FNCE 2023
Session 357. Providing MNT for the Pediatric Type 1 Diabetes Population: What Does the Evidence Show?
Monday, October 9, 8:30 AM - 9:30 AM

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UWL: Association With Outcomes (2009)

Study Design:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
  • Define "frailty" in the Women's Health Initiative Observational Study (WHI-OS) using indicators from widely available instruments that operationalize the characteristics of frailty identified
  • Examine associations between demographics, medical history and behavioral risk factors and baseline and incident frailty after three years of follow-up
  • Determine associations between frailty classification and future risk of death, hospitalizations, hip fractures and activity of daily living (ADL) disability.


Inclusion Criteria:

Women enrolled in the Women's Health Initiative study aged 65-79 years at baseline.

Exclusion Criteria:
  • Age less than 65 years or greater than 79 years
  • Diagnosis of Parkinson's disease
  • Use of medication to treat Parkinson's disease or depression
  • Premenopausal
  • Likely to relocate or die within the three-year follow-up period
  • Enrollment in another clinical trial.
Description of Study Protocol:


Women were recruited for the WHI from 1993 to 1998 from 40 clinical centers in the United States.


Prospective cohort design. Participants completed a validated measure of self-reported physical function, the Rand-36 physical function scale at baseline and at three-year follow-up. Recreational physical activity, unintentional weight loss, depressive symptoms, ADL disability (defined as needing assistance with one or more ADLs) and exhaustion were assessed throughout the study. Demographics, medical history and health behavior characteristics were obtained through self-report at baseline. An annual medical history update was completed by study participants and medical records were reviewed for primary and secondary outcomes in WHI (cardiovascular events, hip fracture, cancer and death).

Blinding used

The use of blinding was not reported.


No intervention was implemented in this study. 

Statistical Analysis

  • Chi-square tests compared baseline demographics, medical history and health behavior characteristics for women classified as frail, intermediate or non-frail
  • A nominal multivariate logistic regression model evaluated frailty at the three-year follow-up for participants not classified as frail at baseline with predictor variables
  • Cox proportional hazards models were used to assess the independent contribution of baseline frailty in predicting hip fractures and death
  • Logistic regression models were used to assess the independent contribution of baseline frailty in predicting ADL disability at three-year follow-up.
Data Collection Summary:

Timing of Measurements

Frailty was classified at baseline and at three-year follow-up using Fried's frailty measure (zero to five). A score of ≥ three was classified as frail, a score of one or two was classified as intermediate and a score of zero was classified as non-frail. The components of the frailty score are listed below:

  • Slowness or weakness measured at baseline and three-year follow-up using the Rand-36 physical function scale. A score in the lowest quartile scored two points on the Fried's frailty measure.
  • Poor endurance or exhaustion measured at baseline and three-year follow-up using the Rand-36 vitality scale. A score in the lowest quartile scored one point on the Fried's frailty measure.
  • Physical activity measured at baseline and three-year follow-up using a detailed physical activity questionnaire assessing frequency and duration of walking and mild, moderate and strenuous activities. Kilocalories per week of energy expenditure was calculated. A score in the lowest quartile scored one point on the Fried's frailty measure.
  • Weight was measured during clinic visits at baseline and at three-year follow-up. Unintentional weight loss of more than 5% in the previous two years scored one point on the Fried's frailty measure.

Demographic, medical history, health behavior characteristics and depressive symptoms were obtained using self-report at baseline.

ADL disability (defined as needing assistance to eat, dress and undress, get in and out of bed and take a bath or shower) was measured at baseline and three-year follow-up.

An annual medical history was taken via mail, phone or at a clinic visit to provide data on significant health events that occurred in the prior year. Data on overnight hospitalizations, hip fractures, cardiovascular events, cancer and deaths was collected. 

Dependent Variables

  • Incident frailty at three-year follow-up
  • ADL disability at three-year follow-up
  • Number of hospitalizations at three-year follow-up
  • Hip fractures at three-year follow-up
  • Death.

Independent Variables

  • Demographics
  • Medical history
  • Health behavior characteristics
  • Depressive symptoms.

Control Variables

 None used

Description of Actual Data Sample:

Initial N

40,657 women

Attrition (final N)

  • All 40,657 women were included in the analysis of baseline characteristics according to baseline frailty classification
  • Of the women free of frailty at baseline (34,038); frailty data was available for 28,181 participants at three-year follow-up
  • Of the 28,181 participants with frailty data at three-year follow-up; information was provided on all of the covariates on 20,767 women.


65-79 years at baseline


White (86%), Black (6.5%), Hispanic (2.5%), American Indian (less than 1%), Asian/Pacific Islander (3%), Unknown (1.5%).

