Diabetes Beyond Hyperglycemia

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Presentation for Family Medicine on Diabetes Medications

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  • ANSWER: A According to the American Diabetes Association, the goal for patients with type 2 diabetes mellitus is to achieve a hemoglobin A  of <7.0% (SOR C). This patient has achieved this goal, and there is no 1c indication for changes in his management.
  • ANSWER: D This geriatric diabetic patient should be treated with insulin.  Metformin is contraindicated in patients with renal insufficiency.  Sitagliptin should not be added to a sulfonylurea drug initially, the dosage should be lowered in patients with renal insufficiency, and given alone it would probably not result in reasonable diabetic control.  Pioglitazone can cause fluid retention and therefore would not be a good choice for a patient with cardiomyopathy.
  • ANSWER: E Repaglinide and nateglinide are nonsulfonylureas that act on a portion of the sulfonylurea receptor to stimulate insulin secretion. Pioglitazone is a thiazolidinedione, which reduces insulin resistance. It is believed that the mechanism for this is activation of PPAR-Y, a receptor that affects several insulin-responsive genes. Acarbose is a competitive inhibitor of -glucosidases, enzymes that break down complex carbohydrates into monosaccharides. This delays the absorption of carbohydrates such as starch, sucrose, and maltose, but does not affect the absorption of glucose. Sitagliptin is a DPP-IV inhibitor, and this class of drugs inhibits the enzyme responsible for the breakdown of the incretins GLP-1 and GIP. Exenatide is an incretin mimetic that stimulates insulin secretion in a glucose-dependent fashion, slows gastric emptying, and may promote satiety.
  • ANSWER: A Of the many currently available medications to treat diabetes mellitus, only metformin and incretin mimetics such as exenatide have the additional benefit of helping the overweight or obese patient lose a significant amount of weight.  Most of the other medications, including all the insulin formulations, unfortunately lead to weight gain or have no effect on weight.
  • Diabetes Beyond Hyperglycemia

