Background: Although recent meta-analyses indicates a consistent significant inverse relation of serum 25 (OH) D and the prevalence of gestational diabetes mellitus (GDM), the mechanism is unclear and conflicting opinions continue to be reported. Objectives: The objectives are: 1) comparison of vitamin D status in diabetic and non-diabetic pregnant women; 2) trying to determine the level of vitamin D associated with GDM, and its sensitivity and specificity; 3) determination of the relation of hypovitaminosis D with insulin resistance. Subjects and Methods: One hundred consecutive pregnant women (<28 weeks gestational period) from the attendants of the out-patient clinic at our hospital were diagnosed for GDM by glucose tolerance test (GTT) (75 g 2 h). Among them, 40 patients met the inclusion criteria for this study (group I). As a comparative group, another 40 pregnant ladies were included, 20 of them (group II) had pre-gestational type II DM, and the other 20 (group III) had normal glucose tolerance (NGT) as a control. For all the participants, we estimated fasting blood glucose, fasting serum insulin, homeostasis model assessment of (HOMA-IR and HOMA-B), quantitative insulin sensitivity check index (QUICKI), and serum 25-OH vit D. The ROC curve analysis was used to determine the optimal threshold value of vit D in relation to DM. Results: Compared to the control group, the diabetic patients showed a statistically significant increase in the levels of fasting glucose, 1-hour postprandial glucose, 2-hour post prandial glucose, fasting insulin, and HOMA-IR, (P=0.000 for all). None of the diabetic patients showed optimal vit D level. Vit D insuficiency (10 - 29 ng/ml) was found in 32.5% of patients in group I, 55% in group II, and 50% in group III. Vit D deficiency (<10 ng/ml) was found in 67.5% of patients in group I, 45% in group II, and 0% in group III. Significant negative correlation was found for vit D with fasting insulin and FBS. The AUC for 25 OH vit D was 97%, CI was 95% and p-value was 0.0001. The sensitivity, specificity, and positive and negative predictive values of 25 OH vit D in GDM versus control persons were 97%, 90%, 95.1%, 94.7% respectively at a cut-off level <22 ng/ml. Conclusions: Although it might seem premature to draw a sharp relation between hypovitaminosis D and GDM, this study showed the importance of vit D in GDM, the need for supplementation below 22 ng/ml, and the role of hypovitaminosis D in increasing insulin resistance. Further randomized studies with vit D supplementation are recommended.
Although, recent evidence suggests that vitamin D deficiency may contribute to the development of type II diabetes mellitus (T2DM), the exact mechanism is unknown [
- Comparison of vit D status in pregnant women;
- Trying to determine the level of vitamin D associated with GDM, and its sensitivity and specificity;
- Determination of the relation of hypovitaminosis D with insulin resistance.
After approval of the local health ethical committee and a written consent, we conducted an observational case control study on pregnant women attending the out-patient clinic at our hospital between September 2013 to September 2015. The inclusion criteria were pregnant ladies <28 weeks gestational age. The exclusion criteria included previous history of GDM or obstetric complications, metabolic bone disease, abnormal liver function, impaired kidney function, or patients receiving medication known to affect calcium & vit D metabolism (except routine prenatal vitamin supplements including calcium). One hundred consecutive pregnant women with GDM were studied. From them, only 40 patients met the inclusion criteria for this study (group I). As a comparative group, another 40 pregnant ladies were included, 20 of them (group II) had pre-gestational type II DM, and the other 20 (group III) had normal glucose tolerance (NGT) as a control. The glucose tolerance test (GTT) (75 g 2 h) was used to diagnose GDM according to the guidelines of the international association of diabetes and pregnancy study groups (IADPSG) 2010. The diagnosis was confirmed when the plasma glucose level exceeded: fasting: ≥92 mg/dL (5.1 mmol/L), 1 h: ≥180 mg/dL (10.0 mmol/L), 2 h: ≥153 mg/dL (8.5 mmol/L).
