constipation, abdominal pain, nausea, vomiting, and diarrhea.

7.  Gastroparesis  intestinal enteropathy which can cause: 1. diarrhea 2. constipation 3. fecal incontinence  and nonalcoholic fatty liver disease.

8.  Gastroesophageal reflux disease (GERD )  more common in diabetics.  may be caused by 1. autonomic neuropathy with decreased lower esophageal sphincter (LES) pressure 2. impaired clearance function of the tubular esophagus 3. delayed gastric emptying.

9.  is rarely clinically relevant  Dysphagia for liquids and/or solids is rarely seen  dysphagia in diabetes mellitus is more suspicious of peptic stricture, esophageal cancer, rings (eg, Schatzki's ring) or webs than dysmotility.

10.  emptying of food from the stomach is delayed, leading to retention of stomach contents  Diabetic autonomic neuropathy may include vagal nerve dysfunction as well as sympathetic nerve damage  can result in disordered motility of the small bowel and the colon

11.  food takes longer to pass through the stomach than usual

12.  Signs and symptoms: 1. bloating 2. early satiety 3. Distention 4. abdominal pain 5. nausea 6. vomiting. 7. gastroesophageal reflux 8. Heartburn 9. Lack of appetite 10. Weight loss

13.  abnormalities at several levels in the process of gastric emptying, including abnormal postprandial proximal gastric accommodation and contraction, and difficulties with antral motor function  these abnormalities are primarily due to 1. autonomic dysfunction 2. or abnormal intrinsic nervous system (eg, nitrergic neurons, or interstitial cells of Cajal, the pacemaker system of the gut) 3. An alternative theory implicates: a role for oxidative stress 4. May be a contribution from hyperglycemia itself- hyperglycemia typically has an acute, reversible effect associated with poorly controlled diabetes (when blood glucose is over 200 mg/dL)

14.  Erratic blood glucose levels  Slower digestion can result in: Bacterial overgrowth Food can harden into solid masses called bezoars that may cause nausea, vomiting, and obstruction of the stomach Bezoars can be dangerous if they block the passage of food into the small intestine.

15.  Symptoms  Upper GI endoscopy  The nuclear medicine gastric emptying test is the best confirmatory test. A test solid-food meal containing a technetium isotopic tracer is ingested, and scintography is used to quantitatively measure the rate of gastric emptying. This test is highly sensitive and specific

16.  a barium X ray : swallow a liquid containing the chemical barium, which shows up on X-ray and highlights its passage through your digestive system  a wireless capsule test – you swallow a small, electronic device that sends information about how fast it moves through your digestive tract to a recording device

17.  Meal and Food Changes  Consumption of frequent small  Avoidance of high-fat and high-fiber foods  liquid diet during an exacerbation of symptoms.  Smoking cessation  light postprandial exercise (such as walking)  Most importantly, careful attention to blood glucose control.

18.  Metclopropamide :a dopaminergic antagonist that enhances gastric emptying and has primary antiemetic properties  Cisapride (Propulsid) is a prokinetic agent - effective at facilitating gastric emptying.  Domperidone (Motilium) is dopaminergic antagonist similar to metclopropamide that accelerates gastric emptying but does not cross the blood-brain barrier and has very few side effects  Erythromycin has unique properties that stimulate gastric motility and may be beneficial in selected individuals.

19.  Nonspecific antiemetic agents: prochlorperazine (Compazine) promethazine (Phenergan) provide symptomatic relief of nausea and vomiting.  Recently use an implantable gastric pacemaker..

20.  surgery : insert a feeding tube. a jejunostomy tube,. The feeding tube allows to put nutrients directly into the small intestine, bypassing the stomach altogether.  A jejunostomy tube can be temporary and is used only if necessary when gastroparesis is severe.  Botulinum toxin : More severe cases of gastroparesis may be treated by injecting botulinum toxin into the valve between the stomach and small intestine, to relax it and keep it open for a longer period of time so food can pass through.The injection is given through an endoscope. found that it may not be very effective, so it is not recommended by all doctors.

21.  a common problem in patients with or without diabetes  Helicobacter pylori,, is no more common in diabetics  treated in the same fashion regardless of whether or not they have diabetes.  Treatment is geared toward suppression of gastric acid secretion with antisecretory medications (i.e., H2 receptor antagonists or proton pump inhibitors).  If H. pylori is present treat with a specific antibiotic regimen along with anti-secretory agents.

