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Health-related quality of life in T1DM patients after high-dose cholecalciferol supplementation: data from a pilot clinical trial

Abstract

Background

Type 1 Diabetes Mellitus (T1DM) impacts health-related quality of life (HRQoL). Cross-sectional studies suggest that low levels of vitamin D (VD) may impair HRQoL, however, the effect of VD supplementation on quality of life in T1DM patients has not yet been clarified. Our study evaluated the effects of high-dose VD supplementation on HRQoL in T1DM.

Methods

We performed a prospective study with 64 patients receiving cholecalciferol (4000 IU/day for patients with 25-OH-vitamin D [25(OH)D] between 30 and 60 ng/mL, and 10,000 IU/day for those with 25(OH)D below 30 ng/mL) for 12 weeks, as part of a research protocol. HRQoL was assessed with EuroQol instruments (EQ-5D and EQ-VAS).

Results

There was an improvement in global EQ-5D index, and analysing specifically the EQ-5D domains, we observed an improvement in mobility (1.3 ± 0.6 versus 1.1 ± 0.3, p < 0.01). Evaluating possible outcome influencing variables, we detected a reduction in albuminuria at the end of the trial, without changes in BMI, lipids, blood pressure, glycemic control and insulin doses. We found correlations between final albuminuria and the dimensions: mobility (r = 0.6; p < 0.01), personal care (r = 0.7; p < 0.01), pain and discomfort (r = 0.6; p < 0.01) and habitual activities (r = 0.6; p < 0.01), suggesting an association between albuminuria reduction and the impact of VD supplementation on HRQoL.

Conclusion

Our data showed that high doses of cholecalciferol supplementation can improve HRQoL in patients with T1DM, and the reduction of albuminuria seems to be an important factor in this context.

Trial registration: (ISRCTN32601947), 03/06/2017 retrospectively registered.

Background

Type 1 diabetes mellitus (T1DM) is the most common endocrinopathy of childhood and adolescence and it is characterized by severe insulin deficiency, corresponding to approximately 10% of all diabetes cases, involving approximately 10 to 20 million individuals worldwide [1]. Due to its high complexity, it is a disease with important physical, psychological and social repercussions and a considerable impact on the quality of life (QoL) of patients and their families [2].

The Brazilian Type 1 Diabetes Study Group (BrazDiab1SG) evaluating over 3000 patients with T1DM, collected information from demographic, economic, clinical-laboratory and health-related quality of life (HRQoL), which was measured using EuroQol [3]. Those data showed that variables as HbA1c, age, socioeconomic status (SES), physical activity, and the presence of micro and macrovascular complications were weakly associated with QoL, suggesting the need to investigate other factors that may affect this scenario [3].

Vitamin D levels are lower in DM patients [4, 5], but whether hypovitaminosis D is associated or not with impared quality of life and if cholecalciferol high-dose supplementation could improve this scenario in this group remains controversial [6,7,8,9]. Thus, the aim of our study was to evaluate the effect of high-dose cholecalciferol supplementation on HRQoL of patients with T1DM.

Methods

Study design and patients

We performed a pilot prospective study in order to evaluate the effect of high dose vitamin D supplementation in health-related quality of life (HRQoL) in patients with T1DM as part of a research protocol (ISRCTN32601947) that has already provided evidence on other aspects of VD supplementation outcomes [10,11,12,13]. This trial was reviewed and approved by University Hospital João de Barros Barreto (HUJBB) ethics committee.

A total of 64 subjects were recruited from the endocrinology ambulatory department from HUJBB, signed consent was obtained from all patients. Participants were divided in two groups: patients with basal VD levels between 30 and 60 ng/mL (who received 4.000 IU /day of cholecalciferol) and patients with basal VD levels below 30 ng/mL (supplemented with 10,000 IU/day), both for 12 weeks. Our intention was to asegurate that patients achieve and maintain VD levels between 30 and 60 at the end of the trial to maximize VD extra-skeletal actions, without collateral effects. Because of that, we used the dose ranged between 4.000 and 10,000 IU/day according to the recommendation of Endocrine Society [14].

