In this largest randomized controlled trial on the effects of weight loss on OSA, weight loss produced by an ILI Significantly improved OSA as measured by AHI. The intervention was most effective for men and for participants with higher baseline values of AHI. The observed reduction in AHI associated with weight loss was less than the results of uncontrolled studies of AHI after weight loss4
but similar to those of a recent controlled trial of mild apnea.5
These mean changes in AHI obscure important clinical changes that occurred with weight loss. It is notable that more than 3 times as many participants in the ILI group than in the DSE group had total remission of their OSA, and the prevalence of severe OSA among the ILI participants decreased to half that among the DSE participants. These decreases in the presence and/or the severity of OSA among obese patients who have type 2 diabetes are likely to confer significant benefit.18
There is emerging evidence that any reduction in AHI appears to be associated with a decrease in cardiovascular risk. A recent observational study revealed that men with untreated severe OSA (AHI, >30 events per hour) experienced a significantly greater incidence of fatal and nonfatal cardiovascular events compared with age- and BMI-matched healthy men.19
A prospective analysis from the Wisconsin Sleep Cohort found a dose-response association between the AHI at baseline and the presence of hypertension 4 years later that was independent of known confounding factors, including BMI.20
Also, an observational cohort study demonstrated that there was an association between increased severity of OSA and increased risk of stroke or death from any cause and that the association between AHI and these outcomes was independent of other cardiovascular and cerebrovascular risk factors, including hypertension.21
These latter findings are supported by the cross-sectional results of the Sleep Heart Health Study, showing that the risk of stroke increases progressively with increasing AHI.22
Collectively, these data suggest that the alleviation or mitigation of OSA severity associated with the weight reduction achieved by participants in our study will, if sustained, decrease exposure to the medical risks of OSA as well as reduce health care use and economic costs.23,24
The second principal finding of our study was that initial AHI and weight loss were the strongest predictors of change in AHI. Although statistically significant, the effect of each variable was modest. Each additional higher value of baseline AHI was associated with a 0.3 decrease in subsequent AHI, while each kilogram of weight loss was associated with a decrease in AHI of 0.6 events per hour. The subset of ILI participants who lost 10 kg or more experienced a reduction in AHI of 11.3 events per hour, a reduction that was significantly greater than all other weight change categories. Given the strong cross-sectional relationships among neck and waist circumference and AHI,25-27
it is somewhat surprising that changes in neck and waist circumference were not more related to changes in AHI. The absence of this association was likely because weight loss and reductions in neck and waist circumferences were highly correlated and because the changes in overall weight were reflected in changes in waist and neck circumference.
The third principal set of findings is cause for concern. The DSE group, which was weight stable (-0.6 kg) over 1 year, had a mean increase in AHI of 4 events per hour, a statistically significant difference. Therefore, the DSE participants had moderate OSA (AHI, 24) at baseline, but their OSA deteriorated to approach the severe category (AHI, 28) over 1 year, even with no weight gain. This finding suggests that untreated OSA in this age group has a relatively rapid natural progression, increasing 4 events per hour in just 1 year. A planned 4-year assessment of this cohort will ascertain whether this progression continues to worsen. It is also troubling that so few participants (ie, 5%) were receiving CPAP therapy at 1 year. The high prevalence of OSA in these obese adults with type 2 diabetes, the rapid progression of untreated OSA in this cohort, and the paucity of CPAP use 1 year after participants and their providers were informed of the diagnosis mean that this patient subset is at greater risk of the adverse consequences of OSA, such as hypertension,20
impaired quality of life,28
This increased risk for adverse consequences of OSA is especially significant for these participants, who are already at greater risk for untoward consequences based on their obesity and type 2 diabetes.
This randomized controlled trial on the effects of weight loss on sleep apnea had several strengths compared with prior studies, including a larger sample of both men and women. Our study also followed up participants for a full year, longer than many previous studies. Our study has several important limitations. The results should not be generalized to younger patients, to patients without type 2 diabetes, or to patients with milder degrees of OSA. Similarly designed randomized controlled trials are needed to assess the effects of weight loss on OSA in these groups. Future studies should also explore the reasons for these improvements in OSA (eg, mechanical, metabolic, and hormonal).
In conclusion, weight loss produced through an ILI significantly improved OSA among obese participants with type 2 diabetes. The greatest benefit was observed in men, in participants with more severe OSA at baseline, and in participants who lost the most weight. The significant increase in AHI over 1 year in participants who were weight stable suggests that OSA is a rapidly progressing syndrome that will worsen without treatment in middle-aged obese adults with type 2 diabetes.