CD: Nutritional Adequacy (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To examine the association of the grade of villous atrophy with the nutritional status in newly diagnosed celiac disease patients.
Inclusion Criteria:
Newly diagnosed celiac disease patients.  Diagnosis was based on the presence of partial, subtotal or total villous atrophy of the duodenal mucosa before the introduction of a gluten-free diet.
Exclusion Criteria:
One patient excluded from analysis of dietary intake because of incomplete food records.
Description of Study Protocol:

Recruitment

All newly diagnosed celiac disease patients from Kuopio University Hospital were recruited for an intervention study examining oat consumption from November 1988 to December 1990.

Design

Randomized Controlled Trial.

Blinding used (if applicable)

Pathologist conducted histopathologic exams without knowledge of the clinical state of the patient.  Investigator also measured histomorphometrically the ratio of the perimeter area to lamina propria area of the same biopsy specimens without knowledge of the patient's clinical state.

Intervention (if applicable)

Gluten-free diet for 1 year, with or without oats.

Statistical Analysis

Results for continuous variables given as the arithmetic mean +/- SD and range.  The results for non-continuous variables are given as the frequency and the percentage.  Parametric tests were used when applicable, otherwise nonparametric tests were used.  The association between the nutritional status of the newly diagnosed celiac disease patients and their grade of villous atrophy was tested by using ANOVA or the Kruskal-Wallis test between groups.  Also, ANOVA standardized for sex was used to test the association between nutritional status and grade of villous atrophy.  Multiple comparison tests and distribution-free multiple comparisons based on previous rank sums test were used after ANOVA and Kruskal-Wallis tests as secondary analyses.  The differences in the frequency or proportion of the categorized variables were analyzed by chi-square test, and the distribution of abnormal laboratory values by the grade of villous atrophy was checked by the nonparametric chi-square test.  The associations between the variables of interest were assessed by non-parametric (Spearman) correlations.  The Wilcoxon test was used in comparisons of continuous variables between the time points (before and after the celiac disease diet). 

Data Collection Summary:

Timing of Measurements

Measurements made at diagnosis and after treatment with gluten-free diet.

Dependent Variables

  • Endoscopic biopsy specimens were obtained at the duodenal bulb and the duodenal mucosa at 5-cm intervals thereafter as far as possible; 2 specimens at each level were taken by jumbo forceps.  Degree of crypt hyperplastic villous atrophy was graded as normal (0), partial (I), subtotal (II), and total (III).
  • Ratio of perimeter area to lamina propria area measured using Quantimet 570 image analyzer on 3 random fields from each biopsy specimen
  • Structured questionnaire collected data on symptoms and signs related to celiac disease and their duration
  • Body weight determined with subject standing barefoot on digital scale and wearing light clothing
  • Height without shoes measured with a wall-mounted stadiometer
  • Skinfold thicknesses measured on the nondominant side of the body using Harpenden skinfold calipers at the biceps, triceps, subscapular and suprailiac sites and mean of 6 measurements at each site calculated
  • Blood samples taken after overnight fast and blood hemoglobin, serum total protein, serum albumin, iron, ferritin, transferrin, vitamin B-12, calcium, magnesium, alkaline phosphatase, and erythrocyte folic acid determined by routine clinical laboratory methods
  • Serum zinc determined through atomic-absorption spectrophotometry
  • Serum vitamin D metabolite (calcidol) assayed as described by Parviainen et al
  • Vitamins A and E determined by HPLC with UV detection
  • Antigliadin antibodies (IgA-AGA) measured by enzyme immunoassay
  • Antireticulin antibodies (IgA-ARA) determined by indirect immunofluorescence

Independent Variables

  • Gluten-free diet:  4 day food records kept by all subjects with amounts determined using household measures.  Nutrient intake calculated using NUTRICA computer program.  Nutrient content data on the gluten-free products used were collected from manufacturers and added to database.  From original study, analysis of oats for gluten content was performed by National Food Administration in Sweden. 

