Goals Of Treatment For Diabetes Mellitus PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Goals of Treatment for Diabetes Mellitus Class Year 2 Course Medicine Lecturer Date  LEARNING OUTCOMES Review landmark studies in our understanding of T2DM Describe the goals of treatment...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Goals of Treatment for Diabetes Mellitus Class Year 2 Course Medicine Lecturer Date  LEARNING OUTCOMES Review landmark studies in our understanding of T2DM Describe the goals of treatment for Diabetes Mellitus Recognize the cardiorenal benefits of SGLT-2 inhibitors and GLP-1 agonists Define hypertension treatment goals in patients with diabetes and approach to management Identify recommendations for lipid lowering therapy in patients with diabetes  FATIMA (CLINICAL CASE SCENARIO) 40-year-old female Type 2 diabetes diagnosed 2 years ago Hypertension Family history of hyperlipidemia Previous gestational DM  FATIMA (CLINICAL CASE SCENARIO) BP 154/78 mm Hg HbA1C 8.2% Cholesterol 6.2 mmol/L (240 mg/dL), HDL 1.03 mmol/L (40 mg/dL), LDL 5.4 mmol/L (210 mg/dL Creatinine 64 umol/L (0.74 mg/dL, eGFR 95 ml/min/1.73 m2 Weight 84, BMI 31.7 kg/m2  FATIMA (CLINICAL CASE SCENARIO) Current Medications – Metformin 1000 mg daily – Perindopril 5 mg daily – Aspirin 75 mg daily  WHAT IS DIABETES? Diabetes mellitus (DM) is a group of diseases characterized by hyperglycemia. T2DM is a metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, and multiple other pathophysiologic defects. The effects of DM include long–term damage, dysfunction, and failure of various organs. 6 DIAGNOSIS  TREATMENT GOALS IN DIABETES MELLITUS – A MULTIFACETED APPROACH Exercise Diet Cholesterol Blood pressure A1c / Anti-platelets 8  OVERVIEW OF TYPE 2 DIABETES PREVENTION TRIALS: LIFESTYLE MODIFICATION INTERVENTION Study n Intervention Treatment Risk reduction Da Qinq1,2 IGT 577 Lifestyle 6 years 51% 20 years 43% Finnish DPS3,4 IGT 523 Lifestyle 3+ years 58% 7 years Diabetes IGT 3,324 Lifestyle 3 years 58% Prevention 10 years 34% Program ()5,6 1. Diabetes Care. 1997,20-537-544 2. Lancet 2006; 371, 1783-1789 3. N Engl J Med. 2001;346, 393-403 4. Lancet 2006; 368, 1673-1679 5. N Engl J Med. 2002; 346, 393-403 6. Lancet 2009; 374, 1677-1686 DIABETES PREVENTION PROGRAM (DPP): 7 KG LOSS ↓ RISK OF TYPE 2 DIABETES 31% 58% 3234 patients; BMI = 34.0 kg/m2 Glucose: 95 – 125 mg/dl Lindstrom J et al. Diabetologia 2013;56:284-93 Diabetes Prevention Program Research Group. N Engl J Med 2002;346:393-403  LIFESTYLE MODIFICATION Encompasses diet, physical activity, and behavioral change Reduced calorie diet: ≥ 500-750 kcal/d deficit Physical activity: typically aerobic, ≥ 150 min/week Behavior therapy: structured behavior change program that includes regular monitoring food intake, activity, and weight, with personalized feedback from a trained interventionist Typically administered weekly in groups for 16 to 26 weeks Can induce weight loss of 7-10%  CARDIOVASCULAR DISEASE & DM Hospitalization rates in the US5 Patients with T2D are 1.8x 1.5x Non-diabetic 2–4x more likely Diabetic to develop CVD and CAD than people without diabetes1-4 Heart attack Stroke Patients with T2D are >50% 2.5x more likely to develop CHF than people without diabetes7 of deaths among patients with T2D are attributable to CVD1-3,6 CS. Trends Cardiovasc Med. 2010;20(3):90-95; 2. Armstrong EJ et al. Circulation. 