1. Dietary Approach to Control Cardiometabolic Syndrome
Dr Sultan Mahmood
Consultant Food Ecologist
First DietCare & Research Center
Lahore
At Faiz Ghar on 15 August, 2011

2. Clustering of Components:
Hypertension: BP. > 140/90
Dyslipidemia: TG > 150 mg/ dL ( 1.7 mmol/L )
HDL- C < 35 mg/ dL (0.9 mmol/L)
Obesity (central): BMI > 30 kg/M2
Waist girth > 94 cm (37 inch)
Waist/Hip ratio > 0.9
Impaired Glucose Handling: IR , IGT or DM
FPG > 110 mg/dL (6.1mmol/L)
2hr.PG >200 mg/dL(11.1mmol/L)
Microalbuninuria (WHO)

3. Global cardiometabolic risk*
We have understood for decades the roles of ‘classical’ risk factors – elevated LDL-cholesterol, hypertension, elevated blood glucose and smoking – in the pathogenesis of cardiovascular disease. More recent research is continuing to define the contribution of emerging risk factors to the risk of developing type 2 diabetes and cardiovascular disease, particularly in the setting of insulin resistance. Abdominal obesity is associated with multiple cardiometabolic risk factors such as atherogenic elevated blood glucose (hypertriglyceridaemia and low HDL-cholesterol), elevated blood glucose and inflammation, which are major drivers of cardiovascular disease and type 2 diabetes. In addition, atherosclerosis is increasingly regarded as an inflammatory condition.
Gelfand EV et al, 2006; Vasudevan AR et al, 2005
* working definition
Gelfand EV et al. Rimonabant: a cannabinoid receptor type 1 blocker for management of multiple cardiometabolic risk factors. J Am Coll Cardiol 2006:47(10):1919–26.
Vasudevan AR, Ballantyne C et al, Cardiometabolic risk assessment: an approach to the prevention of cardiovascular disease and diabetes mellitus. Clin Cornerstone 2005; 7(2-3):7–16.

4. International Diabetes Federation (IDF) Consensus Definition 2005
The new IDF definition focusses on abdominal obesity rather than insulin resistance

5. Central Obesity
IDF:
Central obesity - waist circumference >94 cm for Europid men, >80 Europid women with ethnicity specific values for other groups
WHO:
Waist-hip ratio >0.9 - men or > women
ATP III:
Waist circumference >40 in. - men,
> 35 in. - women
Waist-hip measurement not likely to be done by busy clinicians.
40 in. = cm
35 cm = 88.9 cm

6. Fat Topography In Type 2 Diabetic Subjects
FFA*
TNF-alpha*
Leptin*
IL-6 (CRP)*
Tissue Factor*
PAI-1*
Angiotensinogen*
Intramuscular
Subcutaneous
Intrahepatic
Intra-
abdominal

