Scolaris Content Display Scolaris Content Display

Low glycaemic index, or low glycaemic load, diets for diabetes mellitus

Esta versión no es la más reciente

Contraer todo Desplegar todo

Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

To assess the effects of low glycaemic index, or low glycaemic load, diets in people with diabetes.

Background

Description of the condition
Diabetes mellitus is a metabolic disorder resulting from a defect in insulin secretion, insulin action, or both. A consequence of this is chronic hyperglycaemia (that ist elevated levels of plasma glucose) with disturbances of carbohydrate, fat and protein metabolism. Long‐term complications of diabetes mellitus include retinopathy, nephropathy and neuropathy. The risk of cardiovascular disease is increased. The prevalence of type 2 diabetes is increasing and is being diagnosed at increasingly younger ages (Silink 2002). For a detailed overview of diabetes mellitus, please see under 'Additional information' in the Metabolic and Endocrine Disorders Group section in The Cochrane Library (see 'About', 'Cochrane Review Groups (CRGs)'). For an explanation of methodological terms, see the main glossary on The Cochrane Library.

Description of the intervention
The aim of diabetes management is to normalise blood glucose levels, since improved blood glucose control is associated with a reduction in the development of, and progression of, complications (DCCT 1993). Nutritional factors affect blood glucose levels, however there is currently a lack of agreement among clinicians as to the optimal dietary approach for diabetes (ADA (nutr) 2004). If improvement in glycaemic control is achievable through dietary interventions, this would lessen the risk of diabetic complications, improve quality of life for people with diabetes, increase their life expectancy, and minimise, or even avoid, the necessity for expensive medications and diabetic health care. As different foods have different effects on blood glucose, they can be ranked by their overall effect on the blood glucose levels. The 'glycaemic index' was developed to simplify the comparison of foods in this way (Jenkins 1981). Low glycaemic index foods, such as lentils, beans and oats, contribute a slower gradual supply of glucose to the bloodstream, stimulating less insulin release than that which is stimulated by high glycaemic index foods, such as white bread (Jenkins 1981). Hence, low glycaemic index foods and diets may increase insulin sensitivity by minimising fluctuations in blood glucose levels and reducing the secretion of insulin over the day (Kiens 1996).

There is controversy over whether glycaemic index or glycaemic load is a useful concept in meal planning for people with diabetes. In a recent review, it was concluded that low glycaemic index diets exert a small, but clinically useful effect on medium‐term glycaemic control in diabetes (Brand‐Miller 2003). However, the American Diabetes Association currently recommends that "with regard to the glycaemic effects of carbohydrates, the total amount of carbohydrate in meals or snacks is more important than the source or type" (ADA (nutr) 2004). This recommendation is based on five studies (Franz 2004) in all of which glycated haemoglobin levels did not change. However, this is not surprising, because changes in glycation of haemoglobin would not be expected to become apparent following interventions of six weeks or less (all of these studies). Glycated haemoglobin reflects glycaemic control over two to three months (ADA 2004). Nevertheless, short trials may influence changes in the degree of glycation of serum proteins (mostly albumin), quantified by fructosamine or glycated serum albumin (GSA) assays, since these tests reflect glycaemic control from the preceding one to four weeks (ADA 2004; Goldstein 1995; Winocour 1988). Four of the five studies recorded both glycated haemoglobin and either fructosamine or GSA, and showed they reduced with the intervention, indicating that the low glycaemic index diet was having a positive effect on glycaemic control.

Why it is important to do this review
Our Cochrane systematic review may clarify issues surrounding the role of low glycaemic index, or low glycaemic load, diets in the management of diabetes mellitus. Our review will include all relevant studies with diet interventions lasting four weeks or longer. If alterations in the glycaemic index or glycaemic load of the diet can alone improve glycaemic control in diabetes, the use of low glycaemic index, or low glycaemic load, diets could have significant health and cost benefits for people with diabetes and the community as a whole.

Objectives

To assess the effects of low glycaemic index, or low glycaemic load, diets in people with diabetes.

Methods

Criteria for considering studies for this review

Types of studies

Inclusion criteria
Trial Design
We will consider all randomised controlled trials comparing a low glycaemic index, or low glycaemic load, diet with a higher glycaemic index diet in people with diabetes.

Trial Duration
We will include trials with dietary interventions lasting four weeks or longer.

Exclusion criteria
We will exclude studies in which the intervention is only a generalised recommendation to increase the proportion of low glycaemic index foods in the diet, or to reduce the glycaemic load, without explicit detail; studies in which the intervention is either not directly supervised or well‐documented, for example, through the use of food diaries; studies in which there is a co‐intervention in the experimental group that is not also applied to the control group.