22.  Common antibiotic regimens include a 2-week course of amoxacillin)/clarithromycin - metronidazole  /clarithromycin, metronidazole/tetracycline, or metronidazole/amoxacillin.  In individuals with gastro-esophageal reflux, eradication of H. pylori may result in worsening symptoms because acid secretion increases after this bacteria-related gastritis resolves.

23.  yeast infections in the GI tract, especially with bad glycemic control.  Yeast infection in the mouth is characterized by a thick white coating of the tongue and throat along with pain and burning.  If the infection extends further, candida esophagitis results, which may cause intestinal bleeding, heartburn, and difficulty swallowing.

25.  Oral candida can readily be diagnosed by physical examination  candida esophagitis will usually require endoscopy for accurate diagnosis.  Treatment is highly effective and is focused on the eradication of the yeast infection with antifungal medications such as nystatin (Mycostatin), ketocanazole (Nizoral), or flucanazole (Diflucan).

26.  longstanding diabetes, the enteric nerves supplying the small intestine may be affected, leading to abnormal motility abnormal secretion, or abnormal absorption.

27.  Diarrhea and rarely steatorrhea can occur in diabetics, particularly those with advanced disease  The diarrhea is watery and painless, occurs at night, and may be associated with fecal incontinence.  diarrhea can be episodic or even alternating with periods of constipation.  The prevalence of diabetic diarrhea has been estimated to vary between 8 and 22 percent  Fecal incontinence due to anorectal impairment has also been thought to be relatively common.

28.  occur in up to 22% of patients  related to problems in the small bowel or colon.  Abnormally rapid transit of fluids may occur in the colon, leading to increased stool frequency and urgency.  abnormalities in the absorption and secretion of colonic fluid may develop, leading to increased stool volume, frequency, and water content.

29.  This may be due to autonomic neuropathy leading to abnormal motility and secretion of fluid in the colon.  Abnormal small bowel motility may be associated with small bowel bacterial overgrowth  intestinal problems ?. The most common is the irritable bowel syndrome.

30.  Diabetic autonomic neuropathy may include vagal nerve dysfunction and sympathetic nerve damage  The functional impairment of the enteric nervous system can result in disordered motility of the small bowel and the colon  The impairment in fasting and fed intestinal motor function can cause either delayed or accelerated small bowel transit  Abnormal small bowel motility may be associated with small bowel bacterial overgrowth, resulting in bile acid deconjugation and fat malabsorption  Both of these mechanisms can induce diarrhea by stimulation of small bowel (passive secretion due to osmotic gradient) and colonic (active transport mechanisms) fluid secretion

31.  Fecal incontinence can result from anorectal dysfunction  Medications ( metformin was an independent risk factor for chronic diarrhea and fecal incontinence)  exocrine pancreatic insufficiency is rare in diabetics  association of celiac sprue with juvenile or adult forms of insulin-dependent diabetes.

32.  alterations in the endogenous bile salt pool and increased fecal secretions of hydroxy fatty acids may contribute to the pathogenesis of diabetic diarrhea  Artificial sweeteners such as sorbitol or polyols may have a role for diarrhea in diabetics. The ingestion of as little as 10 g of sorbitol can significantly alter bowel habits in diabetics.  changes in blood glucose concentrations effect on gastrointestinal sensory and motor function.

33.  sprue may lead to diarrhea, weight loss, and malabsorption of food.  This condition responds well to a gluten-free diet, but patients may have difficulty adhering to such a diet. Diagnosis can be made with endoscopic biopsy of the small intestine or with serological evaluation for anti-endomysial and anti-gliadin antibodies.

34.  Putative mechanisms of diabetic small bowel dysmotility 1-Due to autonomic neuropathy  Abnormal small intestinal motility Bacterial overgrowth Abnormal colonic motility Anorectal dysfunction - lowered rectal sensory threshold, weak internal anal sphincter Increased intestinal secretion Exocrine pancreatic insufficiency (?) 2-Due to associated factors  Dietetic foods - sorbitol Concurrent celiac sprue - similar genetic predisposition Bile acid malabsorption (?)

