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Background: Diabetic peripheral neuropathy (DPN) is the most dominant cause of neuropathy worldwide, and there has been no specific treatment until now. The aim of the current study was to assess the probable protective effect of empagliflozin in type 2 diabetics who are suffering from DPN., Methods: Fifty eligible type 2 diabetes mellitus (T2DM) cases with diabetic peripheral neuropathy were recruited in this study and classified into 2 groups. Group I (n=25) (control group) received placebo tablets once daily. Group II (n=25) (empagliflozin group) received empagliflozin 25mg once daily for three months. Empagliflozin efficacy was evaluated using electrophysiological studies, and HbA1c levels, the brief pain inventory short-form item (BPI-SF) score, the diabetic neuropathy symptom (DNS) score, the atherosclerotic cardiovascular disease (ASCVD) risk score, and the serum levels of neuron-specific enolase (NSE), malondialdehyde (MDA) and calprotectin (Calpro), lipid profile, and random blood glucose level (RBG)., Results: After three months, comparing the results of the empagliflozin arm to the control arm showed a significant improvement in the electrophysiological studies and a significant decrease in the BPI-SF score and the mean serum levels of NSE and MDA. However, no significant difference was determined in HbA1c, Calpro, lipid profile, and RBG levels. In addition, the DNS and ASCVD risk scores were not significantly different. The NSE and MDA levels were significantly negatively correlated with the electrophysiological parameters. However, the BPI-SF score showed a non-significant difference., Conclusions: Empagliflozin may be a promising neuroprotective and therapeutic agent for diabetic peripheral neuropathy. Trial registration Identifier: NCT05977465., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Goals: Identify conditioning factors of the foot risk (FR) by comparing two evaluation methods (qualitative and quantitative) for neuropathy, arteriopathy, foot deformities. Concordance between detected the alterations and registered in clinical history (CH)., Material and Methods: It is an observational study. Ambit: in two primary care centers of the Catalan Health Institute., Population: Five hundred thirty-two patients with diabetes, both >18 years with FR records and informed consent., Measurements: Neuropathy: symptom assessment (NSS) and signs of disability (NDS). Arteriopathy: Index ABI. Edinburgh Questionnaire, fart pulses. Foot deformities: Pedigraphy. Quantitative reference: Values Defined neuropathy: NDS>6 points or 3-5 and NSS>5 points. ITB: Normal value (.90-1.30)., Results: Women, 46.42%. Middle ages, 67.29 years (SD 7.69). One hundred fifty-three patients did not present neurovascular alterations., Qualitative: Without differentiating clinical manifestations: 252, patients presented neuropathy; 99, altered ITB; 28, two complications and 101, Edinburgh Quiz: altered., Quantitative: Differentiating clinical manifestations: among the neuropathy group; 110, patients only presented symptoms; 46, definite neuropathy. In 96, NDS and NSS scores without defined neuropathy criteria., Altered Abi: 52, only ABI>1.30; 47, ABI<.90; 12, associated neuropathy and ABI>1.30 and 16, with ABI<.90. Edinburgh questionnaire: 47, presented atypical symptoms and 26, typical. Agreement, between quantitative and recorded neurovascular alterations r=.32 for neuropathy and r=.21 in arteriopathy. The pressure point on the 5th metatarsal, was associated with quantitative neuropathy: OR: 2.32 (1.188-4.546), P=.01., Conclusion: The evaluation, identifying clinical manifestations, improves the identification of FR, although we need more research., (Copyright © 2022 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Peripheral and autonomic neuropathies are one of the major complications in patients with diabetes mellitus (DM). Nerve lesion starts in an early stage. In patients with DM II the above-mentioned lesion starts even before glycemic dysregulation and during the metabolic syndrome stage. In the beginning, the neuropathy may be asymptomatic; therefore, neurophysiologic examination should be conducted for its early detection so that therapeutic measures can be taken on time. Nine patients with early neuropathy were here assessed: three of them with metabolic syndrome and fasting hyperglycemia, one with metabolic syndrome without hyperglycemia and five with glycemic dysregulation without metabolic syndrome. All were asymptomatic and neurologic examination was unremarkable. Techniques for the detection of early neuropathy were carried out (sural/radial ratio, F-waves, H-reflex, sympathetic skin responses, cutaneous silent period and heart rate variability reflexes). Eight patients had an early cardiac autonomic neuropathy, one had a definite autonomic neuropathy. Eight patients had an early somatic neuropathy (seven with a sural/radial ratio < 0.5 and one with abnormal F-waves), and one had an asymptomatic small-fiber neuropathy (abnormal sympathetic skin responses and cutaneous silent period). Detection of early neuropathy through neurophysiology is mandatory before clinical signs and symptoms appear, during this stage, effective therapeutic measures can be warranted.

