Prevalence of peripheral neuropathy, amputation, and quality of life in patients with diabetes mellitus.

Peripheral neuropathy and amputation are common complications of diabetes mellitus (DM) that significantly impact the quality of life of the affected individuals. This study aims to investigate the prevalence of peripheral neuropathy, the level of amputation, and the quality of life in patients with DM. This cross-sectional study was conducted after approval of the synopsis involving 225 diagnosed patients with DM on pre-defined eligibility criteria, selected from public sector OPDs, specialized diabetes centres, and centres manufacturing orthotics and prosthetics. Data were collected through interviews, observations, and the administration of the Michigan Neuropathy Screening Instrument and the Asian Diabetes Quality of Life Questionnaire. The level of amputation was recorded for each participant. Data was entered into SPSS, and results were synthesized. Pearson correlation is applied to find an association between gender and the quality of life of the participants, while P ≤ 0.05 will be considered significant. The prevalence of peripheral neuropathy in a sample of 225, based on a self-administered questionnaire, was (44.4%), and in terms of foot examination was (51.1%). As people progressed in age, the prevalence increased to 20.0% in patients above 60 years and 8.9% in ≤ 35 years of age. The majority of participants (56.0%) have had DM for less than five years. Females were 57.8% of the study population, while 97.8% of participants had type II DM. Below-knee amputation of the right limb was observed in 22(9.8%) of the participants. The QoL was poor in the majority of the participants (96.9%) patients with DM (P = 0.638 and T = -0.471). This cross-sectional study highlights a high prevalence of peripheral neuropathy and amputation and poor QoL in patients with diabetic mellitus.

An Insight into Potential Pharmacotherapeutic Agents for Painful Diabetic Neuropathy.

Diabetes is the 4th most common disease affecting the world's population. It is accompanied by many complications that deteriorate the quality of life. Painful diabetic neuropathy (PDN) is one of the debilitating consequences of diabetes that effects one-third of diabetic patients. Unfortunately, there is no internationally recommended drug that directly hinders the pathological mechanisms that result in painful diabetic neuropathy. Clinical studies have shown that anticonvulsant and antidepressant therapies have proven fruitful in management of pain associated with PDN. Currently, the FDA approved medications for painful diabetic neuropathies include duloxetine, pregabalin, tapentadol extended release, and capsaicin (for foot PDN only). The FDA has also approved the use of spinal cord stimulation system for the treatment of diabetic neuropathy pain. The drugs recommended by other regulatory bodies include gabapentin, amitriptyline, dextromethorphan, tramadol, venlafaxine, sodium valproate, and 5 % lidocaine patch. These drugs are only partially effective and have adverse effects associated with their use. Treating painful symptoms in diabetic patient can be frustrating not only for the patients but also for health care workers, so additional clinical trials for novel and conventional treatments are required to devise more effective treatment for PDN with minimal side effects. This review gives an insight on the pathways involved in the pathogenesis of PDN and the potential pharmacotherapeutic agents. This will be followed by an overview on the FDA-approved drugs for PDN and commercially available topical analgesic and their effects on painful diabetic neuropathies.

Silver Nanoparticles Conjugate Attenuates Highly Active Antiretroviral Therapy-Induced Hippocampal Nissl Substance and Cognitive Deficits in Diabetic Rats.

