EAL

Diabetes and Carbohydrates

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To validate the algorithm used for premeal insulin dose adjustment over a wide range of carbohydrate meal content and to assess the effects of low- and high-carbohydrate diets on basal insulin requirement.

Inclusion Criteria:

1. Type 1 diabetes mellitus

2. Diabetes well controlled.

3. Basal insulin: ultralente; premeal insulin: Humulin R

4. Practicing intensified insulin therapy using basal-bolus and counting carbohydrates

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment: not specified

Study Design: subjects with type 1 diabetes mellitus were randomized to 1 of 2 study diets in a crossover design, with diets followed for 14 days each, while maintaining usual caloric intake.

Blinding: not specified

Intervention:

1. Target blood glucose

Fasting (premeal and bedtime): 4 to 7 mmol/L
1 h postprandial: 7 to 10 mmol/L

2. Insulin regime:

basal: ultralente given at bedtime and adjusted 2 U at a time until FBG met goals
premeal: regular given 15-30 minutes before meal in U/10 g of CHO to be ingested and adjusted by 0.2 U/10 g CHO to achieve and maintain 1 h blood glucose goals.

3. Diet protocol:

Usual kcal intake determined by 24-h recall and FFQ administered and evaluated by RD during screening visit, and RD instructed subjects to follow 1 of the experimental diets for 14 days each

Statistical Analysis: analysis of variance repeated measures with the paired t test when applicable

Data Collection Summary:

Timing of Measurements

HbA1c measured at beginning of study
Fructosamine measured at end of study to assess glycemic control

Dependent Variables

Insulin
Fructosamine

Independent Variables

low carbohydrate diet: 40% carbohydrate, 40% lipids, 20% proteins
high-carbohydrate: 60% carbohydrate, 25% lipids, 15% proteins
All were to consume an evening snack with 20 g CHO.
no instructions given to subjects regarding fiber intake
RD instructed subjects to following one of the experimental diets for 14 d each and either weighing or measuring food and completing a 3-d food diary.
RD reviewed food diaries with subjects at the completion of the study period to clarify information.
Diet analysis using Nutritionist 3 as modified by TMS Wolever for Glycemic Index.

Control Variables: not specified

Description of Actual Data Sample:

Initial N: 9; 7 men, 2 women

Final N: 9

Age: 33.4 ± 2.9 yr

Ethnicity: not specified

Other relevant demographics:

Duration of diabetes: 12.4 ± 2.6 yr
HbA1c: 6.0 ± 0.3%
2 subjects had mild retinopathy
1 subject had peripheral neuropathy

Anthropometrics: BMI: 22.6 ± 1.0

Location: Canada

Summary of Results:

Other Findings

Lab Results

Fructosamine was 296±14.5 micromol/l at baseline and 310±12.4 micromol/l at the end of the low-carbohydrate diet compared with 316±15.4 at the end of the high-carbohydrate diet.
Gastroparesis was ruled out with a radioisotopic test meal.
All subjects were C-peptide-negative

Diet Results

Dietary records provided 162 meals with a wide range of CHO intake (21-188 g).
Data on meal composition, carbohydrate evaluation, and insulin doses were compiled by the patients in 100% of the cases.
There were no significant differences between the low and high CHO diets in kcal, glycemic index, or fiber.
There were significant differences in the percentage of kcal as carbohydrate, fat and protein. The mean intakes of carbohydrate were 38.8% ± 1.32% vs. 52.8% ± 1.6% of kcal (P<0.004); and of fat, 38.1% ± 1.67% vs. 28.7% ± 1.36% of kcal (P<0.001) and of protein: 19.3% ± 7.9% vs. 15.6% ± 0.92% of kcal (P<0.02).
The assessment of meal carbohydrate content by subjects was >85% falling within 15% of computer analysis.

Insulin

When premeal regular insulin was prescribed in U/10 g CHO, the postprandial glycemic rise remained constant (2.4 ± 2.8 mmol/L) over the range of CHO intake (21-188 g).
Postprandial glycemic control was not affected by glycemic index, fiber, kcal or lipid content of the meal.
Tight control was maintained during low and high carbohydrate experimental diets without any significant change in premeal regular insulin requirements:
- Breakfast: 1.5 vs. 1.5 U/10 g CHO
- Lunch: 1.0 vs. 1.0 U/10 g CHO
- Dinner: 1.1 vs. 1.2 U/10 g CHO
No significant change in basal ultralente insulin requirements: 22.5 vs. 21.4 U/day.
The morning premeal insulin dose was 50% higher than the noon and evening premeal dose (1.5 vs. 1.0 U/10 g CHO).

Author Conclusion:

The results indicate that in persons with type 1 diabetes mellitus:

1. Increasing the amount of CHO intake doesn’t influence glycemic control if premeal regular insulin is adjusted to the CHO content of the meals;

2. Algorithms based on U/10 g CHO are effective and safe, regardless of the amount of CHO at meals;

3. The glycemic index, fiber, lipid and kcal content of the meals did not affect premeal regular insulin requirements;

4. Wide variations in CHO intake do not modify basal (ultralente) insulin requirements;

5. The ultralente-regular insulin regimen allows dissection between basal and prandial insulin requirements, so that each can be adjusted accurately and independently.

Funding Source:

Government:

South African Medical Research Council

Industry:

Eli Lilly (South Africa)

Pharmaceutical/Dietary Supplement Company:

Reviewer Comments:

The subjects in this study had excellent glycemic control prior to the study and were familiar with carbohydrate counting and adjusting premeal insulin based on the amount of carbohydrate to be ingested with a meal.

This study demonstrates that well motivated patients are able to estimate carbohydrate content of foods with considerable accuracy and to adjust insulin to maintain glycemic control.

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?	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?		N/A
	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?	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?		N/A
	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?	N/A
	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?	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?	Yes
	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?	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?	No
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?		???
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	???