Embracing complexity – nutrition and type 2 diabetes
What should people eat to manage or prevent type 2 diabetes? The complexity of food has led to confusion over what is healthy, unhealthy or optimal among healthcare professionals and the public alike. However, new nutritional research is beginning to cut through this confusion and show the way forward. Professor Nita Forouhi, from the MRC Epidemiology Unit at the University of Cambridge, reviews some hot topics in nutrition, obesity and type 2 diabetes in a recent Diabetologia article. Dr Susan Aldridge reports.
Diet is a key modifiable factor in the prevention and management of type 2 diabetes. There are three lines of evidence supporting this. First, medical nutrition therapy in type 2 diabetes can achieve glycaemic control as good as (or even better than) glucose-lowering medication. Second, type 2 diabetes can be delayed or prevented in those with non-diabetic hyperglycaemia by intensive lifestyle intervention, including dietary changes. Proof of principle of this approach was established in the early 2000s and it is now widely used in the NHS. Finally, we know from the DiRECT trials that type 2 diabetes can be put into remission with a very low-calorie diet. This work has led to a new understanding of the pathophysiology of the condition, with a focus on liver and pancreatic fat, which suggests that it is potentially reversible rather than being lifelong and progressive.
However, defining the optimal diet for type 2 diabetes is challenging, despite a wealth of research and evidence, because there are so many components of food and influences on its consumption. Reviews of the literature have led to dietary guidelines from various organisations, including the American Diabetes Association and Diabetes UK. In a nutshell, a dietary pattern that reduces the risk of type 2 diabetes and helps to manage the condition includes regular consumption of vegetables, fruits, legumes, wholegrains, nuts and cereal fibre, and dairy products, such as yogurt. In contrast, dietary patterns including regular consumption of processed and unprocessed red meat, refined grains and sugar-sweetened beverages increase the risk of type 2 diabetes. Thus, rather than ‘everything in moderation’, consumption of some foods should be promoted, while others should be avoided.
Weight loss and nutrition
The proof of principle of remission of type 2 diabetes through weight loss actually comes from bariatric surgery. However, this approach isn’t suitable for everyone and, given the high prevalence of the condition, it isn’t practical on such a large scale. This means turning to a dietary approach, such as that used in the DiRECT research. In these trials, involving a very low-calorie diet, the greater the weight loss, the greater the chance of remission. And the effects are durable with 36% of participants still being in sustained remission after two years.
Further research into the longer term impact of DiRECT is awaited, but the evidence thus far does justify the use of this approach in primary care. Endorsing this approach, the UK’s NHS is rolling out a 12-week intervention through general practices consisting of a low-energy meal-replacement diet for people with type 2 diabetes and overweight.
It’s not just the calorie content of foods that matters. Traditional dietary guidance is very much focused on macronutrient composition, recommending consumption of less than 30-35% energy from fat, 45-55% from carbohydrate and the rest from protein. Low-fat diets were long favoured for weight loss because of the higher energy density of fat compared with carbohydrates, but there has recently been more interest in low-carbohydrate diets. Both low-fat and low-carb diets can be effective for weight loss, the challenge being in adherence to them and weight maintenance in the long term.
There has been less research on the role of protein intake in weight loss. Higher protein intake after weight loss has been shown to result in less weight regain because of increased satiety. And a trial comparing different combinations of protein and glycaemic index (GI) for early weight-loss maintenance found that a modest increase in protein and lower GI led to less weight regain than a diet lower in protein and higher GI.
Evidence for long-term weight loss maintenance, which is crucial for prevention and management of type 2 diabetes, is sparse. According to the National Weight Loss Registry, maintenance over 10 years was related to low-fat-based energy restraint combined with physical activity. Clearly further research is needed to uncover the best evidence-based strategies for losing weight and, more importantly, keeping it off.
The focus on energy and macronutrients, described above, is rooted in two different pathways linking nutrition to obesity and type 2 diabetes. In the energy balance model, weight gain occurs when energy intake exceeds energy expenditure. The ability of a low-calorie diet to induce weight loss and type 2 remission supports this view, in which all calories are the same, regardless of their food source.
In contrast, there is the ‘carbohydrate-insulin’ model, where obesity is the cause rather than the consequence of excess calorie intake. Here, recent increases in the consumption of processed, high-glycaemic-load carbohydrates produce hyperinsulinaemia, promoting glucose uptake into tissues, suppressing release of fatty acid from adipose tissue and stimulating fat and glycogen storage. Thus, there is less energy available for use by the rest of the body, which drives hunger and overeating.
Debate between these two views continues, but it is increasingly clear that a focus upon energy intake alone does not take into account the impact of diet quality on long-term weight gain and type 2 diabetes. This occurs through many physiological processes – diet-induced thermogenesis, brain reward, appetite, hunger, satiety, digestion, hormone release and action and the gut microbiome.
Low-carb for glycaemic control
In recent years, research has suggested that the low-carb approach not only reduces weight, but also reduces HbA1c by a mean of 11 mmol/mol, although some studies are thought to be flawed. The UK’s Scientific Advisory Committee on Nutrition has looked at the evidence, including 48 randomised controlled trials from eight systematic reviews. This concluded that lower carbohydrate diets are more effective for glycaemic control compared with higher carbohydrate diets. They led to a greater mean reduction in HbA1c of 4.7 mmol/mol in the short term (three to six months), but this benefit was not maintained at 12 months.