BACKGROUND: The application of nanomedicine to antiretroviral drug delivery holds promise in reducing the comorbidities related to long-term systemic exposure to highly active antiretroviral therapy (HAART). However, the safety of drugs loaded with silver nanoparticles has been debatable. This study is aimed at evaluating the effects of HAART-loaded silver nanoparticles (HAART-AgNPs) on the behavioural assessment, biochemical indices, morphological, and morphometric of the hippocampus in diabetic Sprague-Dawley rats. METHODS: Conjugated HAART-AgNPs were characterized using FTIR spectroscopy, UV spectrophotometer, HR-TEM, SEM, and EDX for absorbance peaks, size and morphology, and elemental components. Forty-eight male SD rats (250 ± 13 g) were divided into nondiabetic and diabetic groups. Each group was subdivided into (n = 8) A (nondiabetic+vehicle), B (nondiabetic+HAART), C (nondiabetic+HAART-AgNPs), D (diabetic+vehicle), E (diabetic+HAART), and F (diabetic+HAART-AgNPs). Morris water maze, Y-maze test, and weekly blood glucose levels were carried out. Following the last dose of 8-week treatment, the rats were anaesthetized and euthanized. Brain tissues were carefully removed and postfixed for Nissl staining histology. RESULTS: 1.5 M concentration of HAART-AgNPs showed nanoparticle size 20.3 nm with spherical shape. HAART-AgNPs revealed 16.89% of silver and other elemental components of HAART. The diabetic control rats showed a significant increase in blood glucose, reduced spatial learning, positive hippocampal Nissl-stained cells, and a significant decrease in GSH and SOD levels. However, administration of HAART-AgNPs to diabetic rats significantly reduced blood glucose level, improved spatial learning, biochemical indices, and enhanced memory compared to diabetic control. Interestingly, diabetic HAART-AgNP-treated rats showed a significantly improved memory, increased GSH, SOD, and number of positive Nissl-stained neurons compared to diabetic-treated HAART only. CONCLUSION: Administration of HAART to diabetic rats aggravates the complications of diabetes and promotes neurotoxic effects on the experimental rats, while HAART-loaded silver nanoparticle (HAART-AgNP) alleviates diabetes-induced neurotoxicity.

Tuina for diabetic peripheral neuropathy: A protocol for a systematic review and meta-analysis.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications of diabetes mellitus, with an incidence ranging from 60% to 90%. With the change in modern dietary structure, the incidence of diabetes is increasing year by year, and DPN is also on the rise. Tuina therapy has been widely used in the treatment of DPN, but there is no systematic review on the treatment of DPN. Therefore, this study aimed to conduct a meta-analysis of Tuina in the treatment of DPN to clarify its efficacy. METHODS: The following electronic databases will be searched: PubMed, the Cochrane Library, Embase, Web of Science, Medline, CNKI, Chinese Biomedical Literature Database, VIP, and Wan Fang databases. We will consider articles published between database initiation and May 2021. We will use Review Manager 5.4, provided by the Cochrane Collaborative Network for statistical analysis. Clinical randomized controlled trials related to Tuina for diabetic peripheral neuropathy were included in this study. Language is limited to both Chinese and English. Research selection, data extraction, and research quality assessments were independently completed by two researchers. We then assessed the quality and risk of the included studies and observed the outcome measures. RESULTS: This study provides a high-quality synthesis to assess the effectiveness and safety of Tuina for treating diabetic peripheral neuropathy. CONCLUSION: This systematic review will provide evidence to determine whether Tuina is an effective and safe intervention for patients with diabetic peripheral neuropathy. ETHICS AND DISSEMINATION: The protocol of the systematic review does not require ethical approval because it does not involve humans. This article will be published in peer-reviewed journals and presented at relevant conferences. REGISTRATION NUMBER: INPLASY202150027.

Decreased Microstructural Integrity of the Central Somatosensory Tracts in Diabetic Peripheral Neuropathy.

