NNNS: Diabetes and Glycemic Response (2011)

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

"To examine the effect of a single high oral dose of sucralose on short-term glycemic control after a liquid breakfast in patients with IDDM or NIDDM."

Inclusion Criteria:
  • Age: Less than 65 years
  • Diagnosed with diabetes: At one year old or older
  • Initial GHb level: Below 10%
  • Adequate glycemic control: Demonstrated by fasting capillary glucose readings below 9.7mmol per liter at three clinic visits before dosing
  • Patients with IDDM: At least 18 years old, C-peptide level below 0.3nmol per liter, 15 minutes of injection of one mg glucagon
  • Patients with NIDDM: Over 40 years old, glucagon stimulated C-peptide level above 0.6nmol per liter.


Exclusion Criteria:
None noted.
Description of Study Protocol:
  • Recruitment: Not described
  • Design: Subjects were randomized to receive sucralose or cellulose placebo at two meal tests scheduled about one week apart
  • Blinding used: Double-blind
  • Intervention: Following a two- to six-week screening phase, after taking their usual insulin or sulfonylurea dose 30 minutes prior, subjects consumed 1,000 sucralose or cellulose placebo in three opaque capsules.  Immediately after receiving the sucralose, test subjects consumed a 360-calorie meal of Ensure Plus (Ross Products Division)
  • Statistical analysis: Measures of gylcemic effect were compared by analysis of variance on factors of treatment, diabetes type and treatment sequence.
Data Collection Summary:

Timing of Measurements

Fasting plasma glucose and serum C-peptide were measured:

  • 40 and five minutes prior to test substance administration
  • 30, 60, 90, 120 and 180 minutes after completing the test meals
  • At the one-week follow-up.

Dependent Variables

  • Short-term glycemic control expressed as plasma glucose
  • Serum C-peptide data expressed as mean+SD and areas under the curves for changes from baseline.

Independent Variables


Control Variables

Cellulose placebo.

Description of Actual Data Sample:

Initial N


Attrition (Final N)

26: One discontinued due to severe hypoglycemia.


  • 13 IDDM completing the trial: 37.8±2.6 years
  • 13 NIDDM completing the trial: 54.3±1.7 years (P<0.001).


  • IDDM: Caucasian
  • NIDDM: Four blacks, one Asian, one Hispanic, seven Caucasian.

Other Relevant Demographics

  • Duration of diabetes: IDDM, 15.5±2.6 years; NIDDM, 6.1±1.4 years (P<0.01)
  • Medications: NIDDM, nine sulfonylurea, two diet alone, two insulin
  • GHb levels: IDDM, 9.4±0.3%; NIDDM, 8.7±0.2% (P<0.05)
  • Glucagon-stimulated C-peptide levels: IDDM, 0.24+0.01nmol/L; NIDDM, 0.97+0.08nmol/L (P<0.001).


  • Mean body weight: IDDM, 72.5±3.6kg; NIDDM, 95.0±7.3kg (P<0.001)
  • Mean BMI: IDDM, 23.7±0.9kg/m2; NIDDM, 32.0±1.9kg/m2 (P<0.001).


  • Clinical Pharmacology Program, Division of Endocrinology, Diabetes and Nutrition, St. Luke's–Roosevelt Hospital Center, New York, NY.
Summary of Results:
  • Neither plasma glucose nor serum C-peptide areas under the curve varied significantly as a function of treatment or test sequence (P>0.05). This lack of effect was independent of diabetes type. Although the areas under the curve of IDDM and NIDDM patients for glucose were not significantly different, the area under the curve for C-peptide was smaller in IDDM patients than in NIDDM patients (P<0.001).
  • Over the course of the trial, no meaningful changes in physcial examination findings, clinical laboratory paramters, intercurrent illnesses or concomittant medications, including insulin or sulfonylureas, were observed.
Author Conclusion:

"These results support the conclusion that sucralose consumption does not adversely affect short-term blood glucose control in indiviudals with diabetes."

Funding Source:
McNeil Specialty Products Company
Food Company:
Reviewer Comments:
These findings provide the foundation for necessary research investigating long-term effects of sucralose.
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) No
  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? 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? No
  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? 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? 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? ???
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  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? 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? 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)? No
  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