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TYPE II DIABETES DIAGNOSIS & DRUGS

TYPE II DIABETES DIAGNOSIS & DRUGS. Ufaq Qazi GP ST1. OBJECTIVES. By the end of this session you will ……. Know the main diagnostic tests for type 2 diabetes in primary care and their respective cut-off values

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TYPE II DIABETES DIAGNOSIS & DRUGS

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  1. TYPE II DIABETESDIAGNOSIS& DRUGS Ufaq Qazi GP ST1

  2. OBJECTIVES • By the end of this session you will ……. • Know the main diagnostic tests for type 2 diabetes in primary care and their respective cut-off values • Have some insight into the various classes of drugs used to treat type 2 diabetes (not including insulin) • Be familiar with the NICE guidelines pathway for treating a newly diagnosed type 2 diabetic patient

  3. TURNING POINT • Electronic voting cards • Interactive session • Everyone can answer questions • Anonymous • Results for the group overall • Everyone has to answer!

  4. HOW CONFIDENT ARE YOU WITH DIABETES DIAGNOSIS? • Grand master • Good • OK • Unsure • Clueless

  5. HOW CONFIDENT ARE YOU WITH DIABETES DRUGS? • Grand master • Good • OK • Unsure • Clueless

  6. DIAGNOSIS IN TYPE II DIABETES

  7. DIAGNOSTIC TESTS • WHO guidance 2006 • Random glucose • Fasting glucose • 2 hour oral glucose tolerance test (OGTT) • 75g oral glucose after 8-12 hour fast • ALL PLASMA VENOUS SAMPLES • FINGER-PRICK TESTS NOT DIAGNOSTIC • Amended in 2011 • Now includes HbA1c

  8. WHAT IS THE DIAGNOSTIC THRESHOLD VALUE FOR RANDOM GLUCOSE? • 10.5 • 10.8 • 11.1 • 11.4 • 11.6

  9. WHAT IS THE DIAGNOSTIC THRESHOLD VALUE FOR FASTING GLUCOSE? • 6.5 • 6.7 • 7.0 • 7.4 • 7.8

  10. WHAT IS THE DIAGNOSTIC THRESHOLD VALUE FOR OGTT? • 7.8 • 8.5 • 9.3 • 10.5 • 11.1

  11. WHAT IS THE DIAGNOSTIC THRESHOLD VALUE FOR HbA1c? • 6.0% (42 mmol/mol) • 6.5% (48 mmol/mol) • 7.0% (53 mmol/mol) • 7.5% (59 mmol/mol) • 8.0% (64 mmol/mol)

  12. DIAGNOSTIC THRESHOLDS • Random glucose > 11.1 • Fasting glucose > 7.0 • 2 hour OGTT > 11.1 • HbA1c > 6.5% (48 mmol/mol)

  13. RULES FOR GLUCOSE TESTS • If Pt symptomatic then only 1 positive test is required • In practice, many GPs often do them all anyway • Fasting glucose up to 30% false -VE (elderly/ethnic minorities) • If Pt asymptomatic then a second test on a separate date is required • If one test negative then others done to prove diagnosis

  14. RULES FOR HbA1c TESTS • If asymptomatic then second test on separate date needed • If < 6.5 then give lifestyle advice and retest at 6/12 • In practice, laboratory glucose tests done to prove diagnosis • HbA1c < 6.5 does not exclude diabetes proven by glucose tests • HbA1c cannot be used • Children and young people • Symptoms less than 2/12 • Patients on steroids (rapid glucose rise) • Haemoglobin or red cell disorders

  15. “PRE-DIABETIC” STATES (INTERMEDIATE HYPERGLYCAEMIA) • Impaired Fasting Glycaemia (IFG) • Fasting glucose between 6.1 and 7.0 • Diabetes UK advises OGTT to rule out diabetes • Impaired Glucose Tolerance • 2 hour glucose between 7.8 and 11.1 • Both managed actively with education and lifestyle advice • High risk for developing diabetes • Both independent cardiovascular risk factors

  16. QUESTIONS?

  17. DRUGS IN TYPE II DIABETES

  18. WHICH OF THESE IS NOT A CLASS OF DIABETIC DRUG? • Thiazolidinedione • Sulphonylurea • DPP-4 Inhibitors • GLP-1 Analogue • Biguanide • IGF-1 Inhibitor

