NTR 644- Advanced Metabolism: Carbohydrates and Lipids - Metabolic Syndrome Case Study

Presented By: Emily Apitz, Erin Burke, Therese Hrncirik, Nicole Rieman

Outline

• Introduction of metabolic syndrome• Case presentation of Bill• Literature review and metabolic concerns• Disease pathophysiology and biochemistry• Carbohydrate metabolism• Lipid metabolism• Nutrition recommendations

Introduction: MetS

• Metabolic Syndrome (MetS) is a cluster of conditions that occur together increasing the risk of heart disease, stroke, and diabetes – Hypertension– Hyperglycemia– Visceral adiposity – Dyslipidemia

Bello-Rodrieguez BM, 2013; Ross AC, 2014 ; Lakka H, 2002.

Underlying Risk Factors of MetS• Causes

o Obesity and physical inactivityo Insulin resistanceo Ageo Raceo Gendero Gestational Diabetes

Kaur J, 2014; Bello-Rodrieguez BM, 2013; Valizadeh M, 2015; Nsiah K, 2015; Regitz-Zagrosek V, 2006, Deboer M, 2011) Medscape.org/viewarticle/558472

Symptoms

• Similar to Diabetes– Increased thirst– Increased urination– Fatigue– Blurred vision

Clark N, 2007

Case Study: Bill S.

Image retrieved from http://www.dynamicchiropractic.com/content/images/metabolic_syndrome__1_1_2019.jpg. Accessed July 7, 2015.

Bill S: Diagnostic Laboratory and Anthropometric Presentation

1. Jialal I. ACJP, 20092. Rosendorff et al. Journal of the American Society of Hypertension, 2015. 3. Ross AC, Modern Nutrition in Health and Disease, 2014.

Image available at http://www.nhlbi.nih.gov/health-pro/guidelines/current/obesity-guidelines/e_textbook/txgd/4142.htm. Accessed August 4, 2015

Bill’s Metabolic Concerns

Image retrieved from http://atvb.ahajournals.org/content/32/9/2052/F1.large.jpg. Accessed July 6, 2015.

Bill’s Main Metabolic and Nutritional Issues

Image retrieved from http://www.microbiota-therapeutics.umn.edu/assets/img/metabolic-syndrome.png. Accessed July 6, 2015.

Literature Review to Support Metabolic Syndrome Case Recommendations

Article Subjects Study Design Results ConclusionSuliga E, Koziel D, Ciesla

E, Gluszek S.12,479 men and women

ages 37-66 with a normal BMI (18.5-25 kg/m2)

Cross-Sectional Study Those who ate the healthiest diet had the lowest odds ratio for

metabolic obesity and HDL levels

A diet that consists of fish and whole grains in

addition to a low intake of refined grains, sugar,

sweets, and cold meat is connected to lower levels of metabolic syndrome.

Von Bibra H, Wulf G, St John Sutton M,Pfutzner,

Schuster T, Heilmeyer P.2

32 overweight men and women between the ages

of 30-70 with type 2 diabetes

Prospective, controlled, matched pair parallel arm with a cross-over study for

comparison of 2 diets

Both those who followed the LC and the LF diets experienced significant reductions in weight,

HgA1C and cholesterol. The LC diet resulted in

improved insulin resistance, fasting and postmeal triglycerides, blood pressure, and

cardiac function. Proinsulin remained intact

with the LF diet.

LC but not LF diets can improve cardiac function

in overweight type 2 diabetic patients and

improve insulin resistance. This may

prevent or delay a future diagnosis of metabolic

syndrome and the onset of diabetic

cardiomyopathy.

Ionela & Georgescu3 12 Men and 18 women ages 30-60

Retrospective 10 month Correlation Study

Reverse correlation between healthy lifestyle

and MetS

Most valuable treatment for MetS focuses on sustained behavior

change and increased physical activity

Literature Review: Metabolic Needs to Manage Case

• General Dietary Recommendations– 1600-1800 kcal intake per day– 55% carbohydrates of mixed glycemic index– 20% low-fat protein– 25% fat

• 10-15% of which is mono-unsaturated fat

Von Bibra, IJC Metabolic & Endocrine, 2014

Literature Review:Exercise Needs to Manage Case

• Exercise at a low to moderate intensity daily in order to burn at least 200-400 kcal per day

Dragusha, Bosn J Basic Med Sci, 2010.

Image retrieved from https://cdn.psychologytoday.com/sites/default/files/styles/article-inline-half/public/blogs/102616/2014/08/157864-161988.jpg?itok=3xnP0lj0. Accessed July 6, 2015.