2013;128(15):1675-1685; 3. American Heart Association. http://www.heart.org/HEARTORG/Conditions/Diabetes/WhyDiabetesMatters/Cardiovascular -Disease-Diabetes_UCM_313865_Article.jsp/. Updated November 10, 2015. Accessed November 11, 2015; 4. Aronson D, Edelman ER. Rev Endocr Metab Disord. 2010;11(1):75-86; 5. Centers for Disease Control and Prevention, Division of Diabetes Translation. Atlanta, GA: US Dept of Health and Human Services; 6. Morrish NJ et al. Diabetologia. 2001;44(suppl 2):S14-S21; 7. Nichols GA et al. Diabetes Care. 2004;27(8):1879-1884.  PREVALENCE OF ASCVD (PACT-MEA STUDY) Verma S, Alamuddin N, Alawadi F, Alkandari H, Almahmeed W, Assaad-Khalil SH, Haddad J, Husemoen LLN, Lombard L, Malik RA, Mashaki Ceyhan E, Sabbour H, Tombak G, Yadav G, Salek S. Prevalence of Diabetes and Cardiovascular Risk in the Middle East and Africa: Primary Results of the PACT-MEA Study. Circulation. 2023 Apr 18;147(16):1251-1255. doi: 10.1161/CIRCULATIONAHA.123.064345. Epub 2023 Mar 6. PMID: 36877670; PMCID: PMC10101130.  SEVERAL RISK FACTORS IN PATIENTS WITH T2DM ARE ASSOCIATED WITH A HIGHER RISK OF MORTALITY & CARDIOVASCULAR DISEASE Risk Factors Albuminuria Elevated glycated Elevated blood (presence of hemoglobin level pressure microalbuminuria or macroalbuminuria) Elevated LDL-C Smoking level Rawshani A, et al. N Engl J Med. 2018;379:633-644  DIABETES CONTROL AND COMPLICATIONS TRIAL (DCCT) 1441 teenagers and young adults with Type 1 diabetes, randomly assigned to two groups: Conventional Care: one or two insulin injections daily and "routine" three month follow-up visits, or Intensive Treatment: with initial hospitalization for education and stabilization, four or more blood sugar tests daily, use of either insulin pump, or multiple daily insulin injections, monthly office visits, and frequent (at least weekly) telephone calls between the patients and the DCCT team.  DCCT & EDIC DCCT Intervention Training EDIC Observation Conventional EDIC mean 8.0% * * * * * P< 0.05 Intensive EDIC mean 7.9% 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 DCCT EDIC Study Year  DCCT SUMMARY: INTENSIVE THERAPY SIGNIFICANTLY REDUCED Retinopathy 76% Nephropathy 50% Neuropathy 60%  PATIENTS WITH T2DM OFTEN HAVE MULTIPLE COMORBIDITIES Diabetes Hypertension Of people with hypertension: Of people with type 2 diabetes: 29% have type 2 diabetes4 75% have hypertension1 60–70% are 90% are overweight/obese2 overweight/obese3 30–60% have dyslipidemia3 49% have dyslipidemia4 31% have chronic kidney disease5 47% have coronary artery disease6 1. Nwankwo T, et al. NCHS Data Brief. 2013;(133):1-8; 4. Thoenes M, et al. Cardiol Res Pract. 2012:925046; 2. Grant B, et al. Clin Med (Lond). 2021;21(4):e327-331; 5. Mozaffarian D, et al. Circulation. 2016;133(4):e38-360; 3. Cosentino F, et al. Eur Heart J. 2020;41(2):255-323; 6. Lawes CMM, et al. Lancet 2008; 371:1513–1518.  CARDIOVASCULAR DISEASE & RISK MANAGEMENT Cardiovascular Disease and Risk Management: Standards of Care in Diabetes - 2023. Diabetes Care 2023;46(Suppl. 1):S158-S190  PHARMACOLOGIC APPROACHES TO GLYCEMIC TREATMENT Pharmacologic Approaches to Glycemic Management: Standards of Care in Diabetes - 2023. Diabetes Care 2023;46(Suppl. 