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DM: Effectiveness of MNT Provided by RD/RDN (2015)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To determine whether intensive treatment of type 1 diabetes, with the goal of maintaining blood glucose concentrations close to the normal range, could decrease the frequency and severity of complications.

 

Inclusion Criteria:
  1. Insulin dependent based on deficient c-peptide secretion.
  2. 13-39 yr of age
  3. Absence of hypertension, hypercholesterolemia, severe diabetic complications or medical conditions.
  4. Primary prevention:
    1. duration of diabetes: 1-5 yr
    2. no retinopathy
    3. urine albumin <40 mg/24 hr
  5. Secondary prevention:
    1. duration of diabetes: 1-15 yr.
    2. very-mild to moderate nonproliferative retinopathy
    3. urine albumin >200 mg/24-hr
Exclusion Criteria:
Excluded if not included above.
Description of Study Protocol:

Recruitment:  1441 subjects were recruited at 29 centers from 1983-1989.

Method of Randomization:  randomization was stratified according to the primary-prevention and secondary-intervention cohorts at each center.

Study Design  A cohort of 1441 patients was followed for a mean of 6.5 years, a total of more than 9300 patient years.  Patients were divided into two cohorts: primary prevention (no retinopathy at baseline, N= 726) and secondary prevention (mild retinopathy, N= 715).  Each cohort was randomized into conventional-treatment or intensive-therapy groups and followed for an average of 6.5 years.

Blinding Used: Neither the investigators nor the patients were aware of the outcome data unless pre-determined criteria, such as the development of severe retinopathy, were met.

Intervention

  1. Conventional therapy:
    • 1 or 2 daily insulin injection of mixed intermediate and regular
    • daily monitoring of blood or urine glucose
    • education on diet and exercise
    • Goals: absence of symptoms of hypoglycemia and hyperglycemia and ketonuria, normal growth and development.
    • Clinic visits every 3 months.
    • 95 women assigned to this group were given intensive therapy while pregnant or planning a pregnancy.
  2. Intensive treatment:
    • Insulin >3 times/d or on insulin pump
    • Self-monitoring of blood glucose >4 times/d
    • Glycemic goals: Preprandial: 70 to 120 mg/dL
      • Postprandial: >180 mg/dL
      • Weekly 3 a.m.: >35 mg/dL
      • Monthly HgA1c: <6.05%
    • Monthly clinic visits including RD visits.

Statistical Analysis: 

  • The Wilcoxon rank-sum test was used to compare the two treatment groups within each cohort
  • Contingency chi-square test was used for comparisons of categorical values
  • For a stratified analysis of proportions, the adjusted log relative risk comparing the results in the two treatment groups within each cohort was calculated by least-squares analysis
Data Collection Summary:

Timing of Measurements-see Intervention (above)

Dependent Variables

  • Retinopathy-Seven-field stereoscopic fundus photographs taken every 6 months and evaluated according to the protocol of the Early Treatment Diabetic Retinopathy Study.  Clinically important retinopathy was defined as a change of at least 3 steps from baseline that was sustained for 6 months.
  • Proliferative retinopathy
  • Severe non-proliferative retinopathy
  • nephropathy, defined as urinary albumin excretion, measured annually, of 40 mg or more per 24 hours
  • neuropathy, defined as either abnormal nerve conduction in at least 2 peripheral nerves or unequivocally abnormal autonomic-nerve testing 
  • macrovascular disease
  • quality of life outcomes

Independent Variables

  • Conventional therapy or intensive treatment as described under Intervention

Control Variables

  •  baseline categories of retinopathy
Description of Actual Data Sample:

Initial N : 1441 subjects

Attrition (final N):  1398 subjects (99% of patients) completed the study; 11 patients died and 32 patients were assigned to inactive status

Age:  The mean age of all subjects was between 26±8 yr and 27±7 yr of age.

Ethnicity:  Not mentioned

Other Demographic Variables:

Anthropometrics:  A statistically significant (P <0.001) difference in the average glycosylated hemoglobin value was maintained after baseline between the intensive-therapy and conventional-therapy groups in both cohorts.

Location:  Multiple major medical centers throughout the US

Summary of Results:

 

 
Reduction in Risk or Appearance of Diabetic Complications in the Intensive-Therapy Group as Compared to the Conventional Therapy Group
 
Primary Prevention Group
Secondary Prevention Group
Retinopathy: sustained progression of retinopathy by 3 steps
-76% reduction in adjusted mean risk*
-54% reduction in adjusted mean risk*
Nephropathy: microalbuminuria
-34% reduction in adjusted mean risk**
-43% reduction in adjusted mean risk*
Neuropathy: abnormal conduction in at least 2 peripheral nerves
-69% reduction in neuropathy at 5 years***
-57% reduction in neuropathy at 5 years*
Macrovascular Disease
Intensive therapy reduced the development of hypercholesterolemia by 34% in the combined cohorts(P<0.02)
 
 
Mortality
No significant difference

 *P<0.001
**P<0.01
***P<0.006

95% of all scheduled examinations were completed and the average percentage of time spent receiving the assigned treatment was 97%.

Subjects in the intensive therapy group had a 2 to 3 fold increase in severe hypoglycemia.

Author Conclusion:

Intensive diabetes therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with Type 1 diabetes mellitus.  The large number of patients studied, the inclusion of a primary-prevention cohort, and the long follow-up period in this study provided the opportunity to demonstrate the effectsof treatment inptients with a range of ages, durations, of diabetes, degrees of severity or retinopathy, and baseline HbAIC values.

The  greater risk of severe hypoglycemia with instensive therapy is greatly outweighed by the reduction in microvascular and neurologic complications.

The authors recommend that most patients with IDDM be treated with closely monitored intensive regimens, with the goal or maintianing their glycemic status as close to the normal range as safely possible.

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

The DCCT showed that intensive diabetes therapy with the goal of achieving near-normal levels of HbA1c reduces by ~50% the overall risk for onset and progression of diabetic retinopathy, nephropathy and neuropathy and reduces the incidence of hypercholesterolemia.

The frequency and duration of RD visits was once/month throughout the study.

The research dietitians in this study determined which subjects would be able to adhere to intensive diabetes treatment (consistent eating pattern, knowledge of diabetes and diet or motivation to learn). Not all patients would be appropriate for intensive therapy.

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? ???
  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
  3.5. 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? Yes
  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? Yes
  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? Yes
  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.) Yes
  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? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  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? Yes
  6.6. Were extra or unplanned treatments described? Yes
  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)? Yes
  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