Working Diagnosis: Metabolic Syndrome

Management of the Case• Low-carbohydrate/high protein diet• Increased exercise• Medication management if needed

Von Bibra et al. IJC Met & End. 2014; Iolena et al. Procedia Soc & Bev Sci. 2013; Dragusha et al. J Basic Med Sci. 2010

Biochemical Pathophysiology: Insulin Resistance

• Decreased GLUT4 activity in muscles• Causes excess secretion of insulin from

pancreatic beta cells• Can lead to many metabolic dysregulations.

– Inhibits lipolysis in adipose– Prevents glucose production in liver– Stimulates glucose disposal in muscle

• IR leads to increased risk of developing DM

Petersen KF, Am J Med, 2006; Ross AC, 2014.

Pathophysiology of Insulin Resistance

Eckels et al. Lancet. 2005

Molecular Mechanisms of Insulin Signalling

Copyright © American Heart Association, Inc. All rights reserved.

Rask-Madsen et al. Arterioscler Thromb Vasc Biol. 2012

Biochemical Pathophysiology: Obesity

• Results from increased energy consumption, lack of exercise, and neurohormonal dysfunction

• Increased energy consumption alters function of adipocytes

• Fatty acid oxidation begins to decline• Releases large amounts of fatty acids• Decrease in perilipin synthesis• Increase in lipolysis

Lieberman et al. 2009.

http://scientopia.org/

Biochemical Physiology: Obesity - Gut-brain signaling

Neural and endocrine signals from and to the brain and gut affect energy expenditure via the autonomic nervous system and the vagus nerve.Beezhold B. Benedictine University.

Biochemical Pathophysiology: Obesity – Adipocyte Function

Rask-Madsen et al. Arterioscler Thromb Vasc Biol. 2012

Biochemical Pathophysiology:Obesity – Adipocyte Function

Maassen JA, Diabetologia. 2005

Biochemical Pathophysiology: Hypertension

• Non-insulin resistant setting– Insulin is a vasodilator– Secondary effects on sodium reabsorption in

the kidney• Insulin resistant setting

– Vasodilatory effect of insulin can be lost– Secondary renal effect preserved– Fatty acids can cause vasoconstriction

Eckels RH, Lancet. 2010

Biochemical Pathophysiology: Obesity – Fatty Acid Metabolism• Decline in mitochondrial β-oxidation

Benson D, 2015

Biochemical Pathophysiology: Hyperlipidemia

Rask-Madsen et al. Arterioscler Thromb Vasc Biol. 2012

Rask-Madsen et al. Arterioscler Thromb Vasc Biol. 2012

Biochemical Pathophysiology: Hyperglycemia

Carbohydrate Metabolism – Fed State –

Image - Study Blue, 2015.

Carbohydrate Metabolism in the Fed State

GLYCOLYSIS•Upregulated when ATP is low and cells need energy

GLYCOGEN SYNTHESIS•Muscle and liver will store glucose when ATP is high

Both happen in the cytosol and upregulated by insulin

Image-TutorVista, 2015

Carbohydrate Metabolism – Fasted State –

Images-TutorVista, 2015. Biology Stack Exchange, 2015.

Lipid Metabolism

-Fed State-

Lipid Metabolism in Fed State

Chaney S, 2005; Xiao C, 2011

Lipid Metabolism

-Fasted State-

Lipid Metabolism in the Fasted State

Powershow.com; Chaney S, 2005

Fatty Acid Synthesis in MetS

Chaney S, 2005; Wakil S, 2009 [Image]

Nutrition Recommendations

Medical Nutrition Therapy for Bill

• Because Bill says that “diets don’t work and are hard to control,” the RD needs to emphasize that he is not going on a “diet”

• Rather, changing eating habits and making overall lifestyle changes will need to be maintained long term.

• There isn’t a quick fix to resolve/control metabolic syndrome.

Medical Nutrition Therapy for MetS

• The following slides contain information regarding other diet plans that have been studied to help with MetS and/or certain components of the disorder– DASH– Mediterranean– Low Carb

• Physical activity is also mentioned as a lifestyle/behavior change to aid in weight loss

DASH Diet• DASH diet has been shown to

reduce blood pressure2

• Because hypertension is one component of MetS, Hikmat et al studied the DASH diet in subjects with MetS (n=99)3

– Results: the DASH diet lowered BP (-4.9/-1.9) in patients with MetS3

• DASH diet has also been shown to prevent osteoporosis, cancer, heart disease, stroke, and diabetes as well as reducing cardiometabolic risks in DM24

1. Image-Sabitoni, AE, 2014. 2. Chobanian AV, Hypertension, 2003.3. Hikmat F, J Human Hypertension, 2014.4. Azadbakht L, Diabetes Care, 2011.