CONTEXT: Although diabetic peripheral neuropathy (DPN) is predominantly considered a disorder of the peripheral nerves, some evidence for central nervous system involvement has recently emerged. However, whether or to what extent the microstructure of central somatosensory tracts may be injured remains unknown. OBJECTIVE: This work aimed to detect the microstructure of central somatosensory tracts in type 2 diabetic patients and to correlate it with the severity of DPN. METHODS: A case-control study at a tertiary referral hospital took place with 57 individuals with type 2 diabetes (25 with DPN, 32 without DPN) and 33 nondiabetic controls. The fractional anisotropy (FA) values of 2 major somatosensory tracts (the spinothalamic tract and its thalamocortical [spino-thalamo-cortical, STC] pathway, the medial lemniscus and its thalamocortical [medial lemnisco-thalamo-cortical, MLTC] pathway) were assessed based on diffusion tensor tractography. Regression models were further applied to detect the association of FA values with the severity of DPN in diabetic patients. RESULTS: The mean FA values of left STC and left MLTC pathways were significantly lower in patients with DPN than those without DPN and controls. Moreover, FA values of left STC and left MLTC pathways were significantly associated with the severity of DPN (expressed as Toronto Clinical Scoring System values) in patients after adjusting for multiple confounders. CONCLUSION: Our findings demonstrated the axonal degeneration of central somatosensory tracts in type 2 diabetic patients with DPN. The parallel disease progression of the intracranial and extracranial somatosensory system merits further attention to the central nerves in diabetic patients with DPN.

Predicting the quality of life based on pain dimensions and psychiatric symptoms in patients with Painful diabetic neuropathy: a cross-sectional prevalence study in Iranian patients.

BACKGROUND: This study aimed to predict the quality of life (QOL) in patients with Painful Diabetic Neuropathy (PDN) based on pain severity, pain catastrophizing, pain acceptance, depression, anxiety, and sleep disturbance. Also, this study was aimed to assess the prevalence of psychiatric symptoms in Iranian patients with PDN. METHOD: 1120 patients (mean age, 53.6 ± 12.6 years) participated in the research. Data were collected by the Quality of life questionnaire (NeuroQoL); Beck Depression Inventory, Beck Anxiety Inventory, the visual analog scale for pain severity, Pain Catastrophizing Scale (PCS), Chronic Pain Acceptance Questionnaire (CPAQ) and Pittsburgh Sleep Quality Index (PSQI). Finally, the data were analyzed using SPSS-26 by multiple regression analysis. RESULTS: The results showed the regression models' significance, and the dependent variables predicted 42% of total changes in the QOL. The most significant predicting factors were depression, pain catastrophizing, pain acceptance, pain severity, sleep disturbance, and anxiety in order. In patients with PDN, the prevalence of sleep disturbances, depression, and anxiety were 85.5%, 68.2%, and 62.1%, respectively. Also, comorbid depression and anxiety were found in 47% of patients. CONCLUSION: Results demonstrated a significant relationship between pain-related and psychiatric dimensions with QOL. Thus, it is suggested to design more specific psychological-based rehabilitation interventions in which these variables are considered. They should focus on more significant variables (such as depression and pain catastrophizing) to reach better treatment outcomes. Furthermore, this research shows a high level of anxiety, depression, and sleep disturbance in Iranian patients with PDN. Thus, experts and clinicians are suggested to focus on reducing these psychiatric symptoms.

Clinical Characteristics of Patients with co-Existent Diabetic Peripheral Neuropathy and Depression: A Systematic Review.

OBJECTIVES: Both diabetic peripheral neuropathy and depression have significant implications on patients' quality of life, management and outcomes. We aimed to evaluate all available evidence concerning patients with co-existent diabetic peripheral neuropathy and depression, and describe their clinical characteristics, in order to promote early recognition and management. METHODS: Systematic search of PubMed for studies providing data on patients with diabetic peripheral neuropathy and depression. The primary outcome was to evaluate all available evidence related to characteristics of diabetes, diabetic peripheral neuropathy and depression. Secondary study outcomes included comorbid conditions and complications in these patients. RESULTS: Final analysis included 24 studies with data on 205 patients. Most patients were adults between 18-65 years of age. Mean HbA1c value was above 8% and most patients were treated with insulin. Neuropathy was predominantly painful and most patients with available data were considered to have major depressive disorder. In addition to diabetic peripheral neuropathy and depression, diabetes-related complications were recorded in 43 patients, the most common being autonomic neuropathy, retinopathy and nephropathy. The most frequently reported comorbidities were weight loss (72 patients), impotence (60 patients), hypertension (23 patients) and coronary artery disease (22 patients). CONCLUSIONS: The present study describes the characteristics of patients with co-existent diabetic peripheral neuropathy and depression, aiming for prompt detection, prevention of further deterioration and improvement of patient outcomes. Available evidence shows that the majority of these patients are adults, with painful peripheral neuropathy and with insulin-treated and inadequately controlled diabetes.

