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Obesity and being overweight

Being overweight and obesity are two conditions registering serious progression among the global population.

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The World Health Organization (WHO) published  recently, on 18 October 2017 a report with some concerning facts:

  • Since 1975, the worldwide obesity has tripled
  • In 2016, more than 1.9 billion adults, 18 years and older, were overweight. Of these over 650 million were obese.
  • 39% of adults aged 18 years and over were overweight in 2016, and 13% were obese.
  • Obesity and being overweight kills more people than being underweight.
  • 41 million children under the age of 5 were overweight or obese in 2016.
  • Over 340 million children and adolescents aged 5-19 were overweight or obese in 2016.
  • Obesity is a modifiable condition.

Once considered a condition associated with lifestyle in the developing countries, now obesity has been spreading to low and middle-income countries also.

 

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The energy imbalance

The energy imbalance between the number of calories consumed and the calories expended is the cause that leads to obesity and overweight Globally. There has been an increased consumption of energy-dense foods high in fat and the increasingly sedentary nature of many forms of work, the use of transportation, and increasing urbanization.

Many organisations, including World Health Organization (WHO), are fighting against obesity creating actions to make people aware of the consequences of obesity, the risks involved, the burden of obesity and the importance of healthy diets and physical activity.

The World Health Assembly adopted, in 2004, the “WHO Global Strategy on Diet, Physical Activity and Health” comprising the proposed strategy to the nations worldwide to take action at global, regional and local levels to improve diets and physical activity patterns at the population level.

With proper patient education, it is believed that unhealthy habits can be reduced and obesity can be prevented.

The Global Action Plan for the Prevention and Control of Noncommunicable Diseases (NCD) 2013-2020 was welcomed by the World Health Assembly in 2017, to guide countries to fight against some diseases, including obesity. It is a  call for lifestyle intervention, raising awareness that some of the most dangerous diseases (like cardiovascular diseases, cancer, diabetes, and chronic respiratory diseases can be prevented with small interventions.

The WHO assembly highlights the fact that more than 36 million die annually from NCDs (63% of global deaths), including 14 million people who die too young before the age of 70. These premature deaths occur mostly in low and middle-income countries and could have largely been prevented. Most premature deaths are linked to common risk factors, like smoking, unhealthy diets, physical inactivity and harmful use of alcohol.

What are obesity and overweight

Overweight and obesity are defined as abnormal or excessive fat accumulation

Body mass index (BMI) is a simple index of weight-for-height that is commonly used to classify overweight and obesity in adults. It is defined as a person’s weight in kilograms divided by the square of his height in meters (kg/m2).

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Adults

For adults, WHO defines overweight and obesity as follows:

  • overweight is a BMI greater than or equal to 25; and
  • obesity is a BMI greater than or equal to 30.

BMI provides a useful population-level measure of overweight and obesity as it is the same for both sexes and for all ages of adults. However, it may not correspond to the same degree of fatness in different individuals. For a complete image, the abdominal circumference must be measured.

For children, age needs to be considered when defining overweight and obesity.

Overweight and obesity are major risk factors for a number of chronic diseases, including diabetes, cardiovascular diseases, and cancer.

Often overweight or obesity is associated with dyslipidemia, hypertension, diabetes or metabolic syndrome.

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What represents the metabolic syndrome (MS)?

There are several definitions of Metabolic Syndrome. Metabolic Syndrome is a group of risk factors, associated with the risk of developing cardiovascular diseases and type 2 diabetes. A subject has the Metabolic Syndrome if he or she has three or more of the following criteria:

  1. Abdominal obesity: waist circumference ≥94 cm in men and ≥80 cm in women (white people of European origin, regardless of where they live in the world)
  2. Hypertriglyceridemia: ≥150 mg/dl (1.7 mmol/l)
  3. Low HDL-C: <40 mg/dl in men and <50 mg/dl in women
  4. High blood pressure (BP): >130/85 mmHg
  5. High fasting glucose: >100 mg/dl (5.6 mmol/l).

