Diabetes mellitus part 2

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  • 2. 1) Classification and dignosis of diabetes 2)Glycemic targets 3)Pharmacological approach to glycemic treatments.
  • 3. # CLASSIFICATION • 1) Type 1 DM : due to autoimmune beta cell destruction, usually leading to absolute insulin deficiency. • Screening for type 1 diabetes with an antibody panel is recommended only in the setting of a clinical research study or in a first-degree family members of a proband with type 1 diabetes. • Type 1 DM can be differentiated from Type 2 DM and MODY by testing for C-Peptide.
  • 4. Staging of Type 1 Diabetes American Diabetes Association Standards of Medical Care in Diabetes. Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24
  • 5. • 2)Type 2 DM : due to progressive loss of insulin secretion on the background of insulin resistance. • Old age • Obesity • Insulin resistance
  • 6. • 3) Gestational DM: diabetes diagnosed in 2nd or 3rd trimester of pregnancy that was not clearly overt diabetes prior to gestation -Test for undiagnosed T2DM at the 1st prenatal visit in those with risk factors. -Test for GDM at 24–28 weeks of gestation in women not previously known to have diabetes. -Screen women with GDM for persistent diabetes at 4–12 weeks postpartum, using the OGTT.
  • 7. • 4)specific type of diabetes: a)monogenic diabetes syndromes b)disease of exocrine pancreas c) drug or chemical induced diabetes
  • 8. MATURITY ONSET DIABETES OF YOUNG (MODY) • Onset at early age , classically before age of 25. • Impaired insulin secretion with no defect in insulin action. • Autosomal dominant • Six subtypes are identified ,of which mody 2 is most common. • Mild, asymptomatic increase in blood glucose • Prominent family history of diabetes in 2-3 generation. • Usually not associated with obesity. • Slowly progressive hypoglycemia.
  • 9. TYPE 1 DM AND MODY SIMILARITIES: 1)Young age 2)Insulin deficiency, no insulin resistance 3)May run in families. 4)Not associated with obesity. DIFFERENCES: 1)Type 1 DM is autoimmune whereas MODY is inherited. 2)Type 1 DM pts are prone to other autoimmune disorders , not so in MODY. 3)Multiple autoantibosies found in type 1 DM. 4)Genetic testing is only definitive way to confirm MODY.
  • 10. LATENT AUTOIMMUNE DIABETES IN ADULTS(LADA):TYPE 1.5 -Autoimmune diabetes which is diagnosed in individuals who are older than usual age of onset of type 1 DM. -Progress to insulin requirement. -Age of onset <50 years. -Acute symptoms. -Nonobese. -Personal or family history of autoimmune disease. -Low C-peptide level. -Anti-GAD (glutamic acid decarboxylase) Ab and Islet cell ab are common. -No insulin resistance.
  • 11. FIBROCALCULOUS PANCREATIC DIABETES(FCPD) • Diabetes secondary to non-alcoholic chronic calcific pancreatitis, in absence of alcohol abuse, predominantly seen in tropical developing countries. • Usually non ketotic. • Classical triad : Diabetes + abdominal pain + pancreatic calculi • Usually requires insulin for tratment.
  • 12. #CRITERIA FOR DIAGNOSIS OF DIABETES • FPG >126 mg/dl(7.0 mmol/L). OR 2Hr PG>200 mg/dl(11.1 mmol/L) during OGTT OR HbA1C>6.5%(48mmol/mol) OR In pts with classic symptoms of hyperglycemia or hyperglycemic crisis, RBS>200 mg/dl(11.1 mmol/L)
  • 13. PREDIABETES?? • PREDIABETES: • FPG between 100 to 125mg/dl OR • 2-hr plasma glucose during 75gm OGTT between 140 to 200mg/dl OR • HbA1C 5.7-6.4%. #RSSDI REC: use of HbA1C as sole diagnostic test for screening is not reccomanded.
  • 14. CRITERIA FOR TESTING DIABETES OR PREDIABETES IN ASYMPTOMATIC ADULTS -Overweight or obese with one or more of the following risk factors: 1.First degree relative with Dm 2.High risk race or ethnicity 3.H/O CVD or HTN 4.HDL chole. <35mg /dl and or triglyceride>250mg/dl 5.Physical inactivity 6.Conditions associted with insulin resistance -Patients with prediabetes should be tested yearly -womens with GDM should be tested lifelong every 3 years. -for all patients testing should begin at age of 45 and every 3 yearly. #RSSDI rec: individual presenting to healthcare setting for unrelated illness, ANC pts, people over age of 30 should be encouraged for voluntary testing.
  • 15. RSSDI REC: The Indian Diabetes Risk Score (IDRS)
  • 16. SCREENING AND DIAGNOSIS OF GDM One-Step Strategy • At 24-28 weeks gestation in women not previously dx’d with overt diabetes • 75-g OGTT; Measure plasma glucose at fasting and at 1 and 2 hours. • GDM dx’d when plasma glucose exceeds: – Fasting: 92 mg/dL (5.1 mmol/L) – 1 h: 180 mg/dL (10.0 mmol/L) – 2 h: 153 mg/dL (8.5 mmol/L) American Diabetes Association Standards of Medical Care in Diabetes. Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24
  • 17. Two-Step Strategy Step 1: • In women not previously dx’d with overt diabetes, perform 50-g GLT (nonfasting); Measure plasma glucose at 1 hour. • If 1 hour plasma glucose level is ≥140 mg/dL* (7.8 mmol/L), proceed to step 2. *ACOG recommends either 135 mg/dL or 140 mg/dL in high-risk ethnic minorities with higher prevalence of GDM. American Diabetes Association Standards of Medical Care in Diabetes. Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24
  • 18. Two-Step Strategy (2) Carpenter/Coustan or NDDG Fastin g 95 mg/dL (5.3 mmol/L) 105 mg/dL (5.8 mmol/L) 1h 180 md/dL (10.0 mmol/L) 190 mg/dL (10.6 mmol/L) 2h 155 mg/dL (8.6 mmol/L) 165 mg/dL (9.2 mmol/L) Step 2: 100-g OGTT is performed while patient is fasting. The diagnosis of GDM is made if 2 or more of the following plasma glucose levels are met or exceeded: American Diabetes Association Standards of Medical Care in Diabetes. Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24
  • 19. #GLYCEMIC TARGETS • Glycemic recommandations for MOST* non pregnant adults with DM: • HbA1C <7.0 %(53mmol/mol) • Preprandial capillary plasma glucose:80- 130mg/dl • Peak postprandial capillary plasma glucose:<180mg/dl *glycemic targets should be individualised based on duration,age/life expectancy, comorbid conditions, hypoglycemia awareness and individual patient consideration.
  • 20. Targets of glucose control: RSSDI Recommended care
  • 21. HbA1C • Is indirect measure of average glycemia over aprox. 3months and has strong predictive value for diabetic complications • Conditions that affects RBC turnover (hemolytic and other anemias, recent blood transfusion, pregnancy, hemodialysis, erythropoitein therepy) plasma glucose criteria should be used.
  • 22. #PHARMACOLOGICAL APPROACH • TYPE 1 DM: -Insulin is mainstay therapy in type 1 DM. Starting insulin dose is based o weight, with starting dose ranging from 0.4- 1.0 units/kg/day of total insulin. -Pramlintide: amylin analogue, agent that delays gastric emptying , blunts pancreatic secretion of glucagon, and enhances satiety.It is FDA approved for use in type 1 DM adults. Starting dose: 15mcg SC injections Max dose :30-60 mcg SC injections S/E: GI intolerence -Surgery.
  • 23. • Type 2 DM: • Lifestyle modification - Metformin is preferred initial pharmacological drug. - Consider initiating insulin therapy in pts with newly diagnosed type 2 DM who are symptomatic or A1C >10.0% and or blood glucose >300mg/dl. - Consider initiating dual therapy in pts with newly diagnosed type 2 DM who have A1C>9.0%. - Patient centered approach. - DM with atherosclerotic cardiovascular disease - Continuous reevaluation.
