GDM: Abnormal Glucose Tolerance During Pregnancy (2008)

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

The research focused on the relationship between the number of abnormal glucose values obtained in the diagnostic oral GTT and the outcome of pregnancy.

Inclusion Criteria:
  • Evaluated the data of 152 women with gestational diabetes, who were consecutively admitted to the diabetes department from March 1997 to March 2000 for an oral GTT because of increased risk for GDM, including a family history of diabetes, previous gestational diabetes, increased body weight, age > 30 years, large for gestational age infants or an adverse obstetric outcome in previous pregnancies.
  • Women gave informed consent to the evaluation of their data after the purpose of the study was explained to them. 
  • Data were compared to those of an age-and BMI-matched control group (304 women) who revealed normal glucose values at the oral GTT.  
Exclusion Criteria:
Exclusion criteria was not detailed.
Description of Study Protocol:

Recruitment : Strategy was not detailed

Design : Cohort

Blinding used:  not applicable 

Intervention

  1. Therapy was based on dietary recommendations when the 2 h pp glucose levels exceeded 6.6 mmol/l insulin therapy was started
  2. Insulin was administered as an intermediate insulin once or twice daily.
  3. Treatment targets were: Fasting glucose values lower than 5.0 mmol/l and 2h pp glucose values lower than 6.6 mmol/l.
  4. Fasting and pp glucose controls, as well as clinical controls, were performed at weekly intervals or, in women under insulin therapy, by glucose-self-monitoring.
  5. Women with one increased glucose value at the GTT underwent weekly controls and obtained the same dietary instructions as well as insulin administration procedures as women with two or more abnormal glucose values and thus manifested GDM.

Statistical Analysis 

  • Continuous variables were compared by Student’s t test or Wilcoxon U-test.
  • A P-value <0.05 was considered statistically significant.
  • Data were characterized by means and standard deviations as well as the range values.
Data Collection Summary:

Timing of Measurements

  1. The oral GTT was performed in the morning after a 12h overnight fast and 3 days of 150-200 g (minimum) carbohydrate diet.
  2. The blood pressure measurements were taken by a standard sphygmomanometer, with patients resting for 5-10 min in the supine position.

Dependent Variables

  • Diagnosis and therapy in relationship to GTT values 
  • Venous plasma glucose values were determined by a hexokinase method (Hitachi 747, Hoffman laRoche, Basle, Switzerland).
  • GDM-diagnosis relied on an oral 100g GTT. GDM was diagnosed if two or more values of the GTT equaled or exceeded the threshold level proposed by Carpenter and Coustan and adopted by the Fourth International Workshop on GDM, with fasting glucose <5.2 mmol/l; 1h pp<9.9 mmol/l; 2h pp <8.5 mmol/l; 3 h pp <7.7 mmol/l .
  • oGTT - weeks of gestation
  • oGTT - glucose (fasting, 1 h, 2h, 3h)
  • Weight gain (kg)
  • Duration of pregnancy
  • Outcome of pregnancy in women: Poly-hydramnion, Urinary tract infection, Hypertension - was defined by blood pressure values of systolic >140 mmHg and diastolic >90mmHg, Caesarean section, Shoulder dystocia
  • Neonatal outcome: Duration of pregnancy, Premature birth, 5 min apgar <7, Birth weight, Large Gestational Age - was defined as a weight above the 90th percentile, Macrosomy- was defined as infants > 4000 grams, Small Gestational Age - was defined as a weight below the 10th percentile, Neonatal hypoglycemia - was defined as a glucose value<1.7 mmol/l, Respiratory complication, Malformation, Increased bilirubin-was defined as a value >12 mg/dl, Phototherapy

Independent Variables

  • Dietary regimen
  • Dietary regimen + insulin

Control Variables

  • Maternal age (years)
  • Body weight (kg) at beginning of pregnancy
  • BMI(kg/m2) – at begin of pregnancy; at diagnosis; percent with BMI > kg/m2
  • Parity - primigravidae, multigravidae
  • Positive history of diabetes
  • Country of origin - Austrian, Turkish, former Yugoslavia, Other European countries  

 

Description of Actual Data Sample:

Initial N: 152 GDM and 152 Control subjects

Attrition (final N):  as above

Age: See Table 1

Ethnicity: Caucasian women

Other relevant demographics:

Anthropometrics

Location: Department of Internal Medicine and Department of Obstetrics and Gynecology, University Hospital, Innsbruck, Austria.

Summary of Results:

Compared with the age-and BMI-matched control group women with one or more abnormal GTT values revealed a significantly higher percentage of a positive family history of diabetes (16.4% in the control group and 24.4% in the GDM group; P<0.05, See Table 1a).

