Peripheral neuropathic and renal complications in patients with diabetes mellitus 2

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It usually coexists with chondyslipidemia, obesity and hypertension and can present complications such as peripheral neuropathy and nephropathy. Method Retrospective cohort study of 441 patients with diabetes mellitus 2. Medical records were reviewed to obtain the variables under study. All patients of both sexes treated between July 2023 and November 2024 in a primary care hospital were included and patients on predialysis or dialysis, total or partial lower limb amputation, and sequelae of cerebrovascular disease were excluded. Logistic regression analysis was used. Results Among the signs of DN, anhidrosis and mycosis predominated in patients of both sexes, and among the symptoms, burning, prickling and leg pain when walking. The majority of patients with neuropathy are between 60 and 79 years of age, female, have hypertension, have a disease duration of 12.83 ± 8.73 years, Hb1Ac of 7.67% ±1.69, glucose of 153.93 ± 66.17 and hemoglobin of 12.98 ± 1.39. Most patients have CKD G1 and G2. The Chi-square test indicates only relationship between age group, sex and stages. In the quantitative analysis, the Krustall Wallis test indicates that there are significant differences in patient stages according to age, time of disease and HbA1c. Conclusions G1 and G2 stages, female sex and hypertension predominated in patients with CKD. The older the patient and the longer the time with diabetes, the higher the CKD stage. There is a relationship with age group, sex and CKD stages. Age < 79 years and the absence of hypertension are protective factors for the progression of CKD and male sex is considered a risk factor. 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F1000Research 2025, 14 :583 ( https://doi.org/10.12688/f1000research.164767.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Peripheral neuropathic and renal complications in patients with diabetes mellitus 2 [version 1; peer review: awaiting peer review] Evelyn Goicochea Rios https://orcid.org/0000-0001-9994-9184 1 , Yupari Azabache Irma Luz https://orcid.org/0000-0002-0030-0172 2 , NELIDA MILLY OTINIANO https://orcid.org/0000-0001-9838-4847 3 , Nestor Ivan Gomez Goicochea 4 Evelyn Goicochea Rios https://orcid.org/0000-0001-9994-9184 1 , Yupari Azabache Irma Luz https://orcid.org/0000-0002-0030-0172 2 , NELIDA MILLY OTINIANO https://orcid.org/0000-0001-9838-4847 3 , Nestor Ivan Gomez Goicochea 4 PUBLISHED 13 Jun 2025 Author details Author details 1 Escuela de Medicina, Universidad Cesar Vallejo, Trujillo, La Libertad, 13001, Peru 2 Institutos y Centros de Investigación, Universidad Cesar Vallejo, Trujillo, La Libertad, 13001, Peru 3 Institutos y Centros de Investigación, Universidad Cesar Vallejo, Trujillo, La Libertad, 13001, Peru 4 Escuela de Medicina, Universidad Cesar Vallejo, Trujillo, La Libertad, 13001, Peru Evelyn Goicochea Rios Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Yupari Azabache Irma Luz Roles: Formal Analysis, Methodology, Validation, Writing – Original Draft Preparation NELIDA MILLY OTINIANO Roles: Formal Analysis, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Nestor Ivan Gomez Goicochea Roles: Data Curation, Investigation, Software, Writing – Original Draft Preparation OPEN PEER REVIEW REVIEWER STATUS AWAITING PEER REVIEW Abstract Introduction Diabetes mellitus is a chronic disease of high prevalence worldwide. It usually coexists with chondyslipidemia, obesity and hypertension and can present complications such as peripheral neuropathy and nephropathy. Method Retrospective cohort study of 441 patients with diabetes mellitus 2. Medical records were reviewed to obtain the variables under study. All patients of both sexes treated between July 2023 and November 2024 in a primary care hospital were included and patients on predialysis or dialysis, total or partial lower limb amputation, and sequelae of cerebrovascular disease were excluded. Logistic regression analysis was used. Results Among the signs of DN, anhidrosis and mycosis predominated in patients of both sexes, and among the symptoms, burning, prickling and leg pain when walking. The majority of patients with neuropathy are between 60 and 79 years of age, female, have hypertension, have a disease duration of 12.83 ± 8.73 years, Hb1Ac of 7.67% ±1.69, glucose of 153.93 ± 66.17 and hemoglobin of 12.98 ± 1.39. Most patients have CKD G1 and G2. The Chi-square test indicates only relationship between age group, sex and stages. In the quantitative analysis, the Krustall Wallis test indicates that there are significant differences in patient stages according to age, time of disease and HbA1c. Conclusions G1 and G2 stages, female sex and hypertension predominated in patients with CKD. The older the patient and the longer the time with diabetes, the higher the CKD stage. There is a relationship with age group, sex and CKD stages. Age < 79 years and the absence of hypertension are protective factors for the progression of CKD and male sex is considered a risk factor. READ ALL READ LESS Keywords Diabetes mellitus, chronic kidney disease, peripheral neuropathy, polyneuropathy, microvascular complications, MNSI test, risk factors, dyslipidemia, hypertension Corresponding Author(s) NELIDA MILLY OTINIANO ( [email protected] ) Close Corresponding author: NELIDA MILLY OTINIANO Competing interests: No competing interests were disclosed. Grant information: Payment for publication will be paid by Universidad César Vallejo within the framework of support for teaching