Mechanisms of Venoarteriolar Reflex in Type 2 Diabetes with or without Peripheral Neuropathy

The aim of this study is to investigate the underlying mechanisms of the venoarteriolar reflex (VAR) in type 2 diabetes mellitus (T2DM), with and without peripheral neuropathy. Laser Doppler flowmetry (LDF) recordings were performed on the medial malleus and dorsal foot skin, before and during leg dependency in healthy controls, in persons with obesity, in those with T2DM, in those with T2DM and subclinical neuropathy, and in those with T2DM and confirmed neuropathy. LDF recordings were analyzed with the wavelet transform to evaluate the mechanisms controlling the flowmotion (i.e., endothelial nitric oxide-independent and -dependent, neurogenic, myogenic, respiratory and cardiac mechanisms). Skin blood perfusion decreased throughout leg dependency at both sites. The decrease was blunted in persons with confirmed neuropathy compared to those with T2DM alone and the controls. During leg dependency, total spectral power increased in all groups compared to rest. The relative contribution of the endothelial bands increased and of the myogenic band decreased, without differences between groups. Neurogenic contribution decreased in controls, in persons with obesity and in those with T2DM, whereas it increased in subclinical- and confirmed neuropathy. In conclusion, this study provides evidence that confirmed diabetic neuropathy alters the VAR through the neurogenic response to leg dependency.

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Concomitant peripheral neuropathy and type 2 diabetes impairs post-exercise cutaneous perfusion and flowmotion

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab414 ◽

2021 ◽

Author(s):

Cécile Reynès ◽

Jean-Baptiste Beaume ◽

Françoise Latil-Plat ◽

Houda Ennaifer ◽

Laure Rocher ◽

...

Keyword(s):

Nitric Oxide ◽

Type 2 Diabetes ◽

Peripheral Neuropathy ◽

Laser Doppler Flowmetry ◽

Blood Perfusion ◽

Laser Speckle ◽

Laser Doppler ◽

Doppler Flowmetry ◽

Post Exercise

Abstract Aim The study investigated changes in microvascular perfusion during post-exercise recovery in those with type 2 diabetes, with or without peripheral neuropathy, as well as in healthy controls and those with obesity. Methods Skin blood perfusion was assessed in each group using laser doppler flowmetry and laser speckle contrast imaging before and immediately after a six-minute walking test. Laser doppler flowmetry recordings underwent wavelet transformation to allow specific control mechanisms of blood perfusion to be studied (e.g. endothelial nitric oxide independent and dependent, neurogenic, myogenic, respiratory and cardiac mechanisms). Results Skin blood perfusion increased after exercise in all groups (22.3±28.1% with Laser speckle contrast imaging and 22.1±52.5% with laser doppler flowmetry). Throughout post-exercise recovery, the decrease was blunted in those with subclinical peripheral neuropathy and confirmed peripheral neuropathy when compared to the other three groups. After exercise, total spectral power increased in all groups. The relative contributions of each endothelial band was lower in those with confirmed peripheral neuropathy than in the healthy controls and those with obesity (nitric oxide-dependent function: 23.6±8.9% versus 35.5±5.8% and 29.3±8.8%, respectively; nitric oxide-independent function: 49.1±23.7% versus 53.3±10.4% and 64.6±11.4%, respectively). The neurogenic contribution decreased less in those with confirmed peripheral neuropathy and in those with type 2 diabetes alone, compared to those with subclinical peripheral neuropathy and those with obesity (-14.5±9.9% and -12.2±6.1% versus -26.5±4.7% and -21.7±9.4%, respectively). Conclusion Peripheral neuropathy, whatever the stage, altered the microvascular response to exercise via impaired endothelial and neurogenic mechanisms.

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Indicators of microcirculation in patients with type 2 diabetes with diabetic peripheral neuropathy during therapy with various doses of vitamin D

Regional blood circulation and microcirculation ◽

10.24884/1682-6655-2019-18-4-19-28 ◽

2019 ◽

Vol 18 (4) ◽

pp. 19-28

Author(s):