A complete set of investigations for the diagnosis of MS should also include: tomographic assessment of visceral adiposity and liver fat, biomarkers of adipose tissue (adiponectin, leptin), apolipoprotein B, LDL particle size, formal measurement of insulin resistance and an oral glucose-tolerance test, endothelial dysfunction, urinary albumin, inflammatory markers (C-reactive protein, tumour necrosis factor , interleukin 6), and thrombotic markers (plasminogen activator inhibitor type 1, fibrinogen).

Metabolic Syndrome identifies people at a higher risk of CVD than the general population. Lifestyle therapy to improve the atherogenic lipid profile is recommended to all subjects with this condition.

 

Cardio 50 study- a very interesting prevention study

Obesity.

Cardio 50 study was initiated in Italy in 2015 by the Department of Prevention and its nurses, in collaboration with health districts and general practitioners, to provide some health strategies based on multifactorial actions. This project was following the WHO Global action plan for the prevention aiming to decrease mortality by 25% by the year 2025.

The objectives of the study were:

  1. to identify among the healthy adult population, aged ≥ 50 years, if lifestyle was altered with  unhealthy habits like smoking, massive alcohol drinking, less than 2 fruit/vegetable per day, no physical activity, had a BMI at least 25, had an abdominal circumference of at least 88 cm in women or 102 in men;
  2. To identify among the healthy adult population, aged ≥ 50 years,  altered parameters such as SBP at least 140 mmHg and/or DBP at least 90 mmHg; TC at least 240 mg/dl; glucose at least 110 mg/dl;
  3. To reduce the cardiovascular risk factors with small lifestyle intervention.

A total number of 2325 participants were screened with lifestyle interview and registration of BMI, blood pressure, glucose, cholesterol and subsequently classified into four risk groups:

A: Normal lifestyle, BP, glucose, and Total Cholesterol ;

B: Altered lifestyle and normal parameters;

C: Elevated Blood Pressure or glucose or Total Cholesterol (according to finger prick test), regardless of lifestyle;

D: Individuals who fulfilled any of the above-listed exclusion criteria after verification by the project nurses, but had not been identified as eligible by the GP (e.g. individuals who were antihypertensive patients without telling their GPs).

Fruit and vegetables and sweets were more consumed by women than by men, whereas cheese and cured meat and sausages were more commonly eaten by men.

Of all individuals in group C, 76% were diagnosed with dyslipidemia, 35% with hypertension, 1% with diabetes, 14% with IFG, 19% were obese and an additional 39% overweight, 21% had metabolic syndrome, 5% dysthiroidism, 11% were at risk of alcohol abuse and 21% were smokers. A total of 78% of the diagnoses of dyslipidemia, hypertension, and hyperglycemia (diabetes or IFG) at the screening visit were confirmed by the cardiologist.

Almost 8% of individuals had some cardio-cerebrovascular or other chronic conditions which were unknown to their GPs: surprising but important information about care pathways in this area.

Each patient (N=2325) received individual lifestyle counselling (on diet, physical activity, and smoking) by the screening nurse.

Overall, the program required 2721 nurse-hours and 563 medical doctor-hours, had a simple design, used low technology, was conducted by specialists in synergy with GPs and succeeded to detect lifestyle abnormalities in a massive percent of the participants, evidencing a remarkable number of conditions with strong cardiovascular impact.

It is a real-world example of collaboration among specialists of prevention, territory, and hospital, according to modern guidelines for an integrated health management.

The average weight reduction of 1.5 kg was also appreciable.

A significant result was obtained in individuals with severe obesity who were followed monthly (weight loss of 8 kg, 6.2% of body weight), although these results were based on very few individuals and should be confirmed by further research.

 

Lose weight concept with person on a scale measuring kilograms

 

Can the changes in the Food industry lead to a decrease in the prevalence of the Cardiovascular diseases?

Food systems once based on local production and local markets, with relatively little processing before foods reached the households is nowadays, characterized by a global web of interactions between multiple actors from farm to fork, geared towards maximizing efficiency to reduce costs and increase production.

The paper Food Consumption and its Impact on Cardiovascular Disease5 outline the correlations between specific macronutrients and cardiovascular diseases,  summarizing how the global food system contributes to dietary patterns that greatly increase the risks for the population to develop cardiovascular risk factors.