 Table 1a:  Patient’s characteristics

 

 

 

 

 

Gestational Diabetes

Control group

P-value

Maternal age (years)

30±6

25±5

0.094

Body weight (kg) at the begin of pregnancy

66±16

66±13

0.790

BMI (kg/m2 ) at the begin of pregnancy

24.8±5.6

23.9±4.3

0.205

BMI (kg/m2 ) at diagnosis

28.1±0.5

27.3±4.3

0.160

% with BMI>25 kg/m2

34.5

32.2

0.670

Parity

2.0±1.2

1.9±1.0

0.762

Primigravidae (%)

43.4

43.8

0.650

Multigravidae (%)

56.6

56.3

0.742

Positive family history of diabetes (%)

24.4

16.4

0.050

Austrian (%)

63.8

65.9

0.092

Turkish (%)

19.1

18.2

0.240

Former Yugoslavia (%)

13.2

13.9

0.780

Other European countries (%)

3.9

2.9

0.340

Women with three abnormal glucose values were with a mean age of 33+ 6 years the oldest subgroup, and BMI and parity was highest in the group of patients with three abnormal GTT values. Premature births were 12.5% in this group, with 39.1% caesarean sections and 48% spontaneous births (Table 1b).

Table 1b: Patient’s characteristics in relation to the number of increased glucose values obtained during the oral GTT. 

 

 

 

 

 

 

 

 

One increased value

(n=66)

Controls

 

 

(n=132)

Two increased values

(n=62)

Controls

 

 

(n=124)

Three increased values

(n=24)

Controls

 

 

(n=48)

Age(years)

29±6

28±6

30±5

29±5

33±6

31±5

Body weight(kg) at the begin of pregnancy

64±15

64±12

64±12

64±11

79±21

75±12

BMI(kg/m2) at begin pregnancy

23.9±5.3

23.2±3.9

24.1±4.4

23.3±3.5

29.1±7.0

27.3±5.1

BMI(kg/m2) at diagnosis

27.1±4.9

26.4±4.0

27.5±3.9

26.7±3.5

32.1±5.4

30.8±4.7

% with BMI>25 kg/m2

30.2

27.2

26.2

25.6

66.7

62.5

Parity

1.9±1.1

1.9±0.9

1.9±1.2

1.9±1.1

2.5±1.5

2.2±1.2

Primigravidae

(%)

45.5

45.4

43.5

44.4

37.5

37.2

Multigravidae

(%)

54.5

54.5

56.5

55.6

62.5

62.5

Insulin therapy was required in 83.3% of all women with three abnormal glucose values, in 65% of the women with two abnormal glucose values and in 32.85 of the women with only one abnormal GTT value (SeeTable 2).

Table 2 Diagnosis and therapy in relation to the number of increased GTT values 

 

 

 

 

 

 

 

 

One increased value

(n=66)

Controls

 

 

(n=132)

Two increased values

(n=62)

Controls

 

 

(n=124)

Three increased values

(n=24)

Controls

 

 

(n=48)

oGTT(weeks of gestation)

29.2±6.1

27.3±4.5

29.3±5.4

28.7±4.7

28.4±6.1

28.2±4.6

oGTT fasting glucose(mmol)(range)

4.4

(4.1-4.8)

4.1

(3.9-4.4)

4.7(4.3-5.1)

4.0

(3.8-4.3)

5.6

(5.3-6.1)

4.1

(4.0-4.5)

oGTT 1 h glucose(mmol)(range)

10.0

(8.8-11.0)

7.2

(6.2-8.1)

11.0(10.2-11.4)

7.1

(6.2-8.4)

11.9 (11.2-12.7)

7.5

(6.4-8.6)

oGTT 2 h glucose(mmol)(range)

8.3

(7.3-8.8)

6.1

(5.5-6.6)

9.2

(8.6-10.0)

6.2

(5.3-7.0)

10.1

(9.2-11.2)

6.3

(5.6-6.8)

oGTT 3 h glucose(mmol)(range)

7.5

(6.9-8.2)

5.1

(4.7-5.7)

8.3

(7.6-9.1)

5.4

(5.0-6.1)

9.1

(8.5-10.3)

5.4

(5.1-6.4)

Dietary regimen (%)

32.8

-

35.0

-

16.7

-

+ Insulin (%)

32.8

-

65.0

-

83.3

-

Weight gain(kg)

(range)

13.0

(5.5-10)

15

(11-19)

12

(9-16)

10

(5-15)

15

(11-18)

14.5

(9-11)

Duration of pregnancy (weeks)

39.2±2.5

39.7± 2.1

38.9±2.1

39.4±2.1)

39.2±1.6)

39.4±1.7)

 Compared with the age-and BMI-matched controls, hypertension was more frequent in all subgroups with abnormal GTT values and reached 20% in the group of women with three abnormal glucose values( SeeTable 3).