It is difficult to draw firm conclusions on the low-carb approach for glycaemic control. First, definitions of a low-carb diet vary, ranging from moderate carbohydrate restriction to very low-carb or ketogenic diets. Across randomised controlled trials, carbohydrate intakes vary widely, from 14% to 50% of energy intake. Second, in the case of comparing diets of equal energy (isoenergetic) intake, if energy intake is kept the same, then the lower carbohydrate diets must be higher in fat. However, some studies do not have an isoenergetic study arm, so it’s hard to know whether changes in glycaemic changes arise from lower carbohydrate intake or from changes in weight due to different energy intakes.
Nutrient type, quality and source
The type and quality of nutrients are as important as the quantity consumed. Foods are complex mixtures of thousands of different components with different properties and health effects. For instance, there is a wealth of evidence distinguishing between the health impact of saturated, polyunsaturated and monounsaturated fats. We see this with different foods that are rich in saturated fats. Research has shown that people eating more saturated fats from red meat and butter were more likely to develop coronary heart disease than those who ate more saturated fats from cheese, yogurt and fish.
And all carbohydrates are not equal – there is sugar, starch and fibre, wholegrain and refined grain, low and high-GI and glycaemic load (GL). There is substantial evidence on the beneficial impact of fibre and wholegrain on prevention of type 2 diabetes, although the evidence for GI and GL is less convincing. Professor Forouhi’s take-home message on this is that multiple aspects of carbohydrate quality are relevant to a healthy diet and that fibre, wholegrain and GI and GL values are likely to be highly correlated. So always consider food sources together with the macronutrients they contain, rather than the macronutrients in isolation.
Highly processed and ultra-processed foods of both plant and animal origin are increasingly consumed globally and have been associated with a number of adverse health effects. One randomised controlled trial involving 20 participants compared ad libitum consumption of ultra-processed foods with unprocessed foods for all meals for 28 days. Consumption of the former led to greater energy intake of 500 calories a day and weight gain. Longer term prospective studies suggest an association between consumption of ultra-processed food and type 2 diabetes. Furthermore, although plant-based diets are generally considered healthy, if they are high in ultra-processed foods or refined carbohydrates, they are also associated with type 2 diabetes.
So appreciating the complexity of diet is key – it is non-binary, unlike tobacco, for which zero consumption is best. Foods are multidimensional and hierarchical in nature. They belong in groups and may be consumed unprocessed or processed. They are best seen as part of overall dietary patterns. So, for example, meat is a small (or non-existent) part of a Mediterranean or vegetarian/vegan diet, but a relatively high proportion of a low-carbohydrate diet. And when less of one food, like meat, is consumed, there will be ‘food substitution’ as the consumption of other foods increases.
Research into diet is usually done using food-frequency questionnaires or dietary recall, which are subject to recall bias. Despite these drawbacks, the use of validated dietary instruments with repeat measures does approximate habitual diet. Digital technologies, such as smartphone apps, cameras for food imaging and wearable devices, are coming but their validity and reliability for research have not yet been established. A promising new approach is the use of objective biomarkers of dietary intake, such as plasma vitamin C and carotenoids for intake of fruit and vegetables.
The randomised controlled trial (RCT) is the gold standard for evidence-based medicine, but diet is a complex, behavioural exposure that is difficult to test in a RCT. Dietary RCTs are challenging because they lack blinding and an appropriate control group, as well as having issues with adherence and attrition. It is also hard to pinpoint the effect of specific nutritional components. Most of our evidence base for nutrition and health actually comes from long-term, observational, prospective cohort studies, which have their weaknesses such as confounding and bias, although when carefully conducted they will produce reliable and valid results.
Finally, there are many influences on what we eat that go beyond individual choice and which can’t easily be accounted for in research. For instance, only around 12% of the European population eats the recommended five portions of fruit and vegetables each day. One reason is income – to comply with this advice costs 52%, 18%, 16% and 2% of household income in low, low-to-middle, middle-to-upper and high-income countries respectively. Issues such as availability, access and food security are impacted by events such as Brexit, COVID-19 and the war in Ukraine.
There is increasing interest in the prescription of a healthy diet like the prescription of medication. Such interventions include food prescriptions or provision of tailored groceries, meals or fresh food, which can achieve improvements in HbA1c similar to those seen with glucose-lowering medication. A study of such programmes has shown that an increase of just 0.8 in daily servings of fruit and vegetables can achieve significant reductions in both HbA1c and BMI.
Meanwhile, greater understanding of the link between eating and circadian biology – chronobiology – looks at the impact of timing of food on metabolic health. For instance, the benefits of intermittent fasting and time-restricted eating are becoming apparent, although research directed at type 2 diabetes is needed. And then there’s precision nutrition, which takes dietary guidelines based on population averages and combines them with information from personal, social and environmental factors to target individuals.
In conclusion, although diet and nutrition play a central role in both the management and prevention of type 2 diabetes, the complexity of diet has posed some challenges. The latest research has shifted the focus from the quantity of isolated nutrients to nutrient quality, food sources and overall dietary patterns. Future directions listed in this paper include integration of nutrition education into medical training and looking at nutritional research in low to middle-income countries, as most is confined to European populations. Many more ideas for new research are listed in Professor Forouhi’s review, which should give much ‘food for thought’ among healthcare professionals and those with, or at risk of, type 2 diabetes.
To read this paper go to: Forouhi NG. Embracing complexity: making sense of diet, nutrition, obesity and type 2 diabetes. Diabetologia online 14 February 2023. https://doi.org/10.1007/s00125-023-05873-z
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Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.