Multiple aspects of diet substantially influence the risk of developing cardiovascular diseases. However, similar data are needed from low middle-income countries as dietary patterns differ in various regions of the world and the context in which foods are accessed differs markedly.

Based on the current evidence, the optimal dietary pattern to reduce CVD is one that emphasizes whole grains, fruits and vegetables, legumes, nuts, fish, poultry, and moderate dairy and heart-healthy vegetable oil intake.

 

Orlistat: What are the alternatives

Pharmacotherapy in obesity is aimed to maintain compliance and ameliorate obesity-related health risks. It can also help reduce the risk of co-morbidities and improve the overall quality of life.

The efficacy of the treatment must be evaluated at every 3 months.

If no weight reduction was achieved, the treatment must be discontinued after 3 months.

When weight loss achieved is satisfactory (>5% weight loss in non-diabetic and >3% in diabetic patients), treatment should be continued.

 

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Lorcaserin

Lorcaserin has appetite reduction properties and acts like an anorectic.

Serotonin plays important role in satiety and hence controls hunger. Intake of food is controlled by satiety centre, located in the ventromedial nucleus of the hypothalamus and hunger centre present in the lateral hypothalamus. Lorcaserin has been available in the USA since June 2013 but is not currently available in the U.K. The recommended dose is 10 mg twice daily. The product licence requires 5% weight loss after 12 weeks of treatment. If a patient does not reach this target, the drug should be discontinued.

Drugs that interfere with serotonin neurotransmission (such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitor, and monoamine oxidase inhibitors) should be used with precaution. The combination with lorcaserin can lead to serotonin syndrome.

 

Phentermine/topiramate

Phentermine/topiramate is a weight-loss combination therapy that can produce and sustain approximately 10% loss of body weight.

The exact mechanism of action of phentermine/topiramate combination therapy is actually unknown. The primary mechanism of action of phentermine in obesity treatment is believed to be appetite suppression; however, other central nervous systems (CNS) actions, or metabolic effects, may also be involved.

 

Bupropion/naltrexone

Bupropion/naltrexone is a combination of two centrally acting medications that had already been approved.

Bupropion is used as an antidepressant and to aid smoking cessation. It is a non-selective inhibitor of the dopamine and norepinephrine transporters.

Oral naltrexone is relatively safe and has a moderate to good clinical efficacy in the management of persons with alcohol and opioids dependence.

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Red yeast rice

Red yeast rice is a well-known lipid-lowering nutraceutical for metabolic syndrome amelioration, validated for hypercholesterolemic effect and as an

anti-inflammatory, antidiabetic, anticancer and osteogenic agents have emerged on numerous clinical studies.

Red yeast rice contains a range of compounds known as monacolins, of which monacolin K-renamed lovastatin by pharmaceutical researchers-was found to be the most potent inhibitor of cholesterol synthesis. Standardized extracts of Red yeast rice, providing 10 mg of monacolins daily, have been shown to lower elevated low-density lipoprotein (LDL) cholesterol by approximately 20%.

Moreover, in a large study population, enrolling 275 subjects, the Red yeast extract proved its beneficial properties in improving lipid profile in patients with mild to moderate hypercholesterolemia, after 4 weeks of treatment with diet, with a good safety and tolerability profile.

A systematic literature review concluded that Red yeast extract exerts a beneficial effect on the reduction of low-density lipoprotein cholesterol with a targeted dose of 10.4 mg (± 4.5) Monacolins K daily, with an acceptable rate of adverse events.

 

Bariatric surgery

Bariatric surgery in severely obese individuals (BMI >35 kg/m2) has led to a paradigm shift of metabolic surgery for the treatment of type 2 diabetes mellitus, including patients with a BMI <35 kg/m2.

A rapidly increasing demand for bariatric/metabolic surgery has been noted worldwide.

Owing to the high incidence of obesity, the bariatric procedure has become the most commonly carried out surgical procedure in the USA. Speaking of the growth rate, it is interesting to see that it was higher in Asia than in other parts of the worldwide.

