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Thursday, December 27, 2012

Treating diabetes: Diets, gyms and scalpels

In the US, 27% of those aged 65 or older have diabetes. Based on fasting blood glucose levels or glycated haemoglobin levels, the estimate of the prevalence of pre-diabetes is 79 million cases. The economic cost has been estimated at around $2,000 per person per annum. The maths aren’t complicated working out at about $22 billion per annum.  Most  cases of type 2 diabetes are treated initially by lifestyle changes and then by drugs to manage blood glucose. In 2009, the American Diabetes Association defined partial remission from diabetes when fasting blood glucose levels were lowered to below the diagnostic norm and complete remission when fasting blood glucose levels returned to normal, in both cases in the absence of drug therapy. Relatively little is really known of the extent to which such partial or complete remission can be achieved with lifestyle interventions. In 2001, a large multicenter study was established in the US known as “Look Ahead”, (Actions for Health in Diabetes)[1]. The trial, funded by the National Institute of Health, involved 2,262 type 2 diabetics given a basic diabetes lifestyle intervention and a group of 2,241 type 2 diabetics given an intensive lifestyle intervention. The former were given 3 group sessions per year while the latter participated in weekly group and one-on-one counseling for the first 6 months followed by 3 sessions per month for the next 6 months and twice monthly sessions thereafter. For this group, a target caloric intake was set between 1,200 and 1,800 calories per day with an exercise goal of 175 minutes of moderately intensive exercise per week (25 minutes per day).  The Look Ahead trial laid out its hypothesis quite clearly: that there would be a significant reduction in heart disease and stroke in the intensively counseled group compared to the group receiving standard advice on lifestyle. The trial has produced over 80 peer reviewed papers and has shown that intensive lifestyle intervention can significantly improve body-weight, blood pressure, blood glucose control and blood lipid levels.

On October 19th this year, when the trial was well into its 11th year, the NIH announced the end of the trial on foot of recommendations from the trial’s data and safety monitoring board. This independent body of experts noted that despite the above improvements on risk factors for cardiovascular disease, there was no statistically significant difference in cardiovascular events between the two groups which was the central hypothesis. Recently, the trial study group published a paper in the Journal of the American Medical Association showing that intensive lifestyle intervention did indeed lead to a greater rate of remission of type 3 diabetes compared to the standard intervention[2]. The big disappointment was, however, that the impact of intensive lifestyle was very small. The rate of partial or complete remission in year 1 was 11. 5% in the intensively tutored group, falling to 7.3% at year 4. In contrast, the group receiving standard counseling showed a 2% reduction at both time points. Very clearly, type 2 diabetes is not a reversible condition for the vast majority of subjects. And just as clearly, this low response rate in correcting diabetes pathologies explains why no differences in heart disease were observed between the two treatment groups.

In the same issue of this journal, an editorial looks at the overall evidence for lifestyle and surgical interventions in obesity[3]. The latter are usually confined to subjects with very severe cases of obesity. The latter leads to type 2 diabetes remission rates, which are 12 to 24 fold greater than intensive lifestyle interventions. The Swedish Obesity Study, also published in this year’s JAMA, reported on the long-term effects of the surgical treatment of obesity. Subjects were morbidly obese at baseline (1987 was the start date) and the average duration of follow up was 14.7 years[4]. Compared to conventional medical and lifestyle treatment, the surgical intervention reduced fatal heart attacks by 47%, all heart attacks by 52% and stroke by 34%. Surgery is expensive but so too is intensive lifestyle interventions and thus some cost comparisons between the two would be interesting.

Clearly, we are in a mess and we must now live with the mess. But how can we prevent the mess for future generations?. Whilst 79 million Americans have prediabetes and are at risk of developing diabetes, the remaining 233 million don’t. Of those aged over 65 years, 11.2 million have type 2 diabetes while the remaining 30 million over 65s do not. They all live in the same obesogenic US environment. One day, not far from now, we will be able to predict who is likely to to draw the short straw and develop obesity-related type 2 diabetes. Moreover, this genetic information will soon be able to zone in on that aspect of diet and lifestyle, which is most responsible for the development of diabetes. For some, it may be a metabolically based genetic factor. For others, it may be a food choice factor that is the driver and for others it may be a defective satiety system. Understanding personal risk and understanding personalised solutions is the future for nutrition and health. In the meantime, we have a mess.