  19. WHICH OF THESE IS NOT A REASON TO STOP METFORMIN? • Severe renal impairment • Sepsis • Radiological contrast • Chronic Heart Failure • Myocardial Infarction • Acute Hypoxia

  20. WHICH OF THESE IS NOT A REASON TO AVOID “GLITAZONES”? • Osteporosis • Bladder Cancer • Lymphoedema • Obesity • Heart Failure • Renal Impairment

  21. WHICH IS THE ONLY ORAL DRUG SAFE IN PREGNANCY? • Metformin • Sulphonylureas • Glitazones • Gliptins

  22. TYPE II DIABETES DRUGS • 1stor 2ndline • Biguanides (Metformin) • Insulin Secretagogues • Sulphonylureas • Meglitinides • Acarbose • 2nd or 3rd line • Thiazolidinediones (“Glitazones”) • DPP-4 inhibitors (“Gliptins”) • 3rd line only • GLP-1 Analogues

  23. METFORMIN • Mode of action • Reduces hepatic gluconeogenesis • Increases peripheral glucose uptake • Particularly helpful for • Overweight • Side effects • GI (diarrhoea!) • Lactic acidosis • Avoid/withhold in • Severe hepatic impairment • Renal Impairment (eGFR < 30), reduce dose if eGFR < 45 • Tissue hypoxia (e.g. sepsis/shock) • Pre-radiological contrast • Acute Heart Failure (actually beneficial in CHF)

  24. INSULIN SECRETAGOGUES –SULPHONYLUREAS • Mode of action • Stimulate pancreatic beta cells to release insulin • Long-acting • Glibenclamide • Avoid in elderly due to hypoglycaemia • Short-acting • Gliclazide, Tolbutamide, Glipizide • Particularly helpful for • Not overweight • Hyperglycaemia • Metformin intolerant • Can be added to Metformin

  25. SULPHONYLUREAS (cont.) • Side effects • HYPOGLYCAEMIA! • Weight gain • More rarely • Cholestatic hepatitis • Hypersensitivity (erythema multiforme) • Avoid in • Severe hepatic impairment • Severe renal impairment • But Gliclazide probably ok as mainly liver metabolism • Low dose and monitor glucose carefully • Watch out for • Drugs which affect cytochrome p450 metabolism • Rifampicin, Phenytoin, Carbamazepine, Erythromycin

  26. INSULIN SECRETAGOGUES –MEGLITINIDES • Repaglinide / Nateglinide • Mode of action • Broadly the same as sulphonylureas • Particularly helpful in • Erratic lifestyles (because rapid-acting) • Can be skipped if meal skipped • Side effects • As for sulphonylureas (less risk of hypoglycaemia)

  27. ACARBOSE • Mode of action • Inhibits alpha-glucosidase(gut enzyme – digests carbohydrate) • Combine with other drugs or insulin for good glycaemic control • Particularly helpful in • Intolerance of other oral drugs • Impaired glucose tolerance • Side effects • Weight loss (can be beneficial) • Flatulence!

  28. “GLITAZONES” (THIAZOLIDINEDIONES) • Pioglitazone • Only one with a licence • Rosiglitazone withdrawn due to cardiac side effects • Mode of action • Complicated! Affects multiple gene transcriptions for glucose metabolism and insulin sensitivity • Better use of glucose by cells • Particularly helpful in • Recurrent hypos on sulphonylureas (elderly, operating machinery) • Poor response to 1st/2nd line Rx • Severe renal impairment (though risk of fluid overload)

  29. “GLITAZONES” (cont.) • Side effects • Weight gain • Increased risk of heart failure • Increased risk of fracture • Hepatotoxicity (monitor LFTs every 3/12 for first year) • Avoid in • Heart Failure / Oedema • Osteopenia/Osteoporosis • Obesity • Bladder Ca or undiagnosed haematuria

  30. “GLIPTINS” (DPP-4 INHIBITORS) • Sitagliptin, Vildagliptin, Saxagliptin • Mode of action • Inhibit breakdown of GLP-1, a gut hormone which stimulates insulin release and inhibits glucagon release • Particularly helpful in • Recurrent hypos on sulphonylureas • Poor response to 1st/2nd line Rx • Can’t use “glitazone” (overweight, contraindication, intolerance) • Side effects • Relatively few common (GI mainly) • Avoid in • Severe hepatic impairment • Caution in severe renal impairment ( low dose)