Mediterranean Diet• Mediterranean diet can “reverse” MetS1

– Of the 3392 participants with MetS at baseline, 958 reversed the condition (28.2%) after 4.8 years

– Participants were able to reduce obesity and lower fasting blood glucose

• Following the Mediterranean diet can also lessen risk of CVD, heart attack, stroke, and pulmonary embolism2

1. Babio N, CMAJ, 2014.2. Hoevenaar-Blom MP, PLoS ONE, 2012.

Low Carbohydrate Diet• Newer research is showing that low carb diets

can prevent CVD (n=148)1

• Comparing a low fat diet (<30% total calories) to a low carb diet (~30% total calories), Bazzano et al found that the low carb diet had greater mean difference in change of the measured variables:– Weight loss (-3.5 kg, p=0.002)– Fat mass (-1.5%, p=0.011)– Ratio of total:HDL (-.44, p=0.002)– Triglycerides (-14.1 mg/dL, p=0.038)– HDL (+7 mg/dL, p<0.001)– CRP (-15.2 nmol/L, p=0.024)

1. Bazzano LA, Ann Intern Med, 2014.

Physical Activity• Research review of 13 investigations and 2 review

articles for consensus of physical activity guidelines1

• Any exercise is better than no exercise but these are the recommendations:– 30 mins/day 5 days/week (helps to increase HDL)– At least moderate intensity aerobic exercise (high intensity is

needed to reduce LDL and TG)– Increased calorie expenditure positively influences LPL

enzyme activity– High weight/low reps weight lifting can be more impactful

compared to low weight/high reps

1. Mann S, Sports Medicine, 2013.

Recommendations for Bill• Based on the research on the previous

slides, overall recommendations for Bill:– Choose healthy fats (MUFAs), not low fat1

– Fruits, vegetables, whole grains, legumes, nuts1,2

– Lower sodium content in food choices1,2 – Reduce overall CHO intake3

– Alcohol consumption in moderation1

– Exercise 30 mins/day, at least 5 days/week and incorporate cardio and weight lifting4

1. Hoevenaar-Blom MP, PLoS ONE, 2012.2. Chobanian AV, Hypertension, 2003.3. Bazzano LA, Ann Intern Med, 20144. Mann S, Sports Medicine, 2013.

Summary

• MetS is a cluster of conditions that when presented together increase the risk of heart disease, stroke, and diabetes

• Bill presents with risk factors for MetS• MNT for Bill includes recommendations for

a low-carbohydrate/high protein diet, low salt intake, and increased exercise.

Reference• Bello-Rodrieguez BM, Sanchez-Cruz G, Delgado-Bustillo F, Asiama G. The relationship between metabolic syndrome and

target organ damage in Ghanaian with stage-2 hypertension. Ghana Medical Journal. 2013, December. 47(4):189-197.• Lakka H, Laaksonen D, Lakka T, et al. The metabolic syndrome and total cardiovascular disease mortality in middle-aged

men. JAMA. 2002;288(21):2709-2716• Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR. Modern Nutrition in Health and Disease, (11th ed). Baltimore,

MD: Lippincott Williams & Wilkins; 2014.• Kaur J. A comprehensive review on metabolic syndrome. Cardiology Research and Practice. 2014; 2014:1-21. Available

from http://www.hindawi.com/journals/crp/2014/943162/cta/. • Deboer M. Ethnicity, obesity and the metabolic syndrome; Implications on assessing risk and targeting intervention. Expert

Rev Endocrinol Metab. 2011; 6(2):279-289.• Valizadeh M, Alavi N, Mazloomzadeh S, et al. The risk factors and incidence of Type 2 Diabetes Mellitus and Metabolic

Syndrome in women with previous Gestational Diabetes. Int J Endocrinol Metab. 2015; 13(2). • Nsiah K, Shang VO, Boateng KA, Mensah FO. Prevalence of metabolic syndrome in type 2 diabetes mellitus patients. Int

J Appl Basic Med Res. 2015; 5:133-138.• Regitz-Zagrosek V, Lehmkuhl E, Weickert MO. Gender differences in the metabolic syndrome and their role for

cardiovascular disease. Clin Res Cardiol. 2006;95:136-147.• Clark N, Fox K, Grandy S, et al. Symptoms of diabetes and their association with the risk and presence of diabetes.