[2] Gregg et al (2012) JAMA 308,2489
[3] Arterburn DE & O’Connor PJ (2012) JAMA 308, 2517
[4] Sjostrom L et al (2012) JAMA 307, 56

Tuesday, December 11, 2012

Obesity and Nature v Nurture re-visited

In the obesogenic environment that we live in, not everyone becomes obese. To the high priests of nutrition, that variability is put down to variation in self-control and self-discipline and that in turn relates to level of education and social class. The idea that this variation might be genetically based is dismissed with the old reliable falsism that since our genes have not changed during the recent epidemic of obesity, it’s the environment that counts. Well, yet another twin study shows that this is nonsense and this twin study is somewhat special since it pooled data from 23 twin cohorts from four countries: Denmark, Australia, Canada and Sweden involving just over 24,000 children[1]. Moreover, this pooling study was able to provide data on twins from birth through 19 years of age. By comparing variation within and between both identical and non-identical twins, it is possible to distinguish the effect of genes from the effect of the environment and the latter can be split into common and unique environments. At birth, only 8% of variation in weight or body mass index (BMI) could be explained by genetic factors. By 5 months this had increased to 65% and rose into the 70% decile up to 9 years of age. In the early teens the genetic variation had reached into to 80% decile and by late teens it had hit 90%.  As children got older, the environmental explanation of obesity had fallen from 74% at birth, to 25% at 6 years and down to about 10% in late teens. While this study clearly shows the powerful effect of genetic factors on obesity, it does raise the question as to why this genetic dimension increased with age. Clearly, the genetic make up remained constant so most likely, changes in gene expression were the contributory factor. Growth in childhood and especially in adolescence is associated with significant biological adjustments, which could create the environment for altered gene expression.

One of the reasons which I personally think public health nutritionists are wary of the genetic influence on obesity is that the subject is strongly orientated toward basic biology, effectively, the digestion, absorption, transport, distribution and utilisation of calories from fat, carbohydrate, protein and alcohol. However, genetic influences on behaviour are to my mind far more important   than the genetics of basic biological elements. A recent twin study has looked at the heritability of taste[2].  Subjects were given a strawberry jelly with or without the hot spice capsaicin derived from chili peppers. They were also asked questions on their liking or otherwise of spicy foods and spices and of foods that have mild, strong and extremely strong pungency properties. 50% of the variation in preference for spicy foods and spices and 58% of the variation in “pleasantness of strong pungency” was explained by genetic factors. Another twin study looked at food neophobia in a group of children aged 8 to 11 years, comprising 5,390 pairs of identical and non-identical twins[3].  Parents were asked about their children’s attitude to foods with four statements: “My child is constantly sampling new and different foods”, “My child doesn’t trust new foods,” “My child is afraid to eat things/he has never had before.” and “If my child doesn’t know what’s in a food s/he won’t try it.” A food neophobia score was worked out and the highly robust finding of the study was that a staggering 78% of variation in food neophobia was genetic in origin. Only 22% was learned from the environment. These studies show that the genetic component of obesity need not be related to the biochemistry of energy metabolism, but rather to more complex behavioural traits such as food choice.

Twin studies of obesity always raise the question of assortative mating, that is fat partners mating with other fat partners and similarly for slim partners. Assortative mating has been shown to occur in personality type, education, religion, politics, age, smoking habits and anti-social behaviour. Researchers at the Rowett Institute in Aberdeen used DEXA scans to accurately measure body fat levels in 42 couples[4]. Strong evidence for assortative mating in relation to body fat was found. For example, subjects with disproportionately large arms assortatively mated with like partners. Given the high heritability of the propensity to develop obesity, assortative mating will accelerate the incidence of obesity sine the children of such parents are likely to inherit genetic patterns from both parents.  

The high priests of public health nutrition may dislike the implications of a genetic dimension to obesity but they are being increasingly isolated from the scientific truth.