The wide ubiquity of GLP-1 receptors in the body has stimulated the search for different extrapancreatic actions of GLP-1 and its receptor agonists. Thus, severe cardioprotective effects directed on myocardial ischaemia and dysfunction as well as diverse antiaterogenic actions have been reported. Also, native and GLP-1 receptor agonists have demonstrated significant beneficial effects on liver steatosis and fibrosis and on neuronal protection in experimental models of Alzheimer, and Parkinson's disease as well as on cerebral ischaemia. Recent evidences suggest that these drugs may also be useful for prevention and treatment of diabetic retinopathy, nephropathy and peripheral neuropathy. Good results have also been reported in psoriasis. Despite we still need confirmation that these promising effects can be applied to clinical practice, they offer new interesting perspectives for treatment of type 2 diabetes associated complications and give to GLP-1 receptor agonists an even more integral position in diabetes therapy.

Diabetes is a metabolic disease affecting approximately 300 million people worldwide. Neuropathy is one of its frequent complications, and may affect sensory, motor, and autonomic nerves. Its pathophysiology has not fully been elucidated. Several hypotheses have been proposed, and mitochondria have been suggested to play a significant role. This article reviews the mechanisms involved in mitochondrial dysfunction and development of diabetic neuropathy, consisting mainly of oxidative and inflammatory stress, changes in intracellular calcium regulation, apoptotic processes, and changes in mitochondrial structure and function that may lead to development of diabetic neuropathy., (Copyright © 2011 SEEN. Published by Elsevier Espana. All rights reserved.)

Background: Neuropathy is a common complication of diabetic patients., Aim: To determine the prevalence of diabetic peripheral neuropathy in Type 2 diabetic patients attended at a family medicine unit., Material and Methods: Cross-sectional assessment of 348 type 2 diabetic patients aged 34-89 years (60% females) with a disease duration of 5 to 15 years. Peripheral neurological status was evaluated using The Michigan Neuropathy Screening Instrument, a tool that includes a self-assessment of symptoms and a physical examination., Results: Diabetic neuropathy was found in 240 patients (69%). The prevalence in males and females was 72 and 67% respectively. The prevalence in patients with a disease duration of 5, 10 and 15 years, was 59, 69 and 77%, respectively. Fifty percent of patients with neuropathy complained of dry skin, 2% had ulcers, 43% had an abnormal perception of vibration and 29% had an abnormal monofilament test., Conclusions: The overall prevalence of peripheral neuropathy in this group of patients was 69% and was directly associated with the duration of the disease.