Inclusion criteria consisted in: (a) patient with T1DM diagnosis aged between 12 and 50 years, in at least a 1-year follow-up and in regular treatment with an endocrinologist; (b) glycated hemoglobin ≥ 7%; (c) insulin dose stability for at least 3 months before participating in the study; (e) NPH, Glargine, Detemir, Aspart, Glulisin, Lispro, and Regular insulin were allowed; (f) patients in use of metformin could participate of the study as long as they were using the same dose for at least 3 months; (g) patients with hypertension and/or diabetic kidney disease (DKD) must be in stable doses of antihypertensive medication for at least four weeks; (h) compliance with diet and exercise regimen. Exclusion criteria were: (a) history of hepatic or bone metabolism disorders; (b) previous VD or Calcium supplementation; (c) abnormal serum creatinine levels (d) anemias; (e) breastfeeding and pregnant women; (f) uncontrolled hypo or hyperthyroidism and allergies to VD supplementation; (g) hemotransfusion and/or blood donation within the 3 months before the first visit. Patients were previously instructed to maintain physical activity regularly according to American Diabetes Association Guidelines [15] to avoid variations during the study.

Data collection

Data collection occurred during scheduled visits, during pre-treatment (baseline) and post-treatment (end of study) phases. Analysis of medical records (demographics, pre-existent clinical conditions, insulin and other medications in use) and physical examination were carried out. Laboratory tests and health-related quality of life evaluation (EQ-5D-5L and EQ- VAS) [16] were performed before and after twelve weeks.

Serum 25(OH)D was measured by DiaSorin LIAISON 25-OH-Vitamin D TOTAL chemiluminescence immunoassay (DiaSorin, Stillwater, MN, USA) [17, 18]; HbA1C was analyzed by HPLC method. Fasting glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by colorimetry. The ultra-sensitive C-reactive protein was evaluated by ARCHITECT turbidimetry, and creatinine by the kinetic/automated method. The glomerular filtration rate (GFR) was calculated by the CKD-EPI formula [19]. Albuminuria was measured in three 24 h urine samples by immunoturbidimetry [20]. Peripheral neuropathy was evaluated by two scores: Total Symptoms Score (TSS) and Neuropathy Disability Score (NDS). Presence of this complication was established by TSS >  = 2 and NDS >  = 3 [21, 22].

Quality of life assessment

Quality of life was assessed by the EuroQol 5 and its two tools: the EQ-5D-5L and EQ-VAS [16]. The first one descriptively analyzes five dimensions of problems: mobility, self-care, pain and discomfort, usual activities, and anxiety and depression. Each dimension has five levels from "no problems" to "extreme problems". The EQ-VAS consists of an analog scale from 0 (poor health status) to 100 (optimal health status) for the patient to mark/say a value that reflects, in his/her perception, his/her health status. The HRQoL assessment tool was applied at basal and final visits.

The health states defined by the EQ-5D-5L responses were translated into EQ-5D utility index by means of sets of values that were derived from large population-based surveys. The utility index scale ranges from 0.0 to 1.0, where 0.0 represents death and 1.0 represents full health. As we did not have a publicly available set of EQ-5D-5L values for Brazilian population, in our study we used the set of values from the following countries: United States, Spain, Zimbabwe, Denmark, France, Germany, Japan, Netherlands, Thailand, and United Kingdom using the link (https://euroqol.org/eq-5dinstruments/eq-5d-5l-about/valuation-standard-value-sets/crosswalk-index-value-calculator/).

Statistical analysis

Before and after VD supplementation, categorical variables were compared by Chi-square, Fisher and McNemar tests, while numerical ones were analysed with Student's T and Mann–Whitney tests, with and without normal distribution, respectively. Also, Paired Student's T and Wilcoxon tests were used to compare paired groups before and after the follow-up period, with normal and non-normal distribution, respectively. Data with normal distribution were represented as mean and standard deviation values, while data with non-normal distribution were represented by median and quartiles. To compare more than two groups, the analysis of variance test (ANOVA) was applied for normal distribution variables and Kruskal–Wallis test for non-normal distribution ones. To calculate the sample size, we used paired T test. We expected a change to be detected = 0.2, with an expected standard deviation exchange of 0.5 with a desired power = 0.8 in EQ-5D-5L dimensions. The sample size to achieve it was 52. Additionally, albuminuria values were converted to log base 10 (log10) to better analyze the data. The level of statistical significance was set at p < 0.05 and all analyses were stored and processed with the software SigmaStat (Jandel Scientific) version 3.5 and SPSS (Statistical Package for Social Sciences) 22.0 IBM.

