Vitamin D Deficiency


I didn't think I would be deficient in vitamin D due to my habit of exercising outdoors every day. I was wrong. Do not assume you are vitamin D sufficient; ask your doctor to check your vitamin D levels.

Summary

Links Between Vitamin D and Diabetes

The Details

About Vitamin D

Studies on Vitamin D and:


Summary

Links Between Vitamin D and Diabetes

There are many hundreds of studies on vitamin D in relation to diabetes. There is evidence from observational studies that having adequate vitamin D levels is protective against type 1 diabetes, and some evidence that vitamin D deficiency could contribute to the development of type 1 and perhaps type 2 diabetes. Further studies that include measurement of vitamin D levels in people before they develop diabetes, and intervention trials that involve ensuring adequate vitamin D levels could confirm these findings. Vitamin D deficiency is also linked to an increased risk of insulin resistance and gestational diabetes, and may affect diabetes management and the development of diabetes complications in all types of diabetes.

In the meantime, vitamin D supplementation offers a safe way to protect against vitamin D deficiency, and perhaps protect against diabetes as well. Vitamin D deficiency is likely to be more of a factor in diabetes development in areas with less UV radiation, but the findings of widespread deficiency in other areas implies that this factor may play a role elsewhere as well. One analysis calculates that if everyone in the UK took vitamin D supplements, 374 cases of type 1 diabetes (out of 1357 total predicted) could be prevented (Zipitis et al. 2016).

Pregnant women should also make sure they are sufficient in vitamin D. Vitamin D deficiency during pregnancy is linked not only to gestational diabetes but also preterm birth. Ensuring vitamin D sufficiency during pregnancy is safe, simple, and cost-effective (Genuis 2015).

Reviews of the evidence suggest that vitamin D may play a role in diabetes by influencing immune system function, inflammation, insulin secretion, and insulin resistance. Most (but not all) studies suggest that vitamin D is protective against diabetes, however, more evidence is needed from intervention studies to constitute conclusive proof (Al-Shoumer and Al-Essa, 2015Harinarayan 2014Papandreou and Hamid, 2015). 

According to a comprehensive review, "Data from epidemiological and association studies clearly indicate a correlation between vitamin D deficiency and a higher prevalence of both forms of diabetes. In animal models, vitamin D deficiency predisposes to type 1 and type 2 diabetes, whereas high doses of vitamin D ... prevent disease. Large scale, randomized, blinded prospective studies however, remain lacking...We propose, in particular, to avoid vitamin D deficiency in individuals at risk of developing T1D or T2D. Applying international guidelines on supplementation of vitamin D using small daily doses of vitamin D (500-1000 IU) may contribute to reduce the burden of diabetes by preventing vitamin D deficiency" (Mathieu 2015). Another review states, "Data from observational studies correlated vitamin D deficiency with risk of type 1 and type 2 diabetes... The results to date generally satisfy Hill's criteria for causality regarding vitamin D and incidence of these pancreatic diseases [diabetes and pancreatic cancer]. However, large randomized, blinded, prospective studies are required to more fully evaluate the potential therapeutic role of vitamin D in preventing pancreatic diseases" (Altieri et al. 2017).

As such, I have organized each section below based on the type of study. Trials, in which people are given vitamin D supplements and followed over time, provide the strongest evidence, especially randomized, controlled trials. Observational studies include those in which vitamin D levels are measured in people who develop or do not diabetes, or studies of population-level associations, are less strong. Reviews and meta-analyses combine evidence from multiple individual studies, and can include trials and/or observational studies. This page describes hundreds of studies, but not all the studies out there. These aim to be representative of the science in general, with enough detail for those interested.


The Details

About Vitamin D

Vitamin D is known as "the sunshine vitamin" because our skin produces it when exposed to sunlight. Dietary sources include fish and fish oil, eggs, and fortified foods, but sun exposure accounts for over 90% of body levels in most people. In people with limited sun exposure, dietary sources become more important (Norris 2001).

Vitamin D is technically a hormone, since it is a chemical signal produced by the body and transported through the blood to other parts of the body. Vitamins cannot be made by the body, and must be obtained in other ways. When exposed to UV radiation, substances in the skin are converted to pre-vitamin D3, which slowly becomes vitamin D3. (Vitamin D can also be obtained via diet).

Vitamin D may be protective against diabetes, and vitamin D deficiency may increase the risk of the disease. Below is some of the evidence, organized by timing of exposure, from the womb through adulthood, since the timing of exposure may make a difference in the risk of diabetes.

Type 1 Diabetes

Do a Mother's Vitamin D Levels During Pregnancy Affect the Later Risk of Type 1 Diabetes or Autoimmunity in her Children?

Trials

I do not know of any trials investigating this issue.

Observational Studies

Reviews and Meta-Analyses

Most say "no" or "we don't know:"
  • A meta-analysis of observational studies found no association between prenatal vitamin D levels and the offspring developing type 1 diabetes, although low vitamin D levels were associated with low birth weight and elevated weight at 9 months (Santamaria et al. 2018).
  • A meta-analysis of data from 11 different studies found that there is not enough evidence to determine whether or not there is an association between on maternal intake of vitamin D and risk of type 1 diabetes in the offspring (Dong et al. 2013).
Individual Observational Studies

Some observational studies say "yes:"
  • A Norwegian study found that cod liver oil taken during pregnancy was associated with a reduced risk of type 1 diabetes in offspring (this association may also be due to the omega-3 fatty acids present in this oil) (Stene et al. 2000).
  • A Norwegian study found that higher vitamin D levels at delivery and in umbilical cord blood were associated with a lower risk of type 1 diabetes in the offspring, with some influence by genetic risk (Tapia et al. 2019).
  • A Norwegian study that measured vitamin D levels in mothers during pregnancy, and their child's later risk of type 1 diabetes by age 15 found that the children of mothers with the lowest vitamin D levels had more than twice the risk of type 1 than those of mothers with the highest levels (Sørensen et al. 2012).
  • Another study by the same authors also found that children had a higher risk of developing type 1 diabetes if their mothers had lower levels of vitamin D-binding protein while pregnant, especially in the third trimester (Sørensen et al. 2016).
  • A Danish study found that exposure to sunshine during the 3rd trimester was associated with a lower risk of type 1 diabetes in boys at age 5-9 (Jacobsen et al. 2016a).
  • A U.S. study found that maternal dietary intake of vitamin D via food (but not supplements) during pregnancy was protective against the development of type 1 diabetes related antibodies in their children after 4 years (Fronczak et al. 2003).
Other observational studies say "not really:"
  • A Finnish study found that maternal intake of vitamin D via food or supplements during pregnancy was not associated with the development of type 1 diabetes or related autoimmunity in their offspring (Marjamäki et al. 2010). (Note that this study did not actually measure the mothers' levels of vitamin D, it only looked at food and supplement intake, which is not necessarily the same as actual vitamin D levels).
  • Another Finnish study found no difference between pregnant women's vitamin D levels during the first trimester and their children's later risk of type 1 diabetes (Miettinen et al. 2012). This study did test the mothers' actual levels of vitamin D. It found that 70% of all the mothers (those whose children developed type 1, and those whose children did not) were deficient or insufficient in vitamin D, quite a high level.
  • A third Finnish study found that it was the mother's vitamin D-related genes that were associated with the offspring's later risk of type 1 diabetes, instead of the vitamin D levels per se. It is possible that these genetic effects are only important if a mother is vitamin D deficient (Miettinen et al. 2015). A reanalysis found that some genes were more important than others (Miettinen et al. 2017).
  • Another Finnish study, which measured vitamin D levels in umbilical cord blood, found no association between vitamin D levels and type 1 diabetes development in the offspring (Mäkinen et al. 2019).
  • A Swedish study found that the mothers' use of vitamin D supplements during pregnancy was associated with a reduced risk of autoimmunity in the offspring at 1 year of age, but not by 2.5 years of age (Brekke and Ludvigsson, 2007).
  • Yet another Swedish study found that mothers' use of vitamin D supplements during pregnancy was not associated with the development of type 1 diabetes in the offspring (however, this study was based on questionnaire data, and did not include measurements of vitamin D levels in the mothers) (Granfors et al. 2016).
  • An Italian study found that newborn vitamin D levels were not associated with type 1 diabetes development up to age 10 in Italian children, although in a subset of immigrant children (who tended to have lower vitamin D levels), there was an association (Cadario et al. 2015).
  • Data from two large population-based studies from Denmark found that despite a high incidence of low vitamin D levels, vitamin D levels at the time of birth were not associated with the offspring's development of type 1 diabetes years later (Jacobsen et al. 2016b).
  • A large study using data from Denmark and Norway found that "normal variation" in maternal vitamin D levels were not associated with the offspring's development of type 1 diabetes (Thorsen et al. 2018). 
  • The international TEDDY study found no difference in offspring autoimmunity risk between those whose mothers took vitamin D during pregnancy and those that did not (Silvis et al. 2019).
So, in conclusion:

While the jury is still out, it wouldn't hurt to get vitamin D levels checked during (or before) becoming pregnant, to make sure to avoid deficiency during pregnancy.

