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Presentation on theme: "Sponsored by National Lipid Association Comprehensive Cardiometabolic Risk-Reduction Program Phase 2 2009."— Presentation transcript:

1 Sponsored by National Lipid Association Comprehensive Cardiometabolic Risk-Reduction Program Phase 2 2009

2 Special Considerations for the Overweight/Obese Patient Case Study

3 Overview A 46-year-old male lawyer is referred by his physician for persistent weight gain and high cardiomyopathy risk Patient has hyperlipidemia and hypertension; comorbidities include asthma, attention- deficit/hyperactivity disorder (ADHD), chronic fatigue, and depression Family history of obesity, type 1 and 2 diabetes Current weight of 305.7 pounds is his highest – Admits poor nutritional habits and a low activity level Reports waking up “snorting” from snoring at night – Experiences morning headaches and daytime somnolence Case Study

4 Brain Central Signals Stimulate NPY AGRP Galanin Orexin-A Dynorphin Inhibit  -MSH CRH/UCN GLP-I CART NE 5-HT External Factors Emotions Food characteristics Lifestyle behaviors Environmental cues Peripheral SignalsPeripheral Organs Food Intake Glucose CCK, GLP-1, Apo A-IV Vagal afferents Insulin Leptin Cortisol – – + Gastrointestinal tract Adipose tissue Adrenal glands Ghrelin + The Regulation of Food Intake Is a Complex Process Zhang Y, et al. Nature. 1994;372:425-432; Schwartz MW, et al. Nature. 2000;404:661-671. NPY=neuropeptide Y, AGRP=agouti-related protein, α-MSH=alpha-melanocyte-stimulating hormone, CRH/UCN=corticotropin-releasing hormone/urocortin, GLP-1=glucagon-like peptide-1, CART=cocaine- and amphetamine- regulated transcript, NE=norepinephrine, 5-HT= seratonin, CCK=cholecystokinin, Apo A-IV= apolipoprotein A-IV.

5 Overview Medications – Metoprolol 100-mg BID – Atorvastatin 10-mg QD – Niacin 1500-mg BID – Paroxetine 40-mg QD – Lithium 900-mg QD – Amphetamine/ dextroamphetamine 40-mg QD Case Study

6 Starting Your Investigation Look for – Obstructive sleep apnea (OSA) – Medications causing weight-gain – Depression – Metabolic syndrome, prediabetes The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. October 2000. NIH Publication No. 00-4084.

7 Weight Gain Sleep Apnea DepressionDepression A Vicious Cycle Clinical Pearl

8 © 2007 Cardiometabolic Support Network Drug-Associated Weight-Change Reference Remember to keep this list in your office!

9 Medications That May Be Contributing to This Patient’s Excess Body Weight MAOIs=monoamine oxidase inhibitors, TCAs=tricyclic antidepressants, ACE=angiotensin-converting enzyme Case Study

10 Laboratory Results Glucose: 106 mg/dL TC: 184 mg/dL HDL-C: 33 mg/dL LDL-C: 103 mg/dL TG: 240 mg/dL Non–HDL-C: 151 mg/dL EKG: sinus bradycardia, rate 56 hs-CRP: 8.2 mg/L=high risk A1 c : 5.9% Creatinine: 1.2 mg/dL AST: 27 U/L ALT: 43 U/L eGFR: >60 mL/min TC=total cholesterol, HDL-C=high-density lipoprotein cholesterol, LDL-C=low-density lipoprotein cholesterol, TG=triglycerides, AST=aspartate aminotransferase, ALT=alanine aminotranferase, hs- CRP=high-sensitivity C-reactive protein Case Study

11 Initial Registered-Dietitian Appointment Weight: 305.1 pounds, height: 72 inches, BMI: 41.4 kg/m 2, waist: 48 inches Former athlete with low activity level Volume eater with little sense of satiety “when he gets started” Daytime fatigue noted, being treated for ADHD Diet – Little fast food/red meat – Eats before bed and sometimes wakes up in the middle of the night to eat – Breakfast: nothing, lunch: salad, snack: fruit, dinner: Greek salad with chicken or stir- fry, snack: “bad” Plan – Keep food records – Begin to eat breakfast – Eat higher lean-protein lunches and dinners and begin to reduce refined carbohydrates – Goal of 30 minutes of walking/day ADHD=attention-deficit/hyperactivity disorder, BMI=body mass index Case Study