Types of participants

People of all ages who are classified as having diabetes mellitus using validated and specified criteria. To be consistent with changes in classification and diagnostic criteria of diabetes mellitus through the years, the diagnosis should have been established using the standard criteria valid at the time of the beginning of the trial. Ideally, diagnostic criteria should have been described. If necessary, authors' definition of type 2 diabetes mellitus will be used.

Types of interventions

We will include studies that compare a low glycaemic index, or low glycaemic load, diet with a higher glycaemic index diet or other diets.

Types of outcome measures

Glycated haemoglobin is the best measure of long term glycaemic control, since it represents the average blood glucose levels over several months (ADA 2004; UKPDS 38 1998; UKPDS33 1998). Hence, for our review, glycated haemoglobin was chosen as the main outcome measure of glycaemic control for studies in which the intervention was used for over six weeks. Fructosamine or glycated serum albumin (GSA) levels will be used, when provided, as the measure of glycaemic control for studies where the intervention lasts six weeks or less, since in these cases, fructosamine or GSA levels give more reliable indications of glycaemic control than does the degree of glycation of haemoglobin (ADA 2004; Winocour 1988). The turnover of human serum albumin is much shorter (half‐life of 14 to 20 days) than that of haemoglobin (erythrocyte life span 120 days), so the amount of glycation of the serum proteins (mostly albumin), indicated by fructosamine or GSA, indicates the level of glycaemia over a shorter period of time than does glycation of haemoglobin (ADA 2004). "Measurements of total glycated serum protein and GSA correlate well with one another and with measurements of glycated haemoglobin" (ADA 2004; Goldstein 1995).

Primary outcomes

  • glycaemic control as measured by glycated haemoglobin, fructosamine, GSA or other test measuring glycated proteins.

Secondary outcomes

  • insulin action (fasting plasma insulin, insulin sensitivity, insulin area under the curve, total insulin released/day, insulin:glucose ratio);

  • adverse events (for example hyper‐ or hypoglycaemic episodes);

  • health‐related quality of life (using a validated instrument);

  • costs;

  • all‐cause mortality;

  • morbidity (for example diabetes and cardiovascular related morbidity, like angina pectoris, myocardial infarction, stroke, peripheral vascular disease, neuropathy, retinopathy, nephropathy, erectile dysfunction, amputation).

Covariates, effect modifiers and confounders

Timing of outcome measurement
Outcomes will be assessed.

Search methods for identification of studies

Electronic searches
We will perform electronic searches of The Cochrane Library (latest issue), MEDLINE (1966 to present), EMBASE (1988 to present) and CINAHL (1982 to present).

We will also search databases of ongoing trials: Current Controlled Trials (www.controlled‐trials.com ‐ with links to other databases of ongoing trials).
The described search strategy (see for a detailed search strategy under 'Additional tables' ‐ Table 1) will be used for MEDLINE. For use with EMBASE and The Cochrane Library this strategy will be slightly adapted.

Open in table viewer
Table 1. search strategy

Search terms

Unless otherwise stated, search terms are free text terms; MeSH = Medical subject heading (Medline medical index term); exp = exploded MeSH; the dollar sign ($) stands for any character(s); the question mark (?) = to substitute for one or no characters; tw = text word; pt = publication type; sh = MeSH; adj = adjacent.

A) Diabetes mellitus, general

1 exp diabetes mellitus/
2 diabet$.tw.
3 IDDM.tw.
4 NIDDM.tw.
5 MODY.tw.
6 insulin$ secret$ dysfunc$.tw.
7 impaired glucose toleran$.tw.
8 exp glucose intolerance/
9 glucose intoleran$.tw.
10 exp insulin resistance/
11 insulin$ resist$.tw.
12 (non insulin$ depend$ or noninsulin$ depend$ or
non insulin?depend$ or noninsulin?depend$).tw.
13 (insulin? depend$ or insulin?depend$).tw
14 metabolic$ syndrom$.tw.
15 (pluri metabolic$ syndrom$ or plurimetabolic$ syndrom$).tw.
16 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15
17 exp diabetes insipidus/
18 diabet$ insipidus.tw.
19 17 or 18
20 16 not 19

B) Controlled trials*

21 randomized‐controlled trial.pt.
22 controlled‐clinical trial.pt.
23 randomized‐controlled‐trials.sh.
24 random allocation.sh.
25 double‐blind method.sh.
26 single‐blind method.sh.
27 21 or 22 or 23 or 24 or 25 or 26
28 animal.sh.
29 human.sh.
30 28 not 29
31 27 not 30

