Obstructive Sleep Apnea and Glucose Metabolism

University of Missouri-Columbia80 enrolled

Overview

Many adults who are overweight have obstructive sleep apnea (OSA) which disrupts sleep and makes it difficult to breath during the night. OSA increases the risk for a person to become insulin resistant and diabetic. It is not known why OSA causes this problem, i.e., whether it is disrupted sleep or lack of oxygen., which can change how the body handles glucose in adipose tissue, muscle tissue and liver. The purpose of this research study is to determine the key issues and mechanisms responsible for dysregulated glucose metabolism in people with OSA. The investigators will do this by comparing glucose metabolism in people who have OSA, and those who do not, and by evaluating the effect of treating OSA by providing continuous positive airway pressure (CPAP) or simply oxygen during the night. The proposed study will evaluate the primary causes(s) (hypoxia, sleep fragmentation, or both) and pathophysiological mechanisms responsible for the OSA-associated metabolic abnormalities. Knowing the primary cause of Obstructive Sleep Apnea and pathophysiological mechanisms responsible for the OSA-associated metabolic abnormalities could help develop potentially novel therapeutic strategies to provide treatment for adults in improving OSA and associated comorbidities.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Sleep Apnea Glucose Metabolism Disorders

Eligibility

Sex: ALLMin age: 30 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

General Inclusion Criteria (for all subjects): * Age: ≥30 and ≤70 years, * BMI: ≥30 and ≤45 kg/m2 or body fat ≥ 30 % for women and ≥ 25 % for men, * Maximum body circumference \<170 cm * Weight stable (≤2% change) * Untrained (≤1 h of structured exercise/wk) for at least 3 months before entering the study * No diabetes (fasting blood glucose \<126 mg/dl, 2h oral glucose tolerance test (OGTT) glucose \<200 mg/dl, HbA1c ≤6.5%) Sleep-related inclusion criteria: Subjects without OSA: * AHI \<5/h of sleep; * Oxygen desaturation index \<3/h * No known sleep disorders and periodic limb movement arousal index \<15/h during polysomnography * Reported sleep duration ≥6 h per night * Regular sleep schedules (i.e. bedtime between 8 pm and 12 am and wake-time between 4 am and 8 am on all days of the week) Subjects with OSA * AHI ≥10/h of sleep (i.e., moderate to severe OSA) * Oxygen desaturation index ≥4/h; * No polysomnogram finding that would trigger immediate PAP treatment as per standard operating protocol in our sleep medicine center (a single SaO2 \<50%, SaO2 \<70% for \>2 minutes, electrocardiogram pause \>5 sec, or ventricular tachycardia \>30 sec), because of the risk of a potentially adverse outcome if they are not randomized to the PAP group * Periodic limb movement arousal index \<15/h during polysomnography, * Reported sleep duration ≥6 h per night, * Regular night-time sleep schedules, defined as bedtime between 8 pm and 12 am and wake-time between 4 am and 8 am on all days of the week. General Exclusion Criteria (for all subjects): * Current treatment for previously diagnosed OSA; * Self-reported severe difficulty sleeping in unfamiliar environments; * Metal implants that are incompatible with magnetic resonance imaging; * Controlled substances, tobacco products, dietary supplements, or medications known or suspected to affect sleep, breathing, upper airway muscle physiology, or glucose metabolism * Evidence of disease (e.g., diabetes, congestive heart failure; chronic obstructive pulmonary disease; hypoventilation, defined as daytime partial pressure of carbon dioxide (pCO2) \>45 mm Hg; major neurological or neuromuscular disorders; cancer; uncontrolled hypertension; etc.); * Contraindications to supplemental oxygen or PAP (e.g., recent trans-sphenoidal surgery). * Unwillingness or inability to provide informed consent * Study physician considers subject to be unable to safely complete the study protocol

Outcomes

Primary Outcomes

Insulin mediated glucose disposal

The hyperinsulinemic-euglycemic clamp technique combined with isotope-labelled tracer infusions will be used to assess insulin mediated glucose rate of disappearance before and after treatment of OSA with three months of night-time supplemental oxygen, PAP, or sham.

Time frame: 3 months

Secondary Outcomes

β-cell function

β-cell responsivity to glucose and the disposition index will be determined to characterize the insulin secretory response to glucose infusion and the relationship between insulin secretion and insulin sensitivity. This outcome will be determined by using an insulin-modified intravenous glucose tolerance test in conjunction with mathematical modelling and insulin sensitivity data from the hyperinsulinemic clamp.

Time frame: 3 months

Tissue oxygenation

Adipose and muscle tissue oxygenation, expressed as mmHg, will be evaluated in situ during the hyperinsulinemic-euglycemic clamp studies.

Time frame: 3 months

Body composition analysis

Detailed body composition analysis using dual energy x-ray absorptiometry (DXA) will provide the researchers with total and appendicular lean body and fat mass, expressed in grams of participants.

Time frame: 3 months

Obstructive Sleep Apnea and Glucose Metabolism

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes