The Relation Between Vitamin D and Gestational Diabetes Mellitus
Condition: Deficiency, Vitamin D; Diabetes, Gestational
MeSH terms: Diabetes, Gestational; Diabetes Mellitus; Avitaminosis; Vitamin D Deficiency
Study type: Observational

Summary: 
      Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with the
      onset or first recognition during pregnancy. The prevalence of GDM varies from 1-14% due to
      its variability worldwide, depending on the ethnicity, race, and the diagnostic criteria
      being applied by each country. In addition to this, approximately 7% of all pregnancies are
      affected by GDM, ending up more than 200,000 women with GDM per year. A recent study of
      literature research indicated that Middle East and North Africa had the highest prevalence
      (median, 12.9%) while Europe had the lowest prevalence (median, 5.8%) in the world. In Turkey
      the prevalence of GDM ranges between 4-10%, based on the reports in different studies.

      As a growing health concern, GDM has been associated with short and long-term detrimental
      health outcomes for women and their offspring. Maternal adverse effects of GDM are
      preeclampsia, elevated risk of development of hypertension, type 2 diabetes mellitus (T2DM),
      urinary tract infection and comorbidities following delivery. Macrosomia, neonatal jaundice,
      birth trauma, respiratory distress syndrome, hypoglycemia are included in short term
      consequence for the neonates whereas risk for development of impaired glucose tolerance,
      T2DM, obesity, vascular disorders are long term adverse effects on infant's health.

      The known risk factors for GDM include family history of T2DM, maternal overweight and
      obesity, advanced maternal age, history of GDM, having macrosomic infant previously, prior
      fetal death, and race/ethnicity. In addition to these risk factors, recent studies have been
      suggested that maternal vitamin D deficiency may be associated with a higher risk of GDM.

      Vitamin D deficiency during the pregnancy has been associated with adverse outcomes for the
      pregnant women, such as gestational diabetes mellitus, urinary tract infection, preeclampsia,
      caesarean section during labour [25]. Furthermore, infants born to mothers with lower vitamin
      D levels have been found to be associated with elevated risk of small for gestational age,
      low birth weight in the neonatal period, increased risk for cardiovascular disease,
      respiratory illnesses, type 2 diabetes mellitus in childhood and adulthood.

      The aim of this study was to compare the serum 25(OH)D levels of women with and without
      gestational diabetes mellitus (GDM) and identify the serum 25(OH)D level associated with GDM
      during pregnancy.
    

Detailed description: 
      In this observational cross-sectional study, 40 women with GDM and 40 healthy pregnant
      between 20-40 years in age, in their 24-28th gestational week applied to Gulhane Education
      and Research Hospital (Ankara, Turkey) were recruited between January 2014 to March 2014.
      Inclusion criteria were singleton pregnancy, aged 20-40 years, gestational age 24-28 weeks,
      non-history of acute or chronic diseases. The exclusion criteria included alcohol using,
      smoking, history of GDM, diagnosed with type 1 and 2 diabetes mellitus, preeclampsia,
      polycystic ovary syndrome, thyroid and parathyroid disease, metabolic bone disease, kidney
      disease, abnormal liver function, multiple pregnancy, or women receiving drugs related to
      calcium and vitamin D metabolism (with the exception of routine vitamin supplements
      prescribed during pregnancy). We randomly selected the 40 pregnant women diagnosed GDM by
      two-step procedure based on Carpenter-Coustan criteria. Women with GDM did not receive any
      type of the medications such as insulin or medical nutrition therapy. We also randomly
      selected 40 healthy pregnant women with normal serum glucose levels in the same period. This
      study must recruit 40 women for each group to have 80% study power with 5% type I error level
      to detect a clinically significant difference.

      The study was approved by the ethic committee of Gulhane Education and Research Hospital,
      Ankara, Turkey with the number 50687469-1491-2721-13/1648.4-2882. Before commencing the
      research, not only women got clued in information about the study procedure and objective but
      also a written informed consent was obtained from all participants.