12 High-frequency telephone- and web-based nutritional counseling can be effective ways to help patients lose weight Clinical Pearl

13 Breakfast and Nighttime Eating Skipping breakfast can drive nighttime eating – Breakfast=none – Lunch=breakfast – Dinner=lunch – Nighttime snack=dinner Nighttime eating drives skipping breakfast The cycle continues… Clinical Pearl

14 A.Low protein B.Low fat C.Low glycemic Which may be the best diet for someone with a lack of satiety? ARS Question

15 Glycemic Index (GI) Although data vary, a low-GI meal may reduce subsequent energy intake 1 Cochrane systematic review indicates that decreasing the GI* of a diet may be an effective way to promote weight-loss and improve lipid profiles 2 1. Flint A, et al. Am J Clin Nutr. 2006;84:1365-73. 2. Thomas DE, et al. Cochrane Database Syst Rev. 2009;(1):CD005105.pub2. *GI=area under the curve (AUC) of the 2-hour blood glucose response curve divided by the AUC of an equal amount of glucose, multiplied by 100 Low GI food/meal = 55 or less

16 Diet: What Is Most Important? Calorie restriction, with high macronutrient quality* *High quality indicates more than 5 servings of fruits and vegetables/day, lean protein sources including some vegetarian sources, nuts, healthy oils, nonfat dairy products, whole grains, low in sweets and refined carbohydrates, low in fat Clinical Pearl

17 Favorable Option for This Patient Low refined-carbohydrate diet with increased fiber intake – Patient has prediabetes – Rapid weight-loss is desirable – Patient’s snacks tend to be refined carbohydrates – Lower refined-carbohydrates reduce hunger in some patients – Higher fiber associated with satiety Higher protein intake – Protein increases satiety – Lean protein has little fat and saturated fat, making it a healthy option for weight loss

18 Practical Tips: Increasing Fiber and Lean Protein Fiber – Fiber One ® bran cereal Sprinkle it on low-fat yogurt as a bedtime snack – Whole grains, fruits, and vegetables Lean protein – Ham, turkey, and roast beef are the leanest sandwich meats Have 1/2 sandwich, but double the thickness – Carnation ® Instant Breakfast ® No Sugar Added with skim milk=inexpensive, low-GI meal replacement – Modified pastas that are no longer “refined carbohydrates” Barilla ® PLUS ® (2-cups cooked)=17-g protein, 7-g fiber, 360- mg omega-3 fatty acid

19 Initial MD Appointment Weight: 305.7 lbs, height: 72 inches, BMI: 41.5 kg/m 2, blood pressure: 138/90, heart rate: 68 bpm, waist: 48 inches Patient is at his highest weight – Several prior weight-loss attempts: no significant progress, has been steadily gaining weight – Admits poor nutritional habits and a low activity level Reports waking up “snorting” from snoring at night – Has morning headaches and daytime somnolence Food records show nighttime eating pattern, with large quantities consumed after 6:00 PM Case Study

20 Medications – Metoprolol 100-mg BID – Atorvastatin 10-mg QD – Niacin 1500-mg BID – Paroxetine 40-mg QD – Lithium 900-mg QD – Amphetamine/dextroamphetamine 40-mg QD Action plan – Reinforce importance of continued dietitian visits – Sleep study to evaluate for obstructive sleep apnea – Stop metoprolol; initiate ramipril, titrate ↑ to 5-mg BID – Begin metformin ER 500-mg QD, with goal to increase Case Study

21 What if β-Blockers Are Necessary? If a β-blocker is necessary as part of a multi-agent antihypertensive regimen, an agent that does not aggravate insulin resistance (eg, carvedilol) may be a favorable choice Clinical Pearl

22 Metformin is appropriate for use in patients with IFG, IGT, and A.A1 c ≥5.0% B.Hypertension C.BMI ≥35 kg/m 2 D.Family history of diabetes in first-degree relative According to the 2007 ADA Consensus Statement on impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), which of the following is not true? ADA=American Diabetes Association, BMI=body mass index ARS Question