Unlabelled: Periodontitis is a frequent pathologic condition in diabetic patient, and has been associated with chronic complications like nephropathy, cardiovascular disease, peripheral artery disease or death., Objective: To document the association between severe periodontitis and edentulism with the presence of sensory-motor neuropathy in diabetic patients., Material and Method: Cross-sectional study in type 2 diabetic patients from the family medicine unit no. 27 of the IMSS in Tijuana, México. Patients were evaluated to identify periodontitis and sensory-motor neuropathy. Information was also obtained about sex, age, duration of diabetes, glycemic control, smoking and alcohol use., Results: Four hundred and thirty-six patients completed all measurements. In 180 (41.3%) neuropathy was identified, and associated with age (p < 0.001); duration of diabetes (p < 0.001); fasting glucose (p < 0.001); severe periodontitis (OR: 2.7; IC 95%: 1.5-4.8);and with edentulism (OR: 4.4; IC 95%: 2.0-9.4). Logistic regression multivariable analysis kept as significative the association between severe periodontitis and edentulism with neuropathy (adjusted OR: 1.7; IC 95%: 1.1-2.6)., Conclusions: Periodontitis and edentulism are associated with the presence of neuropathy in diabetic patients.

Introduction: Diabetes mellitus (DM) can present complications of neuropathy and peripheral arterial disease with high risk for developing foot ulcers and consequent amputations., Objective: To identify the association between peripheral vascular disease, and neuropathy in type 2 Diabetes mellitus patients from the Hospital General de Zona No. 1 IMSS in Colima, Mexico., Material and Methods: Cross-sectional study of 80 patients with diabetes mellitus evaluated by means of the Edinburgh Claudication Questionnaire, Michigan Neuropathy Screening Instrument, ankle-arm index, Motor Nerve Conduction Velocity and H-reflex., Results: 51 women and 29 men were studied. Mean age was 53.9 +/- 9.6 years, mean diabetes mellitus progression was 8 +/- 6.6 years and mean glucose level was 283 +/- 110 mg/mL. Neuropathy presented in 65 patients (81.2%). Ankle/arm index revealed 19% of patients presented with moderate peripheral vascular insufficiency. Motor Nerve Conduction Velocity was abnormal in 40% of patients and H-reflex was absent in 70%., Discussion: Grade 2 motor-sensitive polyneuropathy was found in 70-80% of patients and moderate peripheral vascular insufficiency in 19%. It can thus be inferred that the complication of diabetic neuropathy appears before that of peripheral vessel damage.

Background: The presence of cardiac autonomic neuropathy (CAN) in patients with diabetes mellitus (DM) is associated with increased mortality and chronic microvascular complications of diabetes., Objective: To investigate a possible association between specific findings of CAN during exercise testing (ET) and nephropathy and retinopathy in patients with type 1 DM., Methods: We conducted a cross-sectional study of 84 patients with type 1 DM. All patients underwent clinical laboratory evaluation and performed ET, and those who presented findings suggesting myocardial ischemia were excluded from data analysis (n = 3). The assessment of microvascular complications (retinopathy and nephropathy) was performed in the sample., Results: Patients with nephropathy and those with retinopathy achieved a lower heart rate (HR) at peak exercise (HR max) and smaller increase in HR in relation to rest (Peak ΔHR) compared with those without these complications. These patients also had a smaller reduction in HR in the second and 4(th) minutes after the end of the test (ΔHR recovery 2 and 4 minutes). After performing a multivariate analysis with control for possible confounding factors, the ΔHR recovery in two and four minutes, maximum HR and Peak ΔHR remained significantly associated with retinopathy; and ΔHR recovery in the second and 4(th) minutes remained associated with the presence of nephropathy., Conclusion: The ET can be considered an additional tool for early detection of CAN and to identify patients at increased risk for microvascular complications of diabetes.

In order to evaluate the relationship between cardiovascular autonomic neuropathy and corrected QT interval (QTc) with cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus, we followed up for 5 years 67 patients attending the outpatient Endocrinology Service. 82% completed follow-up and cardiovascular events occurred in 16 patients. We found that long QTc interval was the only variable significantly associated with cardiovascular morbidity and mortality in the multiple logistic regression analysis (RR: 13.56, 95% CI: 2.01-91.36) (p = 0.0074).

