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Type 1 diabetes 3.5X more frequent if low vitamin D - Medscape CME Dec 2012

From Medscape Education Clinical Briefs

Levels of Vitamin D May Affect Type 1 Diabetes Risk CME

News Author: Miriam E. Tucker
CME Author: Penny Murata, MD[|Faculty and Disclosures]CME Released: 12/17/2012; Valid for credit through 12/17/2013Image   [|CME Information]Earn CME Credit »

Clinical Context

According to the Centers for Disease Control and Prevention, the annual incidence rate of type 1 diabetes in the United States is about 13 per 100,000. The risk for type 1 diabetes was found to be 4.5 times higher in children who received less than 2000 IU vitamin D supplementation per day, as reported by Hypponen and colleagues in 2001 (Lancet. 358:1500-1503). However, in 2009, Bierschenk and colleagues found that vitamin D levels were not associated with type 1 diabetes (Diabetes Care. 32:1977-1979).

This nested case-control study assesses whether serum 25-hydroxyvitamin D [25(OH)D] levels are associated with risk for insulin-requiring diabetes.

Study Synopsis and Perspective

Low serum vitamin D concentration was associated with an increased risk of developing "insulin-requiring" diabetes in a nested case-control study of active-duty military service members.

The study, led by Edward D. Gorham, PhD, MPH, a research epidemiologist from the Naval Health Research Center, San Diego, and assistant adjunct professor in the Department of Family and Preventive Medicine at the University of California, San Diego, was published online September 7 and in the December issue of Diabetologia.

Dr. Gorham and colleagues used prediagnostic serum taken as part of a US Department of Defense serological surveillance program between 2002 and 2008. They compared levels of 25(OH)D between 1000 consecutive patients who developed insulin-requiring diabetes and 1000 healthy matched control participants. Case and control participants had all been on active duty at the time of the initial blood draw. Individuals from the 2 groups were matched based on "date that the blood sample was drawn (±2 days), age (±3 months), length of military service (±30 days), sex and whether the control was on active duty when the case was diagnosed," the authors write.

A median of 1 year (range, 1 month - 10 years) elapsed between the blood sample collection and diabetes diagnosis. More than two thirds of all the study participants were younger than 35 years.

Those in the lowest quintile of serum 25(OH)D levels (<43 nmol/L) had a 3.5-fold greater likelihood of developing insulin-requiring diabetes than those in the highest quintile of serum 25(OH)D levels (≥100 nmol/L). Those in the second-lowest quintile of serum 25(OH)D levels (43 - 59 nmol/l) had a 2.5-fold greater risk. Odds ratios (ORs) for the next 3 serum 25(OH)D levels quintiles (60 - 77, 78 - 99, and ≥100 nmol/L) were 0.8, 1.1, and 1.0 (reference), respectively (Ptrend < .001).

"Based on the present study, it may be that no further reduction in risk would be expected once a serum 25(OH)D concentration of >60 nmol/l has been attained," the authors note.

Those who developed diabetes had significantly lower mean 25(OH)D levels than the healthy control patients (62.2 nmol/L vs 72.5 nmol/L; P ≤ .0001).

Among racial groups, blacks were more likely to develop diabetes than other races, but the association between 25(OH)D levels and diabetes was seen in all racial groups.

After adjustment for race, those with the lowest quintile of 25(OH)D were at nearly 2-fold greater risk of developing diabetes compared with those in the highest quintile (OR, 1.9; 95% confidence interval, 1.4 - 2.7; P < .0001). Compared with whites, the OR for blacks was 1.6 (95% confidence interval, 1.2 - 2.0; P < .001).

As the researchers explain, worldwide rates of type 1 diabetes vary by latitude, with annual age-standardized incidences ranging from a low in the tropics (0.5/100,000 in Venezuela) to a high near the Arctic Circle (60/100,000 in Finland).

It is possible, the researchers state, that vitamin D affects immune function. "Vitamin D deficiency is associated with major effects on the innate immune system. This could potentially influence the risk of diabetes by reducing risk of infection of islet cells," the authors write.

A potential study limitation includes the possibility that a small number of patients may have had complicated type 2 diabetes. "Cases in the present study were included solely because they were dependent on insulin," the authors note.