    1. 1. Clinton Pong PGY-3Family Medicine 8/2012
    2. 2.  Review DM management and challenge the limits of our repertoire Discuss A1c’s role in treatment as a goal Review MA, PCHI, ADA and ACE/ACCE algorithms for treatment Discuss most effective, most common and most economical treatments Review EBM If we get to it, talk about some Alternative/Complementary Med
    3. 3.  This is NOT a talk about “diabetes priorities” What are they? (Talk to the “HAND”) 1. Smoking cessation 2. Blood pressure control 3. Lipid control 4. Metformin (and aspirin) 5. Glycemic control 6. Vaccinations
    4. 4. Or: 125+ 30 per % point above 6%.~125~155~185~215~245
    5. 5. David M. Nathan, Judith Kuenen, Rikke Borg, Hui Zheng, DavidSchoenfeld, and Robert J. Heine, for the A1c-Derived AverageGlucose (ADAG) Study Group. Translating the hemoglobin A1cassay into estimated average glucose values. Diabetes Care 2008
    6. 6.  EE Plus, DynaMed, MA and PCHI guidelines all agree: Most validated method is:1. Start with Metformin • crank it up as tolerated • max dose 850mg PO TID1. Add on a Sulfonylurea (or skip to 3) • Glipizide or glimeride1. Then start Insulin
    7. 7. Treatment of Type 2 DiabetesIncretin & DPP-IV inhibitor Skeletal muscle and Metformin adipose TZD Liver TZD tissue Metformin Glucose Hepatic uptake glucose output Pancreas Slowed GI Insulin glucose secretion absorption Decrease SU/Meglitinide HyperglycemiaAlpha-GlucosidaseInhibitor
    8. 8.  A 66-year-old male with type 2 diabetes mellitus is seen for a follow-up visit and has a hemoglobin A1c  of 6.7%. He is currently taking metformin (Glucophage), 1000 mg twice daily He has no history of coronary artery disease or heart failure. Which one of the following would be most appropriate? A) Continuing his current regimen B) Increasing the metformin dosage C) Adding a sulfonylurea D) Adding a thiazolidinedione E) Adding daily long-acting insulin
    9. 9.  $, Cheap and reduces A1c by 1-1.5% Biguanide derived from Goat’s Rue plant (Glucophage, Riomet, Glumetza, Fortamet) MOA: Decreases hepatic glucose production and increases insulin sensitivity ADR: Diarrhea, B12 deficiency and Lactic acidosis In 1970s, Phenformin caused cases of Lactic Acidosis • Onset subtle w/ nonspecific sx incl. malaise, myalgias, resp. distress, incr. somnolence, nonspecific abdominal distress • 40-64 cases/100,000 pt-yr • lead to discontinuation of production in the US rare for metformin (~3-9/100,000 pt-yr vs but fatal in 50% of cases • Risk factors: CRF, sepsis, dehydration, EtOH use, hepatic insufficiency, >80 y/o and acute/unstable CHF Avoid if Cr >1.4 for F, >1.5 for M (some say Ccr <30- 45)
    10. 10.  $, Cheap and reduces A1c by 1- 1.5% Glipizide (Glucotrol) Glyburide (Micronase/Diabeta) Glimepiride (Amaryl) MOA: Stimulates pancreatic beta islet cell production ADR: hypoglycemia, N/V, anemia CKD: dose cut 50%, Avoid Ccr<50
    11. 11.  An 81-year-old male with type 2 diabetes mellitus has a hemoglobin A1c  of 10.9%.  He is already on the maximum dosage of glipizide (Glucotrol).  His other medical problems include mild renal insufficiency and moderate ischemic cardiomyopathy. Which one of the following would be the most appropriate change in this patient’s diabetes regimen? A) Add metformin (Glucophage) B) Add sitagliptin (Januvia) C) Add pioglitazone (Actos) D) Initiate insulin therapy
    12. 12.  $-$$, reduces A1c by >2% Isolated in the 1920s. Hypoglycemia, edema (wt gain of 0.5-2.5kg) Insulin production • normal thin healthy person is 18-40 units/day or 0.2- 0.5units/kg • Type I DM pt ~0.6-0.7units/kg • Obese ~2units/kg 50% is Basal, 10-20% per meal is Bolus Bolus • NovoLOG/HumALOG (“LOGarithmic”) • NovoLIN/HumuLIN R (Regular) Basal • Glargine (Lantus) $$, longer acting • NPH (NovoLIN/HumuLIN N) $, risk of nocturnal hypoglycemia
    13. 13.  Which one of the following treatments for diabetes mellitus reduces insulin resistance? A) Acarbose (Precose) B) Sitagliptin (Januvia) C) Repaglinide (Prandin) D) Exenatide (Byetta) E) Pioglitazone (Actos)
    14. 14.  $$$ Pioglitazone (Actos) MOA: Increases peripheral and hepatic sensitivity to insulin Caution with hepatic disease and contraindicated with CHF Rosiglitazone (Avandia) may increase risk of MI
    15. 15.  $$$, reduces A1c by 0.6-0.8% MOA: inhibits DPP-4, slowing incretin metabolism, increasing insulin synthesis and release and decreasing glucagon levels Sitagliptin (Januvia)
    16. 16.  Which one of the following treatments for type 2 diabetes mellitus often produces significant weight loss? A) Exenatide (Byetta) B) Glipizide (Glucotrol) C) Pioglitazone (Actos) D) Insulin detemir (Levemir) E) Insulin lispro (Humalog)
    17. 17.  $$$, reduces A1c by 1% Exenatide (Byetta) 5-10mcg SC BID, synthetic Gila monster saliva MOA: Stimulate insulin production in response to elevated BG levels, inhibit post- meal glucagon release and slow nutrient absorption Weight loss (but only 4-6# after 30wk) ADR: slows gastric emptying, N/V/D, pancreatitis
    18. 18.  Alpha-lipoic acid 600-1800mg daily (B-1) Chromium 200-400ug daily (B-2) Fish Oil 1-4g daily (B-1) Magnesium 300-700mg daily (B-2) Vanadium 100-300mg daily (B-2) Zinc 15-30mg daily (C-2) Vitamin C 1-2 g daily (B-1) Bilberry for retinal problems (B-2) Ginkgo for vasculopathy (B-1)
    19. 19.  Review DM management and challenge the limits of our repertoire Discuss A1c’s role in treatment as a goal Review MA, PCHI, ADA and ACE/ACCE algorithms for treatment Discuss most effective, most common and most economical treatments Review EBM If we get to it, talk about some Alternative/Complementary Med
    20. 20.  Dynamed “Diabetes Mellitus II” accessed 8/2012 Essential Evidence Plus “Diabetes Mellitus II” accessed 8/2012 Salpeter SR., et al. Cochrane Database Syst Rev. 2010 Apr 14; (4):CD002967. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. M Stang, et al. Incidence of lactic acidosis in metformin users. Diabetes care, 1999 - Am Diabetes Assoc ABFM In-Training Exam 2011 David M. Nathan, Judith Kuenen, Rikke Borg, Hui Zheng, David Schoenfeld, and Robert J. Heine, for the A1c-Derived Average Glucose (ADAG) Study Group. Translating the hemoglobin A1c assay into estimated average glucose values. Diabetes Care 2008 Update on Insulin Management in Type II DM. Journal of Family Practice. 5/2012. Vol 61, No 5. Massachusetts Guidelines for Adult Diabetes Care June 2009. Diabetes Prevention and Control Program. PCHI Diabetes Guidelines 2012 Rakel. Integrative Medicine. 2nd ed. Ch 36. Diabetes. Goodman and Gilman. The Pharmacological Basis of Therapeutics, 11 th ed. Chapter 60 Insulin, oral hypoglycemic agents and the pharmacology of the endocrine pancreas

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