DM: Self-Monitoring of Blood Glucose (2001)

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

The purpose of this study is to report the proportion of newly diagnosed type 2 subjects from the United Kingdom Prospective Diabetes Study (UKPDS) who could maintain target blood glucose and A1C levels recommended by the American Diabetes Association with each of the monotherapy of agents (sulfonylurea, metformin, insulin), or conversely who required more than one agent (multiple therapies) to attain target levels.

Inclusion Criteria:
  • Newly diagnosed type 2 diabetes mellitus using the criteria of fasting plasma glucose (FPG) >6.0 mmol/L (108 mg/dl) on 2 occasions.
  • Age 25-65 years.
Exclusion Criteria:
Not specifically mentioned in this article.
Description of Study Protocol:

Recruitment:  Subjects were recruited between 1977 and 1991 from the first 15 UKPDS centers established.  Additional subjects were recruited from the last 8 UKPDS centers, totalling 23 centers.

Design:  Randomized controlled trial.  Study was conducted from 1977-1997.

Blinding used:  No - lab tests.

Intervention:  All subjects were initially prescribed, by a dietitian, a low-fat, high carbohydrate, high fiber diet. After 3 months on the diet, subjects were stratified into 1 of the following therapies according to the mean FPG taken on 3 separate days:  diet alone, insulin, sulfonylurea, or metformin.  Those who were not initially randomized because FPG <6 mmol/L but later 3 consecutive FPG were > 6 mmol/L (<108 mg/dl) or had hyperglycemia symptoms, were randomized the same as the conventional group, but later.

Statistical Analysis:  Calculations were done to evaluate outcome measures by percentages. Logistic regression analysis was performed using SAS software to assess whether the degree of glycemia, age, ethnic group, sex, measures of obesity, plasma triglycerides, or mode of presentation predicted the probability of failing to achieve glycemic targets.

Data Collection Summary:

Timing of Measurements: 

Subjects were followed in the clinic every 3 mos to monitor plasma glucose and to adjust their allocated therapies to meet glycemic goal of FPG < 6 mmol/L (108 mg/dl).  Cohorts were analyzed at 3, 6, and 9 years after enrollment.

Dependent Variables:  

  • Fasting plasma glucose
  • A1C
  • Proportion of subjects that achieved target A1C <7% or <7.8 mmol/L (140 mg/dL) fasting plasma glucose by the end of the study period.

Independent Variables:  

  • Primary diet failure: FPB > 15 mmol/L (270 mg/dl) or continued symptoms of hyperglycemia randomized to either sulfonylurea or insulin; obese (>120 % IBW) were randomized to sulfonylurea or insulin or metformin.
  • Main randomization/Conventional therapy: Asymptomatic patients with FBG 6-15 mmol/L (108-270 mg/dl) randomized to sulfonylurea or insulin or metformin or diet therapy alone.
  • Diet satisfactory: Those with FPG <6 mmol/L (<108 mg/dl) remained on diet therapy alone.

Control Variables:  The center at which they received their treatment.

Description of Actual Data Sample:

Initial N= 4075 subjects who met the study criteria.

Attrition (Final N):  Some were lost to follow-up or died over the 9 year period.  55% presented (diagnosed) to their general practitioner with symptoms due to hyperglycemia, 13% because of infection, 2% following detection of clinical complications, 30% were a symptomatic and were seen for routine screening evaluation.

Age:  mean age 53+9 yr

Ethnicity:  81% white, 10% Asian-Indian, 9% Afro-Caribbean

Other relevant demographics: 

Mean BMI: 29+6, Median (interquartile range) FPG:11.5 mmol/L (9.0-14.4), Median (interquartile range) A1C: 9.1% (7.5%-10.7%)

Anthropometrics:

Location:  United Kingdom

 

Summary of Results:

The proportion of patients who maintained target glycemic levels declined markedly over the 9 years of follow up.

After 9 yrs of monotherapy with diet, insulin, or sulfonylurea, 8%, 42% and 24% respectively, achieved FPG levels of <7.8 mmol/L and 9%, 28%, and 24% achieved A1C levels <7%.

In obese patients randomized to metformin, 18% attained FPG levels of less than 7.8 mmol/L and 13% attained A1C levels <7%.

Patients less likely to achieve target levels were younger, more obese, or more hyperglycemic than other patients.

 

Author Conclusion:

Each therapeutic agent, as monotherapy, increased 2-3 fold the proportion of patients who attained A1C <7% compared with diet alone.

However, the progressive deterioration of diabetes control was such that after 3 yr ~50% of patients could attain this goal with monotherapy and by 9 yr, this decreased to 25%. The majority of patients with type 2 diabetes mellitus eventually need multiple therapies to attain glycemic goals.

More overweight (compared to both normal weight and overweight) subjects were able to attain goals on diet alone (at 9 years).

Funding Source:
Government: NIDDK, UK Medical Research Council
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:
This study demonstrates that clinic visits q 3 months were necessary to adjust or add medications to meet glycemic goals.  The frequency and duration of RD visits was not reported, however subjects on insulin would need frequent RD follow up for adjustment in diet with changes in the insulin regime.
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? ???
  4.1. Were follow-up methods described and the same for all groups? ???
  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%.) ???
  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? Yes
  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? No
  6.6. Were extra or unplanned treatments described? No
  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? Yes
  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)? 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? No
  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? No
  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