Diabetes distress and peripheral neuropathy are associated with medication non-adherence in individuals with type 2 diabetes in primary care.

BACKGROUND: Psychosocial factors like diabetes distress and social support, as well as the presence of complications, affect an individual's self-management ability; however, their role in adherence behaviours is not yet clear. We examined the role of psychosocial factors and complications in non-adherence behaviours in individuals with diabetes in primary care. METHODS: Baseline survey with nine-month follow up through medical records of patients with type 2 diabetes attending primary care. Medication adherence and diabetes distress were assessed using Morisky Green Levine Medication Adherence Scale and Problem Areas in Diabetes, respectively. Appointment adherence was assessed through medical records. RESULTS: Of the 448 participants studied, 59.8% had medication non-adherence and 21.7% were non-adherent to scheduled appointments. PAID score (odds ratio (OR) 1.01, 95% confidence interval 1.00-1.03, p = 0.013), peripheral neuropathy (OR 1.99, 95%CI 1.18-3.37, p = 0.01), home glucose monitoring (OR 0.46, 95%CI 0.30-0.69, p < 0.001), HbA1c (OR 1.34, 95%CI 1.13-1.61, p = 0.001), and age (OR 0.96, 95%CI 0.93-0.98, p = 0.001) were associated with medication non-adherence. Indian ethnicity (OR 2.93, 95%CI 1.59-5.39, p = 0.001), secondary or higher education (OR 1.94, 95%CI 1.14-3.27, p = 0.014), and HbA1c (OR 1.38, 95%CI 1.18-1.63, p < 0.001) were associated with appointment non-adherence. CONCLUSIONS: Non-adherence behaviours were prevalent and significantly associated with higher HbA1c. Medication non-adherence was more likely in younger individuals, those with higher diabetes distress or peripheral neuropathy. Appointment non-adherence was more likely in individuals of Indian ethnicity or those with higher education. Greater support for these groups may help improve adherence behaviours and outcomes.

Correlates of self-rated health in people with diabetic peripheral neuropathy: a longitudinal study.

AIM: Self-rated health, a measure of self-reported general health, is a robust predictor of morbidity and mortality in various populations, including persons with diabetes. This study examines correlates of self-rated health in adults with diabetic peripheral neuropathy (DPN). METHODS: Participants recruited from the UK and USA (n = 295; mean (± sd) age: 61.5 ± 10.7 years; 69% male; 71% type 2 diabetes) rated their health at baseline and 18 months. DPN severity was assessed using the neuropathy disability score and the vibration perception threshold. Validated self-report measures assessed neuroticism, DPN-symptoms of pain, unsteadiness and reduced sensation in feet, DPN-related limitations in daily activities, DPN-specific emotional distress and symptoms of depression. RESULTS: In the fully adjusted baseline model, younger age, presence of cardiovascular disease and higher depression symptom scores showed likely clinically meaningful independent associations with worse health ratings. Being at the UK study site and presence of nephropathy indicated potentially meaningful independent associations with lower baseline health ratings. These predictors were largely consistent in their association with health ratings at 18 months. CONCLUSION: Results identify independent correlates of health ratings among adults with DPN. Future research should investigate the clinical implications of associations and examine changes in these variables over time and potential effects on changes in health perceptions. If these associations reflect causal pathways, our results may guide interventions to target issues that are likely to have an impact on subjectively experienced health as an important patient-reported outcome in DPN care.

