7/1/2013 ENDOCRINE Elizabeth J. Murphy, MD, DPhil Associate - PDF document

7/1/2013 ENDOCRINE Elizabeth J. Murphy, MD, DPhil Associate Professor of Clinical Medicine, UCSF Chief, Division of Endocrinology, SFGH July 8, 2013 Endocrine Resources  UpEndocrine Society Guidelineshttp ://www.endo- society.org/guidelines/Current-Clinical-Practice-Guidelines.cfm: o Pituitary Incidentaloma o Diagnosis and treatment of hyperprolactinemia o Testosterone Therapy in Adult Men o Primary Aldosteronism o Cushing’s Syndrome o Hirsutism in Premenopausal Women o Post-menopausal Hormone Therapy o Vitamin D deficiency o Adult Growth Hormone Deficiency o Post-Bariatric Surgery Management o Androgen Therapy in Women o Endocrine Treatment of Transsexual Persons 2 Diabetes Resources  Diabetes Care January Supplement: http://professional.diabetes.org/CPR_Search.aspx o American Diabetes Association Clinical Practice Recommendations o Standards of Medical Care in Diabetes 3 1

7/1/2013 Endocrine Content  Diabetes (5-8)  Thyroid (2-4)  Disorders of calcium metabolism and bone (1-5)  Adrenal disorders (0-2)  Testes/Male reproductive health (0-2)  Other (0-1) o Anterior pituitary o Posterior pituitary o Hypothalamic disorders o Polyglandular disorders o (Hypoglycemia not due to insulinoma) o (Nutritional disorders) o (Women’s health endocrine issues) o (Hypertension) o (Ovarian Disorders/Female Reproductive Health)  (Lipids 2-4) 4 Case #1 64 yom with HTN, CAD, CHF, and hyper-TG with a prior episode of pancreatitis is found to have a random plasma glucose of 205 mg/dl on labs obtained for another reason. An A1C was obtained and was 6.4%. The patient has no symptoms such as polyuria, polydipsia or polyphagia. Does he meet the criteria for the diagnosis of diabetes? 5 Diagnosis of Diabetes Meeting any one criteria makes Dx 1) Fasting plasma glucose (FPG) ≥ 126 mg/dl 2) Plasma glucose ≥ 200 mg/dl 2 h after a 75 g oral glucose load (OGTT) 3) Random plasma glucose ≥ 200 mg/dl with symptoms of hyperglycemia 4) A1C ≥ 6.5% In the absence of unequivocal hyperglycemia, results should be confirmed. 6 2

7/1/2013 Diagnosis of Diabetes Meeting any one criteria makes Dx 1) Fasting plasma glucose (FPG) ≥ 126 mg/dl 2) Plasma glucose ≥ 200 mg/dl 2 h after a 75 g oral glucose load (OGTT) 3) Random plasma glucose ≥ 200 mg/dl with symptoms of hyperglycemia 4) A1C ≥ 6.5% In the absence of unequivocal hyperglycemia, results should be confirmed. 7 Pre-diabetes Categories of Increased Risk For Diabetes  Impaired Fasting Glucose: FPG = 100 - 125 mg/dl  Impaired Glucose Tolerance: 2 hr OGTT = 140 - 199 mg/dl  Abnormal A1C: A1C% = 5.7 - 6.4 % 8 Case #1 64 yom with HTN, CAD, CHF, and hyperTG with a prior episode of pancreatitis is found to have a random plasma glucose of 205 mg/dl on labs obtained for another reason. The patient has no symptoms such as polyuria, polydipsia or polyphagia. You obtain a fasting BG which is 154 mg/dl confirming the diagnosis of diabetes mellitus for which he has a strong family history. You obtain further labs and need to chose treatment. EXAM : 100 kg BMI 32 145/94 82 MEDS : furosemide 40 mg BID; lungs: CTA KCl 20 meq; ASA 81 mg; lisinopril CV: S3 gallop 40 mg; metoprolol 100 mg BID Ext: tr edema, feet with no LABS : A1C = 8.8%, 140 111 28 ulcerations, sensation intact 4.5 28 1.9 TC 350 LDL NC HDL 22 TG 505 9 3

7/1/2013 Case #1 Which choice below would be the most appropriate initial therapy for this patient ’ s DM2? a) metformin b) glyburide c) colesevelam d) pioglitazone e) glipizide f) diet and exercise alone 10 Certainties in Glucose Lowering Treatment LOWERING A1C PREVENTS MICROVASCULAR COMPLICATIONS 11 Testing On DM Therapy  Lots of different practice styles  Focus on medications – contraindications and basic prescribing info  Some delay in test question writing so newest medications unlikely to be on the test 12 4

7/1/2013 Sulfonylureas Glinides Sulfonylureas  Stimulates insulin release  Lower A1C 1-2%  Advantages o Long history of use  Disadvantages o Weight gain (  2 kg) o Hypoglycemia o Earlier pancreatic failure? o Increased CV mortality? 14 Sulfonylureas  Glyburide o Micronase, Diabeta, Glynase; Glucovance with metformin o 1.25, 2.5, and 5 gm tabs QD or BID, max 20 mg a day o Non-linear dose response, more effect of 1.25 to 2.5 than 10 to 20 o Caution in renal failure and in elderly  Glipizide o Glucotrol, Glucotrol XL; Metaglip with metformin o 2.5, 5 and 10 mg tabs QD, > 15 mg dose BID, max 20 mg BID; Glucotrol XL, once daily to max of 20 mg, though no significant change in A1C over 10 mg  Glimepiride o Amaryl; Avadaryl with rosiglitazone; Duetact with pioglitazone o 1, 2, 4 mg tabs, max 8 mg daily o Caution in renal failure, liver failure, elderly  Typically discontinued when patient on basal and prandial insulin 15 5