[1] Dubois et al (2012) PLoS ONE 7, e30153
[2] Tornwall et al (2012) Physiology & Behaviour, 107, 381-389
[3] Cooke et al (2007) Am J Clin Nutr 86, 428-433
[4] Speakman et al(2007) Am J Clin Nutr 86, 316-323

Thursday, November 15, 2012

Sugar taxes and weight loss predictions

The Danish government has abandoned its tax on fat and and its plans for a sugar tax.  A spokesperson for the tax ministry is quoted thus: “The suggestions to tax foods for public health reasons are misguided at best and may be counter-productive at worst.  Not only do such taxes not work, especially when they choose the wrong food to tax, they can become expensive liabilities for the businesses forced to become tax collectors on the governments behalf”[1]. Shortly we will have our annual budget here in Ireland and notwithstanding the volte-face of our Danish colleagues, the likelihood is that we will face such a tax soon.  In general, the predicted weight changes associated with projected taxes on sugar sweetened beverages are grossly overestimated.
A recent consensus statement of the American Society of Nutrition (ASN) and the International Life Sciences Institute (ILSI) has examined the topic:  “Energy balance and its components:  Implications for body weight regulation”[2].  One of the areas covered by this paper is the popular and widely held belief that to lose 1lb of body weight, you need to reduce caloric intake by 3,500 kcal.   This figure assumes that a loss of 1lb of body weight is made up entirely of adipose tissue which is 86% fat and the fat has 9 kcal per gram.  This 3,500 kcal figure is widely used in predicting the benefit of weight loss from a sugar sweetened beverage tax.  It has many flaws.
Firstly, a 1lb weight loss will not be 100% fat but will also involve the loss of some lean tissue (muscle and protein elements of adipose tissue and its metabolism).  Whereas fat has an energy value of 9 kcal/g, lean tissue has a value of 4 kcal/g.  The exact ratio of the loss of lean and fat in weight reduction depends largely on the level of fat in the body at the outset.  The higher the intake level of fat, the higher the proportion of fat lost.  However, as a person sheds fat, the ratio of fat to lean changes in favour of the latter, so subsequent weight loss will have a lower ratio of fat to lean.  The blanket use of the 3,500kcal value ignores this.
The second criticism of this rule is that it ignores time.  If you shed 3,500kcal per week every week, that would differ from a deficit of 3,500 kcal per month every month.  The former leads to a daily deficit of 500 kcal while the latter is just 117 kcal.  Even the most non-expert dieter knows that such differences in daily energy deficits will lead to radically different rates of weight loss.  Thirdly, the 3,500 kcal rule assumes complete linearity – in other words the rule equally applies, pound after pound of weight loss. We saw above that progressive weight loss will progressively increase the % of that weight loss as lean tissue but more importantly, the 3,500kcal rule ignores a major adaptation in energy expenditure.  Basically, our basal metabolic rate (BMR) falls as we restrict our caloric intake.  Since BMR accounts for 88% of energy expenditure in most sedentary persons, that means that a fall in BMR represents a significant adaptive response through increased efficiency of energy use making weight loss progressively more difficult.
Researchers at the US National Institute of Health have developed a very detailed mathematical model which predicts weight loss based on a wide variety of inputs[3].  The model has been validated against a number of highly controlled weight loss programmes.  Together with researchers based at the USDA and the economics departments of the universities of Florida and Minnesota, they have examined the likely weight loss that would accrue from a tax of 20% (about 0.5 cents per ounce) on sugar sweetened beverages in the US[4].  They concluded that the nutritional input would be a reduction of energy intake of 34-47 kcal per day for adults.  Using the 3,500 kcal rule, an average weight loss of 1.60kg would be predicted for year 1 rising to 8kg in year 5 and to 16kg in year 10.   However, when the dynamic mathematical model is used, the corresponding figures for years 1, 5 and 10 are, respectively, 0.97, 1.78 and 1.84 kg loss.  The % of US citizens that are over-weight is predicted to fall from existing levels of 66.9% over-weight to 51.5% over-weight in 5 years time using the 3,500 kcal rate but using the dynamic mathematical model, the 5-year figure for the over-weight population in the US would be just 62.3%.  Clearly, the continued use of the 3,500 kcal rule in predicting weight loss should cease and the recommendations of the consensus statement of the ASN and ILSI should apply: “Every permanent 10 kcal change in energy intake per day will lead to an eventual weight change of 1lb when the body reaches a new steady state.  It will take nearly a year to achieve 50% and about 3 years to achieve 95%”.
My back of envelope calculations based on the National Adult Nutrition Survey is that extrapolating from the US model (footnote 4), a tax on sugar sweetened beverages might lead to a weight loss of 0.6 lb at the end of year 1. That of course is subject to an error estimate such that it might be higher but equally, it might be lower. Many of the advocates of fat taxes might argue that they will take that “thank you very much” as a start and then move to the next food. But you cannot continue to add tax to the cost of food.