35.  First line  History and physical examination  Blood chemistry Stool analysis - weight, fat, chymotrypsin, elastase, leukocytes, parasites  Barium studies - looking for gastric retention, malabsorption pattern, small intestinal and colonic wall thickness

36.  Second line  Upper GI endoscopy with duodenal biopsy - histology, bacteriology  Colonoscopy with biopsy - histology [13]  C-acetate or -octanoic acid breath test Glucose hydrogen breath test –  consider bacterial overgrowth  Anorectal manometry and sensory testing if fecal incontinence is present

37.  Third line  Ambulatory small intestinal manometry - to rule out intestinal pseudo-obstruction  Se-HCAT test or empiric cholestyramine - to rule out bile acid malabsorption Push-  enteroscopy with biopsy and enteroclysis Secretin-pancreazyme test - to exclude exocrine pancreatic insufficiency

38.  should be directed at the identified cause of diabetic enteropathy.  Patients with bacterial overgrowth should be treated with antibiotics  For accelerated intestinal transit, a trial with antidiarrheal agents such as lopiramide (2 to 4 mg four times daily), codeine (30 mg four times daily), or diphenoxylate(5 mg four times daily) has been proposed

39.  Clonidine may have beneficial effects on both accelerated intestinal transit and increased small intestinal secretion.  The long-acting somatostatin analogue octreotide has been tested against diabetic diarrhea

40.  Fiber supplementation with bran, Citrucel, Metamucil, or high-fiber foods may also thicken the consistency of the bowel movement and decrease watery diarrhea.  antispasmodic medicines such as hyosymine (Levsin), dicyclomine (Bentyl), and chordiazepoxide (Librax)/clindinium (Clindex) may decrease stool frequency.

41.  treatment of fecal incontinence in diabetics with chronic diarrhea involves two major approaches: - pharmacological intervention to reduce stool volume and enhance stool consistency ( loperamide is recommendede) - and techniques and toilet training  celiac disease or exocrine pancreatic insufficiency should be treated with a gluten- free diet or pancreatic enzyme supplementation.

42.  Sometimes an empiric trial of antibiotics and/or pancreatic enzymes is warranted because pancreatic exocrine insufficiency and bacterial overgrowth may be the etiology.  More recently, the 5HT3 receptor antagonist alosetron (Lotronex) has been used effectively for the treatment of diarrhea-predominant irritable bowel syndrome. Tincture of opium and paregoric have also been used to improve the quality of daily life in some cases  Finally, in severe cases, injections of octreotide (Sandostatin), a somatostatin-like hormone, have been shown to significantly decrease the frequency of diabetic diarrhea.

43.  Diagnosis can be quite difficult and may require small- bowel intubation for quantitative small-bowel bacterial cultures. Breath hydrogen testing and the D-xylose test may be helpful in diagnosing bacterial overgrowth as well. All of these tests are somewhat cumbersome, and an empiric trial of antibiotics is often the most efficient means of diagnosing and treating this condition.  Numerous antibiotic regimens have been shown to be effective, including 5- to 10-day courses of tetracycline, ciprofloxin, amoxacillin, or tetracycline. A short course may provide prolonged relief, but typically, additional courses of antibiotics are required when symptoms recur in several weeks or months.

44.  enteric neuropathy may affect the nerves innervating the colon, leading to a decrease in colon motility and constipation.  Anatomic abnormalities of the colon, such as structure, tumor, or diverticulitis, should be excluded with a barium enema or colonoscopy.  Fiber supplementation with bran or psyllium products, as well as a high-fiber diet, increases the water content of the bowel movement and may relieve constipation.  Mild laxatives and stool softeners will often help as well.  cisapride accelerates colonic movement and may increase the frequency of bowel movements.

45.  Constipation, may alternate with diarrhea, is one of the most common complications of diabetes.  Neuronal dysfunction in the large bowel, along with impairment of the gastrocolic reflex, results in constipation.  It is important to rule out other causes of constipation such as hypothyroidism or medications.  Treatment includes : 1. good hydration 2. regular physical activity 3. and increased fiber intake. 4. Sorbitol or lactulose can also be used to treat constipation

46.  enteric neuropathy may lead to a chronic abdominal pain syndrome similar to the pain of peripheral neuropathy in the feet.  This condition may be very difficult to treat - sometimes respond to pain medications and tricyclic antidepressant medications, such as amitryptilline  narcotic addiction.

