EAL

NSA: Serum Proteins (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this study was to determine the reliability of sex-hormone-binding globulin (SHBG) as a nutritional index in patients with anorexia nervosa.

Inclusion Criteria:

Patients with anorexia nervosa
Healthy control subjects with:
- Documented ovulatory cycles
- BMI within 15th and 85th percentiles of the standards for white females of the same age.

Exclusion Criteria:

Description of Study Protocol:

Recruitment

Not specified.

Design

Serum transferin, prealbumin, retinol binding protein (RBP), ceruloplasmin and SHBG concentrations measured in women with anorexia nervosa before and after weight gain (period of 40±5.0 days), compared to the same values measured in healthy controls on the eighth day of a normal menstrual cycle.

Intervention

For treatment group, intervention involved hospital admission with isolation, psychotherapy and refeeding. Free food intake for all patients.

Statistical Analysis

Mann-Whitney U test to compare patients and control subjects
Wilcoxon signed-rank T-test to compare data before and after weight gain
Linear-regression analysis to test correlations.

Data Collection Summary:

Timing of Measurements

Intervention subjects: Samples drawn on first day of hospital admission (before weight gain) and on last day in the hospital (after weight gain)
Control subjects: Samples drawn on the eighth day of a normal menstrual cycle.

One set of analyses designed to answer unstated question: How are protein-energy malnutrition (PEM) indexes and sex steroid and thyroid hormones different among:

Patients with anorexia nervosa before weight gain
Patients with anorexia nervosa after weight gain
Control subjects.

Dependent Variables

SHBG (mg per L)
RBP (mg per L)
Prealbumin (mg per L)
Transferrin (g per L)
Ceruloplasmin (mg per L)
Testosterone (nmol per L)

Independent Variables

Estradiol (pmol per L)
Free thyroxine (pmol per L)
Triiodothyronine (nmol per L)
Anorexic status (anorectic before and after weight gain or control)

Second set of analyses designed to answer unstated question: How are PEM indexes correlated with each other (including SHBG) and with BMI?

Dependent Variables

SHBG (mg per L)
RBP (mg per L)
Prealbumin (mg per L)
Transferrin (g per L)
Ceruloplasmin (mg per L)
BMI (kg/m²).

Independent Variables

SHBG (mg per L)
RBP (mg per L)
Prealbumin (mg per L)
Transferrin (g per L)
Ceruloplasmin (mg per L)
BMI (kg/m²).

Third set of analyses designed to answer unstated question: How is change in SHBG concentration during the weight gain period correlated with change in BMI and changes in sex steroid and thyroid hormones?

Dependent Variables

Change in SHBG (mg per L).

Independent Variables

Change in BMI (kg/m²)
Change in testosterone (nmol per L)
Change in estradiol (pmol per L)
Change in free thyroxine (pmol per L)
Change in triiodothyronine (nmol per L).

Description of Actual Data Sample:

Initial N: 24 (12 females in the treatment group, 12 females in the control group)
Attrition (final N): Same.

Age

Treatment group: Aged 16 to 31 years
Control group: Aged 18 to 33 years.

Anthropometrics

BMI of treatment group:
- 13.8±0.5 (before weight gain)
- 17.1±0.2 (after weight gain)
BMI of control group: 21.4±0.6.

Location

France.

Summary of Results:

	Treatment Group		Control Group (Mean ± Standard Error)
Variables	Before Weight Gain (Mean ± Standard Error)	After Weight Gain (Mean ± Standard Error)	Control Group (Mean ± Standard Error)
SHBG (mg per L)	7.0±0.7^a	3.8±0.5^b	3.1±0.4
RBP (mg per L)	39±4	50±4^a	35±2
Prealbumin (mg per L)	250±20	300±10^c	270±10
Transferrin (g per L)	2.16±0.21	3.26±0.26^bd	2.55±0.11
Ceruloplasmin (mg per L)	230±20	320±40^cd	230±10

^aSignificantly different from control subjects, P<0.01.

^bSignificantly different from before weight gain, P<0.01.

^cSignificantly different from before weight gain, P<0.05.

^dSignificantly different from control subjects, P<0.05.

