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Review
. 2011 Sep 7;2011(9):CD006165.
doi: 10.1002/14651858.CD006165.pub3.

Interventions for latent autoimmune diabetes (LADA) in adults

Sinead Brophy  1 , Helen Davies, Sopna Mannan, Huw Brunt, Rhys Williams
Affiliations
Review

Interventions for latent autoimmune diabetes (LADA) in adults

Sinead Brophy et al. Cochrane Database Syst Rev. .

Abstract

Background: Latent autoimmune diabetes in adults (LADA) is a slowly developing type 1 diabetes.

Objectives: To compare interventions used for LADA.

Search strategy: Studies were obtained from searches of electronic databases, supplemented by handsearches, conference proceedings and consultation with experts. Date of last search was December 2010.

Selection criteria: Randomised controlled trials (RCT) and controlled clinical trials (CCT) evaluating interventions for LADA or type 2 diabetes with antibodies were included.

Data collection and analysis: Two authors independently extracted data and assessed risk of bias. Studies were summarised using meta-analysis or descriptive methods.

Main results: Searches identified 13,306 citations. Fifteen publications (ten studies) were included, involving 1019 participants who were followed between three months to 10 years (1060 randomised). All studies had a high risk of bias. Sulphonylurea (SU) with insulin did not improve metabolic control significantly more than insulin alone at three months (one study, n = 15) and at 12 months (one study, n = 14) of treatment and follow-up. SU (with or without metformin) gave poorer metabolic control compared to insulin alone (mean difference in glycosylated haemoglobin A1c (HbA1c) from baseline to end of study, for insulin compared to oral therapy: -1.3% (95% confidence interval (CI) -2.4 to -0.1; P = 0.03, 160 participants, four studies, follow-up/duration of therapy: 12, 30, 36 and 60 months; however, heterogeneity was considerable). In addition, there was evidence that SU caused earlier insulin dependence (proportion requiring insulin at two years was 30% in the SU group compared to 5% in conventional care group (P < 0.001); patients classified as insulin dependent was 64% (SU group) and 12.5% (insulin group, P = 0.007). No intervention 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)). In a five year follow-up of GAD65 (glutamic acid decarboxylase formulated with aluminium hydroxide), improvements in fasting and stimulated C-peptide levels (20 μg group) were maintained after five years. Short term (three months) follow-up in one study (n = 74) using Chinese remedies did not demonstrate a significant difference in improving fasting C-peptide levels compared to insulin alone (0.07 µg/L (95% CI -0.05 to 0.19). One study using vitamin D with insulin showed steady fasting C-peptide levels in the vitamin D group but declining fasting C-peptide levels (368 to 179 pmol/L, P = 0.006) in the insulin alone group at 12 months follow-up. Comparing studies was difficult as there was a great deal of heterogeneity in the studies and in their selection criteria. There was no information regarding health-related quality of life, complications of diabetes, cost or health service utilisation, mortality and limited evidence on adverse events (studies on oral agents or insulin reported no adverse events in terms of severe hypoglycaemic episodes).

Authors' conclusions: Two studies show SU leading to earlier insulin dependence and a meta-analysis of four studies with considerable heterogeneity showed poorer metabolic control if SU is prescribed for patients with LADA compared to insulin. One study showed that vitamin D with insulin may protect pancreatic beta cells in LADA. Novel treatments such as GAD65 in certain doses (20 μg) have been suggested to maintain fasting and stimulated C-peptide levels. However, there is no significant evidence for or against other lines of treatment of LADA.

PubMed Disclaimer

Conflict of interest statement

SB was lead investigator on an RCT in LADA examining insulin compared to tablet treatment. This trial is now terminated.

Figures

1
1
Study flow diagram.
2
2
Forest plot of comparison: Insulin compared to tablet , Outcome: Average mean difference in HbA1c from baseline to study endpoint.
3
3
Forest plot of comparison: 2 Sensitivity analysis, outcome: 2.1 HbA1c at final point.
4
4
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
5
5
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 HbA1c mean difference in insulin compared to tablet, Outcome 1 Average mean difference in HbA1c from baseline to endpoint.
1.2
1.2. Analysis
Comparison 1 HbA1c mean difference in insulin compared to tablet, Outcome 2 Mean difference of HbA1c at study end point.
2.1
2.1. Analysis
Comparison 2 Sensitivity analysis, Outcome 1 HbA1c at final point.
2.2
2.2. Analysis
Comparison 2 Sensitivity analysis, Outcome 2 Mean difference from baseline at study endpoint.
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References

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References to ongoing studies

Agardh 2004 {unpublished data only}
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Brophy 2007 {unpublished data only}
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Grill 2010 {unpublished data only}
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Zhou 2010 {unpublished data only}
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