Results

Clinical characteristics at the beginning of the study are presented in Table 1.

Table 1 Clinical characteristics at the beginning of the study

Most patients of our sample (72%) had 25(OH)D levels below 30 ng/ml, and, by the end of the trial, 94% of T1DM patients were classified with normal VD (≥ 30 ng/ml) (p < 0.001).

In Table 2 are described the main clinical and laboratorial parameters before and after VD supplementation. By the end of the study, most analyzed parameters have not changed, except for 25(OH)VD levels (26.7 ± 9 versus 55.1 ± 24.1 ng/mL, p < 0.001).

Table 2 Clinical and laboratory parameters of patients with T1DM before and after vitamin D supplementation

In Table 3 we described EQ-5D utility index in all countries with available datasets given by EuroQol. It included countries that had common geographic conditions as that of Brazil (Thailand and Zimbabwe) or not (Denmark and Japan). We used all EuroQol datasets available. The results were consistently the same. On HRQoL evaluation by EuroQol, we found an improvement on EQ-5D-5L utility index by the end of the study, according to electronic calculators available from evaluated countries, independently of Human Development Index (HDI) (Table 3).

Table 3 Utility index of EQ-5D before and after vitamin D supplementation using a set of values of available countries

In EQ-5D, we observed an important improvement in mobility (1.3 ± 0.6 versus 1.1 ± 0.3, p < 0.01) and there was also a tendency to improve in self-care dimension at the end of VD supplementation. We did not find additional changes in the other EQ-5D dimensions, as in the attributed grade to general health status, evaluated by EQ-VAS (Table 4)

Table 4 Analysis of EuroQol dimensions and grade of EQ-VAS before and after vitamin D supplementation

Main DM chronic complications before and after VD administration are shown on Table 5. We observed significant reduction in albuminuria (1.27 ± 0.7 versus 1.22 ± 0.7, p = 0.01), with no changes in the other parameters.

Table 5 Clinical and laboratorial data concerning chronic T1DM complications before and after vitamin D supplementation

Additionally, it was observed that final 25(OH)D levels showed correlation with final albuminuria (r = − 0.3, p < 0.05) (Fig. 1). Therefore, the higher the 25(OH)D levels, the lower the albuminuria excretion rates by the end of VD supplementation.

Fig. 1
figure 1

Correlation between albuminuria and 25(OH)D levels at the end of the study

In a post-hoc analysis, we compared patients who improved (group 1A, N = 54) or not (group 1B, N = 10) the EQ-5D utility index. We found an albuminuria reduction at the end of VD administration only in group 1A. No other differences were identified, except for increase in non-HDL and LDL cholesterol levels in group 1B at the end of the study (Table 6).

Table 6 Analysis of clinical and laboratorial parameters according to improvement (group 1A) or not (group 1B) of the EQ-5D utility index after vitamin D supplementation

Furthermore, we performed a second post-hoc analysis on patients with improvement (group 2A, n = 25) or not EQ-VAS (group 2B, n = 39), and found a significant increase in the dose of prandial insulin in group 2B (22.1 ± 13.1 IU versus 24.4 ± 12 IU, p < 0.05). Albuminuria reduced significantly only in group 2A (1.2 ± 0.7 versus 0.98 ± 0.7; p < 0.05). Besides that, we found that final albuminuria excretion was significantly lower in group 2A when compared to group 2B (Table 7).

Table 7 Analysis of clinical and laboratorial parameters according to improvement (Group 2A) or not (Group 2B) of EQ-VAS at the end of vitamin D supplementation

On patients with an improvement of EQ-VAS at the end of the study (Group 2A), we also observed a correlation between final albuminuria and the following dimensions of EQ-5D: mobility (r = 0.6; p < 0.01), self-care (r = 0.7; p < 0.01), habitual activities (r = 0.6; p < 0.01) and pain and discomfort (r = 0.6; p < 0.01).