C) Glycaemic index or glycaemic load

32 (diet adj5 glyc?emic$).tw.
33 Glycemic Index/ or glyc?emic index.tw.
34 (all bran or wholegrain or pasta or oat$ or apple$ or appricot$ or bean$ or lentil$ or wheat bran or barley porridge or raw oats or basmati rice).ti, ab.
35 (gi adj10 (diet or food or carbohydrate$)).tw.
36 (food adj5 glyc?emic$).tw.
37 (carbohydrate$ adj5 (blood glucose or blood sugar) adj5 (low or less$ or high$)).tw.
38 (puls$ adj10 (diet or food)).tw.
39 lentil$.tw.
40 or/32‐39
41 dietary carbohydrates/
42 blood glucose.sh,rn,rw.
43 41 and 42
44 40 or 43

D) Systematic reviews, meta‐analyses, health‐technology assessment reports
45 exp meta‐analysis/
46 exp Review Literature/
47 meta‐analysis.pt.
48 systematic review$.tw.
49 search$.tw.
50 medline.tw.
51 cochrane database of systematic reviews.jn.
52 45 or 46 or 47 or 48 or 49 or 50 or 51
53 letter.pt.
54 comment.pt.
55 editorial.pt.
56 historical‐article.pt.
57 53 or 54 or 55 or 56
58 52 not 57
59 exp Technology Assessment, Biomedical/
60 HTA.tw.
61 (health technology adj6 assessment$).tw.
62 (biomedical adj6 technology assessment$).tw.
63 60 or 61 or 62
64 58 or 63

65 31 or 64
66 20 and 44
67 65 and 66

* Robinson KA, Dickersin K. Development of a highly sensitive search strategy for the retrieval of reports of controlled trials using PubMed. International Journal of Epidemiology 2002;31:150‐3.

Other sources
We will contact experts in the field in an effort to identify additional unpublished trials.

Reference lists
Bibliographies of papers will be handsearched.

Data collection and analysis

Selection of studies
Two reviewers will independently review the titles, abstract sections and keywords of every record retrieved from the literature searches to identify potentially eligible studies. Articles that clearly do not meet the inclusion criteria will be rejected at this initial review. We will obtain the full text of the remaining articles for further examination. We will assess each study for eligibility for inclusion against the defined selection criteria and eliminate any trial that does not fulfil this criteria, for example was not a randomised controlled trial, did not involve people who have diabetes, had no comparitor, included a co‐intervention, or in which the trial period was less than four weeks. The decision to eliminate a trial will be based on agreement by both reviewers. If there is any difference in opinion we will calculate the inter‐rater agreement for study selection using the kappa statistic (Cohen 1960), and then resolve the differences through discussion. If we exclude a trial after this, we will retain a record of the article, including the reason for its exclusion. An adapted QUOROM (quality of reporting of meta‐analyses) flow‐chart of study selection will be attached (Moher 1999).

Data extraction and management
Two reviewers will independently extract the data on the relevant outcome measures reported in each included study (for details see under 'Additional tables' Table 2; Table 3; Table 4; Table 5; Table 6).

Open in table viewer
Table 2. Study quality (included studies)

Characteristic

Study a

Study b

Study c

Study d

Study e

Intervention 1 (I1) / intervention 2 (I2) / control 1 (C1)

I1: Pioglitazone
I2: Rosiglitazone
C1: Placebo

Randomised controlled clinical trial (RCT)

Non‐inferiority / equivalence trial

Controlled clinical trial

Design: parallel, crossover, factorial RCT

Design: crossover study

Design: factorial study

Crossover study: wash‐out phase

Crossover study: carryover effect tested

Crossover study: period effect tested

Method of randomisation

Unit of randomisation (individuals, cluster ‐ specify)

Randomisation stratified for centres

Randomisation ratio

Concealment of allocation

Stated blinding (open; single, double, triple blind)

Actual blinding: participant

Actual blinding: caregiver / treatment administrator

Actual blinding: outcome assessor

Actual blinding: others

Blinding checked: participant

Blinding checked: caregiver / treatment administrator

Primary endpoint defined

[n] of primary endpoint(s)

[n] of secondary endpoints

Total [n] of endpoints

Prior publication of study design

Outcomes of prior / current publication identical

Power calculation

[n] participants per group calculated

Non‐inferiority trial: interval for equivalence specified

Intention‐to‐treat analysis (ITT)

Per‐protocol‐analysis

ITT defined

Analysis stratified for centres

Missing data: last‐observation‐carried‐forward (LOCF)

Missing data: other methods

LOCF defined

[n] of screened participants (I1/ I2 / C1 / total)

[n] of randomised participants (I1/ I2 / C1 / total)