Diabetes Care. 2007; 30(11):2868-2873. • Dynamic Chiropractic. [Image]. Retrieved from

http://www.dynamicchiropractic.com/content/images/metabolic_syndrome__1_1_2019.jpg. Accessed July 7, 2015.• National Heart, Lung, and Blood Institute, Guidelines on Overweight and Obesity: Electronic Textbook. Available at

http://www.nhlbi.nih.gov/health-pro/guidelines/current/obesity-guidelines/e_textbook/txgd/4142.htm. Accessed August 4, 2015.

Reference• Jialal I. The role of the laboratory in metabolic syndrome. ACJP. 2009;132:161-162. • Rosendorff C, Lackland D, Allison M, et al. Treatment of hypertension in patients with coronary artery disease. Journal

of the American Society of Hypertension. 2015; 9(6): 453-498. Available at : http://ajcp.ascpjournals.org/content/132/2/161.full. Accessed July 19, 2015.

• American Heart Association. (n.d). [Image].Retrieved from http://atvb.ahajournals.org/content/32/9/2052/F1.large.jpg. Accessed July 6, 2015

• University of Minnesota. (n.d.). [Image]. retrieved from http://www.microbiota-therapeutics.umn.edu/assets/img/metabolic-syndrome.png. Accessed July 6, 2015.

• Suliga E, Koziel D, Ciesla E, Stanislaw G. Association between dietary patterns and metabolic syndrome in individuals with normal weight: a cross-sectional study. Nutrition Journal, 2015;14(55). Doi 10.1186/s12937-015-0045-9.

• Von Bibra H, Wulf G, St John M, et al. Low-carbohydrate/high protein diet improves diastolic cardiac function and the metabolic syndrome in overweight-obese patients with type 2 diabetes. IJC Metabolic & Endocrine. 2014;11-18.

• Iolena M, Tudor, Luminita, Georgescu. A correlational study of the relationship between lifestyle knowledge and metabolic disorders. Procedia Social and Behavioral Sciences. 2013; 76:842-847.

• Dragusha G, Elezi A, Dragusha S, Gorgani D, Begolli L. Treatment benefits on metabolic syndrome with diet and physical activity. Bosn J Basic Med Sci. 2010;10(2):169-76.

• Petersen KF, Shulman GI. Etiology of insulin resistance. Am J Med. 2006; 119 (5 supp 1): s10-s16.• Eckels RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2005; 365: 1415-1428. • Risk-Madsen C, Kahn CR. Tissue specific insulin signaling, metabolic syndrome and cardiovascular disease.

Arterioscler Thromb Vasc Biol. 2012; 32:2052-2059. • Aydin S, Aksoy A, Aydin S et al. Today’s and yesterday’s of pathophysiology: Biochemistry of metabolic syndrome and

animal models. Nutrition. 2014; 30:1-9.

Reference• Stuart CA, Howell MEA, Cartwright BM, et al. Insulin resistance and muscle insulin receptor substrate-1 serine

hyperphosphorylation. Physiological Reports. 2014;2(12):1-7. • Lieberman M, Marks AD. Basic medical biochemistry: A clinical approach (3rd ed). Philadelphia, PA: Lippincott

Williams & Wilkins; 2009. • Aganovic I, Dusek T. University Hospital Center. Pathogenesis of metabolic syndrome. International Federation of

Clinical Chemistry and Laboratory Medicine. Available at http://www.ifcc.org/ifccfiles/docs/Pathophysiology_of_Metabolic_Syndrome.pdf.

• Beezhold B. Homeostatic regulation [Power Point Lecture]. Benedictine University. Accessed August 5, 2015.• Maassen JA, Romijn JA, Heine RJ. Fatty acid-induced mitochondrial uncoupling in adipocytes as a key protective

factor against insulin resistance and beta cell dysfunction: a new concept in the pathogenesis of obesity-associated type 2 diabetes mellitus. Diabetologia. 2005; 50(10): 2036-2041.

• Eckels RH, Alberti KGMM, Grundy SM, Zimmett PZ. The metabolic syndrome. Lancet. 2010; 375(9710): 181-183. doi:10.1016/S0140-6736(09)61794-3.

• Benson D. Beta-Oxidation. US Davis website. http://chemwiki.ucdavis.edu/Biological_Chemistry/Metabolism/Beta-Oxidation. n.d. Accessed August 6, 2015.

