Peripheral sensory nerve hyperaesthesia in women with polycystic ovary syndrome.

Dysfunction of the nervous system is well-known in diabetes and also among patients with prediabetes, obesity and hypertension. However, there is only a limited amount of data available on the changes in neuronal function in polycystic ovary syndrome (PCOs), despite the fact that this condition is also accompanied by metabolic and vascular abnormalities. The aim of our study was to assess the cardiovascular autonomic and peripheral sensory function in patients with PCOs. The study involved 27 women with PCOs, and 24 healthy women as control subjects. Autonomic neuropathy (AN) was assessed using the four standard cardiovascular reflex tests. Peripheral sensory function was determined using the Neurometer. Electric stimulation was applied transcutaneously and the current perception threshold (CPT) values were determined on the median and peroneal nerves. No significant differences were found between the PCOs patients and the control group regarding the cardiovascular autonomic reflex tests and the AN scores. The CPT values of PCOs patients in the median and peroneal nerves were lower at all frequencies in comparison to controls. Conclusions: The cardiovascular autonomic nerve function was normal in the patients with PCOs. The current perception thresholds were consequently lower in the PCOs patients both in the upper and lower extremities at all frequencies, which serves as an early sign of neuropathy. As a novel observation, our results suggest that early neuronal damage manifests in the form of sensory hyperaesthesia in patients with PCOs.

Periodontal Disease in Diabetes Mellitus: A Case-Control Study in Smokers and Non-Smokers.

INTRODUCTION: It is well established that periodontal disease (PD) and diabetes mellitus (DM) can have a detrimental effect on each other's disease course, and that cigarette smoking exacerbates both conditions. However, literature on the periodontal status of smokers with DM is scarce, and the studies conducted to date did not use healthy controls or non-smokers with DM as controls. Consequently, the individual effects of smoking and DM on PD are difficult to untangle and estimate. METHODS: A total of 128 participants were recruited to this study and their data analyzed. They were assigned to four groups: smoking patients with DM (SDM); non-smoking patients with DM (NSDM); smokers without DM (control group, SC) and (4) non-smokers without DM (control group, NSC). Each group consisted of 32 age-matched participants. The periodontal status of the participants was assessed by full oral examination. To express periodontal status, we used the four-stage classification introduced by Fernandes and colleagues (J Periodontol. 80(7):1062-1068, 2009). The control of DM was estimated by measuring hemoglobin A1c (HbA1c) levels in the peripheral blood. RESULTS: A significant difference in the severity of PD was found between the SC and NSC groups (p = 0.027) and between the NSC and SDM groups (p = 0.000), while the difference between the NSDM and SDM groups approached significance (p = 0.052). No person in the smoker groups could be classified as having a healthy periodontal status. The four-stage classification followed a normal distribution in the healthy, non-smoking controls (NSC). Smoking caused a shift toward medium-severe PD, while a marked shift toward the most severe stage was observed when both smoking and DM were present (SDM). There was no significant association between the type of DM and periodontal status, nor between diabetes control and the severity of PD. Persons in the SDM group had significantly fewer teeth than those in the NSC group (mean ± standard deviation: 16.0 ± 7.9 vs. 20.7 ± 5.6; p = 0.02). CONCLUSION: Smoking damages the periodontium of even healthy individuals, but the damage is multiplied in a smoker who has DM, even though the effect of DM alone on periodontium health is relatively mild. Our results suggest a synergy between DM and smoking in terms of damage to the periodontal tissues, but the limited sample size of this study does not allow any hard conclusion to be drawn.

[Rapidly progressive proliferative glomerulonephritis with monoclonal immunoglobulin G deposits despite the mild histological changes. Case report]. / Enyhe szövettani eltérések ellenére gyors progressziójú proliferativ glomerulonephritis monoklonális immunglobulin-G-depozitumokkal.

Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits is characterized by granular deposits of monoclonal IgG; histologically it has typically a membranoproliferative or endocapillary pattern, and seen electronmicroscopically there are dense deposits without substructure. Here, we present the case of a 62-year-old Caucasian woman who was admitted with rapidly progressive kidney failure. The patient's status, the laboratory and imaging examinations did not support prerenal, postrenal and - among the intrinsic causes - vascular and tubulointerstitial origin. The proteinuria and dysmorphic microhematuria suggested rapidly progressive glomerulonephritis. Tests for anti-neutrophil cytoplasmic antibodies, anti-glomerular basement membrane, antinuclear antibodies and cryoglobulins were negative, the C3 and C4 levels were normal. The biopsy evaluation diagnosed proliferative glomerulonephritis with monoclonal IgG deposits because of mesangial granular deposits of IgG3-kappa, C3, and C1q, and ultrastructurally electron-dense deposits (incidence in our adult native kidney biopsy series: 0.18%). 31 glomeruli were assessed histologically. 29 glomeruli displayed mild mesangial hypercellularity, 2 glomeruli were globally sclerotic. Crescents were not observed. Mild arteriolar hyalinosis, interstitial fibrosis and tubular atrophy accompanied the glomerular alterations. In the postbiopsy evaluation, paraprotein or multiple myeloma was not detected. Despite the mild histological findings, the kidney failure progressed, and hemodialysis had to be started two weeks after the biopsy. Steroids, cyclophosphamide and rituximab did not affect her kidney function, and she remained on hemodialysis during the follow-up of 39 months. This report presents for the first time proliferative glomerulonephritis with monoclonal IgG deposits as the possible cause of rapidly progressive nephritic syndrome in the absence of pronounced glomerular proliferative, sclerotic or tubulointerstitial lesions. Orv Hetil. 2018; 159(38): 1567-1572.

Cardiovascular Autonomic Neuropathy and Glucose Variability in Patients With Type 1 Diabetes: Is There an Association?

INTRODUCTION: The oxidative stress associated with glucose variability might be responsible for neuronal damage while autonomic neuropathy (AN) has a detrimental effect on metabolism. The aim of the study was to find relationship between AN and GV in type 1 diabetic patients and to identify further factors that affect GV. PATIENTS AND METHODS: Twenty type 1 diabetic patients were involved (age: 39.5 ± 3.4 years, duration of diabetes: 17.5 ± 2.5 years; HbA1c: 8.1 ± 0.2%, mean ± SE). AN was assessed by the cardiovascular reflex tests. The interstitial glucose levels were determined following insertion of a subcutaneous electrode during the continuous glucose monitoring (CGM) method on six consecutive days. GV was characterized by calculation of four parameters. RESULTS: SD of interstitial glucose values correlated positively with the overall AN score and the degree of the orthostatic reduction of systolic blood pressure (AN-score-SD ρ = 0.47, p < 0.05; orthostasis-SD: ρ = 0.51, p < 0.05). Mean absolute glucose (MAG) correlated with three parameters of AN (AN-score-MAG: ρ = 0.62, p < 0.01; 30/15 ratio-MAG: ρ = -0.50, p < 0.05; orthostasis-MAG: ρ = 0.59, p < 0.01). The HbA1c also correlated with two parameters of GV (HbA1c-continuous overlapping net glycemic action: ρ = 0.56, p < 0.05; HbA1c-MAG: ρ = 0.45, p < 0.05). The frequency of hypoglycemia did not exhibit any correlation with measures of GV. CONCLUSION: Severity of glucose variability but not overall glucose load correlates with both parasympathetic and sympathetic dysfunctions in type 1 diabetes. Higher HbA1c is associated with more severe glucose variability. The observed correlation between increased glucose variability and the severity of AN necessitates the further exploration of this relationship.

Increased Short-Term Beat-to-Beat QT Interval Variability in Patients with Impaired Glucose Tolerance.

Prediabetic states and diabetes are important risk factors for cardiovascular morbidity and mortality. Determination of short-term QT interval variability (STVQT) is a non-invasive method for assessment of proarrhythmic risk. The aim of the study was to evaluate the STVQT in patients with impaired glucose tolerance (IGT). 18 IGT patients [age: 63 ± 11 years, body mass index (BMI): 31 ± 6 kg/m2, fasting glucose: 6.0 ± 0.4 mmol/l, 120 min postload glucose: 9.0 ± 1.0 mmol/l, hemoglobin A1c (HbA1c): 5.9 ± 0.4%; mean ± SD] and 18 healthy controls (age: 56 ± 9 years, BMI: 27 ± 5 kg/m2, fasting glucose: 5.2 ± 0.4 mmol/l, 120 min postload glucose: 5.5 ± 1.3 mmol/l, HbA1c: 5.4 ± 0.3%) were enrolled into the study. ECGs were recorded, processed, and analyzed off-line. The RR and QT intervals were expressed as the average of 30 consecutive beats, the temporal instability of beat-to-beat repolarization was characterized by calculating STVQT as follows: STVQT = Σ|QTn + 1 - QTn| (30x√2)-1. Autonomic function was assessed by means of standard cardiovascular reflex tests. There were no differences between IGT and control groups in QT (411 ± 43 vs 402 ± 39 ms) and QTc (431 ± 25 vs 424 ± 19 ms) intervals or QT dispersion (44 ± 13 vs 42 ± 17 ms). However, STVQT was significantly higher in IGT patients (5.0 ± 0.7 vs 3.7 ± 0.7, P < 0.0001). The elevated temporal STVQT in patients with IGT may be an early indicator of increased instability of cardiac repolarization during prediabetic conditions.