Diabetic neuropathy and neuropathic pain: a (con)fusion of pathogenic mechanisms?

Neuropathy is a common complication of long-term diabetes that impairs quality of life by producing pain, sensory loss and limb amputation. The presence of neuropathy in both insulin-deficient (type 1) and insulin resistant (type 2) diabetes along with the slowing of progression of neuropathy by improved glycemic control in type 1 diabetes has caused the majority of preclinical and clinical investigations to focus on hyperglycemia as the initiating pathogenic lesion. Studies in animal models of diabetes have identified multiple plausible mechanisms of glucotoxicity to the nervous system including post-translational modification of proteins by glucose and increased glucose metabolism by aldose reductase, glycolysis and other catabolic pathways. However, it is becoming increasingly apparent that factors not necessarily downstream of hyperglycemia can also contribute to the incidence, progression and severity of neuropathy and neuropathic pain. For example, peripheral nerve contains insulin receptors that transduce the neurotrophic and neurosupportive properties of insulin, independent of systemic glucose regulation, while the detection of neuropathy and neuropathic pain in patients with metabolic syndrome and failure of improved glycemic control to protect against neuropathy in cohorts of type 2 diabetic patients has placed a focus on the pathogenic role of dyslipidemia. This review provides an overview of current understanding of potential initiating lesions for diabetic neuropathy and the multiple downstream mechanisms identified in cell and animal models of diabetes that may contribute to the pathogenesis of diabetic neuropathy and neuropathic pain.

Beneficial effects of galanin system on diabetic peripheral neuropathic pain and its complications.

Diabetic peripheral neuropathic pain (DPNP) is a distal spontaneous pain, caused by lesion of sensory neurons and accompanied by depression and anxiety frequently, which reduce life quality of patients and increase society expenditure. To date, antidepressants, serotonin-noradrenaline reuptake inhibitors and anticonvulsants are addressed as first-line therapy to DPNP, alone or jointly. It is urgently necessary to develop novel agents to treat DPNP and its complications. Evidences indicate that neuropeptide galanin can regulate multiple physiologic and pathophysiological processes. Pain, depression and anxiety may upregulate galanin expression. In return, galanin can modulate depression, anxiety, pain threshold and pain behaviors. This article provides a new insight into regulative effects of galanin and its subtype receptors on antidepressant, antianxiety and against DPNP. Through activating GALR1, galanin reinforces depression-like and anxiogenic-like behaviors, but exerts antinociceptive roles. While via activating GALR2, galanin is referred to as anti-depressive and anti-anxiotropic compounds, and at low and high concentration facilitates and inhibits nociceptor activity, respectively. The mechanism of the galanin roles is relative to increase in K+ currents and decrease in Ca2+ currents, as well as neurotrophic and neuroprotective roles. These data are helpful to develop novel drugs to treat DPNP and its complications.

Reducing monocarboxylate transporter MCT1 worsens experimental diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is one of the most common complications in diabetic patients. Though the exact mechanism for DPN is unknown, it clearly involves metabolic dysfunction and energy failure in multiple cells within the peripheral nervous system. Lactate is an alternate source of metabolic energy that is increasingly recognized for its role in supporting neurons. The primary transporter for lactate in the nervous system, monocarboxylate transporter-1 (MCT1), has been shown to be critical for peripheral nerve regeneration and metabolic support to neurons/axons. In this study, MCT1 was reduced in both sciatic nerve and dorsal root ganglia in wild-type mice treated with streptozotocin (STZ), a common model of type-1 diabetes. Heterozygous MCT1 null mice that developed hyperglycemia following STZ treatment developed a more severe DPN compared to wild-type mice, as measured by greater axonal demyelination, decreased peripheral nerve function, and increased numbness to innocuous low-threshold mechanical stimulation. Given that MCT1 inhibitors are being developed as both immunosuppressive and chemotherapeutic medications, our results suggest that clinical development in patients with diabetes should proceed with caution. Collectively, our findings uncover an important role for MCT1 in DPN and provide a potential lead toward developing novel treatments for this currently untreatable disease.