• Study Blue. [image]. Available at: https://www.studyblue.com/notes/note/n/11-carbohydrate-protein-lipid--nucleic-acid-digestion--absorption-/deck/10229632. Accessed August 6, 2015.

• Tutor Vista. 2015. Glycogen. [image]. Available at: http://chemistry.tutorvista.com/organic-chemistry/glycogen.html. Accessed July 30, 2015.

• Biology Stack Exchange. 2015. [image]. Available at: http://biology.stackexchange.com/questions/29979/what-is-the-role-pyruvate-carboxylase-in-lipogenesis. Accessed August 6, 2015.

Reference• Chaney S. Overview of Lipid Metabolism. University of North Caroline School of Medicine. Available at

https://www.med.unc.edu/neurology/files/documents/child-teaching-pdf/OVERVIEW%20OF%20LIPID%20METABOLISM.pdf.

• Xiao C, Hseih J, Adeli K et al. Gut-liver interaction in triglyceride-rich lipoprotein metabolism. Am J Phys. 2011; 301(3):E429-E446.

• PowerShow.com, Fatty Acid Metabolism. [Image]. Power Point-PPT. Available from: http://www.powershow.com/view/3bfad6-ZDE5Z/Fatty_Acid_Metabolism_powerpoint_ppt_presentation. Accessed July 31, 2015.

• Wakil S, Abu-Elheiga L. Fatty acid metabolism: target for metabolic syndrome. J Lipid Res. 2009;50:S138-S143. • Sabitoni AE. 2014. [Image]. Available at: http://www.lhsfna.org/index.cfm/lifelines/march-2014/shake-salt-and-

sodium-out-of-your-diet/. Accessed July 30, 2015.• Chobanian AV et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and

Treatment of High Blood Pressure. Hypertension. 2003; 43: 1206-1252.• Hikmat F and Appel LJ. Effects of the DASH diet on blood pressure in patients with and without metabolic

syndrome: results from the DASH trial. J Human Hypertension. 2014; 28: 170-175.• Azadbakht L et al. Effects of the DASH eating plan on cardiovascular risks among type 2 diabetes patients.

Diabetes Care. 2011; 34: 55-57.• Babio N et al. Mediterranean diets and metabolic syndrome status in the PREDIMED randomized trial. CMAJ.

2014; 186(17): E649-E657.• Hoevenaar-Blom MP et al. Mediterranean style diet and 12-year incidence of cardiovascular diseases: the EPIC-

NL cohort study. PLoS-ONE. 2012; 7(9): e45458.• Bazzano LA et al. Effects of low-carbohydrate and low fat diets. Ann Intern Med. 2014; 161: 309-318.

Reference• Mifflin MD and St Joer ST et al. A new predictive equation for resting energy expenditure in healthy individuals.

Am J Clin Nutr. 1990; 51(2): 241-247.

References• László A, Kalabay L, Nemcsik J. Case report of exercise and statin-fibrate

combination therapy-caused myopathy in a patient with metabolic syndrome: contradictions between the two main therapeutic pathways. BMC Research Notes [serial online]. March 2013;6(1):1-5. Available from: Academic Search Complete, Ipswich, MA. Accessed July 30, 2015.

• National Heart, Lung, and Blood Institute, Calculate Your Body Mass Index. Available at http://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmicalc.htm. Accessed July 27, 2015.

• National Heart, Lung, and Blood Institute, Assessing Your Weight and Health Risk. Available at http://www.nhlbi.nih.gov/health/educational/lose_wt/risk.htm. Accessed July 29, 2015.

• Farinde A, Laboratory Reference Ranges in Healthy Adults. Available at http://emedicine.medscape.com/article/2172316-overview. Accessed July 28, 2015.

• American Heart Association, Target Heart Rates. Available at http://www.heart.org/HEARTORG/GettingHealthy/PhysicalActivity/FitnessBasics/Target-Heart-Rates_UCM_434341_Article.jsp. Accessed July 29, 2015.

References• American Heart Association, What Your Cholesterol Levels Mean. Available at

http://www.heart.org/HEARTORG/Conditions/Cholesterol/AboutCholesterol/What-Your-Cholesterol-Levels-Mean_UCM_305562_Article.jsp. Accessed July 29, 2015.

• Platek SM, Singh D. Optimal Waist-to-Hip Ratios in Women Activate Neural Reward Centers in Men.

• World Health Organization, Waist Circumference and Waist-Hip Ratio: Report of a WHO Expert Consultation. Available at http://whqlibdoc.who.int/publications/2011/9789241501491_eng.pdf. Accessed July 31, 2015.