DIABETES UPDATE--Strategies for Achieving Control in an Office Setting

DIABETES MELLLITUS Strategies for Achieving Control in an Office Setting Type 2 Diabetes Global Prevalence of Diabetes Projected to More Than Double by 2030 Diabetes Reduces Lifespan Risk Reduction for Key Endpoints with Intensive Therapy (UKPDS) Tight Glycemic Control Reduces Incidence of Microvascular Complications Intensive Glycemic Control in Type 2 Diabetes Reduces Risk of Complications (UKPDS) Tight Glycemic Control Reduces Long-Term Cardiovascular Risk (DCCT/EDIC Study) Current Treatment Goals for Glycemic Control Glycemic Goals Are Not Being Met Most Patients with Type 2 Diabetes Also Do Not Achieve Risk-Factor Control Mechanism of Postprandial Hyperglycemia: Glucose Production Impaired Glucagon Suppression in IGT Glucose 12.0 Plasma Glucose (mmol/L) Glucagon 45 Glucagon (pmol/L) 10.0 NGT IGT 40 35 8.0 30 6.0 25 NGT IGT 4.0 -60 0 60 120 Time (min) 180 240 300 20 -60 0 60 120 180 Time (min) 240 300 Mitrakou A, et al. N Engl J Med. 1992;326:22-29. Impaired Glucagon Suppression in IGT Insulin 500 NGT IGT 45 Glucagon 400 40 300 Glucagon (pmol/L) Insulin (pmol/L) 35 200 30 100 25 NGT IGT 0 -60 0 60 120 180 240 300 20 -60 0 60 Time (min) 120 180 Time (min) 240 300 Mitrakou A, et al. N Engl J Med. 1992;326:22-29. Impaired Glucagon Suppression in Type 2 Diabetes Glucose 450 NGT T2DM Glucagon 160 NGT T2DM Glucagon (pg/ml) Glucose (mg/dL) 350 140 250 120 150 100 50 -60 0 60 120 180 240 80 -60 0 60 120 180 240 Time (min) Time (min) Müller WA, et al. N Engl J Med. 1970;283:109-115. Impaired Glucagon Suppression in Type 2 Diabetes Insulin 150 NGT T2DM Glucagon 160 NGT T2DM Glucagon (pg/ml) Insulin (mU/ml) 140 100 120 50 100 0 -60 0 60 120 180 240 Time (min) 80 -60 0 60 120 180 240 Time (min) Müller WA, et al. N Engl J Med. 1970;283:109-115. TYPE 1 DIABETES • 15% of the total • INSULIN DEPENDENCE v REQUIRING • GLUCAGON SUPPRESSION TYPE 2 DIABETES • INVOLVES 2 PRIMARY PATHOGENETIC MECHANISMS – PROGRESSIVE DECLINE IN BETA CELL MASS AND FUNCTION • ASSOCIATED WITH THE LACK OF GLUCAGON SUPPRESSION – THE PRESENCE OF A RESISTANCE TO INSULIN ACTION AT THE TISSUE LEVEL ISSUES TO DEAL WITH • AWARENESS • EDUCATION • IMPLEMENTATION OF TREATMENT TREATMENT OPTIONS • • • • FOOD EXERCISE ORAL PARENTERAL • BETA CELL FUNCTION • GLUCAGON SUPPRESSION • INSULIN RESISTANCE TREATMENT OPTIONS • ORAL – SECRETAGOGUES • SULFONYLUREAS • NONSULFONYLUREAS – INSULIN RESISTANCE • THIAZOLIDINEDIONES (TZD) • METFORMIN – GLUCAGON SUPPRESSION • INCRETINS (INtestinal SECRETION of Insulin) – JANUVIA – STARCH BLOCKERS • ACARBOSE