7. Targeting
Cardiometabolic Risk

8. Intra-abdominal adiposity is a major contributor to increased cardiometabolic risk
IAA = high risk fat
Associated with
inflammatory markers
(C-reactive protein) 
Dyslipidaemia
Increased
cardiometabolic
risk
Free fatty
acids 
Insulin
resistance
This slide summarises the relationships between intra-abdominal adiposity (IAA) and increased cardiometabolic risk. Intra-abdominal adiposity drives the progression of multiple risk factors directly, through the secretion of excess free fatty acids and inflammatory adipokines, and decreased secretion of adiponectin. The important contributions of IAA to dyslipidaemia and insulin resistance provide an indirect, though clinically important, link to the genesis and progression of atherosclerosis and cardiovascular disease.
The location of excess IAA is an important determinant of cardiometabolic risk. IAA is associated with insulin resistance, hyperglycaemia, dyslipidaemia, hypertension, and prothrombotic/proinflammatory states. Excess IAA typically is accompanied by elevated levels of C-reactive protein (CRP) and free fatty acids (FFAs), as well as decreased levels of adiponectin. Elevated CRP is an indicator of inflammation. Abdominal obesity has been shown to be associated with the inflammation cascade, with adipose tissue expressing a number of inflammatory cytokines. Inflammation is now believed to play a role in the development of atherosclerosis and type 2 diabetes. Elevated levels of CRP are considered to be predictive of cardiovascular disease and insulin resistance.
Elevated FFA levels appear to play a significant role in the cause of insulin resistance. It has been suggested that elevated FFAs and intracellular lipids inhibit the insulin signaling mechanism, leading to decreased glucose transport to muscle. FFAs also play a mediating role between insulin resistance and β-cell dysfunction, indicating that a reduction in FFA level could be a desirable therapeutic target.
Adiponectin is an adipose tissue-specific circulating protein which is involved in the regulation of lipid and glucose metabolism. Adiponectin has been shown to be reduced in adults with obesity and type 2 diabetes. In non-diabetics, hypertriglyceridaemia and low HDL-cholesterol have been shown to be associated with low plasma adiponectin concentrations.
All of these components help to explain why excess abdominal adiposity is considered to be a great threat to cardiovascular and metabolic health.
Secretion of
adipokines
(↓ adiponectin) 
Inflammation
IAA: intra-abdominal adiposity
Kershaw EE et al, 2004; Lee YH et al, 2005; Boden G et al, 2002
Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004;89:2548–2556.
Lee YH, Pratley RE. The evolving role of inflammation in obesity and the metabolic syndrome. Curr Diab Rep 2005;5:70–75.
Boden G, Shulman GI. Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta-cell dysfunction. Eur J Clin Invest 2002;32:14–23.

9. Waist Circumference

10. Insulin Resistance: Associated Conditions
In addition to type 2 diabetes, insulin resistance is associated with the development of a broad spectrum of clinical conditions. These include hypertension, atherosclerosis, dyslipidemia, decreased fibrinolytic activity, impaired glucose tolerance, acanthosis nigricans, hyperuricemia, polycystic ovary disease, and obesity.
Adapted from Consensus Development Conference of the
American Diabetes Association. Diabetes Care. 1998;21:

11. Targeting Cardiometaboilc Risk Defining cardiometabolic Risk
Cardiovascular Disease
Abdominal Obesity Glucose intolerance
Insulin Resistance
Dyslipedemia Hypertension

12. Targeting Cardiometaboilc Risk Defining cardiometabolic Risk
Major Unmet Clinical Need
Classical Risk Factors
Novel Risk Factors
Cluster Risk Factors
LDL-C BP Smoking DM Insulin HDL-C TNF & IL-6
Abdominal Obesity
Glucose PAI TG
Cardiovascular Disease

13. Resulting Clinical Conditions:
Type 2 diabetes
Essential hypertension
Polycystic ovary syndrome (PCOS)
Nonalcoholic fatty liver disease
Sleep apnea
Cardiovascular Disease (MI, PVD, Stroke)
Cancer (Breast, Prostate, Colorectal, Liver)

14. Multiple Risk Factor Management
Obesity
Glucose Intolerance
Insulin Resistance
Lipid Disorders
Hypertension
Goals: Minimize Risk of Type 2 Diabetes and Cardiovascular Disease

15. Glucose Abnormalities:
IDF:
FPG >100 mg/dL (5.6 mmol. L) or previously diagnosed type 2 diabetes
(ADA: FBS >100 mg/dL [ 5.6 mmol/L ])

16. Hypertension:
IDF:
BP >130/85 or on Rx for previously diagnosed hypertension

17. Dyslipidemia: IDF: Triglycerides - >150mg/dL (1.7 mmol /L)
HDL - <40 mg/dL (men), <50 mg/dL (women)

18. Insulin Resistance:
Hyperinsulinemic individuals are at risk for developing Diabetes, Dyslipidemia, Hypertension & ultimately Cardiovascular disease
Patients with Metabolic Syndrome are 3.5 times as likely to die from Cardiovascular disease compared to normal people

19. Public Health Approach
Public education is key!
Recognizing risk factors and dealing with them is important,
Recognizing clusters of risk factors is important, i.e, when some of the factors are recognized others should be investigated.
Using the correct drugs to treat the various risk factors is important.
ACEI or ARB
TZD’s or Glitazars
Metformin
Statins with or without fibric acid derivatives
Treating to goal.
Smoking cessation.