Discussion

Our findings suggested an improvement in T1DM patients quality of life after supplementation with high doses of cholecalciferol. According to our knowledge, this is the first clinical trial to demonstrate the impact of VD supplementation on HRQoL in this population.

Few studies addressing VD supplementation on HRQol in patients with diabetes have been conducted. Krul-Poel et al. performed a randomized, double-blind, placebo-controlled trial with 275 patients with type 2 diabetes mellitus (T2DM), who monthly supplemented 50,000 IU of cholecalciferol during six months, and found no changes in QoL at the end of the study [8]. Similarly, Mager et al. analyzed the impact of administering different doses of vitamin D3 (2000 IU day or 40,000 IU monthly) for six months in T2DM patients with chronic kidney disease (CKD), and did not detect improvement in their HRQoL [9]. Those results differ from ours since the patients in the present trial received higher doses of cholecalciferol. Furthermore, both studies used cholecalciferol monthly, in contrast to cholecalciferol daily doses in our trial which have a different biological effect [12, 13, 23].

Additionally, the improvement of HRQoL in our study was found by analysis of EQ-5D-5L index after supplementation of cholecalciferol for 12 weeks. We noticed a change in the final EQ-5D-5L index using sets of values from all countries available. It was important to unify the 5 dimensions of problems in a single index to obtain our results. It is our knowledge that additional studies are necessary to establish the importance of each dimension for the Brazilian population. For that, are required both a traditional method validation, performed in Brazil in 2015, and a populational study, which has not happened in this country yet [24]. However, our findings showed improvement of EQ-5D-5L index using sets of values from countries of different continents, with different populations and the most diverse HDIs, which gives a lot of consistency to our results.

When we analysed each dimension of EQ-5D in this trial, we found an improvement of mobility. Moreover, self-care dimension showed a tendency to be better by the end of VD administration. Those results differ from Raymakers et al., who describe, in a cross-sectional study, a greater impact of anxiety/depression dimension in HRQoL, evaluating 473 patients with T1DM in Ireland [25]. Nonetheless, it is important to notice that in BrazDiab1SG, as described by Felício et al., patients in North and Northeast regions reported lower frequency of anxiety and depression when compared to other brazilian regions [3, 25]. In addition, it is known that geographic aspects, especially temperature and sun exposure, can affect quality of life [26]. The consistent improvement of EQ-5D-5L index when evaluated by sets of values from countries that represent almost all geographical regions validates our findings.

It is well known that skeletal muscle fibers carry VD receptors, and their activation is a possible mechanism of muscle growth [23, 27]. Biopsy and consistent findings of muscle atrophy were associated with VD deficiency [28]. Moreover, Sato et al. (2005) showed that calcium and vitamin D supplementation improves muscle fibers in number and size, as well as the lower members function. Randomized controlled trials and meta-analyses have shown that 25(OH)D supplementation decreases risk of falls and fractures in elderly patients [29,30,31,32]. Finally, VD deficiency is associated with muscle atrophy, musculoskeletal pain and worse physical function in the general population [32]. In our sample, most patients had hypovitaminosis D (VD < 30 ng/ml) at the beginning of the study and, by the end of the supplementation, 94% of them had sufficient levels of 25 (OH) D. It could have potentiated extra-skeletal actions of VD [33]. Thus, the hypothesis that VD affected mobility and QoL in our study by its direct action on muscle fibers must be considered.