Table 3

Outcome of pregnancy in women with abnormal GTT values and in non-diabetic women-associated to the member of increased glucose values during the GTT 

 

 

 

 

 

 

 

 

 

 

All GDM

(n=

152)

All Controls (n=304)

One

increased

value

(n=66)

Controls

(n=132)

Two

increased

values

(n=62)

Control

(n=124)

Three

Increased values

(n=24)

Controls

(n=48)

Poly-hydramnion

6.6

5.6

6.1

5.1

8.1

5.6

4.2

4.2

Urinary

tract infection (%)

2.6

4.3

3.0

5.3

3.2

3.2

0

4.2

Hyper-tension(%)

10.5

5.6

12.1

5.3

4.8

2.4

20.8

14.6

Caesarean section(%)

32.7

20.1

32.3

16.8

30.6

24.2

39.1

18.8

Shoulder Dystocia(%)

2.0

0

0

0

3.3

0

4.2

0

  

The percentage of premature birth was significantly increased in women with abnormal GTT values (13.8%) compared to the non-diabetic control group(9,5%; P<0.048). Table 4).

Table 4:  Neonatal outcome in relation to the number of abnormal GTT Values

 

 

 

 

 

 

 

 

 

 

 

All GDM

(n=

152)

All Controls (n=304)

One

increased

value

(n=66)

Controls

(n=132)

Two

increased

values

(n=62)

Control

(n=124)

Three

Increased values

(n=24)

Controls

(n=48)

Duration of pregnancy

(week) (range)

39.6 3

 

(38.1-40.4)

40.0

 

(38.7-40.8)

39.8

 

(38.6- 40.5)

40.3

 

(38.9-40.1)

39.3

 

(37.8- 40.2)

39.7

 

(38.5-40.8)

39.4

 

(38.3- 40.4)

39.6

 

(38.6-40.4)

Premature birth(%)

13.8

9.5

13.6

9.1

14.5

10.5

12.5

 

8.3

5 min apgar<7(%)

0.7

0.3

1.5

0.8

0

0

0

0

Birth weight(g) (range)

3370 (3000-3800)   

3440(3080-3750)   

3250(3000-3800)   

3410(3000-3610)   

3350(2970-3650)   

3420(2970-3690)   

3830

(3349-4150)

3620(3260-3850)   

LGA(%)

20.7

14.9

16.9

15.2

14.8

11.5

45.8

22.9

Marcrosomy

(%)

12.6

9.2

10.8

9.1

7.3

6.5

33.3

14.6

SGA(%)

7.3

7.0

7.7

5.3

9.0

8.2

6.3

4.2

Neonatal hypo-glycaemia(%)

3.9

1.0

6.1

1.5

0

0

8.3

2.1

Respiratory complications(%)

2.0

3.3

3.0

3.8

1.6

3.2

0

2.1

Malformation(%)

6.6

5.6

7.6

6.1

6.5

5.6

4.2

4.2

Increased bilirubin(%)

8.6

8.6

6.1

10.6

9.7

8.9

12.5

2.1

Phototherapy (%)

5.3

3.9

4.5

3.0

6.5

6.5

4.2

0

Other Findings

 

 

 

Author Conclusion:

Conclusions

  1. The results showed that women with three abnormal GTT values were at an overall increased risk with respect to the feto-maternal outcome of pregnancy.
  2. Compared to the age– and BMI-matched control group the percentage of women with hypertension was increased in those with one, two and three abnormal GTT values.
  3. The percentage of LGA and macrosomic infants was significantly increased only in women with three abnormal GTT values.

       Limitations: 

  1. The increased rate of LGA infants in the Control group could be due to the fact that the assignment to this non-diabetic group was based on normal glucose values in the oral glucose tolerance test. The determination of cord blood insulin levels might help to perform a stricter risk stratification.
  2. Because perinatal and long-term health risks of mother and child increased in relation to the severity of maternal hyperglycemia also women with only one abnormal GTT value seemed to need further control and treatment procedures. Larger clinical trials will be necessary to improve and confirm the value of the diagnostic criteria, including “gestational impaired glucose tolerance”, and to optimize therapeutic and control regimes.
Funding Source:
Reviewer Comments:

Analytical longitudinal surveys refer to what epidemiologists term prospective or cohort studies. A Cohort Study is a study in which patients who presently have a certain condition and/or receive a particular treatment are followed over time and compared with another group who are not affected by the condition under investigation. Studies of this kind provide a better opportunity than one time cross sectional studies to examine whether certain behaviors do in fact lead to (or cause) the disease.

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) Yes
  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? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
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.) N/A
  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? N/A
  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? N/A
  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? Yes
  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? Yes
  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? Yes
  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? Yes
  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? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  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)? Yes
  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