Subclinical albuminuria is linked to gray matter atrophy in type 2 diabetes mellitus

Objective

Microalbuminuria (MA), a marker of renal microvascular disease, is associated with brain atrophy and neurovascular changes in older adults with type 2 diabetes mellitus (DM). We evaluated the relationship between urine albumin-to-creatinine ratio (UACR) and regional brain volumes to determine whether subclinical albuminuria may indicate early structural brain changes in type 2 DM.

Materials/Methods

We studied UACR and brain volumes in 85 type 2 DM patients (64.8 ± 8.3 years) and 40 age-matched controls using 3D magnetization prepared rapid acquisition with gradient echo (MP-RAGE) MRI (magnetic resonance imaging) at 3 Tesla. The relationship between UACR and brain volumes was analyzed using the least square models.

Results

In DM patients, UACR ≥ 5 mg/g, UACR ≥ 10 mg/g and clinically significant MA (UACR ≥ 17 mg/g [males] and 25 mg/g [females]) were associated with lower gray matter (GM) volume in the frontal lobe (r²_adj = 0.2–0.4, P = 0.01–0.05) and UACR ≥ 5 mg/g was also related to global GM atrophy (r²_adj = 0.1, P = 0.04), independent of DM duration, glucose levels, HbA_1c and hypertension. For UACR ≥ 5 mg/g, a lower global GM volume was related to worse executive function (P = 0.04) in the DM group. No associations were found for UACR (< 5 mg/g) and controls.

Conclusions

Subclinical albuminuria (UACR ≥ 5 mg/g) is associated with lower GM volume that has clinical impact on cognitive function in older diabetic patients, and these relationships are independent of DM control and hypertension. Therefore, UACR levels may serve as an additional marker of DM-related brain structural changes.     

Coffee polyphenols improve peripheral endothelial function after glucose loading in healthy male adults

Brewed coffee is a widely consumed beverage, and many studies have examined its effects on human health. We investigated the vascular effects of coffee polyphenols (CPPs), hypothesizing that a single ingestion of CPP during glucose loading would improve endothelial function. To test this hypothesis, we conducted a randomized acute clinical intervention study with crossover design and measured reactive hyperemia index (RHI) to assess the acute effects of a 75-g glucose load with CPP in healthy, nondiabetic adult men. Blood glucose and insulin levels were elevated after glucose loading with and without CPP, with no significant differences between treatments. The RHI did not significantly decrease after glucose loading without CPP. With CPP, however, RHI significantly (P < .05) increased over baseline after glucose loading. The difference between treatments was statistically significant (P < .05). No significant changes were observed in an oxidative stress marker after glucose loading with or without CPP. These findings suggest that a single ingestion of CPP improves peripheral endothelial function after glucose loading in healthy subjects.     

The association of the UHRF1BP1 gene with systemic lupus erythematosus was replicated in a Han Chinese population from mainland China

Single-nucleotide polymorphisms (SNPs) in the UHRF gene have been shown to be associated with systemic lupus erythematosus (SLE) in European and Hong Kong Chinese, but statistically significant evidence for association has not been found in a mainland Han Chinese population. Therefore, we selected SNP rs13205210 located in UHRF1BP1 as a candidate association from our previously published genome-wide association study (GWAS) data of SLE (1,047 cases and 1,205 controls from a mainland Han Chinese population) to explore the association between the UHRF1BP1 gene and SLE. We conducted a large-scale replication study in an additional independent sample of 3,509 cases and 8,246 controls from a mainland Han Chinese population. Real-time PCR was used to determine gene expression differences in peripheral blood mononuclear cells (PBMCs) from cases and controls. As a result, we replicated the association between the UHRF1BP1 gene and SLE (rs13205210, missense, P_meta = 2.26E-17, odds ratio = 1.41) by a meta-analysis of our previous GWAS and this replication study involving a total of 4,556 cases and 9,451 controls. The UHRF1BP1 mRNA expression level in PBMCs was significantly decreased in patients with SLE compared with that in healthy controls. SNP rs13205210 exhibited an expression quantitative trait loci effect on the UHRF1BP1 gene in PBMCs from patients. In conclusion, this study not only suggests that the UHRF1BP1 gene was associated with SLE in a mainland Han Chinese population, but also implied that it might be a common genetic factor contributing to SLE susceptibility in multiple populations.     

The Association between the Phenotype of Excessive Daytime Sleepiness and Blood Pressure in Patients with Obstructive Sleep Apnea-Hypopnea Syndrome

Objective Investigate the clinical features and the blood pressure (BP) pattern of the phenotype of excessive daytime sleepiness (EDS) in OSAHS.Methods A total of 508 Chinese adults with suspected OSAHS were referred to our sleep laboratory from October 2009 to May 2012. On the same night of polysomnography (PSG), the levels of blood pressure were measured before sleeping (bedtime BP) and immediately after waking up in the next morning (morning BP). EDS was recognized as Epworth Sleepiness Scale (ESS)≥9. Subjects were classified into four groups based on the apnea-hypopnea index (AHI) from PSG as follows: control (simple snoring) group (control, n=104) with AHI<5; mild group (mild, n=89) with AHI≥5 and <15; moderate group (moderate, n=70) with AHI≥15 and<30; and severe group (severe, n=245) with AHI ≥30. The differences and correlations between BP and PSG parameters in EDS and non-EDS group of OSAHS patients were analyzed.Results In all subjects, ESS was positively correlated with morning diastolic blood pressure (DBP), Mean arterial pressure (MAP) and bedtime DBP (r=0.144, 0.102 and 0.114, respectively, each P value<0.05). In OSAHS patients, ESS was only positively correlated with morning DBP (r=0.137, P<0.05). OSAHS patients with EDS phenotype were younger and were more likely to have the symptom of waking up feeling tired (36.1% vs. 23.2%, p=0.023), who had lower MSaO2, longer SIT90 (the ratio of time of SpO2 below 90% in total sleep time) and higher DBP (bedtime as well as morning). In patients with AHI≥15, ESS was correlated positively with both bedtime and morning DBP after controlling the confounding effects of age, sex, BMI, AHI and nadir nocturnal oxygen saturation( r=0.126,0.143, respectively, both P values<0.05). And in OSAHS patients of EDS phenotype, the bedtime DBP, bedtime MAP, morning DBP, and morning MAP were 3~5 mm Hg higher than that in patients of non-EDS phenotype(P<0.05). In the moderate and severe OSAHS group, patients with EDS phenotype were younger and had a lower mean blood oxygen saturation (MSaO2), longer time of SpO2 below 90% and higher SIT90 than patients with non-EDS phenotype (P<0.05). In hypertensive OSAHS patients, patients with EDS were also younger and had higher micro-arousal index (MiI), as well as higher morning DBP, morning MAP and bedtime DBP than that in non-EDS group (P<0.05).Conclusions EDS in OSAHS patients is a special phenotype, which was characterized by younger age, higher DBP and more severe hypoxic load. This feature is mainly manifested in moderate and severe OSAHS patients. It is very important to identify the phenotype of EDS in patients with OSAHS, who may meet more benefits from effective treatment of OSAHS by correcting the intermittent nocturnal hypoxia and sleep fragmentation.