23 Pharmacological Intervention in the Progression to Diabetes: Recent Statements ADA 2007 Consensus Statement – Metformin as an adjunct/alternative to lifestyle in patients with IFG and IGT, and any of the following 35 kg/m 2, family history of type 2 diabetes in first-degree relative, ↑ triglycerides, ↓ HDL-C, hypertension, A1 C >6.0% ACE 2008 Consensus Statement – Metformin or acarbose as an adjunct to lifestyle in patients with prediabetes at particularly high risk Nathan DM, et al. Diabetes Care. 2007;30:753-759. American College of Endocrinology Task Force on Pre-Diabetes. Available at: Accessed November 1, 2008. ADA=American Diabetes Association, IFG=impaired fasting glucose, IGT=impaired glucose tolerance, BMI=body mass index, HDL-C=high-density lipoprotein cholesterol, ACE=American College of Endocrinology

24 0 10 20 30 40 Cumulative Incidence of Diabetes (%) Years 01234 Placebo Lifestyle Metformin Weight loss Decrease in risk* 0.1 kg 2.1 kg31% 5.6 kg58% P<0.001 for each comparison. *Decrease in risk of developing diabetes compared to placebo group. Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393-403. Diabetes Prevention Program Don’t Forget: Lifestyle Is More Effective Than Metformin

25 Month 2—MD Visit 2 Weight: 294.5 lbs, blood pressure: 140/90, heart rate: 64 bpm, waist: 47 inches Followed diet very strictly for first few weeks – Now on diet ≈70% of the time – Still skips breakfast Patient rescheduled sleep study, reminded of importance by MD – Reports being very fatigued and realizes he eats to stay awake Action plan – Increase metformin 500-mg to BID, eat protein breakfast instead of skipping the meal Case Study

26 Sleep-Study Results Apnea-hypopnea index (AHI) of 57.8 – Diagnosis: severe obstructive sleep apnea- hypopnea syndrome Action plan – Began continuous positive airway pressure (CPAP) treatment with 12 cm H 2 0 Follow-up AHI of 5.0 Case Study

27 Many patients won’t tolerate CPAP… Risk of erectile dysfunction can be a strong motivator Clinical Pearl

28 Month 3—Registered-Dietitian Visit 2 Weight: 290.6 lbs Not eating breakfast – “No time, no interest, not hungry” Eating less at night Patient hurt his back and is going to physical therapy, but little aerobic activity secondary to fatigue Seeing new psychiatrist who will evaluate medical regimen Plan – Meal replacements for breakfast – Continue low-glycemic index diet (increase vegetables, steak only 1x/week) Case Study

29 Meal Replacements Important for patients who have – Little time for food shopping and preparation – Hit a weight plateau – Persistent difficulty managing food and social cues related to overeating Advantages – Provide adequate and consistent nutrition as a low-fat, calorie-controlled replacement for 1 or 2 meals per day – Eliminate food choices and temptations – Simplify food shopping and preparation – Convenient to carry and store

30 *1200–1500 kcal/d diet prescription CF=conventional foods; MR-2=replacements for 2 meals, 2 snacks daily; MR-1=replacements for 1 meal, 1 snack daily 15 10 5 0 Time (mo) Phase 2 Phase 1* MR-2 0246810121824303645 51 MR-1 Weight Loss (%) CF Fletchner-Mors, et al. Obes Res. 2000;8:399. Meal Replacements Promote Short- and Long-Term Weight Loss

31 Month 5—MD Visit 3 Weight: 277.7 lbs (-28 lbs), BMI: 37.7 kg/m 2 ; blood pressure: 130/80, heart rate: 64 bpm, waist: 44 inches Now on CPAP at 12 cm H 2 0 – Notes that he feels much better, with more energy and focus Since sleep study and CPAP use, psychiatrist decreased lithium to 600-mg QD, paroxetine to 20-mg QD, and amphetamine/ dextroamphetamine to 20-mg QD DHA/EPA=docosahexaenoic acid/eicosapentaenoic acid Case Study

32 Lab Results Glucose: 92 mg/dL TC: 176 mg/dL HDL-C: 30 mg/dL LDL-C: 106 mg/dL TG: 200 mg/dL Non–HDL-C: 146 mg/dL hs-CRP: 3.1 mg/L A1 c : 5.6% Creatinine: 1.2 mg/dL AST: 25 U/L ALT: 40 U/L TC=total cholesterol, HDL-C=high-density lipoprotein cholesterol, LDL-C=low-density lipoprotein cholesterol, TG=triglycerides, hs- CRP=high-sensitivity C-reactive protein, AST=aspartate aminotransferase, ALT=alanine aminotranferase Case Study Month 5—MD Visit 3

