Bridging the gap between medical science and policy to reduce the biggest 21st century healthcare burden

Bridging the gap between medical science and policy to reduce the biggest 21st century healthcare burden   In November 2018 the Mayor on London Sadiq Khan, announced that junk food adverts will be banned on all London transport from February 2019 in an attempt to reduce the “ticking time bomb” of childhood obesity in the city. London has one of the highest obesity rates in Europe with some 40% of 10 to 11-year olds either overweight or obese, with children from more deprived areas disproportionately affected. Obesity is a common and costly source of type-2 diabetes (T2DM), which is much more aggressive in youngsters and complications of the condition - blindness, amputations, heart disease and kidney failure - can present earlier. What is happening in London and the UK is replicated in varying degrees in cities and nations throughout the world: there is a global epidemic of obesity and T2DM, which together is often referred to as ‘diabesity’.   The “good” news is that at the same time Khan announced the advertising ban, the UK’s national news outlets were reporting the product of four decades of scientific research, which suggested that T2DM could be reversed by a liquid diet of 800-calories a day for three months.   Although this offers hope for millions of people, an unresolved challenge is whether this simple and cheap therapy will be implemented effectively to significantly dent the burden of diabesity, which arguably is the biggest healthcare challenge of the 21st century.   In this Commentary We describe some of the research behind the news reports about the therapy to reverse T2DM. Although the scientists’ innovative solution of a low-calorie liquid diet has been adopted enthusiastically by some healthcare providers and organizations specifically set up to dent the burden of diabesity, it is questionable whether the gap between science and policy can be bridged. This, we suggest, is because the prevalence of diabesity is growing at a significantly faster rate than the effect of programs to prevent and reduce the condition.   Obesity and T2DM Obesity, which is a significant risk of T2DM, is a complex, multifaced condition, with genetic, behavioural, socioeconomic and environmental origins. Diet and sedentary lifestyles may affect energy balance through complex hormonal and neurological pathways that influence satiety. Also, urbanization, the food environment and the marketing of processed foods are contributory factors to becoming overweight and obese. Notwithstanding, the main driver of weight gain is energy intake exceeding energy expenditure.   T2DM is a chronic, progressive metabolic disease, which until recently has been perceived as incurable. Although genetic predisposition partly determines the condition’s onset, being overweight and obese are significant risk factors. Generally accepted clinical guidelines to treat the condition is to reduce glycated haemoglobin (HbA1c) - blood sugar (glucose) - levels. The HbA1c test assesses your average level of blood sugar over the past two to three months. The normal range for HbA1c is 4% to 5.9%. In well-controlled diabetic patients HbA1c levels are less than 6.5% or 48mmol/moll. High levels of HbA1c mean that you are more likely to develop diabetes complications, such as serious problems with your heart, blood vessels, eyes, kidneys, and nerves. T2DM is treated primarily with drugs and generic lifestyle advice, but many patients still develop vascular complications and life expectancy remains up to six years shorter than in people without diabetes.    Obesity The Organisation for Economic Co-operation and Development’s (OEDC) 2017 Health at a Glance Report warned that obesity in the UK has increased by 92% in the past two decades. Two-thirds of the UK’s adult population are overweight and 27% have a body mass index (BMI) of 30 and above, which is the official definition of obesity. In 2017 there were 0.6m obesity-related hospital admissions in the UK, an 18% increase on the previous year. Each year, obesity cost NHS England in excess of US$10bn in treatment alone.   A 2018 World Health Organization (WHO) report suggests that obesity globally has almost tripled since 1975. In 2016, more than 1.9bn adults, 18 years and older, were overweight. Of these over 650m were obese. According to a 2018 WHO report on childhood obesity 41m children under the age of 5 were overweight or obese in 2016 and over 340m children and adolescents aged 5-19 were overweight or obese.

