Obstructive Sleep Apnea Severity and the Development of T2D

Treating obstructive sleep apnea can decrease catecholamine, increase insulin sensitivity, and decrease pancreatic beta-cell apoptosis, leading to a lower risk of developing T2D.

Obstructive sleep apnea (OSA) triggers intermittent hypoxemia, followed by the activation of the sympathetic nervous system. The cascade leads to increases in catecholamine, decreases in insulin sensitivity, and increases in pancreatic beta-cell apoptosis. All these processes have been suggested mechanisms for OSA’s association with T2D. Epidemiological research found that between 24%–86% of patients with T2D also have OSA. However, previous studies failed to look at the association between OSA severity and the risk of T2DM. Therefore, the researchers of this study looked at observational studies to determine if an association between both conditions exists.

This research was conducted by performing a systematic review and dose-response meta-analysis. It selected cross-sectional studies, cohort studies, and case-control studies that reported hazard ratio (HR), odds ratio (OR), relative risk (RR), and 95% confidence interval (CI) for the association between OSA and T2D. The research excluded data if a patient had T1D. The apnea-hypopnea index (AHI) and the Respiratory disturbance index (RDI) were used for OSA’s severity. The correlation between the AHI and the risk of T2D was evaluated using a spline model. Heterogeneity was assessed using Q and I2, while bias was evaluated with the Funnel plot and Egger’s and Begg’s texts.

Seven cohort studies, comprising of 15,252 participants, were selected for the meta-analysis. The participants of these studies were all >18 years old. The number of females included in the research varied greatly, ranging from 0 to 54.2%. All seven studies investigated the correlation between mild-dose AHI (5–15) and the risk of developing T2D. In addition, three observational studies examined the effect of moderate-to-severe- dose AHI (>15), and two studies investigated the effect of moderate-dose AHI (15–29).

The prevalence of T2DM in patients with OSA was approximately 15.61% (4.18-40.21%). There were statistically significant differences in the risk of T2D among mild-dose, moderate-to-severe-dose, and zero-dose groups of OSA. Researchers found that mild-dose AHI (OR = 1.23, CI =1.06-1.41, P < 0.05), moderate dose AHI (OR =1.35, CI = 1.13-1.61, P < 0.05), moderate-to-severe-dose AHI (OR = 2.14, 95% CI = 1.72-2.67, P < 0.05), and severe-dose AHI (OR = 2.19 95% CI = 1.30-3.68, P < 0.05) increased the risk of T2DM. There was a higher odds ratio with each increase in the dose of AHI. The spline analysis found that the risk of occurrence of T2D increased with increasing OSA severity. The linear analysis found that the risk of occurrence of T2D increased by 1.62% for each event per hour increase in AHI (OR =1.016, 95% CI =1.009–1.023; P < 0.05).

This meta-analysis found a possible dose-response association between the severity of OSA and the risk of T2DM. All included studies found that OSA was a risk factor for a new incidence of T2D; however, not all OSA subgroups were associated with T2D. Appleton et al. found that only severe-dose AHI was associated with the incidence of diabetes (OR= 2.7, 95% CI= 1.3-5.4). Three studies found that mild-dose AHI was not related to the incidence of diabetes. Marshall et al. found that the moderate dose AHI affected the incidence of T2D (OR= 8.62, CI=1.14-65.2). Limitations of the study include limited sample size, errors from the linear and spline models, and an inconsistent OSA measurement. The association between OSA and T2D suggests sleep disorders trigger insulin resistance and increase oxidative stress. Further studies are needed to evaluate if OSA treatment can decrease T2D risk.

Practice Pearls:

• Obstructive sleep apnea triggers intermittent hypoxemia. This leads to increases in catecholamine, decreases in insulin sensitivity, and increases in pancreatic beta-cell apoptosis. All these factors are suggested mechanisms for OSA’s association with T2D.
• Researchers found that mild-dose AHI, moderate-dose AHI, moderate-to-severe-dose AHI, and severe-dose AHI increased the risk of T2DM. In addition, there was a higher odds ratio with each increase in the dose of AHI.
• This meta-analysis found a possible dose-response association between the severity of OSA and the risk of T2D. However, further studies are needed to evaluate if OSA treatment can decrease T2DM risk.

Xu, C. Liang, and J. Zou, “Interaction between obstructive sleep apnea and short sleep duration on insulin resistance: a large-scale study: OSA, short sleep duration and insulin resistance,” Respiratory Research, vol. 21, no. 1, p. 151, 2020. https://pubmed.ncbi.nlm.nih.gov/32546151/

Yu Z, Cheng JX, Zhang D, Yi F, Ji Q. Association between Obstructive Sleep Apnea and Type 2 Diabetes Mellitus: A Dose-Response Meta-Analysis. Evid Based Complement Alternat Med. 2021 Sep 30;2021:1337118. doi: 10.1155/2021/1337118. PMID: 34630603; PMCID: PMC8497107. https://www.hindawi.com/journals/ecam/2021/1337118/

 Kornelia Ilias, Pharm.D. Candidate, Creighton University School of Pharmacy and Health Professions