Postural control in type 2 diabetes mellitus: the role of diabetic neuropathy.

Heart rate variability(HRV)analysis and its circadian rhythm(CR)were determined in 58patients with type 2 diabetes mellitus with lower extremity neuropathy(diabetic neuropathy group), 59 patients with type 2 diabetes mellitus without lower extremity neuropathy(diabetes group), and 50 healthy controls according to 24-hour Holter recording. Frequency domain parameters of HRV were significantly decreased in both diabetes groups. Frequency domain parameter of HRV in healthy controls,and daytime/nighttime difference were statistically significant. CR of HRV was changed in diabetes group and disappeared in diabetic neuropathy group. Impaired and seriously impaired autonomic nervous function developed in type 2 diabetes mellitus without and with lower extremity neuropathy respectively. Key words: Diabetes mellitus, type 2; Diabetic autonomic neuropathy; Heart rate variability; Circadian rhythm

Objective To compare the plasma endogenous secrection receptor for advanced glycation end products (esRAGE) level between normal subjects and type 2 diabetes mellitus (T2DM) patients, and to investigate whether the esRAGE is associated with diabetic peripheral neuropathy in T2DM patients. Methods A total of 24 cases of normal subjects and 61 cases of T2DM patients were involved in the study, and then the patients were divided into two groups, that was, patients with diabetic peripheral neuropathy (DPN) group and without diabetic peripheral neuropathy (non–DPN) group. Plasma esRAGE was measured with Enzyme linked immunosorbent assay (ELISA). Myoelectricity evoked potential equipment was applied to detect nerve conduction studies. Blood pressure, body mass index, fasting plasma glucose, HbA1c, and plasma lipids level were measured as well. Student t test and nonparametric statistics were applied to analysis data between two groups and the related factors of DPN were investigated with logistic regression analysis. Results The plasma esRAGE level did not show significant difference between normal subjects and T2DM patients ((0.28±0.13) μg/L vs (0.25±0.15) μg/L, P>0.05). However there was significant different between DPN group and non–DPN group in patients ((0.21±0.14) μg/L vs (0.33±0.13) μg/L, P<0.05). The logistic regression analysis showed DPN was associated with age, HbA1c, and esRAGE in T2DM patients. Conclusions The plasma esRAGE level has not significant difference between T2DM patients and normal subjects. The plasma esRAGE level is a protective factor for DPN , on the contrary age and HbA1c are risk factors for DPN in T2DM patients. Key words: Diabetes mellitus; Endogenous secrection receptor for advanced glycation end products; Diabetic peripheral neuropathy

The World Health Organisation estimated that in the year 2000, 150 million people had diabetes mellitus, and it is predicted that this number will rise to 366 million by the year 2030.[1][1] Neuropathy is a common complication of diabetes and is characterised by a progressive loss of peripheral

Background: We aimed to investigate whether there was a relationship between diabetic peripheral distal neuropathy (DPDN), one of the most common chronic complications in patients with type 2 diabetes mellitus (T2DM), and the uric acid/HDL ratio, which can be used as an indicator of poor metabolic status.Methodology: The study consisted of a total of 150 subjects, including 50 patients with T2DM (group 1) who were determined to have diabetic peripheral distal neuropathy with electroneuromyography (ENMG), 50 patients with T2DM who were determined to not have DPDN in their ENMG (group 2), and 50 healthy individuals (group 3). Participants’ serum fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), uric acid, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels were analyzed. The uric acid/HDL-C ratio (UHR) was calculated. The relationship between UHR and other parameters was evaluated in all three groups.Results: Patients with T2DM who had diabetic neuropathy (group 1), did not have diabetic neuropathy (group 2), and healthy subjects (group 3) were similar in terms of age and gender (p=0.066, p=0.185). Groups 1 and 2 were similar in terms of the duration of diabetes and FBG values (p=0.825, p=0.572), but these values were lower in group 3 than in groups 1 and 2 (p<0.05). HbA1c did not differ significantly between groups 1 and 2 (p=0.607). Creatinine levels were similar in the three groups. Uric acid levels were significantly higher in group 1 than in group 2 (p=0.040), but there was no significant difference between groups 1 and 3 or between groups 2 and 3 (p>0.05). UHR was significantly lower in group 1 than in groups 2 and 3 (p<0.001), but no significant difference was found between groups 2 and 3.Conclusion: In our study, we found that the UHR level of the group with diabetic neuropathy was statistically significant compared to the levels of the other two groups. However, no significant difference was found between the patients with diabetes who did not have neuropathy and the healthy group. Based on the findings of our study, we can say that the UHR level is a predictor of the microvascular complications of diabetes.