There is not enough data yet to provide clear conclusions regarding the safety of the surgical procedures.

 

In summary…

  • Small benefits from interventions on diet and risk factors such as obesity and overweight produce great advantages.
  • Obesity is a disorder resulting from a complex interplay of personal and environmental factors. It is a disease of the evolving society.
  • One of the most important considerations, if you are overweight or suffering from obesity, is the prevention of the diseases attributable to obesity: type 2 diabetes, uterine cancer, hypertension, coronary heart disease, stroke, myocardial infarction, breast cancer and colon cancer.
  • The hardest part of the process of weight loss is the maintenance of the weight.
  • The weight loss goal must be set realistic after the assessment of the patient motivation.
  • A 5–15% weight loss over a period of 6 months is realistic and of proven health benefit. A greater (20% or more) weight loss may be considered for those with greater degrees of obesity (BMI ≥ 35 kg/m2).
  • Current medical treatment provides alternatives in the treatment of obesity, such as different pharmacological agents and the bariatric surgery
  • Taking into account the Dyslipidemia Management Guidelines, different interventions must be selected according to the cardiovascular risk score

 

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References:

  1. http://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
  2. World Health Organization. Global action plan for the prevention and control of noncommunicable diseases 2013–2020. Geneva, Switzerland: World Health Organization; 2013; http://apps.who.int/iris/ bitstream/10665/94384/1/9789241506236_eng.pdf.
  3. Aliberti et al. The metabolic syndrome-a new worldwide definition. www.thelancet.com Vol 366 September 24, 2005
  4. Bordin P, Picco F, Valent F, Mattiussi B, Vidotto L, Brianti G. Cardiovascular prevention in 50-year-old adults: an Italian intervention study. J Cardiovasc Med(Hagerstown). 2018 Jun 6. doi: 10.2459/JCM.0000000000000682. [Epub ahead of print] PubMed PMID: 29879085.
  5. Anand SS, Hawkes C, de Souza RJ, Mente A, Dehghan M, Nugent R, Zulyniak MA, Weis T, Bernstein AM, Krauss RM, Kromhout D, Jenkins DJA, Malik V, Martinez-Gonzalez MA, Mozaffarian D, Yusuf S, Willett WC, Popkin BM. Food Consumption and its Impact on Cardiovascular Disease: Importance of Solutions Focused on the Globalized Food System: A Report From the Workshop Convened by the World Heart Federation. J Am Coll Cardiol. 2015 Oct 6;66(14):1590-1614. doi: 10.1016/j.jacc.2015.07.050. Review. PubMed PMID: 26429085; PubMed Central PMCID: PMC4597475.
  6. Yumuk V et al. European Guidelines for Obesity Management in Adults
  7. Brashier D.B.S et al. Lorcaserin: A novel antiobesity drug
  8. Garvey W.T. Phentermine and topiramate extended-release: a new treatment for obesity and its role in a complications-centric approach to obesity medical management
  9. D’Addato S., Scandiani L., Mombelli G., Focanti F., Pelacchi F., Salvatori E., Di Loreto G., Comandini A., Maffioli P., Derosa G.- Effect of a food supplement containing berberine, monacolin K, hydroxytyrosol and coenzyme Q10 on lipid levels: a randomized, double-blind, placebo, controlled study. Open Access Full-Text Article. Drug Design, Development and Therapy 2017:11 1585-1592
  10. Gerards MC, Terlou RJ, Yu H, Koks CH, Gerdes VE. Traditional Chinese lipid-lowering agent red yeast rice results in significant LDL reduction but safety is uncertain – a systematic review and meta-analysis. Atherosclerosis. 2015 Jun;240(2):415-23. doi: 10.1016/j.atherosclerosis.2015.04.004. Epub 2015 Apr 12. Review. PubMed PMID: 25897793.
  11. WeiJei Lee and Owaid Almalki . Recent advancements in bariatric/metabolic surgery
  12. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias, European Heart Journal, Volume 37, Issue 39, 14 October 2016, Pages 2999–3058,https://doi.org/10.1093/eurheartj/ehw272

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