research, through Resolution No. P-2024-128-VI-UCV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2025 Goicochea Rios E et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Goicochea Rios E, Irma Luz YA, OTINIANO NM and Gomez Goicochea NI. Peripheral neuropathic and renal complications in patients with diabetes mellitus 2 [version 1; peer review: awaiting peer review] . F1000Research 2025, 14 :583 ( https://doi.org/10.12688/f1000research.164767.1 ) First published: 13 Jun 2025, 14 :583 ( https://doi.org/10.12688/f1000research.164767.1 ) Latest published: 02 Mar 2026, 14 :583 ( https://doi.org/10.12688/f1000research.164767.2 )  There is a newer version of this article available. Suppress this message for one day. Introduction Diabetes mellitus (DM) is a highly prevalent chronic disease worldwide. By the year 2045, a prevalence of 10.9% (700 million people) 1 is expected, and early diagnosis is key to preventing chronic microvascular and macrovascular complications, including neuropathy, retinopathy and nephropathy. 1 , 2 Diabetic peripheral neuropathies are classified as somatic and autonomic. 3 Among the former, bilateral sensory polyneuropathies, paresthesias, numbness and tingling as well as decreased tactile, vibrational and thermal sensitivity, discrimination between two points, achilles and patellar hyporeflexia are more frequent; whereas mononeuropathies and muscular amyotrophy may be accompanied by cachexia and muscle pain especially of the muscles of the pelvis and thighs. 2 , 3 Autonomic neuropathies include a variety of symptoms such as postural hypotension, gastrointestinal and genitourinary changes. 2 Diabetic neuropathy (DN) is the most frequent complication of DM. It can be subclinical, diffuse clinical and focal syndromes. 4 , 5 The first case is detected by alterations in tactile and thermal sensitivity, abnormal test for vibration in the absence of symptomatology. Diffuse clinical neuropathy encompasses distal sensorimotor and autonomic syndromes, the most frequent being diffuse symmetric polyneuropathy (DSP), with distribution in hands and feet, present in more than 90% of DM2 cases. 4 , 6 Among the focal syndromes, mononeuritis predominates, frequent in older adults. 4 Worldwide, the prevalence of DN is reported to be between 8 and 51%. In 10% of cases, it is diagnosed at the onset of DM2, and in 90% during the evolution of DM2. 4 It increases when there are high levels of glycemia, alcohol consumption and smoking, as well as with prolonged illness. 6 Older adults with poor metabolic control are at greater risk of foot ulcers (25%) and amputation associated with diabetic peripheral neuropathy. 7 Among the risk factors for DN are smoking, alcohol abuse, metabolic syndrome, genetic aspects, advanced age, and among the risk factors for painful DN are poor glycemic control, female sex, obesity, renal function problems and the severity of neuropathy. 8 Good glycemic control must be accompanied by strict control of blood pressure to prevent and delay the onset of DN, since hypertension has been described as the main modifiable risk factor for distal symmetric polyneuropathy. 9 Dyslipidemia may affect neuronal function and contribute to DN because, associated with hyperglycemia, they produce reactive oxygen species and initial chronic inflammation of the axon or Schwuann cell and subsequently affect the entire neuronal tree. 8 The DN usually manifests in the hands and lower extremities 8 by producing changes in peripheral nerve and skin tissue irrigation, which results in fiber ischemia and hypoxia in sensory neurons 1 , 3 and carries the risk of foot ulcers and amputations 4 because it affects the sensory, motor and autonomic nerve fibers of the peripheral nervous system. 1 , 3 There are several tests for screening for DN, including the Michigan test, one of the most widely used in outpatient clinics and considered the standard. It has a specificity of 95-100% and sensitivity of 57-93%. It is reproducible and easy to apply in primary care. 10 , 11 It includes a self-administered questionnaire with questions that evaluate the patient’s perception of lower limb symptoms and the physical examination to identify pulses, anhidrosis, calluses, skin lesions, bony deformities and prominences, infections; as well as the Achilles reflex, the vibration perception test and the Semmes-Weinstein monofilament test. 12 The prevalence of chronic kidney disease (CKD) has increased worldwide, especially among people with DM2, 13 , 14 and can vary from 8 to 11% in the United States, Canada, Europe and Japan. 14 In Peru, it was estimated that by the year 2021, 13.07% of Peruvians presented CKD, G1 to G4, and 0.10% of the population was on dialysis. 15 CKD is identified by proteinuria or structural damage evidenced by imaging or biopsy with three to more months’ duration. 16 It may or may not be accompanied by decreased glomerular filtration rate (GFR) < 60 mL/min/1.73 m 2 . 13 , 14 , 17 Proteinuria levels are directly related to renal health prognosis and mortality and are therefore considered a marker of systemic damage. 18 It has been described that up to 40% of patients with DM2 may have CKD. 13 and has an impact on morbidity and mortality, especially cardiovascular morbidity and mortality. 