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. 2017 Aug 25;17(1):161.
doi: 10.1186/s12883-017-0939-6.

Neuropathy-specific alterations in a Mexican population of diabetic patients

Angélica Carbajal-Ramírez  1 , Rebeca García-Macedo  2 , Carlos Manlio Díaz-García  3 , Carmen Sanchez-Soto  3 , Araceli Méndez Padrón  2 , Jorge Escobedo de la Peña  4 , Miguel Cruz  2 , Marcia Hiriart  5
Affiliations

Neuropathy-specific alterations in a Mexican population of diabetic patients

Angélica Carbajal-Ramírez et al. BMC Neurol. .

Abstract

Background: Neuropathy is one of the major complications of type 2 diabetes mellitus. Our first aim was to determine the clinical characteristics of a population of diabetic patients with different types of neuropathy. Our next goal was to characterize the cytokine profile (IL-6 and IL-10), nerve growth factor (NGF) and circulating cell-adhesion molecules in these patients. Finally, we aimed to compare the renal function among the groups of neuropathic patients.

Methods: In a cross-sectional study, we included 217 diabetic patients classified in three groups: sensory polyneuropathy with hypoesthesia (DShP) or hyperesthesia (DSHP), and motor neuropathy (DMN). Two control groups were included: one of 26 diabetic non-neuropathic patients (DNN), and the other of 375 non-diabetic (ND) healthy subjects. The participants were attending to the Mexican Institute of Social Security.

Results: The circulating levels of NGF were significantly lower in diabetic patients, compared to healthy subjects. The range of IL-6 and IL-10 levels in neuropathic patients was higher than the control groups; however, several samples yielded null measurements. Neuropathic patients also showed increased circulating levels of the adhesion molecules ICAM, VCAM, and E-Selectin, compared to the ND group. Moreover, neuropathic patients showed reduced glomerular filtration rates compared to healthy subjects (82-103 ml/min per 1.73 m2, data as range from 25th-75th percentiles), especially in the group with DMN (45-76 ml/min per 1.73 m2).

Conclusions: Some particular alterations in neuropathic patients included -but were not limited to- changes in circulating NGF, cell adhesion molecules, inflammation, and the worsening of the renal function. This study supports the need for further clinical surveillance and interventions considering a neuropathy-related basis.

Keywords: Cardiovascular complications; Cell adhesion molecules; Diabetic complications; Dyslipidemia; Inflammation; Insulin resistance; Neuropathy; Neurotrophin; Renal dysfunction; Type 2 diabetes mellitus.

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Conflict of interest statement

Ethics approval and consent to participate

Prior to the study, we obtained ethical clearance by the Ethics and Research Institutional Review Boards of the Mexican Institute of Social Security (protocol approved under the number 2004–3601-002 for the National Commission for Research), at the facility Unidad Médica de Alta Especialidad (UMAE) “Bernardo Sepúlveda” of the hospital Centro Médico Nacional “Siglo XXI” in Mexico City.

Written informed consent to participate was obtained from patients before their enlistment in the study.

Consent for publication

Informed consent allowing the publication of the conclusions derived from this study was also obtained from patients.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flowchart of the classification criteria for diabetic neuropathies. Patients were screened for diabetic neuropathy using the Michigan Neuropathy Screening Instrument (MNSI) according to the criteria of the consensus of San Antonio
Fig. 2
Fig. 2
Circulating levels of nerve growth factor. Nerve growth factor (NGF) is diminished in diabetic patients respect to non-diabetic subjects. Data are represented as box plots with the median and the 25th–75th percentiles of the distribution. Whiskers comprise the 5th–95th percentiles of the distribution. The raw data is plotted to the right of box plots for all conditions: ND (N = 46), DNN (N = 18), DShP (N = 84), DSHP (N = 38) and DMN (N = 38)
Fig. 3
Fig. 3
Circulating levels of cytokines. (a) Box-plots of pro-inflammatory cytokine IL-6 levels (for non-zero values) showed considerable variability in all groups, although a significant increase was observed in diabetic patients. Data are represented as the median and the 25th–75th percentiles of the distribution. Whiskers comprise the 5th -95th percentiles of the distribution. The raw data is plotted to the right of box plots for all conditions: ND (N = 127), DNN (N = 16), DShP (N = 58), DSHP (N = 28) and DMN (N = 27). Different letters indicate statistical differences with a p < 0.05 and the alphabetical order points toward a decrease in magnitude (i.e. the “a” correspond to the highest value, the “b” to the second, and so on). Groups were compared by a Kruskal-Wallis non-parametric test, using a Mann-Whitney post test for a higher the statistical power with respect to Dunn test (b) A high percentage of measurements of IL-6 in in diabetic patients yielded null values. (c) Box-plots of IL-10 levels (non-zero values) were similar among groups; ND (N = 146), DNN (N = 16), DShP (N = 69), DSHP (N = 31) and DMN (N = 28). (d) A high percentage of measurements of IL-10 in diabetic patients also yielded null values. The percentages were analyzed using a Chi-squared test with Yate’s correction for continuity on 2 × 2 contingency tables
Fig. 4
Fig. 4
Renal function is impaired in diabetic neuropathy. (a) Glomerular Filtration Rate is decreased in all the groups of neuropathic patients. Data are represented as box plots showing the median and the 25th–75th percentiles of the distribution. Whiskers comprise the 5th–95th percentiles of the distribution. The raw data is plotted to the right of box plots for all conditions: ND (N = 361), DNN (N = 3), DShP (N = 30), DSHP (N = 21) and DMN (N = 15). Different letters indicate statistical differences with a p < 0.05 and the alphabetical order points toward a decrease in magnitude (i.e. the “a” correspond to the highest value, the “b” to the second, and so on). Groups were compared by a Kruskal-Wallis non-parametric test, using a Dunn post test
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