Our results also demonstrated a reduction in albumin excretion at the end of cholecalciferol supplementation. It particularly occurred in the subgroups that improved QoL in post-hoc analysis. In addition, there was a correlation between final 25(OH)D levels and final albuminuria. Felício et al. in a pilot study that analyzed patients with T1DM who received 4,000 and 10,000 units of cholecalciferol for 12 weeks according to their previous 25(OH)D levels found a reduction in prevalence of diabetic kidney disease (DKD) and a correlation between the percentage of VD levels variation and albuminuria after cholecalciferol supplementation [11]. There is growing evidence that vitamin D given in high doses can be renoprotective [34, 35]. Humalda et al. (2015) performed a systematic review of all randomized clinical trials with calcitriol or paricalcitol as an antiproteinuric intervention. During follow-up, VD active analogs reduced proteinuria by an average of 16%. These results were obtained, in most cases (84%), in patients under chronic treatment of previous conditions with renin angiotensin aldosterone inhibitors, accentuating the capacity of VD analogs to reduce residual proteinuria. Those authors suggest that compensatory increase in renin is a paradoxical event secondary to the use of SARS inhibitors, and can be antagonized by calcitriol [36]. Furthermore, Wolfgram et al. (2017) presented a secondary analysis of the cross-sectional study SPRINT (Systolic Blood Pressure Intervention Trial), in which they evaluated a subgroup of individuals with age greater than 75 years. In addition to renal indexes (GFR and albuminuria), participants in this subgroup underwent gait speed assessment, self-assessment of HRQoL with a focus on functional status (EQ-5D), and assessment risk of falling. In the unadjusted model, the decrease in eGFR and increase in categories of albuminuria were associated with worse scores in the three tools. This data raises the hypothesis that VD may also contributes to an improvement in quality of life through its positive effect in DKD [37].

Studies have shown that, among patients with CKD, HRQoL gradually declines as the disease progresses, with the worst HRQoL scores obtained when an advanced stage of kidney disease is reached [38, 39]. When CKD coexists with diabetes an accentuated deterioration in HRQoL is expected [40]. However, few studies have examined this relationship in the early stages of CKD or attempted to incorporate albuminuria in this assessment. According to Bowling et al., albuminuria may be more sensitive than glomerular filtration rate (GFR) to identify patients with risk of functional impairment, at least in early stages of CKD [41]. In our study, abnormal creatinine levels were an exclusion criteria. Therefore, our data reinforce these findings.

The main limitations of our study were short duration (12 weeks) and absence of a placebo control group. Following this study, controlled, double-blind, randomized trials with a placebo group and a longer duration of supplementation should be performed to confirm our findings.

Conclusions

Our data demonstrated an improvement in HRQoL after supplementation of high doses of cholecalciferol in patients with T1DM. There was an improvement in the EuroQoL utility index (EQ-5D-5L), and in mobility dimension. Additionally, the reduction of albuminuria seems to be an important factor in this context.

Availability of data and materials

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ANOVA:

Analysis of variance test

BMI:

Body Mass Index

CKD:

Chronic kidney disease

DKD:

Diabetic kidney disease

DM:

Diabetes mellitus

GFR:

Glomerular filtration rate

HDI:

Human development index

HDL-C:

High-density lipoprotein cholesterol

HRQoL:

Health-related quality of life

HUJBB:

University Hospital João de Barros Barreto

IU:

International units

LDL-C:

Low-density lipoprotein cholesterol

NDS:

Neuropathy disability score

QoL:

Quality of life

SES:

Socioeconomic status

TSS:

Total symptoms score

T1DM:

Type 1 diabetes mellitus

T2DM:

Type 2 diabetes mellitus

VD:

Vitamin D

References

  1. International Diabetes Federation. IDF Diabetes Atlas Ninth. Dunia: IDF. 2019.

  2. Felício JS, Silva LSAA, Santos FM. Qualidade de vida do paciente com Diabetes Mellitus tipo 1. In: Diabetes 1 no Brasil. 1st ed. São Paulo: CLANNAD; 2019.

  3. On behalf of the Brazilian Type 1 Diabetes Study Group (BrazDiab1SG), Braga de Souza ACC, Felício JS, Koury CC, Neto JFA, Miléo KB, et al. Health-related quality of life in people with type 1 Diabetes Mellitus: data from the Brazilian Type 1 Diabetes Study Group. Health Qual Life Outcomes. 2015;13:204.

  4. Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham NJ. Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990–2000. Diabetes. 2008;57:10. https://doi.org/10.2337/db08-0593.

    CAS  Article  Google Scholar 

  5. Feng R, Li Y, Li G, Li Z, Zhang Y, Li Q, et al. Lower serum 25 (OH) D concentrations in type 1 diabetes: a meta-analysis. Diabetes Res Clin Pr. 2015;108:3. https://doi.org/10.1016/j.diabres.2014.12.008.

