Obesity and diabetes threaten European quality of life and regional health and social care budgets

Transcription

1 Obesity and diabetes threaten European quality of life and regional health and social care budgets Professor Mike Lean 3rd May 2017

2 Type 2 Diabetes in the 21 st Century A New Treatment Paradigm Professor Mike Lean 3rd May 2017

3 Type 2 Diabetes in the 21 st Century A New Treatment Paradigm Professor Mike Lean 3rd May 2017

4 Type 2 Diabetes in the 21 st Century A New Treatment Paradigm Mike Lean: Declaration of relevant interests General Physician, Specialist trained in Diabetes and Endocrinology Professor of Human Nutrition, Universities of Glasgow and Otago (NZ) Past Director, Health Education Board for Scotland, Chair of Food Standards Agency Advisory Committee on Research Funding for research, meeting attendance and consultancies: Novo Nordisk, Orexigen, Cambridge Weight Plan I have never tasted Coca Cola, Pepsi or any other cola in my life I have never owned a TV I have bought shares costing 10 in Eat Balanced

5 What type of diabetes? Type 1 DM: Pancreas beta-cell failure, insulin deficient Type 1a Secondary autoimmune = juvenile onset. But at any age Type 1b Primary auto-immune endocrine Typically women age Often other endocrine autoimmune diseases (HLA B-27 gene) Type 2 DM: excess fat storage and insulin resistance Disease process depends on fat accumulation Strong genetic-familial link: Metabolic Syndrome / ectopic fat Age related: mostly over age 50 but also in fatter younger people Revealed by inflammation, stress (steroids) Revealed by endocrine changes in puberty and pregnancy Malnutrition-related DM, Pancreatic DM MODY, rare genetic forms, etc

6 Diabetes prevalence in European men Prevalence Normal weight BMI <25 3.7% Overweight BMI % Obese BMI > % Among obese, age % % % % Lean, Tajar & Han, Br Med Bulletin, 2011 European Male Aging Study

7 Outlook for people with T2DM, even treated under current guidelines A very nasty, cruelly progressive, disease. Multiple disabling complications, reduced life expectancy. Commonest cause of blindness Commonest cause of kidney failure Commonest cause of amputations: ulcers, gangrene Painful chronic neuropathies, impotence Premature dementia Premature CHD and strokes Increased cancer risks Polypharmacy, personal and societal costs T2DM is considered by most doctors and patients as a permanent, incurable, inevitably progressive diagnosis

8 There are 518 drugs (84 generic compounds) currently licensed for T2DM (plus >25 seeking licences, and many more in development) Alpha-Glucosidase Inhibitors: acarbose miglitol Biguanides metformin metformin-alogliptin metformin-canagliflozin metformin-dapagliflozin metformin-glipizide metformin-glyburide metformin-linagliptin metformin-pioglitazone metformin-rosigitazone metformin-repaglinide metformin-saxagliptin metformin-sitagliptin Dopamine Agonist bromocriptine Data from Medtrak, April 2017 DPP-4 Inhibitors alogliptin alogliptin-pioglitazone linagliptin linagliptin-empagliflozin saxagliptin saxagliptin -dapagliflosin sitagliptin sitagliptin-simvastatin Glucagon-Like Peptides albiglutide dulaglutide exenatide liraglutide lixisenatide Meglitinides mitiginide nateglinide repaglinide SGLT2 Inhibitors dapagliflozin canagliflozin empagliflozin Sulfonylureas glimepiride glimepiride-pioglitazone glimeperide-rosiglitazone gliclazide glipizide glyburide chlorpropamide tolazamide tolbutamide Thiazolidinediones rosiglitazone pioglitazone lobeglitazone

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

10 21 st Century Medicine Tackling underlying disease processes, - not just symptoms or consequences For T2DM, not just blood sugar/ HbA1c The underlying process of T2DM is fat accumulation, especially in liver and pancreas: ectopic fat Exceeding the Personal Fat Threshold.

11 Weight gain/ obesity is the main cause of T2DM - and necessary, whatever the genes Colditz GA et al. Ann Int Med, 1995 Adjusted RR (BMI <22 = referent) < Median BMI 30 at diagnosis >35 BMI (kg/m 2 )

12

13 Multiple clinical benefits from major weight loss 4 y after weight loss surgery T2DM remission in 75% Hypertension Sleep apnoea Dyspnoea General physical activity Self esteem Diabetes Peripheral Oedema Joint pain Reflux Improved Cured Frigg et al. Obes Surg, 2004

14 - 15% 15 kg weight loss normalises glucose tolerance: 2-year RCT, weight-loss surgery vs diet advice Can we achieve similar results without surgery? -20.7% = 15kg -1.7% 13% 73% Dixon et al (2008) JAMA

15 Pancreas fat content (%) First phase insulin response (nmol/min/m 2 ) 600kcal/d TDR formula diet for type 2 diabetes: 15kg weight loss normalised beta-cell function and pancreas fat Week Week Lim et al, Diabetologia 2011

