Sleep architecture and glucose and insulin homeostasis in obese adolescents

OBJECTIVE

Sleep deprivation is associated with increased risk of adult type 2 diabetes mellitus (T2DM). It is uncertain whether sleep deprivation and/or altered sleep architecture affects glycemic regulation or insulin sensitivity or secretion. We hypothesized that in obese adolescents, sleep disturbances would associate with altered glucose and insulin homeostasis.

RESEARCH DESIGN AND METHODS

This cross-sectional observational study of 62 obese adolescents took place at the Clinical and Translational Research Center and Sleep Laboratory in a tertiary care children’s hospital. Subjects underwent oral glucose tolerance test (OGTT), anthropometric measurements, overnight polysomnography, and frequently sampled intravenous glucose tolerance test (FSIGT). Hemoglobin A_1c (HbA_1c) and serial insulin and glucose levels were obtained, indices of insulin sensitivity and secretion were calculated, and sleep architecture was assessed. Correlation and regression analyses were performed to assess the association of total sleep and sleep stages with measures of insulin and glucose homeostasis, adjusted for confounding variables.

RESULTS

We found significant U-shaped (quadratic) associations between sleep duration and both HbA_1c and serial glucose levels on OGTT and positive associations between slow-wave sleep (N3) duration and insulin secretory measures, independent of degree of obesity, pubertal stage, sex, and obstructive sleep apnea measures.

CONCLUSIONS

Insufficient and excessive sleep was associated with short-term and long-term hyperglycemia in our obese adolescents. Decreased N3 was associated with decreased insulin secretion. These effects may be related, with reduced insulin secretory capacity leading to hyperglycemia. We speculate that optimizing sleep may stave off the development of T2DM in obese adolescents.Sleep deprivation is endemic; 9.3% of U.S. adults sleep <6 h per night (1), and 75% of high-school seniors report getting insufficient sleep (2). This cumulative societal sleep curtailment is significant, as sleep deprivation is associated with a number of metabolic consequences: increased predisposition to obesity (3) and insulin resistance (IR) (4) in both adults and children, increased risk of type 2 diabetes mellitus (T2DM) in adults (5), and higher fasting glucose in young adults with preexisting diabetes (6). The metabolic consequences of insufficient sleep may be the result of a lack of total sleep or insufficiency of a certain sleep component. The American Academy of Sleep Medicine recognizes four different sleep stages indicated as follows: stage 1 (N1), a brief transition between wake and sleep; stage 2 (N2); stage 3 (N3), “slow-wave” or “deep” sleep; and rapid eye movement (REM) (dream) sleep. In adult studies, cerebral glucose utilization declines (7) and plasma glucose rises (8) in N3 sleep. One pediatric study found a negative association between REM sleep duration and obesity (9), but there is little pediatric data on sleep architecture and glucose and insulin homeostasis. A potential confounding factor is obstructive sleep apnea (OSA), a syndrome more common in obesity in which upper airway obstruction leads to sleep fragmentation and desaturation (10). OSA has been associated with T2DM risk in adults (10) and with IR in children (11,12). We hypothesized that in obese adolescents (who are at risk for T2DM), altered sleep architecture is associated with abnormalities of insulin secretion and sensitivity and of glucose homeostasis independently of confounding factors (e.g., degree of obesity, presence of OSA, sex, and pubertal stage). Therefore, the aim of our study was to investigate the relationship between sleep architecture and insulin secretion and sensitivity and overall glycemia in this population.