All the participants were subjected to:
- Full history taking including gestational age, history of previous GDM, family history of diabetes and history of maternal and neonatal complications;
- Thorough clinical examination including assessment of blood pressure, calculation of the body mass index (BMI), and obesity was defined as BMI >30 kg/m and morbid obesity >40 kg/m2;
- Laboratory assay including fasting blood glucose, fasting serum insulin, homeostasis model assessment of insulin resistance and β cell function (HOMA-IR & HOMA-B), quantitative insulin sensitivity check index (QUICKI), and serum 25-OH vit D. The HOMA-IR was calculated by multiplying fasting plasma insulin (FPI) mU/mL by fasting plasma glucose (FPG) mmol/L, then dividing by the constant 22.5, i.e. HOMA-IR = (FPI × FPG)/22.5. HOMA-IR values <3.0 are considered normal, while values ≥ 3.0 indicate insulin resistance. The HOMA-B was calculated as (FPI in mU/mL × 20)/(FPG in mmol/L −3.5). The QUICKI was calculated by the formula (1/log FPI in mU/mL + log FPG in mg/dl) vitamin D sufficiency, insufficiency, and deficiency were defined as serum 25OHD concentrations 30 - 100, 10 - 29 and <10 ng/mL respectively.
Data was collected and included in a data based system and analyzed by statistical package of social sciences ((SPSS, Inc., Chicago, IL, USA)) version 17. Parametric data were expressed as mean ± standard deviation (SD). It was analyzed statistically using student t-test while non-parametric data were expressed as percentages and were analyzed using chi square. The Pearson correlation coefficients (r) were used to study the correlation between different parametric variables. Spearman correlation coefficients were used to study the correlation with non-parametric variables. Logistic regression analysis was done to calculate the odds ratio to determine the contribution of some variables to gestational diabetes. Receiver operating characteristics (ROC) analysis was used to identify the optimal threshold values of 25 OH vitamin D. Sensitivity and specificity, positive and negative predictive values of 25 (OH) vitamin D were profiled by curves.
In the GDM group, serum 25 (OH) vit D had a significant negative correlation with BMI, fasting insulin (P = 0.00, 0.05 respectively), and tendency towards significant positive correlation with HOMA-B (P = 0.09). In the diabetic group; serum 25 (OH) vit D had a highly significant negative correlation with CRP (P = 0.00) (
The main limitations for this study included the small number of patients and absence of evaluation for the effect of vit D supplementation. Controversy still exists about the exact role of vit. D deficiency in the pathogenesis of DM, especially, GDM. Many previous studies [
Race/ethnicity is an important determinant of vitamin D deficiency. Yu et al. [
Group Variables | Group (1) ladies With GDM NO (40) | Group (2) Ladies With pre gestational DM, NO (20) | Group (3) Ladies As normal control NO (20) | P value | ||
---|---|---|---|---|---|---|
1 | 2 | 3 | ||||
Age (years) mean ± SD | 27.8 ± 5.39 | 30.8 ± 6.62 | 26.63 ± 5.67 | 0.254# | 0.557# | 0.632# |
