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CONTEXT: Glucose tolerance during an oral glucose tolerance test (OGTT) is affected by variations in glucose effectiveness (GE) and glucose absorption and thus affects minimal model calculations of insulin sensitivity (SI). The widely used OGTT SI by Dalla Man et al. does not account for variances in GE and glucose absorption. OBJECTIVE: To develop a novel model that concurrently assesses SI, GE, and glucose absorption. DESIGN: Cross-sectional. SETTING: Academic Medical Center. PARTICIPANTS: Eighteen subjects without abnormalities on OGTT (controls) and 88 subjects with diabetes. INTERVENTION: All subjects underwent 75-gram 120-minute 6-timepoint OGTT. MAIN OUTCOMES: SI from the Dalla Man model was validated with the novel model Si using Bland Altman limits of agreement methodology. Comparisons of SI, GE, and gastrointestinal glucose half-life (GIGt1/2); a surrogate measure for glucose absorption were made between subjects with diabetes and controls. RESULTS: In controls and diabetes, the novel model SI was higher than the current OGTT model. SI from both controls (Æ¿=0.90, p < 0.001) and diabetes (Æ¿=0.77, p < 0.001) has high agreement between models. GE was higher in diabetes (median:0.021 1/min, IQR [interquartile range]: 0.020-0.022) compared to controls (median:0.016 1/min, IQR: 0.015-0.017), p = 0.02. GIGt1/2 was shorter in diabetes (median: 48.404â min, IQR: 54.424-39.426) than in controls (median: 55.086â min, IQR: 61.368-48.502) without statistical difference. CONCLUSIONS: Our novel model SI has a good correlation with SI from the widely used Dalla Man's model while concurrently calculating GE and GIGt1/2. Thus, besides estimating SI, our novel model can quantify differences in insulin-independent glucose disposal mechanisms important for diabetes pathophysiology.
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Rationale: Nocturnal hypoxemia is common in sleep-disordered breathing (SDB) and is associated with increased morbidity and mortality. Although impaired diffusing capacity of the lung for carbon monoxide (DlCO) is associated with daytime hypoxemia, its influence on SDB-related nocturnal hypoxemia is not known. Objectives: To characterize the effects of DlCO impairment on SDB-related nocturnal hypoxemia and associated health outcomes. Methods: Data from a multicenter cohort of men with and without human immunodeficiency virus (HIV) infection, with concomitant measures of DlCO and home-based polysomnography (n = 544), were analyzed. Multivariable quantile regression models characterized associations between DlCO and several measures of SDB-related hypoxemia (e.g., total sleep time with oxygen saturation as measured by pulse oximetry [SpO2] < 90% [T90]). Structural equation models were used to assess associations of impaired DlCO and SDB-related hypoxemia measures with prevalent hypertension and type 2 diabetes. Results: DlCO impairment (<80% predicted) was associated with sleep-related hypoxemia. Participants with severe SDB (apnea-hypopnea index ⩾ 30 events/h) and impaired DlCO had higher T90 (median difference, 15.0% [95% confidence interval (CI), 10.3% to 19.7%]) and average SDB-related desaturation (median difference, 1.0 [95% CI, 0.5 to 1.5]) and lower nadir SpO2 (median difference, -8.2% [95% CI, -11.4% to -4.9%]) and average SpO2 during sleep (median difference, -1.1% [95% CI, -2.1% to -0.01%]) than those with severe SDB and preserved DlCO. Higher T90 was associated with higher adjusted odds of prevalent hypertension (odds ratio, 1.39 [95% CI, 1.14 to 1.70]) and type 2 diabetes (odds ratio, 1.25 [95% CI, 1.07 to 1.46]). Conclusions: DlCO impairment in severe SDB was associated with sleep-related hypoxemia, prevalent hypertension, and type 2 diabetes. Assessment of SDB should be considered in those with impaired DlCO to guide testing and risk stratification strategies.
