The effect of high-dose vitamin D supplementation on insulin resistance and arterial stiffness in patients with type 2 diabetes

Abstract

Background/AimsRecent epidemiological studies revealed a striking inverse relationship between vitamin D levels, glucose intolerance/insulin resistance (IR), and cardiovascular disease. However, few interventional studies have evaluated the effect of vitamin D supplementation on cardiovascular risk, such as IR and arterial stiffness, in diabetes. We investigated the role of vitamin D supplementation on cardiovascular risk in type 2 diabetes patients, including metabolic parameters, IR, and arterial stiffness.MethodsWe enrolled patients who were taking antidiabetic medications or managed their diabetes using lifestyle changes. We excluded patients who were taking vitamin D or calcium supplements. We randomized participants into the vitamin D group (cholecalciferol 2,000 IU/day + calcium 200 mg/day, n = 40) or the placebo group (calcium 200 mg/day, n = 41). We compared their IR (homeostasis model of assessment [HOMA]-IR) and arterial stiffness (brachial-ankle pulse wave velocity and radial augmentation index) before and after 24 weeks of intervention.ResultsThe baseline characteristics of the two groups were similar. A total of 62 participants (placebo, 30; vitamin D, 32) completed the study protocol. At the end of the study period, the 25-hydroxyvitamin D [25(OH)D] levels were significantly higher in the vitamin D group than in the placebo group (35.4 ± 8.5 ng/mL vs. 18.4 ± 7.3 ng/mL, p < 0.001). There was no difference in HOMA-IR or changes in arterial stiffness (placebo, 21, vitamin D, 24) between the groups.ConclusionsOur data suggest that high-dose vitamin D supplementation might be effective in terms of elevating 25(OH)D levels. However, we identified no beneficial effects on cardiovascular risk in type 2 diabetes, including IR and arterial stiffness.

Effectiveness of Vitamin D Supplementation for Cardiovascular Health Outcomes

“…Central arterial stiffness is strongly associated with BP [9], and there is a need for interventions aimed at improving central arterial stiffness independent of BP changes. Virtually all RCTs investigating the effect of VitD supplementation on cfPWV reported no improvement [61,64,70,71,77,83,84,85] apart from 1 study in black youths [74]. The results from RCTs on AIx are more contradicting; no improvement was reported in the majority of studies [61,62,64,71,72,77,83].…”

“…In terms of effects on BP, some RCTs have reported significant improvements in brachial BP after short-term supplementation of VitD among participants encompassing a variety of clinical characteristics, including patients with hypercalcaemia [53] or impaired glucose tolerance [54], patients with primary hyperparathyroidism [55], patients with T2DM [56,57,58], patients with elevated BP and VitD deficiency [59] and women with VitD deficiency [60]. However, the majority of RCTs have been ineffective in improving brachial BP in a range of populations as shown in Table 1[61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79]. Indeed, a recent individual-level meta-analysis of RCTs concluded that VitD was ineffective in lowering BP [80].…”

“…Virtually all RCTs investigating the effect of VitD supplementation on cfPWV reported no improvement [61,64,70,71,77,83,84,85] apart from 1 study in black youths [74]. The results from RCTs on AIx are more contradicting; no improvement was reported in the majority of studies [61,62,64,71,72,77,83]. Alternatively, decreases in AIx were observed among patients with T2DM [66], overweight people with elevated BP [75], people with VitD deficiency [84] and those with pre-hypertension and VitD deficiency [85].…”

Impact of vitamin D supplementation on C-reactive protein; a systematic review and meta-analysis of randomized controlled trials

“…In two of the studies, particciopants were summplemned with ergocalciferol at a dose of 50,000 IU at baseline for 26 [30] or 12 [31] weeks. In three studies, calcium supplements had also been administered in doses of 200 [32], 1000 [33], 1200 [34] mg/d, respectively.…”

Effect of vitamin D supplementation on cardiovascular disease risk factors and exercise performance in healthy participants: a randomized placebo-controlled preliminary study

“…Moreover, the intervention period was insufficient as improvement in calcification may take longer than 3 months to the point where arterial compliance may improve and make structural or functional changes to the arteries [Witham et al 2012;Ryu et al 2014]. Therefore, longer trials investigating the potential of vitamin D in stimulating favourable alterations in cardiovascular function are warranted.…”