20. Screening/Public Health Approach
Public Education
Screening for at risk individuals:
Blood Sugar/ HbA1c
Lipids
Blood pressure
Tobacco use
Body habitus
Family history
Public education is key!
Recognizing risk factors and dealing with them is important,
Recognizing clusters of risk factors is important, i.e, when some of the factors are recognized others should be investigated.
Using the correct drugs to treat the various risk factors is important.
ACEI or ARB
TZD’s or Glitazars
Metformin
Statins with or without fibric acid derivatives
Treating to goal.
Smoking cessation.

21. Life-Style Modification: Is it Important?
Exercise
Improves CV fitness, weight control, sensitivity to insulin, reduces incidence of diabetes
Weight loss
Improves lipids, insulin sensitivity, BP levels, reduces incidence of diabetes
Goals:
Brisk walking min./day
10% reduction in body wt.
Finnish Diaabetes Prevention Study - 30 min. walking/day
DPP - Life-style modification 58% effective in preventing diabetes vs 31% for metformin.
Weight loss is difficult to achieve and maintain.
Can be done.
New medications are being developed to assist with this.
Life-style modification programs do not necessarily require professional health care providers to be successful.
Smoking cessation is KEY. Can be more successful with use of counselling, and pharmacologic support - Transdermal nicotine, bupropion or nortriptyline.

22. Smoking Cessation / Avoidance:
A risk factor for development in children and adults
Both passive and active exposure harmful
A major risk factor for:
insulin resistance and metabolic syndrome
macrovascular disease (PVD, MI, Stroke)
microvascular complications of diabetes
pulmonary disease, etc.

23. Diabetes Control - How Important?
Goals:
FBS - premeal <110,
postmeal <180.
HbA1c <7%
For every 1% rise in Hb A1c there is an 18% rise in risk of cardiovascular events & a 28% increase in peripheral arterial disease
Evidence is accumulating to show that tight blood sugar control in both Type 1 and Type 2 diabetes reduces risk of CVD

24. Lifestyle modification
If a 1% reduction in HbA1c is achieved, you could expect a reduction in risk of:
21% for any diabetes-related endpoint
37% for microvascular complications
14% for myocardial infarction
Diet
Exercise
Weight loss
Smoking cessation
Type 2 diabetes is a progressive disease and lifestyle adjustments alone are rarely sufficient in the long term – almost all patients will eventually require drug treatment to control their glucose levels.1
References
1. Turner RC et al. JAMA 1999; 281: 2005–2012.
However, compliance is poor and most patients will require oral pharmacotherapy within a few years of diagnosis
Stratton IM et al. BMJ 2000; 321: 405–412. 24

25. Insulin Insulin Analogues: Lyspro /Aspart /glulysine used with meals
Glargine & Livemer as basal insulin
Continuous Subcutaneous Insulin Infusion (CSII)
NPH/Regular, NPH/logs - Mixed or in fixed combinations (70/30, 75/25, 50/50)
Insulin combined with oral agents
Short-acting analogs: Onset - 15 min. Peak hrs. Duration: 4-6 hrs.
Reg.: Onset min. Peak:2-4 hrs. Duration: 6-8 hrs.
Glargine: Onset hrs. Peak: flat. Duration: 24 hrs R
Insulin analogues offer a much more physiologic insulin profile than do older insulin preparations and allow development of a treatment strategy that gives patients much more dietary freedom using a basal-bolus insulin with carbohydrate counting.
CSII provides the ultimate in physiologic insulin delivery and will soon be linked to a continuous glucose monitoring technology that brings insulin treatment closer to the dream of a closed loop system or “artificial pancreas”.

26. BP Control - How Important?
Goal: BP.<130/80
MRFIT and Framingham Heart Studies:
Conclusively proved the increased risk of CVD with long-term sustained hypertension
Demonstrated a 10 year risk of cardiovascular disease in treated patients vs non-treated patients to be 0.40.
40% reduction in stroke with control of HTN
Precedes literature on Metabolic Syndrome

27. Lipid Control - How Important?
Goals: HDL >40 mg% (>1.1 mmol /l)
LDL <100 mg/dL (<3.0 mmol /l)
TG <150 mg% (<1.7 mmol /l)
Multiple major studies show % reductions in cardiovascular disease risk with use of statins and fibrates in the control of hyperlipidemia.

