GDM: Prevention of GDM Diagnosis (2008)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To determine whether non-anemic women with gestational diabetes mellitus (GDM) diagnosed in third trimester pregnancy have evidence of increased iron stores compared with matched non-diabetic controls.

Inclusion Criteria:
  • Antenatal booking before 20 weeks of gestation
  • Normal hemogobin levels
Exclusion Criteria:
  • Pre-existing anemia
  • Other blood disorders and haemoglobinopathics which might result in a high serum ferritin concentrations owing to a problem with utilization.
Description of Study Protocol:

Recruitment: Women who had antenatal booking before 20 weeks' gestation and without anemia or diabetes mellitus were recruited at the time of the oral glucose toleranc test (OGTT) at 28-31 weeks' of gestation for the study of serum ferritin, iron and transferrin concentrations. 

Design : The cases diagnosed at as GDM were compared with a control group (two controls for each index case matched for parity) selected at random from the at-risk but nondiabetic cases.

Blinding used -The laboratory results were blinded to the managing obstetetricians.

Intervention (if applicable):  not applicable 

Statistical Analysis :

Statistical calculations and correlations were performed with the chi square test for categorical variables, Student's t-test and Mann-Whitney U-Test (with 95% confidence interval for the difference where appropriate) for normally and non-normally distributed continuous variables, and Spearman's correlation coefficient (rho) for non-normally distributed variables, using a commercial computer package (SPSS/PC; SPSS Inc, Chicago, Il).

 

Data Collection Summary:

Timing of Measurements

One time measurement.

Dependent Variables

  • Serum ferritin concentration - aliquoted for the later batched assay (Microparticle Enzyme Immunoassay, IMX System, Abbott Laboratories, Abbott Park, IL, USA)
  • Serum iron and transferrin - measured as total iron binding capacity (Calorimetric Method, Sigma, St Louis, Mo)
  • Transferrin saturation was calculated as the result of the serum iron divided by the total iron binding capacity. 

Independent Variables

  • Age (years)
  • Weight (kg)
  • Height (cm)
  • Body Mass Index (kg/m2)
  • Booking haemoglobin (g/dl)
  • 3rd trimester haemoglobin (g/dl)
  • Mean cell volume (fl)
  • Mean cell haemoglobin (pg)
  • mean cell haemoglobin concentration (g/dl)
  • Hematocrit (%)
  • Post partum haemoglobin (g/dl)
  • OGTT- fasting, 2 h (nmol/L)
  • Infant gestational age (w)
  • Birth weight (g)
  • Infant body mass index (kg/m2 )  

Control Variables

 

Description of Actual Data Sample:

Initial N: 401

Attrition (final N): 97 with GDM, 194 controls

Age: see Table I

Ethnicity: Chinese women

Other relevant demographics:

Anthropometrics

Location: Department of Obstetrics and Gynaecology. The University of Hong Kong,Tsan Yuk Hospital. Hong Kong,  PRC.

 

Summary of Results:

Compared to the controls, GDM patients were were older, but there were no significant differences in their anthropometric parameters ( Table 1).

Table 1  Maternal characteristics in gestational diabetes mellitus(GDM) and control groups

  GDM(n=97) Controls(n=194) P
Age (years)

32.5±4.9

30.2±5.3

0.001
Weight (kg)

54.0±8.4

52.9±7.8

NS

Height (cm)

154.5±5.8

155.5±5.7

NS

Body Mass index (kg/m2)

22.6±3.2

22.0±2.8

NS

Booking haemoglobin (g/dl)

12.5±1.1

12.3±1.0

NS

3rd trimester haemoglobin (g/dl)

11.7±0.9

11.5±0.9

NS

Mean cell volume (fl)

91.5±5.1

90.4±5.5

NS

Mean cell haemoglobin (pg)

30.6±1.9

30.2±2.1

NS

Mean cell haemoglobin concentration (g/dl)

33.4±0.7

33.4±0.7

NS

Haematocrit (%)

34.8±3.1

34.8±3.1

NS

Post-partum haemoglobin (g/dl)

12.1±1.0

11.8±0.9

0.034
OGTT (mmol/l)

 -

 -

 

fasting

4.5±0.5

4.3±0.4

0.000
2 h

8.9±0.9

6.4±0.9

-

Infant gestational age (week)

38.7±1.5

39.0±1.4

NS

Birthweight (g)

3122±512

3268±439

0.013
Infant body mass index (kg/m2)

12.9±1.2

13.0±1.2

NS

 Results expressed in mean± SD.