I1: 400
I2: 350
C1: 700
Total: 1450

[n] of participants finishing the study (I1/ I2 / C1 / total)

[n] of patients analysed (I1/ I2 / C1 / total)

Description of discontinuing participants

Drop‐outs (reasons explained)

Withdrawals (reasons explained)

Losses‐to‐follow‐up (reasons explained)

[n] of participants who discontinued (I1/ I2 / C1 / total)

[%] discontinuation rate (I1/ I2 / C1 / total)

Discontinuation rate similar between groups

[%] crossover between groups

Differences [n] calculated to analysed patients

[n] of subgroups

Subgroups: pre‐defined

Subgroups: post‐hoc

[n] of statistical comparisons

Adjustment for multiple outcomes / repeated measurements

Baseline characteristics: clinically relevant differences

Treatment identical (apart from intervention)

Timing of outcomes' measurement comparable between groups

Compliance measured

Other important covariates measured (specify)

Co‐morbidities measured

Co‐medications measured

Specific doubts about study quality

Funding: commercial

Funding: non‐commercial

Publication status: peer review journal

Publication status: journal supplement

Publication status: abstract

Publication status: other

Notes

Symbols & abbreviations: Y = yes; N = no; ? = unclear I = intervention; C = control

Open in table viewer
Table 3. Baseline characteristics (included studies)

Characteristic

Study a

Study b

Study c

Study d

Study e

Intervention 1 (I1) / intervention 2 (I2) / control 1 (C1)

I1: Pioglitazone
I2: Rosiglitazone
C1: Placebo

[n] (I1/ I2 / C1 / total)

Sex [n,%] (I1/ I2 / C1 / total)

Age [years] mean (SD) (I1/ I2 / C1 / total)

I1: 43 (12)
I2: 41 (11)
C: 45 (12)
Total: 42 (10)

Ethnic groups [%] (I1/ I2 / C1 / total)

Duration of disease [years] mean (SD) (I1/ I2 / C1 / total)

Body mass index [kg/m2] mean (SD) (I1/ I2 / C1 / total)

Pharmaco‐naive patients [n,%] (I1/ I2 / C1 / total)

Co‐morbidity [%] (I1/ I2 / C1 / total)

Co‐medication [%] (I1/ I2 / C1 / total)

HbA1c [%] mean (SD) (I1/ I2 / C1 / total)

Notes

Symbols & abbreviations: Y = yes; N = no; ? = unclear
I = intervention; C = control

Open in table viewer
Table 4. Adverse events (included studies)

Characteristic

Study a

Study b

Study c

Study d

Study e

Intervention 1 (I1) / intervention 2 (I2) / control 1 (C1)

I1: Pioglitazone
I2: Rosiglitazone
C1: Placebo

[n] of participants who died

[n] adverse events (I1/ I2 / C1 / total)

[%] adverse events (I1/ I2 / C1 / total)

[n] serious adverse events (I1/ I2 / C1 / total)

[%] serious adverse events (I1/ I2 / C1 / total)

[n] drop‐outs due to adverse events (I1/ I2 / C1 / total)

I1: 3/40
I2: 5/30
C1: 6/50
Total: 14/120

[%] drop‐outs due to adverse events (I1/ I2 / C1 / total)

[n] hospitalisation (I1/ I2 / C1 / total)

[%] hospitalisation (I1/ I2 / C1 / total)

[n] out‐patient treatment (I1/ I2 / C1 / total)

[%] out‐patient treatment (I1/ I2 / C1 / total)

[n] hypoglycaemic episodes (I1/ I2 / C1 / total)

[%] hypoglycaemic episodes (I1/ I2 / C1 / total)

[n] severe hypoglycaemic episodes (I1/ I2 / C1 / total)

[%] severe hypoglycaemic episodes (I1/ I2 / C1 / total)

[n] nocturnal hypoglycaemic episodes (I1/ I2 / C1 / total)

[%] nocturnal hypoglycaemic episodes (I1/ I2 / C1 / total)

[n] with symptoms (I1/ I2 / C1 / total)

[%] with symptoms (I1/ I2 / C1 / total)

Symbols & abbreviations: Y = yes; N = no; ? = unclear I = intervention; C = control

Open in table viewer
Table 5. Primary outcome data (included studies)

Characteristic

Study a

Study b

Study c

Study d

Study e

Intervention 1 (I1) / intervention 2 (I2) / control 1 (C1)

I1: Pioglitazone
I2: Rosiglitazone
C1: Placebo

All‐cause mortality: [n] of participants who died
(I1/ I2 / C1 / total)"

I1: 2/200
I2: 1/300
C1: 2/500
Total: 5/1000

Notes

Symbols & abbreviations: Y = yes; N = no; ? = unclear I = intervention; C = control

Open in table viewer
Table 6. Secondary outcome data (included studies)

Characteristic

Study a

Study b

Study c

Study d

Study e

Intervention 1 (I1) / intervention 2 (I2) / control 1 (C1)

I1: Pioglitazone
I2: Rosiglitazone
C1: Placebo

Weight change [kg] at 12 weeks (mean/SD)
(I1/ I2 / C1 / total)

I1: ‐2.5 (1.2)
I2: ‐1.3 (0.8)
C1: +0.3 (0.4)
Total: ‐1.2 (0.9)

Notes

Symbols & abbreviations: Y = yes; N = no; ? = unclear; I = intervention; C = control

We will extract the following data:

  • general information: published or unpublished, title, authors, study setting, funding source, reference or source, contact address, country, language of publication, year of publication, duplicate publication;

  • trial characteristics: design, duration, randomisation (and method), allocation concealment (and method), blinding of the outcome assessors.

  • intervention and comparitor;

  • participants: sampling method, exclusion criteria, total number and number in comparison groups, number who did not consent to participate, sex, age, health status, medication status, type of diabetes, criteria used to diagnose diabetes, similarity of groups at baseline, assessment of compliance, withdrawals or losses to follow‐up (reasons or description), subgroup;

  • outcomes: outcomes specified above, including the measures of dispersion; the main outcome assessed in the study; energy intake, any other outcomes assessed, length of follow‐up, quality of outcome reporting;

  • results: for outcomes and times of assessment (including a measure of variation), converted to measures of effect if appropriate, intention‐to treat analysis.

We will resolve any differences in data extraction by consensus, referring back to the original paper and discussion. We will contact primary authors when necessary to clarify data or to request additional information.

Assessment of methodological quality of included studies
Two reviewers will independently assess the quality of each included trial. We will calculate the level of inter‐rater agreement using the kappa statistic (Cohen 1960) and then resolve any difference in opinion through discussion. We will explore the influence of individual quality criteria in a sensitivity analysis (see under 'sensitivity analyses').

We will furtheron assess the internal validity of each included trial, based on the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2005). In particular, the following factors will be studied:

(1) Minimisation of selection bias ‐ a) was the randomisation procedure adequate? b) was the allocation concealment adequate?
(2) Minimisation of attrition bias ‐ a) were withdrawals and dropouts completely described? b) was the analysis by intention‐to treat?
(3) Minimisation of detection bias ‐ were the outcome assessors blind to the intervention?

Blinding of the people administering the intervention, as well as the participants actually eating the food, is generally impossible in dietary intervention trials, so blinding will not be assessed as a quality criterion. Blinding of outcome assessors to the intervention will be recorded.

Based on these criteria, the studies will be subdivided into the following three categories (Cochrane Handbook for Systematic Reviews of Interventions):
A ‐ low risk of bias: all quality criteria met
B ‐ moderate risk of bias: one or more of the quality criteria only partially met
C ‐ high risk of bias: one or more quality criteria not met

If appropriate, we will perform a sensitivity analysis based on this classification to compare the effect of quality on results in studies of high and low quality.

Measures of treatment effect
Dichotomous data

For dichotomous outcomes, we will express the effect size in terms of relative risk with 95% confidence interval (CI).

Continuous data
For continuous outcomes, if appropriate, we will calculate weighted mean differences. We will extract the baseline and post‐intervention means with standard deviations (SD) (or standard error of the mean (SEM) or 95% confidence interval (CI)) for the intervention and control groups, transforming any SEM or 95% CI into SD if appropriate. For absolute changes in outcome between baseline and post‐intervention for the control and intervention groups, mean difference will be calculated, if required, by subtracting the control absolute change from the intervention absolute change. The estimate of variance for each of these changes will equal Vpre + Vpost ‐ 2r(SEpre x SEpost), where Vpre and SEpre are the variance and standard error of the mean baseline value; Vpost and SEpost are the variance and standard error of the mean post‐intervention value; and r is the correlation between baseline and post‐intervention values. The variance of the total change is then the sum of the variance of the change in the intervention group and the variance of the change in the control group. If the value of r is not given, we will assume that r equals 0.5.
When post‐intervention measures of dispersion are not given (for example if the results are presented as percentage change from baseline), the baseline measures of dispersion will also be used as the post‐intervention values. This is a conservative approach, since variation at baseline should be larger than that at post‐intervention, but this approach will only be taken when pre‐ and post‐ measures of dispersion for the same outcome are similar to each other in other trials. If the results are given on different scales, we will use standardised mean differences or develop dichotomous variables. When data are only presented graphically, an estimate of the mean and SD will be obtained from the graph.

