Faculty Bibliography

STUDY OBJECTIVES/OBJECTIVE:The landscape of HIV infection has shifted dramatically over the last few decades. An extended lifespan has led to an increase in comorbidities, including disorders of sleep. While self-reported sleep disturbances in people living with HIV are common, differences in sleep architecture between those living with and without HIV have not been previously described. METHODS:Polysomnography data from the Multicenter AIDS Cohort Study were used to characterize differences in sleep architecture between men living with and without HIV. Parameters assessed included total sleep time, sleep stage distribution, arousal index, and frequency of sleep stage transitions. Multivariable regression was employed to adjust for demographic variables and explore effect modification by sleep-disordered breathing (SDB) severity. RESULTS:Compared to men without HIV (N = 349), men with HIV (N = 447) exhibited comparable total sleep time, but lower sleep efficiency and greater wake time after sleep onset. Independent of HIV status, SDB was associated with a greater percentage of N1 sleep and lower percentages of N2 and REM sleep. However, those with both HIV and severe SDB displayed the lowest sleep efficiency, the highest percentage of N1 sleep, and the lowest frequency of sleep stage transitions from nonrapid eye movement (non-REM)-to-REM sleep compared to all other HIV and SDB subgroups. CONCLUSIONS:This study found an independent association between HIV, SDB, and altered sleep architecture, characterized by lower sleep efficiency, greater time in stage N1 sleep, and higher sleep stage instability. Further research is needed on the potential health implications of disrupted sleep in those with HIV and SDB.

IMPORTANCE/UNASSIGNED:Insomnia and obstructive sleep apnea (OSA) are associated with pregnancy complications. OBJECTIVE/UNASSIGNED:To evaluate the association of insomnia and OSA during pregnancy with the risk of ischemic placental disease (IPD) and severe morbidity (SM) and to compare these risks between the 2 sleep disorders. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cross-sectional study included a statewide population-based sample of liveborn singleton births with linked birth certificates for birthing people and their infants in California from January 1, 2011, through December 31, 2020. The analysis was performed on July 22, 2024. EXPOSURES/UNASSIGNED:Insomnia and OSA. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The main outcomes were IPD, defined as preeclampsia, placental abruption, and birth of a neonate small for gestational age (SGA), and SM, defined according to the Centers for Disease Control and Prevention definition. RESULTS/UNASSIGNED:During the study period, there were 4 145 096 singleton live births among birthing people aged 13 to 55 years; 4783 (0.1%) had insomnia, 5642 (0.1%) had OSA, and 4 134 671 (99.7%) had neither condition. The prevalence of insomnia and OSA was 116 and 136 cases per 1000 live births, respectively. Compared with patients without insomnia or OSA (738 660 [17.9%]), the adjusted relative risk (ARR) of any IPD was 1.42 (95% CI, 1.35-1.50) for those with insomnia (1406 patients [29.4%]) and 1.57 (95% CI, 1.50-1.64) for those with OSA (1848 [32.8%]). Compared with patients with neither disorder, the ARR of birth of an SGA neonate was higher for those with insomnia (1.23; 95% CI, 1.13-1.35) than for those with OSA. The ARR of preterm birth was 1.81 (95% CI, 1.68-1.95) for insomnia (711 patients [14.9%]) and 1.73 (95% CI, 1.62-1.85) for OSA (870 [15.4%]) vs neither disorder (279 364 [6.8%]). The ARR of SM was 2.26 (95% CI, 2.03-2.50) for insomnia (366 patients [7.7%]) and 2.81 (95% CI, 2.58-3.06) for OSA (545 [9.7%]) vs neither disorder (93 857 [2.3%]). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cross-sectional study of singleton live births, pregnant individuals with insomnia or OSA were at increased risk for IPD, SM, and preterm birth compared with those without these sleep disorders. Further study is needed to determine the biological mechanisms for these risks and whether early identification and targeted preventive interventions may improve pregnancy outcomes.

