How to work up the patient with Diabetes and Obesity

Transcription

1 How to work up the patient with Diabetes and Obesity Ken Fujioka, M.D. Director of Nutrition and Metabolic Research Scripps Clinic Dept. of Diabetes and Endocrine Panama Boca Del Toro 2015 AACE Boston 2018

2 WHAT ARE YOU TRYING TO TREAT IN THE PATIENT WITH OBESITY AND TYPE 2 DIABETES? The patient is easy: they want to lose weight As a physician what are your goals Which patient do you choose What treatment do you choose Need to know your Metrics Diabetes Care Metrics

3 METRICS : WHAT ARE THE METRICS Check Two HbA1c tests with the most recent <8.0% Most recent blood pressure < 140/90 LDL, 100 or on a statin Medical attention to nephropathy with the past 12 months What is considered medical attention for nephropathy? Medical attention for nephropathy can be met with any one of the following: 1) Urine Micro Albumin testing 2) ACE/ARB prescription (electronically prescribed or recorded) 3) Diagnosis of chronic kidney disease stage 4 (ICD or ICD10 N18.4) 4) Visit with a nephrologist

4 METRICS: THE GOOD, THE BAD, AND THE REAL UGLY Bundle package : need to meet all Metrics (all or nothing) to collect If you meet all of metric criteria for a group of patients then you will get paid a lump sum (Bonus) at the end of the year If you do not meet the metric criteria for a percentage of your patients you get NOTHING at the end of the year They obviously don t expect Health Care providers to meet all these goals in all patients Usually need to hit a percentage of your total diabetic patients (50%) Example if you have 100 diabetics in your practice then 50 or more of them need their metrics at goal (all of the metrics) The metrics most often missed are A1c <8 and LDL <100 or on a statin

5 CAN YOU TREAT ALL OF THIS WITH WEIGHT LOSS? WHAT METRICS ARE IMPROVED BY WEIGHT LOSS Improve very nicely A1c Blood pressure Proteinuria Clinically speaking Weight loss does not improve the LDL measurement LDL (the size and athrogenicity will decrease or improve)

6 HOW MUCH WEIGHT LOSS IS NEEDED TO IMPROVE GLYCEMIC CONTROL? Improvement begins with >2% weight loss 0 Change in A1C (%) by Weight-Loss Category Change in A1C (%) P < Gained >2% Gained 2%- Lost <2% Lost 2%- Lost <5% Lost 5%- Lost <10% Lost 10%- Lost <15% Lost 15% A1C = glycated hemoglobin. Wing RR, et al. Diabetes Care. 2011;34:

7 HOW MUCH WEIGHT LOSS IS NEEDED TO IMPROVE BP? Effect of amount of weight loss on SBP and DBP: direct and linear 0 Change in BP by Weight-Loss Category Change in BP (mm Hg) SBP: P <.0001 DBP: P <.0001 SBP DBP -14 Gained >2% Gained 2%- Lost <2% Lost 2%- Lost <5% Lost 5%- Lost <10% Lost 10%- Lost <15% Lost 15% DBP = diastolic blood pressure; SBP = systolic blood pressure. Wing RR, et al. Diabetes Care. 2011;34:

8 HOW MUCH WEIGHT LOSS IS NEEDED TO IMPROVE LIPIDS? Effect of amount of weight loss on HDL-C and TGs is direct and linear; effect on LDL-C is less pronounced Change in TGs (mg/dl) P <.0001 Change in TGs by Weight-Loss Category Change in HDL-C/LDL-C (mg/dl) Change in HDL-C/LDL-C by Weight-Loss Category HDL-C: P <.0001 LDL-C: P =.3614 HDL-C LDL-C -100 Gained >2% Gained 2%- Lost 2%- Lost 5%- Lost 10%- Lost 15% Lost <2% Lost <5% Lost <10% Lost <15% HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol. Wing RR, et al. Diabetes Care. 2011;34: Gained >2% Gained 2%- Lost 2%- Lost 5%- Lost 10%- Lost 15% Lost <2% Lost <5% Lost <10% Lost <15% 8

