WEIGHT LOSS AND DIABETES RISK

Intentional loss of a median of just 13% of body weight reduces the relative risk of developing type 2 diabetes by around 40% in people with obesity, among many other health benefits, shows a large real-world study in half a million adults.

Other findings associated with the same modest weight loss included a reduction in the risk of sleep apnea by 22%-27%, hypertension by 18%-25%, and dyslipidemia by 20%-22%.

Christiane Haase, PhD, Novo Nordisk, Denmark, led the work, and spoke to Medscape Medical News, together with Nick Finer, MD, senior principal clinical scientist, Novo Nordisk.

"This is powerful evidence to say it is worthwhile to help people lose weight and that it is hugely beneficial. These are not small effects, and they show that weight loss has a huge impact on health. It's extraordinary," Finer asserted.

"These data show that if we treat obesity first, rather than the complications, we actually get big results in terms of health. This really should be a game-changer for those health care systems that are still prevaricating about treating obesity seriously," he added.

The size of the study, of over 550,000 UK adults in primary care, makes it unique. In the real-world cohort, people who had lost 10%-25% of their body weight were followed for a mean 8 years to see how this affected their subsequent risk of obesity-related conditions. The results were presented during the virtual European and International Congress on Obesity (ECOICO 2020).

"Weight loss was real-world without any artificial intervention and they experienced a real-life reduction in risk of various obesity-related conditions," Haase told Medscape Medical News. 

Carel le Roux, MD, PhD, from the Diabetes Complications Research Centre, University College Dublin, Ireland, welcomed the study because he says it shows those with obesity who maintained more than 10% weight loss experienced a significant reduction in the complications of obesity.

"In the study, intentional weight loss was achieved using mainly diets and exercise, but also some medications and surgical treatments. However, it did not matter how patients were able to maintain the 10% or more weight loss as regards the positive impact on complications of obesity," he highlighted.

From a clinician standpoint, "it helps to consider all the weight loss options available, but also for those who are not able to achieve weight loss maintenance, to escalate treatment. This is now possible as we gain access to more effective treatments," he added.

Also commenting on the findings, Matt Petersen, vice president of medical information and professional engagement at the American Diabetes Association, said: "It's helpful to have further evidence that weight loss reduces risk for type 2 diabetes."

However, "Finding effective strategies to achieve and maintain long-term weight loss and maintenance remains a significant challenge," he 

Large Database of Half a Million People With Obesity

For the research, anonymized data from over half a million patients documented in the Clinical Practice Research Datalink (CPRD) database, which holds information from 674 general practices in the UK, were linked to Hospital Episode Statistics and prescribing data to determine comorbidity outcomes.

At baseline, characteristics for the full study population included a median age of 54, around 50% of participants had hypertension, around 40% had dyslipidemia, and around 20% had type 2 diabetes. Less than 10% had sleep apnea, hip/knee osteoarthritis, or history of cardiovascular disease. All participants had a body mass index of 25.0–50.0 kg/m² at the start of the follow-up, between January 2001 and December 2010.

Patients may have been advised to lose weight, or take more exercise, or have been referred to a dietician. Some had been prescribed antiobesity medications available between 2001-2010. (Novo Nordisk medications for obesity were unavailable during this period.) Less than 1% had been referred for bariatric surgery.

"This is typical of real-world management of obesity," Haase pointed out.

Participants were divided into two categories based on their weight pattern during the 4-year period: one whose weight remained stable (492,380 individuals with BMI change within –5% to +5%) and one who lost weight (60,573 with BMI change –10% to –25%).

The median change in BMI in the weight-loss group was –13%. The researchers also extracted information on weight loss interventions and dietary advice to confirm intention to lose weight.

The benefits of losing 13% of body weight were then determined for three risk profiles: BMI reduction from 34.5 to 30 kg/m² (obesity class I level); 40.3 to 35 kg/m² (obesity class II level), and 46 to 40 kg/m² (obesity class III level).

Individuals with a baseline history of any particular outcome were excluded from the risk analysis for that same outcome. All analyses were adjusted for BMI, age, gender, smoking status, and baseline comorbidities.

Study strengths include the large number of participants and the relatively long follow-up period. But the observational nature of the study limits the ability to know the ways in which the participants who lost weight may have differed from those who maintained or gained weight, the authors said.

Type 2 Diabetes, Sleep Apnea Showed Greatest Risk Reductions

The researchers looked at the risk reduction for various comorbidities after weight loss compared to before weight loss. They also examined the risk reductions after weight loss compared to someone who had always had a median 13% lower weight.

Effectively, the analysis provided a measure of the effect of risk reduction due to weight loss compared to having that lower weight as a stable weight.

"The analysis asks if the person's risk was reversed by the weight loss to the risk associated with that of the lower weight level," explained Haase.

"We found that the risks of type 2 diabetes, dyslipidemia, and hypertension were reversed while the risk of sleep apnea and hip/knee osteoarthritis showed some residual risk," she added.

With sleep apnea there was a risk reduction of up to 27% (compared to before weight loss).

"This is a condition that can't be easily reversed except with mechanical sleeping devices and it is under-recognized and causes a lot of distress. There's actually a link between sleep apnea, diabetes, and hypertension in a two-way connection," noted Finer, who is also honorary professor of cardiovascular medicine at University College, London, UK.

"A reduction of this proportion is impressive," he stressed.

Dyslipidemia, hypertension, and type 2 diabetes are well-known cardiovascular risk factors. "We did not see any impact on myocardial infarction," which "might be due to length of follow-up," noted Haase.

Response of Type 2 Diabetes to Weight Loss

Most patients in the study did not have type 2 diabetes at baseline, and Finer commented on how weight loss might affect type 2 diabetes risk.

"The complications of obesity resolve with weight loss at different speeds," he said.

"Type 2 diabetes is very sensitive to weight loss and improvements are obvious in weeks to months."

In contrast, reductions in risk of obstructive sleep apnea "take longer and might depend on the amount of weight lost." And with osteoarthritis, "It's hard to show improvement with weight loss because irreparable damage has [already] been done," he explained.

The degree of improvement in diabetes due to weight loss is partly dependent on how long the person has had diabetes, Finer further explained. "If someone has less excess weight then the diabetes might have had a shorter duration and therefore response might be greater."

Lucy Chambers, PhD, head of research communications at Diabetes UK, said: "We've known for a long time that carrying extra weight can increase your risk of developing type 2 diabetes, and this new study adds to the extensive body of evidence showing that losing some of this weight is associated with reduced risk." 

She acknowledged, however, that losing weight is difficult and that support is important: "We need government to urgently review provision of weight management services and take action to address the barriers to accessing them."

Finer and Haase are both employees of Novo Nordisk. Le Roux has reported no relevant financial relationships.

ECOICO 2020. Presented September 1-4, 2020. Abstract 0497.

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