EAL

Weight Management

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate baseline risk factors for coronary artery disease in patients with type 2 diabetes.

Inclusion Criteria:

1. Type 2 diabetes as diagnosed by fasting plasma glucose concentration >6 mmol/L (measured on 2 occasions).

2. 25-65 years of age

Exclusion Criteria:

1. MI within the past year.

2. Current angina or heart failure

3. Accelerated hypertension

4. Proliferative or preproliferative retinopathy

5. Renal failure with a plasma creatinine concentration >175 µmol/L

6. Other life threatening disease such as cancer

7. Taking steroid medications

8. An occupation precluding insulin treatment

9. Language difficulties

10. Ketonuria >3 mmol/L

Description of Study Protocol:

Recruitment:

Subjects were white with a recent diagnosis of diabetes

Design

All subjects were treated with diet for the first 3 months followed by random assignment to treatment (different medications not referred to in this report).
Subjects were assessed at baseline for:

a. height, waist circumference, hip circumference measured

b. smoking status and usual exercise determined by questionnaire

c. retinopathy assessed by modified Wisconsin grading of 4 color photographs of each eye taken at 30° to the horizontal

d. blood pressure measured at 2 and 9 months after diagnosis of diabetes (hypertension defined as systolic >160 and diastolic >90 mm Hg or on antihypertensive medications)

e. biochemical measurements at 3 months after following diet fasting plasma glucose, A1C, LDL-chol, HDL-chol, insulin

subjects were seen every 3 months in the clinics and clinically important events were noted. Two independent doctors determined whether endpoint outcomes were reached.

Blinding Used:

Two independent doctors who assessed patients for outcomes received full information on the patients but without details of treatment.

Intervention:

Not applicable.

Statistical analysis:

Multivariate selection of risk factors was done by a stepwise procedure after adjustment for age and sex

Data Collection Summary:

Timing of Measurements

Assessed for baseline risk factors after initial treatment by diet for 3 months.

Dependent Variables

Three aggregate endpoints evaluated:

Coronary artery disease: fatal or non-fatal MI or clinical angina with confirmatory abnormal EKG
Fatal or non-fatal MI
Fatal MI.

Independent Variables

LDL
HDL
triglyderides
HA1C
Systolic blood pressure
Fasting blood glucose
smoking
height
weight
waist circumference
amount of exercise

Control Variables

Description of Actual Data Sample:

Initial N:

Of the 7,108 subjects recruited for the United Kingdom Prospective Diabete study, 28% were excluded based on study criteria. Additional exclusions were made for the analysis in this study, including failure to complete initial diet treatment, and evidence of CVD. Complete data was available for 2,693 white patients who had no previous indication of disease related to atheroma.
Men who were included in the United Kingdom Prospective Diabetes Study but were excluded from the analysis in this study due to previous CVD were older, had higher systolic BP, were more likely to be hypertensive, and more likely to be smoker. Excluded women were older and had higher systolic BP.
Sufficient data were available from 3055 patients for the final Cox model analysis

Attrition (Final N): See above

Age: Men: 52 +/- 9 years, Women 53 +/- 9 years

Ethnicity: Not reported

Other relevant demographics:

Anthropometrics:

Location: 23 centers in the United Kingdom

Summary of Results:

Baseline demographic data:

Measure	Men	Women
N	1564	1129
Age, yr	52±9	53±9
BMI	27.1±4.7	29.4±6.4
Waist:hip ratio	0.95±0.06	0.87±0.08
Blood pressure Systolic, mm Hg	133±18	139±20
Diastolic, mm Hg	82±10	83±10
Hypertensive, %	32	45
A1C, %	6.9±1.7	7.4±8.1
LDL-chol, mmol/L	3.3±0.9	3.8±1.1
HDL-chol, mmol/L	1.04±0.23	1.10±0.24
Physical activity
Sedentary, %	17	22
Moderate, %	32	39
Active, %	44	38
Fit, %	7	1
Smoking
Never, %	22	44
Ex-smoker, %	46	27
Current, %	32	29

Other Findings:

After 10 years, 280 study participants developed CAD, 192 experienced fatal or non-fatal MI, and 79 had a fatal MI.

CAD was significantly associated with elevated LDL-chol, low HDL-chol, A1C, systolic blood pressure, fasting plasma glucose and a history of smoking.

The estimated hazard ratios for the upper third relative to the lower third were:

LDL-chol: 2.26 (95% CI, 1.70 to 3.00)
HDL-chol: 0.55 (0.41 to 0.73)
A1C: 1.52 (1.15 to 2.01)
Systolic blood pressure: 1.82 (1.34 to 2.47)
Smokers: 1.41 (1.06 to 1.88)

Author Conclusion:

The modifiable risk factors for CAD in patients with type 2 diabetes are elevated concentrations of LDL cholesterol, low HDL-cholesterol, elevated blood pressure, hyperglycemia and smoking.

There was an increased risk of CAD with A1C >6.2%. The study showed an increased risk of 11% for each increment of 1% in A1C.

There was a 15% increased risk of CAD with an increase in systolic blood pressure of 10 mm Hg; elevated blood pressure was a major risk factor for fatal MI.

Risk factors for development of CAD in the general population may not apply once type 2 diabetes has developed. Obesity, central obesity, low physical activity, and high insulin, provide an increased risk for CVD, but in patients with type 2 diabetes, we found that none of these were risk factors.

Funding Source:

Government:

United Kingdom Prospective Diabetes Study Group

Reviewer Comments:

The risk factors for CAD in those with type 2 diabetes are similar to those without diabetes:

increased LDL-chol, low HDL-chol, elevated systolic blood pressure, and a history of smoking. In addition, hyperglycemia was a risk for CAD.

Many exclusions were made, but no mention was made of patients who withdrew from the study of their own accord.

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?	???
	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?	???
	4.4.	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?		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?	Yes
	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)?	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?	No
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