13 , 14 Diabetic CKD is a microvascular complication that affects about 35% of patients with DM2 and usually progresses to advanced stages. It presents as two phenotypes: albuminuria and altered GFR. 19 When the altered glomerular filtration rate is accompanied by microalbuminuria, it can increase mortality up to ten times, with a high health and social cost. 20 Patients with CKD have higher rates of diabetic peripheral neuropathy and peripheral artery disease as documented in 520 patients hospitalized for DM2 followed for 4 years in whom CKD is associated with diabetic foot ulcers (DFU). This relationship was significant only in patients with albuminuric CKD. 21 According to a cross-sectional study, microalbuminuria is strongly and independently associated with DFU. 22 Since insensitivity of the foot predicts subsequent deterioration of renal function, subjects with GFRe 30 mg/24H are more prone to diabetic foot ulcer (DFU). 23 Neuropathy affects almost 50% of the diabetic population 7 , 24 while DM2 nephropathy affects approximately 25% of this population. The duration of DM2, together with glycemic control, blood pressure and lipids, are common risk factors for the development of these complications. 24 In Peru, in the first quarter of 2021, DM2 complications were identified with a predominance of polyneuropathy (29.5%), followed by nephropathy (14.4%), retinopathy (9%) and diabetic foot (12.8%). 25 We consider it important to identify both PN and CKD in patients with DM2 treated in primary care in order to have updated local clinical-epidemiological information that will allow us to adapt treatment protocols. For this reason, the aim of this research was to identify peripheral neuropathic and renal complications in patients with DM2 in a primary care center and the specific objectives were: to analyse the clinical features of peripheral neuropathy and the clinical and laboratory features of chronic kidney disease in patients with diabetes mellitus 2; to analyse the modifiable and non-modifiable risk factors associated with peripheral neuropathy and chronic kidney. Methods Study design, population, and sample A retrospective, observational, analytical, applied cohort study was conducted. 26 The population consisted of 441 patients with DM2 treated between July 2023 and November 2024 at a primary care hospital in the province and district of Trujillo. The sample was of a census nature, so information was collected from all patients with DM2 who attended for medical control during the study period and who met the following inclusion criteria: diagnosis of DM2, male and female sex, with screening for peripheral neuropathy; evaluation of renal function by determination of glomerular filtration rate and proteinuria/creatinuria ratio 27 ; with results of glycemia, glycosylated hemoglobin (HbA1c), hemoglobin (Hb), with diagnosis of dyslipidemia and complete clinical records. Medical records of patients with glomerulonephritis, renal hypoplasia or monorenal, patients in predialysis, dialysis or with renal transplant and patients with sequelae of cerebrovascular disease and total or partial amputation of the lower limb were excluded because they were treated at another level of complexity. Medical records with incomplete data were not analysed. Data collection techniques and instruments The documentary analysis technique, whose instrument was a data collection form based on the information in the clinical histories, was used, Information was collected about non-modifiable factors: age and sex; clinical factors: glycemia, glycosylated hemoglobin (Hba1c) and hemoglobin (Hb) values; comorbidities such as arterial hypertension, hypothyroidism and obesity. Peripheral neuropathy was determined with the Michigan test (MNSI). 10 , 11 This test has two parts: a questionnaire and a brief physical examination. The 15-question questionnaire is self-administered and is considered abnormal if there are 7 to more affirmative answers on the questionnaire except for questions 4 and 10 which are not scored (≥7/13). The second part is the physical examination and includes the appearance of the foot (deformities, anhidrosis, nail or skin infections and corns), assessment of the Achilles reflex and semiquantitative assessment of vibration sensation on the dorsum of the big toe; vibration assessment and monofilament test. Patients scoring positive on the clinical part of the MNSI (>2 points on a 10-point scale) were considered neuropathic. 28 The Ipswich test and the evaluation of pedial and posterior tibial pulses were also applied. Likewise, a reflex hammer was used to evaluate the Achilles reflex. For these evaluations it was considered present or absent. The monofilament test, using the 10 g Semmes-Weinstein monofilament was considered normal if eight of 10 responses were correct, reduced sensation one to seven responses out of 10 applications and no correct responses were recorded as no sensation. 28 Chronic kidney disease was determined with the blood creatinine value (mg/dL), age in completed years and sex (CKD EPI formula) 27 with or without the presence of albuminuria. 16 CKD was considered when the glomerular filtration rate was 30 for women and >20 for men. The CKD EPI formula was used for the staging of CKD 18 , 27 and blood pressure was considered controlled when the values were <140/90 mm Hg. 29 The CKD was classified into five stages according to the glomerular filtration rate. It is classified into stages G3 to G5 with a decrease in GFR < 60 ml/min/1.73 m 2 in the absence of albuminuria and stages G1 and G2 in the presence of proteinuria. 17 , 18 Laboratory data were performed during the medical evaluations and were obtained from the medical records of each patient included in the study. This information made it possible to assess the characteristics of peripheral neuropathy and CKD in the study population. DM2 was recorded as controlled if Hba1c was < 7% and fasting glycemia <120 mg/dL. Anemia was considered if hemoglobin was <12 g/dL for females and <13 g/dL for males. 30 Validation of the data collection instrument was performed, with the evaluation of experts (neurologists, nephrologists and family physicians) and the Aiken V of 0.96 31 was obtained. Procedure: Authorization was requested for access to the clinical records of outpatients with DM2 in search of polyneuropathy, CKD, comorbidities and laboratory tests. The information per patient was organized in a database and then the information was analyzed. All variables recorded by the responsible physician were considered and the results were presented taking into account the STROBE checklist. 32 Statistical analysis: Descriptive statistics were used to organize the data in tables and graphs, as well as measures of central tendency and dispersion to analyze the behavior of the study variables. 33 For the inferential analysis, measures of association were processed using freely available statistical software. Likewise, a logistic regression model was developed to predict the risk factors associated with peripheral neuropathy and chronic kidney disease. 34 Ethical considerations The protocol that gave rise to this article was presented to the Research and Ethics Committee of the Gerencia de la Red Asistencial La Libertad - EsSALUD (Management of the La Libertad - EsSALUD Health Care Network) before carrying out the research. This committee issued the certificate N° 68 on May 20, 2024, authorizing the execution of the research. The project was also reviewed and approved by the Ethics Committee of the School of Medicine - UCV (Expert opinion 317-CEI-EPM-UCV-2024 of May 30, 2024). The ethical principles of the Declaration of Helsinki were applied with respect to the confidentiality and veracity of the data collected during the course of the study, which are faithfully presented. Personal identity data and patient privacy were protected. Authorship contributions and transparency in conflicts of interest were reported. 35 Results Table 1 , shows clinical manifestations of neuropathy by age group and gender. Among the signs of DN, anhidrosis and infections predominated in patients of both sexes and different age groups, especially among those over 80 years of age. Anhidrosis was more frequent in the female sex, while infections were more frequent in the male sex. More than 66% of participants had more than two signs of diabetic neuropathy. As for symptoms, burning, prickling and leg pain when walking predominated. These had a greater occurrence in women over 80 years of age. Table 1. Clinical manifestations of neuropathy by age group and gender. AGE GROUP 80 YEARS TOTAL SEX MALEC. FEM. MALEC. FEM. MALEC. FEM. Signs Mallet Fingers 30.36% 13.85% 19.82% 26.47% 31.25% 17.39% 23.13% Overlapped fingers 3.57% 0.00% 10.81% 8.24% 31.25% 17.39% 8.39% Hallux valgus 37.50% 40.00% 39.64% 55.29% 62.50% 47.83% 46.71% Metatarsal Prominence 30.36% 46.15% 36.94% 47.06% 62.50% 21.74% 41.50% Anhidrosis 64.29% 67.69% 54.95% 62.94% 56.25% 69.57% 61.90% Calluses/Corns 25.00% 47.69% 28.83% 44.12% 43.75% 34.78% 37.87% Infections/cracks 58.93% 58.46% 66.67% 58.82% 75.00% 60.87% 61.45% Absent Aquilian reflex 12.50% 12.31% 13.51% 12.94% 6.25% 13.04% 12.70% Absent vibration 16.07% 21.54% 22.52% 18.24% 31.25% 13.04% 19.73% Negative monofilament test 21.43% 6.15% 18.92% 8.82% 18.75% 13.04% 13.15% Signs of NPD 71.43% 66.15% 66.67% 73.53% 87.50% 60.87% 70.29% Symptoms of NPD Numbness 53.57% 41.54% 52.25% 38.24% 31.25% 43.48% 44.22% Burning 35.71% 44.62% 48.65% 43.53% 37.50% 56.52% 44.44% Sensitivity 44.64% 35.38% 37.84% 33.53% 31.25% 52.17% 37.19% Prickling 55.36% 53.85% 49.55% 51.76% 37.50% 56.52% 51.70% Sheet rubbing 10.71% 16.92% 9.01% 19.41% 12.50% 21.74% 15.19% Hot sensation 19.64% 13.85% 13.51% 11.76% 12.50% 17.39% 13.83% Open wound 14.29% 15.38% 9.01% 11.18% 6.25% 4.35% 11.11% Neuropathy diagnosis 37.50% 30.77% 27.93% 28.82% 25.00% 39.13% 30.39% Nocturnal symptoms 35.71% 43.08% 39.64% 32.35% 25.00% 47.83% 36.73% Leg pain on walking 44.64% 47.69% 36.04% 48.24% 37.50% 52.17% 44.44% Feeling your feet 5.36% 6.15% 3.60% 2.35% 6.25% 13.04% 4.31% Cracks 7.14% 6.15% 3.60% 4.71% 6.25% 8.70% 5.22% Amputation history 0.00% 1.54% 0.00% 0.00% 0.00% 0.00% 0.23% Symptoms (+) NPD 19.64% 13.85% 9.91% 12.35% 6.25% 21.74% 13.15% With the bivariate analysis, Table 2 shows that the majority of patients with neuropathy are between 60 and 79 years of age (45.1%), female (41.3%), and present hypertension (51.2%). The average age was 66.71 ± 11.19 years, average time of illness was 12.83 ± 8.73 years, average Hb1Ac was 7.67% ± 1.69, glucose was 153.93 ± 66.17 and hemoglobin was 12.98 ± 1.39. For the variables analyzed, the Chi-square statistical tests indicated no association and the Man Whitney U test indicated no significant differences in relation to neuropathy. Therefore, in this case, multivariate analysis was no longer performed. Table 2. Modifiable and nonmodifiable risk factors in patients with peripheral neuropathy. Factors Neuropathy (Signs) Total NO % YES % % Sig. Age Group Less than 60 38 8.6 83 18.8 121 27.4 0.884 from 60 to 79 82 18.6 199 45.1 281 63.7 Over 80 11 2.5 28 6.3 39 8.8 Sex Man 55 12.5 128 29.0 183 41.5 0.89 Woman 76 17.2 182 41.3 258 58.5 Dyslipidemia No 98 22.2 243 55.1 341 77.3 0.41 Yes 33 7.5 67 15.2 100 22.7 Obesity No 100 22,7 245 55,6 345 78,2 0.53 Yes 31 7,0 65 14,7 96 21,8 Hypothyroidism No 126 28.6 290 65.8 416 94.3 0.27 Yes 5 1.1 20 4.5 25 5.7 Anemia No 98 22.2 230 52.2% 328 74.4 0.89 Yes 33 7.5 80 18.1% 113 25.6 Hypertension No 40 9.1 84 19.0 124 28.1 0.46 Yes 91 20.6 226 51.2 317 71.9 Total 131 29.7 310 70.3 441 100.0 Age 65.57 ± 10.31 66.71 ± 11.19 66.38 ± 10.93 0.17 Disease duration 11.59 ± 7.69 12.83 ± 8.73 12.46 ± 8.44 0.22 HbA1c 7.90 ± 2.03 7.67 ± 1.69 7.74 ± 1.87 0.63 Glucose 164.26 ± 78.33 153.93 ± 66.17 157 ± 70.07 0.48 Hemoglobin (woman) 12.43 ± 1.16 12.61 ± 1.09 12.55 ± 1.11 0.50 Hemoglobin (man) 13.91 ± 1.50 13.52 ± 1.61 13.64 ± 1.58 0.15 Table 3 shows that most patients are in G I and G II, are female, and have hypertension. The highest average age was found in G IIIB and G IV with 71.08 ± 10.52 years. Likewise, the average time of disease was higher in G IIIB and G IV, with 15.41 ± 8.87years, the higher average HbA1c was 8.14% ± 2.07 located in G I and GII. In G I and G II, we found an average higher glucose of 171.66 ± 87.28; average higher hemoglobin of 13.13 ± 1.42. For qualitative variables, the Chi-square statistical test indicates only a relationship among age group, sex and stages. In the quantitative analysis, the Krustall Wallis test indicates that there are significant differences among patient stages according to age, time of disease and HbA1c. Table 3. Modifiable and nonmodifiable risk factors according to stages of chronic kidney disease in patients with diabetes mellitus 2. Characteristics Stages Total % Sig. No CKD % G I y GII % G III A % G IIIB y G IV % Age group Younger than 60 60 13,6 50 11,3 6 1,4 5 1,1 121 27,4 0.00 From 60 to 79 years 130 29,5 102 23,1 36 8,2 13 2,9 281 63,7 Over 80 9 2,0 14 3,2 10 2,3 6 1,4 39 8,8 Sex man 65 14.7 80 18.1 29 6.6 9 2.0 183 41.5 0.00 woman 134 30.4 86 19.5 23 5.2 15 3.4 258 58.5 Dyslipid-emia No 154 34.9 130 29.5 38 8.6 19 4.3 341 77.3 0.88 Yes 45 10.2 36 8.2 14 3.2 5 1.1 100 22.7 Obesity No 153 34,7 128 29,0 45 10,2 19 4,3 345 78,2 0.48 Yes 46 10,4 38 8,6 7 1,6 5 1,1 96 21,8 Hypothyroidism No 189 42.9 154 34.9 51 11.6 22 5.0 416 94.3 0.83 Yes 10 2.3 12 2.7 1 0.2 2 0.5 25 5.7 Anemia No 156 35.4 124 28.1 34 7.7 14 3.2 328 74.4 0.07 Yes 43 9.8 42 9.5 18 4.1 10 2.3 113 25.6 Hyper-tension No 65 14.7 47 10.7 8 1.8 4 0.9 124 28.1 0.05 Yes 134 30.4 119 27.0 44 10.0 20 4.5 317 71.9 Total 199 45.1 166 37.6 52 11.8 24 5.4 441 100.0 Age 64.49 ± 10 66.66 ± 10.44 70.54 ± 14.07 71.08 ± 10.52 66.38 ± 10.93 0.00 Disease duration 11.16 ± 8.13 12.85 ± 7.80 14.83 ± 10.43 15.41 ± 8.87 12.46 ± 8.44 0.01 HbA1c 7.52 ± 1.76 8.14 ± 2.07 7.25 ± 1.18 7.69 ± 1.84 7.73 ± 1.86 0.01 Glucose 147.97 ± 56.34 171.66 ± 87.28 145.02+ ± 43.74 149.58 ± 67.34 156.63 ± 69.87 0.24 Hemoglobin (woman) 12.55 ± 0.99 12.55 ± 1.22 12.68 ± 1.81 12.36 ± 1.40 12.55 ± 1.11 0.86 Hemoglobin (man) 13.841.63 13.74 ± 1.37 13.21 ± 1.60 12.611 ± 2.43 13.64 ± 1.58 0.06 Table 4 shows the ordinal regression after analysis of the requirements. The dependent variable was the stages of chronic kidney disease. The variables included in the model were the age group in the categories of less than 60 and 60 to 79 years and the absence of hypertension as protective factors. Male sex is also included as a risk factor. The age groups younger than 79 years and the absence of hypertension are considered protective factors since their coefficients are negative and their ORs are less than 1, interpreted as meaning that patients of these ages who do not have hypertension are less likely to increase the stage of chronic kidney disease. Male sex, however, is considered a risk factor for progression of CKD. Table 4. Ordinal regression model for chronic kidney disease in patients with diabetes mellitus 2. Parameter B Dev. Error 95% Wald confidence interval Contrast of hypotheses OR 95% Wald confidence interval for Exp (B) Inferior Superior Wald Chi-square gl Sig. Inferior Superior [Age group = less than 60] -1.353 0.3862 -2.110 -0.596 12.276 1 0.000 0.258 0.121 0.551 [Age group = from 60 to 79 -1.145 0.3313 -1.794 -0.496 11.948 1 0.001 0.318 0.166 0.609 [Sex = male] 0.570 0.2272 0.125 1.015 6.292 1 0.012 1.768 1.133 2.760 [Dyslipidemia = No] -0.132 0.2231 -0.569 0.305 0.351 1 0.554 0.876 0.566 1.357 [Obesity = .No] 0.802 0.8167 -0.799 2.402 0.964 1 0.326 2.229 0.450 11.051 [Hypo-thyroidism =No] -0.158 0.3927 -0.928 0.611 0.162 1 0.687 0.854 0.395 1.843 [Anemia = .No] -0.298 0.3116 -0.909 0.313 0.914 1 0.339 0.742 0.403 1.367 [Hyper-tension = No] -0.502 0.2126 -0.919 -0.086 5.582 1 0.018 0.605 0.399 0.918 Time of disease 0.016 0.0119 -0.008 0.039 1.740 1 0.187 1.016 0.992 1.040 HbA1c 0.019 0.0694 -0.117 0.155 0.073 1 0.788 1.019 0.889 1.167 Glucose 0.002 0.0018 -0.001 0.006 1.437 1 0.231 1.002 0.999 1.006 Hemoglobin 0.010 0.1052 -0.197 0.216 0.008 1 0.927 1.010 0.822 1.241 Discussion Diabetic neuropathy (DN) is a common complication in patients with diabetes. It is often overlooked, underdiagnosed and undertreated 5 due to its wide spectrum of presentations and variable intensity of symptoms, ranging from a mild or asymptomatic clinical picture to a debilitating neuropathy. 5 The prevalence of DN is highly variable and is a function of age, disease duration, metabolic control and lifestyle. 7 The variability in the clinical picture of DN is related to the changes that chronic hyperglycemia produces in the nerve fiber. Decreased glutathione depletion and regeneration, with consequent oxidative stress and triggering of proinflammatory reactions and fibrosis, 4 , 7 have been reported to be responsible. Autooxidation of glucose and its metabolites would be other factors associated with nerve fiber damage, changes that are intensified in poorly controlled diabetics. 4 It has also been described that DN generates axon damage with variable demyelination, 5 microvascular insufficiency at the level of peripheral nervous tissue and skin, with fiber ischemia and secondarily hypoxia mainly in sensory neurons. 