Dealing with missing data
Relevant missing data will be obtained from authors, if feasible. Evaluation of important numerical data such as screened, eligible and randomised patients as well as intention‐to‐treat and per‐protocol population will be carefully performed. Drop‐outs, misses to follow‐up and withdrawn study participants will be investigated. Issues of last‐observation‐carried‐forward (LOCF) will be critically appraised and compared to specification of primary outcome parameters and power calculation.

Dealing with duplicate publications
In the case of duplicate publications and companion papers of a primary study, we will try to maximise yield of information by simultaneous evaluation of all available data. In cases of doubt, the original publication (usually the oldest version) will obtain priority.

Assessment of heterogeneity
We will test for heterogeneity between the trial results using the standard chi‐squared test to examine whether the observed variation in study results could be due to any variation expected by chance alone, with significance set at P < 0.1. Quantification of the effect of heterogeneity will be assessed, if appropriate, by means of I2, ranging from 0% to 100% including its 95% confidence interval (Higgins 2002). I2 demonstrates the percentage of total variation across studies due to heterogeneity and will be used to judge the consistency of evidence. I2 values of 50% and more indicate a substantial level of heterogeneity (Higgins 2003). If heterogeneity is found, we will explore it using subgroup and sensitivity analyses. If summarising the results still seems appropriate (sufficiently similar studies of similar quality), we will use a random effects model which assumes the effect size varies across studies. We will use an intent‐to treat analysis, provided that the required information is obtainable.

Assessment of reporting biases
We will assess funnel plot asymmetry, if feasible, to explore the possibility of, for example, small sample bias (Cooper 1994; Tang 2000).

Data synthesis (meta‐analysis)
All data will initially be analysed with a fixed effect model. We will summarize the data statistically, including meta‐analysis of trial results if appropriate, that ist if the data are available and results are sufficiently homogeneous and of sufficient quality.

Subgroup analyses and investigation of heterogeneity
Subgroup analyses will only be performed if one of the primary outcome parameters demonstrates statistically significant differences between treatment groups. Subgroup analyses will be mainly used to explore clinical or methodological or statistical heterogeneity. The following subgroup analyses are planned:

  • age: less than or equal to 18 years, 19 to 40 years, 41 to 65 years, more than 65 years;

  • duration of trial intervention: short term (less than or equal to three months), medium term (three to six months), long term (more than six months)

  • difference in the glycaemic index, or load, between the comparitor and trial interventions<

  • diagnosis (type 1 or type 2 diabetes);

  • duration of diabetes;

  • initial body mass,

  • follow‐up timing: less than or equal to six months, 6 to 12 months, more than 12 months

Sensitivity analyses
We will perform sensitivity analyses in order to explore the influence of the following factors on effect size:

  • repeating the analysis excluding unpublished studies;

  • repeating the analysis taking account of study quality, as specified above;

  • repeating the analysis excluding any very long or large studies to establish how much they dominate the results;

  • repeating the analysis excluding studies using the following filters: diagnostic criteria, language of publication, source of funding (industry versus other), country.

The robustness of the results will also be tested by repeating the analysis using different measures of effects size (risk difference, odds ratio etc.) and different statistical models (fixed and random effects models).

Table 1. search strategy

Search terms

Unless otherwise stated, search terms are free text terms; MeSH = Medical subject heading (Medline medical index term); exp = exploded MeSH; the dollar sign ($) stands for any character(s); the question mark (?) = to substitute for one or no characters; tw = text word; pt = publication type; sh = MeSH; adj = adjacent.

A) Diabetes mellitus, general

1 exp diabetes mellitus/
2 diabet$.tw.
3 IDDM.tw.
4 NIDDM.tw.
5 MODY.tw.
6 insulin$ secret$ dysfunc$.tw.
7 impaired glucose toleran$.tw.
8 exp glucose intolerance/
9 glucose intoleran$.tw.
10 exp insulin resistance/
11 insulin$ resist$.tw.
12 (non insulin$ depend$ or noninsulin$ depend$ or
non insulin?depend$ or noninsulin?depend$).tw.
13 (insulin? depend$ or insulin?depend$).tw
14 metabolic$ syndrom$.tw.
15 (pluri metabolic$ syndrom$ or plurimetabolic$ syndrom$).tw.
16 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15
17 exp diabetes insipidus/
18 diabet$ insipidus.tw.
19 17 or 18
20 16 not 19

B) Controlled trials*

21 randomized‐controlled trial.pt.
22 controlled‐clinical trial.pt.
23 randomized‐controlled‐trials.sh.
24 random allocation.sh.
25 double‐blind method.sh.
26 single‐blind method.sh.
27 21 or 22 or 23 or 24 or 25 or 26
28 animal.sh.
29 human.sh.
30 28 not 29
31 27 not 30

C) Glycaemic index or glycaemic load

32 (diet adj5 glyc?emic$).tw.
33 Glycemic Index/ or glyc?emic index.tw.
34 (all bran or wholegrain or pasta or oat$ or apple$ or appricot$ or bean$ or lentil$ or wheat bran or barley porridge or raw oats or basmati rice).ti, ab.
35 (gi adj10 (diet or food or carbohydrate$)).tw.
36 (food adj5 glyc?emic$).tw.
37 (carbohydrate$ adj5 (blood glucose or blood sugar) adj5 (low or less$ or high$)).tw.
38 (puls$ adj10 (diet or food)).tw.
39 lentil$.tw.
40 or/32‐39
41 dietary carbohydrates/
42 blood glucose.sh,rn,rw.
43 41 and 42
44 40 or 43

D) Systematic reviews, meta‐analyses, health‐technology assessment reports
45 exp meta‐analysis/
46 exp Review Literature/
47 meta‐analysis.pt.
48 systematic review$.tw.
49 search$.tw.
50 medline.tw.
51 cochrane database of systematic reviews.jn.
52 45 or 46 or 47 or 48 or 49 or 50 or 51
53 letter.pt.
54 comment.pt.
55 editorial.pt.
56 historical‐article.pt.
57 53 or 54 or 55 or 56
58 52 not 57
59 exp Technology Assessment, Biomedical/
60 HTA.tw.
61 (health technology adj6 assessment$).tw.
62 (biomedical adj6 technology assessment$).tw.
63 60 or 61 or 62
64 58 or 63

65 31 or 64
66 20 and 44
67 65 and 66

* Robinson KA, Dickersin K. Development of a highly sensitive search strategy for the retrieval of reports of controlled trials using PubMed. International Journal of Epidemiology 2002;31:150‐3.

Figuras y tablas -
Table 1. search strategy
Table 2. Study quality (included studies)

Characteristic

Study a

Study b

Study c

Study d

Study e

Intervention 1 (I1) / intervention 2 (I2) / control 1 (C1)

I1: Pioglitazone
I2: Rosiglitazone
C1: Placebo

Randomised controlled clinical trial (RCT)

Non‐inferiority / equivalence trial

Controlled clinical trial

Design: parallel, crossover, factorial RCT

Design: crossover study

Design: factorial study

Crossover study: wash‐out phase

Crossover study: carryover effect tested

Crossover study: period effect tested

Method of randomisation

Unit of randomisation (individuals, cluster ‐ specify)

Randomisation stratified for centres

Randomisation ratio

Concealment of allocation

Stated blinding (open; single, double, triple blind)

Actual blinding: participant

Actual blinding: caregiver / treatment administrator

Actual blinding: outcome assessor

Actual blinding: others

Blinding checked: participant

Blinding checked: caregiver / treatment administrator

Primary endpoint defined

[n] of primary endpoint(s)

[n] of secondary endpoints

Total [n] of endpoints

Prior publication of study design

Outcomes of prior / current publication identical

Power calculation

[n] participants per group calculated

Non‐inferiority trial: interval for equivalence specified

Intention‐to‐treat analysis (ITT)

Per‐protocol‐analysis

ITT defined

Analysis stratified for centres

Missing data: last‐observation‐carried‐forward (LOCF)

Missing data: other methods

LOCF defined

[n] of screened participants (I1/ I2 / C1 / total)

[n] of randomised participants (I1/ I2 / C1 / total)

I1: 400
I2: 350
C1: 700
Total: 1450

[n] of participants finishing the study (I1/ I2 / C1 / total)

[n] of patients analysed (I1/ I2 / C1 / total)

Description of discontinuing participants

Drop‐outs (reasons explained)

Withdrawals (reasons explained)

Losses‐to‐follow‐up (reasons explained)

[n] of participants who discontinued (I1/ I2 / C1 / total)

[%] discontinuation rate (I1/ I2 / C1 / total)

Discontinuation rate similar between groups

[%] crossover between groups

Differences [n] calculated to analysed patients

[n] of subgroups

Subgroups: pre‐defined

Subgroups: post‐hoc

[n] of statistical comparisons

Adjustment for multiple outcomes / repeated measurements

Baseline characteristics: clinically relevant differences

Treatment identical (apart from intervention)

Timing of outcomes' measurement comparable between groups

Compliance measured

Other important covariates measured (specify)

