Obesity and Diabetes - Future Management

Transcription

1 Obesity and Diabetes - Future Management Professor Mike Lean Human Nutrition University of Glasgow and Otago Edinburgh 12 th September 2016

2 Disclosures: Research/conference support and advisory boards: (Novo Nordisk, Orexigen, Janssen, Cambridge Weight Plan) Medical consultancy for Counterweight Ltd I have never tasted Coca Cola, Pepsi or any other cola I have never owned a TV I have bought shares costing 10 in Eat Balanced Ltd

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5 Proportions of UK overweight (BMI>25) adults with and without obesity-related diseases Comorbidities: Diabetes, Hypertension, Stroke, Angina, MI. Vlassopoulos, Combet & Lean 2014, ICO in KL Data from the SHS ( ) n=24,831

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7 Life expectancy with obesity: BMI 30-35: reduced 2-4 years BMI 40-50: reduced 8-10 years Prospective Studies Collaboration (Whitlock et al) Lancet 2009 (cf, Fontaine et al 2003)

8 % patients affected Consequences of metabolic syndrome IGT/DM - driven by age and body fat Blood Glucose (mmol/l) (Fasting or 2h)

9 Current management priorities for Metabolic Syndrome/T2DM 1. Reduce HbA1c 2. Delay vascular complications 3. Arrest the underlying disease process Prevention Remission from diabetes

10 Diabetes Prevention: weight control is vital DPP and DPS: mean 4kg maintained weight loss, and exercise, prevented most progression from IGT to T2DM (57% prevented) Weight loss is the dominant element Better than metformin (Torgerson, XENDOS trial) Further (minor) T2DM prevention Regular physical activity (increase type-1 muscle fibres) Low saturated fat diet Fruit and vegetables Magnesium Cereal fibre Low GI Wing et al., Diabetes Care 1998

11 Diabetes Prevention: weight control is vital DPP and DPS: mean 4kg maintained weight loss, and exercise, prevented most progression from IGT to T2DM (57% prevented) Better than metformin Weight loss is the dominant element (Torgerson, XENDOS trial) Further (minor) T2DM prevention Regular physical activity (increase type-1 muscle fibres) Low saturated fat diet Fruit and vegetables Magnesium Cereal fibre Low GI Wing et al., Diabetes Care 1998

12 75 drugs currently licensed for reducing HbA1c int2dm (with multiple trade names) (plus 25 in the licensing pipeline) (plus countless more in development) Alpha-Glucosidase Inhibitors: acarbose miglitol Biguanides metformin metformin-alogliptin metformin-canagliflozin metformin-glipizide metformin-glyburide metformin-linagliptin metformin-pioglitazone metformin-repaglinide metformin-saxagliptin metformin-sitagliptin Dopamine Agonist bromocriptine DPP-4 Inhibitors alogliptin alogliptin and pioglitazone linagliptin saxagliptin sitagliptin sitagliptin and simvastatin Glucagon-Like Peptides albiglutide dulaglutide exenatide liraglutide Meglitinides nateglinide repaglinide SGLT2 Inhibitors dapagliflozin canagliflozin empagliflozin Sulfonylureas glimepiride glimepiride and pioglitazone glimeperide and rosiglitazone gliclazide glipizide glyburide chlorpropamide tolazamide tolbutamide Thiazolidinediones rosiglitazone pioglitazone 40 listed

13 SIGN 115 Obesity (2010) Dietary interventions in adults Calculated to produce a 600 kcal/day deficit Tailored to the dietary preferences of the individual Emphasise achievable and sustainable healthy eating Very Low Calorie Diets for rapid weight loss, under medical supervision Drugs Orlistat should be considered as an adjunct to lifestyle interventions Surgery BMI 35 kg/mƒ 2 & severe comorbidities expected to improve ƒsignificantly with weight reduction (eg severe mobility problems, arthritis, T2 diabetes). AND completion of a structured weight management programme involving diet, ƒphysical activity, psychological and drug interventions, without significant and sustained improvement in the comorbidities.

14 NICE: bariatric surgery and VLCD (2014) BMI of >40 kg/m 2 or and other significant disease. All appropriate non-surgical measures have been tried without maintained adequate, clinically beneficial weight loss.

15 NICE Clinical Guideline for Type 2 Diabetes Update June % overweight or obese Available from: 15

16 Life-expectancy is still reduced 6-10 years by T2DM, despite all our drug treatments (Wirral) Nwaneri et al Postgrad Med J 2012)

17 Once you have T2 Diabetes. Treatment aims: To reduce HbA1c?To reduce vascular complications??to arrest the underlying disease process (Remission from diabetes)

18 Multiple clinical benefits from major weight loss 4 y after laparoscopic adjustable gastric banding Hypertension Sleep apnoea Dyspnoea General physical activity Self esteem Frigg et al. Obes Surg, 2004 Diabetes T2DM cured in 75% Peripheral Oedema Joint pain Reflux T2DM resolved in 78% N=4070, mean age 40, BMI 48, Systematic review and meta-analysis Buchwald et al Am J Med, 2009 Improved Cured

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20 ...since my surgery I felt that I wanna die feeling... It was HORRIBLE... If I eat too many carbs at one time, I get so tired immediately after and almost feel drunk and may even slur my words Treating Dumping syndrome: Acarbose, Octreotide...