4 Thus, DN manifests as decreased tactile and thermal sensitivity, paresthesias, hypoalgesia, among other symptoms. 1 The earliest changes of peripheral ND occur at the level of unmyelinated C-fibers, resulting in pain, allodynia and hyperesthesias. Late changes include segmental axonal demyelination, axonal degeneration of myelinated fibers; resulting in progressive loss of distal sensation in the affected nerve. 7 In the present study, burning, prickling and leg pain when walking predominated, with greater occurrence in women over 80 years of age. Regarding these sensory symptoms, a study conducted in Mexico reported similar data, finding dysesthesia, pain, burning and sensation of electric shock at the level of the toes. 4 On physical examination, anhidrosis and fungal infections of the skin and nails predominated in patients of both sexes and especially among those over 80 years of age. Mycoses are the most frequent group of skin infections in patients with DM, especially of nails and feet, generally caused by dermatophytes or Candida species. Anhidrosis or hypohidrosis is also frequent in this type of patient 36 and is due to the sudomotor dysfunction characteristic of DM. 36 , 37 It has been observed that patients with diabetes, whose age is over 64 years, had twice the risk of developing onychomycosis. It also occurs when repeated microtrauma to the nails, longer exposure to pathogenic fungi, weakened immune system, increased work activity and venous insufficiency occur. Likewise, it has been observed that patients with diabetes who have amputations and structural deformities are more likely to develop onychomycosis. 38 Almost two thirds of the participants presented more than two signs using the MNSI 28 and were therefore diagnosed as DN. The detection of DN by screening in the diabetic population is important to identify the risk of foot ulceration and prevent amputations, so periodic foot examinations, pain treatment and control of glycemia and glycosylated hemoglobin are recommended. 7 The present study used the MNSI, an instrument considered standard for detecting DN in outpatients in primary care. Its specificity is 95-100% and its sensitivity 57-93%. 4 , 28 Among the most important factors associated with neuropathy, age, 8 , 11 obesity, arterial hypertension, 11 , 39 smoking 8 , 11 poor glycemic control, 11 , 39 , 40 duration of diabetes >10 years 11 , 36 , 37 hypoinsulinemia, and dyslipidemia were mentioned. 11 Other factors associated with DN (p60 years, glycemic imbalance (HbA1c > 8%). 39 , 40 and risk factors for painful DN include poor glycemic control, female sex, obesity, renal function problems and severity of neuropathy. 8 In the present study, the majority of patients with DN are between 60 and 79 years of age, are female and among the comorbidities, arterial hypertension predominates. The average duration of DM is 12.83 ± 8.73 years, and there is not a good metabolic control reflected in elevated Hb1Ac and glycemia values. However, no statistical significance was found based on Chi-square and Man Whitney U tests. Regarding the duration of diabetes, an investigation in Ethiopia showed that the duration of DM was an important variable that was negatively associated with DN in patients with newly diagnosed DM2. In addition, more than half of the DN occurred within 6 years after the diagnosis of diabetes mellitus. These findings could indicate that most diabetic patients were diagnosed with DM in late stages and were at risk of developing DN in early stages. 41 On the other hand, it has been shown that the risk of DN increases with age. This could be attributed to the convergence of three fundamental pathological mechanisms: inflammation, oxidative stress and mitochondrial dysfunction, all of which are related to the aging process. The inflammatory response leads to the activation of intracellular pathways such as nuclear factor kappa B (NF-κB), activator protein-1 (AP-1) and mitogen-activated kinases (MAPKs) that play a crucial role in neuronal damage. Likewise, oxidative stress generated by chronic hyperglycemia is mediated by several altered metabolic pathways including the polyol and hexosamine pathways, activation of protein kinase C, formation of advanced glycosylation end products and dysfunctional glycolysis. On the other hand, mitochondrial dysfunction is responsible for the production of most reactive oxygen and nitrosative species, whose toxic actions lead to lipid peroxidation, structural modifications of proteins and damage to nucleic acids. These processes culminate in axonal degeneration and segmental demyelination, characteristic of DN. 42 It has been described that strict control of blood pressure is the main modifiable risk factor for distal symmetric polyneuropathy and should accompany glycemic control. 9 and that dyslipidemia associated with hyperglycemia affect neuronal function by producing reactive oxygen species and initial chronic inflammation of the axon or Schwuann cell and subsequent alteration of the entire neuronal tree. 8 Hence the importance of maintaining stable lipid and blood pressure values. Some observational studies suggest that treatment of dyslipidemia could prevent neuropathy (HR: 0.52 [95% CI: 0.27, 0.98] with use of fibrates, HR: 0.65 [95% CI: 0.46, 0.93] with use of statins, p ≤ 0.042. 37 Multifactorial intervention in lifestyle, physical activity and body weight represent the basis for the treatment of diabetic distal symmetric polyneuropathy, so it is important to identify risk factors or comorbidities associated with DN in the early stages of the disease. 