Interventions for latent autoimmune diabetes (LADA) in adults.
BACKGROUND
Latent autoimmune diabetes in Adults (LADA) is a slowly developing type 1 diabetes which presents as non-insulin dependent diabetes and progresses to insulin dependence. However, the best treatment strategy for LADA is unclear.


OBJECTIVE
To compare interventions used for LADA.


METHODS
Studies were obtained from searches of electronic databases (including MEDLINE, EMBASE), supplemented by hand searches, conference proceedings and consultation with experts.


METHODS
Selection was in duplicate by two independent reviewers. RCT and controlled clinical trials evaluating interventions for LADA or type 2 diabetes with antibodies were included.


METHODS
Two reviewers independently extracted data and assessed study quality. Studies were summarised in a descriptive manner.


RESULTS
Searches identified 8067 citations. Eight publications (seven studies) were included, involving 735 participants. All studies had high risk of bias. There were no data on use of metformin or glitazones alone. Rosiglitazone or sulphonylurea (SU) with insulin did not improve metabolic control significantly more than insulin alone. SU alone gave either poorer (one study, mean difference in HbA1c 2.8% (95% confidence interval (CI) 0.9 to 4.7) or equivalent metabolic control compared to insulin alone (two studies). There was evidence that SU caused earlier insulin dependence (insulin treated at two years: 60% (SU) and 5% (conventional care) (P < 0.001); classified insulin dependent: 64% (SU) and 12.5% (insulin group) (P = 0.007)). No interventions influenced fasting C-peptide, but insulin maintained stimulated C-peptide better than SU (one study, mean difference 7.7 ng/ml (95% CI 2.9 to 12.5) and insulin with rosiglitazone was superior to insulin alone (one study) at maintaining stimulated C-peptide. A pilot study showed better metabolic control at six months with subcutaneously administered glutamic acid decarboxylase (GAD) GAD65, a major autoantigen in autoimmune diabetes, compared to placebo. There was no information regarding quality of life, mortality, complications or costs in any of the publications. Time from diagnosis varied between recruitment at diagnosis to recruitment at nine years of disease duration and there was a great deal of variation in the selection criteria for LADA patients, making it difficult to generalise findings from these studies.


CONCLUSIONS
There are few studies on this topic and existing studies have a high risk of bias. However, there does seem to be an indication that SU should not be a first line treatment for antibody positive type 2 diabetes. There is no significant evidence for or against other lines of treatment of LADA.
Brophy
S
S
University of Wales, Swansea, Swansea School of Medicine, Grove Building, Sigleton Park, Swansea, UK, SA2 8PP. s.brophy@swansea.ac.uk
Brunt
H
H
Davies
H
H
Mannan
S
S
Williams
R
R
D000328:Adult; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D005968:Glutamate Decarboxylase / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D000077154:Rosiglitazone; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use
D002096:C-Peptide; D004365:Drugs, Chinese Herbal; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000077154:Rosiglitazone; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human