Gestational age (wk) Mean ± SD | 34.5 ± 2.96 | 30 ± 4 | 30.42 ± 4.18 | 0.340# | 0.276# | 0.541# |
Gravity mean ± SD | 3.22 ± 1.77 | 4.05 ± 2.08 | 3.57 ± 1.67 | 0.462# | 0.441# | 0.140# |
Parity mean ± SD | 1.47 ± 1.53 | 1.95 ± 1.9 | 2.21 ± 1.43 | 0.080# | 0.632# | 0.340# |
FH of DM (yes/No) % | (30/10) 7% | (13/7) 65% | (0/20) 0% | 0.000** | 0.000** | 0.000** |
SBP (mmHg) mean ± SD | 126.75 ± 17.3 | 122.5 ± 24.03 | 109.73 ± 15.49 | 0.001** | 0.05* | 0.487# |
DBP (mmHg) mean ± SD | 78.13 ± 14.26 | 78 ± 11.965 | 70 ± 8.81 | 0.010** | 0.023* | 0.972# |
Pre preg BMI (kg/m2) mean ± SD | 31.01 ± 3.73 | 29.26 ± 4.18 | 23.05 ± 2.51 | 0.000** | 0.000** | 0.123# |
TG (mg/dl)mean ± SD | 179.7 ± 78.73 | 188.4 ± 97.7 | 103.57 ± 25.28 | 0.000** | 0.001** | 0.734# |
T-Chol (mg/dl) mean ± SD | 191.8 ± 58.23 | 186.9 ± 37.48 | 86.84 ± 18.87 | 0.000** | 0.000** | 0.698# |
HDL-Chol (mg/dl) mean ± SD | 42.9 ± 10.62 | 44.6 ± 15.19 | 59.63 ± 15.79 | 0.104# | 0.318# | 0.657# |
LDL-Chol (mg/dl) mean ± SD | 122.79 ± 56.73 | 114.57 ± 31.32 | 26.03 ± 9.06 | 0.000** | 0.000** | 0.473# |
Total Ca (mg/dl) mean ± SD | 8.23 ± 1.71 | 8.07 ± 1.7 | 9.87 ± 0.627 | 0.000** | 0.000** | 0.740# |
Ionized Ca (mmol/l) mean ± SD | 0.9 ± 0.157 | 0.92 ± 0.105 | 1.19 ± 0 .086 | 0.000** | 0.000** | 0.572# |
FBS (mg/dl) mean ± SD | 112.4 ± 14.63 | 120.65 ± 14.47 | 81.73 ± 6.14 | 0.000** | 0.000** | 0.046* |
1 hour glucose (mg/dl) mean ± SD | 204.45 ± 30.91 | 237.95 ± 32.95 | 158.57 ± 13.47 | 0.000** | 0.000** | 0.001** |
2 hour glucose (mg/dl) mean ± SD | 160.65 ± 20.11 | 177.95 ± 18.36 | 128.42 ± 13.88 | 0.000** | 0.000** | 0.002* |
HbA1C (%) mean ± SD | 6.79 ± 0.53 | 9.15 ± 6.1 | 6.11 ± 0.26 | 0.000** | 0.038* | 0.101# |
Fasting insulin (µu/ml) mean ± SD | 45.35 ± 22.75 | 39.8 ± 29.43 | 10.58 ± 2.65 | 0.000** | 0.000** | 0.465# |
HOMA-IR mean ± SD | 1.79 ± 0.75 | 1.81 ± 0.98 | 0.21 ± 0.051 | 0.000** | 0.000** | 0.774# |
HOMA-B mean ± SD | 36.84 ± 24.91 | 24.73 ± 18.52 | 38.29 ± 68.03 | 0.929# | 0.411# | 0.042* |
QUICKI mean ± SD | 2.66 ± 0.087 | 2.79 ± 0.167 | 2.9 ± 0.126 | 0.000** | 0.022* | 0.005** |
Vitamin D (ng/ml) mean ± SD | 8.85 ± 6.42 | 10.83 ± 5.45 | 30.92 ± 8.47 | 0.000** | 0.000** | 0.220# |
CRP mean ± SD | 41.15 ± 37.03 | 48.10 ± 35.38 | 13.89 ± 20.78 | 0.001** | 0.001** | 0.484# |
Quantitative variables are expressed as mean ± SD and compared using student t test. Categorical variables are expressed as percentage and compared using Chi square. FH = family history; BMI = body mass index; SBP = systolic blood pressure; DBP = diastolic blood pressure. IUFD = intra uterine fetal death; Hb = hemoglobin, WBCS = white b1lood cells, TG = triglycerides, T-Chol = total cholesterol, HDL-Chol = high density lipoprotein cholesterol, LDL-Chol = low density lipoprotein cholesterol, Ca = calcium. FBS = fasting blood sugar, HbA1c = glycated hemoglobin, HOMA-IR = homeostatic model assessment-insulin resistance. HOMA-B = homeostatic model assessment B cell function, QUICKI = Quantitative insulin sensitivity check index, CRP = C-reactive protein. * = significant; ** = highly significant; # = insignificant. 1) group I versus III, 2) group II versus III, 3) group I versus II.
found that Middle Eastern (64%), black (58%), Asian women (47%), and Caucasian women (13%) had a high prevalence of very poor vitamin D status (25 OH vit D <25 nmol/L. In Saudi Arabia, Ardawi et al. [
Demographic and clinical characters | 25 (OH) D | |||||
---|---|---|---|---|---|---|
Group (1) GDM | Group (2) Diabetic | Group (3) Control | ||||
R | P | R | P | R | P | |
SBP (mmHg) | 0.123 | 0.449 | −0.099 | 0.679 | 0.180 | 0.461 |
DBP (mmHg) | −0.091 | 0.577 | −0.043 | 0.858 | 0.141 | 0.564 |
Pre preg BMI (kg/m2) | −0.623 | 0.000** | −0.256 | 0.276 | −0.159 | 0.516 |
TG (mg/dl) | 0.001 | 0.993 | 0.007 | 0.977 | −0.049 | 0.842 |
T-Cholesterol (mg/dl) | −0.001 | 0.997 | −0.468 | 0.038* | −0.109 | 0.656 |
HDL-Cholesterol (mg/dl) | −0.117 | 0.474 | 0.102 | 0.668 | −0.124 | 0.613 |
LDL-Cholesterol (mg/dl) | 0.021 | 0.897 | −0.507 | 0.023* | 0.027 | 0.912 |
Total Ca (mg/dl) | 0.169 | 0.297 | 0.026 | 0.914 | 0.662 | 0.002** |
Ionized Ca (mmol/l) | 0.362 | 0.0704 | 0.420 | 0.065 | 0.428 | 0.068 |
FBS (mg/dl) | −0.058 | 0.723 | −0.055 | 0.817 | 0.230 | 0.344 |
1-hour glucose (mg/dl) | 0.067 | 0.681 | −0.172 | 0.469 | −0.015 | 0.953 |
2-hour glucose (mg/dl) | 0.252 | 0.116 | −0.241 | 0.306 | 0.136 | 0.579 |
HbA1c (%) | −0.124 | 0.446 | 0.188 | 0.469 | 0.204 | 0.402 |
Fasting insulin (µu/ml) | −0.597 | 0.05* | −0.077 | 0.748 | 0.011 | 0.963 |
HOMA-IR | 0.202 | 0.211 | −0.095 | 0.691 | 0.108 | 0.661 |
HOMA-B | 0.271 | 0.091 | −0.050 | 0.840 | 0.090 | 0.713 |
QUICKI | −0.229 | 0.154 | −0.118 | 0.620 | 0.011 | 0.964 |
CRP | −0.059 | 0.716 | −0.610 | 0.004** | 0.054 | 0.826 |
BMI = body mass index; SBP = systolic blood pressure; DBP = diastolic blood pressure. IUFD = intra uterine fetal death. Hb = hemoglobin, WBCS = white b1lood cells, TG = triglycerides, T-Chol = total cholesterol, HDL-Chol = high density lipoprotein cholesterol, LDL-Chol = low density lipoprotein cholesterol, Ca = calcium. FBS = fasting blood sugar, HbA1c = glycated hemoglobin, HOMA-IR = homeostatic model assessment-insulin resistance. HOMA-B = homeostatic model assessment B cell function, QUICKI = Quantitative insulin sensitivity check index, CRP = C-reactive protein.