Advances in the management of diabetic neuropathy.

The authors review current advances in the therapy of diabetic neuropathy. The role of glycemic control and management of cardiovascular risk factors in the prevention and treatment of neuropathic complications are discussed. As further options of pathogenetically oriented treatment, recent knowledge on benfotiamine and alpha-lipoic acid is comprehensively reviewed. Alpha-lipoic acid is a powerful antioxidant and clinical trials have proven its efficacy in ameliorating neuropathic signs and symptoms. Benfotiamine acts via the activation of transketolase and thereby inhibits alternative pathways triggered by uncontrolled glucose influx in the cells comprising polyol, hexosamine, protein-kinase-C pathways and formation of advanced glycation end products. Beyond additional forms of causal treatment, choices of symptomatic treatment will be summarized. The latter is mostly represented by the anticonvulsive agents pregabalin and gabapentin as well as duloxetine widely acknowledged as antidepressant. Finally, non-pharmacological therapeutic alternatives are summarized. The authors conclude that combination therapy should be more often suggested to our patients; especially the combination of pathogenetic and symptomatic agents.

Relevance of α-defensins (HNP1-3) and defensin ß-1 in diabetes.

AIM: To investigate the genetic background of human defensin expression in type 1 and 2 diabetes. METHODS: Associations between DEFA1/DEFA3 gene copy number polymorphism and diabetes as well as between the promoter polymorphisms of DEFB1 and diabetes were studied. The copy number variation of the DEFA1/DEFA3 genes was determined in 257 diabetic patients (117 patients with type 1 and 140 with type 2 diabetes). The control group consisted of 221 age- and gender-matched healthy blood donors. The cumulative copy numbers of the DEFA1/DEFA3 genes were detected by using quantitative PCR analysis. To evaluate the HNP 1-3 (human neutrophil peptide 1-3 or α-defensin) levels in the circulation, plasma HNP 1-3 concentrations were measured by ELISA. The expression of DEFA1/A3 in peripheral leukocytes of the diabetic patients was measured by quantitative RT PCR analysis. Three SNPs of the human DEFB1 (human defensin ß-1) gene: DEFB1 G-20A (rs11362), DEFB1 C-44G (rs1800972) and DEFB1 G-52A (rs1799946) were genotyped by Custom TaqMan(®) Real Time PCR assay. RESULTS: Significant differences were observed in HNP1-3 levels between the healthy subjects and both groups of diabetic patients. The mean ± SE was 28.78 ± 4.2 ng/mL in type 1 diabetes, and 29.82 ± 5.36 ng/mL in type 2 diabetes, vs 11.94 ± 2.96 ng/mL in controls; P < 0.01 respectively. There was no significant difference between patients with type 1 and type 2 diabetes in the high plasma concentrations of HNP1-3. The highest concentrations of α-defensin were found in diabetic patients with nephropathy (49.4 ± 4.8 ng/mL), neuropathy (38.7 ± 4.8 ng/mL) or cardiovascular complications (45.6 ± 1.45 ng/L). There was no significant difference in the cumulative copy numbers of DEFA1/DEFA3 genes between controls and patients, or between patients with the two types of diabetes. Comparisons of HNP 1-3 plasma level and DEFA1/A3 copy number of the same patient did not reveal significant relationship between defensin-α levels and the gene copy numbers (r (2) = 0.01). Similarly, no positive correlation was observed between the copy numbers and the mRNA expression levels of DEFA1/A3. Regarding the C-44G polymorphism of DEFB1, the GG "protective" genotype was much less frequent (1%-2%) among both groups of patients than among controls (9%). CONCLUSION: Elevated HNP1-3 levels in diabetes are independent of DEFA1/DEFA3 copy numbers, but GG genotype of C-44G SNP in DEFB1 gene may result in decreased defensin ß-1 production.