9 WEIGHT LOSS TREATMENT OPTIONS: 2018 Diet Meal replacements, VLCDs, standard low calorie diets, Keto diet, Paleo, alternate day fasting or intermittent fasting Exercise Cardio or resistance training or both? Medications 4 6 to choose from Bariatric surgery Sleeve Gastrectomy Gastric bypass

10 JAMA, 2010; 304:

11 HbA1c by Month and Group 7.80 Intention-toTreat Analysis (n=262) 7.70 Control HbA1c, % Resistance Aerobic Combo Month And yes the combination of Resistance and Aerobic exercise group lost more weight

12 THE NEUROPHYSIOLOGY OF HUMAN FOOD INTAKE: PLEASE TRY NOT TO FALL ASLEEP HOW TO PICK A WEIGHT LOSS MEDICATION

13 Eat (Hunger) Stop Eating NYP Hypothalamus POMC Fat Cells Leptin Gastrointestinal Track GLP-1, GLP-2, PYY, and many more Pancreas Amylin, Insulin

14 Brain Eat (Hunger) Stop Eating Dorsal Vagal Complex Hind Brain Stop Eating NYP Hypothalamus POMC Vagal Afferent fibers Gastrointestinal tract Fat Cells Gastrointestinal Track Pancreas

15 Dopamine Nor-epinephrine Motivated reward eating Eat (Hunger) Stop Eating Dorsal Vegal Complex Hind Brain Stop Eating Mesolimbic system NYP Hypothalamus POMC Vagal Afferent fibers Fat Cells Gastrointestinal Track Pancreas

16 Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline Caroline M. Apovian, Louis J. Aronne, Daniel H. Bessesen, J Clin Endocrinol Metab 100: , 2015 MECHANISM

17 WHAT TO LISTEN TO IN THE PATIENT HISTORY Listen or ask about the patient s eating behavior Does the patient Crave any particular food Is Meal Size a problem Is the patient struggling with eating a normal portion of food Does the patient Binge Eat (eating large amounts of food feeling out of control ) Does the patient Night Eat (goes to sleep and gets up and eats) Or is the patient just simply Hungry (increased drive to eat)

18 CRAVINGS A motivational state whereby a person experiences an intense desire to eat a specific food The specificity of the food, drink, or taste that distinguishes food cravings from hunger If someone is hungry any food or drink will satisfy the hunger If someone craves a particular food then they will not be satisfied until they get that particular food Surprisingly craving is not a function of hunger but rather its specific to a trigger or environment cue Example: things like menses, boredom, watching TV, or even just simply being unhappy can trigger a craving for a specific food. Up to 48% of patients seeking weight loss will describe cravings as a problem M. MacMillan et. Al. What weight loss treatment options do geriatric patients with overweight and obesity want to consider? Obesity Science & Practice 2016 doi: /osp4.66

19 NALTREXONE ER/BUPROPION SR Mechanism of Action Naltrexone Opioid receptor antagonist Approved for Drug and alcohol addiction Bupropion Dopamine/noradrenaline reuptake inhibitor Approved for Depression and Smoking cessation Nonclinical studies suggest that naltrexone and bupropion have effects on at least two separate areas of the brain involved in the regulation of food intake: The hypothalamus (appetite regulatory center) The mesolimbic dopamine circuit (reward system, cravings) Approved 2014

20 CHANGE IN SELECTED ITEMS FROM THE CONTROL OF EATING QUESTIONNAIRE AT WEEK 56 * * * * * * *P <.05 vs placebo. Greenway FL, Fujioka, K, et al. Lancet. 2010;376, How hungry have you felt? How full have you felt? How difficult has it been to control your eating? Less Change from baseline (mm) More * * How difficult has it been to resist any food cravings? How often have you eaten in response to food cravings How often have you had food cravings for starchy foods? Placebo (n=511) Naltrexone 16 mg plus bupropion (n=471) Naltrexone 32 mg plus bupropion (n=471)

21 LORCASERIN AND PHENTERMINE MEANT WEIGHT LOSS Candida J. Rebello1, Elena V. Nikonova2, Sharon Zhou et. Al. Effect of Lorcaserin Alone and in Combination with Phentermine on Food Cravings After 12-Week Treatment: A Randomized Substudy; Obesity (2018) 26, doi: /oby.22094

22 CRAVINGS LORCASERIN AND PHENTERMINE

23 DEFINITION OF BINGE EATING An episode of binge eating is characterized by both: Eating, in a discrete period of time (example: within any 2-hour period), an amount of food definitely larger than most people would eat during a similar period of time and under similar circumstances 2 times a normal portion A sense of lack of control over eating during the episode (example: a feeling that one cannot stop eating or control what or how much one is eating) American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-V-TR. 5th ed. Washington, DC: American Psychiatric Association; 2013.