16 Years life expectancy at age 64 15kg intentional weight loss normalised life expectancy (Type 2 diabetes, BMI >25, mean age 64) Non-diabetic life expectancy % CI mean 95% CI Weight loss (kg) in first 12 months Lean et al. Diabetic Medicine, kg loss

17 Remission of Type 2 Diabetes Weight loss >10% />15kg achieves Remission of T2DM for about 40-70% of all people. HbA1c, OGTT, - no longer diabetic Insulin response to food normal Loss of ectopic liver and pancreas fat Massive personal benefits Massive healthcare savings... Results of DiRECT late 2017 (funded by Diabetes UK, using Counterweight-Plus TDR)

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

19 Counterweight-Plus Feasibility Study 40-50% maintain >15kg loss at 12 months 820kcal/day TDR for weight loss phase People prefer to use commercial TDR products. TDRs need to be widely available, at affordable prices. Support programme with trained staff is vital to maintain weight loss and diabetes remission.

20 Possible Safety concerns with Total Diet Replacement for weight loss Constipation: Add Fibogel, avoid Mg depletion Mg: depletion causes T2DM, constipation, depression: Current Magnesium 400mg/day is probably sufficient (Diarrhoea is NOT a problem: laxative dose is 2-4g/day) Essential Fatty Acids? Needed to help reduce BP & lipids Current content is sufficient: BP and lipids fall during weight loss Reduced requirement during weight loss Choline??? No problems reported Choline is NOT required by healthy humans, (made in the liver) No deficiency disease in humans, or deficiency reported with TDR

21 Diabetes causes and prevention: weight control is vital 4kg weight loss, and exercise, prevents most progression to T2DM (57% prevented: DPP and DPS) Weight loss is the dominant element Better than metformin (Torgerson, XENDOS trial) Other factors for T2DM prevention Regular physical activity (increase type-1 muscle fibres) Magnesium (Mg) Low saturated fat diet Fruit and vegetables Cereal fibre Low GI

22 Daily magnesium intake and diabetes Recommendations Average Intakes EFSA (AI 2015) m 350mg; f 300mg m 360mg; f 280mg US (RDA 2016) m 420mg; f 320mg m 450mg; f 390mg Risk of Type 2 Diabetes falls 15% per 100mg/day extra Magnesium Larsson & Wolk 2017

23 Diabetes Depression Stroke Heart Disease Gallstones Epilepsy

24 Macronutrients (Fat, Carbohydrate, Protein) in Formula Diets for weight loss Proportion of macronutrients in a formula TDR: Does not affect weight loss Does not affect change in lean body mass Does not affect improvement in blood lipids Does not affect improvement in diabetes

25 Evidence: Fat/Carbohydrate and weight loss on TDR Weight loss is entirely predicted by calorie deficit Fat/ Carbohydrate content is unimportant A calorie is a calorie Bortz, 1967, 1968

26 Evidence: protein content, muscle and Lean Body Mass Muscle mass is maintained by protein intake >0.6g/kg in weightstable healthy people, and by physical activity. Protein requirement is reduced during weight loss Adipose tissue is 75-80% fat, and 20-25% lean tissue Weight loss must always include loss of some lean body mass Adding extra protein cannot prevent loss of lean tissue during TDR weight loss Extra dietary protein is metabolised in the same way as carbohydrate.

27 Composition of Total Diet Replacement (TDR) needed for healthy weight loss: different to requirements for weight-stable health MINIMUM level Commission proposal CODEX Standard 1995/EFSA Scientific opinion 2011 Protein 75g 50g Essential Fatty Acids: Linoleic 11g ALA 1.4g 0.5g Choline 400mg No set value 3g MAXIMUM Commission proposal EFSA AI 2015 United States RDA 2016 Magnesium 250mg 350mg (m) 300mg (f) 420mg (m) 320mg (f)

28 Dietary Recommended Values (DRV) and requirements during TDR for weight loss Nutrient DRVs are for weight-stable healthy people. For some nutrients, DRVs are not known but we quote the Adequate Intake (AI) of healthy people There are several types of DRV: Maximum level above which some people may become ill Minimum intake below which some people may become ill Average amount for healthy weight (for macronutrients) These figures, especially AI, should not be extrapolated to people who are losing weight, rapidly, on TDR. Metabolic rate falls 15-20% Most nutrient requirements fall Protein turnover and requirement falls Instead, we should first base recommendations on the AI of nutrients in TDR, provided no deficiency or toxicity is reported

29 The bottom line! If it ain t broke, don t fix it! Current Formula Diets: Are well accepted Excellent safety record Generate 15kg weight loss & remission of T2DM for 40-70% Improve BP and lipids (with current EFA content) Contain appropriate macro-nutrients: do not alter Contain adequate Mg: do not reduce Do not require more EFAs (rancidity problem) Do not require more protein (more expense & less palaable) Do not require choline (not a nutritional requirement for adults) Must be kept simple to become more affordable Research needed to improve support programmes

30 Type 2 Diabetes in the 21 st Century A New Treatment Paradigm Professor Mike Lean 3rd May 2017