7/1/2013 Glinides  Enhances insulin release  Lowers A1C 1-1.5%  Advantages: o Short acting, take 15 minutes prior to meal and skip dose if meal is missed  Disadvantages o Short acting, TID dosing o Hypoglycemia o No head to head comparison with first generation SU o Expensive o Metabolized by CYP2C8 and CYP3A4 16 Glinides  Nateglinide (Starlix) o 60 and 120 mg tabs o 30-360 mg before meals  Repaglinide (Prandin) o Better A1C lowering o 0.5, 1 and 2 mg tabs o 0.5-4 mg before meals 17 Biguanides Sulfonylureas Glinides 6

7/1/2013 Biguanides (Metformin)  Improves hepatic insulin sensitivity  Lowers A1C 1.5-2%  Advantages: o Weight loss (0-2 kg) o Lowers TG, LDLc; Increases HDLc o No hypoglycemia when used alone o Inexpensive o CVD benefit  Disadvantages o Majority of patients with GI SE o Risk of lactic acidosis o Impaired B12 absorption (5% or more of patients) 19 Metformin  metformin (Glucophage, Glucophage XR) o 500, 850, 1000 mg tabs. Start 500 mg daily with meals, increase q week, max dose 2550 mg (850 mg TID) o 500, 750 mg XR tabs, max dose 2000 mg q evening.  Works especially well in obese/overweight patients and for fasting hyperglycemia  First choice agent for DM2 20 Metformin - Contraindications  Decreased renal function (check Cr q yr) o Cr < 1.5, men o Cr < 1.4, women o “Abnormal CrCl”  During IV contrast studies  Age ≥ 80 unless renal fn wnl  Hypoxemia  Excessive alcohol consumption  Impaired liver function  CHF (now more relaxed contraindication) 21 7

7/1/2013 Sulfonylureas Glinides Biguanides Bile Acid Sequestrants Bile Acid Sequestrants  Approved for years for cholesterol lowering  Lower A1C 0.4%  Advantages: o Lowers LDLc o Presumed CVD benefit o Not absorbed  Disadvantages: o GI SE, constipation o Lots of pills o Increases TG, theoretical risk of pancreatitis  Colasevelam HCL (Welchol) o Contraindicated TG > 500 mg/dl or history of TG induced pancreatitis, caution • >300 mg/dl Bowel obstruction •  Cholestyramine (Questran) 23 Sulfonylureas Glinides Biguanides Bile Acid Sequestrants PPAR-  Agonists PPAR-  Agonists 8

7/1/2013 PPAR-  Agonists  Activate PPAR-  , improve insulin sensitivity  Lower A1C 0.5-1.4%  CVD risk unclear (possibly increased rosi, decreased pio)  Advantages: o Improved lipid profile with decrease in TG, increase in HDL (pioglitazone only) o No hypoglycemia when used alone  Disadvantages: o Weight gain (  2 kg) o Fluid retention o Two-fold increased risk of CHF o Increased fracture risk o Pioglitazone associated with increased incidence of bladder cancer 25 PPAR-  Agonists  Thiazoladinediones - PPAR-  agonists o rosiglitazone (Avandia; AvandaMet with metformin, Avandaryl with glimepiride) o pioglitazone (Actos;ActoplusMet with MF, Duetact with glimepiride)  Use – o Used in combination with metformin or sulfonylurea o Fluid retention worse when used in combination with insulin (consider stopping when insulin started) o Extreme caution in CHF 26 Case #1 64 yom with HTN, CAD, CHF, and hyperTG with a prior episode of pancreatitis is found to have a random plasma glucose of 205 mg/dl on labs obtained for another reason. The patient has no symptoms such as polyuria, polydipsia or polyphagia. You obtain a fasting BG which is 154 mg/dl confirming the diagnosis of diabetes mellitus for which he has a strong family history. You obtain further labs and need to chose treatment. EXAM : 100 kg BMI 32 145/94 82 MEDS : furosemide 40 mg BID ; lungs: CTA KCl 20 meq; ASA 81 mg; lisinopril CV: S3 gallop 40 mg; metoprolol 100 mg BID Ext : tr edema , feet with no LABS : A1C = 8.8% , 140 111 28 ulcerations, sensation intact 4.5 28 1.9 TC 350 LDL NC HDL 22 TG 505 27 9

7/1/2013 Case #1 Which choice below would be the most appropriate initial therapy for this patient ’ s DM2? a) metformin b) glyburide c) colesevelam d) pioglitazone e) glipizide f) diet and exercise alone 28 Case #2 54 yow with DM2 diagnosed 7 years ago presents to you for f/u complaining of increasing hypoglycemia and several URIs. At your last visit you added sitigliptin (Januvia) to her medications for an A1C of 7.6% and persistent SMBG values in the 200s. DM MEDS: LABS : A1C = 7.0%, 140 111 28 metformin 1 gm BID 4.5 28 1.9 glyburide 10 mg daily CrCl is 45 ml/min sitagliptin 100 mg daily Which of the following statements is true? The addition of sitigliptin: a) did not contribute to hypoglycemia b) should have been done with renal dosing c) was not related to the increased number of URIs d) typically results in a 1-2 kg weight loss 29 Sulfonylureas Glinides GLP-1 Analogues Biguanides DPPIV Inhibitors Bile Acid Sequestrants GLP-1 Analogues DPPIV Inhibitors PPAR-  Agonists PPAR-  Agonists 10