We estimate that about 10-15% of incident cases of MS could be prevented if we could prevent childhood and adolescent obesity. This is easier said than done. Obesity is now one of the major social determinants of health (SDoH). Obesity is strongly linked to deprivation and lower socioeconomic class. Why? Because cheap food is to blame. I have little doubt that most obesity is attributable to the imbalance in our macronutrient content and the relative excessive consumption of processed and ultra-processed carbohydrates.
Changing our diet at a population level will require government intervention and specific policies to address poor diets. For example, the sugar tax needs to be increased and the WHO guidelines on daily limits of sugar consumption need to be implemented. Sadly, the food industrial complex is very powerful and have developed covert ways of influencing government policy and dietary guidelines. Although their methods are gradually being exposed by brave journalists and scientists the general public have yet to understand what the food industry has done to our health.
As you can see preventive medicine, including preventive neurology, is not just about science, but politics as well. So what can be done at an individual level? I would recommend reflecting on your diet and your family’s diet and making a decision about what your diet means to you. I have written a Medium blog post on diet as a philosophy, which tries to explain why what you eat is more than just feeding yourself.
For those of you who are obese, there is some amazing news. In this week's New England Journal of Medicine a trial of semaglutide a biological therapy that is given by subcutaneous injection once weekly resulted in a 15% drop in weight and improvement in obesity-associated metabolic profile compared to only a 2.4% drop in weight in placebo-treated subjects. These results are similar to what is achieved with bariatric surgery. Semaglutide is a so-called glucagon-like peptide-1 receptor agonist and increases the production of insulin, a hormone that lowers the blood sugar level. It also appears to enhance the growth of the so-called β cells in the pancreas, which are the sites of insulin production. The downside of increased insulin production is likely to be an increased risk of some cancers. However, the takehome message should be that when you treat obesity as a metabolic maelstrom, an endocrine disorder, a disease and you unpack the biology you realise it is a treatable disease.
This will be the beginning of a new era in the management of obesity and that I am sure we will begin to see a falling prevalence of obesity and the downstream effects such as a lower incidence of MS and dementia in the future. Do you agree?
We are living in an exciting era, the era of the ‘unpacking of biology’ and unprecedented advances in the treatment of disease, including obesity; let's celebrate it for that.
Paper 1: semaglutide as a treatment for obesity
Wilding et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10.
Background: Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed.
Methods: In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary endpoints were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions.
Results: The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhoea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]).
Conclusions: In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with a sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).
Paper 2: obesity as a risk factor for MS
Pakpoor et al. Estimated and projected burden of multiple sclerosis attributable to smoking and childhood and adolescent high body-mass index: a comparative risk assessment. Int J Epidemiol. 2021 Jan 23;49(6):2051-2057.
Background: Smoking and childhood and adolescent high body-mass index (BMI) are leading lifestyle-related risk factors of global premature morbidity and mortality, and have been associated with an increased risk of developing multiple sclerosis (MS). This study aims to estimate and project the proportion of MS incidence that could be prevented with the elimination of these risk factors.
Methods: Prevalence estimates of high BMI during childhood/adolescence and smoking in early adulthood, and relative risks of MS, were obtained from published literature. A time-lag of 10 years was assumed between smoking in early adulthood and MS incidence, and a time-lag of 20 years was assumed between childhood/adolescent high BMI and MS incidence. The MS population attributable fractions (PAFs) of smoking and high BMI were estimated as individual and combined risk factors, by age, country and sex in 2015, 2025 and 2035 where feasible.
Results: The combined estimated PAFs for smoking and high BMI in 2015 were 14, 11, 12 and 12% for the UK, USA, Russia and Australia in a conservative estimate, and 21, 20, 19 and 16% in an independent estimate, respectively. Estimates for smoking are declining over time, whereas estimates for high early-life BMI are rising. The PAF for high early-life BMI is highest in the USA and is estimated to increase to 14% by 2035.
Conclusions: Assuming causality, there is the potential to substantially reduce MS incidence with the elimination of lifestyle-related modifiable risk factors, which are the target of global public health prevention strategies.
Paper 3: obesity as risk factor for dementia
Ma et al. Higher risk of dementia in English older individuals who are overweight or obese. Int J Epidemiol. 2020 Aug 1;49(4):1353-1365. doi: 10.1093/ije/dyaa099.
Background: Several risk factors contribute to dementia, but the role of obesity remains unclear. This study investigated whether increased body weight or central obesity were associated with a higher risk of developing dementia in a representative sample of older English adults.
Methods: We studied 6582 participants from the English Longitudinal Study of Ageing (ELSA) who were aged ≥50 years and were dementia-free at baseline, that being either wave 1 (2002-2003) for study members who started at wave 1, or at either wave 2 (2004-2005) or 4 (2008-2009) for those who began the study as refreshment samples. Body mass index (BMI) was measured at baseline and categorized into normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2) and obese (≥30 kg/m2). Central obesity was defined as a waist circumference (WC) >88 cm for women and >102 cm for men. Cumulative incidence of dementia was ascertained based on physician-diagnosed dementia, an overall score >3.38 on the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and Hospital Episodes Statistics (HES) data at every ELSA wave from baseline until wave 8 (2016-2017). Cox proportional hazards models were used to assess the association between baseline BMI levels or abdominal obesity in relation to dementia incidence during the mean follow-up period of 11 years.
We are living in an exciting era, the era of the ‘unpacking of biology’ and unprecedented advances in the treatment of disease, including obesity; let's celebrate it for that.
Paper 1: semaglutide as a treatment for obesity
Wilding et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10.
Background: Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed.
Methods: In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary endpoints were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions.
Results: The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhoea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]).
Conclusions: In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with a sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).
Paper 2: obesity as a risk factor for MS
Pakpoor et al. Estimated and projected burden of multiple sclerosis attributable to smoking and childhood and adolescent high body-mass index: a comparative risk assessment. Int J Epidemiol. 2021 Jan 23;49(6):2051-2057.
Background: Smoking and childhood and adolescent high body-mass index (BMI) are leading lifestyle-related risk factors of global premature morbidity and mortality, and have been associated with an increased risk of developing multiple sclerosis (MS). This study aims to estimate and project the proportion of MS incidence that could be prevented with the elimination of these risk factors.
Methods: Prevalence estimates of high BMI during childhood/adolescence and smoking in early adulthood, and relative risks of MS, were obtained from published literature. A time-lag of 10 years was assumed between smoking in early adulthood and MS incidence, and a time-lag of 20 years was assumed between childhood/adolescent high BMI and MS incidence. The MS population attributable fractions (PAFs) of smoking and high BMI were estimated as individual and combined risk factors, by age, country and sex in 2015, 2025 and 2035 where feasible.
Results: The combined estimated PAFs for smoking and high BMI in 2015 were 14, 11, 12 and 12% for the UK, USA, Russia and Australia in a conservative estimate, and 21, 20, 19 and 16% in an independent estimate, respectively. Estimates for smoking are declining over time, whereas estimates for high early-life BMI are rising. The PAF for high early-life BMI is highest in the USA and is estimated to increase to 14% by 2035.
Conclusions: Assuming causality, there is the potential to substantially reduce MS incidence with the elimination of lifestyle-related modifiable risk factors, which are the target of global public health prevention strategies.
Paper 3: obesity as risk factor for dementia
Ma et al. Higher risk of dementia in English older individuals who are overweight or obese. Int J Epidemiol. 2020 Aug 1;49(4):1353-1365. doi: 10.1093/ije/dyaa099.
Background: Several risk factors contribute to dementia, but the role of obesity remains unclear. This study investigated whether increased body weight or central obesity were associated with a higher risk of developing dementia in a representative sample of older English adults.
Methods: We studied 6582 participants from the English Longitudinal Study of Ageing (ELSA) who were aged ≥50 years and were dementia-free at baseline, that being either wave 1 (2002-2003) for study members who started at wave 1, or at either wave 2 (2004-2005) or 4 (2008-2009) for those who began the study as refreshment samples. Body mass index (BMI) was measured at baseline and categorized into normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2) and obese (≥30 kg/m2). Central obesity was defined as a waist circumference (WC) >88 cm for women and >102 cm for men. Cumulative incidence of dementia was ascertained based on physician-diagnosed dementia, an overall score >3.38 on the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and Hospital Episodes Statistics (HES) data at every ELSA wave from baseline until wave 8 (2016-2017). Cox proportional hazards models were used to assess the association between baseline BMI levels or abdominal obesity in relation to dementia incidence during the mean follow-up period of 11 years.
Results: From the overall sample, 6.9% (n = 453) of participants developed dementia during the follow-up period of maximum 15 years (2002-2017). Compared with participants with normal weight, those who were obese at baseline had an elevated risk of dementia incidence [hazard ratio (HR) = 1.34, 95% confidence interval (CI) 1.07-1.61] independent of sex, baseline age, apolipoprotein E-ε4 (APOE-ε4), education, physical activity, smoking and marital status. The relationship was slightly accentuated after additionally controlling for hypertension and diabetes (HR = 1.31, 95% CI 1.03-1.59). Women with central obesity had a 39% greater risk of dementia compared with non-central obese women (HR = 1.39, 95% CI 1.12-1.66). When compared with a normal BMI and WC group, the obese and high WC group had 28% (HR = 1.28, 95% CI 1.03-1.53) higher risk of dementia.
Conclusions: Our results suggest that having an increased body weight or abdominal obesity are associated with increased dementia incidence. These findings have significant implications for dementia prevention and overall public health.
CoI: multiple
Twitter: @gavinGiovannoni
CoI: multiple
Twitter: @gavinGiovannoni
Medium: @gavin_24211
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