journal club the effect of high-dose vitamin d supplementation on insulin resistance and arterial...
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Journal ClubThe effect of high-dose vitamin D supplementation on insulin resistance and arterial stiffness in patients with
type 2 diabetes
Prepared by: Amanda Bullock
OverviewVitamin D reviewLiterature reviewJournal article
◦Purpose◦Methods◦Results◦Conclusion
Discussion
Vitamin DHealth claims:
◦Promotes healthy bones by assisting with calcium absorption
◦Reduces risk of diabetes, heart disease, rheumatoid arthritis and multiple sclerosis
◦Regulates immune system
◦Prohibits cancer cell growth
Vitamin DRecommended blood
level: 30-74ng/mL
Food sources: ◦Fatty fish: tuna, mackerel, salmon◦Cheese◦Egg yolks◦Fortified foods: milk, soy milk,
orange juice
Vitamin DBest source: The SUN!
◦Dubbed the “sunshine vitamin”
◦Levels decrease during the winter months, especially if you are far from the equator
(von Hurst, 2010)
Literature ReviewVitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient - a randomised, placebo-controlled trial.
A randomized, controlled, double-blind study was performed on 100 non-diabetic insulin-resistant Asian females. Participants were given 4,000 IU of Vitamin D daily for 6 months..
(von Hurst, 2010)
Literature ReviewVitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient - a randomised, placebo-controlled trial.
When serum Vitamin D levels reached >32ng/mL, subjects showed significantly improved insulin resistance and sensitivity.
(Witham, 2013)
Literature ReviewCholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: the VitDISH randomized controlled trial
A parallel-group, double-blind, placebo-controlled randomized trial was conducted with 159 subjects >70 years old who had low levels of Vitamin D and isolated systolic hypertension. 1,000 IU of Vitamin D or a placebo was administered each day.
(Witham, 2013)
Literature ReviewCholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: the VitDISH randomized controlled trial
12 months later when the study concluded, no improvement was seen in blood pressure or other markers of vascular health.
Authors’ Review of Current Data
“Vitamin D deficiency is more prevalent and severe in patients with type 2 diabetes compared with the normal population. Epidemiological studies revealed that vitamin D deficiency accompanied by type 2 diabetes is associated with an increased risk of all-cause and cardiovascular mortality.”
(Ohk-Hyun, 2014)
PurposeMany claims have been made in
support of Vitamin D supplementation, especially in regards to diabetes and heart disease
This study aims to determine any impact on insulin resistance AND arterial stiffness secondary to Vitamin D supplementation in subjects with type 2 DM
HypothesisAuthors hypothesize that insulin
resistance may link arterial stiffness and Vitamin D deficiency in type 2 DM…
(Ohk-Hyun, 2014)
Subject Inclusion CriteriaDM2Vitamin D levels < 20ng/mLAmbulatory, aged 30-69 yearsHbA1c levels 6.5-8.4% Unchanged medications 3
months prior to studyNormal calcium levelsBMI > 23
(Ohk-Hyun, 2014)
Subject Exclusion CriteriaUse of osteoporosis-related
medications within 3 months before study
Use of insulin 1 month before studySystolic BP >160mmHg or diastolic
BP >100mmHgAcute MI/stroke within 6 monthsAbnormal liver function testAlcoholism
(Ohk-Hyun, 2014)
Methods: DesignProspective
Randomized
Double-blind
Placebo-controlled
(Ohk-Hyun, 2014)
Methods: DesignFor 24 weeks, participants
received either:
◦1,000 IU Vitamin D with 100mg calcium twice daily (n = 40)
--or--◦Placebo containing 100mg of
calcium twice daily (n = 41)
(Ohk-Hyun, 2014)
Methods: DesignParticipants were evaluated at:
◦Baseline
◦12 weeks +/- 2 weeks
◦24 weeks +/- 4 weeks
(Ohk-Hyun, 2014)
Methods: DesignAll participants received
education regarding Vitamin D rich foods
Participants were instructed to maintain the same lifestyle as before the study
(Ohk-Hyun, 2014)
Methods: DesignPhysicians not allowed to change
antihypertensive, antiplatelet or antilipid drugs during the study.
Only antidiabetic drugs allowed to be altered
(Ohk-Hyun, 2014)
Methods: Outcome MeasuresVitamin D
levelsFasting glucose Lipid profilesHbA1cInsulin
The homeostasis model of assessment-IR [HOMA-IR]
High-sensitivity C-reactive protein
(Ohk-Hyun, 2014)
Methods: Outcome MeasuresBrachial-ankle
pulse wave velocity
Radial augmentation index
Central systolic blood pressure
Safety of high-dose vitamin D supplementation◦Serum calcium◦Liver and kidney
function
(Ohk-Hyun, 2014)
Methods: Data CollectionBlood pressure was tested after a
10-minute resting period
Blood tests were drawn after an overnight fast from 7pm-9am
Arterial stiffness was measured while the subject was in a supine position for 10 minutes
(Ohk-Hyun, 2014)
(Ohk-Hyun, 2014)
Statistical AnalysisAt the conclusion of the study, subjects
were evaluated if they: ◦Took the supplements/placebo >80% of the
time◦Didn’t change medications
A value of p < 0.05 was considered to be significant
Two-tailed t-tests were used to compare the Vitamin D and placebo group
A chi-square test was also used for categorical variables
(Ohk-Hyun, 2014)
ResultsVitamin D levels (adequate = > 30
ng/mL):◦Placebo group: 10% (n = 3) ◦Vitamin D group: 68.8% (n = 22) ◦p < 0.001
No significant change in arterial stiffness or insulin resistance between the two groups◦(No significant change in any outcome
measure)(Ohk-Hyun, 2014)
ResultsVitamin D supplementation at
2000 IU daily is safe in regards to liver/kidney function and serum calcium
(Ohk-Hyun, 2014)
ConclusionsNo bias from the researchers was
evident
The conclusions are appropriate
EALThe evidence in this article
receives an overall Fair (II) grade
Elements Grade
Quality Good (I)
Consistency Fair (II)
Quantity Fair (II)
Clinical Impact Limited (III)
Generalizability Fair (II)
DiscussionPotential weaknesses of article:
◦All subjects on different medications
◦Low number or participants
◦Not a high amount of Vitamin D tested
DiscussionDiscrepancies in conclusions of
different articles
◦More research needs to be done
◦Consensus of a correlation between Vit D and metabolic syndrome
Discussion Questions
If there is a link between Vitamin D deficiency and metabolic
syndrome, should we fortify foods?
Discussion Questions
Have any of you been asked about Vitamin D by patients? If so, what
have they asked?
Discussion Questions
If a link was proven between DM2 or cardiovascular disease and Vitamin D deficiency, do you
think hospitals might incorporate supplements into clinical
practice?
References
1. Ohk-Hyun R, Wankyo C, Sungwha L, Kyung-Soon H, Moon-Gi C, Hyung J Y. The effect of high-dose vitamin D supplementation on insulin resistance and arterial stiffness in patients with type 2 diabetes. Korean J Intern Med. 2014; 29(5): 620– 629.
2. von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient: a randomised, placebo-controlled trial. Br J Nutr. 2010; 103: 549–555.
3. Witham MD, Price RJ, Struthers AD, et al. Cholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: the VitDISH randomized controlled trial. JAMA Intern Med. 2013; 173: 1672–1679.