HighlightsWhat are the main findings?We proposed a posturography test protocol using only the IMU embedded on a smartphone fixed at the low back area. The smartphone-based postural analysis yields similar results compared to traditional center-of-pressure analysis.The smartphone-based postural analysis was able to identify specific deficits in patients with type 2 diabetes that were not present in healthy individuals.What are the implications of the main findings?Temporal analysis of IMU data from regular smartphones is suitable for relevant postural analysis in healthy people and patients with type 2 diabetes.The proposed analysis has the potential to allow widespread assessments of postural control in remote settings, with patients at home and/or at local clinics.Background: There is a growing need for highly accessible and simplified methods to track postural control in adults affected by neurodegenerative diseases. Therefore, the aim of this study was to assess the validity of smartphone-derived postural control analyses compared with traditional center-of-pressure (COP) measures in healthy adults and people with type 2 diabetes mellitus (T2DM). Methods: A total of 36 participants (21 controls, 15 T2DM) completed static postural testing during single- and double-leg stance, also with eyes open and eyes closed. Data from a smartphone attached to the lower back measured trunk acceleration (SP-ACC) concurrently with gold-standard center of pressure (COP). The root mean square (RMS) and movement velocity (MV) were extracted from both trunk acceleration and COP data. The effect of balance condition and groups were statistically evaluated using non-parametric statistical tests. Results: SP-ACC and COP metrics showed progressive sway increases with task difficulty in both groups (all p < 0.001). RMS-ACC demonstrated moderate-to-strong correlations with RMS-COP across conditions (r = 0.55–0.90). Compared with controls, the T2DM group exhibited significantly higher RMS-ACC in DLS-EC and SLS-EO (both p < 0.01) and higher MV-ACC in DLS-EO, SLS-EO, and SLS-EC (p = 0.04–<0.001), reflecting impaired postural control. Conclusions: Smartphone-based IMU assessments showed good agreement with COP analysis and detected condition-specific balance deficits in T2DM. These findings support smartphone-based IMU metrics as a promising tool for accessible and scalable balance screening in diabetes care.

Muscle dysfunction is an early complication of diabetic peripheral neuropathy (DPN). As a convenient and low-cost tool, muscle ultrasound has been used to assess muscle quality and muscle mass. However, the relationship between different muscle ultrasound parameters and DPN is unclear. This study was designed to investigate the relationship between ultrasound parameters of different muscles and DPN among patients with type 2 diabetes mellitus, including the rectus femoris (RF), tibialis anterior (TA), and medial head of gastrocnemius (MG). The research enrolled 90 patients with type 2 diabetes mellitus (T2DM). All images were attained from both sides. Muscle measurements contained muscle thickness (MT), cross-sectional area (CSA), echo intensity (EI), and corrected EI. The binary logistic regression and multiple linear regression were used to investigate the association between muscle ultrasound parameters and DPN or vibration perception threshold (VPT). EI, corrected EI, MT of MG, and EI of TA were associated with DPN separately after adjusting other clinical variates. Among these muscle parameters, the EI of MG had a better predictive value (OR: 1.114, 95% CI: 1.039, 1.196) of DPN. Combined with CSA of RF, peripheral artery disease (PAD), and sex, the corrected EI of MG was associated with the vibration perception threshold (VPT) (standard β = 0.242, p < 0.001), better than the EI of MG (standard β = 0.215, p = 0.002). MG (MT, EI, and corrected EI) and TA (EI) were associated with DPN, respectively. CSA of RF and corrected EI or EI of MG combined with PAD and sex were associated with VPT significantly, which supported that muscle ultrasound might be a substantial quantitative tool for detecting the exercise benefits for DPN.