Do Vitamin D Levels in Infancy and Early Childhood Affect the Later Risk of Type 1 Diabetes or Autoimmunity?

Trials

I do not know of any trials investigating this issue.

Observational Studies

Reviews and Meta-Analyses

A review and meta-analysis of the data from five different studies found that type 1 diabetes risk was significantly reduced in people who had been given supplements of vitamin D in infancy. Higher doses appeared more protective (Zipitis and Akobeng 2008). Another meta-analysis of the data from 11 different studies also found that higher vitamin D intake during early life may in fact decrease the risk of type 1 diabetes (Dong et al. 2013). Another makes the point that supplementation at current recommended levels (400 IU per day) shows no benefit for type 1 diabetes prevention, but that some evidence supports that vitamin D sufficiency in pregnancy, or supplementation in early life, does decrease risk (Miller et al. 2017).

Individual Observational Studies

Again, some say "yes:"
  • In a study spanning 30 years, Hyppönen et al. (2001) found that regular dietary supplementation of 2000 IU vitamin D per day in the first year of life was associated with an 80% reduced risk of type 1 diabetes in Finnish children.
  • In a Europe-wide study, the EURODIAB Substudy 2 Study Group (1999) found that vitamin D supplementation in infancy was associated with a reduced risk of type 1 diabetes.
  • A large international study found that higher childhood vitamin D levels were associated with a lower risk of type 1-related autoimmunity, especially in people with certain genes (Norris et al. 2018).
  • An Egyptian study found that vitamin D supplementation in the first year of life was associated with a lower risk of type 1 diabetes (Awadalla et al. 2017).
  • A long-term study of German children found that vitamin D levels were lower in children with multiple islet autoantibodies and in children with type 1 diabetes than in autoantibody-negative children. However, vitamin D deficiency was not associated with faster progression to type 1 diabetes in children with multiple islet autoantibodies (Raab et al. 2014). This finding suggests that low vitamin D levels may play more of a role in the development of autoimmunity than the subsequent development of type 1 diabetes.
While others say "no:"
  • U.S. researchers who followed type 1 development over time found that vitamin D intake and vitamin D levels during childhood were not associated with the development of either autoantibodies or type 1 diabetes in genetically at-risk children (Simpson et al. 2011).
  • A Finnish study found that vitamin D levels during childhood (age 3 months on) were not associated with the development of either autoantibodies or type 1 diabetes (Mäkinen et al. 2016).
  • A Swedish study found that the supplementation of vitamin D during infancy was not associated with the of autoimmunity at 1 or 2.5 years of age (Brekke and Ludvigsson 2007).
  • A study from Finland and Estonia found that there was no association between vitamin D levels and islet autoantibodies (Reinert-Hartwall et al. 2014).
In conclusion:

So while not all studies agree, most do find that vitamin D supplements in infancy and early childhood-- enough to bring someone up to adequate vitamin D levels-- may be protective against later type 1 diabetes.

Do Vitamin D Levels in Youth or Young Adulthood Affect the Later Risk of Type 1 Diabetes?

Trials

I do not know of any trials investigating this issue.

Observational Studies

Two longitudinal studies of U.S. military personnel have looked at this question, and say "yes:"
  • One found that those with lower vitamin D levels had a higher risk of later developing insulin-dependent diabetes than those with higher levels (Gorham et al. 2012).
  • Another found that for non-Hispanic whites, those with the highest vitamin D levels were less likely to later develop type 1 diabetes (there was no association in blacks or Hispanics) (Munger et al. 2013).
Observational studies of youth without diabetes do not always find a link between vitamin D levels and diabetes-related measures:
  • A study of black and white children without diabetes found that vitamin D levels did not affect insulin sensitivity, glucose levels, or beta cell function. However, this study did not examine children with diabetes, nor immune system markers (Rajakumar et al. 2012).

Can Adequate Vitamin D Levels Help Delay or Prevent the Onset of Type 1 Diabetes?

This question is being investigated by the D*Action Project to Prevent Type 1 Diabetes, currently open for enrollment. I do not know of any other published trials aside from the case studies below, but there may be other ongoing trials out there.

Individual Trials: Case studies
  • Two young women who developed type 1 diabetes (antibody positive) had "clinical remission" of their diabetes for 4 years (!) with treatment with vitamin D and sitagliptin (Januvia, a drug used for type 2 diabetes) (Although only one of the patients did not use ANY insulin) (Pinheiro et al. 2016).
  • A case study of one man who had developed type 1 diabetes (LADA) and was treated with vitamin D, sitagliptin, and metformin (a drug used for type 2 diabetes). He had very deficient vitamin D levels. After 8 weeks, his fasting blood sugar became normal and his HbA1c declined to normal levels as well, which has continued for 2 years. He never took insulin. His GAD autoantibody levels also declined to normal (Rapti et al. 2016).
  • An 8 year old child took high-dose vitamin D and omega-3 fatty acids, and shows near-normal blood sugar levels 1.5 years after diagnosis, only taking 1.5-2 units of insulin per day (Cadario et al. 2017); at least one other person also had a similar result (Cadario et al. 2018).
  • A case study of a newly diagnosed 14 year old found that high doses of vitamin D and omega 3 fatty acids (see the nutrition page) helped preserve beta cell function (Baidal et al. 2016).

Do People Newly Diagnosed with Type 1 Diabetes Have Lower Vitamin D Levels than Those Without Diabetes?

Many observational studies say "yes:"
  • A U.S. study found that vitamin D deficiency and insufficiency are common in children newly diagnosed with type 1 diabetes, especially those with ketoacidosis (Al-Zubeidi et al. 2016).
  • Children in Italy were found to have lower vitamin D levels at the time of type 1 diabetes diagnosis than children hospitalized for other diseases (Franchi et al. 2014).
  • Children in northern India were found to have lower vitamin D levels at the time of type 1 diagnosis than healthy controls; over 90% of children with type 1 diabetes were deficient in vitamin D (Daga et al. 2012).
  • Young adults in Sweden had lower vitamin D levels at the time of type 1 diagnosis than controls; 54% percent of those newly diagnosed had insufficient levels of vitamin D, especially men (Littorin et al. 2006).
  • Children and adolescents (both newly diagnosed and those with established type 1) in China had lower vitamin D levels than controls  (Liu et al. 2018).
Others say "no:"
  • A study from Florida found that vitamin D levels did not differ among people without diabetes and those newly diagnosed (Bierschenk et al. 2009).
  • A Danish study found no relationship between vitamin D levels and autoantibody levels in children newly diagnosed (Thorsen et al. 2018).

Do People with Type 1 Diabetes Have Low Vitamin D Levels?

Yes, a number of observational studies have found that people with type 1 diabetes are often deficient in vitamin D:

Reviews and Meta-Analyses
  • A meta-analysis of 23 studies found that both children and adults with type 1 diabetes have lower vitamin D levels than those without diabetes (Feng et al. 2015).
  • A meta-analysis of 10 studies of children found that those with type 1 diabetes have lower vitamin D levels than those without diabetes (Liu et al. 2015).
  • A meta-analysis of 12 studies found that children with type 1 diabetes have lower levels of vitamin D than those without diabetes, but that the association was not significant in people 14 and older (Shen et al. 2016).
Individual Observational Studies
  • A Swiss study has found that children and adolescents with type 1 diabetes had high levels of vitamin D deficiency (60% overall, rising to 84% in winter) (Janner et al. 2010).
  • A study of young adults with type 1 diabetes in Sweden found that vitamin D levels declined 8 years after diagnosis (Littorin et al. 2006).
  • U.S. residents with type 1 diabetes were more vitamin D deficient than healthy controls (Devaraj et al. 2011).
  • U.S. youth with type 1 diabetes had a high rate of vitamin D deficiency (49%) (The et al. 2013).
  • Floridians with type 1 diabetes have lower vitamin D-binding protein levels, a molecule important in the actions of vitamin D (Blanton et al. (2011).
  • Korean youth with type 1 diabetes have lower levels of vitamin D than those without diabetes (48% were deficient) (Bae et al. 2018).
Even in areas with abundant sunshine, people with type 1 diabetes (and often those without diabetes as well) have low vitamin D levels:
  • In Saudia Arabia, fully 100% of adults with type 1 diabetes tested were deficient in vitamin D, a higher percentage than those without diabetes (although deficiency levels were high in controls as well) (Al-Dahgri et al. 2014).
  • In Qatar, 91% of children with type 1 diabetes were vitamin D deficient, as were 85% of children without diabetes (Bener et al. 2009).
  • Fully 84% of Saudi Arabian children with type 1 diabetes were vitamin D deficient, as compared to 59% of children without diabetes (Bin-Abbas et a. 2011).
  • In Kuwait, 99% of children with type 1 diabetes were deficient or insufficient in vitamin D, compared to 92% of controls (Rasoul et al. 2016).
  • Middle Eastern children with type 1 had lower vitamin D levels than those without diabetes (Talaat et al. 2016).
  • An Australian study found lower vitamin D levels in children and adolescents with type 1 diabetes than controls without diabetes (Greer et al. 2013).
  • In an Israeli study, vitamin D levels were sufficient in less than 20% of youth with type 1 diabetes, especially in those who were religious and dressed more heavily (Brody et al. 2016).
  • While a study from Florida found that vitamin D levels did not differ among people without diabetes and those with established type 1 diabetes, all groups had low vitamin D levels, despite living in the "sunshine state" (Bierschenk et al. 2009).
Other factors may combine to increase risk as well. Overweight and obese children with both celiac disease and type 1 diabetes had lower vitamin D levels than controls (Setty-Shah et al. 2014). Genetic background also may affect the risk; people with certain vitamin D receptor (VDR) genes have an increased risk of type 1 diabetes (Penna-Martinez and Badenhoop 2017; Rasoul et al. 2019Sahin et al. 2017) as well as other autoimmune diseases (Gallone et al. 2017).