Demographic and clinical characters | HOMA-IR | |||||
---|---|---|---|---|---|---|
Group (1) GDM | Group (2) Diabetic | Group (3) Control | ||||
R | P | R | P | R | P | |
SBP (mmHg) | 0.110 | 0.500 | −0.288 | 0.218 | 0.031 | 0.900 |
DBP (mmHg) | 0.152 | 0.350 | −0.140 | 0.555 | 0.211 | 0.387 |
FBS (mg/dl) | 0.291 | 0.050* | 0.538 | 0.014* | 0.114 | 0.644 |
1 hour glucose (mg/dl) | 0.142 | 0.382 | 0.242 | 0.304 | 0.354 | 0.137 |
2 hour glucose (mg/dl) | 0.339 | 0.032* | 0.180 | 0.449 | 0.199 | 0.414 |
HbA1c (%) | 0.104 | 0.522 | −0.023 | 0.923 | −0.547 | 0.015* |
CRP | −0.110 | 0.499 | −0.078 | 0.745 | −0.116 | 0.636 |
Pre preg BMI (kg/m2) | −0.088 | 0.589 | −0.137 | 0.566 | 0.075 | 0.759 |
BMI = body mass index; IUFD = intra uterine fetal death. SBP = systolic blood pressure; DBP = diastolic blood pressure. * = significant; ** = highly significant; # = insignificant. FBS = fasting blood sugar, HbA1c = glycated hemoglobin, CRP = C-reactive protein. * = significant; ** = highly significant; # = insignificant.
OR (95%CI) | P value | |
---|---|---|
Age | 0.93 (0.84 - 1.03) | 0.150 |
SBP | 1.07 (1.03 - 1.11) | 0.002* |
DBP | 1.06 (1.01 - 1.11) | 0.021* |
TG | 1.04 (1.02 - 1.07) | 0.001* |
TC | 1.21 (1.04 - 1.41) | 0.015* |
HDL | 0.96 (0.92 - 1.001) | 0.055 |
LDL | 1.17 (1.04 - 1.3) | 0.007* |
BMI | 1.93 (1.34 - 2.76) | <0.001* |
CRP | 1.04 (1.01 - 1.07) | 0.013* |
CI, confidence interval, OR; Odds ratio, BMI = body mass index; SBP = systolic blood pressure; DBP = diastolic blood pressure. TG = triglycerides, T-Chol = total cholesterol, HDL-Chol = high density lipoprotein cholesterol, LDL-Chol = low density lipoprotein cholesterol.
Cut of point | AUC | Sensitivity | Specificity | PPV | NPV | Accuracy | P value |
---|---|---|---|---|---|---|---|
≤22 | 0.975 | 97.5 | 90 | 95.1 | 94.7 | 95% | <0.001* |
high prevalence (72%) of vitamin D deficiency among Saudi women of childbearing age.
Vit D deficiency may predispose to glucose intolerance, altered insulin secretion and type 2 diabetes [
In concordance with several cross-sectional studies, the present study reported an association between low maternal vitamin D status and GDM. Group I and II have low serum vitamin D levels in comparison with control with more deficiency in GDM group. The mean levels were 8.8, 10.8 and 30.9 ng/ml respectively). A cutoff point for vit D serum level in prediction of GDM was determined by application of receiver operating characteristic (ROC) curve. It was found to be at a level of 22 ng/ml with a sensitivity of 97.5% and a specificity of 90% (P = 0.00).
There is a complex relationship between vitamin D and obesity. While our and other many studies [
Some authors [
In agreement with Farrant et al. [
In agreement with [
A number of studies [
Maghbooli et al. [
In the Third National Health and Nutrition Examination Survey (NHANES III) and a meta-analysis of cross- sectional studies, serum 25OHD levels were found to be inversely associated with the risk of diabetes in non- Hispanic whites and Mexican Americans, but not in non-Hispanic blacks [
Borissova et al. [
In agreement with Pradhan et al. [
Although it might seem premature to draw a sharp relation between hypovitaminosis D and GDM, this study showed the importance of vit D in GDM, the need for supplementation below 22 ng/ml, and the role of hypovitaminosis D in increasing insulin resistance. Further randomized studies with vit D supplementation are recommended.
Ghada M.El-Sagheer,AsmaaKasem,Iglal M.Shawky,AhmedAbdel-Fadeel, (2016) Vitamin D Deficiency and Gestational Diabetes Mellitus in Egyptian Women. Open Journal of Endocrine and Metabolic Diseases,06,109-119. doi: 10.4236/ojemd.2016.62015