Axonal swellings are related to type 2 diabetes, but not to distal diabetic sensorimotor polyneuropathy

Abstract Aims/hypothesis Distal diabetic sensorimotor polyneuropathy (DSP) is a common complication of diabetes with many patients showing a reduction of intraepidermal nerve fibre density (IENFD) from skin biopsy, a validated and sensitive diagnostic tool for the assessment of DSP. Axonal swelling ratio is a morphological quantification altered in DSP. It is, however, unclear if axonal swellings are related to diabetes or DSP. The aim of this study was to investigate how axonal swellings in cutaneous nerve fibres are related to type 2 diabetes mellitus, DSP and neuropathic pain in a well-defined cohort of patients diagnosed with type 2 diabetes. Methods A total of 249 participants, from the Pain in Neuropathy Study (UK) and the International Diabetic Neuropathy Consortium (Denmark), underwent a structured neurological examination, nerve conduction studies, quantitative sensory testing and skin biopsy. The study included four groups: healthy control study participants without diabetes (n = 45); participants with type 2 diabetes without DSP (DSP−; n = 31); and participants with evidence of DSP (DSP+; n = 173); the last were further separated into painless DSP+ (n = 74) and painful DSP+ (n = 99). Axonal swellings were defined as enlargements on epidermal-penetrating fibres exceeding 1.5 μm in diameter. Axonal swelling ratio is calculated by dividing the number of axonal swellings by the number of intraepidermal nerve fibres. Results Median (IQR) IENFD (fibres/mm) was: 6.7 (5.2–9.2) for healthy control participants; 6.2 (4.4–7.3) for DSP−; 1.3 (0.5–2.2) for painless DSP+; and 0.84 (0.4–1.6) for painful DSP+. Swelling ratios were calculated for all participants and those with IENFD > 1.0 fibre/mm. When only those participants with IENFD > 1.0 fibre/mm were included, the axonal swelling ratio was higher in participants with type 2 diabetes when compared with healthy control participants (p < 0.001); however, there was no difference between DSP− and painless DSP+ participants, or between painless DSP+ and painful DSP+ participants. The axonal swelling ratio correlated weakly with HbA1c (r = 0.16, p = 0.04), but did not correlate with the Toronto Clinical Scoring System (surrogate measure of DSP severity), BMI or type 2 diabetes duration. Conclusions/interpretation In individuals with type 2 diabetes where IENFD is >1.0 fibre/mm, axonal swelling ratio is related to type 2 diabetes but is not related to DSP or painful DSP. Axonal swellings may be an early marker of sensory nerve injury in type 2 diabetes. Graphical abstract

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Faculty Opinions recommendation of Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718289800.793492653 ◽

2014 ◽

Author(s):

Rayaz Malik

Keyword(s):

Type 2 Diabetes ◽

Confocal Microscopy ◽

Early Detection ◽

Skin Biopsy ◽

Nerve Fiber ◽

Corneal Confocal Microscopy

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Close relationship between cardiovagal function and sural sensory nerve action potential in type 2 diabetes

Clinical Neurophysiology ◽

10.1016/j.clinph.2019.03.036 ◽

2019 ◽

Vol 130 (7) ◽

pp. 1160-1165

Author(s):

Yun-Ru Lai ◽

Chih-Cheng Huang ◽

Wen-Chan Chiu ◽

Rue-Tsuan Liu ◽

Nai-Wen Tsai ◽

...

Keyword(s):

Type 2 Diabetes ◽

Action Potential ◽

Sensory Nerve ◽

Sensory Nerve Action Potential ◽

Nerve Action ◽

Close Relationship ◽

Sensory Nerve Action

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Elabela levels in patients with type 2 diabetes: can it be a marker for diabetic nephropathy?

African Health Sciences ◽

10.4314/ahs.v20i2.37 ◽

2020 ◽

Vol 20 (2) ◽

pp. 833-840

Author(s):

Erhan Onalan ◽

Yusuf Doğan ◽

Ebru Onalan ◽

Nevzat Gozel ◽

Ilay Buran ◽

...