Can Adequate Vitamin D Levels Facilitate Blood Glucose Control and Reduce the Risk of Complications in People with Type 1 Diabetes?

Perhaps! 

Trials: Type 1 Diabetes Complications and Control

Reviews of Trials
  • A review of seven randomized controlled trials of vitamin D supplementation in people newly diagnosed with type 1 found that certain types of vitamin D supplements (alphacalcidole and cholecalciferol, but not calcitriol) had beneficial effects on beta cell function (Gregoriou et al. 2017).
Individual Trials: Beta Cell Function

Most trials of vitamin D supplementation and beta cell function in people with type 1 diabetes found positive results:
  • A randomized, controlled trial for people with type 1 diabetes in Germany found that those given 4000 IU vitamin D per day for 3 months had a lower insulin requirement, better blood sugar control (lower HbA1c), and in six people, even a rising c-peptide (a marker of beta cell function). Men also had better immune system function (Bogdanou et al. 2017).
  • One placebo-controlled, double-blind, randomized, 18-month long study from Brazil found that 2000 IU of daily vitamin D given to newly diagnosed people with type 1 diabetes was safe and appeared to have slowed the destruction of pancreatic beta cells (Gabbay et al. 2012).
  • A 6-month long intervention study of children newly diagnosed found that vitamin D supplementation may have helped stem the decline in beta cell function, but the results were not statistically significant (Mishra et al. 2016).
  • A study of children with type 1 from India found that vitamin D supplementation was associated with higher beta cell function than in children who did not receive supplements (Sharma et al. 2017).
  • In Iranian children with new-onset type 1 diabetes, sufficient levels of vitamin D helped preserve insulin secretion and beta cell function (Habibian et al. 2018).
  • In Polish children with new-onset type 1 diabetes, vitamin D supplementation helped preserve beta cell function (Panjiyar et al. 2018).
However, not all trials found positive results:
  • An umbilical cord infusion plus vitamin D and omega 3 fatty acids in newly diagnosed type 1 patients did not appear to preserve beta cell function (Haller et al. 2013).
  • An Italian trial found that vitamin D supplementation did not preserve beta cell function in people newly diagnosed with type 1 diabetes (Bizzarri et al. 2010).
Individual Trials: Blood Glucose Control/HbA1c

Most trials of vitamin D supplementation and blood glucose control in people with type 1 diabetes found positive results:
  • A controlled trial from Saudi Arabia found that people with type 1 diabetes and vitamin D deficiency who given 4000 IU of daily vitamin D had better blood sugar control if their vitamin D levels were higher after treatment than those whose levels did not rise as much. In other words, the higher the vitamin D level, the better the blood sugar control in type 1 diabetes (Aljabri et al. 2010).
  • A trial from Iran found that children with vitamin D deficiency and type 1 diabetes treated with vitamin D (high doses) had better blood glucose control (lower HbA1c) (Mohammadian et al. 2015).
  • Another trial from Iran found that youth with type 1 could reduce their HbA1c by taking vitamin D without changing their insulin dose (Ordooei et al. 2017).
  • A trial from Egypt found that 3 months of vitamin D supplementation improved HbA1c levels in children with type 1 diabetes (Hafez et al. 2017).
  • A U.K. trial found that treating children with vitamin D deficiency or insufficiency and type 1 diabetes improved their HbA1c (Giri et al. 2017).
  • A Brazilian trial found that both glycemic variability and insulin dose were lower when vitamin D levels were higher (Felício et al. 2018).
Again, not all trials found positive results:
  • A trial from the U.K. found that treating children with vitamin D deficiency and type 1 diabetes did not improve their HbA1c (Perchard et al. 2017).
  • A U.S. study found that adolescents with vitamin D deficiency and type 1 diabetes given supplements did not have better blood sugar control when supplemented (Shih et al. 2016).
  • A study of Massachusetts children with diabetes and vitamin D deficiency found that in those with type 1, vitamin D supplements did not improve HbA1c levels. (Interestingly, there was improvement for children with type 2 diabetes) (Nwosu and Maranda, 2014).
Individual Trials: Immune System Function and Inflammation

Most trials on vitamin D supplementation on the immune system in people with type 1 diabetes found positive results:
  • A randomized, double-blind, placebo-controlled study found that vitamin D supplementation in new-onset type 1 diabetes improved immune system function (Treiber et al. 2015).
  • A small study found that vitamin D reduced the reactivity of immune cells against beta cells in youth with type 1 (Federico et al. 2014).
  • A double-blind, placebo controlled trial found that adults given high doses of vitamin D for 3 months had enhanced levels of immune cells that are thought to be protective against autoimmunity (beta cell function was not affected) (Bock et al. 2011).
  • Canadian adolescents with type 1 and vitamin D deficiency were given vitamin D supplements, and their levels of inflammation decreased, and their vascular function increased (although blood pressure, cholesterol, and HbA1c were not affected) (Deda et al. 2018).
Individual Trials: Diabetes Complications

Most trials found positive results for kidney-related complications; I don't know of trials for other complications:
  • Danish adults with type 1 diabetes and kidney disease showed some improvement in kidney function markers when given vitamin D (Joergensen et al. 2015).
  • In Brazil, high dose vitamin D actually reduced the prevalence of kidney disease in a small study of people with type 1 (Felício et al. 2017).
  • Chinese people with type 1 diabetes and insufficient vitamin D levels given supplements had reduced inflammation and improved markers of kidney disease (Mao et al. 2014).
  • An Iranian trial found that vitamin D supplementation helped reduce markers of kidney damage in people with type 1 diabetes (Esfandiari et al. 2019).
Observational Studies: Type 1 Diabetes Complications and Control

Reviews of Observational Studies
  • A review found that vitamin D deficiency might be associated with more type 1 diabetes complications, although studies are sparse and not always consistent (Chakhtoura and Azar, 2013).
  • There is insufficient evidence to determine if vitamin D is linked to bone or skeletal complications in people with type 1 diabetes, according to a systematic review of the evidence (Gil-Díaz et al. 2019).
Individual Observational Studies: Blood Glucose Control and HbA1c

Most observational studies on beta cell function, blood glucose control, and HbA1c find that people with type 1 diabetes and higher vitamin D levels have better outcomes, although not all findings reached the level of statistical significance:
  • Egyptian adults with type 1 (and type 2) diabetes with low vitamin D levels had more beta cell dysfunction than those with higher levels (Omar et al. 2018).
  • Polish adolescents with type 1 diabetes and vitamin D deficiency had higher hemoglobin A1c levels than those with adequate levels of vitamin D (Wierzbicka et al. 2016).
  • Italian youth with type 1 diabetes had better HbA1c if they were not deficient in vitamin D (Savasito et al. 2016).
  • Middle Eastern children with type 1 and low vitamin D levels had higher autoantibody levels, HbA1c levels, and markers of inflammation (Talaat et al. 2016).
  • In Lebanon, vitamin D levels in people with type 1 diabetes were higher after the sunny season, and lower after the cloudy season. Hemoglobin A1c levels were lower after the sunny season and higher after the cloudy season, although the difference was not statistically significant (El Baba et al. 2011).
  • In U.S. youth with type 1 diabetes, those with low vitamin D levels had higher HbA1c levels, however, the relationship was not quite statistically significant (Al Sawah et al. 2016).
Individual Observational Studies: Inflammation
  • In U.S. people with type 1 diabetes, those with lower vitamin D levels had higher levels of inflammation (Devaraj et al. 2011).
Individual Observational Studies: Insulin Sensitivity/Insulin Resistance

