Abstract Hyperglycemia explains the development of late diabetic complications in patients with diabetes type 1 and type 2 only partially. Most therapeutic efforts relying on intensive glucose control failed to decrease the absolute risk for complications by more than 10%, especially in patients with diabetes type 2. Therefore, alternative pathophysiological pathways have to be examined, in order to develop more individualized treatment options for patients with diabetes in the future. One such pathway might be the metabolism of dicarbonyls, among them methylglyoxal and the accumulation of advanced glycation end products. Here we review currently available epidemiological data on dicarbonyls and AGEs in association with human diabetes type 1 and type 2.
Abstract Introduction/aims Diabetic small fiber neuropathy (SFN) is caused by damage to thinly myelinated A‑fibers (δ) and unmyelinated C‑fibers. This study aimed to assess associations between quantitative sensory testing (QST) and parameters of peripheral nerve perfusion obtained from dynamic contrast enhanced (DCE) magnetic resonance neurography (MRN) in type 2 diabetes patients with and without SFN. Methods A total of 18 patients with type 2 diabetes (T2D, 8 with SFN, 10 without SFN) and 10 healthy controls (HC) took part in this cross-sectional single-center study and underwent QST of the right leg and DCE-MRN of the right thigh with subsequent calculation of the sciatic nerve constant of capillary permeability (K trans ), extravascular extracellular volume fraction (V e ), and plasma volume fraction (V p ). Results The K trans (HC 0.031 min −1 ± 0.009, T2D 0.043 min −1 ± 0.015; p = 0.033) and V e (HC 1.2% ± 1.5, T2D: 4.1% ± 5.1; p = 0.027) were lower in T2D patients compared to controls. In T2D patients, compound z‑scores of thermal and mechanical detection correlated with K trans (r = 0.73; p = 0.001, and r = 0.57; p = 0.018, respectively) and V e (r = 0.67; p = 0.002, and r = 0.69; p = 0.003, respectively). Compound z‑scores of thermal pain and V p (r = −0.57; p = 0.015) correlated negatively. Discussion The findings suggest that parameters of peripheral nerve microcirculation are related to different symptoms in SFN: A reduced capillary permeability may result in a loss of function related to insufficient nutritional supply, whereas increased capillary permeability may be accompanied by painful symptoms related to a gain of function.
Studies on magnetic resonance neurography (MRN) in diabetic polyneuropathy (DPN) have found proximal sciatic nerve lesions. The aim of this study was to evaluate the functional relevance of sciatic nerve lesions in DPN, with the expectation of correlations with the impairment of large-fiber function. Sixty-one patients with type 2 diabetes (48 with and 13 without DPN) and 12 control subjects were enrolled and underwent MRN, quantitative sensory testing, and electrophysiological examinations. There were differences in mechanical detection (Aβ fibers) and mechanical pain (Aδ fibers) but not in thermal pain and thermal detection clusters (C fibers) among the groups. Lesion load correlated with lower Aα-, Aβ-, and Aδ-fiber but not with C-fiber function in all participants. Patients with lower function showed a higher load of nerve lesions than patients with elevated function or no measurable deficit despite apparent DPN. Longer diabetes duration was associated with higher lesion load in patients with DPN, suggesting that nerve lesions in DPN may accumulate over time and become clinically relevant once a critical amount of nerve fascicles is affected. Moreover, MRN is an objective method for determining lower function mainly in medium and large fibers in DPN.