[2] Hall et al (2012) Am J Clin Nutr 12, 989-994
[3] Hall et al (2011) Lancet 378,826-837
[4] Biing-Hwan et al (2011) Econ Hum Biol 9, 329-341

Tuesday, October 30, 2012

Dolly Parton and the art of dieting

Sometime back in the early 1990s or thereabouts, Dolly Parton was being interviewed by the famous BBC chat show host, Michael Parkinson. When asked about what diet she used to keep her figure, she replied: “Honey, if you want to lose weight, get your head out of the slop bucket”.  In other word, just eat less. No truer words were ever uttered in the vast realm of advice on dieting. This year we have seen a number of scientific papers published on sugar sweetened beverages, some designed to boost weight gain and some designed to induce weight loss, all adding to the belief that sugar sweetened beverages are both the cause and the cure for modern obesity. A recent paper from the Department of Nutrition at Harvard will help put things in perspective, but only for those wishing to have an accurate perspective.

The first [1] of the sugar papers looked at four groups each given 1-liter of a beverage per day for 6 months. Group 1 receiver a liter of regular sugar sweetened Coke. Group 2 were given a liter of semi-skimmed milk with an approximate equal calorie level to the Coke. Groups 3 and 4 respectively received 1 liter of diet Coke or water. According to the authors, the consumption of the energy-containing beverages led to a compensation effect with a reduction in the intake of other foods and no overall change in energy intake. No dietary data are provided in the paper but 1 liter of regular Coke would have diluted out its equivalent caloric value from all other foods, leading to a reduction in the intake of the latter by 430 calories per day. This Coke group showed a significant accumulation of fat in the liver compared to others but we will never know if it was due to the absurdly high total intake of sugars (about double the normal according to my calculations) or to a reduction in the intakes of micro-nutrients associated with 430 less food than normal every day. Coke for example, does not contain, the B-vitamin riboflavin, but low riboflavin status will lead to increased blood pressure, and the authors did see a rise in blood pressure with regular Coke. 

So, 1 liter of Coke per day did not lead to weight gain ( for example a 1.3% gain with Coke and a 0.8% gain with water). However, two studies reported in the New England Journal of Medicine show that if sugar sweetened beverages in children are replaced with a calorie free version, then weight loss does occur [2]. These studies will be widely cited as evidence that sugary drinks cause obesity. In fact, these studies simply show that if you do as Dolly Parton says, and simply eat less, you will lose weight so the weight loss could have been with any caloric source, not just sugar-sweetened beverages.

Which brings me to the Harvard paper [3]. This study (a subset of a larger dietary intervention) looked at how variation in the distribution of calories in a weight loss regimen influenced weight change and also changes in body composition. Four dietary treatments were used and an energy deficit of 750 kcal per day was the target for each participant. The diets varied the level of fat, protein and carbohydrate. At 6 months, the average amount of fat lost was 4.2 kg and the loss of lean tissue was 2.1 kg.  About half of this fat loss was due to loss of fat from the abdominal fat with about a third lost from subcutaneous fat. Only 0.1 kg of fat was lost from the liver but this represented a loss of 16% of liver fat. There were no differences in any of these measures according to the composition of the weight reduction diets, again, upholding the Dolly Parton rule.

In summary, the first study tells us that if you oblige subjects to eat a 1-liter bottle of regular Coke every day, you won’t gain weight because you reduce your intake of other foods keeping energy intake constant. The second tells us that extracting calories from children’s diets will lead to a weight loss, in this case using sugar sweetened beverages as the target food. The third tells us that Dolly Parton was correct. It really doesn’t matter what the composition of your weight reducing diet is so long as the caloric restriction operates.

So for what its worth, here are my basic rules about successful dieting:

1.      Never start a diet until you have though about it long and hard given that the relapse rate of weight loss is so high.
2.      Never start a diet until you have built physical activity into your daily routine. Physical activity will reverse the negative effects of obesity such as poor glucose management, higher blood pressure and elevated blood lipids.
3.      Don’t diet on your own. Join a weight loss group and get the benefit of the social network of dieting and maintaining weight loss. 
4.      Heed Dolly Parton and just eat less and eat according to your preferences

[1] Maersk M et al (2012) Amer J Clin Nutr 95 (2) 283
[2] de Ruyter et al (2012) New Engl J Ned 367 (15) 1397
[3] de Souza RJ et al (2012) Amer J Clin Nutr 95 614