Lower heart rate variability is associated with higher plasma concentrations of IL-6 in type 1 diabetes

OBJECTIVE: In type 1 diabetes, cardiovascular autonomic neuropathy (CAN) is associated with cardiovascular risk factors related to insulin resistance, which in turn are associated with low-grade systemic inflammation. Reduced heart rate variability (HRV) is considered one of the first indicators of CAN. Since the autonomic nervous system interacts with systemic inflammation, we evaluated CAN to study its possible association with low-grade systemic inflammation. DESIGN: Cross-sectional study of a group of 120 subjects diagnosed with type 1 diabetes mellitus 14 years before. METHODS: Information recorded: 1) clinical characteristics: sex, age, body mass index, waist-to-hip ratio (WHR), blood pressure (BP), smoking, alcohol intake, insulin dose, HbA1c, and lipid profile; 2) plasma levels of soluble fractions of tumour necrosis factor alpha receptors 1 and 2, IL-6, and C-reactive protein; 3) insulin resistance by estimation of the glucose disposal rate (eGDR); and 4) tests for CAN: HRV in response to deep breathing (E/I ratio), HRV in response to the Valsalva maneuver, and changes in systolic BP responding to standing. RESULTS: A significant negative correlation was found between E/I ratio and plasma concentrations of IL-6 (r=-0.244, P=0.032), which remained significant after adjusting for potential confounding factors (age, sex, HbA1c, WHR, diastolic BP, triglycerides, HDL-cholesterol, retinopathy, nephropathy, peripheral neuropathy, insulin dose, and smoking; r=-0.231, P=0.039). No other significant associations were found between inflammation-related proteins, tests for CAN, and eGDR. CONCLUSIONS: These findings suggest a link between low-grade inflammation and early alterations of CAN in type 1 diabetes and may be of importance in the pathogenesis of CAN and/or its clinical implications.     

Increased glutamate/glutamine compounds in the brains of patients with fibromyalgia: A magnetic resonance spectroscopy study

Objective

Fibromyalgia (FM) has been defined as a systemic disorder that is clinically characterized by pain, cognitive deficit, and the presence of associated psychopathology, all of which are suggestive of a primary brain dysfunction. This study was undertaken to identify the nature of this cerebral dysfunction by assessing the brain metabolite patterns in patients with FM through magnetic resonance spectroscopy (MRS) techniques.

Methods

A cohort of 28 female patients with FM and a control group of 24 healthy women of the same age were studied. MRS techniques were used to study brain metabolites in the amygdala, thalami, and prefrontal cortex of these women.

Results

In comparison with healthy controls, patients with FM showed higher levels of glutamate/glutamine (Glx) compounds (mean ± SD 11.9 ± 1.6 arbitrary units [AU] versus 13.4 ± 1.7 AU in controls and patients, respectively; t = 2.517, 35 df, corrected P = 0.03) and a higher Glx:creatine ratio (mean ± SD 2.1 ± 0.4 versus 2.4 ± 1.4, respectively; t = 2.373, 35 df, corrected P = 0.04) in the right amygdala. In FM patients with increased levels of pain intensity, greater fatigue, and more symptoms of depression, inositol levels in the right amygdala and right thalamus were significantly higher.

Conclusion

The distinctive metabolic features found in the right amygdala of patients with FM suggest the possible existence of a neural dysfunction in emotional processing. The results appear to extend previous findings regarding the dysfunction in pain processing observed in patients with FM.

     

Disposition of gamma-hydroxybutyric acid in conventional and nonconventional biologic fluids after single drug administration: issues in methodology and drug monitoring

Little controlled drug administration data are available to aid in the interpretation of gamma-hydroxybutyric acid (GHB) distribution in conventional and nonconventional fluids and the potential correlation between the pharmacokinetics of GHB and drug effects. Single oral sodium GHB doses of 50 mg/kg were administered to five volunteers. Plasma, oral fluid, urine, and sweat were analyzed for GHB by gas chromatography-mass spectrometry. GHB stability in plasma was studied at different storage temperatures. Subjective effects were measured using a set of 13 different visual analog scales. Mean peak GHB plasma concentrations at 30 minutes were 83.1 microg/mL. After the absorption phase, concentrations declined to mean values of 0.9 microg/mL at 6 hours. GHB was found in oral fluid at peak value concentrations equivalent to one third to one fourth of those found in plasma. The oral fluid-to-plasma ratio varied two fold in the 1- to 6-hour time range but always was lower than unit. The mean half-life (t1/2) of GHB was approximately 0.7 hour in plasma and approximately 1.2 hours in oral fluid. GHB urinary excretion is less than 2% of the dose administered. GHB was also detected in sweat at low concentrations. GHB showed a mixed sedative-stimulant pattern with subjective effects peaking between 1 and 1.5 hours after drug administration and lasting for 2 hours. Oral fluid and sweat appeared not to be suitable biologic matrices for monitoring GHB consumption. GHB-mediated subjective effects are related to GHB plasma concentrations.