EAL

DM: Prevention and Treatment of CVD (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine at what levels of LDL and HDL cholesterol, triglycerides, and blood pressure the relative risks of Type 1 diabetes complications increase significantly.

Inclusion Criteria:

1. Onset of type 1 diabetes <17 yr of age.

2. Diagnosis of type 1 diabetes between January 1, 1950 and May 30, 1980.

3. >18 years of age when baseline data collected.

Exclusion Criteria:

Not specifically mentioned.

Description of Study Protocol:

Recruitment: The Pittsburgh Epidemiology of Diabetes Complications Study was a 10-yr prospective study of adults with type 1 diabetes.

Design

1. Baseline data with follow-up data collection 2 times/year over the study period.

2. Questionnaires were used to collect demographic data, medical history, and health care behaviors.

3. A trained internist conducted a medical history and clinical exam to document complications of diabetes.

Blinding Used: Not applicable

Intervention Not applicable

Statistical Analysis : Cox proportional hazards modeling was used to determine the relative hazard for each risk factor group; the lowest risk factor group was used as the reference. Adjustments were made for age and glycemic control.

Data Collection Summary:

Timing of Measurements : biennially

Dependent Variables

coronary artery disease defined as angina diagnosed by a clinic physician
MI confirmed by EKG or hospital records.
coronary artery stenosis >=50% confirmed by angiography
death confirmed by death certificate.
lower extremity arterial disease defined as amputation for vascular cause, intermittent claudication (Rose questionnaire) or ankle brachial index <0.9.
Proliferative retinopathy was determined by stereoscopic fundus photography

Independent Variables

blood pressure with random-zero sphygmomanometer according to standardized protocol after a 5 minute rest.
HDL
LDL
triglycerides
diastolic blood pressure
systolic blood pressure

Control Variables

Age
Glycemic control

Description of Actual Data Sample:

Initial N: 658 (325 women and 333 men) subjects met the criteria for the study, but only those age 18 and over were used (n=589)

Attrition(final N): 589 subjects

Age: mean 28.7 years

Ethnicity: Not mentioned

Other Relevant Demographics: duration of diabetes 20.1 years

Anthropometrics:

Location: Pittsburgh, PA

Summary of Results:

Outcomes	n	% of total sample
Mortality	67/589	11 %
CAD	105/540	17 %
Lower extremity Arterial disease	92/542	15%
Nephropathy	52/420	8%
Polyneuropathy	120/351	20%
Proliferative Retinopathy	148/203	25%

Other findings There was a strong relationship between LDL- cholesterol, HDL-cholesterol, TG, systolic blood pressure, diastolic blood pressure and the end points of mortality, CAD and overt nephropathy.

Therefore goals were established for serum lipids and blood pressure based on the values associated with the lowest risk for mortality, CAD and nephropathy.

Goals

LDL-C <100 mg/dL

HDL-C >45 mg/dL

TG <150 mg/dL

Systolic blood pressure <120 mmHg

Diastolic blood pressure < 80 mmHg

Adjustments for age, sex, and glycemic control had little influence on these goals.

Author Conclusion:

Although observational in nature, these data strongly support the case for vigorous control of lipids and blood pressure in patients with type 1 diabetes mellitus. These should be separate issues, rather than secondary to hyperglycemia.

In this study, adjustment for HbA1c had only a minor effect overall and marginally strengthened CAD associations. This observation is in agreement with observations that glycemic control is not strongly associated with CAD in this cohort.

Funding Source:

Government:

NIH

Reviewer Comments:

Study protocol described in detail. HbA1c was not reported in this study. If HbA1c levels were in the normal range, that could explain the lack of relationship between HbA1c and outcomes as was shown in DCCT.

Dietary intake was not evaluated in this cohort.

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)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	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?	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%.)	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?	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?	Yes
	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