Association between serum adipocytokine levels and microangiopathies in patients with type 2 diabetes mellitus

Aims/Introduction

It is thought that adipocytokines contribute to the increased risk of vascular complications in type 2 diabetes. However, there is still limited information on the relationship between microangiopathies and adipocytokines, such as adiponectin, leptin and tumor necrosis factor‐α (TNF‐α) in patients with type 2 diabetes.

Materials and Methods

The present study examined the relationship between fasting serum adiponectin, leptin, and TNF‐α levels and microangiopathies in Korean type 2 diabetes. A total of 153 patients were recruited and evaluated for diabetic nephropathy, retinopathy and neuropathy. Serum adiponectin, TNF‐α and leptin levels were measured.

Results

Serum adiponectin levels were significantly lower in patients with nephropathy than in those without nephropathy (P = 0.017), and were significantly higher in patients with retinopathy or neuropathy than those without retinopathy or neuropathy (P = 0.01 and P = 0.002, respectively). The mean levels of leptin were significantly higher in patients with neuropathy than in those without neuropathy (P = 0.002). The mean levels of TNF‐α were not significantly different according to any of the three microangiopathies. Multivariate logistic regression analysis showed that the odds ratio for the presence of neuropathy in the highest tertile of adiponectin was 4.3 (95% confidence interval 1.59–11.62), as compared with the patients in the lowest tertile of adiponectin level.

Conclusions

Levels of adipocytokines were significantly different according to the presence of each microangiopathy. In particular, higher serum adiponectin was independently associated with increased odds for the presence of neuropathy. Future prospective studies with larger numbers of patients are required to establish a direct relationship between plasma adipocytokine concentrations and the development or severity of diabetic microangiopathies.     

Tonic GABAA conductance bidirectionally controls interneuron firing pattern and synchronization in the CA3 hippocampal network

The spiking output of interneurons is key for rhythm generation in the brain. However, what controls interneuronal firing remains incompletely understood. Here we combine dynamic clamp experiments with neural network simulations to understand how tonic GABA_A conductance regulates the firing pattern of CA3 interneurons. In baseline conditions, tonic GABA_A depolarizes these cells, thus exerting an excitatory action while also reducing the excitatory postsynaptic potential (EPSP) amplitude through shunting. As a result, the emergence of weak tonic GABA_A conductance transforms the interneuron firing pattern driven by individual EPSPs into a more regular spiking mode determined by the cell intrinsic properties. The increased regularity of spiking parallels stronger synchronization of the local network. With further increases in tonic GABA_A conductance the shunting inhibition starts to dominate over excitatory actions and thus moderates interneuronal firing. The remaining spikes tend to follow the timing of suprathreshold EPSPs and thus become less regular again. The latter parallels a weakening in network synchronization. Thus, our observations suggest that tonic GABA_A conductance can bidirectionally control brain rhythms through changes in the excitability of interneurons and in the temporal structure of their firing patterns.Rhythmic activity paces signal transfer within brain circuits. Brain rhythms are believed to depend heavily on the networks of inhibitory interneurons (1–4). In addition to synaptic inputs, interneuron excitability in the hippocampus is determined by tonic GABA_A conductance (5, 6), which could thus contribute to hippocampal rhythmogenesis. Indeed, GABA transaminase inhibitor vigabatrin increases the ambient GABA concentration, enhancing the power of the theta-rhythm in rats (7). In mice expressing GFP under the GAD67 promoter the reduced levels of ambient GABA correlate with a decreased power of kainate-induced oscillations in vitro (8). The latter decrease is reversed by a GABA uptake inhibitor, guvacine, which raises ambient GABA. GABA release by astrocytes also increases the gamma oscillation power in hippocampal area CA1 in vivo (9). Intriguingly, in hippocampal slices of animals lacking δ subunit-containing GABA_A receptors (which mediate tonic conductance in many local cell types including interneurons) the average frequency of cholinergically induced gamma oscillations is increased, whereas the oscillation power tends to drop (10). However, cellular mechanisms underlying such phenomena remain poorly understood.One possible explanation is the influence of tonic GABA_A conductance on the firing pattern of interneurons. Activation of GABA_A receptors inhibits most neurons, through either membrane hyperpolarization or shunting or both (11). In the adult brain, a depolarizing action of GABA has also been reported in various cell types, including hippocampal interneurons (3, 12–15). GABAergic depolarization can prompt spike generation, thus countering the shunting effects (14, 16). Therefore, experimental evidence indicates that the net effect of GABA_A receptor activation combines the excitatory action of depolarization and the inhibitory consequences of shunting, with the latter prevailing when the GABA_A receptor conductance is sufficiently strong. As a result, increasing the tonic GABA_A signaling can have a biphasic effect on individual hippocampal interneurons: excitatory at weak conductances and inhibitory at strong (14). Here we find that weak tonic GABA_A conductance favors a more regular firing pattern of interneurons, thus facilitating synchronization of the CA3 network. In contrast, strong GABA_A conductance makes the firing pattern more dependent on the stochastic excitatory synaptic input, thus reducing network synchrony.     

