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

Transcriptomic Characterization of Temperature Stress Responses in Larval Zebrafish

Temperature influences nearly all biochemical, physiological and life history activities of fish, but the molecular mechanisms underlying the temperature acclimation remains largely unknown. Previous studies have identified many temperature-regulated genes in adult tissues; however, the transcriptional responses of fish larvae to temperature stress are not well understood. In this study, we characterized the transcriptional responses in larval zebrafish exposed to cold or heat stress using microarray analysis. In comparison with genes expressed in the control at 28°C, a total of 2680 genes were found to be affected in 96 hpf larvae exposed to cold (16°C) or heat (34°C) for 2 and 48h and most of these genes were expressed in a temperature-specific and temporally regulated manner. Bioinformatic analysis identified multiple temperature-regulated biological processes and pathways. Biological processes overrepresented among the earliest genes induced by temperature stress include regulation of transcription, nucleosome assembly, chromatin organization and protein folding. However, processes such as RNA processing, cellular metal ion homeostasis and protein transport and were enriched in genes up-regulated under cold exposure for 48 h. Pathways such as mTOR signalling, p53 signalling and circadian rhythm were enriched among cold-induced genes, while adipocytokine signalling, protein export and arginine and praline metabolism were enriched among heat-induced genes. Although most of these biological processes and pathways were specifically regulated by cold or heat, common responses to both cold and heat stresses were also found. Thus, these findings provide new interesting clues for elucidation of mechanisms underlying the temperature acclimation in fish

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 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

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

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

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