24 BED: DIAGNOSTIC CRITERIA Binge eating episodes associated with at least 3 behavioral indicators of loss of control Eating much more rapidly than usual Eating until feeling uncomfortably full Eating large amounts of food when not physically hungry Eating alone because of embarrassment over how much one is eating Feeling disgusted with oneself, depressed, or very guilty after overeating American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-V-TR. 5th ed. Washington, DC: American Psychiatric Association; 2013.

25 BED: EVALUATING FOR DIAGNOSIS To evaluate for BED, the clinician need only ask two questions Do you eat an unusually large amount of food in a short period? Do you feel out of control as you do so? Carter WP. Curr Psychiatry. 2002;1:51-58.

26 DRUG-INDUCED BINGE EATING AND WEIGHT GAIN 74 patients with psychotic disorders receiving clozapine (N=57) or olanzapine (N=17) were studied for Appearance of binge eating, as well as lifetime BED and BN Increased weight and BMI 37 (50%) were positive for binge eating 12 (16%) for BED or BN In 29 (78%) patients, binge eating began with antipsychotic exposure Bingeing patients showed increased weight as compared with non-bingers BMI: 27 vs 24; P=.007 Study concluded that clozapine or olanzapine may induce binge eating and eating disorders ( medication-induced eating disorders ), resulting in weight gain Theisen FM et al. J Neural Transm. 2003;110:

27 BED: GENETICS AND ASSOCIATED PSYCHOPATHOLOGY BED is associated with a genetic mutation also linked to severe childhood obesity MC4 receptor mutation Branson R et al. N Engl J Med. 2003;348: ; Farooqi IS et al. N Engl J Med. 2003;348: ;

28 TOPIRAMATE AND BED: TREATMENT PARADIGM Washout Phase 25 mg/ qhs 25 mg/ qhs 50 mg/ qhs 50 mg/ qhs 100 mg/ qhs 100 mg/ qhs Median dose 212 mg/d Topiramate (May be increased to a maximum of 600 mg/qhs) Placebo Median dose 200 mg/d Topiramate open label 50 mg/wk 75 mg/wk Maintenance 35 Screening/ Washout Phase Study Week Double-Blind Phase Open-Label Phase 56 McElroy SL et al. Am J Psychiatry. 2003;160: ; Mc

29 TOPIRAMATE AND BED: MEAN BINGES/WEEK Mean Binges/wk Placebo Topiramate Weeks P= McElroy SL et al. Am J Psychiatry. 2003;160:

30 TOPIRAMATE AND BED: MEAN WEIGHT CHANGE ITT Mean Weight Change (kg) Placebo Topiramate Weeks (2.6 lb) (12.8 lb) P=.005. McElroy SL et al. Am J Psychiatry. 2003;160:

31 Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline Caroline M. Apovian, Louis J. Aronne, Daniel H. Bessesen, J Clin Endocrinol Metab 100: , 2015 MECHANISM

32 BODY CONTINUES TO FIGHT AGAINST WEIGHT LOSS LONG AFTER DIETING HAS STOPPED 50 obese men and women Men 233 lbs/average, women 200 lbs/average Extreme low-calorie diet Optifast shakes + 2 cups of low-starch vegetables Total 500 to 550 calories a day for eight weeks At 10 weeks: 30-lb ave. weight loss At year one: 11-lb ave. weight regain Reported feeling more hungry and preoccupied with food than before the weight loss Sumithran P et al. N Engl J Med. 2011;365:

33 LONG-TERM PERSISTENCE OF HORMONAL ADAPTATIONS TO WEIGHT LOSS Changes in Weight from Baseline to Week lb loss ITT = intention to treat 11 lb gain 10 wk weight loss program Sumithran P et al. N Engl J Med. 2011;365:

