Short Sleep Duration and Its Association with Obesity and Other Metabolic Risk Factors in Kuwaiti Urban Adults.

BACKGROUND: Efficient sleep duration and its quality are increasingly recognized as important contributors for maintaining normal body weight. However, lifestyle and social structure within the Arab-gulf region differ compared to those in the western world. This study was specifically conducted in Kuwait's population to investigate the link between sleep quality (SQ) and obesity in the absence of sleep apnea (SA) onset. METHODS: SQ was measured by the Pittsburgh Sleep Quality Index (PQSI) in 984 participants, then verified in 60 individuals including 20 lean (Body mass index/BMI: 18.5-24.9 kg/m2), 20 overweight (BMI: 25-29.9 kg/m2) and 20 obese (BMI: ≥30 kg/m2) through actigraph worn over the right-hip for 7 consecutive days to characterize their sleep-wake cycle, rest-activity, and physical activity. Blood samples were collected for metabolic markers. RESULTS: 59.6% of participants reported a PSQI score higher than 5, with 57.6% of the participants reporting less than 6 hours of sleep per day. The data show that both SQ and sleep duration are considered inadequate in comparison to the international SQ standards. We found a significant association between SQ and obesity independent of age and sex. Actigraph data further supported the independent association of sleep duration on BMI within the population (p < 0.001). Additionally, total sleep time (TST) was found to significantly correlate with several other metabolic factors including diastolic blood pressure, elevated resting heart rate (RHR), triglycerides, total cholesterol, homeostatic model assessment for insulin resistance (HOMA-IR), C-peptide, and C-Reactive Protein (CRP) secretion. Further multiple-regression analysis showed a significant independent association between blood pressure (p < 0.03), HOMA-IR (p < 0.04), and C-peptide (p < 0.3) and sleep duration. CONCLUSION: These findings suggest that sleep deprivation and disturbance could be indirect factors involved in the development of not only obesity in Kuwait but also other metabolic syndromes such as type 2 diabetes.

Repetitive Intermittent Hyperglycemia Drives the M1 Polarization and Inflammatory Responses in THP-1 Macrophages Through the Mechanism Involving the TLR4-IRF5 Pathway.

Repetitive intermittent hyperglycemia (RIH) is an independent risk factor for complications associated with type-2 diabetes (T2D). Glucose fluctuations commonly occur in T2D patients with poor glycemic control or following intensive therapy. Reducing blood glucose as well as glucose fluctuations is critical to the control of T2D and its macro-/microvascular complications. The interferon regulatory factor (IRF)-5 located downstream of the nutrient sensor toll-like receptor (TLR)-4, is emerging as a key metabolic regulator. It remains unclear how glucose fluctuations may alter the IRF5/TLR4 expression and inflammatory responses in monocytes/macrophages. To investigate this, first, we determined IRF5 gene expression by real-time qRT-PCR in the white adipose tissue samples from 39 T2D and 48 nondiabetic individuals. Next, we cultured THP-1 macrophages in hypo- and hyperglycemic conditions and compared, at the protein and transcription levels, the expressions of IRF5, TLR4, and M1/M2 polarization profile and inflammatory markers against control (normoglycemia). Protein expression was assessed using flow cytometry, ELISA, Western blotting, and/or confocal microscopy. IRF5 silencing was achieved by small interfering RNA (siRNA) transfection. The data show that adipose IRF5 gene expression was higher in T2D than nondiabetic counterparts (P = 0.006), which correlated with glycated hemoglobin (HbA1c) (r = 0.47/P < 0.001), homeostatic model assessment of insulin resistance (HOMA-IR) (r = 0.23/P = 0.03), tumor necrosis factor (TNF)-α (r = 0.56/P < 0.0001), interleukin (IL)-1ß (r = 0.40/P = 0.0009), and C-C motif chemokine receptor (CCR)-2 (r = 0.49/P < 0.001) expression. IRF5 expression in macrophages was induced/upregulated (P < 0.05) by hypoglycemia (3 mM/L), persistent hyperglycemia (15 mM/L-25 mM/L), and RIH/glucose fluctuations (3-15 mM/L) as compared to normoglycemia (5 mM/L). RIH/glucose fluctuations also induced M1 polarization and an inflammatory profile (CD11c, IL-1ß, TNF-α, IL-6, and monocyte chemoattractant protein (MCP)-1) in macrophages. RIH/glucose fluctuations also drove the expression of matrix metalloproteinase (MMP)-9 (P < 0.001), which is a known marker for cardiovascular complication in T2D patients. Notably, all these changes were counteracted by IRF5 silencing in macrophages. In conclusion, RIH/glucose fluctuations promote the M1 polarization and inflammatory responses in macrophages via the mechanism involving TLR4-IRF5 pathway, which may have significance for metabolic inflammation.

Increasing the Duration of Light Physical Activity Ameliorates Insulin Resistance Syndrome in Metabolically Healthy Obese Adults.

Obesity is a well-known risk factor for insulin resistance syndrome (IRS). Nevertheless, limited data are available regarding the effects of physical activity (PA) intensity on the ability to modulate IRS. The study aim was to investigate the beneficial effects of the longer duration of light PA vs. a single bout of the acute moderate or vigorous PA for improvement in IRS indicators. Sixty metabolically healthy obese (MHO) participants, 30 males and 30 females, with body mass index (BMI) of ≥30 were enrolled in this study. PA levels were measured using an accelerometer, and the expression of monocytic surface markers was analyzed using flow cytometry. Plasma cytokines' secretion was determined by enzyme-linked immunosorbent assay (ELISA). Univariate regression analysis evaluated the actigraphy-assessed PA measures, inflammatory cytokines, and insulin resistance. The longer duration of PA was found to be associated with the homeostatic model assessment of insulin resistance (HOMA-IR), a lower lipid profile, and the expression of inflammatory cytokines by monocytes. Even though, higher intensities of PA were found to be associated with lower body fat percentage, only the light intensity PA was found to be beneficial as it associated with the improved insulin sensitivity and lower expression of inflammatory markers. In conclusion, maintaining the longer duration of low-intensity PA throughout the day could be more beneficial for reducing inflammation and improving insulin resistance. This study supports a more feasible approach model to gain beneficial lifestyle changes for the prevention of IRS in metabolically healthy adults with obesity.