21 Common malabsorptive deficiencies after gastric bypass surgery Iron 20-50% Zinc Calcium 25-50% Vitamins A B1 B % Folate 45% D 25-50% Protein 10% Drugs variable Sawaya et al, 2013

22 The new epidemic: Severe and complicated obesity SIGN 115: Management of Obesity 2010 weight loss interventions should be targeted to improving these comorbidities; in many individuals a greater than 15-20kg weight loss (will always be over 10%) will be required to obtain a sustained improvement in comorbidity.

23 The new epidemic: Severe and complicated obesity SIGN 115: Management of Obesity 2010 weight loss interventions should be targeted to improving these comorbidities; in many individuals a greater than 15-20kg weight loss (will always be over 10%) will be required to obtain a sustained improvement in comorbidity.

24 Pancreas fat content (%) First phase insulin response (nmol/min/m 2 ) 15kg weight loss on 450kcal/d diet Normalised beta-cell function and pancreas fat Week Week Lim et al, Diabetologia 2011

25 15kg intentional loss might normalise life expectancy Life expectancy (mean age 64 at diagnosis) Normalise life expectancy Weight loss (kg) in first 12 months Lean et al. Diabetic Medicine, kg loss? 95% CI mean 95% CI

26 Meta-analysis of non-surgical trials with 1-year follow-up: BEST RESULTS WITH MOST RAPID WEIGHT LOSS 15 kg Average weight loss in subjects completing 1-year 80 studies, n = 26,455, completers =18,199 (69%) (Franz et al JADA 2007)

27 To maintain weight loss, behaviours must counteract environment and physiology: drugs and surgery are most effective (Greenway 2015) Obesogenic Environment Physical environment Food environment Educational environment Cultural environment Social environment Social Marketing (normalised behaviours) Obesogenic medications Biological & Physiological Satiety signals - fall with weight loss (Leptin, PYY, CCK, amylin, insulin, GLP-1) Orexigenic signals - rise with weight loss (eg. Ghrelin, GIP) Metabolic Rate falls with energy restriction & with weight loss Leslie et al 2007; Sumithran et al 2011; Maclean 2011; Leibel et al 1995;

28 Increasing awareness of Behavioural Therapy: SIGN 2010 Diabetes Guidelines 3 pages out of 21 on Diet/Lifestyle, before drug treatment. improves self-management, metabolic and psychological outcomes Intensive, frequent contact with trained professionals Telephone contact, computer-assisted programmes Theory-based psychological interventions, motivational interviews Structured education curriculum, evidence-based, underpinning philosophy, specific aims and learning objectives Quality-assured, independent audit assessment vs. predefined criteria Similar emphasis is needed for obesity treatment more generally

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31 Medical weight loss in primary care for overweight & obese non-diabetic reduces all risk factors at 1-2 years (Naude et al meta-analysis 2014)

32 Weight loss maintenance programmes after VLCD/TDR: a meta-analysis of RCTs (Johansson et al 2014) Thin lines = control Thick lines = intervention

33 Body Weight (kg) Copenhagen Weight Loss in Knee Osteoarthritis trial: more liberal TDR allowed more patients to do well Little difference in weight loss 415kcal VLED vs. 810kcal LED D = structured food/formula maintenance programme (No anti-obesity drug) weeks (D) 1500kcal/d part food/part formula [average one formula meal daily] (E) Knee exercises group ) (C) Control no intervention weeks 810kcal/d 98.0liquid formula 415kcal/d liquid formula weeks 1200kcal Part food/part formula 2 meals /day Time (weeks) n=96 per group n=64 per group (Bliddal et al, secondary care, dietitian managed)

34 Counterweight-Plus - Protocol Nutritionally complete Total Diet Replacement (TDR) Homemade (811calories/day) Commercial (832calories/day) Cambridge Weight Plan Plus: Structured patient education Step down approach optional >2.25l fluid per day (4 pints) Fibre supplement Screening TDR Stage Food Reintroduction Weight Loss Maintenance Lean et al, Br J GP (2013)

35 Weight Loss Maintenance- Protocol Stepped Food Reintroduction Introduce one kcal meal Add a meal every two weeks Meals based on eatwell plate Offer Orlistat Maintenance Low fat diet (30% fat) Estimate 500 kcal/d deficit 2500 kcal/d upper limit Relapse Management - Offer orlistat - Second attempt LELD stage Screening TDR Stage Food Reintroduction Weight Loss Maintenance Lean et al, Br J GP (2013)

