Association between poor glycemic control, impaired sleep quality, and increased arterial thickening in type 2 diabetic patients.

Poor sleep quality is an independent predictor of cardiovascular events. However, little is known about the association between glycemic control and objective sleep architecture and its influence on arteriosclerosis in patients with type-2 diabetes mellitus (DM). The present study examined the association of objective sleep architecture with both glycemic control and arteriosclerosis in type-2 DM patients.Cross-sectional study in vascular laboratory.The subjects were 63 type-2 DM inpatients (M/F, 32/31; age, 57.5±13.1) without taking any sleeping promoting drug and chronic kidney disease. We examined objective sleep architecture by single-channel electroencephalography and arteriosclerosis by carotid-artery intima-media thickness (CA-IMT).HbA1c was associated significantly in a negative manner with REM sleep latency (interval between sleep-onset and the first REM period) (β=-0.280, p=0.033), but not with other measurements of sleep quality. REM sleep latency associated significantly in a positive manner with log delta power (the marker of deep sleep) during that period (β=0.544, p=0.001). In the model including variables univariately correlated with CA-IMT (REM sleep latency, age, DM duration, systolic blood pressure, and HbA1c) as independent variables, REM sleep latency (β=-0.232, p=0.038), but not HbA1c were significantly associated with CA-IMT. When log delta power was included in place of REM sleep latency, log delta power (β=-0.257, p=0.023) emerged as a significant factor associated with CA-IMT.In type-2 DM patients, poor glycemic control was independently associated with poor quality of sleep as represented by decrease of REM sleep latency which might be responsible for increased CA-IMT, a relevant marker for arterial wall thickening

AAV-based gene therapy ameliorated CNS-specific GPI defect in mouse models

Thirty genes are involved in the biosynthesis and modification of glycosylphosphatidylinositol (GPI)-anchored proteins, and defects in these genes cause inherited GPI deficiency (IGD). PIGA is X-linked and involved in the first step of GPI biosynthesis, and only males are affected by variations in this gene. The main symptoms of IGD are neurological abnormalities, such as developmental delay and seizures. There is no effective treatment at present. We crossed Nestin-Cre mice with Piga-floxed mice to generate CNS-specific Piga knockout (KO) mice. Hemizygous KO male mice died by P10 with severely defective growth. Heterozygous Piga KO female mice are mosaic for Piga expression and showed severe defects in growth and myelination and died by P25. Using these mouse models, we evaluated the effect of gene replacement therapy with adeno-associated virus (AAV). It expressed efficacy within 6 days, and the survival of male mice was extended to up to 3 weeks, whereas 40% of female mice survived for approximately 1 year and the growth defect was improved. However, liver cancer developed in all three treated female mice at 1 year of age, which was probably caused by the AAV vector bearing a strong CAG promoter

Correlations between HbA1c, REM sleep latency, and log delta power and their effects on CA-IMT.

<p><b>(a)</b> HbA1c exhibited significant negative correlation with REM sleep latency (ρ = −0.342, p = 0.007). <b>(b)</b> REM sleep latency exhibited significant and positive correlation with log delta power during REM sleep latency (ρ = 0.510, p = 0.001). <b>(c)</b> CA<b>-</b>IMT exhibited significant and negative correlation with REM sleep latency (ρ = −0.274, p = 0.031) and log delta power during REM sleep latency (ρ = −0.300, p = 0.018). HbA1c, glycosylated hemoglobin; REM, rapid eye movement; CA-IMT, carotid artery intima-media thickness.</p

Clinical and biochemical profiles of patients.

<p>Continuous variables are summarized as mean (SD), whereas medians [interquartile range] are shown for variables with skewed distributions. Prevalence was reported as a percentage. BMI = body weight (kg)/height (m²). Delta power is the total power of the electroencephalograph signal within the delta frequency bands during REM sleep latency.</p><p>CA-IMT, carotid artery intima-media thickness; HbA1c, glycosylated hemoglobin; non-HDL-C, non-high density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; REM, rapid eye movement.</p><p>Clinical and biochemical profiles of patients.</p