  31. GLP-1 ANALOGUES • Exenatide / Liraglutide • s/c injection • Mode of action • Stimulates insulin release and inhibits glucagon release • Decrease gastric motility • Particularly helpful in • Overweight (BMI >35) • 3rd line Rx if insulin not acceptable • Weight loss would benefit other comorbidites • Side effects • Weight loss! • GI, particularly nausea and reduced appetite • Avoid in • Severe GI disorders • Severe renal impairment (eGFR < 30)

  32. PREGNANCY • Metformin is OK • Everything else is not OK • Insulin is mainstay

  33. QUESTIONS?

  34. HOW TO MANAGE A NEWLY DIAGNOSED PATIENT

  35. NICE GUIDELINES 2011 • Patient education and lifestyle changes • Absolutely crucial alongside drug Rx • X-PERT programme • NICE gives option of trial before drug Rx • UK Prospective Diabetes Study (1977-2007) • Up to 50% have microvascular complications at diagnosis • Intensive glycaemic Rx superior to standard Rx (lifestyle changes) • So why trial lifestyle? • In practice, need for drug Rx almost inevitable in all Pts at 3/12 • “Bedding in period” aids acceptance + commitment to lifestyle change • Meds usually started early now without formal trial period

  36. NICE GUIDELINES 2011 • 1st line is Metformin or Sulphonylurea (based on Pt and clinical characteristics) • Check HbA1c every 6/12 • If remains > 6.5% on 1st line then add the other of these drugs as 2nd line • If intolerant of either 1st line drugs, or hypoglycaemia an issue on sulphonylureas, then add gliptin or glitazone as 2nd line • If HbA1c > 7.5% on 2nd line then can trial 3rd line • Gliptin/Glitazone if not already tried • At this point insulin would be considered in addition • Could try GLP-1 analogue if BMI >35 or insulin not acceptable

  37. NICE GUIDANCE ON 2ND/3RD LINE DRUGS • All must be reviewed at 6 months and stopped if inadequate response • HbA1c decrease by 0.5% (1% for GLP-1 analogues) • ANDweight loss of 3% with GLP-1 analogue

  38. CASE STUDY • 61 y.o. man with BMI 35 • Inpatient with LRTI, now resolved • PMH – MI, chronic heart failure, COPD, OA • Meds – Aspirin, Furosemide, Bisoprolol, Ramipril, Simvastatin, Prednisolone, Salbutamol • Finger-prick glucose found to be raised • Further tests • Random glucose 13.5 • Fasting glucose 7.2

  39. THIS PATIENT HAS DIABETES • True • False

  40. CASE STUDY (cont.) • Prednisolone is stopped while in hospital • 2 weeks later he has the following blood results with his GP • Fasting glucose 6.6 • 2 hour OGTT glucose 12.4 • eGFR 47

  41. THIS PATIENT HAS DIABETES • True • False

  42. WHAT TREATMENT WOULD YOU CHOOSE AS 1ST LINE? • Lifestyle changes • Metformin • Sulphonylureas • A+B • A+C

  43. CASE STUDY (cont.) • After 6 months • HbA1c is 8.9% • eGFR 42 • Weight increased, BMI now 37 • Worsening OA in R knee and hip

  44. WHAT IS THE NEXT STEP IN Rx? • Add Gliclazide to current dose Metformin • Add Gliclazide to reduced dose Metformin • Add Pioglitazone to reduced dose Metformin • Add Sitagliptin to current dose Metformin • Add Exenatide to reduced dose Metformin

  45. CASE STUDY (cont.) • Now on Gliclazide and Metformin • After further 6 months • HbA1c is 8.5% • eGFR is 42 • BMI still 38 • Severe pain and reduced mobility due to OA

  46. WHAT WOULD YOU NOT GO FOR NOW? • Insulin • Sitagliptin • Pioglitazone • Exenatide

  47. CASE STUDY (cont.) • He is put on Exenatide injections in addition to Gliclazide and Metformin • After 6 months • HbA1c is 8.0% (reduced by 0.5%) • Weight loss of 4% • Trouble with recurrent hypoglycaemiacausing falls and multiple A+E attendances

  48. NOW WHAT? • Continue with current treatment • Stop Exenatide and replace with Sitagliptin • Stop Exenatide and and replace with Insulin • Stop Exenatide and Gliclazide and replace with Sitagliptin

  49. HOW CONFIDENT ARE YOU WITH DIABETES DIAGNOSIS? • Grand master • Good • OK • Unsure • Clueless

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