This research was supported by a Congressional allocation to the University of Miami Diabetes Research Institute through the Department of the Navy, Bureau of Medicine and Surgery. The authors have disclosed no relevant financial relationships.

Diabetologia. 2012;55:3224-3227. Full text

Study Highlights

  • Prediagnostic serum was obtained during 2002-2008 from military service members on active duty who were screened through a US Department of Defense serological surveillance program.
  • 1000 cases of insulin-requiring diabetes were identified in 2002-2011.
  • Insulin-requiring diabetes cases were defined by hospitalization with discharge diagnosis of insulin-requiring diabetes certified by a physician, 3 or more outpatient visits with primary diagnosis of insulin-requiring diabetes during a 12-month period, or 7 or more outpatient visits with a primary diagnosis of insulin-requiring diabetes.
  • Healthy control participants were matched 1:1 by blood draw date (within 2 days), age (within 3 months), length of service (within 30 days), and sex.
  • The median time between serum collection and diabetes diagnosis was 1 year (range, 1 month - 10 years).
  • Serum 25(OH)D concentration was categorized into quintiles, with the highest quintile of more than 100 nmol/L used as the reference.
  • The risk for insulin-requiring diabetes was increased for the lowest quintile compared with for the highest quintile of serum 25(OH)D concentration (P for trend < .001):
    • OR, 3.5 for serum 25(OH)D concentration lower than 43 nmol/L;
    • OR, 2.5 for serum 25(OH)D concentration 43 to 59 nmol/L;
    • OR, 0.8 for serum 25(OH)D concentration 60 to 77 nmol/L;
    • OR, 1.1 for serum 25(OH)D concentration 78 to 99 nmol/L; and
    • OR, 1.0 for serum 25(OH)D concentration 100 nmol/L or higher (reference).
  • The mean serum 25(OH)D concentration was lower in case patients vs in control participants (62.2 vs 72.5 nmol/L; P < .0001).
  • Among case patients, 56.1% were white, 27.6% were black, and 16.3% were other race.
  • Among control participants, 66.9% were white, 16.3% were black, and 16.8% were other race.
  • The mean serum 25(OH)D concentration was lower in case patients vs control participants.
  • In subgroups by race, case vs control, they were:
    • white: 62.2 vs 72.5 nmol/L,
    • black: 41.8 vs 46.5 nmol/L, and
    • other: 60.8 vs 69.2 nmol/L.
  • After adjusting for race, the risk for insulin-requiring diabetes by quintile of serum 25(OH)D concentration was as follows (P < .0001):
    • OR, 1.9 for serum 25(OH)D concentration lower than 43 nmol/L;
    • OR, 1.7 for serum 25(OH)D concentration 43 to 59 nmol/L;
    • OR, 1.1 for serum 25(OH)D concentration 60 to 77 nmol/L;
    • OR, 1.2 for serum 25(OH)D concentration 78 to 99 nmol/L; and
    • OR, 1.0 for serum 25(OH)D concentration 100 nmol/L or higher (reference).
  • Study limitations were possible inclusion of cases with type 2 diabetes, only 1 serum sample, lack of specific body mass index data (except for military standards), and need for caution in generalizing results.

Clinical Implications

  • The risk for insulin-requiring diabetes is higher if the serum 25(OH)D concentration is lower, with a 3.5-fold increased risk for diabetes if the serum 25(OH)D concentration is lower than 43 nmol/L compared with 100 nmol/L or more.
  • A serum 25(OH)D concentration of at least 60 nmol/L does not increase the risk for insulin-requiring diabetes.

CME Test

To receive AMA PRA Category 1 Credit™, you must receive a minimum score of 70% on the post-test.

Which of the following most accurately describes the risk for insulin-requiring diabetes and quintile of serum 25(OH)D level?Decreased risk for diabetes in lowest vs highest quintileIncreased risk for diabetes in lowest vs highest quintileIncreased risk for diabetes in middle quintile vs highest quintileNo link between risk for diabetes and 25(OH)D level
A healthy 30-year-old patient undergoes serum 25(OH)D testing.
Which of the following serum 25(OH)D levels is most likely to have the lowest OR for risk for insulin-requiring diabetes?
35 nmol/L
45 nmol/L
55 nmol/L
65 nmol/L


See also VitaminDWiki

Pages listed in BOTH of the categories Diabetes and Infant/Child

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