30. Thank You

32. Determinants and dynamics of the CVD Epidemic in the developing Countries
Data from South Asian Immigrant studies
Excess, early, and extensive CHD in persons of South Asian origin
The excess mortality has not been fully explained by the major conventional risk factors.
Diabetes mellitus and impaired glucose tolerance highly prevalent. (Reddy KS, circ 1998).
Central obesity, ↑triglycerides, ↓HDL with or without glucose intolerance, characterize a phenotype.
genetic factors predispose to ↑lipoprotein(a) levels, the central obesity/glucose intolerance/dyslipidemia complex collectively labeled as the “metabolic syndrome”
Several studies around the world have consistently revealed excess, early, and extensive CHD in persons of South Asian origin. The excess mortality has not been fully explained by the major conventional risk factors in cross-sectional comparisons with other population groups. Diabetes mellitus and impaired glucose tolerance are, however, highly prevalent in South Asian migrants. Central obesity, high levels of triglycerides, and low levels of HDL cholesterol, with or without glucose intolerance, seem to characterize a phenotype frequently noted among South Asian migrants.
Thus, South Asians in urban and migrant environments may be at a higher risk of CHD due to the confluence of (1) genetic factors that predispose to higher lipoprotein(a) levels, the central obesity/glucose intolerance/dyslipidemia complex collectively labeled as the "metabolic syndrome," and a possible "thrifty gene" effect with (2) environmental influences that lead to weight gain, rise in plasma cholesterol and blood pressure levels, and, as yet inadequately studied, probable psychosocial risk factors.

33. Determinants and dynamics of the CVD epidemic in the developing countries
Other Possible factors
Relationship between early life characteristics and susceptibility to NCD in adult hood ( Barker’s hypothesis) (Baker DJP,BMJ,1993)
Low birth weight associated with increased CVD
Poor infant growth and CVD relation
Genetic–environment interactions
(Enas EA, Clin. Cardiol. 1995; 18: 131–5)
Amplification of expression of risk to some environmental changes esp. South Asian population)
Thrifty gene (e.g. in South Asians)
There are also possible adverse effects of poor childhood nutrition14 that, if conclusively proven, would have an enormous impact on the developing countries, which still have a substantial fraction of the population that was underweight at birth.
Ref: Barker DJP, Martyn CN, Osmond C, et al. Growth in utero and serum cholesterol concentrations in adult life. Br. Med J. 1993; 307: 1524–7
The possibility of such programming, or as yet unascertained genetic factors, may underlie the enhanced susceptibility of some ethnic groups (e.g. South Asian migrants) to CHD15. This excess risk may be explained by gene–environment interactions or fetal programming in these groups, but public health action must focus on the environmental changes that trigger the expression of susceptibility
Ref: Enas EA, Mehta J. Malignant coronary artery disease in young Asian Indians. Thoughts on pathogenesis, prevention and therapy. Clin. Cardiol. 1995; 18: 131–5.
Such genetic environmental interactions may need to be clarified in the varied ethnocultural populations of the developing countries so that the relevant environmental interventions could be preferentially promoted for CVD prevention.

34. CVD epidemic in developing & developed countries. Are they same?
Urban populations have higher levels of CVD risk factors related to diet and physical activity (overweight, hypertension, dyslipidaemia and diabetes)
Tobacco consumption is more widely prevalent in rural population
The social gradient will reverse as the epidemics mature.
The poor will become progressively vulnerable to the ravages of these diseases and will have little access to the expensive and technology-curative care.
The scarce societal resources to the treatment of these disorders dangerously depletes the resources available for the ‘unfinished agenda’ of infectious and nutritional disorders that almost exclusively afflict the poor
At present, urban populations in most developing countries have higher levels of cardiovascular risk factors that are related to diet and physical activity (overweight, hypertension, dyslipidaemia and diabetes), while tobacco consumption is more widely prevalent in rural populations27,28. This suggests that tobacco consumption is influenced more by education and is the earliest risk factor to demonstrate a reversal of the social gradient. The other risk factors are influenced by more complex social interactions affecting diet and exercise and their social gradients reverse relatively slowly.
The economic and social consequences of the CVD epidemics in the developing countries will be devastating. The social gradient will reverse as the epidemics mature, as has happened in other nations that have experienced their fury in full form. Even at present, several of the risk factors of chronic diseases are showing a reversal of the social gradient in many developing countries4. The poor will become progressively vulnerable to the ravages of these diseases and will have little access to the expensive and technology-intensive management that clinical care demands. Also, the diversion of scarce societal resources to the treatment of these disorders dangerously depletes the resources available for the ‘unfinished agenda’ of infectious and nutritional disorders that almost exclusively afflict the poor