1):S140-S157  ADAM: 66-YEAR-OLD MAN WITH T2M ACS MI CKD PAD Retinopathy 2013 2014 2015 2016 2017 2018 MI Bypass Neuropathy Stroke Ischemic Toes Amputation  COMPLICATIONS OF DM Macrovascular Microvascular CAD- ACS, MI (requiring CKD bypass) Neuropathy Stroke Retinopathy Peripheral arterial disease s/p ischemic toes amputation BLOOD PRESSURE TARGETS IN T2DM  BLOOD PRESSURE TARGETS IN T2DM Hypertension should be confirmed via multiple readings on 2 different occasions – Hypertension diagnosed if confirmed as systolic >130 mmHg or diastolic > 80 mmHg and treatment should be initiated – If reading >180/110 + known cardiovascular disease – can Dx hypertension on one reading – Patients should also monitor BP at home – If BP >120/80 consider weight management, decreased sodium intake, decreased alcohol intake, increased physical activity BLOOD PRESSURE TARGETS IN T2DM Initial BP ≥130/80 and 1.8 mmol/l despite statin, consider ezetimibe or PCSK9 therapy – T2DM adults >75 years of age – consider moderate intensity statin  LIPID TARGETS IN T2DM Secondary prevention: T2DM adults of any age with atherosclerotic disease – use high intensity statin – T2DM adults of any age with atherosclerotic disease with LDL >1.4 mmol/l despite statin, consider ezetimibe or PCSK9 therapy Other lipids: – If triglycerides 1.5 – 5.6 despite statins consider icosapent ethyl (not approved in Ireland yet) over fibrates  ANTI-PLATELETS AND T2DM Secondary prevention: – Aspirin 75mg (or clopidogrel if aspirin allergy) – Possible indication for long-term dual anti-platlet therapy in high-risk patients – Possible indication for low-dose rivaroxaban and aspirin in patients with stable coronary artery or peripheral artery disease Primary prevention: – Controversial! – Consider if between 50-70 years of age and other major risk factors and low risk of bleeding but note not recommended by NICE and ESC and Prof Barry (Medications Management Programme, Ireland)  WEIGHT MANAGEMENT IN T2DM Obesity is a chronic and complex disease of its own Weight loss of >5% = metabolic and cardiovascular benefits Weight loss of 10% = possible remission of T2DM Refer to “Overview of Obesity Lecture” WEIGHT MANAGEMENT IN T2DM  WEIGHT MANAGEMENT IN T2DM Nutrition: – No diet is ‘best’ – All diets struggle with maintenance of weight loss Recommend: – Structured weight management program – >16 sessions in 6 months initially – Long term follow-up to support weight loss maintenance – Aim to achieve a 500-750kcal/day deficit – Short-term VLCD may be prescribed in specialist settings – Ireland – Integrated Care Hub Dietician-led Programme  WEIGHT MANAGEMENT IN T2DM Pharmacotherapy & Glycemia: – More likely to use GLP-1 RA and SGLT2-i – Less likely to use sulphonylureas, TZDs and insulin Pharmacotherapy for obesity (target of >5% weight loss) – Orlistat (Xenical, licensed for obesity) – Naltrexone/buproprion (Mysimba, licensed for obesity) – Liraglutide 1.8-3.0 mg/day Victoza licensed for diabetes, Saxenda licensed for obesity – Semaglutide 1-2.4 mg weekly Ozempic licensed for diabetes, Wegovy licensed for obesity – Tirzepatide (Mounjaro, licensed for diabetes…and recently for obesity)  WEIGHT MANAGEMENT IN T2DM Ireland: Need for ‘metabolic surgery centres’ Efficacy of Bariatric Surgery for Obesity  WEIGHT MANAGEMENT TARGETS IN T2DM Metabolic Ventilatory Reproductive CV risk -5 -10 -15 -20 -25 - ADL / QoL 30 Anxiety / depression Body Image dysphoria Economic cost Alw in, 2 005  PATIENT-CENTERED COLLABORATIVE CARE Eye care professional for annual dilated eye exam Registered dietician nutritionist for medical nutrition therapy Diabetes self-management education and support Dentist for comprehensive dental and periodontal examination Mental health professional, if indicated Social worker/community resources if indicated Podiatrist for foot care Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes - 2023. Diabetes Care 2023;46(Suppl. 1):S49-S67