TREATMENT OPTIONS PARENTERAL – SUBCUTANEOUS • INCRETIN MIMETICS • INSULIN – TRANSPULMONARY TREATMENT OPTIONS • ORAL – SECRETAGOGUES • SULFONYLUREAS • NONSULFONYLUREAS – INSULIN RESISTANCE • THIAZOLIDINEDIONES (TZD) • METFORMIN – GLUCAGON SUPPRESSION • INCRETINS (INtestinal SECRETION of Insulin) – JANUVIA – STARCH BLOCKERS • ACARBOSE TREATMENT OPTIONS ORAL • ORAL – SECRETAGOGUES • SULFONYLUREAS – GLYBURIDE – GLIPIZIDE – GLIMEPIRIDE (LONG ACTING) • NONSULFONYLUREAS – NATEGLINIDE (STARLIX) – REPAGLINIDE (PRANDIN) TREATMENT OPTIONS ORAL • ORAL – INSULIN RESISTANCE • THIAZOLIDINEDIONES (TZD) – PIOGLITAZONE (ACTOS) – ROSIGLITAZONE (AVANDIA) • METFORMIN TREATMENT OPTIONS ORAL • ORAL Insulin (mU/ml) 150 NGT T2DM – GLUCAGON SUPPRESSION • INCRETINS (GLP-1) – SECRETED BY THE L-CELLS OF THE DISTAL ILEUM – CIRCULATES TO THE PANCREAS – STIMULATES INSULIN SECRETION – INHIBITS GLUCAGON SECRETION 100 50 0 -60 0 60 120 180 240 Time (min) 160 NGT T2DM Glucagon (pg/ml) 140 120 100 80 -60 0 60 120 180 240 Time (min) TREATMENT OPTIONS ORAL • GLUCAGON SUPPRESSION – INCRETINS (GLP-1)---”GLIP-ONE” • THERE ARE NO ORAL INCRETINS – BUT THERE IS AN ORAL WAY TO HELP NATURALLY OCCURRING INCRETINS • GLIPTINS (DPP-4 INHIBITORS) – SITAGLIPTIN (JANUVIA) – VILDAGLIPTIN (GALVUS -not yet released) Synthesis, Secretion, and Metabolism of GLP-1 and GIP DPP-4 Degrades GLP-1 TREATMENT OPTIONS PARENTERAL • INCRETIN MIMETICS – DIRECT STIMULATION OF INSULIN – DIRECT INHIBITION OF GLUCAGON • Exenatide (BYETTA) • Amylin (SYMLIN) – NOT DEGRADED BY DPP-4 • LONG-ACTING TREATMENT OPTIONS PARENTERAL – SUBCUTANEOUS • INCRETIN MIMETICS • INSULIN – TRANSPULMONARY • INSULIN INSULIN THERAPY • LONG ACTING ANALOGUES – LANTUS – LEVEMIR • RAPID ACTING ANALOGUES – HUMALOG – NOVOLOG – APIDRA INSULIN THERAPY • MIXTURES – 75/25 HUMALOG MIX – 70/30 NOVOLOG MIX INSULIN THERAPY • IS INSULIN INEVITABLE ? b-Cell Function Declines Regardless of Intervention in Type 2 Diabetes AVAILABLE INSULINS AVAILABLE INSULINS INSULIN HUMALOG ONSET PEAK DURATION < 30 minutes 30-90 minute < 90 minutes AVAILABLE INSULINS INSULIN HUMALOG ONSET PEAK DURATION 3-5 hours < 30 minutes 30-90 minute < 90 minutes NOVOLOG < 15 minutes 1-3 hours AVAILABLE INSULINS INSULIN HUMALOG ONSET PEAK DURATION 3-5 hours 6-12 hours < 30 minutes 30-90 minute < 90 minutes NOVOLOG REGULAR < 15 minutes 1-3 hours 30-60 min 2-4 hours AVAILABLE INSULINS INSULIN HUMALOG ONSET PEAK DURATION 3-5 hours 6-12 hours < 30 minutes 30-90 minute < 90 minutes NOVOLOG REGULAR < 15 minutes 1-3 hours 30-60 min 2-4 hours NPH 1-2 hours 4-14 hours 10-24 hours AVAILABLE INSULINS