Objective To investigate the morbidity rate of diabetic peripheral neuropathy (DPN) and analyze its related factors through the testing of the vibration perception threshold (VPT) in outpatients with type 2 diabetes mellitus (T2DM). Methods VPT on both feet in 1018 T2DM outpatients was examined by the quantitative examination equipment of vibration perception. The participants were then assigned to the low–risk group ( 25 V, n=232). The clinical characteristics and biochemical parameters were compared. Results The patients in the low–risk, mediate–risk, and high–risk group accounted for 47.54%, 29.67%, and 22.79%, respectively. The patients with neuropathy symptoms accounted for 39.26%, 61.26%, and 65.52% in the low–risk, mediate–risk, and high–risk group, respectively. There were significant differences in age, diabetic duration, systolic blood pressure (SBP), glycated hemoglobin (HbA1c) and glycated serum albumin (GA) among the three groups (all P< 0.05). VPT of male patients was worse than that of female patients (P<0.01). VPT was positively correlated with age, gender, diabetic duration, SBP, HbA1c, GA, and fasting plasma glucose (FPG) (all P<0.05). In multiple stepwise regression analysis, age (P=0.000), HbA1c (P=0.046), and GA (P=0.030) were independent influencing factors of VPT. Conclusions The prevalence of DPN was 22.79% screened by VPT examination in type 2 diabetic outpatients. Age, HbA1c and GA may be independent influencing factors of VPT. Key words: Diabetic peripheral neuropathy; Vibration perception threshold; Influencing factors

Objective To observe the changes of serum ferritin and 25-(OH) vitamin D3 in patients with diabetic cranial neuropathy. Methods There were 50 patients without diabetic Cranial neuropathy, 46 patients with diabetic cranial neuropathy, and 40 cases of normal control group. The changes of serum ferritin and 25-hydroxy vitamin D3 were observed in each group. The correlation between two indexes and the correlation with diabetic cranial neuropathy were analzyzed. Results The serum ferritin levels in diabetic group and diabetic neuropathy group were significantly higher than those in normal control group (P<0.01), and its level in patients with diabetic cranial neuropathy [(687.54±65.38)ng/ml] was significantly higher than that of patients without diabetic cranial neuropathy [(497.28±46.39)ng/ml, P<0.01]. The serum 25-(OH) vitamin D3 levels in the diabetic group and diabetic neuropathy group were lower than those in the control group (P<0.01), and its level in patients with diabetic cranial neuropathy [(26.45±8.93)nmol/l] was significantly less than that of patients without diabetic cranial neuropathy [(37.19±9.74)nmol/L, P<0.01]. Serum ferritin levels were positively correlated with 25- (OH) vitamin D3 (r=-0.59, P<0.01). Multivariate unconditional Logistic regression analysis showed that diabetic neuropathy was negatively correlated with 25-(OH) vitamin D3 (P<0.05). Conclusions The increases of serum ferritin and 25-(OH) vitamin D3 are closely related to the occurrence and development of diabetic cranial neuropathy, which provides the theoretical basis for clinical intervention therapy. Key words: Diabetic neuropathies/ME; Cranial nerve diseases/CO/ME; Ferritins/ME; Calcitriol/ME