33 A.Increase statin dosage B.Switch to a different statin C.Add a fibrate D.Discontinue niacin and add omega-3 FAs Which of the following would you be most likely to consider as part of the action plan for this visit? ARS Question

34 TC=total cholesterol, HDL-C=high-density lipoprotein cholesterol, LDL-C=low-density lipoprotein cholesterol, TG=triglycerides, hs- CRP=high-sensitivity C-reactive protein, AST=aspartate aminotransferase, ALT=alanine aminotranferase Case Study Action plan Discontinue niacin Start omega-3 (DHA/EPA) fatty acids (FA) 2000-mg QD,  to BID Increase metformin to 850-mg BID Month 5—MD Visit 3 Due to the negative effect of niacin on glucose control and insulin resistance 1,2, omega-3 fatty acids may be a preferred alternative in patients at risk for diabetes* Clinical Pearl *Reflects opinion of program Steering Committee. 1. Vittone F, et al. J Clin Lipidol. 2007;1:203-210. 2. Goldberg RB, et al. Mayo Clin Proc. 2008; 83:470-8.

35 Month 6—Registered-Dietitian Visit 3 Weight: 274.6 lbs Patient has been doing well with breakfast meal replacements, but is bored with diet and feels he has hit a weight plateau Plan – Congratulate him on losing 30 lbs! – Continue low-glycemic index diet, but brainstorm alternative breakfast and snack options – Food records 3 days/week, self-monitor weight every day for next 2 weeks – Reinforce need for physical activity Case Study

36 Month 8—MD Visit 4 Weight: 270.7 lbs (-35 lbs [-11%]), blood pressure: 124/82, heart rate: 68 bpm, waist: 43 inches Current meds: atorvastatin 10-mg QD, metformin 850- mg BID, omega-3 fatty acids (DHA/EPA) 2000-mg BID, ramipril 5-mg BID, amphetamine/dextroamphetamine 20-mg QD, paroxetine 20-mg QD, lithium 600-mg QD Using CPAP regularly and has good energy level Fair compliance to diet secondary to stress/family – Has some night eating, but generally minimizing sugar and carbohydrates He now feels active enough to exercise and is walking 20 min/day 4x/week Case Study

37 Month 8—MD Visit 4, Laboratory Results Glucose: 90 mg/dL TC: 157 mg/dL HDL-C: 42 mg/dL LDL-C: 91 mg/dL TG: 120 mg/dL Non–HDL-c: 115 mg/dL A1 c : 5.2% hs-CRP: 1.2 mg/L TC=total cholesterol, HDL-C=high-density lipoprotein cholesterol, LDL-C=low-density lipoprotein cholesterol, TG=triglycerides, hs-CRP=high-sensitivity C-reactive protein Case Study

38 Month 8—MD Visit 4, Action Plan Psychiatrist stopped lithium, reduced paroxetine to 10-mg QD and reduced amphetamine/dextroamphetamine to 10- mg QD Continue metformin 850-mg BID and use of CPAP Prescribe exercise regimen Case Study

39 In addition to lifestyle factors, biology favors weight regain Eckel RH. N Engl J Med. 2008;358:1941-1950. Clinical Pearl

40 A.60 B.120 C.180 D. >300 US Department of Health and Human Services. Available at: Accessed February 6, 2009. According to the US Department of Health and Human Services 2008 guidelines, how many minutes per week of moderate-intensity exercise do many people need to maintain their weight after a significant amount of weight loss? ARS Question

41 Although caloric restriction is the key to weight loss, regular physical activity is crucial to maintaining a lower body weight Clinical Pearl

42 National Weight Control Registry: Cardinal Behaviors of Successful Long-Term Weight Management Self-monitoring – Diet: record food intake daily, limit certain foods or food quantity – Weight: check body weight >1x/week Low-calorie, low-fat diet – Total energy intake: 1300–1400 kcal/day – Energy intake from fat: 20%–25% Eat breakfast daily Regular physical activity: 2500–3000 kcal/week (eg, walk 4 miles/day) Klem, et al. Am J Clin Nutr. 1997;66:239. McGuire, et al. Int J Obes Relat Metab Disord.1998;22:572.