INSULIN HUMALOG ONSET PEAK DURATION 3-5 hours 6-12 hours 10-24 hours < 30 minutes 30-90 minute < 90 minutes NOVOLOG REGULAR NPH < 15 minutes 1-3 hours 30-60 min 1-2 hours 2-4 hours 4-14 hours LENTE 1-3 hours 6-16 hours 12-24 hours AVAILABLE INSULINS INSULIN HUMALOG ONSET PEAK DURATION 3-5 hours 6-12 hours < 30 minutes 30-90 minute < 90 minutes NOVOLOG REGULAR < 15 minutes 1-3 hours 30-60 min 2-4 hours NPH LENTE 1-2 hours 1-3 hours 4-14 hours 6-16 hours 10-30 hours 10-24 hours 12-24 hours 18-36 hours ULRALENTE 4-8 hours NEWER INSULINS INSULIN ONSET PEAK 1-4 hours 2-4 hours NONE NONE DURATION 12-24 hours 6-12 hours 24 hours 24 hours NOVOLOG < 15 min MIX 70/30 HUMALOG <30 min MIX 75/25 LANTUS LEVEMIR 1 hour 1 hour NEWER INSULINS INSULINS APIDRA ONSET <15 minutes PEAK DURATION 1-2 hour 3-4 hours THERAPEUTIC GOALS HbA1C as low as possible REDUCE BASAL HYPERGLYCEMIA Provide a basal amount of insulin REDUCE POSPRANDIAL EXCURSIONS Supplemental insulin with the meal REDUCING BASAL HYPERGLYCEMIA  NPH bid  LANTUS qd  LEVEMIR qd  INSULIN PUMP w  HUMALOG  NOVOLOG  APIDRA • • • • • METFORMIN AMARYL BYETTA JANUVIA TZD REDUCE POSTPRANDIAL GLUCOSE • • • • HUMALOG NOVOLOG APIDRA BYETTA • STARLIX • PRANDIN • JANUVIA TREATMENT STRATEGIES • FOR SIGNIFICANTLY ELEVATED HbA1C – GET THE FBS DOWN FIRST – AS THE HbA1C DECLINES • THE POST-PRANDIAL GLUCOSES PLAY A GREATER ROLE TREATMENT STRATEGIES FOR FASTING GLUCOSE  NPH bid  LANTUS q HS  LEVEMIR q HS • • • • METFORMIN AMARYL BYETTA JANUVIA TREATMENT STRATEGIES FOR POST PRANDIAL GLUCOSES • APPROACH WITH RAPID ACTING INSULIN – TWO ISSUES DETERMINE THE PPG • CARB CONTENT OF THE MEAL • PRE-MEAL GLUCOSE LEVEL TREATMENT STRATEGIES FOR POST PRANDIAL GLUCOSES • CARB CONTENT CORRECTION – 1 unit for every (15 grams) carbs consumed • 1:15 carb ratio • PRE MEAL GLUCOSE CORRECTION • 1 Unit drops FS 50 mg% TREATMENT STRATEGIES FOR POST PRANDIAL GLUCOSES • CHOOSE A TARGET FOR CORRECTION • e.g., 100 mg% • FORMULA combines CORRECTION + CARBS FS CORRECTION + CARB RATIO = TOTAL (FS-target)/50 + 1:15 = TOTAL SAMPLE COMPUTATION • Patient has a 60 gm CHO meal – Uses 1 unit for 15 gm • 4 units • Patient has a target of 120 mg% – Correction factor = 40 (1 unit drops 40mg%) • Current FS is 240 – Will need 3 units • (FS-target)/40 + 4 units for carbs • (240-120) = 120/4 =3 units for FS SUMMARY – TYPE 2 DIABETES IS MULTIFACTORIAL – GO AFTER FBS FIRST • METFORMIN • GLIMEPIRIDE hs • LEVEMIR or LANTUS – MEALTIME CONTROL • • • • NATEGLINIDE or REPAGLINIDE EXENATIDE JANUVIA RAPID ACTING INSULIN ANALOGUES SUMMARY • DIET and EXERCISE – Cannot be emphasized more