Global Burden of Disease (GBD): Focus on Obesity.

It is an interesting fact that the mortality rate rises as the BMI falls below 18.5 and above 25 kg/m2.  Overweight refers to a weight above the “normal” range, with normal defined on the basis of actuarial data. This is determined by calculating the body mass index (BMI, defined as the weight in kilograms divided by height in meters squared).

Overweight is defined as a BMI of 25 to 29.9 kg/m2; obesity is defined as a BMI of ≥30 kg/m2. Severe obesity is defined as a BMI ≥40 kg/m2 (or ≥35 kg/m2 in the presence of comorbidities). Although these categorical definitions are clinically useful, it is clear that the risks imparted by increasing body mass follow a continuum. From where did the concept that of linking obesity to morbidity and mortality arise? Health insurance studies showed the link in order to determine the premium to be paid by people at higher risk.

Lesson to be learnt: weigh your patient and work out the BMI.

Some interesting facts to mull over.

  • The  tripling of obesity is seen in youth and young adults of developing, middle-income countries such as China, Brazil, and Indonesia. We have no statistics for Pakistan but obesity is definitely on the rise.
  • Population-level age-adjusted rates of death and disability has not grown, which suggests that obese persons are healthier and live longer now than in previous decades because of better care and risk-factor management.
  • The incidence of type 2 diabetes in youth has increased substantially in minority populations in the USA, in China and other countries where there has been an increase in the average income of the family.
  • When type 2 diabetes occurs in youth, it brings a much higher prevalence of complications than does type 1 diabetes.
  • Reductions in diabetes complications among older adults coupled with an increased incidence of diabetes among children may shift a proportionately greater load of morbidity into middle age.
  • An early onset of obesity is likely to translate into a high cumulative incidence of type 2 diabetes, hypertension, and chronic kidney disease.
  • At any given level of BMI, Asians have been shown to have a higher absolute risk of diabetes and hypertension and African-Americans to have a lower risk of cardiovascular disease than other groups.
  • There may be important, missed variation in the high-end of the BMI distribution, which disproportionately drives the development of type 2 diabetes and other coexisting illnesses.
  • Although obesity and diabetes have become a shared global burden requiring a strong response from governments, their determinants and effects — and particularly their solutions — also depend on the specific environment in which people live.
  • Better data systems would permit policymakers in the hardest hit areas of the world to respond more quickly and to shorten the long learning period that is typically required to overcome chronic diseases.

These facts are taken from: Global Health Effects of Overweight and Obesity
Edward W. Gregg, Ph.D., and Jonathan E. Shaw, M.D.  N Engl J Med 2017;377:13-27. DOI: 10.1056/NEJMoa1614362.

The Abu Dhabi Childhood Obesity Forum  aims to dissect the different aspects of the fight against childhood obesity, including examining the role of food providers in the fight against child obesity, enhancing obesity assessment and management programmes, boosting physical activity of children at home and in schools, encouraging them to make healthy lifestyle choices; and leveraging data and technology to bring education and communication campaigns to life.

What does UptoDate have to say about obesity?

Metabolically healthy obese patients — The term “metabolically healthy” obese and overweight refers to individuals who do not have adiposity-associated cardiometabolic abnormalities (hypertension, hypertriglyceridemia, low high-density lipoprotein [HDL] cholesterol, impaired fasting glucose and/or evidence of insulin resistance, abnormal C-reactive protein). Evidence suggests that obesity varies in its impact on health risk and often may require many years to render deleterious effects.

In a pooled analysis of four studies with 10-year follow-up, “metabolically healthy obese” individuals had a significantly increased risk of mortality compared with metabolically healthy normal-weight individuals. However, in metabolically healthy overweight individuals, the increased risk of mortality did not reach statistical significance, even when the analysis was restricted to studies with at least 10 years of follow-up (relative risk [RR] 1.21, 95% CI 0.91-1.61). Thus, some of the variability in mortality estimates among overweight people may be due to inadequate adjustment in the analyses for these metabolic factors; a follow-up that is too short to demonstrate a significantly increased mortality risk in overweight, metabolically healthy individuals; or from studies that are too small. However, the most likely explanation is that risks are proportional to excess fat mass, and overweight individuals represent a spectrum of risk that is generally lower than obese individuals.

Obesity paradox — Some studies have concluded that elevated BMI may improve survival in individuals with CVD, primarily congestive heart failure, a phenomenon called the “obesity paradox”. However, these studies have not considered body fat distribution. Abdominal (versus gluteal) fat mass is strongly predictive of metabolic disease and mortality when measured by dual-energy x-ray absorptiometry (DXA), waist-to-hip ratio, or waist circumference. Thus, people with BMI <25 kg/m2 but with central obesity appear to have an increased mortality risk and should be targeted for lifestyle modification strategies.

In contrast to the many studies reporting that overweight is associated with higher mortality, there are data that suggest lower mortality for those with BMI in the 25 to 30 kg/m2 range. Nevertheless, this was challenged by a large Australian study of 246,314 individuals, again showing the lowest mortality in those with a BMI of 22.5 to 24.99 kg/m2, not BMI 25 to 29.99 kg/m2.