A. P. Stepanova ◽

T. L. Karonova ◽

M. M. Galagoudza

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Peripheral Neuropathy ◽

Diabetic Peripheral Neuropathy ◽

Functional Tests ◽

Disability Score ◽

Doppler Flowmetry ◽

Group I ◽

Group Ii

Aim of the study. To study the effect of therapy with prophylactic and supraphysiological doses of cholecalciferol on skin microcirculation (MC) indicators in patients with type 2 diabetes mellitus with diabetic peripheral neuropathy (T2DM with DPN).Material and methods. The study included 62 participants with T2DM with DPN (according to the Neuropathy Disability Score (NDS) scale, more than 4 points). By the method of consecutive numbers, patients were randomized into two groups: Group I (n=31, 15 men/16 women, 52.4±5.7 years) and Group II (n=31, 16 men/15 women, 51.4±6.1 years). Antihyperglycemic treatment was stable during the study. For 24 weeks, cholecalciferol participants from Group I received once a week at a dose of 5,000 IU, and from Group II - once a week at a dose of 40,000 IU. Body mass index (BMI), serum levels of 25(OH)D (25-hydroxycalciferol) and serum glycated hemoglobin (HbA1c) were evaluated before and after 24 weeks of taking cholecalciferol. The method of laser Doppler flowmetry (LDF) compared the initial and final indicators of the baseline level of blood flow and microcirculation indicators against the background of functional tests (postural and occlusive). Control measurements of LDF parameters were performed on 16 subjects without revealed diabetes mellitus (8 men/8 women, 51.8±3.7 years).Results. Patients from Group II, after 24 weeks of taking supraphysiological doses of cholecalciferol, against the background of 100% normalization of the serum 25(OH)D level, significantly improved the parameters of skin MC and functional tests, HbA1c and BMI decreased.Conclusions. Acceptance of high doses of cholecalciferol for 24 weeks has been associated with an improvement in the parameters of glycaemia and indicators of cutaneous MC in patients with T2DM with DPN.

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Microcirculation disorders in patients with vibration disease and comorbidity

Russian Journal of Occupational Health and Industrial Ecology ◽

10.31089/1026-9428-2019-59-9-672-673 ◽

2020 ◽

pp. 672-672

Author(s):

A. N. Kuks ◽

N. V. Slivnitsyna

Keyword(s):

Type 2 Diabetes ◽

Laser Doppler Flowmetry ◽

Laser Doppler ◽

Combined Effects ◽

Doppler Flowmetry ◽

Vibration Disease ◽

History Of

The results of laser Doppler flowmetry in patients with vibration disease associated with the combined effects of local and general vibration with a history of type 2 diabetes are presented.

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Microcirculatory Vasomotor Changes in Type 2 Diabetes With Peripheral Neuropathy

Case Medical Research ◽

10.31525/ct1-nct03847779 ◽

2000 ◽

Author(s):

Keyword(s):

Type 2 Diabetes ◽

Peripheral Neuropathy

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Which Occurs First in Patients with Type 2 Diabetes Mellitus? Central or Peripheral Neuropathy

International Archives of BioMedical and Clinical Research ◽

10.21276/iabcr.2016.2.2.16 ◽

2016 ◽

Vol 2 (2) ◽

Author(s):

Raju Panta ◽

Dr. Rita Khadka ◽

Dilip Thakur ◽

Nirmala Limbu ◽

Bishnu Hari Paudel

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Peripheral Neuropathy

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Balance and motion coordination parameters can be improved in patients with type 2 diabetes with physical balance training: non-randomized controlled trial

BMC Endocrine Disorders ◽

10.1186/s12902-021-00804-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Artur Stolarczyk ◽

Igor Jarzemski ◽

Bartosz M. Maciąg ◽

Kuba Radzimowski ◽

Maciej Świercz ◽

...

Keyword(s):

Type 2 Diabetes ◽

Peripheral Neuropathy ◽

Balance Control ◽

Balance Training ◽

Control Group ◽

Study Group ◽

Muscle Coordination ◽

Risk Of Falling ◽

Increased Risk

Abstract Background Type 2 diabetes (T2D) is a cause of multiple complications, including retinopathy and peripheral neuropathy. These complications are well understood and believed to contribute to gait instability. Poor balance control and increased falling risk have also been reported in people with diabetic peripheral neuropathy (DPN). Patients with DPN have increased risk of falling due to decreased proprioceptive feedback. Effective balance training should improve postural control in patients with DPN. For this purpose further evaluation was conducted and balance training was designed. Methods The goal of our study was to determine values of proprioception, balance, muscle coordination and strength in patients with T2D and analyze whether biofeedback balance training with use of the Biodex Balance System could improve these parameters. To assess the fall risk the general stability index (GSI), the index of frontal-posterior (FPI) and medial–lateral (MLI) stability were evaluated. 37 patients with diagnosed type 2 diabetes mellitus were recruited to this study. Their results were compared with control group consisting of 41 healthy participants who were homogenic to the study group in terms of age and body mass index (BMI). Results There were statistically significant differences between patients with diabetes compared to healthy subjects in GSI (2.79 vs 1.1), FPI (1.66 vs 0.7), MLI (0.88 vs 0.52) and risk of falling (5.18 vs 2.72) p < 0.05. There were also statistically significant changes before and after training in all stability indices (GSI: 2.79 vs 1.26, FPI: 1.66 vs 0.77, MLI: 0.88 vs 0.54 accordingly) p < 0.05 and risk of falling (5.18 vs 3.87) p < 0.05 in the study group who had undergone training with biofeedback. Conclusions This study found that there is a decreased balance and motor coordination and an increased risk of falling in patients with type 2 diabetes. These parameters improved in patients who have undergone training programme with biofeedback. Furthermore, an age-dependent deprivation of static balance was observed along with an increased risk of falling as a result of increasing BMI.

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Vitamin D Status in a Bulgarian Population With Type 2 Diabetes and Diabetic Foot Ulcers

The International Journal of Lower Extremity Wounds ◽

10.1177/1534734620965820 ◽

2020 ◽

pp. 153473462096582

Author(s):

Ani S. Todorova ◽

Edward B. Jude ◽

Rumyana B. Dimova ◽

Nevena Y. Chakarova ◽

Mina S. Serdarova ◽

...