Sleep duration and health-related quality of life in Korean adults: 2007-2015 Korea National Health and Nutrition Examination Survey

Sleep and Breathing - To evaluate the association of sleep duration with health-related quality of life (HRQOL) and examine the influence of age, sex, and common comorbidities on this association....     

End-expiratory lung volume decreases during REM sleep despite continuous positive airway pressure

Sleep and Breathing - Patients with obstructive sleep apnea (OSA) may experience apneas and hypopneas primarily during stage R (REM) sleep when end-expiratory lung volume (EELV) reaches its nadir....     

Preservation of renal function by thyroid hormone replacement therapy in chronic kidney disease patients with subclinical hypothyroidism

Context: Subclinical hypothyroidism is not a rare condition, but the use of thyroid hormone to treat subclinical hypothyroidism is an issue of debate. Objective: This study was undertaken to investigate the impact of thyroid hormone therapy on the changes in estimated glomerular filtration rate (eGFR) in subclinical hypothyroidism patients with stage 2-4 chronic kidney disease. Patients: A total of 309 patients were included in the final analysis. Main Outcome Measure: The changes in eGFR over time were compared between patients with and without thyroid hormone replacement therapy using a linear mixed model. Kaplan-Meier curves were constructed to determine the effect of thyroid hormone on renal outcome, a reduction of eGFR by 50%, or end-stage renal disease. The independent prognostic value of subclinical hypothyroidism treatment for renal outcome was ascertained by multivariate Cox regression analysis. Results: Among the 309 patients, 180 (58.3%) took thyroid hormone (treatment group), whereas 129 (41.7%) did not (nontreatment group). During the mean follow-up duration of 34.8 ± 24.3 months, the overall rate of decline in eGFR was significantly greater in the nontreatment group compared to the treatment group (-5.93 ± 1.65 vs. -2.11 ± 1.12 ml/min/yr/1.73 m(2); P = 0.04). Moreover, a linear mixed model revealed that there was a significant difference in the rates of eGFR decline over time between the two groups (P < 0.01). Kaplan-Meier analysis also showed that renal event-free survival was significantly lower in the nontreatment group (P < 0.01). In multivariate Cox regression analysis, thyroid hormone replacement therapy was found to be an independent predictor of renal outcome (hazard ratio, 0.28; 95% CI, 0.12-0.68; P = 0.01). Conclusion: Thyroid hormone therapy not only preserved renal function better, but was also an independent predictor of renal outcome in chronic kidney disease patients with subclinical hypothyroidism.     

Impact of routine angiographic follow-up after percutaneous coronary intervention with drug-eluting stents in the SPIRIT III randomized trial at three years

Routine angiographic follow-up after bare-metal stent implantation has been associated with an increase in coronary revascularization. The impact of angiographic follow-up after drug-eluting stent placement remains poorly characterized. The prospective, randomized, single-blinded SPIRIT III trial assigned patients to the everolimus-eluting stent or the paclitaxel-eluting stent (PES). Major adverse cardiovascular events (cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization [ID-TLR]) at 3 years were assessed by angiographic versus clinical-only follow-up at 8 months ± 28 days and a landmark survival analysis from 9 months to 3 years. Of 1,002 patients, 564 patients were assigned to angiographic follow-up at 8 months ± 28 days and 438 patients underwent clinical follow-up alone. Three-year major adverse cardiovascular event rates were 10.6% in the angiographic group and 12.0% in the clinical follow-up group (p = 0.64). Ischemia-driven revascularization increased twofold at 9 months, but no difference was noted in ID-TLR for either device. Non-ID-TLR was significantly higher in patients in the angiographic group (4.5% vs 1.0%, p = 0.002), a difference resulting from PES (9.1% vs 0.7%, p = 0.0007) rather than everolimus-eluting stent (2.2% vs 1.1%, p = 0.36) treatment. The landmark analysis showed no significant differences between the angiographic and clinical follow-up groups from 9 months to 3 years of major clinical outcomes. In conclusion, routine angiographic follow-up in SPIRIT III did not increase rates of ID-TLR compared to clinical follow-up alone. Despite higher nonischemia-driven revascularization rates with angiographic follow-up of patients with PESs, none of the safety end points were adversely affected.