Most observational studies find that low vitamin D levels are linked to higher insulin resistance and lower insulin sensitivity in people with type 1 diabetes:
  • Turkish children with type 1 diabetes who had low vitamin D levels used more insulin (and had higher insulin resistance) than those with higher vitamin D levels (Thnc et al. 2011).
  • Polish adults with type 1 diabetes have higher insulin resistance if they have lower vitamin D levels (Kamiński et al. 2019).
  • U.S. youth with type 1 diabetes and vitamin D deficient were more insulin resistant (The et al. 2013).
But not all studies find a link:
  • Mexican adults with adult-onset type 1 (LADA) had low vitamin D intake, but it was not associated with insulin resistance (however, in those with type 2 diabetes, it was) (Cardoso-Sánchez et al. 2015).
Individual Observational Studies: Kidney Disease

Most observational studies find that people with type 1 diabetes and low vitamin D levels have a higher risk of kidney disease or related markers:
  • The Diabetes Complications and Control Trial (DCCT), a long-term study from the U.S. and Canada, found that low vitamin D levels were associated with an increased risk of microalbuminuria (a sign of kidney disease) in people with type 1 diabetes (de Boer et al. 2012).
  • A prospective European study of people with type 1 diabetes found that low vitamin D levels were associated with a higher risk of macroalbuminuria (Engelen et al. 2015).
  • Brazilians with type 1 diabetes and low vitamin D had a higher risk of, and more severe, kidney disease (Felício et al. 2016).
But not all studies found associations between vitamin D levels and kidney disease markers:
  • A long-term Danish study found that severely deficient people with type 1 diabetes had a higher risk of all-cause mortality, but not kidney complications (Joergensen et al. 2011).
  • A U.S. study of children with type 1 did not find an association between low vitamin D and albuminuria, a sign of kidney disease (Nandi-Munshi et al. 2017).
Individual Observational Studies: Retinopathy

Some studies have found links between retinopathy and vitamin D levels in people with type 1 diabetes:
  • Vitamin D deficiency is associated with retinopathy in Japanese youth with type 1 diabetes (Shimo et al. 2014).
  • Vitamin D deficiency is associated with retinopathy in Australian youth with type 1 diabetes (Kaur et al. 2011).
But most have not:
  • The long-term study Danish study cited above also found that severely deficient people with type 1 diabetes did not have microvascular complications of the eye (Joergensen et al. 2011).
  • The prospective European study cited above also found that vitamin D levels were not associated with the risk of retinopathy (Engelen et al. 2015).
Individual Observational Studies: Neuropathy
  • In people from Turkey with type 1 diabetes, those with neuropathy had lower vitamin D levels (Ozuguz et al. 2016).
Individual Observational Studies: Cardiovascular Disease and Related Measures

Some studies have found links between vitamin D levels and cardiovascular-related outcomes in people with type 1 diabetes:
  • In Spanish children with type 1 diabetes, those with vitamin D deficiency had higher triglyceride levels than those who were vitamin D sufficient (Zambrana-Calví et al. 2016).
  • In Spanish people with type 1 diabetes, arterial stiffness was associated with lower vitamin D levels (Llauradó et al. 2015).
  • In Saudi Arabian children with type 1 diabetes, boys with vitamin D deficiency had a higher risk of hypoglycemia, high blood pressure, and high triglycerides (Al Shaikh and Al Zahrani 2015).
  • In Danish people with type 1 or type 2 diabetes, both high and low levels of vitamin D were associated with cardiovascular autonomic neuropathy (Hansen et al. 2017).
But many have not:
  • The DCCT study cited above also found that vitamin D levels were not associated with hypertension (de Boer et al. 2012).
  • The prospective European study cited above also found that vitamin D levels were not associated with cardiovascular disease (Engelen et al. 2015).
  • In Spanish adults with type 1 diabetes, there was no association between vitamin D levels and coronary artery disease (Serra-Planas et al. 2015).  
  • In Italian adults with type 1 diabetes, vitamin D levels were not linked to non-alcoholic fatty liver disease (NAFLD) (Cipponeri et al. 2019).

Vitamin D and the Immune System

Vitamin D can affect the function of the immune system, and in this capacity may be protective against autoimmune diseases (Norris 2001). Vitamin D deficiency is also associated with an increased risk for other autoimmune diseases, including multiple sclerosis and inflammatory bowel disease (Lapillonne 2010). A prospective, population-wide study from Denmark found an increased risk of autoimmune diseases in people with lower vitamin D levels (Skaaby et al. 2015). Baeke et al. (2010) review how vitamin D affects the immune system, and its role in the development of autoimmune diseases. Rak and Bronkowska (2019) review the effect of vitamin D on the immune system, and its role in type 1 diabetes prevention and treatment.

Interestingly, vitamin D may interact with other environmental factors linked to diabetes, such as viruses (Federico et al. 2018).

Laboratory Studies: Type 1 Diabetes

In non-obese diabetic (NOD) mice, early, long-term, high doses of vitamin D can prevent diabetes (Takiishi et al. 2014). Vitamin D delays the onset of diabetes via immune system modulation; vitamin D deficiency also can impair insulin secretion from beta cells (Mathieu et al. 2005).

In a different animal model of type 1 diabetes (mice given the chemical STZ to kill beta cells), vitamin D improved diabetic kidney disease (Deng et al. 2016). In laboratory mice with chemically induced type 1 diabetes, vitamin D reduced the incidence of diabetes, enhanced insulin secretion, and reduced pancreatic inflammation. Vitamin D also decreased beta cell death (Wang et al. 2016). 

Rats with chemically induced beta cell destruction showed better cognitive function when given vitamin D (Calgaroto et al. 2014). They also showed better lipid levels, which may help prevent cardiovascular complications (Calgaroto et al. 2015). These rats given vitamin D also had lower inflammation, less liver damage, and lower insulin resistance (Liu et al. 2016). 

In rats, animals who received both vitamin D and omega 3 fatty acids had lower blood sugar levels than untreated rats after islet transplantation (Gurol et al. 2016).

Cell Culture Studies

Beta cells exposed to vitamin D show both increased and decreased insulin secretion, depending on the amount of glucose they were exposed to, and how long they were exposed to vitamin D (Jeddi et al. 2015). Whether or not beta cells secrete insulin also depends on the type of vitamin D used (Bornstedt et al. 2019).

Exposure During Development

Low vitamin D levels in mother mice led to offspring with modified pancreas development, leading to changes in beta cell mass and insulin secretion in adulthood (Maia-Ceciliano et al. 2016).

Geographic and Historical Patterns

One reason vitamin D was suspected of being protective against type 1 diabetes is that countries with high incidence of type 1 tend to be found near the polar regions (e.g., Finland, Sweden), where there is a lack of sunlight during long stretches of the year (see the incidence page). In northern Finland, there are only 2 hours of sun each day during December. In a study of 51 regions around the world, Mohr et al. (2008) found that lower levels of ultraviolet (UV) radiation (the main source of vitamin D in humans) was associated with higher incidence of type 1 diabetes.
 
Yet differences in vitamin D status do not explain all of the differences in type 1 diabetes incidence. For example, type 1 diabetes rates are six times higher than those in a neighboring section of Russia, despite similar genetic background (and similar latitudes). Vitamin D levels have been found to be essentially the same in both regions, in children and in pregnant women. More people in Russia, in fact, were deficient in vitamin D than in Finland. A number of Scandinavian researchers point out that vitamin D supplementation has long been common in these countries (Viskari et al. 2006). And yet vitamin D deficiency is still common in these countries, perhaps because the recommended supplementation dose has decreased over time.

Using historical data, Mohr et al. (2010) showed that in Finland, the incidence of type 1 diabetes rose gradually after the recommended daily dose of vitamin D was reduced from 4500 IU to 2000 IU, in 1964. In 1992, the recommended daily dose was lowered again, to 400 IU. This change was followed by a steep rise in type 1 diabetes incidence. And then, in 2003, vitamin D intake increased again, and by 2006 the incidence of type 1 diabetes had plateaued (Mäkinen et al. 2014). Is this an interesting coincidence or a causal correlation? That remains to be seen.

People who develop type 1 diabetes tend to be born in certain seasons. A Danish study found that the association between type 1 and season of birth in males disappeared during the years that margarine was fortified with vitamin D. This finding implies that in utero exposure to vitamin D may reduce the seasonality of diabetes diagnosis in males (Jacobsen et al. 2016c). However, the same authors also found that supplementing margarine with vitamin D in that country did not affect the overall risk of type 1 diabetes in children (Jacobsen et al. 2015).

Type 2 Diabetes and Insulin Resistance

Vitamin D deficiency may also contribute to the development of type 2 diabetes (Palomer et al. 2008) by contributing to both insulin resistance and beta cell death (Berridge 2017). A review of the mechanisms connecting vitamin D and insulin resistance shows that a variety of mechanisms may be involved, including inflammation, oxidative stress, and epigenetics (Szymczak-Pajor and Śliwińska, 2019).