Diabetic neuropathy and other diabetic complications at the Diabetic Neuropathy Center of the University of Debrecen / A diabeteses neuropathia és egyéb szövodmények elofordulása a Debreceni Egyetem Diabeteses Neuropathia Centrumában

INTRODUCTION: The prevalence of diabetes mellitus is significantly increasing worldwide. Distal sensorimotor neuropathy (DSPN) is the most common and the earliest detectable microvascular complication. Due to its diverse clinical appearance and atypical symptoms, DSPN is often recognized in an advanced stage. AIM AND METHOD: In our study, the data of 431 patients who were examined using the Neurometer® between 2011 and 2018 at the Diabetic Neuropathy Center of the University of Debrecen were processed and the correlations between cardiovascular and microvascular complications, laboratory parameters and the severity of DSPN were investigated. RESULTS: The average age of patients was 63.4 years, 62% of them were women, and 92% had type 2 diabetes mellitus. The average duration of diabetes was 13.7 years. Cardiovascular disease (CVD) was diagnosed in 42% of the patients. The incidence of retinopathy was 12%, persistent microalbuminuria was 16%. Despite DSNP complaints, neuronal damage could not be detected in 19%; in the examined patients 49% had mild, 19% moderate and 13% severe neuropathy. Diabetes-related neurological damage was more serious in the presence of both diabetic retinopathy (p<0.001) and microalbuminuria (p<0.001). The incidence of these microvascular complications and the severity of DSPN showed a significant positive correlation (p<0.001). There was no correlation between the severity of peripheral neuropathy and the development of CVD, and we did not find any correlations between the severity of DSPN and CVD. CONCLUSION: Based on our investigation, correlation between the progression of diabetic neuropathy and cardiovascular complications was not found, although the progression of diabetic neuropathy indicated the development of other microvascular diseases. Peripheral neurological examination using the Neurometer® is appropriate for controlling the DSPN status and the establishment of the severity of neuropathy determines the quality of life in diabetic patients. Among these patients, the risk of CVD can be assessed by Ewing's test for autonomic nervous system function. Orv Hetil. 2020; 161(30): 1243-1251.

Awareness of hypoglycemia and spectral analysis of heart rate variability in type 1 diabetes.

AIMS: To investigate the relationship of unawareness of hypoglycemia with spectral analysis of heart rate variability (HRV) and clinical variables in type 1 diabetes (T1D) individuals. METHODS: Participants with type 1 diabetes mellitus (type 1 diabetes) were prospectively assessed for hypoglycemia awareness using the Pedersen-Bjergaard method and were classified as normal hypoglycemia awareness, impaired hypoglycemia awareness and hypoglycemia unawareness. Indices of HRV in frequency domain were evaluated and Ewing tests were used for the diagnosis of cardiovascular autonomic neuropathy (CAN). RESULTS: Ninety-eight participants with T1D (mean age 26 years, average diabetes duration 13 years, and mean HbA1c 8.4%) were included in this study. The prevalence of hypoglycemia unawareness was 28%. No significant difference was observed on the prevalence of CAN among groups of different hypoglycemia awareness (p = 0.740). On regression analyses, abnormal results of HRV in frequency domain were not associated with unawareness of hypoglycemia. On univariable regression analysis, age, diabetes duration and estimated creatinine clearance were associated with unawareness of hypoglycemia. CONCLUSION: CAN as assessed by Ewing tests and spectral analysis of HRV is not associated with unawareness of hypoglycemia. There is association of age, diabetes duration and renal deficit with unawareness of hypoglycemia.

Gongronema latifolium Benth. leaf extract attenuates diabetes-induced neuropathy via inhibition of cognitive, oxidative stress and inflammatory response.