What are the causes of a high mortality in obesity?

  • Type 2 diabetes accompanied by insulin resistance.
  • Dyslipidemia.  The prevalence of obesity-associated dyslipidemia may be decreasing. Unfavorable obesity-related effects include high serum concentrations of cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, triglycerides, and a reduction in serum high-density lipoprotein (HDL) cholesterol of approximately 5 percent. The last effect may be most important since a low serum HDL cholesterol concentration carries a greater RR of coronary heart disease (CHD) than hypertriglyceridemia.
  • Hypertension — Blood pressure is often increased in obese subjects. The risk of hypertension is greatest in those subjects with upper body and abdominal obesity. Weight loss in obese subjects is associated with a decline in blood pressure.
  • Heart disease — Obesity is associated with increased risks of CHD, heart failure, and, as described above, cardiovascular and all-cause mortality. Weight loss (if achieved through lifestyle interventions, medication, or surgery) is associated with an improvement in cardiovascular risk factors.
  • Coronary heart disease – Obesity has long been associated with an increased risk for CHD. The risk of CHD in obese and overweight persons is compounded by the frequent coexistence of other CHD risk factors, such as hypertension, dyslipidemia, and diabetes. How much of the risk is due to obesity alone has been uncertain.
  • Heart failure – There is an important association between obesity and heart failure. There are a number of mechanisms by which obesity could predispose to heart failure . Myocardial steatosis – One potential mechanism for heart disease in obesity is thought to be excessive lipid accumulation in the myocardium. Electrocardiogram findings – Morbid obesity can cause changes in cardiac morphology that can alter the surface electrocardiogram (ECG).
  • Atrial fibrillation – Obese individuals (BMI >30 kg/m2) are significantly more likely to develop atrial fibrillation (AF) than those with a normal BMI (<25 kg/m2).
  • Stroke — Obesity is associated with an increased risk of stroke, and stroke risk is mitigated by weight loss.
  • Venous thrombosis — Obesity has been associated with an increased risk of deep vein thrombosis and pulmonary embolus. This topic is reviewed in detail elsewhere.
  • Cancer — Excess weight is associated with an increased risk of multiple cancer types. Overweight and obesity were estimated to cause 40 percent of all cancers in the United States in 2014.

In the Look AHEAD (Action for Health in Diabetes) trial, 5145 individuals with type 2 diabetes and BMI >25 kg/m2 were randomly assigned to an intensive lifestyle intervention (group and individual meetings to achieve weight loss with diet and exercise) or standard diabetes education.

What did this trial find?

After a median follow-up of 9.6 years, the composite primary outcome (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for angina) occurred in a similar number of patients in the intervention and control groups.

Why did this happen? Possible reasons for the lower-than-expected rates of cardiovascular events in both groups were  improved overall cardiovascular risk factor treatment with medical therapy (eg, antihypertensive, statins), enrollment of a relatively healthy patient population, and gradual weight loss in the control group such that the differential weight loss between the two groups was only 2.5 percent at study end. Of note, the active intervention group achieved its results with significantly less use of CVD risk-lowering medications than the control group.

How to manage obesity?

  • For the low risk and medium risk group: eat fewer calories, behavioral modification and exercise fo 150 minutes of leisure time per week. Objective:  to achieve 7% weight loss.
  • For high risk patients life style change plus as above plus pharmocological therapy and bariatric surgery.

Behavior modification or behavior therapy is one cornerstone in the treatment for obesity. The goal of behavioral therapy is to help patients make long-term changes in their eating behavior by modifying and monitoring their food intake, modifying their physical activity, and controlling cues and stimuli in the environment that trigger eating.

Pharmacologic options for the treatment of obesity include orlistat, liraglutide (daily injection), lorcaserin, combination phentermine-extended release topiramate (in one capsule), combination bupropion-naltrexone (in one extended-release tablet, not recommended by most experts because of side effects), phentermine, benzphetamine, phendimetrazine, and diethylpropion. In meta-analyses of randomized trials comparing pharmacologic therapy with placebo, all active drug interventions are effective at reducing weight compared with placebo. Sympathomimetic drugs should not be prescribed to patients with coronary artery disease, heart failure and hypertension.




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I am a Professor of Medicine and a Nephrologist. Having served in the Army Medical College, Pakistan Army for 27 years I eventually became the Dean and Principal of the Bahria University Medical and Dental College Karachi from where I retired in 2016. My passion is teaching and mentoring young doctors. I am associated with the College of Physicians and Surgeons Pakistan as a Fellow and an examiner. I find that many young doctors make mistakes because they do not understand how they should answer questions; basically they do not understand why a question is being asked. My aim is to help them process the information they acquire as part of their education to answer questions, pass examinations and to best take care of patients without supervision of a consultant. Read my blog, interact and ask questions so that I can help you more.

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