	Treatment Group		Control Group (Mean ± Standard Error)
Variables	Before Weight Gain (Mean ± Standard Error)	After Weight Gain (Mean ± Standard Error)	Control Group (Mean ± Standard Error)
Testosterone (nmol per L)	1.25±0.14^a	1.18±0.14^a	1.66±0.14
Estradiol (pmol per L)	73.4±1.1^b	77.0±0.7^b	176.2±22.0
Free thyroxine (pmol per L)	10.5±0.6	9.8±1.7	12.1±1.2
Triiodothyronine (nmol per L)	1.6±0.1^a	2.2±0.2^c	2.1±0.1

^aSignificantly different from control subjects, P<0.05.

^bSignificantly different from before control subjects, P<0.01.

^cSignificantly different from before weight gain, P<0.05.

Other Findings

RBP and prealbumin were significantly and positively correlated in patients before weight gain (R=0.90; P<0.001) and in control subjects (R=0.89; P<0.001)
No significant correlation was found between:
- SHBG concentrations and BMI before or after weight gain
- SHBG concentrations and PEM indexes before or after weight gain
- PEM indexes and BMI before or after weight gain
- Change in SHBG concentrations and change in BMI
- Change in SHBG concentrations and change in testosterone, estradiol, and free thyroxin concentrations.

Author Conclusion:

The changes of SHBG concentrations that we found are not explained by modifications of the sex-steroid milieu or thyroidal status. During weight gain, SHBG decreased and reached the normal range, whereas there was no significant change in testosterone and estradiol concentrations. SHBG concentrations seem to depend on dietary intake or energy balance rather than body weight. The normal values of binding proteins that we found before weight gain are likely to be related to the type of malnutrition (marasmus).

Taken together, the increase of serum SHBG concentrations and the normality of PEM indexes that the patients with anorexia nervosa displayed before weight gain make SHBG determination a reliable index of nutritional status in this type of eating disorder.

Funding Source:

University/Hospital:

Departments of Endocrinology and Biochemistry, Purpan Medical School, Toulouse, France

Reviewer Comments:

With a small sample size, the fact that findings were statistically significant indicates a rather large effect. Results of power analysis not given; therefore, it is unsure if nonsignificant findings may be related to small sample size. It may have been useful to see the results of linear regression analyses in a table format. Details of sample were sparse; it is not clear how members of the control group were recruited. It is also unclear about other characteristics of the two groups that might have made them similar or different (health status of intervention group and mean age of groups, for example). It is also unclear how many subjects started vs. how many finished the study. More details might have eliminated concerns about bias. This study does suggest that SHBG may be a useful indicator of nutrition status in patients with anorexia nervosa when other indicators fall within the normal range.

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
	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
	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
	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)	N/A
	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.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	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
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
	1.3.	Were the target population and setting specified?	Yes
	2.	Was the selection of study subjects/patients free from bias?	???
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?	No
	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?	No
	2.2.	Were criteria applied equally to all study groups?	???
	2.2.	Were criteria applied equally to all study groups?	???
	2.3.	Were health, demographics, and other characteristics of subjects described?	No
	2.3.	Were health, demographics, and other characteristics of subjects described?	No
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
	3.	Were study groups comparable?	???
3.	Were study groups comparable?		???
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	No
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	No
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	???
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	???
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	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
	3.4.	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
	3.5.	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
	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?	No
4.	Was method of handling withdrawals described?		No
	4.1.	Were follow-up methods described and the same for all groups?	No
	4.1.	Were follow-up methods described and the same for all groups?	No
	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%.)	No
	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%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	???
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	???
	4.4.	Were reasons for withdrawals similar across groups?	???
	4.4.	Were reasons for withdrawals similar across groups?	???
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	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?	No
5.	Was blinding used to prevent introduction of bias?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	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.)	No
	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.)	No
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	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
	5.4.	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
	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.	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
	6.1.	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
	6.2.	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?	Yes
	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
	6.4.	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?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	No
	6.6.	Were extra or unplanned treatments described?	No
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	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
	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.	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
	7.1.	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
	7.2.	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
	7.3.	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
	7.4.	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
	7.5.	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
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	N/A
	7.7.	Were the measurements conducted consistently across groups?	N/A
	8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?	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
	8.1.	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
	8.2.	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
	8.3.	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
	8.4.	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)?	???
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	???
	8.6.	Was clinical significance as well as statistical significance reported?	No
	8.6.	Was clinical significance as well as statistical significance reported?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
	9.	Are conclusions supported by results with biases and limitations taken into consideration?	???
9.	Are conclusions supported by results with biases and limitations taken into consideration?		???
	9.1.	Is there a discussion of findings?	Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	No
	9.2.	Are biases and study limitations identified and discussed?	No
	10.	Is bias due to study's funding or sponsorship unlikely?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes