John Hopkins Modules - Diabetes

1. John Hopkins Modules - Diabetes N. Regmi

2. Diagnosis of Diabetes • Options for evaluation a) Fasting glucose • no calorie for > 8 hrs • Ease of use, Low cost, Acceptable to patients b) Random plasma glucose • Useful when symptoms suggestive of hyperglycemia(polyuria, polydipsia) c) Glycosylated Hb • represents the pathologic process of persistent hyperglycemia that is associated with the microvascular complications of diabetes (i.e., protein glycosylation).  • Levels correlate more with retinopathy than FPG

3. Diagnostic criteria for Diabetes

4. Prediabetes – Individual at increased risk

5. Diabetes Variants • Most common – 90% - Type II diabetes – insulin resistance with hyperinsulinemia. • Even though, insulin are elevated – inadequate relative to hyperglycemia --- relative insulin deficiency • Type I diabetes – 5-7% with diabetes • characterized by islet cell failure, insulinopenia, and ketosis, and is due to autoimmune destruction of beta cells. • The peak age of incidence - is the early-teens but can occur at older ages • Require Insulin to remain healthy • Secondary Diabetes – • corticosteroids, Cushing syndrome, hemochromatosis, acromegaly, pheochromocytoma, glucagonoma, Chronic pancreatitis

6. MODY • Mature Onset Diabetes of Young • syndrome in which a relatively young individual presents with hyperglycemia, but is relatively unlikely to develop ketosis • individual is young, presenting at an age in which type 1 diabetes is predominant, but with clinical characteristics of type 2 diabetes • autosomal dominant disorder --- the most common monogenic syndrome associated with diabetes (defect is on the short arm of chromosome 7 in the glucokinase gene).

7. LADA • Latent Autoimmune Diabetes of Adults • autoimmune destruction of beta cells (as seen in type 1 diabetes), but presenting at a later age (i.e., age > 25) • anti-islet antibodies (anti-GAD 65 antibodies) will be present, C-peptide levels will be low, and insulin resistance is not seen

8. Screening for Diabetes

9. Screening for DM associated Morbidity

10. Screening for DM associated Morbidity

11. Prevention of Diabetes – Risk Factors • Most imp risk factor- Obesity • Increased risk with increasing BMI even in the normal range • Other RF - lack of exercise, regardless of BMI, and cigarette smoking. • A diet rich in fiber and polyunsaturated fat that is low in saturated fats and concentrated sweets is associated with a reduced risk of developing diabetes, as is moderate alcohol intake.

12. Lifestyle modification • losing an average of 4.2kg and exercising reduced the risk of developing diabetes by 58%. • Those that lost weight but did not exercise, and those that exercised but did not lose weight, also had significant reductions in the development of diabetes.

13. Pharmacotherapy for prevention • Metformin decreases the incidence of diabetes by 31%. • Lifestyle intervention is nearly twice as effective, reducing the incidence of diabetes by 58%. 

14. ADA recommendations for Prevention • Patients at increased risk of developing diabetes should have goal weight loss of 5-10% and increase physical activity to 150 minutes a week • Metforminmay be considered in those under age 60 with an increased risk of diabetes who are obese and have at least one other risk factor for developing diabetes (e.g., family history, low HDL-C, others). • The ADA does not recommend use of drugs other than metformin to prevent diabetes, due to expense, risk of side effects, and lack of long term efficacy

15. Dietary recommendations for Diabetics

16. Non Insulin pharmacotherapy • Metformin • Cornerstone of therapy • Less wt gain, low risk of hypoglycemia • Demonstrated efficacy in reducing complications • Adr- lactic acidosis esp in renal failure, hepatic failure and CHF • Contraindicated if GFR < 30ml/min

17. Insulin secretagogues: Sulfonylureas and glitinides • Stimulate beta cells to produce insulins • Sulfonylureas • Reduce HbA1c by 1.5%, decrease microvascular complications • Glinitides • Less potent than sulfonylureas • shorter half-life -- dosed with meals and serve a role in those with irregular eating patterns • Repaglinide + Gemfibrozil= hypoglycemia - contraindicated

18. GLP-1 agonist • Injectibles - Decrease glucose with low risk of hypoglycemia • Evidence that  liraglutide reduces cardiovascular mortality when added to standard of care • Adr • Nausea and Vomiting, avoid in gastroparesis, • increased risk of pancreatitis • theoretical risk of Medullary carcinoma of thyroid, avoid in MEN 2

19. DPP-4 Inhibitos • Dipeptidyl peptidase 4 (DPP-4) -enzyme that degrades incretin • Should not be used in combination with GLP-1 agonist • No weight gain • Few side effects - pancreatitis

20. Thiazolidinediones and alpha-glucosidaseinhiitos • Thiazolidinediones • sensitize muscle, fat and liver cells to the effects of insulin •  reductions in fasting plasma glucose levels and hemoglobin A1C, and have a low risk of hypoglycemia • ADR- CHF and fluid retention esp when used with insulin • Acarbose • intra-intestinal polysaccharidase activity, preventing breakdown of carbohydrates  • Limited role in management of DM • Adr – GI effects

21. SGLT inhibitos • locking glucose reabsorption in the kidney, essentially causing glycosuria • genital fungal infections and dehydration are possible side effects • should not be used in chronic kidney disease (i.e., GFR < 60ml/min/m2

22. Insulins • Insulin • Very effective to reduce microvascular complications • no scientific evidence that newer formulations improve outcomes relative to older, less-expensive insulins (e.g., NPH insulin) • treatment of choice for women who are, or who may become pregnant • monotherapy with insulin --becomes less effective over time, but there is no ceiling in insulin use

24. Does "tight" glycemic control reduce microvascular or macrovascular complications?

25. DCCT trial • compared those treated with usual care (usually with one or two insulin injections daily) to those treated with intensive therapy (frequent monitoring and adjustment of insulin dosing, which was administered three to four times daily) •  Compared to the usual care group, those getting intensive control experienced the following: • 50% reduction of new-onset retinopathy (primary prevention) • 54% reduction in progression of established retinopathy (secondary prevention) • 34% reduction of new-onset microalbuminuria (primary prevention) • 43% reduction of progression of established microalbuminuria (secondary prevention) • 69% reduction of new-onset neuropathy (primary prevention) • 57% reduction of progression of established neuropathy (secondary prevention)

26.  What level of tight glycemic control is best – ADA guidelines • A reasonable A1C goal for many non-pregnant adults is <7%. • Providers might reasonably suggest more stringent A1C goals (such as <6.5%) for selected individual patients if this can be achieved without significant hypoglycemia or other adverse effects of treatment. Appropriate patients might include those with short duration of diabetes, type 2 diabetes treated with lifestyle of metformin only, long life expectancy, or no significant cardiovascular disease. • Less stringent A1C goals (such as <8%) may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, extensive comorbid conditions, or long-standing diabetes in whom the general goal is difficult to maintain despite diabetes self-management education, appropriate glucose monitoring, and effective doses of multiple glucose-lowering agents including insulin.

28. Management of Diabetes • Metformin based approach vs Insulin based approach • Choosing based on the clinical presentation (i.e., the severity of hyperglycemia), patient preferences, resources, and goals of therapy • In all patients, the first step in glycemic control is to control the morning fasting glucose.

29. Hyperglycemia and initial pharmacotherapy

30. Monotherapy • Metformin – should be the 1st choice • Dosing • Start with metformin 500mg once or twice) daily, or 850mg once daily • After 5-7 days, if GI side effects absent, double dose • Maximal dose is either 850mg twice daily or 1000mg twice daily for most individuals • If GI side effects occur, lower dose to previous tolerated dose  • Once metformin dose is at the maximally-tolerated dose, check the A1C every three months, and continue without change if the A1C is at goal.

31. Dual therapy • Metformin plus oral agent or metformin plus basal insulin • Metformin- not tolerated/contraindicated, then dual therapy will be with two oral agents from different classes, or an oral agent plus basal insulin • Avoid GLP-1 agonist and DPP-4 inhibitor

33. When choosing the 2nd or 3rd drug for dual therapy and triple therapy

35. Insulin based therapy

37. Thank You