Can Adequate Vitamin D Levels Help Delay or Prevent the Onset of Type 2 Diabetes?

Reviews

A review and meta-analysis of 19 studies found that people with the highest vitamin D levels had the lowest risk of type 2 diabetes (Mitri et al. 2011). A more recent meta-analysis of 21 long-term prospective studies found a clear, statistically significant association between vitamin D levels and type 2 diabetes. Those with higher vitamin D levels had lower risk, across a broad range of vitamin D levels in diverse populations (Song et al. 2013). Another meta-analysis of 11 studies found that people with type 2 diabetes had lower vitamin D levels than those without diabetes (Shen et al. 2016).

Most studies of vitamin D in obese adolescents have found associations between low vitamin D levels and insulin resistance, and clinical trials have reported beneficial effects (Peterson et al. 2014). 

A review of vitamin D in type 2 diabetes and obesity concludes, "Although the evidences of a significant role of Vitamin D on inflammation, insulin resistance and insulin secretion in the pathogenesis of obesity, metabolic syndrome and type 2 diabetes, its potential function in treatment and prevention of type 2 diabetes mellitus is unclear. Encouraging results have emerged from Vitamin D supplementation trials on patients at risk of developing diabetes and further studies are needed to fully explore and understand its clinical applications." (Garbossa and Folli 2017).

A review of 39 studies on vitamin D and type 2 diabetes/insulin resistance concludes that "it is not possible to state that vitamin D supplementation has any effect on type 2 diabetes incidence or on insulin resistance" (Wallace et al. 2016). Yet these and other authors also point out that more randomized controlled trials of vitamin D supplementation should help to clarify the issue (Muñoz-Garach et al. 2019).

A review of vitamin D in type 2 diabetes found that vitamin D promotes pancreatic islet function and survival, as well as modulates liver glucose and metabolism, and is potentially protective against diabetes (Leung 2016).

Trials

Reviews of Trials

A review of four randomized controlled trials found that vitamin D supplementation had no effect on type 2 diabetes prevention (Seida et al. 2014). 

Individual Trials

Many trials have found that vitamin D supplementation has beneficial effects on people with pre-diabetes or before type 2 diabetes onset:
  • A trial of middle aged adults found that vitamin D and calcium supplementation reduced insulin resistance in people with pre-diabetes (Gagnon et al. 2014). 
  • A 12 week trial of vitamin D supplementation in overweight/obese African Americans with pre-diabetes or early diabetes found that compared to a placebo, vitamin D improved insulin secretion and insulin resistance, but not glucose levels (Harris et al. 2012). 
  • A trial of men deficient or insufficient in vitamin D without diabetes found that after a year of supplements, those on the placebo had increased levels of insulin resistance and insulin, but those who took vitamin D stayed the same. So, in other words, the vitamin D did help stop increasing insulin resistance (Tepper et al. 2016).
  • A trial of healthy Japanese adults found that one year of vitamin D supplementation improved fasting glucose levels and lowered insulin resistance (Sun et al. 2016).
  • A trial that provided obese adolescents with vitamin D supplements found that compared to those who took a placebo, those who took 4000 IU vitamin D per day had lower insulin resistance after 6 months (Belenchia et al. 2013). 
While many other trials found no beneficial effects:
  • A large U.S. trial, using 4000 IU/day over 2.5 years, found that supplementation had no effect on the development of type 2 diabetes in people at high risk (Pittas et al. 2019).
  • A trial of higher doses given to people with pre-diabetes for a year found that glucose, insulin secretion, insulin resistance, blood pressure, and lipid (cholesterol) levels did not improve in those given vitamin D compared to a placebo (note that vitamin D levels were higher to start with in this study though) (Sollid et al. 2014). 
  • A trial found that high dose vitamin D supplementation did not prevent the development of type 2 diabetes in people with pre-diabetes, over a 5 year time period. Again, however, the people in this trial started with normal average vitamin D levels, not deficient levels (Jorde et al. 2016). 
  • A trial found that high-dose vitamin D supplementation over 8 weeks did not affect insulin secretion, insulin resistance, or glucose levels in people who started at a lower vitamin D level (Wagner et al. 2016). 
  • A Canadian trial found that 24 weeks of high dose vitamin D supplementation did not affect glucose tolerance, insulin resistance, or other diabetes-related measures (Moreira-Lucas et al. 2017).
  • A trial of healthy children found no effects on glucose, insulin, or insulin resistance after 12 weeks of supplementation (Ferira et al. 2016). 
  • Another trial of obese adolescents found no effect on insulin resistance either (Grunwald et al. 2017).
Observational Studies

Most observational studies have found associations between low vitamin D levels and insulin resistance in people without diabetes.
  • In the U.K., low vitamin D levels were associated with the later development of increased insulin resistance and high blood sugar in people without diabetes (Forouhi et al. 2008).
  • In U.S. sedentary, obese or overweight, black and white post-menopausal women without diabetes, low vitamin D levels were associated with higher fasting glucose levels, insulin resistance, abdominal fat, and triglyceride levels (Sorkin et al. 2014). These authors found that there is a certain level of vitamin D in the blood below which these effects occur (about 26 μg/L); vitamin D levels above this amount were associated with normal blood sugar control.
  • In U.S. Hispanics and African Americans without diabetes, low vitamin D levels were associated with higher insulin resistance (Lee et al. 2017).
  • A study of a sample of the general U.S. population found that abdominal obesity and vitamin D insufficiency interact to increase the risk of insulin resistance (Kabadi et al. 2012). 
  • In Greek children, vitamin D insufficiency was associated with insulin resistance, independent of obesity (Moschonis et al. 2018). 
  • The association between vitamin D and insulin resistance also appears to depend on genetic background (Rahmadhani et al. 2017).

Can Adequate Vitamin D Levels Facilitate Blood Glucose Control and Reduce the Risk of Complications in People with Type 2 Diabetes?

Trials

Reviews of Trials: Blood Glucose Control, Inflammation, Insulin Resistance

Most reviews of trials found beneficial effects of vitamin D supplementation in people with type 2 diabetes: 
  • Numerous meta-analyses found that vitamin D supplementation was associated with lower levels of inflammation in people with type 2 diabetes (Mansournia et al. 2018; Mousa et al. 2018Yu et al. 2018).
  • A review and meta-analysis of 24 trials found that vitamin D supplementation did have an effect-- it was associated with lower HbA1c (long-term blood glucose) levels, lower insulin resistance, and lower fasting blood glucose levels in people with type 2 diabetes (Mirhosseini et al. 2017).
  • A systematic review found that in people with type 2 diabetes, vitamin D supplementation did not improve blood glucose control (but these were small studies). In people with glucose intolerance, however, vitamin D supplementation improved insulin resistance (Mitri et al. 2011).
  • A meta-analysis of 37 studies found that vitamin D supplementation improved blood glucose control in people with type 2 diabetes (Sahebi et al. 2019).
  • A literature review and meta-analysis found that vitamin D supplementation only led to small improvements in fasting blood sugar and insulin resistance in people with diabetes or impaired glucose tolerance (George et al. 2012). 
  • A literature review found that vitamin D supplementation improved glycemic measures and reduced insulin resistance, although the effects varied by age, calcium supplements, duration of supplementation, and vitamin D levels before and after (Mirhosseini et al. 2018). 
  • A review found (not surprisingly) that the beneficial effects of vitamin D supplementation are mainly found in people deficient in vitamin D (Lips et al. 2017).
Although not all reviews of trials found beneficial effects:
  • A review of 35 randomized controlled trials found that vitamin D supplementation had no effect on insulin resistance, insulin secretion, or blood glucose control (HbA1c) (although there were no adverse effects either) (Seida et al. 2014).
Reviews of Trials: Diabetes Complications
  • A review of randomized controlled trials of people with kidney disease and diabetes found that vitamin D supplementation is safe and effective (Zhao et al. 2014).
  • A meta-analysis of studies of vitamin D supplementation in people with diabetic nephropathy found beneficial effects in some markers but not all (Wang et al. 2019).
Individual Trials: Blood Glucose Control, Insulin Resistance