This executive summary highlights evidence-based recommendations for using lifestyle interventions in the treatment and remission of type 2 diabetes (T2D) and prediabetes in adults. The summary and guideline are intended for any clinician or healthcare professional in a community or non-inpatient healthcare setting involved in managing non-pregnant adults with T2D, prediabetes or a history of gestational diabetes mellitus (GDM). The purpose of this executive summary is to provide a succinct overview of the key action statements (recommendations) from Lifestyle Interventions for Treatment and Remission of Type 2 Diabetes and Prediabetes in Adults: A Clinical Practice Guideline from the American College of Lifestyle Medicine. This is the first diabetes guideline to emphasize lifestyle interventions as the foundation of management and is also the first to focus on all six pillars of lifestyle medicine (plant-predomination nutrition, regular physical activity, restorative sleep, stress reduction, social connectedness, and avoiding risky substances), including behavior change strategies. This summary is not intended to substitute for the full guideline, which should be read before taking the recommended actions. The guideline on which this summary is based was developed with a priori methodology that has been previously published, refined, and used in over 20 multidisciplinary, trustworthy, and evidence-based national guidelines. The guideline development group included 20 members representing consumers, advanced practice nursing, cardiology, clinical pharmacology, behavioral medicine, endocrinology, family medicine, lifestyle medicine, nutrition and dietetics, health education, health and wellness coaching, sleep medicine, sports medicine, and obesity medicine. We developed 14 key action statements and associated evidence profiles, each with a distinct quality improvement goal in the context of lifestyle interventions for T2D. Strong recommendations were made regarding advocacy for lifestyle interventions; assessing baseline lifestyle habits; establishing priorities for lifestyle change; prescribing aerobic and muscle strength physical activity; reducing sedentary time; identifying sleep disorders; prescribing nutrition plans for prevention and treatment; promoting peer/familial support and social connections; counseling regarding tobacco, alcohol, and recreational drugs, and establishing a plan for continuity of care. Recommendations were made regarding identifying the need for psychological interventions and for adjusting (deprescribing) pharmacologic therapy. We include numerous tables and figures to facilitate implementation, a plain-language summary for consumers, and an executive summary for clinicians as separate publications. Although not a substitute for the full clinical practice guideline, this executive summary can provide insight into the key guideline recommendations, to whom they apply, and to how they might alter care. These recommendations offer detailed, explicit, and evidence-based strategies for successful lifestyle behavior change, making them relevant not only to our guideline but to other guidelines and standards that advocate for lifestyle change in managing adults with T2D.

STUDY OBJECTIVES/OBJECTIVE:Sex-specific differences in OSA-associated symptoms and polysomnographic findings are well recognized. However, sex differences in intermediate pathways potentially linking OSA and cardiometabolic outcomes are limited. OSA is known to be associated with decreased nitric oxide (NO)-related vasodilation and endothelial dysfunction. The current study sought to characterize the independent association between OSA severity and overnight NO metabolites (i.e. markers of oxidative stress) and determine if there were differences by sex in persons with type 2 diabetes mellitus (T2DM). METHODS:Adults with T2DM and undiagnosed OSA were recruited from the community. Demographic information, an overnight polysomnogram, and pre- and post-sleep plasma samples were collected. The association between OSA and nitrite and nitrate levels were examined using multivariable linear regression. Analyses were done for the entire sample and stratified by sex. RESULTS:The sample included 83 participants with 52 % men. Stratified, fully adjusted models showed that compared to women with mild OSA, women with moderate or severe OSA did not exhibit the expected decline in overnight nitrate levels: 4.84 μM (-12.3, 2.7: p = 0.09) and 5.82 μM (-4.7, 16.3: p < 0.01) for moderate and severe OSA, respectively. Overnight nitrate levels decreased in males regardless of OSA severity, without significant differences across severity categories. An interaction between OSA severity and sex was seen for post-sleep nitrates in women with severe OSA. CONCLUSION/CONCLUSIONS:The association between OSA and overnight nitrates varies by sex and OSA severity. Women with severe OSA did not have a decline in overnight nitrate levels whereas men did, suggesting they have higher overnight oxidative stress.

BACKGROUND:Sleep-disordered breathing (SDB) is a known risk factor for hypertension. Despite the well-established link between HIV infection and hypertension, it remains to be determined whether HIV infection modifies the association between SDB and hypertension. SETTING:The Multicenter AIDS Cohort Study. METHODS:SDB was assessed using in-home polysomnography in 779 men (436 with and 343 without HIV). The apnea-hypopnea index (AHI) based on oxyhemoglobin desaturation threshold of ≥3% or arousal (AHI 3a ) and ≥4% (AHI 4 ) along with oxygen desaturation index (ODI) were used to quantify SDB severity. Hypertension was defined as a blood pressure ≥140/90 mm Hg, use of antihypertensive medication, or self-report of a clinical diagnosis. The associations between HIV, SDB, and hypertension were characterized using multivariable logistic regression. RESULTS:The prevalence of hypertension and SDB (AHI 3a ≥ 5 events/hr) was high, with estimates of 53.8% and 82.8%, respectively. Among men without SDB, HIV was independently associated with hypertension, with an adjusted odds ratio (OR) of 3.05 [95% confidence interval (CI): 1.33 to 7.01]. In men without HIV, SDB was associated with hypertension (OR: 2.93; 95% CI: 1.46 to 5.86). No significant increase in the odds of hypertension was noted in men with both HIV and SDB compared with men with either factor alone, with an OR of 3.24 (95% CI: 1.62 to 6.47). These results were consistent across different measures used to define SDB (AHI 3a , AHI 4 , ODI 3 , and ODI 4 ). CONCLUSIONS:Predictors of hypertension differed by HIV status. SDB was associated with hypertension in men without HIV, but not in men with HIV. Among men with HIV, SDB did not affect the odds of hypertension.

