Tipos de desengrase

Our intention was to identify all of the trials and other studies of treatment of hyperglycaemia in CF, to data extract the good-quality ones, and, if appropriate, to carry out a meta-analysis. A highly sensitive search strategy was run in order to identify all aspects of patients with CF with diabetes and hyperglycaemia, including treatment, screening and diagnosis.

The databases searched were MEDLINE (1950 to May 2008), EMBASE (1980 to 2008 Week 20), Web of Science databases (1970 to May 2008), ISI Proceedings (1990 to May 2008) and Cochrane Central Register of Controlled Trials (Issue 2, 2008). Auto-alerts were run in Ovid MEDLINE and EMBASE from May 2008 to December 2010. No restrictions were placed on language and several papers were translated. Full details of the search strategies are shown in Appendix 1. Reference lists of included studies and relevant review articles were scanned.

The internet was searched for grey literature, publications and reports, including websites of the Cystic Fibrosis Trust UK and similar organisations worldwide.

The meeting abstracts of Diabetes UK, ADA, the European Association for the Study of Diabetes (EASD), the European Cystic Fibrosis Society, the Annual North American Cystic Fibrosis Conference, and the International Society for Pediatric and Adolescent Diabetes (ISPAD) were searched up until 2010.

Research in progress was searched on ClinicalTrials.gov, Controlled-trials.com and the UK Clinical Research Network.

Full details are shown in Appendix 1, Figure 5.

We started from the position that insulin treatment is beneficial in CFRD (compared with no glucose-lowering treatment), so most interest was in the following four questions:

■ Are oral agents, such as sulfonylureas or meglitinide analogues, useful?

■ Are any treatments beneficial at lesser stages of hyperglycaemia, such as IGT or PPH? ■ How big a difference does insulin treatment make, not just to glycaemic control, but also to

lung function and other morbidities that are specifically associated with CF? ■ Which form(s) of insulin is/are best?

We use the term ‘PPH’ here to refer to the lag storage state, with glucose elevated after meals, including at the intermediate time points in the OGTT (30, 60 and 90 minutes) but normal by 2 hours, hence excluding IGT. This creates two problems. First, most studies use the reduced OGTT with only fasting and 2-hour glucoses measured. Second, most of the literature on PPH refers to hyperglycaemia 2 hours after a meal.

It is believed that PPH is a risk factor for macrovascular disease, even when levels of HbA_1c and FPG are normal.87 _{The DECODE (Diabetes Epidemiology: Collaborative Analysis of Diagnostic} Criteria in Europe) study140 _{found that there was a relative risk for heart disease (compared with} people with normal glucose levels) of 1.5 for men and 1.6 for women with IGT, whereas there was little increase in risk for those with only IFG. However, macrovascular risk is not currently a problem in CFRD.

Unfortunately, the quantity and quality of evidence were disappointing. There are very few randomised trials, and only one RCT141 _{that addresses the question of whether or not treatment} of CFRD IGT is beneficial (although it included only those with ‘severe IGT’). Some studies (9 out of 27) were available only as abstracts. Some of these abstracts appeared several years ago, making it unlikely that all will be followed by full publications.

A Cochrane review published in 2005136 _{looked at the use of insulin and other oral agents for} managing CFRD and examined the evidence that these agents have a beneficial impact on lung function and weight when used on patients with CF. The authors did a thorough search

of relevant databases to find studies that compared different insulin regimens with each other and with regimens of oral diabetic medications. The results and outcome measures to be used were glycaemic control, pulmonary function, nutritional status and mortality, together with the prevalence of CFRD complications and its therapeutic management. Twenty references to 14 studies were identified by searches, but none was deemed eligible for inclusion in the review, as none was a RCT. The authors concluded that no firm conclusions can be made about the optimal management method for controlling glucose metabolism in CFRD, and identified the need for a multicentre RCT examining both the efficacy of insulin or oral agents and their possible adverse effects in managing CFRD. An update in 2009 found little change.136

A survey was conducted recently by Mohan et al.81 _{looking at the management of CFRD in} the UK. A questionnaire survey regarding screening, diagnosis, treatment and monitoring of CFRD was sent to all 45 recognised UK CF centres (19 adults, 22 paediatric and 4 joint, with > 50 patients), asking about clinical practice and the extent to which this adhered to the recommendations published by the UK CF Trust Diabetes Working Group in 2004. Completed questionnaires were returned by 37 centres (82%). The overall prevalence of CFRD at these centres was 18%; 6% in paediatric (126 of 2083 patients), 28% in adult (659 of 2340), and 18% in joint centres (174 of 955), respectively, which suggests that they were representative of the UK estimated 10–15% prevalence of CFRD in all people with CF.

Insulin was the preferred treatment of choice in all but one centre. Oral glucose-lowering drugs were little used. Twenty-one centres (57%) reported that they would never use them and the remainder considered them only in the early stage of disease, when patients could not cope with insulin treatment or when glucose intolerance was induced by treatment with steroids. Oral glucose-lowering drugs were even less popular in paediatric centres than in adult centres [used in 4/17 (23.5%) vs 9/16 (56%); p < 0.05 – as reported by authors, but our calculations give Fisher’s exact test p = 0.08]. Twenty-six (70%) centres would consider short-term insulin when faced with hyperglycaemia (≥ 11.1 mmol/l) in patients admitted for pulmonary exacerbation and arrange outpatient investigation during clinical stability. No centres imposed any significant dietary restrictions, but 18 (49%) advised against sugary drinks.