    CAS  Article  Google Scholar 

  6. Alcubierre N, Castelblanco E, Martínez-Alonso M, Granado-Casas M, Esquerda A, Traveset A, et al. Vitamin D deficiency is associated with poorer satisfaction with diabetes-related treatment and quality of life in patients with type 2 diabetes: a cross-sectional study. Health Qual Life Outcomes. 2018;16:44. https://doi.org/10.1186/s12955-018-0873-3.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Anand S, Kaysen GA, Chertow GM, Johansen KL, Grimes B, Dalrymple LS, et al. Vitamin D deficiency, self-reported physical activity and health-related quality of life: the Comprehensive Dialysis Study. Nephrol Dial Transplant. 2011;26:3683–8. https://doi.org/10.1093/ndt/gfr098.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Krul-Poel YHM, Westra S, van Wijland HJJ, Stam F, Lips P, Pouwer F, et al. Vitamin D status and health-related quality of life in patients with type 2 diabetes. Diabet Med. 2016;33:300–6. https://doi.org/10.1111/dme.12834.

    CAS  Article  PubMed  Google Scholar 

  9. Mager DR, Jackson ST, Hoffmann MR, Jindal K, Senior PA. Vitamin D 3 supplementation, bone health and quality of life in adults with diabetes and chronic kidney disease: Results of an open label randomized clinical trial. Clin Nutr. 2017;36:686–96. https://doi.org/10.1016/j.clnu.2016.05.012.

    CAS  Article  PubMed  Google Scholar 

  10. de Queiroz NNM, de Melo FTC, de Souza RF, Janaú LC, de Souza Neto NJK, de Lemos MN, et al. High-dose cholecalciferol supplementation reducing morning blood pressure in normotensive DM1 patients. Curr Diabetes Rev. 2021;17:378–86. https://doi.org/10.2174/1573399816999200729131508.

    CAS  Article  PubMed  Google Scholar 

  11. Felício JS, de Oliveira AF, Peixoto AS, de Souza ACCB, Abrahão Neto JF, de Melo FTC, et al. Albuminuria reduction after high dose of vitamin D in patients with type 1 diabetes mellitus: a pilot study. Front Endocrinol. 2017;8:199. https://doi.org/10.3389/fendo.2017.00199.

    Article  Google Scholar 

  12. Felício JS, Luz RM, de Melo FTC, de de Souza Resende F, Oliveira AF, Peixoto AS, et al. Vitamin D on early stages of diabetic kidney disease: a cross-sectional study in patients with type 1 diabetes mellitus. Front Endocrinol. 2016. https://doi.org/10.3389/fendo.2016.00149.

    Article  Google Scholar 

  13. Felício KM, de Souza ACCB, Neto JFA, de Melo FTC, Carvalho CT, Arbage TP, et al. Glycemic variability and insulin needs in patients with type 1 diabetes mellitus supplemented with vitamin D: a pilot study using continuous glucose monitoring system. Curr Diabetes Rev. 2018;14:395–403. https://doi.org/10.2174/1573399813666170616075013.

    CAS  Article  PubMed  Google Scholar 

  14. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30. https://doi.org/10.1210/jc.2011-0385.

    CAS  Article  PubMed  Google Scholar 

  15. American Diabetes Association. Standards of medical care in diabetes—2021 abridged for primary care providers. Clin Diabetes. 2021;39(1):14–43. https://doi.org/10.2337/cd21-as01.

    Article  PubMed Central  Google Scholar 

  16. Balestroni G, Bertolotti G. EuroQol-5D (EQ-5D): an instrument for measuring quality of life. Monaldi Arch Chest Dis. 2015. https://doi.org/10.4081/monaldi.2012.121.

    Article  Google Scholar 

  17. DiaSorin. LIAISON 25 OH vitamin D TOTAL Assay [Brochure]. [Internet]. https://www.diasorin.com/en/node/8476

  18. Wagner D, Hanwell HEC, Vieth R. An evaluation of automated methods for measurement of serum 25-hydroxyvitamin D. Clin Biochem. 2009;42:1549–56. https://doi.org/10.1016/j.clinbiochem.2009.07.013.

    CAS  Article  PubMed  Google Scholar 

  19. Levey AS, Stevens LA, Schmid CH, Zhang Y (Lucy), Castro AF, Feldman HI, et al. A New Equation to Estimate Glomerular Filtration Rate. Ann Intern Med 2009;150:604. https://doi.org/10.7326/0003-4819-150-9-200905050-00006.

  20. Bragd J, Adamson U, Bäcklund LB, Lins PE, Moberg E, Oskarsson P. Can glycaemic variability, as calculated from blood glucose self-monitoring, predict the development of complications in type 1 diabetes over a decade? Diabetes Metab. 2008;34:612–6. https://doi.org/10.1016/j.diabet.2008.04.005.

    CAS  Article  PubMed  Google Scholar 

  21. Young MJ, Boulton AJM, Macleod AF, Williams DRR, Sonksen PH. A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia. 1993;36:150–4. https://doi.org/10.1007/BF00400697.

    CAS  Article  PubMed  Google Scholar 

  22. Ziegler D, Hanefeld M, Ruhnau KJ, Hasche H, Lobisch M, Schutte K, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Diabetes Care. 1999;22:1296–301. https://doi.org/10.2337/diacare.22.8.1296.

    CAS  Article  PubMed  Google Scholar 

  23. Pfeifer M, Begerow B, Minne HW, Nachtigall D, Hansen C. Effects of a short-term vitamin D3 and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women1. J Clin Endocrinol Metab. 2001;86:1633–7. https://doi.org/10.1210/jcem.86.4.7393.

    CAS  Article  PubMed  Google Scholar 

  24. Santos M, Cintra MACT, Monteiro AL, Santos B, Gusmão-filho F, Andrade MV, et al. Brazilian valuation of EQ-5D-3L health states: results from a saturation study. Med Decis Making. 2016;36:253–63. https://doi.org/10.1177/0272989X15613521.

    Article  PubMed  Google Scholar 

  25. Raymakers AJN, Gillespie P, O’Hara MC, Griffin MD, Dinneen SF. Factors influencing health-related quality of life in patients with Type 1 diabetes. Health Qual Life Outcomes. 2018;16:27. https://doi.org/10.1186/s12955-018-0848-4.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. McCue M, Fairman A, Pramuka M. Enhancing quality of life through telerehabilitation. Phys Med Rehabil Clin N Am. 2010;21:195–205. https://doi.org/10.1016/j.pmr.2009.07.005.

    Article  PubMed  Google Scholar 

  27. Boonen S, Bischoff-Ferrari HA, Cooper C, Lips P, Ljunggren O, Meunier PJ, et al. Addressing the musculoskeletal components of fracture risk with calcium and vitamin D: a review of the evidence. Calcif Tissue Int. 2006;78:257–70. https://doi.org/10.1007/s00223-005-0009-8.24.

    CAS  Article  PubMed  Google Scholar 

  28. Bischoff HA, Helin HBS, Dick W, Akos R, Knecht M, Salis C, et al. Effects of vitamin D and calcium supplementation on falls: A randomized controlled trial. J Bone Miner Res. 2003;18(2):343–51. https://doi.org/10.1359/jbmr.2003.18.2.343.

    CAS  Article  PubMed  Google Scholar 

  29. Sato Y, Iwamoto J, Kanoko T, Satoh K. Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial. Cerebrovasc Dis. 2005;20:187–92. https://doi.org/10.1159/000087203.

    CAS  Article  PubMed  Google Scholar 

  30. Broe KE, Chen TC, Weinberg J, Bischoff-Ferrari HA, Holick MF, Kiel DP. A higher dose of vitamin D reduces the risk of falls in nursing home residents: a randomized, multiple-dose study: VITAMIN D AND FALLS IN NURSING HOME RCT. J Am Geriatr. 2007;55:234–9. https://doi.org/10.1111/j.1532-5415.2007.01048.x.

    Article  Google Scholar 

  31. Flicker L, MacInnis RJ, Stein MS, Scherer SC, Mead KE, Nowson CA, et al. Should older people in residential care receive vitamin d to prevent falls? Results of a randomized trial: VITAMIN D TREATMENT TO PREVENT FALLS. J J Am Geriatr. 2005;53:1881–8. https://doi.org/10.1111/j.1532-5415.2005.00468.x.