Control Variables

 

Description of Actual Data Sample:

Initial N: 40 adult patients, 12 men, 28 women

Attrition (final N):  6 patients withdrew from follow-up.

Age:  Men: mean age 47 +/- 12 years (24 - 65 years), women:  mean age 44 +/- 13 years (18 - 62 years).

Ethnicity:  Not mentioned. 

Other relevant demographics:  Duration of celiac disease related symptoms:  men:  15.8 +/- 19.2 years (0 - 51 years), women:  13.1 +/- 18.4 years (0 - 57 years). 

Anthropometrics 

Location:  Finland

 

Summary of Results:

 

Variable Abnormal Value Partial (n=5) Subtotal (n=17)

Total (n=15)

Hemoglobin-Men <135 g/L 0 3 0
Hemoglobin-Women <125 g/L 0 (0) 4 (41) 5 (33)
Serum vit B-12 <150 pmol/L 0 4 (24) 2 (13)
RBC folate <300 nmol/L 1 (20) 4 (24) 9 (60)
Serum ferritin-men <25 ug/L 0 2 2
Serum ferritin-women <12 ug/L 2 (40) 1 (18) 6 (53)
Serum iron-men <14 umol/L 0 2 1
Serum iron-women <13 umol/L 2 (40) 6 (47) 4 (33)
Serum protein <64 g/L 0 1 (6) 0
Serum zinc <13 umol/L 1 (20) 9 (53) 9 (60)
Serum vit A <1 umol/L

1 (20)

1 (6)

3 (20)

Serum ferritin & RBC folate

0

1 (6)

7 (47)

Other Findings

At the time of diagnosis, the mean histomorphometric index of the patients was 0.018 +/- 0.003 in patients with partial villous atrophy, 0.015 +/- 0.002 in those with subtotal villous atrophy, and 0.013 +/- 0.002 in patients with total villous atrophy (P = 0.004 for trend).

IgA ARA values at diagnosis were abnormal in 5 of 8 patients with partial villous atrophy, 12 of 17 with subtotal villous atrophy, and 13 of 15 patients with total villous atrophy (P = 0.53).

IgA AGA values were abnormal in 5 of 8 patients with partial villous atrophy, 13 of 17 with subtotal villous atrophy, and 12 of 15 with total villous atrophy (P = 0.27).

Anthropometric results did not differ among the 3 atrophy groups, but serum ferritin (P < 0.05) and erythrocyte folate (P < 0.05) were lower in patients with total villous atrophy than in the other groups.

Most of the abnormal biochemical values were normalized during 1 year of gluten-free diet.  Villous atrophy improved in all patients within 12 months of follow-up:  only 2 patients had subtotal villous atrophy (mean histomorphometric index of 0.016 +/- 0.003), 29 patients had partial villous atrophy (0.019 +/- 0.002) and 3 patients had normal villous architecture (0.022 +/- 0.002).  The severity of villous atrophy did not differ between the oat and control groups.

Nutrient intakes, except for thiamine, anthropometric measurements, and biochemical measurements did not differ between the groups with and without oats.

Author Conclusion:
In conclusion, newly diagnosed celiac patients with different grades of villous atrophy did not differ from each other with respect to height, weight, BMI, fat mass, or most of the laboratory values reflecting nutritional status.  The onyl exceptions were serum ferritin and erythrocyte folate concentrations, which were lower in patients with total villous atrophy than in those with partial or subtotal atrophy.
Funding Source:
Not-for-profit
1
Foundation associated with industry:
Reviewer Comments:
6 out of 40 withdrew, all from Oat group.
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? ???
  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? ???
  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? ???
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? N/A
  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? ???
  4.1. Were follow-up methods described and the same for all groups? Yes
  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%.) ???
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? No
  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? Yes
  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.) Yes
  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? Yes
  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? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  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)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? N/A
  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