OVERWEIGHT AND OBESITY. Dharma Lindarto Div. Endokrin-Metabolik Departemen Penyakit Dalam FK USU/RSUP H Adam Malik Medan.

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1 OVERWEIGHT AND OBESITY Dharma Lindarto Div. Endokrin-Metabolik Departemen Penyakit Dalam FK USU/RSUP H Adam Malik Medan.

2 Defining obesity Obesity - an excessive accumulation of body fat sufficient to impair health WHO 894 Obesity Report

3 Obesity is a Growing Problem 127 million adults in the U.S. are overweight, 60 million obese, and 9 million severely obese percent of U.S. adults are overweight (BMI 25) 30.5 percent are obese (BMI 30) 4.7 percent are severely obese (BM 40) Obesity is the No. 2 preventable cause of death and disability (smoking is #1)

4 Media coverage of obesity

5 Adipose Tissue White adipose tissue Stored under the skin, in mesenteries and omentum, behind the peritoneum Primarily fat, also small amounts of protein and water Stores triglycerides, Brown adipose tissue Large amounts in infants, small amounts in adults Found primarily in scapular, sub-scapular areas Heat production, cold adaptation, dissipation of excess energy

6 Adipose Tissue Mass vs. Function Dysfunctional adipose tissue without increase in mass Dysfunctional adipocyte Normal adipose tissue Dysfunctional adipose tissue with increase in mass Increased number of enlarged adipocytes Abnormal cytokine production Inflammation NEFA Systemic Insulin Resistance

7 Type 2 DM Arthritis Asthma Abnormal production of hormones (Adipocytokines ) in fat IL - 6 Lactate Inflammation Leptin TNF- α Adipsin (Complement D) ASCVD Lipoprotein Lipase Fat Stores ❽Adiponectin Angiotensinogen FFA Resistin Plasminogen Activator Inhibitor 1 (PAI-1) Hypertension Dyslipidemia DM=diabetes mellitus; FFA=free fatty acid; PAI-1=plasminogen activator inhibitor-1; TNFα=tumor necrosis factor alpha; IL-6=interleukin 6. Slide: After Dr. G Bray Estrogen Insulin Type 2 DM Thrombosis

8 Adipocytokines The term adipocytokines : adipocyte-derived biologically active molecules which may influence the function as well as the structural integrity of other tissues Some examples of these substances are: - leptin, - acylation-stimulating protein (ASP), - tumor necrosis factor-a (TNF-a), - plasminogen activator inhibitor-1 (PAI-1) - interleukin-6

9 Adipocytokines Leptin is considered to be a fundamental signal of satiety to the brain and has a variety of actions, ranging from interference with sympathetic activity to hematopoiesis and reproductive function ASP increases triglyceride synthesis by increasing adipocyte ASP increases triglyceride synthesis by increasing adipocyte glucose uptake, activating diacylglycerol acyltransferase, and inhibiting hormone-sensitive lipase

10 TNF: is involved in insulin resistance in obesity PAI-1: is a well-recognized causative factor for vascular thrombosis Resistin; adipose-specific cysteine-rich protein with a capacity to impair insulin sensitivity and glucose tolerance in murine models Adiponectin ; have anti-atherogenic and anti-inflammatory properties

11 Weight is controlled by a feedback system. Afferent EC-CB1 Hypothalamus, etc Efferent Ghrelin PYY CCK External Factors * food availability, palatability Vagus Nerve Gut and Liver Meal Size Autonomic Nervous System Food Intake Insulin Leptin Adrenal Steroids Pancreas Adipose Tissue Adrenal Cortex Energy Balance and Adipose Stores Energy Expenditure Adiponectin Aronne LJ. Adapted from Campfield LA, et al. Science. 1998;280: ; and Porte D, et al. Diabetologia. 1998;41:

12 Sugars please our brain, promote insulin secretion The paraventricular & arcuate nuclei contain neurons capable of stimulating/inhibiting food intake. Korner J and R Leibel NEJM 349; Y1R/Y2R denote subtypes of the neuropeptide Y (NPY) rec MC4R melanocortin 4 rec PYY peptide YY 3 36, GHsR GH hormone secretagogue rec AgRP agouti-related protein, POMC propio o melanocortin a-msh a -melanocyte stimulating protein LEPR leptin rec, and INSR insulin rec.

13 Estimation of Body Fat Bioelectrical impedance Low-energy current to the body that measures the resistance of electrical flow Fat is resistant to electrical flow; the more the resistance, the more body fat you have DEXA (dual x-ray photon absorptiometry) An X-ray body scan that allows for the determination of body fat Infrared light Assess the interaction of fat and protein in the arm muscle

14 Body Mass Index (kg/m 2 ) Dose - Response Risk Relationship Underweight < 18.5 Normal Overweight Obese > 30 Class I Class II Class III >40

15 BMI Criteria (WHO 2000) Kategori BMI (kg/m2) BMI Asia Underweight < 18.5 < 18.5 Normoweight Overweight: > 25 > 23 Pre-obese Obese I Obese II > 30.0 Obese III > 40.0

16 Waist Circumference Waist circumference, independent of BMI / weight, confers additional health risk with: Glucose intolerance / Diabetes mellitus Hypertension Dyslipidemia Important - WC in any weight category confers similar risk

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19 Central Adiposity

20 Regional Distribution The regional distribution of body fat affects risk factors for the heart disease and type 2 diabetes

21 Body Fat Distribution: Gynecoid Lower-body obesity--pear shape Encouraged by estrogen and progesterone Less health risk than upper-body obesity After menopause, upper-body obesity appears

22 Body Fat Distribution: Android Upper-body obesity--apple shape Associated with more heart disease, HTN, Type II Diabetes Abdominal fat is released right into the liver Encouraged by testosterone and excessive alcohol intake Defined as waist measurement of > 40 for men and >35 for women

23 Obesity: Causes and Consequences

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25 Etiology: i) Enzyme deficiency - responsible for alphaglycerophosphate oxidation. ii) Differences in thermogenesis - thin people are better able to dissipate excess calories through heat production. iii) Reduced ATPase activity - results in decreased ability to burn calories. iv)"hibernation response" - relic of human evolutionary past initiates overeating.