<p dir="ltr">We aimed to investigate the characteristics and longitudinal course of sensory phenotypes identified through Quantitative Sensory Testing in the frame of diabetic polyneuropathy (DSPN). 316 individuals with diabetes mellitus (DM) were examined (78.8% T2DM), of which 250 were follow-up visits 1, 2 and/or 4 (2.88±1.27) years. Allocation into four sensory phenotypes (healthy, thermal hyperalgesia-TH, mechanical hyperalgesia-MH, and sensory loss-SL) at every timepoint was based on QST profiles of the right foot. Cross-sectional analyses demonstrated a gradual worsening of clinical and electrophysiological sensory findings, and increased DSPN prevalence across the groups culminating in SL. Motor nerve impairment was observed solely in SL. Longitudinal analysis revealed a distinct pattern of the phenotype’s developmental course (healthy to TH, to MH, to SL). Baseline MH exhibited the highest risk of transition to SL. Regression to healthy was uncommon and mostly observed in TH. Among those without DSPN initially, presence or future occurrence of SL was associated with a three- to fivefold higher likelihood of DSPN development. Our comprehensive longitudinal study of phenotyped patients with DM elucidates the natural course of DSPN. QST-based sensory examination together with other tools for phenotyping may perhaps be useful to determine the natural course of diabetic neuropathy, to identify patients at high risk for DSPN and guide preventive and therapeutic interventions. </p>
Einführung Die Messung von Erregbarkeit erlaubt die Beurteilung der C-Faser-Funktion bei Polyneuropathien. Ziel der Studie war es, die Erregbarkeit der C-Fasern mittels transkutaner elektrischer Stimulation bei diabetischer sensomotorischer Neuropathie (DSPN) und ihren Zusammenhang mit der epidermalen Innervation und quantitativen sensorischen Testung zu untersuchen. Das Schmerzempfinden wurde bei glukosetoleranten Menschen (n=14) und Patienten mit Typ-2-Diabetes mit folg. DSPN-Kriterien untersucht: keine DSPN (n=15), mögliche DSPN (n=21), wahrscheinliche DSPN (n=19) und bestätigte DSPN (n=11). Darüber hinaus wurde die Erregbarkeit der C-Faser bei Patienten mit positiven (n=17) und negativen Symptomen (n=16) analysiert.
Objective: The measured and calculated values of blood pressure (BP) recorded by ambulatory blood pressure monitoring (ABPM) [mean 24-hour BP, daytime BP, nighttime BP, diurnal pattern, BP variability visit by visit (standard deviation, coefficient of variation), vascular elasticity characterized by ambulatory arterial stiffness index (AASI)] are more appropriate predictors of long-term cardiovascular morbidity and mortality than office-based BP measurement. Design and method: The BP-reducing effect of the fix-dose combination perindopril/amlodipine (5 mg/5 mg, 5 mg/10 mg, 10 mg/5 mg, 10 mg/10 mg) was investigated in hypertensive patients with high cardiovascular risk from the ABPM subgroup of the large Hungarian trial, the PErindopril/Amlodipine Reduction of blood pressure Level study (PEARL). ABPM was performed in 262 patients (from 10335) (144 males, average age 60,4 ± 11,7 years) at the first- and at the 3-months visit. Data were presented as mean ± SD. For comparisons of BP measurements one sample t-test and Chi-square test were performed. A 2-sided α level of 0.05 was considered statistically significant. Results: The fixed combination perindopril/amlodipine reduced the mean office BP from 159.8/94.3 mmHg to 131.0/80.0 mmHg (p < 0.001) and the 24-hour BP from 146.1/84.3 mmHg to 127.6/75.9 mmHg (p < 0.001) in the ABPM subgroup. The diurnal pattern was not changed. The SD dropped from 15.3/11.4, to 10.5/8.9 (p < 0.01) and the CV from 10.5/13.5% to 8.2/11.7 % (p < 0.01). The AASI also decreased from 0.4571 ± 0.11 to 0.4168 ± 0.12 (p < 0.01). Conclusions: The results of our study show a significant and safety BP reduction in office as well as in ABPM in hypertensive patients with high cardiovascular risk and whose BP was uncontrolled by a suitable previous treatment. In our study we were able to illustrate a higher BP variability at the first visit compared with the 3 months visit. In addition we found an AASI reduction (which might reflect arterial rigidity). These rapid changes, observed in our study, might correlate with the results of the randomized, controlled ASCOT-BPLA study and are appropriate to predict the cardiovascular morbidity and mortality.
Aim To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to dysmetabolism (indexes of insulin resistance-IR, Metabolic Syndrome-MetS) in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development.
Abstract There is growing evidence that reactive metabolites, such as reactive oxygen species and dicarbonyls contribute to diabetic complications. Formation, accumulation, and detoxification of these metabolites are controlled by several enzymes, some of which have genetically determined levels of expression or function. This review not only gives an overview of the different SNPs studied in patients with diabetes mellitus type 1 and type 2, but in addition attempts to bridge the gap between a genetic study and clinical use. Therefore, not only the results of the studies are reviewed, but also their use in identification of subgroups where an increased or decreased risk for a diabetic complication is described, as well as their use in developing novel therapeutic options based on understanding the contribution of an enzyme to a given complication.