Continuous glucose monitors (CGMs) are increasingly used to measure blood glucose levels and provide information about the treatment and management of diabetes. Our motivating study contains CGM data during sleep for 174 study participants with type II diabetes mellitus measured at a 5-min frequency for an average of 10 nights. We aim to quantify the effects of diabetes medications and sleep apnea severity on glucose levels. Statistically, this is an inference question about the association between scalar covariates and functional responses observed at multiple visits (sleep periods). However, many characteristics of the data make analyses difficult, including (1) nonstationary within-period patterns; (2) substantial between-period heterogeneity, non-Gaussianity, and outliers; and (3) large dimensionality due to the number of study participants, sleep periods, and time points. For our analyses, we evaluate and compare two methods: fast univariate inference (FUI) and functional additive mixed models (FAMMs). We extend FUI and introduce a new approach for testing the hypotheses of no effect and time invariance of the covariates. We also highlight areas for further methodological development for FAMM. Our study reveals that (1) biguanide medication and sleep apnea severity significantly affect glucose trajectories during sleep and (2) the estimated effects are time invariant.

BACKGROUND:Glycemic variability is associated with increased risk for cardiovascular disease in patients with type 2 diabetes independent of glycosylated hemoglobin A1c (HbA1c) levels. Given the conflicting evidence on the effect of positive airway pressure (PAP) therapy for OSA on HbA1c, elucidating its effect on glycemic variability has value. RESEARCH QUESTION/OBJECTIVE:Does the use of PAP therapy for OSA improve glycemic variability in patients with type 2 diabetes? STUDY DESIGN AND METHODS/METHODS:A randomized controlled trial was conducted in 184 patients with type 2 diabetes and moderate-to-severe OSA. Participants received either 3 months of PAP therapy with lifestyle counseling or lifestyle counseling alone. End points included the SD of glucose levels along with other metrics derived from continuous glucose monitoring and self-monitoring of blood glucose. RESULTS:No differences were noted in either primary or secondary continuous glucose monitoring end points between the two groups. Average use of PAP therapy was 5.4 h/night (SD, 1.6). Exploratory analyses by sex showed significant differences in the primary and secondary outcomes. In women, PAP therapy was associated with improvement in the SD of glucose levels, with a mean difference in change between intervention and control groups of 3.5 mg/dL (P = .02). PAP therapy was also associated with lower postdinner and bedtime glucose levels: 20.1 mg/dL (P < .01) and 34.6 mg/dL (P < .01), respectively. INTERPRETATION/CONCLUSIONS:PAP therapy did not improve glycemic control or variability in patients with moderate-to-severe OSA and type 2 diabetes. Exploratory analyses suggested that PAP therapy may improve glucose variability in women. Postdinner and bedtime glucose levels were higher in those who did not receive PAP therapy. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov; No.: NCT02454153; URL: www. CLINICALTRIALS/RESULTS:gov.

BACKGROUND:The glucose management indicator (GMI) is an estimated measure of hemoglobin A1c (HbA1c) recommended for the management of persons with diabetes using continuous glucose monitoring (CGM). However, GMI was derived primarily in young adults with type 1 diabetes, and its performance in patients with type 2 diabetes is poorly characterized. METHODS:We conducted a prospective cohort study in 144 adults with obstructive sleep apnea and type 2 diabetes not using insulin (mean age: 59.4 years; 45.1% female). HbA1c was measured at the study screening visit. Participants simultaneously wore 2 CGM sensors (Dexcom G4 and Abbott Libre Pro) for up to 4 weeks (2 weeks at baseline and 2 weeks at the 3-month follow-up visit). GMI was calculated using all available CGM data for each sensor. RESULTS:Median wear time was 27 days (IQR: 23-29) for the Dexcom G4 and 28 days (IQR: 24-29) for the Libre Pro. The mean difference between HbA1c and GMI was small (0.12-0.14 percentage points) (approximately 2 mmol/mol). However, the 2 measures were only moderately correlated (r = 0.68-0.71), and there was substantial variability in GMI at any given value of HbA1c (root mean squared error: 0.66-0.69 percentage points [7 to 8 mmol/mol]). Between 36% and 43% of participants had an absolute difference between HbA1c and GMI ≥0.5 percentage points (≥5 mmol/mol), and 9% to 18% had an absolute difference >1 percentage points (>11 mmol/mol). Discordance was higher in the Libre Pro than the Dexcom G4. CONCLUSIONS:GMI may be an unreliable measure of glycemic control for patients with type 2 diabetes and should be interpreted cautiously in clinical practice.Clinicaltrials.gov Registration Number: NCT02454153.

BACKGROUND:Data on the prevalence of sleep-disordered breathing (SDB) in people with HIV are limited. Moreover, whether the associations between SDB and age or BMI differ by HIV status is unknown. RESEARCH QUESTION/OBJECTIVE:Is SDB more prevalent in men with HIV than those without HIV, and do the predictors of SDB differ between the two groups? STUDY DESIGN AND METHODS/METHODS:). RESULTS:definitions (57.9% vs 50.4%; P = .06). Mild and moderate SDB were more common in men with than without HIV. Associations between SDB prevalence and age, race, and BMI were similar in men with and without HIV. Among men with HIV, viral load, CD4 cell count, and use of antiretroviral medications were not associated with SDB prevalence. INTERPRETATION/CONCLUSIONS:threshold definition. Efforts to diagnose SDB are warranted in those with HIV, given that SDB is associated with daytime sleepiness and impaired quality of life.