BACKGROUND: Gongronema latifolium (G. latifolium) Benth. leaves are traditionally used to treat diabetes mellitus (DM) and other diseases in Nigeria and West Africa. This study was performed to evaluate the neuroprotective effect of aqueous extract of G. latifolium leaf against DM. Antidiabetic activity of G. latifolium extracts (6.36, 12.72 and 25.44 mg kg-1 , i.p.) was determined in alloxan-induced diabetic rats. Fasting blood glucose level and oxidative stress markers catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), and nitric oxide (NO) levels were measured. Cognitive biomarkers acetylcholinesterase (AChE), butyrylcholinesterase (BChE), dopamine (DOPA), serotonin, epinephrine and norepinephrine and cyclooxygenase (COX-2) were measured in the brain of controls and of G. latifolium-treated diabetic rats. RESULTS: Administration of G. latifolium leaf extract to diabetic rats significantly restored the alterations in the levels of fasting blood glucose (FBG). The MDA and NO levels were significantly reduced with an improvement in CAT, SOD, and GPx activity in the kidneys and brains of diabetic rats treated with G. latifolium. Gongronema latifolium also significantly decreased the levels of AChE, BChE, DOPA, serotonin, epinephrine, and nor-epinephrine in diabetic rats. G. latifolium effectively ameliorated COX-2 in diabetic rats. CONCLUSION: This study showed that leaf extract of G. latifolium improved antioxidant defense against oxidative stress. It displays a neuroprotective effect resulting in the modulation of brain neurotransmitters, which could be considered as a promising treatment therapy. © 2020 Society of Chemical Industry.

Hypoglycemia unawareness and autonomic dysfunction in diabetes: Lessons learned and roles of diabetes technologies.

Impaired awareness of hypoglycemia (IAH) is a reduction in the ability to recognize low blood glucose levels that would otherwise prompt an appropriate corrective therapy. Identified in approximately 25% of patients with type 1 diabetes, IAH has complex pathophysiology, and might lead to serious and potentially lethal consequences in patients with diabetes, particularly in those with more advanced disease and comorbidities. Continuous glucose monitoring systems can provide real-time glucose information and generate timely alerts on rapidly falling or low blood glucose levels. Given their improvements in accuracy, affordability and integration with insulin pump technology, continuous glucose monitoring systems are emerging as critical tools to help prevent serious hypoglycemia and mitigate its consequences in patients with diabetes. This review discusses the current knowledge on IAH and effective diagnostic methods, the relationship between hypoglycemia and cardiovascular autonomic neuropathy, a practical approach to evaluating cardiovascular autonomic neuropathy for clinicians, and recent evidence from clinical trials assessing the effects of the use of CGM technologies in patients with type 1 diabetes with IAH.

[Diabetic polyneuropathy]. / Diabetische Polyneuropathie.

Approximately one of three people with diabetes is affected by distal symmetric sensorimotor polyneuropathy (DSPN) which is associated with marked impairment in quality of life due to partly excruciating neuropathic pain on the one hand and painless foot ulcers on the other hand. The prevalence of painful DSPN may reach up to one quarter of patients with diabetes, while DSPN may be asymptomatic in up to half of the patients affected. Regrettably, DSPN still remains underdiagnosed. Typical neuropathic symptoms include pain, paresthesias and numbness particularly in the feet and calves. The management of DSPN includes three cornerstones: (1) lifestyle modification, causal treatment aimed at near-normoglycemia and multifactorial cardiovascular risk intervention, (2) pathogenesis-derived treatment and (3) symptomatic treatment of neuropathic pain. Multimodal pain treatment should not only aim at pain relief, but also allow for improvement in quality of sleep, mobility, and general quality of life.

Mediators and moderators of change in mindfulness-based stress reduction for painful diabetic peripheral neuropathy.