In the GDM group, all the parameters of iron status were significantly different with higher serum ferritin and iron concentrations , and transferrin saturation, while the serum transferrin concentration was lower (Table 2).

Table 2  Maternal iron status in gestational diabetes mellitus(GDM) and control groups

 

GDM(N=97)

Controls(n=198)

95% CI for difference

P

Serum ferritin(pmol/l) 47.4 (29.5)

22.5 (21.0)

15.5-34.3

0.0000
Serum iron(umol/l) 14.9 (12.7)

12.6 (11.0)

0.42-4.04

0.0073
Serum transferrin(umol/l) 69.4 (68.5)

74.7 (74.0)

-7.7 to -2.8

0.0000
Transferrin saturation(%) 22.0 (19.5)

17.2 (15.6)

1.9-7.6

0.0004

Results expressed in mean (median). CI, confidence interval.

Analysis by the Mann-Whitney U-test.

For the entire group of GDM and controls, correlation analysis indicated that the OGTT 2-h glucose value, but not the fasting glucose, was positively correlated with serum ferritin concentration and transferrin saturation, and inversely with serum transferrin concentration (Table 3).

Table 3 Correlation (Spearman's rho) between iron parameters with maternal age, body mass index (BMI) and oral glucose tolerance test (OGTT) results

 -

OGTT

Value

>>

>>

 -

 -

 -

 -

 -

 -

Fasting

2-h

Age

BMI

Serum ferritin -0.117

0.1685¶

0.1532**

0.0455

Serum iron -0.0392

0.1152

0.1808**

-0364

Serum transferrin 0.0316

-0.1642¶

-0.0735

-0.0524

Transferrin saturation -0.0390

0.1429*

0.1907***

-0.0200

Analysis based on overall population.

*P<0.05,  ¶ P< 0.02,**P<0.01, *** P=0.0001

Other Findings

Multiple regression analysis was performed with log-transformed values of serum ferritin, iron, transferrin and transferrin saturation, maternal age, weight, BMI, to determine the relationship between these parameters and the OGTT glucose values. Maternal BMI was the only significant determinant of the OGTT fasting glucose value (P=0.0061), while maternal BMI (P= 0.0427) and log-tranformed ferritin concentration (P= 0.0312) were significant determinants of the 2-h glucose.

Author Conclusion:

The results suggest an association between increased iron stores and glucose intolerance at the third trimester in non-anemic women.

Limitations:

  • The increased iron stores in the GDM group could have been the result of increased intake and/or absorption, because the dose of iron prescribed was insufficient to prevent the depletion of iron stores.
  • Although both the GDM and the control groups were of the same ethnic background, a detailed diet history was not taken, and it is possible that differences in their dietary habits or cooking methods contributed to the differences in iron stores.
Funding Source:
University/Hospital: University of Hong Kong, Tsan yuk Hospital
Reviewer Comments:

Case control studies are studies in which patients who already have a certain condition are compared with people who do not. Case control studies are less reliable than cohort studies. Just because there is a statistical relationship between two conditions does not mean that one condition actually caused the other.

The limitations and critique of the study, as stated by the authors appear to be very appropriate.

Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) N/A
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? ???
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) N/A
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? Yes
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) Yes
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? Yes
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? N/A
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? ???
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? N/A
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? ???
  7.6. Were other factors accounted for (measured) that could affect outcomes? ???
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes