Endocrine News focuses on some of the latest obesity-related endocrine research presented at ENDO 2019. From the use of a CPAP machine and the impact of excess weight on migraine headaches to the causal effects of eating late in the day and weight gain, it’s clear that obesity is a risk factor for a variety of comorbidities.
We are, by now, well aware that obesity has extremely deleterious effects on overall health. From causing direct harm on the body to worsening or predisposing to comorbidities, obesity is a serious danger, making weight management counseling an important clinical priority.
Two studies initially presented at ENDO 2019 examine some of the ways that losing weight can improve certain comorbidities; a third, also presented at ENDO 2019, looks at a new risk factor for developing obesity and offers a solution for circumventing it.
Obesity: A Real Headache
In “Effects of Bariatric and Non-Bariatric Weight Loss on Migraine Headache in Obesity. A Systematic Review and Meta-Analysis,” published in the Journal of the Endocrine Society in April, lead study author Claudio Pagano, MD, PhD, an associate professor of internal medicine at the University of Padova in Padova, Italy, and team aimed to tease out whether weight loss improves migraine characteristics like frequency per month, pain severity, duration of attacks, and disability related to headache such as diminished productivity.
“Obesity is associated with a variety of comorbidities, such as cardiovascular disease, diabetes, respiratory complications, and cancer,” Pagano says. “However, mechanisms underlying obesity complications, in particular, chronic low-grade inflammation, are also linked to the development of migraine. Several studies reported that weight excess is associated with increased prevalence of migraine headache and, in addition, with an increased risk of progression to a worse form of headache called chronic migraine.”
The team was also aware that patients with obesity have a greater incidence of migraine than non-obese individuals. “The most striking link is between obesity and migraine characteristics,” Pagano explains. “People with obesity have worse manifestations of migraine such as more days in a month with headache attacks, longer duration, and a deeper impact on their quality of life.”
In their meta-analysis of 473 pediatric and adult patients with migraine from 10 international studies that reported a behavioral or surgical approach to treat obesity, the team found that weight loss significantly improved all parameters of migraine, regardless of both weight at baseline and amount of weight lost. The improvements were also not correlated with how the weight was lost, whether through lifestyle changes or bariatric surgery, and they were seen in both adult and pediatric patients.
“The mechanisms linking obesity, weight loss, and migraine headache remain unclear. They may include alterations in chronic inflammation that characterizes both obesity and migraine, adipocytokines … obesity comorbidities such as obstructive sleep apnea, and other sleep disturbances often affecting obese patients, and behavioral and psychological risk factors.” – Claudio Pagano, MD, PhD, associate professor of internal medicine, University of Padova, Padova, Italy
This finding makes clear that losing even a little bit of weight will have a big impact on the quality of life of a patient with obesity and migraine, but how and why this is so has not yet been established. “The mechanisms linking obesity, weight loss, and migraine headache remain unclear,” Pagano says. “They may include alterations in chronic inflammation that characterizes both obesity and migraine, adipocytokines (namely, resistin, tumor necrosis factor alpha, c-reactive protein, interleukin-6, and adiponectin), obesity comorbidities such as obstructive sleep apnea, and other sleep disturbances often affecting obese patients, and behavioral and psychological risk factors.”
Putting Obesity to Bed
Speaking of obstructive sleep apnea (OSA), Yuanjie Mao, MD, PhD, assistant clinical professor, Ohio University Heritage College of Osteopathic Medicine and medical director, Ohio University Diabetes Institute in Athens, and his team derived their cross-sectional study from their patients themselves. “In patients with obesity, two thirds will have sleep apnea,” Mao says. “Sometimes, we refer these patients to a sleep study and also tell them they might need sleep apnea treatment. The patients always ask us, ‘Do I need to start right now, or can I wait to see if losing weight will help my sleep apnea?’. This was a very common question, so I looked back through the literature to see if I could find an answer for my patients who wanted to avoid the burden of additional treatment.”
The literature, however, was wildly inconsistent. According to a small study and some animal studies, for example, participants with OSA gained weight due to lack of activity during the day as a result of being tired from lack of sleep the previous night. There were also hormonal changes, such as leptin resistance and secretion of ghrelin, both of which cause weight gain, as well as secretion of catecholamines and cortisol. Treating patients with continuous positive airway pressure (CPAP), however, reversed the decreased activity level and the hormonal disruption. On the other hand, a large-scale study demonstrated the opposite — that CPAP caused minor weight gain of a couple of pounds over the course of six months, possibly because, prior to CPAP treatment, they expended more energy in struggling to breathe. Notably, participants in the large-scale study were not on any kind of weight management program.
“There was no data on what happens when a patient is on both a dietary management program and CPAP treatment, so this is why we chose to look at that to see if CPAP treatment would cause weight loss or weight gain,” Mao explains. At their weight loss clinic in Athens, Mao and team started a very strict 16-week weight-loss program for 501 adults with body mass index (BMI) ≥30 but under 50. The diet consisted of a low-calorie (800 kilocalorie/day) meal replacement plus exercise and counseling with nutritionists. They excluded patients with uncontrolled diabetes, thyroid disfunction, acute or chronic active infection, active malignancy, end-organ damage, and those requiring supplemental oxygen. The participants were broken down into three groups based on self-reported OSA symptoms: One asymptomatic group, one group with symptoms but not on treatment, and the third group with symptoms and also on CPAP treatment.
