Male Gender Aggravates Insomnia-Associated Disturbances in IPGTT, Insulin Level and Insulin Resistance, with Less Improvement on Retrieval of Normal Sleep Compared to Aged Females
Authors: Hamid Gehad Salah Abd El , Gamil Nehal Mohamed Bhgat , Nassef Noha Abdel - Aziz , Hassan Ghida Mohamed , Sabry Yasmine Gamal , Khalaf Megahed Gehan 
Published: November 2024

Abstract

Background and Aim
Prevalence of type 2 diabetes is growing worldwide in the last decades. Recent studies showed that sleeping hours had decreased in the last decades amongst both young and aged population. This study was conducted to investigate the effects of chronic insomnia and its relief on the intraperitoneal glucose tolerance test (IPGTT),insulin level and insulin resistance in aged male and female rats with insight in the underlying mechanisms.

Methods
The study was carried out on 66 local strain aged rats of both sexes. Range of male and female rat weights was 350-400 and 250-350 gm, respectively. Range of ages of male and female rats were 23-25 and 24-26 months, respectively. Rats were allocated into two study groups, males (n°= 32) and females (n°= 34). The male group was further subdivided into the following 4 subgroups: Male one month control group (MC1, n°=7); Male sleep -deprived group for one month (MSD, n°=10); Male two -month control group (MC2, n°=7); Male sleep deprived group for one month followed by one month reversion to regular sleep (MSDR, n°=8). The female group was further subdivided into 4 subgroups; Female one month control group (FC1, n°=9); Female sleep deprived group for one month (FSD, n°=7); Female two -month control group (FC2, n°=9); Female sleep deprived group for one month followed by one month reversion to regular sleep (FSDR, n°=9). The experimental method of sleep restriction was the modified multiple platform method (MMPM) which deprives the animal from rapid eye movement (REM) sleep, while the non-REM sleep unaffected without the need for monitoring the EEG. The study duration was 2 months, Rats were assessed for IPGTT, fasting serum insulin (FSI) and homeostasis model assessment of insulin resistance (HOMA-IR) as well as serum levels of corticosterone (Cs) and melatonin (Mt).

Results
After one month of insomnia, male rats (MSD) became prediabetic with fasting hyperglycemia (FBG 107 mg/dl) and significantly elevated blood glucose values in the IPGTT and area under the curve (AUC), FSI and HOMA-IR as well as Cs and significant decrease of Mt. compared to their matched controls (MC1). Reversion to normal sleep normalized the FBG of MSDR group and blood glucose levels at 30, 90, 120 minutes and area under the curve (AUC), with significant decrease of FSI and HOMA-IR, although not yet normalized compared to MC2 rat group. Similarly, Cs and Mt. levels showed partial improvement compared to MSD group, but not fully normalized compared to MC2 group. On the other hand, FSD rat group had no significant change in their FBG compared to FC1 group but had significant increase in their blood glucose levels at 60, 90, 120 min., AUC of IPGTT as well as FSI and HOMA-IR, Cs and significant decrease of Mt. compared to FC1 group. Reversion to normal sleep normalized IPGTT value of FSDR rats, although FSI and HOMA-IR, remained significantly high compared to FC2 rat group. Similarly, Cs and Mt. levels showed partial improvement compared to FSD group, but not fully normalized compared to FC2 group. When MSD and FSD rat groups were compared, MSD rats showed significantly high FBG and IPGTT values compared to FSD rat group with no significant difference in insulin and insulin resistance values, with significantly higher values of Cs in MSD compared to FSD rat groups, with no significant difference in Mt. levels. Reversion to normal sleep in MSDR and FSDR rats caused more improvement in all values of IPGTT as well as AUC, insulin level and insulin resistance in females (FSDR) compared to males (MSDR) with significantly higher values of Mt in FSDR compared to MSDR rat groups, although Cs.

Conclusion
chronic insomnia has deleterious effects on glucose utilization and insulin resistance in aged male compared to aged female rats with lack of full recovery with reversion to normal sleep in IPGTT parameters, insulin levels and insulin resistance in aged males compared to aged females. These changes can be attributed to the hormonal changes of Cs. and Mt. who showed significant changes in both insomniac male and female rats with better improvement in Mt. in recovered female rat group compared male recovered group. Assessment of sleep history in prediabetic aged males should be recommended as well as assessment of IPGTT and insulin resistance in insomniac aged patients particularly males.