Many individual trials found beneficial effects of vitamin D supplementation on insulin resistance or blood glucose control:
  • A double-blind, randomized clinical trial from Saudi Arabia found that vitamin D supplementation for 12 weeks did not improve blood glucose control (HbA1c levels), but did improve beta cell activity in people with type 2 diabetes (Al-Sofiani et al. 2015).
  • Vitamin D transiently improved fasting glucose levels in people with newly-diagnosed Australians with type 2 diabetes, but did not show any effect after 6 months (Elkassaby et al. 2014).
  • Supplementation with both vitamin D and calcium (but neither alone) improved blood sugar control (HbA1c levels) and beta cell function, and lowered insulin levels as well as insulin resistance in adults with type 2 diabetes who were vitamin D insufficient (Tabesh et al. 2014).
  • In people with type 2 diabetes, daily consumption of a yogurt drink enriched with vitamin D improved blood glucose control (Nikyooeh et al. 2011) and glycemic markers (Jafari et al. 2016).
  • A study of Massachusetts children with diabetes and vitamin D deficiency found that in those with type 2, vitamin D supplements was associated with lower HbA1c levels and lower BMI as well. (Interestingly, there was no improvement for those children with type 1 diabetes) (Nwosu and Maranda, 2014).
  • A trial from Iran found that 6 months of vitamin D supplementation in people with type 2 diabetes and coronary artery disease resulted in lower insulin resistance, lower blood glucose levels, and lower insulin levels (Farrokhian et al. 2017).
  • Another Iranian trial found that vitamin D supplementation improved blood glucose levels (HbA1c) in people with type 2 diabetes (Safarpour et al. 2018).
  • A trial from Saudi Arabia found that people with diabetes lowered their HbA1c after supplementing with vitamin D (Buhary et al. 2017).
  • In people with type 2 diabetes who also had insufficient vitamin D levels, calcium and vitamin D supplements (either together or alone) lowered inflammation levels (Tabesh et al. 2014).
Although some did not:
  • A randomized, double-blind placebo-controlled trial in the Netherlands found that people with well-controlled type 2 diabetes who received intermittent high-dose vitamin D supplementation did not show any improvement in blood sugar control or insulin resistance. Even those with low vitamin D levels or higher HbA1c levels (over 7%) did not show improvement (Krul-Poel et al. 2015).
  • A trial from Norway found that a high dose of vitamin D did not improve insulin resistance or insulin secretion in people with type 2 diabetes (Gulseth et al. 2017).
Individual Trials: Diabetes Complications

Many individual trials found beneficial effects of vitamin D supplementation on diabetes complications and metabolic outcomes:
  • Vitamin D supplementation improved painful neuropathy in people with type 2 diabetes (Alam et al. 2017).
  • Supplementing with vitamin D helped wound healing in people with a diabetic foot ulcer (including better blood glucose and cholesterol levels (Razzaghi et al. 2017). 
  • High-dose intramuscular vitamin D treatment led to lower pain levels in people with diabetes and neuropathy (Basit et al. 2016).
  • A study of kidney dialysis patients with type 2 diabetes found that after vitamin D supplementation, the patients had better fasting blood sugars, lower HbA1c, better beta cell function-- but interestingly, also more insulin resistance (Ibrahim et al. 2015).
  • 12 weeks of vitamin D, K, and calcium supplementation improved insulin resistance and cholesterol levels in people with type 2 diabetes and coronary heart disease (Asemi et al. 2016).
  • High level vitamin D supplementation improved vascular function in people with type 2 diabetes who were deficient in vitamin D (Anandabaskar et al. 2017).
  • 8 weeks of vitamin D supplementation helped Brazilians with type 2 diabetes improve cholesterol levels, insulin and glucose levels, and more (Fagundes et al. 2019). 
  • Vitamin D supplementation improved cholesterol levels in people with diabetes and nephropathy with low vitamin D levels (Barzegari et al. 2019).
  • Women with type 2 diabetes given vitamin D supplements showed improved triglyceride levels (Muñoz-Aguirre et al. 2015).
Although some did not:
  • 24 weeks of vitamin D supplementation had no effect on non-alcoholic fatty liver disease (NAFLD) in people with type 2 diabetes (Barchetta et al. 2016).
Observational Studies: Diabetes Control and Complications

Reviews of Observational Studies: Diabetes Control and Complications

Most reviews of observational studies on type 2 diabetes control and complications found that low vitamin D levels were associated with worse health parameters:
  • A meta-analysis of three studies found that vitamin D deficiency was associated with a higher risk of peripheral neuropathy in people with type 2 diabetes (Lv et al. 2015).
  • A review found that, "An increasing body of literature suggests a possible pathogenetic role of vitamin D in the long-term complications of diabetes and vitamin D deficiency may also exacerbate symptoms of painful diabetic peripheral neuropathy. It remains unknown if supplementation of vitamin D to normal or non-deficient levels alters pathogenetic processes related to diabetic microvascular complications." (Alam et al. 2016).
  • A meta-analysis of 14 studies found that vitamin D deficiency was associated with a higher risk of diabetic retinopathy in people with diabetes (Zhang et al. 2017).
  • A review suggests that vitamin D is protective against diabetic kidney disease via multiple mechanisms (Guan et al. 2014). 
  • A review found that vitamin D shows improvement of kidney function in people with type 2 diabetes and kidney disease (Chokhandre et al. 2015).
  • A systematic review and meta-analysis of 7 studies found that severe vitamin D deficiency was associated with an increased risk of foot ulcers in people with diabetes (Dai et al. 2019).
  • A review of cardiovascular disease and vitamin D found that numerous studies have found links between low vitamin D levels and cardiovascular disease. However, as with diabetes, vitamin D's role has not been definitively established, due to the lack of large, randomized controlled trials. The authors argue that despite the lack of large trials, there is adequate evidence to promote treatment of low vitamin D levels (Mandarino et al. 2015).
Individual Observational Studies

Most observational studies on type 2 diabetes control and complications found that low vitamin D levels were associated with worse health parameters:
  • A study of U.S. adults found that people with lower levels of vitamin D had higher HbA1c levels, including people who did not have diabetes (Kositsawat et al. 2010).
  • Newly diagnosed women with type 2 diabetes and higher vitamin D levels had better insulin sensitivity and better beta cell function than those with lower vitamin D levels; there was no difference in men (Gao et al. 2015).
  • A study from Iran found higher fasting blood glucose levels in non-obese people with type 2 diabetes and low vitamin D levels. Most participants had very low vitamin D levels (Haidari et al. 2016).
  • A study from Egypt found people with type 2 diabetes and low vitamin D levels had a higher HbA1c (Saif-Elnasr et al. 2017).
  • A Malaysian study found that lower vitamin D levels were associated with higher HbA1c levels in people with type 2 diabetes and chronic kidney disease (Lim et al. 2018). 
  • Vitamin D deficiency was associated with neuropathy, retinopathy, and nephropathy in a study of Indian adults with type 2 diabetes (Bajaj et al. 2014), 
  • Vitamin D deficiency was associated with nephropathy in Turkish adults with type 2 diabetes, as well as with more severe microvascular complications (Usluogullari et al. 2015).
  • Europeans with painful neuropathy had lower vitamin D levels than controls (Shillo et al. 2018).
  • U.S. adolescents with type 2 diabetes and low vitamin D levels had higher arterial stiffness (a risk factor for cardiovascular disease) -- but not those without diabetes (Jha et al. 2015).
  • People with diabetes who had an infected foot were more likely to be vitamin D deficient, and have higher levels of inflammation (Tiwari et al. 2014).
  • People with type 2 diabetes and periodontal disease had low levels of vitamin D (Joseph et al. 2015).
  • People with kidney disease plus diabetes are more likely to be deficient in vitamin D than those without diabetes, and at higher risk of mortality than people with kidney disease and diabetes who are sufficient in vitamin D (Schiller et al. 2015).
  • The severity of albuminuria (a sign of kidney disease) in people with type 2 diabetes was associated with lower vitamin D receptor expression (Yi et al. 2016). 
  • Men with type 2 diabetes and low vitamin D levels had a higher risk of mortality in a study from Sweden (but not women with type 2) (Jennersjö et al. 2015).
  • Genetic risk might also play a role in these associations. People with diabetes who had certain vitamin D-related genes were more susceptible to nephropathy than those without those genes (Liu et al. 2014).
Although not all:

Obesity

Obesity is sometimes associated with vitamin D deficiency, probably because vitamin D can be deposited in fat stores and then not be available to the body (Holick 2004). For example, obese children and adolescents have high rates of vitamin D deficiency (Zakharova et al. 2019). A study of obese people found that those who were metabolically healthy had higher vitamin D levels than those who were metabolically unhealthy (Estghamati et al. 2014).

Laboratory Studies: Type 2 Diabetes and Obesity

Vitamin D reduces insulin resistance in rats with type 2 diabetes (Amin et al. 2018).

Long-term ultra-violet radiation (which produces vitamin D in the skin) suppresses weight gain, glucose intolerance, and insulin resistance in mice fed a high-fat diet. However, many of these benefits did not appear with vitamin D supplementation-- perhaps other mechanisms are at work (Geldenhuys et al. 2014).

Exposure During Development

Prenatal vitamin D levels influenced the development of long-term fatty tissue damage in mice (Belenchia et al. 2017).

Gestational Diabetes and Vitamin D in Pregnant Women

Can Vitamin D Sufficiency Help Prevent Gestational Diabetes?