34 FASTING/POSTPRANDIAL HORMONE LEVELS Mean (±SE) Fasting and Postprandial Levels of Ghrelin, Peptide YY, Amylin, and CCK at Baseline, 10 Weeks, 62 Weeks Sumithran P et al. N Engl J Med. 2011;365:

35 HOW STRONGLY DOES APPETITE COUNTER WEIGHT LOSS? QUANTIFICATION OF THE FEEDBACK CONTROL OF HUMAN ENERGY INTAKE David Polidori, Arjun Sanghvi, Randy J. Seeley, and Kevin D. Hall Obesity (2016) 24,

36 FIND A SITUATION IN THE FREE LIVING WORLD WHERE HUMANS LOSE CALORIES (WITHOUT CHANGING BEHAVIOR ) In patients with type 2 diabetes, treatment with canagliflozin at a dose of 300 mg/day increases mean daily UGE by approximately 90 g/day A. does not effect central energy regulating pathways B. patients are not aware of the energy deficit Thus observed increased energy intake countering the weight loss induced by SGLT2 inhibition reflects the activity of the feedback control system.

37 HOW TO FIND OUT HOW MUCH MORE WE EAT IN RESPONSE TO LOSING CALORIES WITHOUT TRYING calculated the free-living energy intake changes in: 153 free living DM patients treated with 300 mg/day canagliflozin 52-week trial using the measured body weight data assume mean UGE of 90 g/day input into a fancy mathematical model validate against expensive biomarker method

38 HOW STRONGLY DOES APPETITE COUNTER WEIGHT LOSS? QUANTIFICATION OF THE FEEDBACK CONTROL OF HUMAN ENERGY INTAKE Obesity Volume 24, Issue 11, pages , 2 NOV 2016 DOI: /oby

39 TAKE HOME MESSAGE: ONCE A PATIENT LOSES ABOUT 5% OF THEIR WEIGHT, THE BODY WILL TRY TO STOP FURTHER WEIGHT LOSS On average, energy intake increased by 100 kcal/day per kilogram of weight lost This is a lot more than anyone thought Compared to 30 kcal/kg/day changes in energy expenditure observed with 10% weight loss in subjects with obesity (1) 1. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med 1995;332:

40 PATIENT HISTORY: I CAN T SEEM TO LOSE WEIGHT ANYMORE Patient describes going on a weight loss program on her own She is eating healthy She started exercising Her family is helping out and being supportive She describes losing 10% of the weight (20 lbs) but needs to lose another 20 pounds She now comes to you for help because she can t seem to lose weight anymore

41 PATIENT LOST WEIGHT ON HER OWN BUT NOW HAS HIT A PLATEAU Weight maintenance and additional weight loss with liraglutide after lowcalorie-diet-induced weight loss: The SCALE Maintenance randomized study T Wadden P Hollander, S Klein et al. International Journal of Obesity (2013) pts that had to lose at least 5 % of their weight on their own without medications just by diet and lifestyle were then randomized to Liraglutide or Placebo Patients follow for one year

42 LIRAGLUTIDE 3.0 MGS GIVEN TO PATIENTS AFTER A 6% WEIGHT LOSS Liraglutide Liraglutide Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: The SCALE Maintenance T Wadden P Hollander, S Klein et al. International Journal of Obesity (2013)

43 ITT WEIGHT LOSS AT ONE YEAR Phentermine/topiramate ER 15 mg/92 mg 9.8% vs 1.2% placebo Lorcaserin 10 mg BID 5.8% vs 2.5% placebo* Naltrexone/bupropion 32 mg/360 mg 5.4% vs 1.3% placebo Liraglutide 3.0 mg 7.4% vs 3.0% placebo Fujioka K. Current and emerging medications for overweight or obesity in people with comorbidities. Diabetes and Obesity 2015

44 ODDS & ENDS AND SUMMARY All weight loss meds category X One of the new meds may have specific effects on the fetus The FDA does not want weight loss in a pregnant female All of the meds above will give an average of over 10% weight loss if you follow nonresponder recommendations Get a feel for why the patient is obese and also what part of dieting they are struggling with This will help you choose your medication Look at the co-morbid medical problems The four new weight loss medications are approved for chronic use and can be used chronically (> 5years)

45 Thanks for Listening