DM: Blood Glucose Self-Monitoring (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
  • To compare glycemic patterns by mode of therapy in children with type 1 diabetes using the continuous glucose monitoring system (CGMS).
  • To determine if the CGMS can improve glycemic control and glucose patterns.
Inclusion Criteria:
  • ages 8-14 yrs
  • treatment with insulin for at least 2 yrs
  • deficient C-peptide secretion (fasting level, < 0.6ng/ml)
  • absence of other health problems except for treated hypothyroidism or antibody-negative celiac disease controlled with a gluten-free diet.

 

 

 

Exclusion Criteria:
None given.
Description of Study Protocol:

Recruitment:

The first 23 consecutive patients who

  • met the inclusion criteria
  • were motivated to participate in the study
  • agreed to perform 4 - 6 SBGMs daily
  • had the ability to cope, together with their parents, with the treatment procedures, as judged by the diabetic team.

Design

Comparison of glycemic patterns (rate, degree, and duration of hypoglycemia and hyperglycemia and the variability in glucose levels), measured at two weeks and 3-1/2 months, of children and adolescents treated by continuous subcutaneous insulin infusion (CSII) or muliple daily injections (MDI)

Blinding used (if applicable):  no

Intervention (if applicable)

After a two week run-in subjects were randomized to start with CSII or MDI for 3-1/2 months and then crossed over after a two week washout period. 

  • The MDI intervention consisted of NPH and regular insulin before breakfast, regular insulin before lunch and supper, and NPH at bedtime, with the regular insulin given 20-30 min before meals. Patients were instructed to use a fixed caloric amount of carbohydrates for each meal and then adjust the insulin dose according to postprandial glucose values.
  • The CSII was delivered using the MiniMed 508 pump using lispro, with the lispro given immediately before meals and snacks.  Before initiation of CSII, subjects were taught carbohydrate counting and insulin bolus dosing based on the insulin-carbohydrate ratio, using 1 U of insulin per 10-20 g of carbohydrate.

Statistical Analysis

  • Analysis of variance (ANOVA), to compare CGMS tracings between modes of therapy
  • Repeated measures ANOVA  to compare CGMS readings between the first and second sensor recordings in each study arm, by mode of therapy
  • Pearson correlation coefficients calculated between mean glucose levels during CGMS and SBGM
  • Fisher exact test to compare frequencies

 

 

Data Collection Summary:

Timing of Measurements

Two weeks after start of study and end of study (3-1/2 months after start).

 Dependent Variables

  • HbA1c by DCA 2000 analyzer (Bayer Diagnostics, Tarrytown, NY)
  • Mean glucose levels by CGMS (Minimed); software for calculation of variables and comparison between modes of therapy and between the first and second sensor readings developed by one of study authors. 
  • Hypoglycemia by CGMS (Minimed) 
  • Hyperglycemia by CGMS (Minimed) 

Independent Variables

  •  duration of diabetes

Control Variables

  • none

 

Description of Actual Data Sample:

Initial N: 23 (10 boys, 13 girls)

Attrition (final N): 22 (9 boys, 13 girls)

Age: 9-1/4 to 13-3/4 (median, 11.9 yrs)

Ethnicity: not provided

Other relevant demographics: duration of diabetes: 2-1/2 to 11 yrs (median, 6.0 yrs)

Anthropometrics: not provided

Location: Schneider Children's Medical Center of Israel, Tiqva

 

Summary of Results:

 Table: Comparison of results at 3-1/2 months

Variables

CSII, n=22

Mean (SD)

MDI, n=22

Mean (SD)

Statistical Significance between groups

HbA1c (%) 8.0 (0.8) 8.2 (0.8)

P=0.25

Mean glucose levels, 24 hr (mg/dL)

187 (36)

191 (45) 

P= 0.63

Hypoglycemia, AUC, night (mg/dL per day)

198 (300)

433 (544)

P=0.01

Hypoglycemia, AUC, 24h (mg/dL per day) 377 (377) 638 (727) P=0.04
Hypoglycemia, AUC postprandial (mg/dL per day) 24 (42) 64 (113) P=0.03
Hyperglycemia, AUC, postprandial (mg/dL per day) 1454 (1292) 2282 (2174) P=0.05
Hyperglycemia, number of events per 24 h 3.4 (1.2) 2.9 (1.0) P=0.04
Duration of within-target values before breakfast (%) 0.27 (0.20) 0.17 (0.16) P=0.01

Other Findings

No other measures were significantly different between treatment modalities at the end of 3-1/2 months

Author Conclusion:
  • The findings indicate that the advantages of pump therapy are modest and that both modalities are equally efficient for achieving tight metabolic control in this age group.
  • Intensive treatment with CSII seemed to be associated with slightly better prebreakfast, postprandial, and within-target glucose profiles than MDI, as well as smaller area under the curve for hypoglycemia. 
  • Lower hypoglycemia-related variables indicate that the CGMS may serve as an educational tool to decrease the rate and magnitude of hypoglycemia, and postprandial glycemic control 
Funding Source:
Reviewer Comments:
  • While this study indicated initial concern with possible confounding variables (e.g.: education in carbohydrate counting, etc) there is no indication that these factors were "measured" at the 3-1/2 month endpoint.
  • There is no discussion about how the washout period could erradicate the "education" for the CSII group when they were crossed over to the MSI group for the 2nd period.
  • There is no discussion of study limitations.
  • In the discussion, P values for AUC, postprandial hyperglycemia and hypoglycemia are reversed; however, they are correct in the abstract.
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? ???
  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? ???
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? ???
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) No
  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.) 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? ???
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? No
  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? ???
  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? ???
  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? ???
  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)? ???
  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? ???
  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