Background &amp; objective: Diabetes mellitus is quite common and globally prevalent condition affecting patients’ quality of life. Patients who have type 2 diabetes mellitus (T2DM), are more likely to get diabetic peripheral neuropathy (DPN), which may affect feet, legs, hand, and arm. A BDNF gene rs6265 polymorphism in humans results in the substitution of valine with methionine at codon 66 (Val66Met). We aimed to find the possible link between human BDNF rs6265 gene polymorphism and T2DM with and without peripheral neuropathy and compare it with healthy subjects in Kirkuk City, Iraq. Methodology: One hundred subjects were chosen to participate in this research, aged from 35 to 75 y and divided into three groups: 35 DPN, 35 T2DM patients, and 30 healthy controls were selected randomly for BDNF gene rs6265 SNP screening by using conventional PCR with specific sets of primers. Products of PCR for patients and control groups were run on the gel electrophoresis to detect the SNP rs6265 fragment. A nerve-conducting study was used to examine DPN. Results: The observed results demonstrated the presence of two types of alleles identified as genotypic variants (GG and GA) among all participants in this investigation. By applying the Hardy-Weinberg Equilibrium principle (HWE) for both patient and control groups, the results proved that there was a statistically significant variance (P &lt; 0.05) in the genotypic frequencies between each of the groups that had been studied. The wild homozygous GG genotype in type 2 diabetic without neuropathy, with DPN, and healthy control group were 51.4%, 40% and 80% respectively. The heterozygous GA genotype were 48.6%, 60% and 20%, respectively in the three groups. Conclusion: The present study showed that the BDNF (Val66Met) rs6265 polymorphism is associated with type 2 diabetes mellitus and diabetic peripheral neuropathy in heterozygous allele G/A (Met/Met) and homozygous allele GG (Val/Val) genotype. Also, the current study found the absence of the mutant genotype AA, possibly due to the evidence that the distribution of the BDNF polymorphisms varies widely among different ethnic groups. Abbreviations: BDNF - Brain-derived neurotrophic factor; DPN - Diabetic peripheral neuropathy Keywords: Type2 diabetes mellitus; Diabetic peripheral neuropathy; Brain-Derived Neurotrophic Factor; BDNF rs6265 SNP; BDNF Val66Met polymorphism. Citation: Hamid R, Al-Wasiti E, Jabbar AM. Correlation between human BDNF rs6265 gene polymorphism and type-2 diabetes and diabetic peripheral neuropathy. Anaesth. pain intensive care 2024;28(4):752−756. DOI: 10.35975/apic.v28i4.2517 Received: March 08, 2024; Reviewed: April 20, 2024; Accepted: April 28, 2024

Diabetic neuropathy (DN) is a "Cinderella" complication, particularly in the Middle East. A high prevalence of undiagnosed DN and those at risk of diabetic foot ulceration (DFU) is a major concern. We have determined the prevalence of DN and its risk factors, DFU, and those at risk of DFU in patients with type 2 diabetes mellitus (T2DM) in secondary care in Qatar. Adults with T2DM were randomly selected from the two National Diabetes Centers in Qatar. DN was defined by the presence of neuropathic symptoms and a vibration perception threshold (VPT) ≥ 15 V. Participants with a VPT ≥ 25 V were categorized as high risk for DFU. Painful DN was defined by a DN4 score ≥4. Logistic regression analysis was used to identify predictors of DN. In 1082 adults with T2DM (age 54 ± 11 years, duration of diabetes 10.0 ± 7.7 years, 60.6% males), the prevalence of DN was 23.0% (95% CI, 20.5%-25.5%) of whom 33.7% (95% CI, 27.9%-39.6%) were at high risk of DFU, and 6.3% had DFU; 82.0% of the patients with DN were previously undiagnosed. The prevalence of DN increased with age and duration of diabetes and was associated with poor glycaemic control (HbA1c ≥ 9%) AOR = 2.1 (95% CI, 1.3-3.2), hyperlipidaemia AOR = 2.7 (95% CI, 1.5-5.0), and hypertension AOR = 2.0 (95% CI, 1.2-3.4). Despite DN affecting 23% of adults with T2DM, 82% had not been previously diagnosed with one-third at high risk for DFU. This argues for annual screening and identification of patients with DN. Furthermore, we identify hyperglycaemia, hyperlipidaemia, and hypertension as predictors of DN.