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Infecções por HIV , Hipóxia , Oximetria , Polissonografia , Capacidade de Difusão Pulmonar , Síndromes da Apneia do Sono , Humanos , Masculino , Hipóxia/fisiopatologia , Pessoa de Meia-Idade , Síndromes da Apneia do Sono/fisiopatologia , Síndromes da Apneia do Sono/complicações , Infecções por HIV/complicações , Infecções por HIV/fisiopatologia , Adulto , Saturação de Oxigênio , Hipertensão/fisiopatologia , Hipertensão/complicações , Hipertensão/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Análise Multivariada , Estados Unidos/epidemiologia , Monóxido de Carbono/metabolismoRESUMO
Study Objectives: Although poor sleep quality is associated with lower CD4+â T cell counts among people living with HIV (PLWH), the association between objective sleep metrics and T lymphocyte subset counts is unknown. We evaluated the association between polysomnography (PSG) derived sleep metrics and T lymphocyte subpopulations in a cohort of men living with HIV. Methods: Virally suppressed men living with HIV participating in the Multicenter AIDS Cohort Study underwent home overnight PSG. We assessed the association of PSG parameters with CD4+â and CD8+â T cell counts and the CD4+/CD8+â T cell ratio. Results: Overall, 289 men with mean (±SD) age 55.3â ±â 11.3 years and mean CD4+â T cell count 730â ±â 308 cells/mm3 were evaluated. Total sleep time (TST) was significantly associated with CD8+â but not CD4+â T cell counts. After adjusting for age, race, depressive symptoms, antidepressant use, and non-nucleoside reverse transcriptase inhibitors use, every hour of shorter TST was associated with an additional 33 circulating CD8+â T cells/mm3 (pâ =â 0.05) and a 5.6% (pâ =â 0.0007) decline in CD4+/CD8+â T cell ratio. In adjusted models, every hour of shorter rapid eye movement (REM) sleep was associated with an additional 113 CD8+â T cells/mm3 (pâ =â 0.02) and a 15.1% lower CD4+/CD8+â T cell ratio (pâ =â 0.006). In contrast, measures of sleep efficiency and sleep-disordered breathing were not associated with differences in T lymphocyte subpopulations. Conclusions: Our findings suggest that shorter TST and REM sleep durations are associated with differences in T lymphocyte subpopulations among men living with HIV. Addressing sleep may reflect a novel opportunity to improve immune function in PLWH.
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BACKGROUND: A positive bronchodilator response has been defined as a 12% increase in the forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) from their respective pre-bronchodilator values, combined with at least a 0.2 L absolute change. Recent recommendations suggested the use of the percent change in FEV1 and FVC relative to their predicted normal values without having applied them in patients with airflow obstruction. The aim of the current study was to compare the two approaches over a wide range of pre-bronchodilator FEV1 and FVC values. METHODS: A retrospective review of consecutive patients undergoing spirometry and bronchodilator testing was completed. The change in FEV1 and FVC with a bronchodilator was expressed relative to the pre-bronchodilator and predicted normal FEV1 and FVC. RESULTS: In 1,040 patients with a non-paradoxical change in FEV1, 19.0% had a ≥ 12% change in FEV1 using their pre-bronchodilator value compared to 5.7% using their predicted normal value. For FVC, the respective values were 12.7% vs. 5.8%. The difference was retained in patients with a ≥ 0.2 L change in FEV1 or FVC. In unobstructed patients, the upper threshold (two standard deviations above the mean) of the bronchodilator response was 14% for FEV1 and 10% for FVC using predicted normal values. CONCLUSIONS: Expressing the percent change in FEV1 and FVC relative to predicted normal values reduces the over-estimation of the bronchodilator response, especially in patients with a very low pre-bronchodilator FEV1, including in those with a ≥ 0.2 L change in FEV1. Irrespective of pre-bronchodilator values, a ≥ 14% change in FEV1 and ≥ 10% change in FVC relative to the predicted normal values could be considered a positive bronchodilator response.
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Broncodilatadores , Doença Pulmonar Obstrutiva Crônica , Humanos , Broncodilatadores/farmacologia , Broncodilatadores/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Valores de Referência , Pulmão , Capacidade Vital , Espirometria , Volume Expiratório ForçadoRESUMO
Background: Mild obstructive sleep apnoea (OSA) is a common disorder associated with daytime sleepiness and impaired quality of life. Given that adherence to positive airway pressure (PAP) therapy in OSA is suboptimal, alternative strategies are needed particularly for patients with mild OSA. Daytime neuromuscular electrical stimulation (NMES) of the tongue is a new therapeutic modality for mild OSA. The objective of this study was to determine if patients with mild OSA adhere to daytime NMES. Methods: A randomised, sham-controlled, double-masked controlled trial was conducted in 40 patients with mild OSA who received either high-intensity (active) or low-intensity (sham) NMES for 6â weeks. The primary end-point was adherence to therapy. Exploratory outcomes included the respiratory event index (REI) and the Epworth Sleepiness Scale (ESS) score. Results: More than 90% of participants in each arm were adherent to NMES. Exploratory analyses revealed a 32.7% (95% CI 15.5-49.9%) drop in the REI with active NMES, with no significant change in the REI with sham NMES. Improvements were larger in the supine than non-supine REI. Both the apnoea index and hypopnoea index improved with active NMES. Finally, the ESS score improved with active but not with sham NMES. Conclusions: Daytime NMES was well accepted, with a majority using it for the recommended period. NMES of the tongue use was associated with improvements in OSA severity and daytime sleepiness. Additional research is needed to define its role in the treatment armamentarium across the spectrum of OSA severity and in patients who are intolerant to PAP therapy.