Impaired Glucose Tolerance in Sleep Disorders

BACKGROUND: Recent epidemiological and experimental data suggest a negative influence of shortened or disturbed night sleep on glucose tolerance. Due to the high prevalence of sleep disorders this might be a major health issue. However, no comparative studies of carbohydrate metabolism have been conducted in clinical sleep disorders. METHODOLOGY/PRINCIPAL FINDINGS: We performed oral glucose tolerance tests (OGTT) and assessed additional parameters of carbohydrate metabolism in patients suffering from obstructive sleep apnea syndrome (OSAS, N = 25), restless legs syndrome (RLS, N = 18) or primary insomnia (N = 21), and in healthy controls (N = 33). Compared to controls, increased rates of impaired glucose tolerance were found in OSAS (OR: 4.9) and RLS (OR: 4.7) patients, but not in primary insomnia patients (OR: 1.6). In addition, HbA1c values were significantly increased in the same two patient groups. Significant positive correlations were found between 2-h plasma glucose values measured during the OGTT and the apnea-arousal-index in OSAS (r = 0.56; p<0.05) and the periodic leg movement-arousal-index in RLS (r = 0.56, p<0.05), respectively. Sleep duration and other quantitative aspects of sleep were similar between patient groups. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that some, but not all sleep disorders considerably compromise glucose metabolism. Repeated arousals during sleep might be a pivotal causative factor deserving further experimental investigations to reveal potential novel targets for the prevention of metabolic diseases

Baseline Characteristics of Study Participants.

<p>Data are mean (SD). Statistical comparison was done using Gabriel- or Games-Howell-corrected oneway ANOVA.</p><p>OSAS, Obstructive sleep apnea syndrome; RLS, Restless legs syndrome; INS, Insomnia; CON, controls; BMI, Body mass index; PSQI, Pittsburgh Sleep Quality Index; ESS, Epworth Sleepiness Scale.</p><p>* p<0.05, † p<0.01, ‡ p<0.001, vs controls.</p><p>⁺ p<0.05, □ p<0.01, ∇ p<0.001, between groups.</p><p>OSAS: χ² (1) = 18.21, p<0.001; RLS: χ² (1) = 0.433, p>0.05; INS: χ² (1) = 0.163, p>0.05, vs controls.</p

Frequency of Patients with Normal or Elevated HbA1c (≥5.5%) & FPG (≥100mg/dl).

<p>OSAS, Obstructive sleep apnea syndrome; RLS, Restless legs syndrome; INS, Insomnia; CON, controls; FPG = Fasting plasma glucose.</p><p>χ² (3) = 25·31, p<0·001.</p

Frequency of Patients with Normal Glucose Tolerance or Impaired Glucose Tolerance.

<p>Normal Glucose Tolerance: 2h-PG≤140 mg/dl; Impaired Glucose Tolerance: 2h-PG≥140 mg/dl.</p><p>OSAS, Obstructive sleep apnea syndrome; RLS, Restless legs syndrome; INS, Insomnia; CON, controls.</p><p>χ² (3) = 7.95, p<0.05.</p

Metabolic Parameters.

<p>Data are mean (SD). Statistical comparison was done using ANCOVA.</p><p>OSAS, Obstructive sleep apnea syndrome; RLS, Restless legs syndrome; INS, Insomnia; CON, controls; FPG = Fasting plasma glucose; FPI = Fasting plasma insulin; 2h-PG = 2h-Postload glucose; 2h-PI = 2h-Postload insulin; AUCg = Area under the curve for glucose; HOMA1-IR = Homeostasis model assessment-1 of insulin resistance; ISIcomposite = Insulin sensitivity index composite.</p><p>* p<0.05, † p<0.01, ‡ p<0.001.</p

Association between the 2 hour-plasma glucose and the PLMS-arousal-index in restless legs patients.

<p>Pearson's correlation coefficient; r = 0.56, <i>p</i><0.05.</p

Sleep Parameters.

<p>Data are mean (SD). Mean comparison was done using Gabriel- or Games-Howell-corrected oneway ANOVA.</p><p>OSAS, Obstructive sleep apnea syndrome; RLS, Restless legs syndrome; INS, Insomnia; CON, controls; TIB, Time in bed; TST, Total sleep time; SEI, Sleep efficiency; WASO, Wake time after sleep onset; REM, Rapid eye movement sleep; S1, Stage 1 sleep; S2, Stage 2 sleep, SWS, Slow wave sleep; SO, Sleep onset latency; SLREM, REM sleep latency; SLSWS, SWS sleep latency; AHI, Apnea-hypopnea-index; ODI, Oxygen-desaturation-index; PLMS-Index, Periodic leg movements per hour of sleep; PLMS-arousal-index, PLMS associated with arousals per hour of sleep; Apnea-arousal-index, Apneas and/or hypopneas associated with arousals per hour.</p><p>* p<0·05, † p<0·01, ‡ p<0·001.</p

Association between 2 hour-plasma glucose and the oxygen-desaturation-index in obstructive sleep apnea patients.

<p>Partial correlation coefficient (corrected for the BMI); r = 0.59, <i>p</i><0.05.</p