Painful diabetic peripheral neuropathy (PDPN) is a chronic pain condition with modest response to pharmacotherapy. Participation in mindfulness-based stress reduction (MBSR) leads to improvements in pain-related outcomes but the mechanisms of change are unknown. The present study examined the mediators and moderators of change in 62 patients with PDPN who participated in a randomized controlled trial comparing MBSR to waitlist. Changes in mindfulness and pain catastrophizing were tested simultaneously as mediators. Increased mindfulness mediated the association between participation in MBSR and improved pain severity, pain interference, and the physical component of health-related quality of life (HRQoL) 3 months later. The mediation effect of pain catastrophizing was not significant. Linear moderated trends were also found. Post-hoc moderated mediation analyses suggested that MBSR patients with longer histories of diabetes might increase their mindfulness levels more, which in turn leads to improved pain severity and physical HRQoL. These results allow for a deeper understanding of pathways by which MBSR benefits patients with PDPN.

Beneficial effects of nano-curcumin supplement on depression and anxiety in diabetic patients with peripheral neuropathy: A randomized, double-blind, placebo-controlled clinical trial.

Depression in patients with diabetes is associated with poor glycemic control and linked to an increased risk for diabetes complications such as neuropathy. Curcumin has shown potential antidepressant-like activities in some studies. The present study is the first randomized controlled trial to test the efficacy of nano-curcumin supplementation on depression, anxiety, and stress in patients with diabetic polyneuropathy. Eighty patients with diabetes were enrolled in this parallel, double-blind, randomized, placebo-controlled clinical trial. The participants were allocated randomly to the intervention (n = 40) and control (n = 40) groups. They received 80 mg of nano-curcumin or placebo capsules daily for 8 weeks. At baseline and end of study, anthropometric measurements, dietary intake, physical activity, glycemic indices, and severity of neuropathy were assessed. The depression, anxiety, and stress level were measured by Depression, Anxiety, Stress Scale (DASS-21-items) questionnaire before and after the intervention. After intervention, there was a significant reduction in the mean score of depression in the nano-curcumin group (from 16.7 [3.1] to 15.3 [2.6]) compared with placebo group (17.5 [3.2] to 17.3 [3.1]; p = .02). In addition, a significant fall was found in the mean score of anxiety in the nano-curcumin group (from 22.4 [4.03] to 20.6 [3.4]) compared with the placebo group (21.9 [3.5] to 21.2 [3.5]; p = .009). Changes in stress score were not statistically significant between the two groups. These findings suggested that nano-curcumin supplementation for 8 weeks was effective in reducing depression and anxiety scores in patients with diabetic polyneuropathy.

Diabetic polyneuropathy and pain, prevalence, and patient characteristics: a cross-sectional questionnaire study of 5,514 patients with recently diagnosed type 2 diabetes.

Most studies of diabetic polyneuropathy (DPN) and painful DPN are conducted in persons with longstanding diabetes. This cross-sectional study aimed to estimate the prevalence of DPN and painful DPN, important risk factors, and the association with mental health in recently diagnosed type 2 diabetes. A total of 5514 (82%) patients (median diabetes duration 4.6 years) enrolled in the Danish Centre for Strategic Research in Type 2 Diabetes cohort responded to a detailed questionnaire on neuropathy and pain. A score ≥4 on the MNSI questionnaire determined possible DPN, whereas pain presence in both feet together with a score ≥3 on the DN4 questionnaire determined possible painful DPN. The prevalence of possible DPN and possible painful DPN was 18% and 10%, respectively. Female sex, age, diabetes duration, body mass index, and smoking were associated with possible DPN, whereas only smoking showed a clear association with possible painful DPN (odds ratio 1.52 [95% confidence interval: 1.20-1.93]). Possible DPN and painful DPN were independently and additively associated with lower quality of life, poorer sleep, and symptoms of depression and anxiety. Possible DPN itself had greater impact on mental health than neuropathic pain. This large study emphasizes the importance of careful screening for DPN and pain early in the course of type 2 diabetes.