Co‐morbidities measured

Co‐medications measured

Specific doubts about study quality

Funding: commercial

Funding: non‐commercial

Publication status: peer review journal

Publication status: journal supplement

Publication status: abstract

Publication status: other

Notes

Symbols & abbreviations: Y = yes; N = no; ? = unclear I = intervention; C = control

Figuras y tablas -
Table 2. Study quality (included studies)
Table 3. Baseline characteristics (included studies)

Characteristic

Study a

Study b

Study c

Study d

Study e

Intervention 1 (I1) / intervention 2 (I2) / control 1 (C1)

I1: Pioglitazone
I2: Rosiglitazone
C1: Placebo

[n] (I1/ I2 / C1 / total)

Sex [n,%] (I1/ I2 / C1 / total)

Age [years] mean (SD) (I1/ I2 / C1 / total)

I1: 43 (12)
I2: 41 (11)
C: 45 (12)
Total: 42 (10)

Ethnic groups [%] (I1/ I2 / C1 / total)

Duration of disease [years] mean (SD) (I1/ I2 / C1 / total)

Body mass index [kg/m2] mean (SD) (I1/ I2 / C1 / total)

Pharmaco‐naive patients [n,%] (I1/ I2 / C1 / total)

Co‐morbidity [%] (I1/ I2 / C1 / total)

Co‐medication [%] (I1/ I2 / C1 / total)

HbA1c [%] mean (SD) (I1/ I2 / C1 / total)

Notes

Symbols & abbreviations: Y = yes; N = no; ? = unclear
I = intervention; C = control

Figuras y tablas -
Table 3. Baseline characteristics (included studies)
Table 4. Adverse events (included studies)

Characteristic

Study a

Study b

Study c

Study d

Study e

Intervention 1 (I1) / intervention 2 (I2) / control 1 (C1)

I1: Pioglitazone
I2: Rosiglitazone
C1: Placebo

[n] of participants who died

[n] adverse events (I1/ I2 / C1 / total)

[%] adverse events (I1/ I2 / C1 / total)

[n] serious adverse events (I1/ I2 / C1 / total)

[%] serious adverse events (I1/ I2 / C1 / total)

[n] drop‐outs due to adverse events (I1/ I2 / C1 / total)

I1: 3/40
I2: 5/30
C1: 6/50
Total: 14/120

[%] drop‐outs due to adverse events (I1/ I2 / C1 / total)

[n] hospitalisation (I1/ I2 / C1 / total)

[%] hospitalisation (I1/ I2 / C1 / total)

[n] out‐patient treatment (I1/ I2 / C1 / total)

[%] out‐patient treatment (I1/ I2 / C1 / total)

[n] hypoglycaemic episodes (I1/ I2 / C1 / total)

[%] hypoglycaemic episodes (I1/ I2 / C1 / total)

[n] severe hypoglycaemic episodes (I1/ I2 / C1 / total)

[%] severe hypoglycaemic episodes (I1/ I2 / C1 / total)

[n] nocturnal hypoglycaemic episodes (I1/ I2 / C1 / total)

[%] nocturnal hypoglycaemic episodes (I1/ I2 / C1 / total)

[n] with symptoms (I1/ I2 / C1 / total)

[%] with symptoms (I1/ I2 / C1 / total)

Symbols & abbreviations: Y = yes; N = no; ? = unclear I = intervention; C = control

Figuras y tablas -
Table 4. Adverse events (included studies)
Table 5. Primary outcome data (included studies)

Characteristic

Study a

Study b

Study c

Study d

Study e

Intervention 1 (I1) / intervention 2 (I2) / control 1 (C1)

I1: Pioglitazone
I2: Rosiglitazone
C1: Placebo

All‐cause mortality: [n] of participants who died
(I1/ I2 / C1 / total)"

I1: 2/200
I2: 1/300
C1: 2/500
Total: 5/1000

Notes

Symbols & abbreviations: Y = yes; N = no; ? = unclear I = intervention; C = control

Figuras y tablas -
Table 5. Primary outcome data (included studies)
Table 6. Secondary outcome data (included studies)

Characteristic

Study a

Study b

Study c

Study d

Study e

Intervention 1 (I1) / intervention 2 (I2) / control 1 (C1)

I1: Pioglitazone
I2: Rosiglitazone
C1: Placebo

Weight change [kg] at 12 weeks (mean/SD)
(I1/ I2 / C1 / total)

I1: ‐2.5 (1.2)
I2: ‐1.3 (0.8)
C1: +0.3 (0.4)
Total: ‐1.2 (0.9)

Notes

Symbols & abbreviations: Y = yes; N = no; ? = unclear; I = intervention; C = control

Figuras y tablas -
Table 6. Secondary outcome data (included studies)