  • 24. Individualized treatment • For a patients who has been diagnosed with diabetes consider a combination of metformin and one of these treatment options based on Patients • Drug choice should be based on patient preferences as well as presence of various comorbidities and complications, and drug characteristics, with the goal of reducing blood glucose levels while minimizing side effects, especially hypoglycemia and weight gain  Age  BMI  CKD  Duration of Diabetes  Established CVD  Financial concern  Glycemic status  Hypoglycemia concern
  • 25. RSSDI Diabetes Therapeutic Wheel
  • 26. Meglitinide Analogs Sulphonylureas Thiazolindinediones Metformin (Biguanides) Alpha Glucosidase Inhibitors
  • 27. BIGUANIDES Metformin - It is primary drug of choice for type 2 diabetes. -Act by inhibiting liver gluconeogenesis & increasing insulin sensitivity in other tissues. - It reduces fasting plasma glucose, improves lipid profile, weight neutral. Causes little or no hypoglycemia. Prevents macrovascular and microvascular complications of diabetes’ -Contraindicated in: Organ Failure:renal failure, Liver failure, CHF, Hypotension/Sepsis, Active Vitamin B12 Deficiency, alcoholism -Adverse effects : GI disturbance, lactic acidosis, Vitamin B12 Deficiency (0.5%) Starting dose:500 mg OD or BD, Max dose:2500 mg, A1C reduction:1-2%
  • 28. SULFONIYLUREAS: Insulin secretogogues • Stimulate insulin secretion by interacting with ATP sensitive K channel on beta cells. • Most effective in recent onset type 2 DM, who have residual endogenous insulin production. • Reduces both fasting and postprandial glucose. • First G:chlorpropamide,tolazamide, tolbutamide . have longer half life, greater incidence of hypoglycemia and drug interactions. Rarely used. • Second G:glimeperide, glipizide, gliburide, gliclazide. • S/E:Causes profound and persistent hypoglycemia and weight gain. • Secreted in milk. • C/I: renal and hepatic impairement. • Dose: Glimepiride (1-8mg), Glipizide (5-40mg),Gliburide(1.25-20mg) • HbA1c reduction: 1-2%
  • 29. GLP-1 RECEPTOR AGONISTS • GLP-1 induces insulin release from pancreatic beta cells, inhibit glucagon release from alpha cells, suppresses appetite. • Exenatide and Liraglutide • Lowers postprandial and fasting blood glucose, HbA1C, and body weight. • Liraglutide is C/I in pts with medullary ca of thyroid and multiple endocrine neoplasia.
  • 30. DPP-4 INHIBITORS • Inhibits Dipeptidyl peptidase-4 enzyme and prolonges endogenous GLP-1 action. • Saxagliptan, vildagliptan and sitagliptan • Do not cause hypoglycemia. • Reduce dose in renal impairement. • HbA1C reduction:0.5-0.8%
  • 31. THIAZOLIDINEDIONE (PPAR-gamma agonist) • Pioglitazone: selective agonist for nuclear peroxisome proliferator-activated receptor. It enhances transcription of several insulin responsive genes. • Reduces insulin resistance. • C/I:CHF ,liver ds • HbA1C reduction:0.5-1.4%
  • 32. ALPHA GLUCOSIDASE INHIBITOR • Acarbose, voglibose, migitol • Slows down and decreases digestion and absorption of polysaccharide and sucrose. • Use in prediabetes, reduces occurance of type 2 diabetes, HTN and cardiac ds. • C/I:renal and liver failure, inflammatory bowel ds, gastroparesis. • HbA1C reduction:0.5-0.8%
  • 33. SGLT-2 INHIBITORS • SGLT-2 inhibition induces glycosuria and lowers blood glucose level. • Canagliflazone, empagliflazone , dapagliflazone • Causes weight loss, reduces major cardiovascular events and cardiovascular mortality. • S/E:urinary and genital tract infection, electrolyte imbalance, increased frequency.
  • 34. THANK YOU
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