EAL

DM: Blood Glucose Self-Monitoring (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine whether the continuous glucose monitoring system (CGMS) could provide criteria for an objective assessment of the status of hypoglycemia awareness in patients with type 1 diabetes.

Inclusion Criteria:

type 1 diabetes
age < 18 years
duration of diabetes >5 years
fasting C peptide less than or equal to 0.6 ng/ml
commitment to achieving glycemic control
- HbA1c less than or equal to 9%
- use of continuous subcutaneous insulin infusion/multiple daily insulin doses
- pre- and postprandial SMBG at least 4 times a day

Exclusion Criteria:

pregnant/breast-feeding
serum creatinine >2.0 mg/dl
unstable cardiovascular disease
history of recent substance abuse
poor cognitive function at the time of informed consent
diagnosis of a major comorbid condition other than longterm complications of diabetes

Description of Study Protocol:

Recruitment

Consecutive patients receiving care through an adult diabetes clinic of a medical group located in suburban Los Angeles after Dec 1, 2002.

Design

Comparison of hypoglycemia unawareness (HUN) by questionnaire with factors identified during a 72-hr glucose monitoring session (CGMS) in 60 individuals with type 1 diabetes

Blinding used (if applicable): no

Intervention (if applicable): none

Statistical Analysis

discrete variables for association with HUN by chi square testing
continuous variables tested by a two-tailed t test
factors independently associated with HUN estimated by multivariate independent analysis (stepwise logistic regression model with the presence of HUN as a dependent variable)

Data Collection Summary:

Timing of Measurements

One time - 72 hrs of monitoring with the use of the CGMS.

Dependent Variables

HUN by validated questionnaire:Janssen Diabetes Care 2000
CGMS by Medtronic-MiniMed; analysis with software version 3.0.13
SMBG by patients

Independent Variables

type 1 diabetes

Control Variables

Description of Actual Data Sample:

Initial N: 27 men and 33 women with type 1 diabetes

Attrition (final N): final n = 60 (no attrition)

Age: mean of 50.4±1.9 years (range 18-84)

Ethnicity: not provided

Other relevant demographics:

duration of diabetes: mean of 23.8±16 yrs (range 5-56)
mean A1c: 7.5±0.11%
education: 20 with no college degree

Anthropometrics:

mean BMI: 26.7±0.7 kg/m²

Location:

Adult diabetes clinic in suburban Los Angeles.

Summary of Results:

Variables	Hypoglycemic Awareness (n=35) Measures and confidence intervals	Hypoglycemic Unawareness (n=25) Measures and confidence intervals	Statistical Significance of Group Difference
Low blood glucose index (based on SMPG)	3.33±0.42	3.68±0.45	NS (p=0.57)
CGMS: time in hypoglycemia (%)	5.8±1.0	11.2±1.9	p=0.006
CGMS: time in nocturnal hypoglycemia (%)	5.5±1.6	15.5±2.8	p=0.003
CGMS: Maximal duration of hypoglycemia (min)	77.0±15.0	164.0±17.6	p=0.001

Other Findings

1. Duration of diabetes was associated with hypoglycemia unawareness (20.2 yrs for awareness, 28.8 years for unawareness, p = 0.009). Other demographic/anthropometric variables (age, BMI, insulin dose, low blood glucose index, sex, education, use of CSII) were not associated with unawareness.

2. Taking ACE inhibitors (or ARBs) was significantly associated with hypoglycemia unawareness (p= 0.010), but other medications (ß-Adrenergic blocking agents, CNS depressants) wre not associated with unawareness.

3. Overall glucose control (A1c) and GAD65 antibodies were not associated with unawareness

4. Neuropathy (impaired vibration-perception threshold), nephropathy (albumin/creatinine ratio) and retinopathy were not associated with unawareness.

Author Conclusion:

The duration of low interstitial fluid glucose detected by the CGMS is an objective method for identification of patients with hypoglycemic unawareness.

Funding Source:

Reviewer Comments:

This report uses recently updated design features for the CGMS, which improve the reliability of the testing at low glucose levels
Conclusions are limited to adults with type 1 diabetes who have good cognitive function when blood glucose levels are in the euglycemic range.

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?	???
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?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	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%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	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.)	Yes
	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?	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?	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?	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