Objective: To determine the prevalence of diabetic autonomic neuropathy (DAN) in patients with type 2 diabetes using a cardiovascular test., Design: Observational, descriptive, cross-sectional study., Setting: Primary care clinics in Fronteras de Torrejón de Ardoz Health Centre, Area 3, Madrid, Spain., Participants: Of the 361 diabetics assigned to 3 participating patient quotas, 317 patients had type 2 diabetes. Of those, 104 were excluded due to being immobile, cardiac arrhythmia, and/or on treatment with chronotropic drugs. Of the 213 patients included, 169 had the test and 44 were lost., Interventions: Performing of the orthostatic response test., Main Measurements: Age, sex, years since diagnosed with diabetes (measured by patient anamnesis), treatment (hygiene-diet measures, oral antidiabetics, insulin) were recorded, along with the R-R'30:15 ratio (classified as normal: 31.04, borderline: 1.01 to 1.03, and pathological: pound1.00)., Results: The prevalence of DAN using the orthostatic response test was 56.2% (95 patients with a pathological R-R'30:15 index) out of a total of 169 patients with type 2 diabetes. The definitive diagnosis of DAN found in the clinical histories reviewed was 1.8%., Conclusions: DAN goes unnoticed in our evaluation of the patient with diabetes. The improvement in diagnosing this complication and incorporating cardiovascular autonomic dysfunction tests in primary care follow-up protocols, would enable closer metabolic control and improve the prognosis of the disease.

Diabetes mellitus (DM) is the most common cause of neuropathy in the western world. Recent studies estimate prevalence around 28,5% but results vary depending on measure used to define diabetic neuropathy. Early detection and careful attention to risk factors determining diabetic foot may avoid or delay complications. Pain generation is due to biologic causes as well as physical and emotional ones. Neuropathy may result in amputation through different ways including loss of one or more functions in peripheral nerves. Glycaemic control, symptom control and feet care are standard measures that affect all health professionals implied in diabetic patients attention. Deeper knowledge of pathogenic mechanisms should result in new treatments which seem to be more effective if administered early, when abnormalities are more likely to be reversible.

Cardiovascular autonomic neuropathy is a common complication of diabetes mellitus. There are several diagnostic methods currently used. New techniques are described. The purpose of this review paper is to describe and analyze the clinical relevance of all this methods and propose an algorithm for the diagnosis of the cardiovascular autonomic neuropathy at daily medical practice.

Objective: To review the literature on the advanced glycation end products (AGEs) in diabetes, with especial interest on their role in the pathophysiology of the chronic complications of diabetes mellitus., Materials: Representative papers were selected through a computer MEDLINE search from 1985 to 2000., Results: Hyperglycemia causes irreversible microvascular and macrovascular complications, including retinopathy, neuropathy, nephropathy, atherosclerosis and cerebrovascular disease. There is evidence that glycation leads to chemical modification of proteins, and other macromolecules and it contributes to the pathogenesis of diabetic complications. Several AGEs and their receptors have been identified. The inhibition of AGE formation is under intensive investigation to prevent diabetic complications. From several inhibitors studied, Amadorins offer great therapeutic potential., Conclusions: It is known that a heterogeneous group of AGEs is formed by glycation. The mechanism of AGE formation is partially understood, making it difficult to identify the precise chemical products responsible for in vivo damage and also to develop specific inhibitors.