    Article  Google Scholar 

  32. Houston DK, Cesari M, Ferrucci L, Cherubini A, Maggio D, Bartali B, et al. Association between vitamin D Status and physical performance: the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2007;62:440–6. https://doi.org/10.1093/gerona/62.4.440.

    Article  PubMed  Google Scholar 

  33. Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev. 2016;96:365–408. https://doi.org/10.1152/physrev.00014.2015.

    CAS  Article  PubMed  Google Scholar 

  34. de Zeeuw D, Agarwal R, Amdahl M, Audhya P, Coyne D, Garimella T, et al. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial. Lancet. 2010;376:1543–51. https://doi.org/10.1016/S0140-6736(10)61032-X.

    CAS  Article  PubMed  Google Scholar 

  35. Zhang Z, Sun L, Wang Y, Ning G, Minto AW, Kong J, et al. Renoprotective role of the vitamin D receptor in diabetic nephropathy. Kidney Int. 2008;73:163–71. https://doi.org/10.1038/sj.ki.5002572.

    CAS  Article  PubMed  Google Scholar 

  36. Humalda JK, Goldsmith DJA, Thadhani R, de Borst MH. Vitamin D analogues to target residual proteinuria: potential impact on cardiorenal outcomes. Nephrol Dial Transplant. 2015;30:1988–94. https://doi.org/10.1093/ndt/gfu404.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. Wolfgram DF, Garcia K, Evans G, Zamanian S, Tang R, Wiegmann T, et al. Association of albuminuria and estimated glomerular filtration rate with functional performance measures in older adults with chronic kidney disease. Am J Nephrol. 2017;45:172–9. https://doi.org/10.1159/000455388.

    CAS  Article  PubMed  Google Scholar 

  38. Zimbudzi E, Lo C, Ranasinha S, Teede H, Usherwood T, Polkinghorne KR, et al. Health-related quality of life among patients with comorbid diabetes and kidney disease attending a codesigned integrated model of care: a longitudinal study. BMJ Open Diab Res Care. 2020;8: e000842. https://doi.org/10.1136/bmjdrc-2019-000842.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Wyld MLR, Morton RL, Clayton P, Wong MG, Jardine M, Polkinghorne K, et al. The impact of progressive chronic kidney disease on health-related quality-of-life: a 12-year community cohort study. Qual Life Res. 2019;28:2081–90. https://doi.org/10.1007/s11136-019-02173-1.

    Article  PubMed  Google Scholar 

  40. Krishnan A, Teixeira-Pinto A, Lim WH, Howard K, Chapman JR, Castells A, et al. Health-related quality of life in people across the spectrum of CKD. Kidney Int Rep. 2020;5:2264–74. https://doi.org/10.1016/j.ekir.2020.09.028.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Bowling CB, Bromfield SG, Colantonio LD, Gutiérrez OM, Shimbo D, Reynolds K, et al. Association of reduced eGFR and albuminuria with serious fall injuries among older adults. Clin J Am Soc Nephrol. 2016;11:1236–43. https://doi.org/10.2215/CJN.11111015.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Programa de Pós Graduação em Oncologia e Ciências Médicas of HUJBB for their contribution to the research.

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No funding was received for conducting this study.

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All persons who meet authorship criteria are listed as authors, and all authors certify that they have participated sufficiently in the work to take public responsibility for the content, including participation in the concept, design, analysis, writing, or revision of the manuscript. ACCBS, MCNIO, GNL, ALA, ERS, took part in conception and design of study. NMS, SRP, AAAM, LVM were responsible for acquisition of data, while WMS, IJAS, and JFAN have done the analysis and interpretation of data. NNMQ, FTM, KMF, LSDS, SLG, NAM, PPFP, IJCL, JSF have drafted the manuscript together. All authors have revised the manuscript critically and approved the version to be published.

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Correspondence to João Soares Felício.

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de Souza, A.C.C.B., de Oliveira, M.C.N.I., de Lemos, G.N. et al. Health-related quality of life in T1DM patients after high-dose cholecalciferol supplementation: data from a pilot clinical trial. Diabetol Metab Syndr 14, 46 (2022). https://doi.org/10.1186/s13098-022-00817-w

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Keywords

  • Type 1 diabetes mellitus
  • Quality of life
  • Vitamin D
  • Albuminuria