Tobacco and Metabolic Disorders

1. TOBACCO AND OTHER METABOLIC DISORDERS Mini-Lecture 2 Module: Tobacco and Endocrine Problems

2. Objectives of the Mini Lecture Goal of Mini-Lecture: Provide students with knowledge of how tobacco affects metabolic disorders other than diabetes Learning Objectives: Student will be able to: • Discuss the association between tobacco use and obesity and dyslipidemia. • Advise smoking cessation for patients and populations with other CVD risk factors, i.e. obesity and dyslipidemia.

3. Contents Core Slides: Optional Slides: Smoking, Weight Gain, and Women Lipid Profile Changes: Pathways Role of Plasma FFAs Smoking and LDL Oxidation Smoking and Free Radicals • Smoking and Metabolic Disorders • Smoking and Insulin Resistance • Body Fat Distribution in Smoking • Smoking and Changes in Lipid Profile • Smoking and HDL • Centripetal Adiposity • Smoking and Obesity: Mortality • Smoking Cessation and Weight Gain • What Should Doctors Do?

4. CORE SLIDES TOBACCO AND ENDOCRINE PROBLEMS Mini-Lecture 2 Module: Tobacco and Endocrine Problems

5. Smoking and Metabolic Disorders • Metabolic syndrome is more prevalent in active smokers than in those who are exposed to secondhand smoke or those who have no exposure.1 • Smoking cessation should be advised to all patients who smoke who have metabolic disorders and/or dyslipidemia.2 1. Chiolero et al. 2008; 2. Erhardt 2009

6. Smoking and Insulin Resistance • Smoking has direct and indirect effects on increasing insulin resistance. • Smoking can lead to accumulation of visceral fat, which increases insulin resistance. • Most smokers exhibit insulin resistance syndromes.1 • Cigarette smoking leads to reduced insulin sensitivity, decreased glucose utilization, and reduction in insulin receptor affinity.2 1. Chiolero et al., 2008; 2. Berlin 2008

7. Body Fat Distribution in Smokers1 • Decreased body mass index, increased waist circumference, and decreased hip circumference. • Increased metabolic rate (i.e. increased energy expenditure and decreased metabolic efficiency). • Acute anorexic effect → decreased caloric absorption. 1. Chiolero et al. 2008

8. Smoking and Changesin Lipid Profile • Increased total plasma cholesterol, increased plasma triglycerides and decreased HDL cholesterol → leads to development of plaque • Smoking also increased lipid peroxidation → increased levels of OxLDL-C (oxidized LDL-C) http://z.about.com/f/p/440/graphics/images/en/19289.jpg 1. Berlin 2008; 2. Erhardt 2009

9. Smoking and HDL • Plasma HDL levels reduced in adults, adolescents, and children1,2 • HDL protein structure modified by cross-linking apo A1 and A21 • Interrupts reverse cholesterol transport pathway • Impairs HDL mediated movement of cholesterol across cell membranes http://www.phillips-fit.co.uk/pfiles/images/HDL%20LDL.jpg 1. McCall et al. 1994; 2. Neufeld et al. 1997

10. Centripetal Adiposity • Abdominal fat accumulation1: • High levels of plasma cortisol • Increased testosterone concentration • Increased accumulation of adipose tissue in abdomen compared to femoral-gluteal area2 http://musicforchange.com/cms/images/rapid_weight_loss.jpg 1. Chiolero et al. 2008; 2. Troisi et al. 1991

11. Smoking and Obesity: Mortality • Compared to normal weight never smokers, obese current smokers have1: • 3.5 to 5 times higher risk of all-cause mortality • 6 to 11 times higher risk of cardiovascular mortality (among those less than 65 years old) • The associated risk of cardiovascular mortality among former smokers is significantly lower (about 4 times). 1. Freedman et al. 2006

12. Smoking Cessationand Weight Gain • Smoking cessation results in weight gain but less upper-body fat deposition1,2 • Upper body fat distribution in women puts them at higher risk for CAD, stroke, diabetes and unfavorable lipid profiles than generalized obesity1 • No evidence of large or steady weight gain2 http://conservativehome.blogs.com/torydiary/images/2007/10/18/barrie_free2bme.gif 1. Lissner et al. 1992; 2. Gruber et al. 2006

13. What Should a Doctor Do? • Explain that smoking worsens lipid profile and increased risk of cardiovascular/ atherosclerotic diseases • Any patient with unfavorable lipids or centripetal obesity: advise to quit smoking http://media.counton2.com/wcbd/gfx.php?max_width=300andimgfile=images/uploads/MEDICAL_SIGN_ON_BACKGROUND.JPG

14. OPTIONAL SLIDES TOBACCO AND ENDOCRINE PROBLEMS Mini-Lecture 2 Module: Tobacco and Endocrine Problems

15. Smoking, Weight Gain, and Women Studies in high-income countries found that : • Women viewed smoking as a weight control tool (39%)1 • Women smokers made fewer attempts to quit smoking when compared to men due to fear of ensuing weight gain2 • Weight gain and increased appetite: reasons for relapse1 http://obesitynews.com.au/wp-content/uploads/2009/05/fat-smoker-drinker-300x292.jpg 1. Lissner et al. 1992; 2. Gruber et al. 2006

16. Lipid Profile Changes: Pathways • Inhibits lecithin cholesterol acyl transferase (LCAT) activity1 • Increases levels of cholesteryl ester transfer protein (CETP) activity2 • Smoking releases catecholamines: increasesplasma free fatty acids (FFA)3 • Inhibits and decreases serum paraoxonase activity: increases LDL oxidation by arterial wall myeloperoxidases and lipoxygenases3 http://www.theheart.org/displayItem.do?primaryKey=113939andtype=img 1. McCall et al. 1994; 2. Dullaart et al. 1994; 3. Tsiara et al. 2003

17. Role of Plasma FFAs1 • Smoking releases catecholamines  increases plasma free fatty acid (FFA) concentration • Stimulates myocardial oxygen consumption • Decreases PGI2 synthesis and bioavailability  enhances atherogenesis • Increases arterial blood pressure • Adversely affects endothelial structure • Adversely affects endogenous, endothelium dependent, platelet inhibitor system – adenosine diphosphatase (ADPase) 1. Tsiara et al. 2003

18. Smoking and LDL Oxidation • Cigarette smoke exposure produces oxidized low-density lipoprotein (oxLDL)  accumulation of cholesteryl esters in macrophages1 • Cigarette smoke inhibits and decreases serum paraoxonase activity  diminishes its capacity to protect LDL from oxidation2 • Stimulates arterial wall monocyte infiltration, adhesion, and migration into the sub-intimal space and smooth muscle cell proliferation2  induces foam cell formation and atherosclerosis1 • Induces apoptosis of the endothelial cells and atherosclerotic plaque erosion2 • Increases levels of TNF-α and C-Reactive Protein2 • Smoking cessation reduces the susceptibility of LDL to oxidation2 1. Craig et al. 1990; 2. Tsiara et al. 2003

19. Smoking and Free Radicals1 • Smoking induces free radical generation • Free radicals enhance atherogenic effect of lipid peroxidation  induces endothelial dysfunction and increases incidence of vascular events • Antioxidants – vitamin C and α-tocopherol: provide protection against LDL oxidation • Smoking associated with low dietary vitamin intake, altered metabolism, and decreased serum concentrations of antioxidant vitamins • Smokers of both genders  lower serum vitamin C and β-carotene 1. Tsiara et al. 2003

20. The most important health message a doctor can give to patients is to quit smoking.