Trials

Reviews
  • A systematic review of data from 87 studies and 25 trials found that low vitamin D levels were associated with an increased risk of gestational diabetes (Zhang et al. 2018).
  • A review and meta-analysis of 13 randomized, controlled trials found that there was no association between vitamin D supplementation and gestational diabetes (there were other benefits however). As these studies were small and varied a lot in their design, this will not be the last word on the topic (Pérez-López et al. 2015).
Individual Trials
  • Taking vitamin D before pregnancy has been linked to a lower risk of developing gestational diabetes (Bao et al. 2018).
  •  In a study from India, pregnant women given vitamin D supplements had a lower risk of gestational diabetes (as well as other benefits) than those who took a placebo (Sablok et al. 2015). 
  • In Asian women with prior gestational diabetes, a double-blind randomized controlled trial showed that six months of supplementation with 4000 IU vitamin D safely restored vitamin D levels, improved beta cell function, and reduced blood glucose levels (HbA1c) (Yeow et al. 2015). 
  • Results may also depend on the type of supplementation. A randomized trial of Iranian women with low vitamin D levels found that those who received 50,000 IU vitamin D every two weeks had a lower incidence of gestational diabetes than those given 400 IU per day (Mojibian et al. 2015). 
  • Another Iranian trial of the high dose levels also found that women at risk of gestational diabetes who took vitamin D for the 1st and 2nd trimesters had a lower incidence of gestational diabetes (as compared to those who took a placebo) (Shahgheibi et al. 2016). 
  • Another, however, found no statistically significant difference (Tehrani et al. 2017).
  •  In obese pregnant European women without diabetes, supplementation with 1600 IU vitamin D3/day achieved vitamin D sufficiency in virtually all pregnant women and a small effect in fasting glucose levels at 35-37 weeks, but mostly had no effect (Corcoy et al. 2019).
Observational Studies

Reviews of Observational Studies
  • A meta-analysis that consolidated the data from seven different studies found that gestational diabetes was associated with vitamin D deficiency in pregnant women (Poel et al. 2012). 
  • A literature review also concluded that vitamin D deficiency and insufficiency is common in pregnant women, and is associated with gestational diabetes and poor glucose control (Senti et al. 2012). 
  • More recent meta-analyses of 20 studies found that vitamin D deficiency was associated with the development of gestational diabetes (although whether vitamin D can prevent gestational diabetes is still not known) (Lu et al. 2016; Zhang et al. 2015). 
  • A meta-analysis of 29 studies found vitamin D insufficiency is associated with gestational diabetes (Hu et al. 2018). 
  • A systematic review and meta-analysis of 26 studies, found that vitamin D deficiency may increase the risk of gestational diabetes (Amraei et al. 2018).
Individual Observational Studies

While most individual observational studies have found a link between vitamin D deficiency and gestational diabetes (e.g., Al-Ajlan et al. 2018Arnold et al. 2015; Ede et al. 2019Haidari et al. 2016; Wen et al. 2017; Xia et al. 2019Xu et al. 2018), not all have (e.g., Gustafsson et al. 2018Lee et al. 2017; Makgoba et al. 2011). Some have found an association between low vitamin D levels and higher fasting blood glucose, but not gestational diabetes (Al-Shaikh et al. 2016; Sahin et al. 2019). Others find general diabetes-related benefits of higher vitamin D levels during pregnancy (Benaim et al. 2019). 

Other factors may also play a role, for example, one study has found that the risk of gestational diabetes is higher in women who have low vitamin D levels and who also smoke during pregnancy (Dodds et al. 2016). Another found that genetic variations affect the relationship between vitamin D levels and gestational diabetes (Shi et al. 2016). Obesity also increases the level of risk between vitamin D levels and gestational diabetes (Valkama et al. 2018). In obese women, low vitamin D levels are associated with higher cardiovascular risks during pregnancy and worse pregnancy outcomes (Mousa et al. 2017). 

Do Vitamin D Levels Affect Blood Glucose Control in Women With Gestational Diabetes?

Trials

Reviews of Trials
  • A review and meta-analysis of trials of vitamin D supplementation in women with gestational diabetes found benefits for both mothers and infants (Jahanjoo et al. 2018).
Individual Trials
  • In an Iranian trial, women with gestational diabetes who took vitamin D and evening primrose oil for 6 weeks had better glucose and lipid levels, and lower insulin resistance (Jamilian et al. 2016). 
  • Another Iranian study found that magnesium-zinc-calcium-vitamin D co-supplementation for 6 weeks had beneficial effects on blood glucose control and a few markers of cardio-metabolic risk in women with gestational diabetes (Karamali et al. 2018). 
  • Another found that combining vitamin D and probiotics also had beneficial effects in women with gestational diabetes (Jamilian et al. 2018). 
  • In a Chinese study, women with gestational diabetes who drank a yogurt drink enriched with vitamin D had lowered insulin resistance (Li and Xing 2016).
  • A randomized, placebo-controlled trial from Iran found that women with gestational diabetes who were given vitamin D and calcium supplements had lower fasting glucose levels, lower insulin levels, lower insulin resistance, and better cholesterol levels than those given a placebo (Asemi et al. 2014).
  • Other Iranian studies found the same results with a combination of vitamin D and omega 3 fatty acids (Jamilian et al. 2017), and that this combination lowered inflammation and oxidative stress, and improved pregnancy outcomes (Razavi et al. 2017). 
  • Another study also found improved fasting glucose levels and long-term glucose levels in women with gestational diabetes (Yazdchi et al. 2016). 
  • Additional studies found that vitamin D supplements for women with gestational diabetes improved outcomes for both mother and child (Asemi et al. 2015Karamali et al. 2016), and improved insulin resistance in these women (Zhang et al. 2016).
  • An Iranian intervention trial of women with gestational diabetes found that while high dose supplementation with vitamin D raised vitamin D levels, it did not affect glucose levels in the short-term post-pregnancy (Valizadeh et al. 2016).
Individual Observational Studies

Among women with gestational diabetes, those with lower vitamin D levels had worse blood glucose control (El Lithy et al. 2014). A study of pregnant Australian women found that even in women with normal blood sugar and vitamin D levels, those with lower vitamin D levels had higher fasting blood sugar and lower beta cell function (but insulin resistance was not different) (McLeod et al. 2012). Having adequate vitamin D levels in early pregnancy is associated with lower blood glucose levels throughout the entire pregnancy (Walsh et al. 2018). 

A Czech study found that vitamin D levels tended to be lower post-partum in women who had had gestational diabetes (although levels during pregnancy did not differ in those with/without gestational diabetes) (Pleskačová et al. 2015).

Vitamin D levels, however, may not affect the later risk of developing diabetes following gestational diabetes. At least that is the finding of one study from Sweden. While low vitamin D levels were associated with beta cell dysfunction and insulin resistance in women with gestational diabetes, these levels were not associated with the later development of diabetes (Shaat et al. 2017). A study from Hungary found that higher vitamin D levels were associated with lower insulin resistance 3 years after pregnancy (although not with gestational diabetes (Tänczer et al. 2017).

Pregnant Women with Type 1 Diabetes

Among pregnant women with type 1 diabetes, a UK study found that cord blood vitamin D levels correlate with those of the mothers, and that they tend to be low throughout pregnancy, delivery, and post-delivery. Women with low vitamin D levels had worse blood sugar control (higher HbA1c levels) (Bennett et al. 2014). Pregnant Danish women with type 1 diabetes and lower vitamin D levels had a higher risk of preterm delivery, although the difference was not statistically significant after adjusting for other factors. They did not have an increased risk of pre-eclampsia (Vestgaard et al. 2017). In the UK, pregnant women with type 1 diabetes were found to be deficient in vitamin D, although so were controls. All babies' cord blood was also deficient in vitamin D, especially in obese women (Bennett et al. 2013). Pregnant women with type 1 diabetes had higher hemoglobin A1c levels than those with lower vitamin D levels, implying that having adequate vitamin D may help improve blood glucose control in people with type 1 diabetes (Bennett et al. 2013).

Effects on the Offspring

Low vitamin D levels in pregnant women may also affect the offspring (bringing us back to the topic at the top of this page, whether a mother's vitamin D levels can affect the risk of type 1 in the offspring). A Brazilian study found that vitamin D deficiency in women with gestational diabetes is associated with hypoglycemia in infants, and small for gestational age incidence (Weinert et al. 2016). 

Surprisingly, prenatal exposure to extra vitamin D from fortification may lower the offspring's risk of gestational diabetes as well, in girls born in the spring (Keller et al. 2018).

A study from Singapore found that if pregnant women were deficient in vitamin D, there was no effect on birth outcomes, growth, or weight gain in the offspring in the first 2 years of life (however, very few people in the study were deficient in vitamin D) (Ong et al. 2016). 