Keyword(s):

Type 2 Diabetes ◽

Diabetic Nephropathy ◽

High Serum ◽

Control Group ◽

Diabetic Patients ◽

Healthy Individuals ◽

Urine Albumin ◽

Healthy Control ◽

Group 2

Backround: Elabela (ELA) is a hormone that is secreted at high levels in the kidneys of a healthy adult. This study aims to investigate whether serum ELA levels of patients with Type 2 Diabetes vary with the severity of renal damage. Methods: Our study included 50 healthy control subjects and 100 diabetic patients, who were categorized into groups based on urine albumin/creatinine ratios (ACR). Patients included in the study were assigned to four groups: Group 1 (healthy control), Group 2 (ACR<29mg/g), Group 3 (ACR=30-299 mg/g), and Group 4 (ACR>300 mg/g normal or high serum creatinine). Physical examination findings, demographic characteristics of the study group were recorded, and serum ELA levels and other laboratory parameters were assessed using appropriate methods. Results: The results of the study indicated that ELA levels determined in healthy individuals gradually decreased through stages of normal albuminuria, microalbuminuria, and macroalbuminuria. Moreover, ELA had a significant negative corre- lation with LDL-C (r=-0.201, p=0.014), glucose (r=-0.437, P<0.001), retinopathy (r=-0.222, P=0.006), serum BUN (r=- 0.161, P=0.049), and a positive correlation with eGFR (r=0.250, P=0.002). Conclusions: The fact that ELA levels are higher in healthy individuals compared to diabetic patients without microalbu- minuria, and higher in diabetic patients without microalbuminuria compared to patients with advanced albuminuria and kidney damage, suggests that the ELA level can be an important clinical prognostic variable and even a promising agent for the treatment of diabetic nephropathy patients. Keywords: Elabela, diabetes, diabetic kidney disease, albuminuria.

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Isometric knee extension force in Japanese type 2 diabetic patients without apparent diabetic polyneuropathy: Data from the Multicenter Survey of the Isometric Lower Extremity Strength in Type 2 Diabetes study

SAGE Open Medicine ◽

10.1177/2050312118823412 ◽

2019 ◽

Vol 7 ◽

pp. 205031211882341 ◽

Cited By ~ 7

Author(s):

Takuo Nomura ◽

Tomoyasu Ishiguro ◽

Masayoshi Ohira ◽

Hiroyuki Oka ◽

Yukio Ikeda

Keyword(s):

Type 2 Diabetes ◽

Diabetic Polyneuropathy ◽

Knee Extension ◽

Diabetic Patients ◽

Control Subjects ◽

Multicenter Survey ◽

Isometric Knee Extension ◽

Extension Force ◽

Healthy Control

Objectives: To determine standard reference values for isometric knee extension force using a cohort of Japanese type 2 diabetic patients without diabetic polyneuropathy. Methods: Patient data were collected from the Multicenter Survey of the Isometric Lower Extremity Strength in Type 2 Diabetes study and compared with previously published data of healthy control subjects. In total, we enrolled 898 patients with type 2 diabetes aged 30–87 years, who did not have diabetic polyneuropathy. The control group included 510 healthy subjects aged 30–88 years. Maximum isometric knee extension force (KEF) values were obtained by using a hand-held dynamometer with belt stabilization. In addition, KEF (kgf) was adjusted for bodyweight (kg) to calculate %KEF. Results: KEF and %KEF decreased with age in both patients with diabetes and healthy control subjects. The mean values of KEF and %KEF in patients with diabetes were reduced by 9.7% and 20.8%, respectively, in males, and by 11.6% and 23.0%, respectively, in females compared to the values in healthy control subjects. Conclusion: KEF and %KEF in patients with type 2 diabetes without diabetic polyneuropathy may reduce by approximately 10% and 20%, respectively, compared to these values in healthy control subjects. This study provides reference values for isometric KEF with respect to sex in a population covering a wide age range.

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Utility of Tissue Inhibitor Metalloproteinase-1 and Osteopontin as Prospective Biomarkers of Early Cardiovascular Complications in Type 2 Diabetes

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2018.081 ◽

2018 ◽

Vol 6 (2) ◽

pp. 314-319 ◽

Cited By ~ 1

Author(s):

Doaa Samir Salah El-Din ◽

Ahmed Ibrahim Amin ◽

Ahmed Osman Egiza

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Complications ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Diabetic Patients ◽

Tissue Inhibitor ◽

Type 2 Diabetic Patients ◽

Healthy Control ◽

Clinical Measurements

AIM: This work investigated associations between tissue inhibitor metalloproteinase-1 and diabetic cardiovascular diseases in type 2 diabetic patients; also it investigated the role of osteopontin in the diagnosis of type 2 cardiovascular diabetes complications.SUBJECTS AND METHODS: These were examined on eighty subjects, divided into three groups as follows: twenty volunteer healthy control subjects, thirty type 2 diabetes mellitus (DM) patients, and thirty cardiovascular, diabetic patients. Full clinical measurements were carried out, and the expression level of tissue inhibitor metalloproteinase-1 in blood samples was analysed by real-time PCR, using gene-specific primer pairs. Also osteopontin concentrations had been measured by the enzyme-linked immunosorbent assay. Data were tested statistically by parametric tests.RESULTS: The concentrations of osteopontin and the expression levels of tissue inhibitor metalloproteinase-1 were significantly increased in diabetic and cardiovascular diabetic groups compared to control group also they were significantly increased in the cardiovascular diabetic group compared to the diabetic group.CONCLUSION: Tissue inhibitor metalloproteinase-1 and osteopontin concentrations were significantly increased in diabetic patients with cardiovascular complications than other groups.

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Inhibition of Protein Kinase Cβ Does Not Improve Endothelial Function in Type 2 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-0286 ◽

2010 ◽

Vol 95 (8) ◽

pp. 3783-3787 ◽

Cited By ~ 16

Author(s):

Joshua A. Beckman ◽

Allison B. Goldfine ◽

Alison Goldin ◽

Adnan Prsic ◽

Sora Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Healthy Subjects ◽

Vascular Dysfunction ◽

Endothelial Damage ◽

Markers Of Inflammation ◽

Resistance Vessels ◽

Healthy Control ◽

And Oxidative Stress

Context: Antagonism of protein kinase Cβ (PKCβ) restores endothelial function in experimental models of diabetes and prevents vascular dysfunction in response to hyperglycemia in healthy humans. Objective: We tested the hypothesis that PKCβ antagonism would improve vascular function in subjects with type 2 diabetes compared with healthy control subjects. Design: The effect of PKCβ was evaluated in a randomized, placebo-controlled, double-blinded crossover trial. Setting: The study was performed in the outpatient setting of a university medical center. Participants: Thirteen subjects with type 2 diabetes without evidence of cardiovascular disease and 15 healthy control subjects were recruited via newspaper advertisement. Intervention: Subjects underwent a randomized, double-blind, crossover, placebo-controlled trial of the selective PKCβ antagonist ruboxistaurin mesylate. Subjects received each treatment for 14 d. Main Outcome Measure: Endothelium-dependent and endothelium-independent vasodilation of forearm resistance vessels was measured with mercury-in-silastic, strain-gauge plethysmography during intraarterial administration of methacholine chloride and verapamil, respectively. Markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress were measured after each treatment. Results: Endothelium-dependent vasodilation of forearm resistance vessels was attenuated in diabetic subjects when compared with healthy subjects (P = 0.001). Endothelium-independent vasodilation did not differ between groups (P value not significant). Ruboxistaurin did not significantly change endothelium-dependent or endothelium-independent vasodilation or blood-based markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress in either diabetic or healthy subjects. Conclusion: Endothelial dysfunction of forearm resistance vessels was not improved by 2 wk of selective PKCβ inhibition in patients with diabetes. These results suggest that PKCβ does not contribute significantly to vascular dysfunction in otherwise healthy patients with type 2 diabetes.

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Salivary Procalcitonin and Periodontitis in Diabetes

Journal of Dental Research ◽

10.1177/154405910808700707 ◽

2008 ◽

Vol 87 (7) ◽

pp. 630-634 ◽

Cited By ~ 18

Author(s):

C.W. Bassim ◽

R.S. Redman ◽

D.J. DeNucci ◽

K.L. Becker ◽

E.S. Nylen

Keyword(s):

Type 2 Diabetes ◽

Serum Levels ◽

Serum Marker ◽

Control Group ◽

Diabetes Group ◽

Severe Periodontitis ◽

Healthy Control ◽

First Time ◽

Morbid Conditions

Periodontitis and type 2 diabetes are co-morbid conditions, both characterized by infectious susceptibility. We investigated procalcitonin (ProCT) levels in the serum and saliva of persons with periodontitis and type 2 diabetes (n = 20), to determine if these levels are altered by periodontitis activity or by hyperglycemia. Persons with severe periodontitis showed higher levels of salivary-ProCT than did those with moderate periodontitis (241 ± 71 vs. 77 ± 516 pg/mL, p = 0.02) and higher levels than did healthy control individuals (118 ± 26 pg/mL, p = 0.05). Salivary-ProCT levels were correlated with bleeding-on-probing (r = 0.45, p = 0.05), as well as with HgbA1c (r = 0.49, p = 0.03). Salivary levels of ProCT were higher than serum levels for the periodontitis/diabetes group (152 ± 37 vs. 78 ± 17 pg/mL, p = 0.02) and the control group (118 ± 146 vs. 48 ± 17 pg/mL, p = 0.01). Persons with periodontitis and type 2 diabetes have salivary-ProCT levels that reflect their degree of periodontitis activity and hyperglycemia. This study demonstrates, for the first time, the presence of procalcitonin (ProCT), an established serum marker of infection, in saliva.

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Inflammatory Cytokines and the Risk of Cardiovascular Complications in Type 2 Diabetes

Disease Markers ◽

10.1155/2013/931915 ◽

2013 ◽

Vol 35 ◽

pp. 235-241 ◽

Cited By ~ 24

Author(s):

Fadia Mahmoud ◽

Ebaa Al-Ozairi

Keyword(s):

Type 2 Diabetes ◽

T Cells ◽

T Lymphocyte ◽

Healthy Subjects ◽

Inflammatory Cytokine ◽

Cardiovascular Complications ◽

Cd4 Cells ◽

Th 17 ◽

Healthy Control

This study evaluates peripheral blood T lymphocyte expression of inflammatory and proinflammatory cytokines as well as T regulatory (Treg) (FOXP3+CD25+CD4+) cells in type 2 diabetes (T2DM). Participants included 40 T2DM and 30 healthy control subjects. Twenty-four patients had no complications while 16 were afflicted with coronary heart disease (CHD). Relative to healthy subjects, all T2DM patients showed a significant increase in expression of CD4+IFN-ϒ+, CD4+TNF-α+, and CD4+IL-8+ T cells () as well as CD4+IL-6+, CD4+IL-1β+, and IL-17+ T cells () while the ratios of Treg/Th1(CD4+IFN-ϒ+) and Treg/Th-17(CD4+IL-17+) cells were significantly decreased ( and ). T2DM patients with CHD showed a significant increase in CD4+IFN-ϒ+, CD4+TNF-α+, and CD4+IL-17+ T cells and a significant decrease in Treg/Th1 and Treg/IL-17 cells compared to T2DM patients without CHD (). In CHD-afflicted T2DM, HbA1c correlated positively with CD4+IFN-ϒ+ T cells (), HDL correlated negatively with each of CD4+IL-8+ T cells and CD4+IL-17+ T cells (), and LDL correlated positively with CD4+IL-1β+ T cells ().Conclusion. This study shows that hyperglycemia and dyslipidemia correlate with increased inflammatory cytokine expression and suggests the involvement of T cells in the development of diabetes and its complications.

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