Peripheral neuropathy does not invariably coexist with autonomic neuropathy in diabetes mellitus

It is generally believed that gait characteristics of diabetic neuropathic patients differ from those of non-diabetic ones. However, it is still unclear how the abnormal foot sensation influences the gait during walking in type 2 diabetes mellitus (T2DM). For the purpose of gaining a better insight into the alterations of detailed gait parameters and figuring out important aspects in the gait indexes by peripheral neuropathy in elder T2DM patients, we compared the gait features in participants with normal glucose tolerance (NGT) controls and diabetic individuals complicated by peripheral neuropathy or not. Gait parameters were observed during the 10-m walk on flat land among different conditions of diabetes in 1,741 participants from three clinical centers. Subjects were divided into four groups: persons with NGT were taken as the control group; patients with T2DM included three subgroups: DM control (no chronic complications), DM-DPN (DM complicated by only peripheral neuropathy), and DM-DPN+LEAD (DM complicated by both neuropathy and artery disease). The clinical characteristics and gait parameters were assessed and compared among these four groups. Analyses of variance were employed to verify possible differences of gait parameters between groups and conditions. Stepwise multivariate regression analysis was performed to reveal possible predictors of gait deficits. Receiver operating characteristic (ROC) curve analysis was employed to find any discriminatory power of diabetic peripheral neuropathy (DPN) for the step time. In participants burdened with DPN, whether complicated by lower extremity arterial disease (LEAD) or not, step time increased sharply (p < 0.05). Stepwise multivariate regression models showed that independent variables of gait abnormality were sex, age, leg length, vibration perception threshold (VPT), and ankle-brachial index (ABI) (p < 0.01). Meanwhile, VPT was a significant independent predictor of step time, spatiotemporal variability (SDA), and temporal variability (SDB) (p < 0.05). ROC curve analysis was explored to find the discriminatory power of DPN for the occurrence of increased step time. The area under the curve (AUC) value was 0.608 (95% CI: 0.562-0.654, p < 0.01), and the cutoff point was 538.41 ms accompanied by a higher VPT. A significant positive association was observed between increased step time and the highest VPT group [odds ratio (OR) = 1.83, 95% CI: 1.32-2.55, p< 0.01]. In female patients, this OR value elevated to 2.16 (95% CI: 1.25-3.73, p< 0.01). In addition to sex, age, and leg length, VPT was a distinct factor that associated with altered gait parameters. DPN is associated with increased step time, and the step time increases with worsening VPT in type 2 diabetes.

Objective: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes; timely detection is critical for preventing severe complications. Traditional nerve conduction studies (NCS) are the gold standard for assessing neuropathy, but traditional NCS cannot detect neuropathy in very early or mild cases. The sural/radial amplitude ratio (SRAR) and dorsal sural/radial amplitude ratio (DSRAR) have emerged as potential markers for identifying early, length-dependent neuropathy in diabetic patients, though standardized cut-off values remain unexplored. This study evaluates the diagnostic effectiveness of the SRAR and DSRAR in identifying diabetic neuropathy (DPN) among individuals with type 2 diabetes mellitus (T2DM). By analyzing sensory nerve conduction parameters of the foot and arm, the study aims to compare the efficacy of these amplitude ratios in distinguishing neuropathic from non-neuropathic individuals. Materials and Methods: A cross-sectional study was conducted among patients with T2DM, classified into neuropathic (VPT &gt; 15) and non-neuropathic (VPT &lt; 15) groups based on vibration perception threshold (VPT). Sural and dorsal sural nerve amplitudes were recorded alongside radial nerve amplitudes, and the SRAR and DSRAR were calculated. A total of 103 participants (mean age: 53.55 ± 10.57 years; mean body mass index: 25.34 ± 4.31 kg/m2) with T2DM (mean duration: 9.28 ± 6.54 years) were included. Diagnostic accuracy, sensitivity, specificity, and predictive values were assessed using receiver operating characteristic analysis and the area under the curve (AUC) was calculated for both SRAR and DSRAR. Results: Sural and dorsal sural nerve amplitudes were significantly lower in the neuropathic group (P &lt; 0.01). The mean SRAR was 0.72 ± 0.23 in non-neuropathic participants and 0.56 ± 0.25 in those with neuropathy (P = 0.004). Similarly, DSRAR was markedly reduced in the neuropathic group (0.22 ± 0.03 vs. 0.28 ± 0.02; P = 0.001). At cut-off values of 0.59 (SRAR) and 0.26 (DSRAR), the sensitivity and specificity of DSRAR (83.72% and 86.36%) surpassed those of SRAR (68.97% and 62.16%). Conclusion: Both SRAR and DSRAR demonstrate diagnostic potential for detecting diabetic neuropathy; however, DSRAR exhibits superior sensitivity, specificity, and overall diagnostic accuracy. With its higher predictive values and robust AUC, DSRAR may be a more reliable non-invasive marker for the clinical evaluation of neuropathy in T2DM patients.

Objective To evaluate the clinical significance of quantitative sensory testing (QST) in screening diabetic peripheral neuropathy of the early stage. Methods One hundred patients with type 2 diabetes mellitus were examined by nerve conduction velocity (NCV) and QST examination. With the NCV positive as the gold criterion for screening diabetic peripheral neuropathy of the early stage, the sensitivity and specificity of QST was further analyzed for diagnosis of the early stage diabetic peripheral neuropathy. Results Among the 100 patients with type 2 diabetes mellitus,there were 41 cases positive and 59 cases negative in NCV examination. On the other hand,there were 74 cases positive,and 26 cases negative in QST. The sensitivity and specificity of QST for the diagnosis of early stage diabetic peripheral neuropathy was 97.56% (40/41) and 42.37% (25/59). Conclusions In the screening of early stage diabetic peripheral neuropathy,QST shows higher detection sensitivity,but lower specificity than NCV examination. Therefore, QST may be an examination for the supplement of the routine electromyography. Key words: Diabetic neuropathies; Sensitivity and specificity; Electromyography; Quantitative sensory testing

This study aimed to assess subclinical peripheral diabetic neuropathy (PDN) in adolescents with type 1 diabetes mellitus (T1DM). Subjects included 53 T1DM patients (age (mean ± SE): 15.8 ± 0.54 years, disease duration: 6.0 ± 0.51 years and HbA1c: 7.9 ± 0.19%), and 37 healthy gender matched controls (age: 15.6 ± 0.52 years). PDN was assessed by vibration perception threshold (VPT) and by quantitative sensory testing (QST). In controls, 95% confidence intervals were calculated. Among patients, VPT prevalence of abnormality ranged from 60-73.4% on different sites. Higher VPT was found in patients on all examined sites (p < 0.01). In controls, VPT correlated with height (r = 0.48, p = 0.05). Regarding QST prevalence of abnormality, cold detection threshold (CDT) ranged 7.3-39.0%, cold pain threshold (CPT) ranged 22.22-29.63%, hot detection threshold (HDT) ranged 34.14-63.41%, and hot pain threshold (HPT) ranged 15.79-36.84%. In patients, CPT correlated with BMI (r = 0.42, p = 0.05) and diabetes duration, (r = 0.40, p = 0.05), HPT correlated with age (r = 0.36, p = 0.05) and height (r = 0.35, p = 0.05), while in controls with BMI (r = 0.51, p = 0.05). No correlation of VPT or QST with HbA1c was observed. Adolescents with T1DM in this study, although asymptomatic, showed a high prevalence of impaired indices of PDN, highlighting potential clinical implications of early identification of PDN.