47.  Pancreatic exocrine dysfunction occurs in up to 80% of individuals with type 1 diabetes  Rarely lead to any clinical problems with digestion  The exocrine pancreas may also be affected in some patients with type 2 diabetes but to a lesser extent  who have secondary diabetes because of severe pancreatitis or surgical removal of the pancreas usually have more severe symptoms of pancreatic exocrine insufficiency

48.  Treatment with pancreatic enzyme replacement therapy is usually effective.  A trial of oral enzyme replacement therapy can be done safely for diagnostic and therapeutic purposes.

50.  NAFLD (non-alcoholic fatty liver disease)  NASH (non-alcoholic steatohepatitis)  At least 30% of type 2 patients  Underdiagnosed  Type 2 also higher risk of hepatitis C  Current treatment is weight loss, possible future medication role

51.  Fatty infiltration of the liver (nonalcoholic steatohepatitis) is common in obese individuals (up to 90%) as well as in type 2 diabetic individuals (up to 75%).  People with type 1 diabetes in very poor control may also develop this syndrome, although it is much less common.

52.  Fatty liver may lead to tender hepatomegally, elevated liver enzyme tests, and abdominal pain syndromes.  may progress to fibrosis and cirrhosis of the liver.  The diagnosis on the basis of the clinical presentation - confirmed with abdominal ultrasonography and, if needed, percutaneous liver biopsy.  Metabolic abnormalities such as hemochromatosis and infectious etiologies such as viral hepatitis need to be excluded as part of the evaluation.  Therapy is geared toward improving glycemic control and instituting a low-calorie, low-fat diet. Caloric restriction will lead to weight loss, better glycemic control, lower serum triglycerides and cholesterol, and improvement in the fatty infiltration of the liver. Ursodiol (Actigal) may provide some benefit in the treatment of hepatic steatosis.

53.  Usually marked by minor liver function test abnormalities (alkaline phosphatase, ALT, AST)  No specific treatment, but metformin, TZD, glp-1, insulin may improve  If persistent LFT abnormalities: -imaging (ultrasound, CT, MRI) -screen for hepatitis -consider gastroenterology referral

54.  Diabetic patients seem to have an increased incidence of gallstones and gall bladder problems are primarily related to the obesity associated with type 2 diabetes and not to the diabetes itself.  Obesity leads to secretion of bile by the liver that is supersaturated with cholesterol, leading to crystallization and stone formation  Typical symptoms of biliary colic include intermittent right upper abdominal pain, jaundice, or pancreatitis.  In the past, patients with diabetes have been instructed to have surgery for asymptotic  more recent experience with modern medical and surgical care indicates that this is no longer the case.  patients with diabetes and gallstones should be managed in a fashion similar to nondiabetic patients. Surgery is generally recommended only for those individuals whose gallstones are causing symp

56.  Eating disorders (ED) and DM:  ED include:-  Bulimia nervosa.  Anorexia nervosa, v.v rare in D.M.  Eating disorders not otherwise specified.  ED  two times more in diabetic girls.

57.  A1C < 7% for most non-pregnant adults  Treat blood pressure to target of <130/<80  Treat cholesterol profiles to target  Low dose aspirin for appropriate patients  Lifestyle changes  Meal Plan  Appropriate exercise plan  Smoking Cessation  Proper and timely follow-up with providers

58.  GI problems in diabetes are common but not commonly recognized in clinical practice  The duration of diabetes and the degree of glycemic control are major determinants in the incidence and severity of GI problems  The entire GI tract can be affected, including the mouth, esophagus, stomach, small intestine, colon, liver, and pancreas, leading to a variable symptom complex.  The workup starts with a thorough patient history and appropriate laboratory, radiographic, and GI testing. In addition to pharmacological therapy, glycemic control and dietary manipulation play an important role in managing GI disorders in people with diabetes.

60.  Gastrointestinal complications of diabetes typically occur in patients who have had the disorder for more than five years; ocular, renal, or neurologic involvement is common  the increasing longevity of patients with type 2 diabetes mellitus has led to an increasing frequency of gastrointestinal complications.