35. Why people physically inactive?
Lack of awareness regarding the of physical activity for health fitness and prevention of diseases
Social values and traditions regarding physical exercise (women, restriction).
Non-availability public places suitable for physical activity (walking and cycling path, gymnasium).
Modernization of life that reduce physical activity (sedentary life, TV, Computers, tel, cars).

36. Prevention of CVD
There is an urgent need to establish appropriate research studies, increase awareness of the CVD burden, and develop preventive strategies.
Prevention and treatment strategies that have been proven to be effective in developed countries should be adapted for developing countries.
Prevention is the best option as an approach to reduce CVD burden.
Do we know enough to prevent this CVD Epidemic in the first place.
Validated nationally representative estimates of cause specific mortality are not available for any country in South Asia
Therefore, there is an urgent need to establish appropriate research studies, increase awareness of the CVD burden, and develop preventive strategies in developing countries. In the meantime, as it is likely that most risk factors will be of some importance in all ethnic populations in the world, prevention and treatment strategies that have been proven to be effective in developed countries should be adapted for developing countriesb
Establishment of surveillance systems for noncommunicable diseases and their risk factors is essential for developing prevention strategies and monitoring the impact of control programmes. Pilot programmes are now under way in some of the countries to establish and evaluate such systems.

37. Recommendations for treatment
Primary management for the Metabolic Syndrome is healthy lifestyle promotion. This includes:
moderate calorie restriction (to achieve a 5-10% loss of body weight in the first year)
moderate increases in physical activity
change dietary composition to reduce saturated fat and total intake, increase fibre and, if appropriate, reduce salt intake.

38. Management of the Metabolic Syndrome
Appropriate & aggressive therapy is essential for reducing patient risk of cardiovascular disease
Lifestyle measures should be the first action
Pharmacotherapy should have beneficial effects on
Glucose intolerance/diabetes
Obesity
Hypertension
Dyslipidaemia
Ideally, treatment should address all of the components of the syndrome and not the individual components

39. 11 Questions About Metabolic Syndrome
Metabolic syndrome is a group of risk factors -- unhealthy cholesterol levels, high blood pressure, high blood sugar, and excess belly fat -- that may raise your risks of serious illness, such as diabetes, and blood vessel and heart disease.
If you've been diagnosed with metabolic syndrome -- or are worried you might have it -- here are some questions to ask your doctor. Print them out before your next appointment.
Do I have any metabolic syndrome risk factors?
Will I need medicine to control them? If so, how will the medicine help? What are the side effects?
Do I need to have blood tests to see if I have a higher risk of blood clots and inflammation?
What is my BMI (body mass index)?
Should I lose weight? What's a reasonable weight goal for me?
What changes should I make to my diet? Do I need to take any special precautions?
Should I consider seeing a nutritionist to talk about improving my diet?
Do you have suggestions for how I could get more physical activity?
Could any medicines I'm taking be affecting my metabolic syndrome risk factors?
How might my family history affect my risk of getting metabolic syndrome and having cardiovascular problems?
Should I be taking aspirin therapy?
Remember that when you meet with your doctor, tell him or her about all of the medicines, herbs, and supplements you use. "Natural" medicines can be powerful, and they can interfere with the effectiveness of other drugs.
You could also keep a food diary for about a week before your next appointment. Just jot down the foods you eat each day. Then, you and your doctor can go over it together and talk about ways of improving your eating habits.