BACKGROUND/AIMS: Poor sleep quality (SQ) is associated with increased cardiovascular mortality and morbidity. Additionally, asymmetric dimethylarginine (ADMA) is an independent predictor of cardiovascular mortality and morbidity. However, no sufficient data regarding the relationship between ADMA levels and SQ have been reported. The goal of the current study was to evaluate the association between SQ and ADMA levels in normotensive patients with type 2 diabetes mellitus. METHODS: The study participants consisted of 78 normotensive type 2 diabetics. The SQ of all participants was assessed using the Pittsburgh Sleep Quality Index (PSQI). Patients with a global PSQI score > 5 were defined as "poor sleepers." Factors associated with poor SQ were analyzed using a multiple regression model. Serum ADMA levels were measured using high performance liquid chromatography. RESULTS: The median ADMA levels of the poor sleepers were increased compared with patients defined as good sleepers (5.5 [4.2 to 6.6] vs. 4.4 [2.9 to 5.4], p < 0.01, respectively). However, the L-arginine/ADMA ratio was decreased in poor sleepers (p < 0.01). Global PSQI scores were positively correlated with ADMA levels (p < 0.01) and negatively correlated with the L-arginine/ADMA ratio (p = 0.02). ADMA levels were correlated with sleep latency (p < 0.01) and sleep efficiency (p = 0.01). Logistic regression analysis showed that ADMA levels (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.16 to 2.44; p = 0.01) and body mass index (OR, 1.15; 95% CI, 1.01 to 1.31; p = 0.04) were associated with poor SQ independently of glomerular filtration rate, sex, age, duration of diabetes, hemoglobin A1c, total cholesterol, and systolic blood pressure. CONCLUSIONS: Self-reported SQ was independently associated with ADMA levels in normotensive patients with diabetes mellitus.
Adult ; Arginine/*analogs & derivatives/blood ; Biomarkers/blood ; Cardiovascular Diseases/blood/*etiology/physiopathology ; Chi-Square Distribution ; Chromatography, High Pressure Liquid ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/blood/*complications/diagnosis/physiopathology ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Risk Factors ; *Sleep ; Sleep Wake Disorders/blood/*complications/diagnosis/physiopathology ; Surveys and Questionnaires

BACKGROUND: P-glycoprotein (P-gp) transports many chemicals that vary greatly in their structure and function. It is normally expressed in renal proximal tubular cells. We hypothesized that P-gp expression influences light chain excretion. Therefore, we investigated whether renal tubular P-gp expression is altered in patients with plasma cell disorders. METHODS: We evaluated renal biopsy specimens from patients with plasma cell disorders (n = 16) and primary focal segmental glomerulosclerosis (the control group, n = 17). Biopsies were stained with an anti-P-gp antibody. Loss of P-gp expression was determined semi-quantitatively. Groups were compared for loss of P-gp expression, and clinical variables. RESULTS: P-gp expression loss was more severe in patients with plasma cell disorders than it was in those with glomerulonephritis (P = 0.021). In contrast, clinical and histological parameters including serum creatinine, level of urinary protein excretion, and interstitial fibrosis/tubular atrophy grade were not significantly different between the groups. P-gp expression loss increased with age in patients with plasma cell disorders (P = 0.071). This expression loss was not associated with serum creatinine, the level of urinary protein excretion or the interstitial fibrosis/tubular atrophy grade. There was no significant association between the severity of P-gp expression loss with the types and serum levels of light chains, isotypes and serum immunoglobulin levels. CONCLUSION: Renal tubular P-gp expression is significantly down-regulated in patients with plasma cell disorders characterized by nephrotic range proteinuria. Additional studies are needed to determine whether reintroduction of renal tubular P-gp expression would mitigate the proximal tubular injury that is caused by free-light chains.
Amyloidosis ; Atrophy ; Biopsy ; Creatinine ; Glomerulonephritis ; Glomerulosclerosis, Focal Segmental ; Humans ; Immunoglobulin Light Chains ; Immunoglobulins ; P-Glycoprotein ; Plasma Cells ; Plasma ; Proteinuria