We assessed the effect of different doses of vitamin D supplementation on microcirculation, signs and symptoms of peripheral neuropathy and inflammatory markers in patients with type 2 diabetes (T2DM). Sixty-seven patients with T2DM and peripheral neuropathy (34 females) were randomized into two treatment groups: Cholecalciferol 5000 IU and 40,000 IU once/week orally for 24 weeks. Severity of neuropathy (NSS, NDS scores, visual analogue scale), cutaneous microcirculation (MC) parameters and inflammatory markers (ILs, CRP, TNFα) were assessed before and after treatment. Vitamin D deficiency/insufficiency was detected in 78% of the 62 completed subjects. Following treatment with cholecalciferol 40,000 IU/week, a significant decrease in neuropathy severity (NSS, p = 0.001; NDS, p = 0.001; VAS, p = 0.001) and improvement of cutaneous MC were observed (p < 0.05). Also, we found a decrease in IL-6 level (2.5 pg/mL vs. 0.6 pg/mL, p < 0.001) and an increase in IL-10 level (2.5 pg/mL vs. 4.5 pg/mL, p < 0.001) after 24 weeks of vitamin D supplementation in this group. No changes were detected in the cholecalciferol 5000 IU/week group. High-dose cholecalciferol supplementation of 40,000 IU/week for 24 weeks was associated with improvement in clinical manifestation, cutaneous microcirculation and inflammatory markers in patients with T2DM and peripheral neuropathy.

Background: Inflammation plays an important role in the pathogenesis of diabetic neuropathy (DN) in patients with type 2 diabetes (DM2). It seems that vitamin D ((VitD) could be involved in this process, however, the relationship between VitD status and inflammatory markers has not been wildly studied. Hypothesis: The aim was to study the association between VitD status and inflammatory markers in patients with DM2 and DN. Methods: The single-centre randomized study included 62 subjects with DM2 and DN (more than 4 points according to NDS), HbA1c up to 9%. Antihyperglycemic treatment was stable during the study. Patients were randomized in two groups: 5000 IU (group I) and 40000 IU (group II) of cholecalciferol supplementation per week. Body mass index (BMI), glycated hemoglobin (HbA1c), serum 25(OH)D level, Interleukins 6, 10 (IL-6, IL-10) were determined at baseline and after 24 weeks of treatment. The correlation analysis was evaluated by Pearson test. Results: Group I (n = 31, F16) and Group II (n = 31, F15) were matched for age, gender, BMI and baseline HbA1c levels. VitD insufficient/deficiency was revealed in 78% of diabetic patients with DN. After 6 months of VitD supplementation, the BMI, HbA1c and IL-6 levels significantly decreased, and 25(OH)D and IL-10 concentration increased only in Group II. We found associations between serum 25(OH)D and IL-6 (r = -0.912, p = 0.017) as well as IL-10 (r = 0.903, p = 0.014), and between HbA1c and IL-6 (r = 0.825, p = 0.031) and IL-10 (r = -0.897, p = 0.025) exclusively in Group II after treatment. Conclusions: VitD supplementation in 40000 IU of cholecalciferol per week during 6 months was associated with improved vitamin D status, pro-inflammatory markers and better glycemic control in patients with DM2 and DN. Vitamin D supplementation in 5000 IU per week did not change vitamin D status and inflammatory markers in this population. Disclosure A.P. Stepanova: None. T.L. Karonova: None. M. Galagoudza: None. E.Y. Vasileva: None. E.B. Jude: None.

Type 2 diabetes mellitus (DM) is a global epidemic associated with severe vascular complications development. Diabetic neuropathy is the most common chronic complication of DM that worsens patients life quality and prognosis. Therefore, studies dealing with DM and diabetic neuropathy underlying mechanisms are extremely relevant. The review discusses current views on vitamin D role in glucose metabolism and inflammatory processes. It is reported that vitamin D deficiency can contribute to insulin resistance development, and change in vitamin D receptor activity or extra- and intracellular calcium concentration due to vitamin D deficiency can affect pancreatic -cells function and lead to decrease in insulin production. Key pathogenic mechanisms of diabetic neuropathy as well as possible relationship between vitamin D deficiency and neuropathy development are in focus of this review. Results of recent clinical trials regarding vitamin D supplementation in patients with DM are also discussed. The presented data suggest that vitamin D deficiency can be considered as a non-classical risk factor for the development of not only DM but its complications as well.

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.

Type 2 diabetes mellitus (T2DM) is often combined with vitamin D (VD) deficiency. It is known that VD affects glycemic control as well as systemic inflammation and could play a role in diabetic neuropathy (DN) pathogenesis. High VD dose supplementation decreases impaired microcirculation in diabetic patients and reduces DN severity. NTSS-9, NDS scales were used, 25(OH)D, HbA1c were studied in 24 (12F) patients with T2DM and DN. Parameters of microcirculation (value of perfusion - M, standard deviation - σ, Kv - coefficient of microcirculation) by laser Doppler fluorometry (LAKK-M, Russia) baseline and after 24 weeks of VD supplementation. Inclusion criteria: T2DM duration more then 5 years, HbA1c ≤9.0%, NDS index 4 and more, signed IC. Patients were randomized in to two groups: 5000 IU (group I) and 40000 IU (group II) per week cholecalciferol treatment without hypoglycemic treatment changes. At baseline the two groups were comparable by sex, age, BMI, HbA1c level. We included in group I twelve pts (6F) aged 56,1±5,4 with mean HbA1c 8.2±0.4% and 25(OH)D level 21.4±3.4 nmol/l. In group II we included 12 pts (6F), mean age 51,3±5,9, HbA1c 8.4±0.6%, 25(OH)D 20.9±4,1 nmol/l. Baseline NDS index did not differ between the two groups 10.1±3.3 and 12.3± 4.7 accordingly, as well as the NTSS-9 index 15.8±5.2 and 17.1±6.8 (p&gt;0.05). Parameters of microcirculation were the same M=10.63±1.37 and 12.36±2.51 BPU, σ=5.32±0.79 and 4.44±1.05, Kv=11.36±1.59 and 10.64±2.93. After 24 weeks of VD treatment we did not find changes in group I - HbA1c 8.1±0.4%, 25(OH)D 24,7±2.5 (p=0,07), M=10.30±1.14 (p=0.08), σ=4.98±0.56 (p=0.05) and Kv=11.82±2.38 (p=0.87). HbA1c significantly decreased till 7.4±0.7% (p=0.023) in group II. 25(OH)D level increased to 60,9±3.1 (p=0,003). We found improvement of all microcirculation parameters M=19.69±2.52 (p=0.003), σ=6.05±0.93 (p=0.005), Kv=13.36±3.15 (p=0.017) compared to baseline. High dose of VD supplementation could improve microcirculation parameters in T2DM patients with DN. Disclosure A.P. Stepanova: None. T.L. Karonova: None. E.B. Jude: Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Novo Nordisk A/S, Takeda Development Centre Europe Ltd., Bayer AG, Boehringer Ingelheim GmbH, Eli Lilly and Company.