Lower vitamin D levels in pregnant women were associated with lower birth weight but higher fat mass in offspring at 4 and 6 years of age (Crozier et al. 2012) and in another study, higher weight at 1 year but not at 4 years (Morales et al. 2015). A Denver study found that prenatal vitamin D levels were associated with body composition in infants (Sauder et al. 2017).

Laboratory Studies: Gestational Diabetes

In guinea pigs, higher vitamin D levels before pregnancy were protective against gestational diabetes, however, vitamin D levels during pregnancy did not affect risk (Tabatabaei et al. 2014). In animals, maternal vitamin D deficiency during pregnancy leads to insulin resistance in the offspring (Zhang et al. 2014).

An Epidemic of Vitamin D Deficiency

One surprising thing that most of the above studies have in common is the finding that many people have insufficient levels of vitamin D in their bodies-- even people who live in regions with bountiful sunshine (e.g., in Florida (Bierschenk et al. 2009), the Mediterranean region (Karras et al. 2016), the Middle East (Singh et al. 2019), and India (Sharma et al. 2019)). Ginde et al. (2009) found that based on a nation-wide sample, 77% of the U.S. population has insufficient vitamin D levels (including nearly all African Americans and almost all Mexican Americans). In addition, levels of vitamin D have declined in the U.S. population, comparing the periods 1988-1994 to 2001-2004. Even in the hot, sunny climate of Saudi Arabia, most people tested were vitamin D deficient (Al-Daghri et al. 2014). I just don't think sunshine is enough.
 
Mohr et al. (2008) suggest that children over age 1 who live more than 30 degrees from the equator (that includes almost all of the U.S.), take 1000-2000 IU vitamin D3 per day, especially during the winter, "to substantially reduce their risk of type 1 diabetes." The current U.S. recommendations are only 200 IU vitamin D per day, a level that is inadequate to address the growing epidemic of vitamin D deficiency (Ginde et al. 2009). Others recommend that children under 1 receive 1000 IU/day, older children 3000 IU/day, and young adults even more (Papadimitriou 2017). I don't know enough to make recommendations here; please contact your doctor. During pregnancy, the current recommendations of 200-400 IU per day are likely inadequate to maintain normal levels of vitamin D during pregnancy and lactation (Mulligan 2010). Parents of children at risk of developing type 1 might take note and supplement. And, during the sunnier months, parents might also try the "leave no child indoors" method of vitamin D "supplementation." Although, be aware that while the urban myth may argue that adequate vitamin D can be obtained from the sun, it appears that few US residents make adequate vitamin D even without sunscreen, at any time of the year (Godar et al. 2012).
 
Norris (2001) suggests that various public health initiatives may have acted together to reduce vitamin D exposure in children, including keeping babies out of the sun, using sunscreen on young children, and exclusive breastfeeding. Exclusively breastfed infants are at higher risk of vitamin D deficiency than are formula-fed infants (Kovacs 2008); each month of breastfeeding (without supplementation) increases the risk of vitamin D deficiency by 6% (Darmawikarta et al. 2016). This deficiency can be remedied however, with sufficient supplementation for pregnant and nursing mothers. During pregnancy, if the mother has sufficient levels of vitamin D (which may require supplementation), then the fetus should too. After birth, the mother may need up to 4000 IU per day to maintain sufficient levels in her and her exclusively breastfed baby (Kovacs 2008). 
 
Vitamin D is known to improve the absorption of calcium (Norris 2001); adults with type 1 diabetes have lower bone mineral density and a higher risk of bone fractures (Carnevale et al. 2004).

Vitamin D and the Gut

In infants, vitamin D levels are associated with gut microbiota (Sordillo et al. 2017). Vitamin D levels also appear to affect the gut microbiota of mice (Jin et al. 2015). A review argues that the interactions between vitamin D and the gut microbiota may be critical factors in the increasing incidence of type 1 diabetes (Clark and Mach 2016). See the Diet and the Gut page for more information on how the gut might be related to diabetes.

Vitamin D and Environmental Chemicals

Environmental Chemical Levels Are Associated With Low Vitamin D Levels

vitamin D and chemicals

In U.S. pregnant women, higher levels of both phthalates and BPA were associated with an increased risk of vitamin D deficiency. In these graphs you can see as chemical levels increase, vitamin D levels decrease. 
Unfortunately, some contaminants may be able to affect vitamin D levels, including air pollutants, heavy metals, persistent organic pollutants, and endocrine disrupting chemicals such as BPA and phthalates (for a free full text review, see Mousavi et al. 2019). 

The first human study published on this topic found associations between vitamin D levels and persistent organic pollutants (POPs) in U.S. adults. That is, adults with higher levels of POPs in their blood had lower levels of vitamin D, especially people in old age, who were white, or who had chronic diseases (Yang et al. 2012). Another study, of pregnant women, found that women with high levels of some PCBs had lower vitamin D levels (Morales et al. 2013). In the U.S., one perfluoroalkyl substance (PFAS) was associated with lower vitamin D levels, and another with higher levels (Etzel et al. 2018).

In newborns, those whose mothers were exposed to higher levels of air pollutants during pregnancy (especially in the third trimester) had lower vitamin D levels than infants whose mothers were exposed to lower levels of air pollutants (Baïz et al. 2012). Likewise, children exposed to higher levels of air pollution (in Mexico City) had lower vitamin D levels than those exposed to lower levels (Calderón-Garcidueñas et al. 2015). Similarly, higher air pollution was associated with lower vitamin D levels in Iranian adolescents (Feizabad et al. 2017). Really high air pollution levels may also just block the sun, reducing vitamin D levels (Yan et al. 2017). 

And, a study from Korea found that a combination of vitamin D deficiency and arsenic exposure were associated with an increased risk of diabetes in adults (Lee and Kim 2013). In U.S. adults, higher phthalate and BPA levels (in women) are associated with lower vitamin D levels (Johns et al. 2016), and with an increased risk of vitamin D deficiency in pregnant women (Johns et al. 2017). In Bangladesh, higher cadmium levels are associated with lower vitamin D levels in children (Malin Igra et al. 2019). Thus, a number of chemicals have been linked to lower vitamin D levels in humans.

However, not all human studies have found a link between chemical exposures and vitamin D levels. A study of adolescents from Mexico found that lead and cadmium levels were not associated with vitamin D levels, and that those with higher levels of molybdenum, thallium, uranium, and arsenic in fact had higher levels of vitamin D (Zamoiski et al. 2014).

Laboratory studies have also examined the possibility that chemicals may influence vitamin D levels. For example, early life exposure to the pesticide permethrin leads to low vitamin D levels in adult rats (Fedeli et al. 2013).

After vitamin D3 forms in the body, or is obtained via diet, it is then converted to other forms of vitamin D. In the liver, it is converted to 25-hydroxyvitamin D (25-D) and in the kidney to the more active form, 1,25 dihydroxycholecalciferol (1,25-D) (Norris 2001). Some chemicals may affect the conversion of one type of vitamin D to another. When researchers fed mother rats a mixture of PCBs similar to those found in human breastmilk, they found that the PCBs caused reductions in the levels of 1,25-D in the mothers at birth and weaning, and these reduction were dependent on PCB dosage. Levels of 1,25-D were also reduced in the offspring at higher exposure levels. Levels of 25-D were lower mothers at the time of delivery, and in the offspring at the highest dosage levels. In the mothers, levels of 1,25-D were reduced even at the lowest PCB treatment level, although this level was still higher than the PCB levels normally found in humans (Lilienthal et al. 2000). Rats given PCBs had lower vitamin D levels than unexposed controls (Alvarez-Lloret et al. 2009).
 
Another animal study found that POPs may disrupt vitamin D conversion processes in seals. It compared vitamin D levels in seals from the highly polluted Baltic Sea to seals from other less polluted waters. It found that while vitamin D3 levels in the liver were higher in the Baltic seals (probably due to sunlight or diet), levels of 1,25-D were lower. Both the contaminant levels and the hormone levels also varied by species. The authors suggest that these findings might explain the bone abnormalities found in gray seals in the Baltic Sea (Routti 2008).
 
Another study on bone toxicity examined the effects of dioxin, another POP, on vitamin D levels in mice. This study found that dioxin actually increased levels of 1,25-D in the mice, but also impaired bone mineralization (Nishimura et al. 2009). How exactly contaminants can affect vitamin D processes in animals, whether the same effects occur in humans, and whether these processes could be a factor in type 1 diabetes development all deserve further study.
 
Persistent organic pollutants, including PCBs, evaporate and migrate to the polar regions of the earth (Tanabe 2002). Perhaps exposure to environmental contaminants may also help explain the high and increasing incidence of type 1 diabetes in polar regions (especially high in some countries surrounding the Baltic Sea, as described on the diabetes incidence page), and why even many Floridians have low levels of vitamin D in their bodies. More research on these possibilities is necessary.

References

To see or download the references cited on this page, as well as many others on this topic, see the collection Vitamin D and diabetes/obesity in PubMed.