DM: Protein (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To identify determinants of albuminuria in people with type 2 diabetes
Inclusion Criteria:
  • type 2 diabetes mellitus
  • age < 79 yrs
Exclusion Criteria:
  • in a period of recovery from severe morbidity
  • protein-losing enteropathy, venous leg/pressure ulcer, malignancy, psychiatric/serious psychosocial problems
  • nitrite-positive urine/substantial leucocyturia
Description of Study Protocol:

Recruitment

46 general practitioners selected all their patients with type 2 diabetes who met inclusion criteria and not exclusion criteria 

Design

This cross sectional study assessed albumin-creatinine ratio (ACR) in a group of 335 individuals with type 2 diabetes.  After dividing subjects into two groups (ACR </= 2 mg/mmol or > 2) it was compared to a number of variables, including protein intake and anthropometric, biochemical, and other  measures.    

Blinding used (if applicable)

 Not applicable

Intervention (if applicable)

 Not applicable

Statistical Analysis

  • Student's two-sided t-test/×2 (numeric and categorical variables)
  • Mann-Whitney test (number of cigarette pack years, alcohol intake, diabetes duration)
  • Linear and logistic regression
Data Collection Summary:

Timing of Measurements

 two 24h urine samples on two consecutive days

Dependent Variables

  • Albuminuria, expressed as the mean of the ratio of
    • albumin concentration (analyzed nepholometrically, Beckman Instruments)
    • and creatinine concentration (Jaffé method, BM/Hitachi 747/737, Boeringer Mannheim)

Independent Variables

  • Date of diabetes diagnosis (from general practitioner/patient)
  • Family history of diabetes (from patient, includes grandparent, parent, sibling, children)
  • Family history of MI, stroke or hypertension ( from patient, includes parent/sibling before the age of 60)
  • Ethnic origin (from patient, Note that caucasian is defined as both parents from European or Mediterranean origin)
  • Education (from patient,  defined as highest level attained by patient/partner)

Control Variables

  • protein intake (urea excretion from BM/Hitachi 747/737, Boeringer Manheim and semiquantitative food-frequency questionnaire)
  • alcohol intake (semiquantitative food-frequency questionnaire)
  • smoking (number of cigarette pack years - smoking years x cigarettes/day/25)
  • Body weight (no shoes, coat, keys)
  • Height (no shoes)
  • Systolic and diastolic blood pressure (mean of 2nd and 3rd readings, mercury sphygmomanometer)
  • Current medication (patient information/general practice records)
  • Glycosuria (Uristix 4, Miles)
  • HbA1c (HPLC, Modular Diabetes Monitoring System, Bio-Rad)
  • Cimetidine-influenced level of serum creatinine (Jaffé method, BM/Hitachi 747/737, Boeringer Mannheim)
  • Waist circumference (level of umbilicus)
  • Hip circumference (level of largest circumference 
Description of Actual Data Sample:

Initial N: 658 original subjects.  201 did not give informed consent, 106 gave consent but were excluded due to comorbidity.  351 subjects; 16 excluded due to nitrite-positive test result or substantial leucocyturia 

Attrition (final N): 335 signed informed consent (164 men, 171 women)

Age: average 64±8 yrs

Ethnicity: 326 caucasian, 9 non-caucasian

Other relevant demographics: diabetes duration (average 6 yrs±5)

Anthropometrics:

  • weight, males - average 84 kg; females - average 79 kg
  • height , males - average 69 in; females - average 64 in

Location: Amsterdam, The Netherlands

 

Summary of Results:

Other Findings

Prevalence of microalbuminuria (30-300 mg/24h) was 25%; macroalbuminuria (>/= 300 mg/24h) was 4%; an ACR > 2.0 mg/mmol was observed in 1/3 of subjects

Modifiable and non-modifiable factors associated with albuminuria (all P < 0.05):

  • glycemic control (glycosuria, HbA1c, Odds Ratio = 2.41)
  • smoking (current smoker but not # of cigarettes smoked, Odds Ratio = 2.36 / 4.89)
  • systolic blood pressure (Odds Ratio = 1.32)
  • male (Odds Ratio = 2.50)
  • older (Odds Ratio = 1.60)
  • taller height (Odds Ratio = 0.47)

Modifiable and nonmodificable factors NOT associated with albuminuria:

  • protein intake
    • total according to urinary urea: 1.03±0.23 g/kg/d for lower ACR group and 1.10±0.25 for higher ACR group
    • total according to food-frequency questionnaire: 1.09±0.34 g/kg/d for lower ACR group and 1.15±0.37 for higher ACR group
  • alcohol intake
  • BMI and waist-hip ratio
  • diabetes duration
  • family history

 

Author Conclusion:

In patients with type 2 diabetes, differences in modifiable factors (systolic blood pressure, smoking habits and glycosuria, but not protein intake) independently explain significant but small parts of the wide variation in albuminuria between patients

Higher albuminuria was observed in patients with short stature.  Thus, when studying variables such as protein intake/kg body weight, the associations of its components (such as body weight) with the outcome should be analyzed separately.

Albuminuria is increased in men vs women, in older men vs younger, and in younger women vs older

Funding Source:
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:

Cross-sectional associations do not prove cause and effect relationships; however, they can provide guidance for future controlled clinical trials.

Authors note that selection bias might be present - findings based on 270 - 335 out of 658 patients selected by general practitioners.

No information was obtained concerning serum lipids/creatinine clearance, both associated with albuminuria; no information was collected about physical exercise (which can affect albuminuria in 24 h collections)

Cross-reference other articles about this study:

  •  published baseline and 6 and 12 mo data (Pijls LTJ et al, Nephrology Dialysis Transplantation 1999;14:1445-1453)
  • 24 month data (Pijls LTJ et al, Eur J Clin Nutr 2002;56:1200-1207 
  • compliance data (Pijls LTJ et al, Eur J Clin Nutr 2000;54:347-352)

 

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) N/A
  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) N/A
 
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? 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? ???
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.) Yes
  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%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  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? 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.) 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
  5.5. 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? 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? N/A
  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? N/A
  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? ???
  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