Bad diets   Diets in the UK, and in most wealthy advanced industrial economies, tend to have insufficient fruit and vegetables, fibre and oily fish and too much added sugar, salt and saturated fat. Rising consumption of processed food and sugary drinks are significant contributors to the global obesity epidemic. A typical 20-ounce soda contains 15 to 18 teaspoons of sugar and upwards of 240 calories. A 64-ounce cola drink could have up to 700 calories. People who consume such drinks do not feel as full as if they had eaten the same number of calories from solid food and therefore do not compensate by eating less. While healthy diets are challenging for most populations, low income levels and poor education are associated with less healthy diets. You might also like: Excess weight and type-2 diabetes linked to 16% of cancers in the UK and Weight loss surgery to treat T2DM

T2DM brief epidemiology Almost 4.6m people in the UK and 30m Americans are living with diabetes:  90% of whom have T2DM. It is estimated that 12.3m people in the UK and some 70m in the US are considered pre-diabetic, which is when you have high blood glucose levels, but not high enough to be diagnosed with diabetes. The first WHO Global report on diabetes published in 2016 suggests that 422m adults (1 in 11) worldwide are living with the condition, which has quadrupled over the past three decades. The International Diabetes Federation (IDF) estimates that this figure will rise to 642m by 2040.  A further challenge is the undiagnosed. A December 2017 paper in Nature Reviews: Endocrinology suggests 46% of all cases of diabetes globally are undiagnosed and therefore at enhanced risk of complications. Until complications develop, most T2DM patients are managed within primary care, which constitutes a significant part of general practice activity. International data suggest that medical costs for people with diabetes are two to threefold greater than the average for people without diabetes.   T2DM treated but not cured The most common therapy for T2DM patients who are overweight is metformin, which is usually prescribed when diet and exercise alone have not been enough to control your blood glucose levels. Metformin reduces the amount of sugar your liver releases into your blood and also makes your body respond better to insulin. Insulin is a hormone produced by your pancreas that allows your body to use sugar from carbohydrates in food that you eat for energy or to store glucose for future use. The hormone helps to keep your blood sugar levels from getting too high (hyperglycaemia) or too low (hypoglycaemia). Metformin does not cure T2DM and does not get rid of your glucose, but simply transfers your excess sugar from your blood to your liver. When your liver rejects your excess sugar, the medicine passes the glucose onto other organs: kidneys, nerves, eyes and heart. Much of your excess sugar gets turned into fat and hence you become overweight or obese. T2DM has long been understood to progress despite glucose-lowering therapy, with 50% of patients requiring insulin therapy within 10 years. This seemingly inexorable deterioration in control has been interpreted to mean that T2DM is treatable but not curable. Research briefly described in this Commentary suggests that T2DM can be beaten into ‘remission’, but it requires losing a lot of weight and keeping it off.   Reversing T2DM Over the past decade a series of studies, led by Roy Taylor, Professor of Medicine and Metabolism at the University of Newcastle, England and colleagues from Glasgow University have explored the notion that losing weight could be the solution for controlling T2DM and lowering the risk of debilitating and costly complications.   Findings of a study in the December 2017 edition of the  Lancet, suggested that nearly 50% of people living with T2DM who had participated in a low-calorie liquid diet of about 800 calories a day for three to five months had lost weight and had reverted to a non-T2DM state. The study was comprised of 298 adults between 20 and 65 who had been diagnosed with T2DM within the past six years drawn from 49 primary care practices in Scotland and Tyneside in England. Half of the practices put their patients on the low-calorie diet, while the rest were in a control group and received the standard of care of anti-diabetic medicines to manage their blood glucose levels. About 46% of 149 individuals with T2DM who followed a weight loss regimen achieved ‘remission’, which the study defined as a HbA1c of less than 6.5% after one year. Only 4% of the control group managed to achieve ‘remission’. ‘Remission’ rather than ‘cure’ was used to describe the reversal of T2DM because if patients put weight back on, they may become diabetic again. Results improved according to the amount of weight lost: 86% of those who lost more than 33 pounds attained remission, while 57% of those who lost 22 to 33 pounds reached that goal.   Another paper by Taylor and his colleagues published in the October 2018 edition of Cell Metabolism, examined reasons why substantial weight loss - (15kg) in some patients - produces T2DM remission in which all signs and symptoms of the condition disappear, while in other patients it does not. Using detailed metabolic tests and specially developed MRI scans, Taylor observed that fat levels in the blood, pancreas and liver were abnormally high in people with T2DM. But after following an intensive weight loss regimen, all participants in the study were able to lower their fat levels. As fat decreased inside the liver and the pancreas, some participants also experienced improved functioning of their pancreatic beta cells, which store and release insulin, controls the level of sugar in their blood and facilitates glucose to pass into their cells as a source of energy. The likelihood of regaining normal glucose control depends on the ability of the beta cells to recover. But, losing less than 1gm of fat from your pancreas through diet can re-start your normal production of insulin and thereby reverse T2DM.   “The good news for people with T2DM is that our work shows that you are likely to be able to reverse T2DM by moving that all important tiny amount of fat out of your pancreas. At present, this can only be done through substantial weight loss,” says Taylor. While a significant proportion of participants in Taylor’s study responded to the weight loss program and achieved T2DM remission, others did not. To better understand this, researchers focused on 29 participants who achieved remission after dieting and 16 who dieted but continued to have T2DM. Taylor and his colleagues observed that people who were unable to restart normal insulin production had lived with T2DM for a longer time than those that could. Individuals who had lived with T2DM for an average of 3.8 years could not correct their condition through weight loss, while those who had the condition for an average of 2.7 years were able to regain normal blood sugar control. “Many [patients] have described to me how embarking on the low-calorie diet has been the only option to prevent what they thought - or had been told - was an inevitable decline into further medication and further ill health because of their diabetes. By studying the underlying mechanisms, we have been able to demonstrate the simplicity of T2DM and show that it is a potentially reversible condition. but commencing successful major weight loss should be started as early as possible,” says Taylor.   Click on Newcastle University to find out more information about reversing T2DM by weight loss.   Bridging the gap between science and policy Taylor and his colleagues describe their research findings as “very exciting” because “they could revolutionise the way T2DM is treated”, but caution that a series of management issues will need to be overcome before their therapy becomes common practice. This includes, (i) familiarizing primary care doctors and T2DM patients with the treatment regimen, (ii) establishing a generally accepted standard for what actually constitutes “remission”. Taylor and colleagues recommend “remission” to be when a patient has not taken diabetes medicines for at least two months and then has two consecutive HbA1c levels, taken two months apart, which are less than 6.5%. Researchers also recommend that data on T2DM reversal rates should be routinely collected, stored, analysed and reported. Notwithstanding, the ‘elephant in the room’ is the vast extent of diabesity, the eye-watering rate at which it is growing and the general ineffectiveness of policy makers and prevent programs to dent the burden. Research findings presented at the 2018 European Congress on Obesity in Vienna emphasize the magnitude of the problem. If current trends continue, almost a quarter (22%) of the world’s population will be obese by 2045 (up from 14% in 2017), and 12% will have T2DM (up from 9% in 2017). Findings also suggest that in order to prevent the prevalence of T2DM from going above 10% by 2045, global obesity levels must be reduced by 25%. The problem is no less grave at the national level. For example, in the UK, if current trends continue obesity will rise from 32% today to 48% in 2045, while diabetes levels will rise from 10.2% to 12.6%, a 28% rise. This is unsustainable. Here’s the challenge for policy makers. To stabilise UK diabetes rates over the next 25 years at 10%, which is high and extremely costly, obesity prevalence must fall from 32% to 24%. Similarly, in the US, if current trends continue over the next 25 years, then to keep diabetes rates stable over the same period, obesity in the US would have to be reduced by 10%: from 38% today to 28%.   Takeaways Taylor and his colleagues have delivered a simple and cheap solution to one of the biggest burdens of the 21st century. But unless there is effective strategy to implement this solution the four decades of research undertaken by Taylor and his colleagues will be wasted. Previous Commentaries have described the vast and crippling burden of diabesity and the failure of well-funded programs to make any significant dent in this vast and escalating burden, which is out of control. We have suggested, this is partly because, at the operational level, programs have tended to be predicated upon inappropriate, old fashioned, 20th century organizational methods and technology and focused on “activities” rather than “outcomes”. At a policy level, government agencies have systematically failed to slow the rise of processed food becoming the “new tobacco”.  Most UK endeavours to reduce the burden of diabesity are like putting up an umbrella to fend off a tsunami. This must change if we are to harness and effectively deploy the research findings of Professor Taylor et al.