“After the 16-week program, we found that the group on CPAP treatment lost more weight than the other two groups, about 12 kg/26.5 lbs, and the groups not on CPAP lost 8 kg/17.5 lbs to 9 kg 19.8 lbs,” Mao says. “This is the first study that actually showed that simultaneous CPAP treatment and dietary management enhances weight loss. Based on these data, in my approach, I will tell patients to start CPAP treatment immediately because it can actually help your weight loss. Once you have lost weight successfully, then we can reevaluate you to see if you still need CPAP treatment or not.”
“This is the first study that actually showed that simultaneous CPAP treatment and dietary management enhances weight loss. Based on these data, in my approach, I will tell patients to start CPAP treatment immediately because it can actually help your weight loss. Once you have lost weight successfully, then we can reevaluate you to see if you still need CPAP treatment or not.” – Yuanjie Mao, MD, PhD, assistant clinical professor, Ohio University Heritage College of Osteopathic Medicine; medical director, Ohio University Diabetes Institute, Athens, Ohio
Mao says it makes sense to treat both conditions simultaneously as good current practice and also because of the potential for synergistic enhanced effects. In fact, the American Thoracic Society has issued “The Role of Weight Management in the Treatment of Adult Obstructive Sleep Apnea” in 2018, a guideline stating that: “Weight-loss interventions, especially comprehensive lifestyle interventions, are associated with improvements in OSA severity, cardiometabolic comorbidities, and quality of life. The American Thoracic Society recommends that clinicians regularly assess weight and incorporate weight management strategies that are tailored to individual patient preferences into the routine treatment of adult patients with OSA who are overweight or obese.”
The team hopes to do an interventional study as a next step that will have larger statistical power. “For example, we could include one group for whom we start CPAP treatment and weight management right away, and, for another group, we wait until weight loss has occurred to see whether CPAP treatment is still warranted. It’s a very simple, practical question that lots of patients ask and doing this kind of study could help a lot of people,” Mao says.
Early Birds Get the (Leaner) Worms
Adnin Zaman, MD, of the University of Colorado in Denver, Colo., and team wanted to look more closely at the association between delayed eating, sleep timing, and body mass index (BMI) that has been established for at least the last decade. “Few studies have assessed both meal and sleep timing in adults with obesity. We wanted to understand whether temporal feeding and sleep patterns are associated with body composition to help us potentially design novel weight loss interventions,” Zaman explains. “It has been challenging to apply sleep and circadian science to medicine due to a lack of methods for measuring daily, free-living patterns of human behavior. We used a novel set of methods for simultaneous measurement of daily sleep, physical activity, and meal-timing patterns in order to evaluate relationships between these daily behaviors and body weight and fat mass.”
Zaman and team studied 31 healthy adults aged 18–50 years with a BMI 27–45 kg/m2 who were participating in a weight-loss trial either in a group on a reduced-calorie diet (RCD) or on RCD plus time-restricted feeding (TRF). Participants used wearable devices and apps for one week to collect baseline measures of activity, sleep, and energy intake: An accelerometer worn on the thigh monitored physical activity and sedentary behavior (time spent sitting/lying, standing, and stepping); a watch worn on the non-dominant wrist documented free-living sleep/wake patterns by measuring activity and light exposure; an app logged all mealtimes, energy-intake events, and feeding duration; and a continuous glucose monitor on the back of the upper arm measured plasma glucose levels. They also measured body composition, including fat mass, via dual-energy x-ray absorptiometry. The results the team presented at ENDO19 were based on baseline data, but that cohort has now completed the intervention, and a second cohort is underway. “We do not yet have findings to report on the success of the intervention since the study is ongoing,” Zaman says. “However, from this baseline data of cohort 1, we found that those who ate meals later into the day — meaning that the midpoint of their duration of eating was later — also had a later bedtime (though they generally slept for the same amount of time as those who finished eating earlier on). Eating later into the day was also associated with a higher BMI and greater body fat.”
“Evidence suggests that a number of metabolic systems are entrained to circadian rhythms, including hormone, lipid and glucose concentrations, intestinal lipid absorption, and autonomic nervous system activity. Restriction of energy intake to a window of time and, by necessity, the extension of the fasting period may alter diurnal patterns and circadian rhythms in glucose and lipid metabolism in a manner that favors decreased obesity risk.” – Adnin Zaman, MD, University of Colorado, Denver, Colo.
Prior studies have circled around the underlying mechanism for why eating earlier in the day may contribute to leaner body composition. For instance, a few studies have shown that consuming more calories in the morning instead of at night supports weight loss, even if the overall caloric intake and physical activity level is the same. Likewise, food intake at night is linked to obesity regardless of calories consumed. More recently, explains Zaman, “evidence suggests that a number of metabolic systems are entrained to circadian rhythms, including hormone, lipid and glucose concentrations, intestinal lipid absorption, and autonomic nervous system activity. Restriction of energy intake to a window of time and, by necessity, the extension of the fasting period may alter diurnal patterns and circadian rhythms in glucose and lipid metabolism in a manner that favors decreased obesity risk.”
— Horvath is a freelance writer based in Baltimore, Md. She wrote about the effects of ethnicity on women’s health in the September issue.