Introduction: Diabetic neuropathy is a common neurological complication in patients with diabetes mellitus which affects their quality of life. The risk factors involved in this are not completely clear., Objective: To determine the frequency of symmetrical distal diabetic neuropathy and the risk factors associated with its occurrence in the group studied., Patients and Methods: A transversal study was made in the Hospital Clinico Quirurgico Hermanos Ameijeiras of Ciudad de la Habana (Cuba), in 200 patients diagnosed as having type 1 or type 2 diabetes mellitus, between January 1997 and December 1999. A clinical neurological examination and neurophysiological investigations were done on all patients to make a diagnosis of diabetic neuropathy. Subsequently, we compared those with diabetic neuropathy and those without in relation to the risk factors. Statistical analysis included the chi squared test and estimation of the relative risk. RESULTS. The frequency of symmetrical distal diabetic neuropathy was 30.0%. Related risk factors were: smoking (p= 0.00, RR= 2.59), raised serum cholesterol (p= 0.00, RR= 4.12), poor metabolic control of diabetes mellitus (p= 0.00, RR= 4.13), associated disorders (p= 0.00, RR= 5.31) including arterial hypertension (p= 0.03, RR= 1.90) and duration of diabetes mellitus (p= 0.00, RR= 2.01)., Conclusions: In our study symmetrical distal diabetic neuropathy was a common complication of diabetes mellitus associated with various risk factors.

Objective: This study aimed to assess if activation with acetazolamide increases the diagnostic capacity of baseline SPECT with (99m)Tc-HMPAO in the study of brain perfusion in type I diabetic patients with no history of neurological symptoms., Material and Methods: A baseline SPECT was carried out in 11 diabetes mellitus type I patients with no neurological symptoms with 555 MBq of (99m)Tc-HMPAO; 1 g of acetazolamide was administered during the examination and a second SPECT was obtained 20' later with the same methodology used in the baseline SPECT. The images were visually analyzed. The post-acetazolamide studies were analyzed with (CBS) and without (WBS) baseline image subtraction and both methods were compared., Results: The baseline SPECT showed 48 hypoperfused cortical areas. The post-acetazolamide SPECT analyzed without baseline image subtraction detected 14 new hypoperfused areas and those analyzed with it detected 26 areas. 69% of the baseline hypoperfused areas were hyporeactive in the WBS analysis and 54% in the CBS analysis., Conclusion: The perfusion SPECT with acetazolamide improves the diagnostic capacity of the baseline perfusion (99m)Tc-HMPAO SPECT, and makes it possible to classify the abnormalities as metabolic or vascular, with a preference for the post-acetazolamide CBS imaging analysis.

Diabetic neuropathy (DN) is chronic complication which occurs in 50% of long standing diabetes mellitus. DN is a consequence of hyperglycemia probably through the following mechanisms: a) activation of aldose-reductase, intracellular sorbitol accumulation and myoinositol depletion, reduced activity of Na+/K+ATPase, loss of Na+ channels and demyelination; b) proteins glycation; c) microangiopathy; the first mechanism being the best known and the most reliable. DN may be subclinical or clinical. The main clinical picture is a peripheral, bilateral, symmetric polyneuropathy with a "socks and gloves" sensory impairment, muscular weakness, hyporeflexia, plantar ulcers and arthropathy. Less frequent syndromes are proximal motor neuropathy and mononeuropathy of cranial nerves or thoraco-abdominal roots. Diagnosis is based on clinical data, and may be sustained on impaired nerve conduction velocity, abnormal evoked somatosensory potentials, or sural nerve biopsy. These methods are highly sensitive but unspecific. Etiopathogenic treatment is based on glycemic control and aldose reductase inhibitors. Improvement in clinical, electrophysiologic and histopathologic data have been obtained with the latter. Symptomatic treatment includes carbamazepin, phenytoin, tricyclic antidepressives and a phenotiazin. Mononeuropathies tend to complete recovery in less than 6 months. Polyneuropathy is thought to be irreversible and progressive; however, with excellent glycemic control or with aldose reductase inhibitors nerve damage may be stabilized or even reversed.

Diabetes mellitus is an endocrinologic illness that affects multiple systems. One of then is the nervous system. It has been attempted to establish a relationship between metabolic abnormalities associated with diabetes and the degree of nervous system affectation. We present a case of mononeuritis involving the left peroneal nerve which occurred suddenly during the postoperative phase of a thoracoplasty in a patient with type II diabetes mellitus. The clinical picture was associated with a hyperglycemic nonketotic decompensation. We analyze the precipitating factors and their possible prevention.