36 Behavioural Strategies Weight Loss Maintenance All Appointments for months: Review of outcome goals Weight Tracker - Provide feedback on performance Rewards - For effort or progress towards behaviour Preventing Relapse - Self talk- cognitive restructuring Maintaining Change -Provide normative information about the -behaviours of others

37 Weigtht Change (kg) Counterweight-Plus feasibility study in severe obesity (n = 91, mean BMI 47) (820kcal Total Diet Replacement, Food Reintroduction and Maintenance) Days Lean et al, Br J General Practice (2013)

38 Weigtht Change (kg) Popular Belief: Patients regain all the weight, or more In Fact: 25% fail to engage at all Maintaining Lose <5kg weight (yet claim loss to 15kg be adhering at 12 months: to programme) 33% of all 91 patients 50% follow some or most of the programme 44% of patients with a known 12-month weight Achieve 57% of those and maintain who lost >15kg 5-20kg on weight LELD loss ) 25% adhere fully Highly cost-effective: Lose and maintain >20kg weight loss 4 times more lose >15kg as with bariatric surgery 25% 50% 25% Days Lean et al, Br J General Practice (2013)

39 Efficiency of Obesity treatment Cost-effectiveness: Per 1 million NHS spend: Lap Band surgery, complications and follow 7, patients can be treated: 80% achieve >15kg 12m weight loss >15kg loss for 106 patients Counterweight-Plus TDR & Maintenance patients can be treated: 30% achieve >15kg 12m weight loss >15kg loss for 383 patients plus >10kg loss for 459 patients Lean et al, Br J General Practice (2013)

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41 funded by DiABETES UK to Mike Lean and Roy Taylor Cluster-Randomised Trial: Counterweight-Plus* 810kcal/d LELD and weight maintenance programme vs usual care Both arms follow current clinical guidelines 280 patients, BMI >27, diagnosed T2DM <6 years, not on insulin Co-primary endpoints: weight loss >15kg and non-diabetic HbA1c at 12 & 24 months off all drugs (plus life-long clinical monitoring) Mechanistic and Magnetic Resonance studies Qualitative and process evaluation Planned economic analyses * Supported by Cambridge Weight Plan

42 Obesity Crisis Solutions: Ethics of treatments for obesity and type 2 diabetes No drug should be prescribed without providing trained professional support, for an optimal diet and lifestyle change programme No clinical trial should be permitted unless an optimal diet and lifestyle change programme is provided, to both intervention and placebo arms

43 Epidemic!* Medical Responsibility Political Responsibility * WHO: Critical Threshold for Intervention Optimal medical care within available resources Government interventions to remove primary causes Diet & lifestyle Drugs Surgery Catering outlets increasing Meals/snacks outside home increasing Portion sizes increasing Palliative Physical inactivity

44 Health by Stealth: Eat Balanced pizzas now reach 32,000 Scottish children every week PIZZA POWER KIDS by Eat Balanced now in Primary Schools in: East Renfrewshire Moray Argyle and Bute Aberdeen City South Ayrshire Trials in another 10 councils: Fife East Ayrshire North Ayrshire Clackmannanshire Edinburgh City Glasgow City Highland Tayside (includes Dundee, Perth & Kinross, Angus)

45 9-month weight changes in 20,975 young adults randomised to an on-line public health intervention Control Group n = 2,134 Rational Model (NTICV) n = 1,810 Stealth Model (GD) n = 2,057 Nikolaou, Hankey & Lean, Obesity 2015

46 Future: Address body fat or adipose tissue mass (not BMI) Best R 2 vs MRI (total body fat) BMI /0.82 R 2 (m/f) Algindan et al MRI validation study (total adipose tissue) Waist /0.78 Body fat equation (Algindan et al 2015) /0.89 DEXA BIA massive variability - Algindan, Hankey, Govan, Gallagher, Heymsfield, Lean Br J Nutrition 2015

47 Prospective associations of beverage consumption with incident type 2 diabetes: random effects metaanalysis. *Unadjusted for adiposity. Adjusted for adiposity. Adjusted for adiposity and within person variation. (Imamura et al. BMJ 2015) 2015 by British Medical Journal Publishing Group

48 SSBs and BMI-adjusted risk of diabetes in EPIC-Interact (Europe) Romaguera-Bosch et al. Diabetologia 56:1520, 2013

49 Future management: Conclusions Measure and deal with excess body fat, not BMI Direct major resources for research and routine management of obesity, not its complications Target an amount of weight loss relevant to obese people and their medical needs, not statistics Tackle the real problem faced by patients ie weight-loss maintenance, not weight loss Provide optimal non-surgical weight-management routinely, and accept that not all will succeed (they may not do well with surgery either) End manipulation of consumers, with damage to health, for profit

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