Other relevant demographics



40 clinical centers in the United States


Summary of Results:

Baseline characteristics according to baseline frailty:

  • 6,619 women (16.3% of participants) were classified as frail at baseline
  • Black women and Hispanic women were more likely to be classified as frail than White or Asian/Pacific Islander women
  • Scores on the six-item Center for Epidemiologic Studies Depression Scale were significantly associated with baseline frailty
  • Number of reported falls in the previous 12 months was significantly associated with baseline frailty.
Baseline Characteristic Not Frail (N=22,521) Frail (N=6,619) P- value
Age greater than 70 years 11,131 (49.4%) 4,080 (61.6%) <0.001
Family Income ≤$20,000 3,313 (16.1%) 2,104 (35.0%) <0.001
Education ≤ High school/general equivalency degree 4,395 (19.7%) 2,239 (34.1%) <0.001
BMI ≥30.0kg/m² 3,267 (14.7%) 2,877 (44.1%) <0.001
Coronary heart disease 1,275 (5.8%) 1,111(17.2%) <0.001
Congestive heart failure 132 (0.6%) 232 (3.5%) <0.001
Stroke 250 (1.1%) 290 (4.4%) <0.001
Diabetes 577 (2.6%) 651 (9.9%) <0.001
Hypertension 9,630 (43.3%) 3,972 (60.8%) <0.001
Arthritis 10,730 (48.1%) 5,128 (78.2%) <0.001
Cancer 3,140 (14.1%) 1,183 (18.1%) <0.001
Chronic obstructive pulmonary disease 558 (2.5%) 635 (9.8%) <0.001
Reported at least two comorbid disease conditions 10,669 (47%) 5,148 (78%) <0.001


Baseline characteristics relating to incident frailty at three-year follow-up:

  • Of the 28,181 women who were free of frailty at baseline and who provided frailty information at three-year follow-up, 4,158 (14.8%) were classified as frail
  • Black women were less likely to develop incident frailty at three-year follow-up after accounting for other covariates than white women
  • Age, education, income, smoking, moderate alcohol intake, hormone use, history of coronary heart disease, stroke, hip fracture, COPD, diabetes and arthritis were all significantly related to incident frailty.
  • Underweight participants (BMI less than 18.5) were at higher risk of frailty than normal weight participants (OR equal to 1.65, 95% CI equal to 1.11-2.45) similar to the risk for overweight participants (BMI 25.0-29.9)
  • The risk of frailty for obese participants (BMI greater than 30.0) was significant higher than normal weight participants (OR equal to 3.95, 95% CI equal to 3.50-4.47).

 Baseline frailty relating to health and functional status at three-year follow-up:

  • Baseline frailty was strongly and significantly associated with ADL disability at three-year follow-up, higher mean number of hospitalizations, hip fractures and death
  • Odds ratios adjusted for age, ethnicity, education and income showed that baseline frailty increased the risk of these outcomes by about two to five times
  • Multivariate adjustment diminished the magnitude of the associations between baseline frailty and each outcome, but in every case, the odds ratios remained significantly elevated
  • Intermediate frailty was a statistically significant, although more modest, predictor of all four health outcomes.

Intermediate Frailty

OR (95% CI)


OR (95% CI)

ADL disability at three-year follow-up partially* adjusted

2.16 (1.79-2.60) 5.44 (4.54-6.52)
ADL Disability at three-year follow-up fully adjusted 1.64 (1.31-2.04) 3.15 (2.47-4.02)

Average no hospitalizations per year during follow-up partially* adjusted

less than 0.5

≥ 0.5


1.32 (1.26-1.39)

1.77 (1.62-1.93)




Average no hospitalizations per year during follow-up fully adjusted

less than 0.5

greater than 0.5


1.17 (1.10-1.25)

1.30 (1.17-1.45)




Hip fracture partially* adjusted 1.43 (1.15-1.77) 1.74 (1.37-2.22) 
Hip fracture fully adjusted 1.31 (1.00-1.71)  1.57 (1.11-2.20) 
Death partially* adjusted 1.38 (1.25-1.52)  2.45 (2.21-2.72) 
Death fully adjusted 1.25 (1.11-1.41)  1.71 (1.48-1.97) 

 *adjusted for age, ethnicity, education and income only

Author Conclusion:

A multi-component measure of frailty was found to be strongly and independently associated with risk of death, hip fracture, disability and hospitalization after adjusting for demographic variables, health risk factors, ADL disability and comorbid conditions.

Funding Source:
Government: The Women's Heart Institute Project Office at the National Heart, Lung and Blood Institute
Reviewer Comments:
  • Details of the study design, recruitment and data collection methods were published in earlier papers. To avoid duplicity, the authors reported limited details in this paper.
  • Data was unavailable on a number of subjects at three-year follow-up, reason for attrition not known for many subjects.
  • Study conducted in older women, extent to which data can be generalized to men is unknown.
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.) 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? 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? 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
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? No
  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
5. Was blinding used to prevent introduction of bias? ???
  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? ???
  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? 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? Yes
  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? N/A
  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)? 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