Keyword(s):

Type 2 Diabetes ◽

Vitamin D ◽

Peripheral Neuropathy ◽

Diabetic Foot ◽

Diabetic Peripheral Neuropathy ◽

Foot Ulcers ◽

Diabetic Foot Ulcers ◽

Vitamin D Status ◽

Active Infection

The aim of this study was to assess vitamin D status in patients with type 2 diabetes and diabetic foot ulcers (DFU). A total of 242 participants with type 2 diabetes, mean age 59.1 ± 10 years, mean body mass index 31.4 ± 6.3 kg/m2, and estimated glomerular filtration rate ≥45 mL/min/1.73m2, were divided into 2 groups: 73 with DFU (35 with and 38 without active infection) and 169 without DFU (106 with diabetic peripheral neuropathy, 63 without complications). Neuropathy was assessed by 10 g monofilament, Rydel-Seiffer 128 Hz tuning fork, and temperature discrimination. Serum 25(OH)D (25-hydroxy vitamin D) was assessed by ECLIA (electro-chemiluminescence immunoassay) method. Median 25(OH)D level was 12.6 ng/mL (IQR [interquartile range] 9.3-17.6 ng/mL) in the studied cohort. The DFU group presented with lower 25(OH)D level as compared with diabetic patients without foot ulcers (non-DFU group): 11.6 ng/mL (IQR 8.5-15.8 ng/mL) versus 13.5 ng/mL (IQR 9.6-18.6 ng/mL), P = .001; the diabetic peripheral neuropathy subgroup demonstrated lower 25(OH)D level in comparison with participants without complications: 12.5 ng/mL (IQR 9-17.2 ng/mL) versus 15.9 ng/mL (IQR 10.4-20.8 ng/mL), P = .031. This remained significantly different even after correction for age and duration of diabetes. There was no difference in 25(OH)D level between the subgroups according to the presence of active infection. In conclusion, vitamin D deficiency may play a role in the development of diabetes complications.

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Obesity, type 2 diabetes, and impaired insulin-stimulated blood flow: role of skeletal muscle NO synthase and endothelin-1

Journal of Applied Physiology ◽

10.1152/japplphysiol.00286.2016 ◽

2017 ◽

Vol 122 (1) ◽

pp. 38-47 ◽

Cited By ~ 30

Author(s):

Leryn J. Reynolds ◽

Daniel P. Credeur ◽

Camila Manrique ◽

Jaume Padilla ◽

Paul J. Fadel ◽

...

Keyword(s):

Nitric Oxide ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Blood Flow ◽

Vastus Lateralis ◽

Glucose Disposal ◽

Endothelin 1 ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Increased endothelin-1 (ET-1) and reduced endothelial nitric oxide phosphorylation (peNOS) are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), but studies examining these links in humans are limited. We sought to assess basal and insulin-stimulated endothelial signaling proteins (ET-1 and peNOS) in skeletal muscle from T2D patients. Ten obese T2D [glucose disposal rate (GDR): 6.6 ± 1.6 mg·kg lean body mass (LBM)−1·min−1] and 11 lean insulin-sensitive subjects (Lean GDR: 12.9 ± 1.2 mg·kg LBM−1·min−1) underwent a hyperinsulinemic-euglycemic clamp with vastus lateralis biopsies taken before and 60 min into the clamp. Basal biopsies were also taken in 11 medication-naïve, obese, non-T2D subjects. ET-1, peNOS (Ser1177), and eNOS protein and mRNA were measured from skeletal muscle samples containing native microvessels. Femoral artery blood flow was assessed by duplex Doppler ultrasound. Insulin-stimulated blood flow was reduced in obese T2D (Lean: +50.7 ± 6.5% baseline, T2D: +20.8 ± 5.2% baseline, P < 0.05). peNOS/eNOS content was higher in Lean under basal conditions and, although not increased by insulin, remained higher in Lean during the insulin clamp than in obese T2D ( P < 0.05). ET-1 mRNA and peptide were 2.25 ± 0.50- and 1.52 ± 0.11-fold higher in obese T2D compared with Lean at baseline, and ET-1 peptide remained 2.02 ± 1.9-fold elevated in obese T2D after insulin infusion ( P < 0.05) but did not increase with insulin in either group ( P > 0.05). Obese non-T2D subjects tended to also display elevated basal ET-1 ( P = 0.06). In summary, higher basal skeletal muscle expression of ET-1 and reduced peNOS/eNOS may contribute to a reduced insulin-stimulated leg blood flow response in obese T2D patients. NEW & NOTEWORTHY Although impairments in endothelial signaling are hypothesized to reduce insulin-stimulated blood flow in type 2 diabetes (T2D), human studies examining these links are limited. We provide the first measures of nitric oxide synthase and endothelin-1 expression from skeletal muscle tissue containing native microvessels in individuals with and without T2D before and during insulin stimulation. Higher basal skeletal muscle expression of endothelin-1 and reduced endothelial nitric oxide phosphorylation (peNOS)/eNOS may contribute to reduced insulin-stimulated blood flow in obese T2D patients.

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