37 In the bivariate analysis, no association was found between DN and obesity, dyslipidemia, anemia, and hyperthyroidism. However, another study did report an elevated BMI 40 and obesity as risk factors. 39 Furthermore, another study reported that hyperglycemia and dyslipidemia may affect peripheral nerve function in distinct but overlapping ways. While hyperglycemia causes damage, preferentially to large myelinated nerve fibers, which is reflected in motor nerve conduction velocity, dyslipidemia and obesity preferentially affect small nerve fibers and the damage is evident by the density of intraepidermal nerve fibers. These risk factors may be particularly important in sensory axon loss of all sizes, which is the primary pathology underlying the patient’s symptoms and disability. 38 , 43 These risk factors may be particularly important in sensory axon loss of all sizes, which is the primary pathology underlying the patient’s symptoms and disability. 38 , 43 The other complication analyzed in this study is chronic kidney disease. It has been described that the patients with CKD present higher rates of diabetic peripheral neuropathy and peripheral arteriopathy, especially in cases of albuminuric CKD, 17 , 21 and microalbuminuria has been associated with a higher prevalence of diabetic foot ulcer. 22 It has been described that the underlying mechanism of both neuropathy and nephropathy is the microvascular involvement that nearly 35% of patients with DM2 present. 19 , 24 In the present study, most patients were in stages GI and GII, were female, and had hypertension. The older the patient and the longer the duration of DM2, the higher the frequency of stages GIII B and G IV. These findings are consistent with previous studies that have found a directly proportional relationship between these variables and advanced stage 40 , 44 or progression of CKD. 20 Regarding sex, some studies report that there is no difference by sex in the association with CKD. However, the risk of progression and terminal CKD is higher among women than among men with diabetes. 45 The highest levels of HbA1c and glycemia were observed among patients in stages GI and GII. Likewise, a relationship was found among age group, sex, and CKD stages. According to the Krustall Wallis test, there were significant differences among CKD stages and age, time of duration of DM2, and glycemia and HbA1c values. Glycemic control is beneficial both in reducing the risk of peripheral neuropathy 37 and in preventing progression of CKD. An observational study of 32 patients followed over 24 years demonstrated impairment of sensory motor peripheral nerve function and onset of clinical neuropathy in 64% of members of the group with HbA1c ≥ 7.0%) As opposed to patients with HbA1c <7%. 46 It has been described that, in patients with CKD, the severity of diabetic peripheral neuropathy (DPN) correlates directly with the duration of the disease, the degree of glycemic control and the degree of uremia. DPN in patients with CKD G4- G5 is presented as a distal symmetrical polyneuropathy with greater involvement of the lower limbs than the upper limbs. The most frequent clinical features of uremic neuropathy are involvement of thick fibers, with paresthesias, altered or absent deep tendon reflexes, altered vibratory sensation, distal foot muscle atrophy, and weakness. 39 , 47 Likewise, it has been reported that, in patients with diabetes, the development of cardiac autonomic neuropathy and DPN depends on complex interactions between the degree of hyperglycemia, the duration of the disease, age-related neuronal wasting, and systolic and diastolic blood pressures. The diabetic population with stages 4-5 CKD presents an extremely high risk of lower limb amputation. 47 In the ordinal regression, the dependent variable was the stages of chronic kidney disease. It was found that the age group in its categories of less than 60 and 60 to 79 years and the absence of hypertension are protective factors; male sex is a risk factor for CKD. This last variable has been described in several studies associated with CKD 48 as well as uncontrolled arterial hypertension and age over 65 years. 44 , 48 We believe that the results of this research justify a prospective study of the cohort analyzed, as well as the comparison of these results with controlled diabetic population, lifestyles and medications received for the treatment of DM, DN and CKD. The key areas that justify research to prevent the development or progression of DN and CKD in patients with DM are early screening, periodic follow-up, metabolic and blood pressure control, as well as control of dyslipidemia and obesity. In addition, education on risk factors for DN and CKD, healthy eating, physical activity, and adherence to treatment. We consider that the results of the study can be generalised to the Peruvian population with similar characteristics. Limitations of the study Referred to the limitations of the retrospective observational design used. One of the limitations is that the registries do not include information on all relevant risk factors. On the other hand, by working only with records of patients who sought medical care or were hospitalized, patients without access to medical care or those with less severe forms of neuropathy were excluded. Conclusion Diabetic neuropathy produces changes in the somatic and autonomic peripheral nervous system, requiring intervention in the initial phase of the disease through lifestyle changes, detection of modifiable factors such as dyslipidemia, arterial hypertension and obesity, and timely treatment to achieve and maintain glycemic control. Diagnosis and treatment of fungal infections, anhidrosis and other clinical examination findings, as well as DN symptoms, are also required. DN is more frequent in patients between 60 and 79 years of age, female, with arterial hypertension, with hyperglycemia (elevated Hb1Ac and glycemia values) and with a disease duration (DM) of 12.83 ± 8.73 years. Stages G1 and G2, female sex, and hypertension predominated in patients with CKD. The older the patient and the longer the time with DM, the higher the CKD stage. A relationship was found between age group, sex and CKD stages. Age <79 years and the absence of hypertension are protective factors that prevent the progression of CKD, whereas male sex is considered a risk factor. Ethical considerations and consent The protocol that gave rise to this article was presented to the Research and Ethics Committee of the Gerencia de la Red Asistencial La Libertad - EsSALUD (Management of the La Libertad - EsSALUD Health Care Network) before carrying out the research. This committee issued the certificate N° 68 on May 20, 2024, authorizing the execution of the research. The project was also reviewed and approved by the Ethics Committee of the School of Medicine - UCV (Expert opinion 317-CEI-EPM-UCV-2024 of May 30, 2024). The Ethics Committee of the Faculty of Medicine - César Vallejo University and the EsSalud Research Committee (with institutional review committee functions) gave authorisation to conduct the research. Due to the research design (retrospective), informed consent was not required. The ethical principles of the Declaration of Helsinki were applied with respect to the confidentiality and veracity of the data collected during the course of the study, which are faithfully presented. Personal identity data and patient privacy were protected. Authorship contributions and transparency in conflicts of interest were reported. 35 Data availability Zenodo: Data base Peripheral neuropathic and renal complications in patients with diabetes mellitus 2. Available at https://doi.org/10.5281/zenodo.15468019 49 This project contain the following underlying data: 1. Dictamen 317 Ethic Committee UCV, 2. Dictamen Ethic Committee Essalud 3. Risk diabetes foot database 4. STROBE check list Reporting guidelines Zenodo: STROBE checklist for ‘Peripheral neuropathic and renal complications in patients with diabetes mellitus 2. A retrospective Study’. https://doi.org/10.5281/zenodo.15468019 49 Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Acknowledgement None References 1. Jiménez-Castillo GA, Martínez-Bravo LE, Anaya-Escamilla A: Neuropatía Diabética: Una revisión narrativa de fisiopatología, diagnóstico y tratamiento. Acta Médica Peru. 2023; 40 (3). Publisher Full Text 2. Lázaro-Carrasco Hernández I, Pina S: Complicaciones crónicas de la diabetes mellitus tipo 2. Trabajo de fin de grado, Facultad de Farmacia. Universidad Complutense.2017. Reference Source 3. 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Ling XW: Severity of albuminuria as an early indicator for wound healing in type 2 diabetic foot ulcers Wound Repair Regen. Wound Repair Regen. 2021. 23. Pan C-F, Chuang S-M, Lin K-C, et al. : Risk associated with estimated glomerular filtration rate and albuminuria for PAD among patients with type 2 diabetes. J. Investig. Med. 2021; 69 (6): 1182–1188. Publisher Full Text 24. Faselis C, Katsimardou A, Imprialos K, et al. : Microvascular complications of type 2 diabetes mellitus. Curr. Vasc. Pharmacol. 2020; 18 (2): 117–124. Publisher Full Text 25. Revilla T: Luis. Epidemiología de la diabetes en el Perú, Ministerio de Salud- CDC Perú.2021. 26. Paulina SF, Carlos MD, Guissela QS, et al. : Estudios de cohortes. 1 a parte. Descripción, metodología y aplicaciones. Rev. Cir. 2019 Oct [citado 2024 Mar 23]; 71 (5): 482–493. Publisher Full Text Reference Source 27. Levey AS, Stevens LA: A new equation to estimate glomerular filtration rate. Ann. Intern. Med. 2009; 150 : 604–612. 28. 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Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 13 Jun 2025 ADD YOUR COMMENT Comment Author details Author details 1 Escuela de Medicina, Universidad Cesar Vallejo, Trujillo, La Libertad, 13001, Peru 2 Institutos y Centros de Investigación, Universidad Cesar Vallejo, Trujillo, La Libertad, 13001, Peru 3 Institutos y Centros de Investigación, Universidad Cesar Vallejo, Trujillo, La Libertad, 13001, Peru 4 Escuela de Medicina, Universidad Cesar Vallejo, Trujillo, La Libertad, 13001, Peru Evelyn Goicochea Rios Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing Yupari Azabache Irma Luz Roles: Formal Analysis, Methodology, Validation, Writing – Original Draft Preparation NELIDA MILLY OTINIANO Roles: Formal Analysis, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Nestor Ivan Gomez Goicochea Roles: Data Curation, Investigation, Software, Writing – Original Draft Preparation Competing interests No competing interests were disclosed. Grant information Payment for publication will be paid by Universidad César Vallejo within the framework of support for teaching research, through Resolution No. P-2024-128-VI-UCV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (2) version 2 Revised Published: 02 Mar 2026, 14:583 https://doi.org/10.12688/f1000research.164767.2 version 1 Published: 13 Jun 2025, 14:583 https://doi.org/10.12688/f1000research.164767.1 Copyright © 2025 Goicochea Rios E et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. 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