title: Intensive versus conventional glycaemic control for treating diabetic foot ulcers.
abstract: BACKGROUND
  The estimated likelihood of lower limb amputation is 10 to 30 times higher amongst people with diabetes compared to those without diabetes. Of all non-traumatic amputations in people with diabetes, 85% are preceded by a foot ulcer. Foot ulceration associated with diabetes (diabetic foot ulcers) is caused by the interplay of several factors, most notably diabetic peripheral neuropathy (DPN), peripheral arterial disease (PAD) and changes in foot structure. These factors have been linked to chronic hyperglycaemia (high levels of glucose in the blood) and the altered metabolic state of diabetes. Control of hyperglycaemia may be important in the healing of ulcers.
  
  
  OBJECTIVE
  To assess the effects of intensive glycaemic control compared to conventional control on the outcome of foot ulcers in people with type 1 and type 2 diabetes.
  
  
  METHODS
  In December 2015 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; Elsevier SCOPUS; ISI Web of Knowledge Web of Science; BioMed Central and LILACS. We also searched clinical trial databases, pharmaceutical trial databases and current international and national clinical guidelines on diabetes foot management for relevant published, non-published, ongoing and terminated clinical trials. There were no restrictions based on language or date of publication or study setting.
  
  
  METHODS
  Published, unpublished and ongoing randomised controlled trials (RCTs) were considered for inclusion where they investigated the effects of intensive glycaemic control on the outcome of active foot ulcers in people with diabetes. Non randomised and quasi-randomised trials were excluded. In order to be included the trial had to have: 1) attempted to maintain or control blood glucose levels and measured changes in markers of glycaemic control (HbA1c or fasting, random, mean, home capillary or urine glucose), and 2) documented the effect of these interventions on active foot ulcer outcomes. Glycaemic interventions included subcutaneous insulin administration, continuous insulin infusion, oral anti-diabetes agents, lifestyle interventions or a combination of these interventions. The definition of the interventional (intensive) group was that it should have a lower glycaemic target than the comparison (conventional) group.
  
  
  METHODS
  All review authors independently evaluated the papers identified by the search strategy against the inclusion criteria. Two review authors then independently reviewed all potential full-text articles and trials registry results for inclusion.
  
  
  RESULTS
  We only identified one trial that met the inclusion criteria but this trial did not have any results so we could not perform the planned subgroup and sensitivity analyses in the absence of data. Two ongoing trials were identified which may provide data for analyses in a later version of this review. The completion date of these trials is currently unknown.
  
  
  CONCLUSIONS
  The current review failed to find any completed randomised clinical trials with results. Therefore we are unable to conclude whether intensive glycaemic control when compared to conventional glycaemic control has a positive or detrimental effect on the treatment of foot ulcers in people with diabetes. Previous evidence has however highlighted a reduction in risk of limb amputation (from various causes) in people with type 2 diabetes with intensive glycaemic control. Whether this applies to people with foot ulcers in particular is unknown. The exact role that intensive glycaemic control has in treating foot ulcers in multidisciplinary care (alongside other interventions targeted at treating foot ulcers) requires further investigation.
authors.affiliation: Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia, 4814.
authors.forename: Malindu E
authors.initials: ME
authors.lastname: Fernando
authors.forename: Ridmee M
authors.initials: RM
authors.lastname: Seneviratne
authors.forename: Yong Mong
authors.initials: YM
authors.lastname: Tan
authors.forename: Peter A
authors.initials: PA
authors.lastname: Lazzarini
authors.forename: Kunwarjit S
authors.initials: KS
authors.lastname: Sangla
authors.forename: Margaret
authors.initials: M
authors.lastname: Cunningham
authors.forename: Petra G
authors.initials: PG
authors.lastname: Buttner
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D017719:Diabetic Foot / Q000209:etiology / Q000628:therapy*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000628:therapy*