43 Look for sleep apnea and treat it Get your patients off drugs that cause obesity (when possible) Consider insulin sensitizers Assess medications for aggravation of comorbidities Ask patients how well they are sticking to their intended lifestyle changes Key Learnings: Medical

44 Adapt the diet to your patient Inform patients that breakfast is associated with weight loss/lower body- weight Encourage self-monitoring – Food records – Regular “weigh-ins” Reinforce that exercise is critical for the maintenance of weight loss Key Learnings: Behavioral

45 Laboratory Test Results TC: 184 mg/dL HDL-C: 33 mg/dL LDL-C: 103 mg/dL TG: 240 mg/dL Non–HDL-C: 151 mg/dL Glucose: 106 mg/dL A1 c : 5.9% hs-CRP: 8.2 mg/L At the initial clinical presentation, would this patient have been a candidate for bariatric surgery? Weight: 305.7 lbs, BMI: 41.5 kg/m 2, waist: 48 inches, blood pressure: 138/90, heart rate: 68 bpm Patient at his highest weight and gaining – Several weight-loss attempts without significant progress Hyperlipidemia, hypertension, asthma, attention- deficit/hyperactivity disorder, fatigue, depression, obstructive sleep apnea Family history of obesity, type 1 and 2 diabetes BMI=body mass index

46 Bariatric Surgery Indications – BMI >40 kg/m 2 or BMI 35–39.9 kg/m 2 and life- threatening cardiopulmonary disease, severe diabetes, or lifestyle impairment – Failure to achieve adequate weight-loss with nonsurgical treatment Contraindications – History of noncompliance with medical care – Certain psychiatric illnesses: personality disorder, uncontrolled depression, suicidal ideation, substance abuse – Unlikely to survive surgery Adapted from NIH Consensus Development Panel. Ann Intern Med. 1991;115:956.

47 Surgeon experience is the single best predictor of success To locate an ASMBS Center of Excellence ASMBS=American Society of Metabolic and Bariatric Surgery. Clinical Pearl

48 A.It has not yet been associated with a significant improvement in overall mortality B.At 10-years postprocedure, it is associated with a decrease in the incidence of hypertension C.At 10-years postprocedure, over 1/3 of patients with diabetes at baseline no longer had the disease Which of the following is true about the effects of bariatric surgery? ARS Question

49 Bariatric Surgery: Long-Term Effects on Weight and Cardiovascular Risk Factors Prospective, controlled intervention trial of 4047 obese subjects (age=48 years, BMI=41 kg/m 2 ); gastric surgery* vs conventional treatmentProspective, controlled intervention trial of 4047 obese subjects (age=48 years, BMI=41 kg/m 2 ); gastric surgery* vs conventional treatment At 10 yearsAt 10 years – Weight change—surgery:  16.1% – Weight change—control:  1.6% (P<0.001) – Lower incidence of diabetes, hypertriglyceridemia, and hyperuricemia (P<0.05 for each) Sjostrom L, et al. N Engl J Med. 2004;351:2683-2693. Hypertri- glyceridemia Rate of Recovery (% of Subjects) 2410060 20 0 40 80 46 Low HDL Cholesterol 53 73 Diabetes 13 36 Hypertension 11 19 Hyperuricemia 27 48 Control Surgery *Banding, vertical-banded gastroplasty, gastric bypass † P≤0.001 ‡ P=0.02 ‡ † † † † Swedish Obese Subjects Study

50 Years 01234681015 0 10 -20 -30 Change in Weight (%) Control Banding Vertical-Banded Gastroplasty Gastric Bypass Years 0246810 16 14 0 2 4 6 8 10 12 1214 Cumulative Mortality (%) Control Surgery P=0.04 Sjostrom L, et al. N Engl J Med. 2007;357:741-752. *Surgical group vs control group at 16 years Swedish Obese Subjects Study Up to 16 years follow-upUp to 16 years follow-up Overall mortalityOverall mortality – Hazard ratio*=0.76 (95% CI: 0.59–0.99), P=0.04 Bariatric Surgery: Long-Term Weight Loss and Decreased Mortality

51 Advantages – “Forced” lifestyle changes – Improved cardiometabolic risk-factors – Decrease in diabetes Both recovery and  incidence – Decrease in mortality Pitfalls – Surgical complications – “Forced” lifestyle changes – Patients can “get around” the surgery Key Learnings: Bariatric Surgery

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