Thirty-one diabetic subjects, 19 males and 12 females, with a mean age of 40.5 +/- 14.0 years, 17 of whom were insulin dependent (IDDM) and 14 non-insulin dependent (NIDDM) treated with insulin and diet, were followed for a period of six months. Patients were diagnosed of diabetic autonomic cardiopathy (without other neuropathy causes, nor use of drugs except for insulin) by the alteration of at least 2 of the 5 cardiovascular tests (tCV) performed. Patients underwent an educational diabetes program and self-control, and after 6 months of treatment they were divided into two groups according to the degree of metabolic control. In group 1, in which there was a good control with mean blood sugar levels of 108 +/- 12 mg/dl (5.9 +/- 0.6 mmol/l) and triglycerides of 101 +/- 21 (1.1 +/- 0.2 mmol/l), an improvement in tCV was observed: Valsalva coefficient of 1.16 +/- 0.13 and 1.22 +/- 0.13 (initial and final respectively) (p less than 0.001), with and improvement in 56% of cases; E/I (expiration/inspiration) ratio increased from 1.13 +/- 0.11 to 1.21 +/- 0.11, improving 53% of cases (p less than 0.001); 30/50 index (RR in 30/RR beat in beat 15 after orthostatism) (n.s.); difference in systolic arterial pressure after standing (p less than 0.001) and increase in diastolic arterial pressure with isometric muscular exercise (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

With the purpose of knowing which metabolic disorders and clinical complications are more frequently developed by diabetic patients, and to analyze the relationship between the hyperglycemia state and appearance of these complications, we studied a group of patients from a Metabolic Diseases Clinic in Maracaibo, Venezuela. Fifty-four Type II diabetics patients were evaluated by means of: physical examination, anthropometric measurements, biochemical control of glycemia, insulin and lipid pattern, as well as evaluation of the complications presented. The sample consisted of 33 men and 21 women, 75% of which had glycemic values over 140 mg/dl. Basal insulin values were significantly high (29.9 +/- 8.3 uU/ml in men and 30.9 +/- 10.1 uU/ml in women) in relation to a control group (14.5 +/- 2.4 uU/ml), concluding that our diabetics presented basal hyperinsulinemia and insulin resistance. The lipid pattern of the subjects studied showed hypertriglyceridemia (70%) and hypercholesterolemia (67%). A positive association between glycemia and triglycerides values was found in the total group. HDL-cholesterol values were significantly lower in relation to the control group, obtaining a negative correlation between HDL-cholesterol and triglycerides. The clinical complications observed in these diabetics were: non-specific visuals alterations, signs of arterial illness and sensorial disorders distributed in a similar percentage (63, 61 and 51%, respectively). When the independence test X2 was applied, we obtained association (p less than 0.05) between glycemia and the frequency of complications.

To find out if ventricular dysfunction is related with diabetes duration or diabetic chronic complications, resting and exercise electrocardiograms, chest X-ray, echocardiograms and dynamic scintigraphy with left ventricular ejection fraction measurement (LVEF) were performed to three groups of diabetic subjects without known cardiopathy or hypertension: (I) twelve subjects with less than five-years diabetes, (II) eleven with five to ten years, (III) nineteen with diabetes lasting more than ten years. Results were compared with ten healthy volunteers. 90.4% of diabetics had at least one abnormality. LVEF was significantly lower in diabetics (P less than 0.001) than in control group. No important differences were found according to diabetes duration. Lower fractional shortening and lower cardiac output were found in group III than in control group (P less than 0.05). Impaired ventricular function in group III was related (P less than 0.05) with the evidence of diabetic late complications. Relationship between ventricular dysfunction and other microvascular abnormalities might suggest that microangiopathy participates in some extent to the pathogenesis of ventricular disorder.