      GDM screening at this hospital involves a two-step procedure. At the outset, 50 g 1 hour
      glucose challenge test (GCT) was used to screen for GDM at 24th and 28th weeks of gestation.
      Women with abnormal glucose levels ≥130 mg/dL (7.2 mmol/L) after 1 hour GCT underwent a
      standard 100 g 3 hour oral glucose tolerance test (OGTT) performed in the morning after eight
      hours overnight fasting. The diagnosis of GDM was confirmed if at least 2 of 4 glucose levels
      exceed Carpenter-Coustan criteria: fasting ≥ 95 mg/dL (5.3 mmol/L), 1 hour ≥ 180 mg/dL (10.0
      mmol/L), 2 hours ≥ 155 mg/dL (8.6 mmol/L), and 3 hours ≥ 140 mg/dL (7.8 mmol/L).

      Demographic and individual information such as maternal age, gestational week, parity were
      recorded. Weight and height of women with light clothes and without shoes were measured via a
      digital Seca Scale. BMI (Body Mass Index) was calculated by using the following formula:
      BMI=Weight (kg)/[Height (m) × Height (m)] and evaluated based on classification of (World
      Health Organisation) WHO as follows: >18.5 kg/m2 defined as underweight, 18.5-24.9 kg/m2
      defined as normal weight range, 25.0-29.9 kg/m2 defined as overweight and ≥30.0 kg/m2 defined
      as obese. Investigators collected blood samples from each women between 24th and 28th weeks
      of pregnancy during their scheduled antenatal visit to determine the serum 25-hydroxyvitamin
      D [(25OHD)] concentration.

      Levels of 25(OH)D on serum was measured by high performance liquid chromatography (HPLC) in
      biochemistry laboratory at Gulhane Education and Research Hospital. Investigators used
      clinical cutoffs based Institute of Medicine (IOM) criteria to categorize 25(OH)D levels:
      severe deficiency (<10 ng/mL), deficiency (10-20 ng/mL) and insufficiency (20-30 ng/mL).

      Firstly, the variables were tested using Kolmogorov-Smirnov test to determine whether they
      are normally distributed. Descriptive analyses were presented as mean±standard deviation (SD)
      for normally distributed variables. Since the maternal age, serum 25(OH)D, log-transformed 50
      g 1 hour GCT and log-transformed fasting blood glucose values were normally distributed; the
      Student's t-test was used to compare these parameters between women with and without GDM.
      Descriptive analyses were presented as median(min-max) for the non-normally distributed.
      Since the gestational age, gravity, and parity were not normally distributed; Mann-Whitney U
      test was used to compare these parameters between groups. Chi square test was used for
      categorical variable to compare the proportions in different groups. As both parameters were
      normally distributed, the correlation coefficients and their significance were calculated
      using the Pearson test. For the multivariate analysis, the possible factors identified with
      univariate analyses were further entered into the logistic regression analysis to determine
      independent predictors of women outcome. Hosmer-Lemeshow goodness of fit statistics were used
      to assess model fit. A 5% type-I error level was used to infer statistical significance.
      Receiver operating characteristics (ROC) analysis was done to identify the optimal cutoff
      point values of maternal serum 25OHD levels. All the data collected from the participants
      were analyzed using Statistical Package for the Social Sciences (SPSS) version 22.0 (SPSS
      Inc., Chicago, Illinois, USA) and p<0.05 was considered statistically significant.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        In this observational cross-sectional study, 40 women with GDM and 40 healthy pregnant
        between 20-40 years in age, in their 24-28th gestational week applied to Gulhane Education
        and Research Hospital were recruited. This study must recruit 40 women for each group to
        have 80% study power with 5% type I error level to detect a clinically significant
        difference.
      
Keywords: Pregnancy, deficinecy, vitamin D, diabetes, gestational