26 v) Genetic Etiology inheritance of increased # and size of fat cells child with one obese parent has 40% chance two obese parents has 80% chance vi) Socioeconomic factors Obesity is more common: children & adults from lower socioeconomic grps black vs white women white vs black men vii) Psychological - psychogenic component in 90% of cases, however, it is NOT primary cause.

27 Obesity TG HDL FFA Insulin resistance Blood pressure Blood glucose Type 2 diabetes Cardiovascular disease Metabolic syndrome : The role of obesity.

28 Role of obesity in insulin resistance Visceral Obesity Caloric intake Sedentary lifestyle Genetic factors Free fatty acids Glucose Lipids Oxidative stress Inflammation Insulin resistance Adapted from Wellen KE, Hotamisligil GS. J Clin Invest. 2005;115:

29 Fat Cell Products and Hypertension Visceral Fat Stores Portal FFA Hepatic Insulin Clearance Plasma Insulin Vascular Constriction Renal Na + Reabsorption Angiotensinogen Angiotensin II Angiotensin I Hypertension Bray GA. Contemp Diagn Obes

30 Medical Complications of Obesity: Almost every organ system is affected Pulmonary disease abnormal function obstructive sleep apnea hypoventilation syndrome Nonalcoholic fatty liver disease steatosis steatohepatitis cirrhosis Gall bladder disease Gynecologic abnormalities abnormal menses infertility polycystic ovarian syndrome Osteoarthritis Skin Gout Idiopathic intracranial hypertension Stroke Cataracts Coronary heart disease Diabetes Dyslipidemia Hypertension Severe pancreatitis Cancer breast, uterus, cervix colon, esophagus, pancreas kidney, prostate Phlebitis venous stasis

31 Obesity Prevention and Management

32 Therapy of weight loss: 1. Non pharamcological 2. Pharmacological

33 Non pharmacological therapy of Weight loss Diet Exercise i.e. Life style modifications

34 Food Guide Pyramid

35 Health Benefits of Weight Loss Decreased risk for cardiovascular disease. Decrease glucose and insulin levels. Decreased blood pressure. Decreased LDL and triglycerides Increased HDL. Decrease in severity of sleep apnea. Reduced symptoms of degenerative joint disease.

36 Treatment of Obesity Goal of treatment: 10% weight loss Caloric restriction: -500 kcal/day Moderate physical activity 30 minutes daily Behavioral modification Drug therapy National Institutes of Health. Obes Res. 1998; 6 (suppl 2): 51S 209S.

37 Impact of Weight Loss on Risk Factors HbA1c Blood Pressure Total Cholesterol HDL Cholesterol Triglycerides ~5% Weight Loss %-10% Weight Loss Wing RR et al. Arch Intern Med. 1987;147: Mertens IL, Van Gaal LF. Obes Res. 2000;8: Blackburn G. Obes Res. 1995;3 (Suppl 2):211S-216S. 4. Ditschunheit HH et al. Eur J Clin Nutr. 2002;56:

38 Pharmacological therapy of obesity

39 A Guide to Selecting Treatment BMI Category Treatment < >40 Diet, exercise, With co- With co behavior therapy morbidities morbidities Pharmacotherapy With co morbidities Surgery With co- + morbidities Source: The Practical Guide to the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults.

40 Obesity Pharmacotherapy System Digestive Approved for Long-Term Use Mechanism Inhibition of lipase Examples Orlistat(Xenical) CNS Inhibit norepinephrine, Sibutramine(Meridia) serotonin and dopamine reuptake CNS Approved for short-term term use Norepinephrine release Phentermine, others

41 absorption of fat Xenical Chitosan absorption of CHO Acarbose Gymenemic acid Anorexic drugs Sibutramine energy expenditure by Sibutramine gastric emptying by Acarbose

42 Conclusion Overweight and obese individuals are more likely to develop type 2 diabetes than their normal-weight counterparts. In addition, the incidence of insulin resistance, hyperinsulinemia, and the insulin resistance syndrome is greater as BMI increases.

43 This is the at risk patient I m talking about

44 Chronic kidney disease

45 Metabolic syndrome as predictor of CVD MS increases risk of CHD MS predicts 25% of all new-onset CVD 10-year risk of MS in men is between 10-20% Women with MS <10% of CVD risk No advantage above Framingham risk factors

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47 Approaches to the Treatment of the Metabolic Syndrome Behavioral Weight loss Increased physical activity Pharmacological (treat underlying conditions) Lipid disorders Hypertension Diabetes Should treatment of these underlying disorders be intensified because the subject has the metabolic syndrome? Should underlying insulin resistance be treated in nondiabetic subjects? No clinical trial data to date support the use of pharmacological agents to improve insulin sensitivity in nondiabetic subjects, although this is an area of active interest

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51 It s everywhere Some 56 percent of South African women are now either obese or overweight, compared to fewer than 10 percent who are underweight. More than 17 percent of adolescents here are overweight for teenage girls, it's 25 percent, according to the Medical Research Council. According to the same report only 2% of South Africans are diabetic. Why? World Total Cost of diabetes: $153,000,412-$286,844,446 World Total Cost of diabetes: $153,000,412-$286,844,446 depending on the degree of optimism