Interventions for latent autoimmune diabetes (LADA) in adults

Sinead Brophy, H. Brunt, H. Davies, Sopna Choudhury, R. Williams

Research output: Contribution to journalReview article

36 Citations (Scopus)

Abstract

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. Objectives: To compare interventions used for LADA. Search strategy: Studies were obtained from searches of electronic databases (including MEDLINE, EMBASE), supplemented by hand searches, conference proceedings and consultation with experts. Selection criteria: 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. Data collection and analysis: Two reviewers independently extracted data and assessed study quality. Studies were summarised in a descriptive manner. Main 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: 30% (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. Authors' 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.

Original languageEnglish
Article numberCD006165
JournalCochrane Database of Systematic Reviews
Issue number3
DOIs
Publication statusPublished - 1 Dec 2007
Externally publishedYes

Fingerprint

Insulin
Type 1 Diabetes Mellitus
rosiglitazone
C-Peptide
Type 2 Diabetes Mellitus
Patient Selection
Publications
Latent Autoimmune Diabetes in Adults
Metabolic Equivalent
Confidence Intervals
Thiazolidinediones
Glutamate Decarboxylase
Antibodies
Metformin
Controlled Clinical Trials
Autoantigens
MEDLINE
Fasting
Referral and Consultation
Placebos

Keywords

  • Autoimmune diseases [*drug therapy; immunology]
  • C-peptide [blood]
  • Diabetes mellitus, type 1 [*drug therapy; immunology]
  • Diabetes mellitus, type 2 [*drug therapy; immunology]
  • Drugs, chinese herbal [therapeutic use]

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Interventions for latent autoimmune diabetes (LADA) in adults. / Brophy, Sinead; Brunt, H.; Davies, H.; Choudhury, Sopna; Williams, R.

In: Cochrane Database of Systematic Reviews, No. 3, CD006165, 01.12.2007.

Research output: Contribution to journalReview article

@article{b63c28e20e8144e9b7d9f0c2f02ca2ad,
title = "Interventions for latent autoimmune diabetes (LADA) in adults",
abstract = "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. Objectives: To compare interventions used for LADA. Search strategy: Studies were obtained from searches of electronic databases (including MEDLINE, EMBASE), supplemented by hand searches, conference proceedings and consultation with experts. Selection criteria: 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. Data collection and analysis: Two reviewers independently extracted data and assessed study quality. Studies were summarised in a descriptive manner. Main 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: 30{\%} (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. Authors' 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.",
keywords = "Autoimmune diseases [*drug therapy; immunology], C-peptide [blood], Diabetes mellitus, type 1 [*drug therapy; immunology], Diabetes mellitus, type 2 [*drug therapy; immunology], Drugs, chinese herbal [therapeutic use]",
author = "Sinead Brophy and H. Brunt and H. Davies and Sopna Choudhury and R. Williams",
year = "2007",
month = "12",
day = "1",
doi = "10.1002/14651858.CD006165.pub2",
language = "English",
journal = "Cochrane Database of Systematic Reviews",
issn = "1361-6137",
publisher = "John Wiley and Sons Ltd",
number = "3",

}

TY - JOUR

T1 - Interventions for latent autoimmune diabetes (LADA) in adults

AU - Brophy, Sinead

AU - Brunt, H.

AU - Davies, H.

AU - Choudhury, Sopna

AU - Williams, R.

PY - 2007/12/1

Y1 - 2007/12/1

N2 - 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. Objectives: To compare interventions used for LADA. Search strategy: Studies were obtained from searches of electronic databases (including MEDLINE, EMBASE), supplemented by hand searches, conference proceedings and consultation with experts. Selection criteria: 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. Data collection and analysis: Two reviewers independently extracted data and assessed study quality. Studies were summarised in a descriptive manner. Main 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: 30% (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. Authors' 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.

AB - 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. Objectives: To compare interventions used for LADA. Search strategy: Studies were obtained from searches of electronic databases (including MEDLINE, EMBASE), supplemented by hand searches, conference proceedings and consultation with experts. Selection criteria: 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. Data collection and analysis: Two reviewers independently extracted data and assessed study quality. Studies were summarised in a descriptive manner. Main 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: 30% (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. Authors' 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.

KW - Autoimmune diseases [drug therapy; immunology]

KW - C-peptide [blood]

KW - Diabetes mellitus, type 1 [drug therapy; immunology]

KW - Diabetes mellitus, type 2 [drug therapy; immunology]

KW - Drugs, chinese herbal [therapeutic use]

UR - http://www.scopus.com/inward/record.url?scp=44949210532&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44949210532&partnerID=8YFLogxK

U2 - 10.1002/14651858.CD006165.pub2

DO - 10.1002/14651858.CD006165.pub2

M3 - Review article

JO - Cochrane Database of Systematic Reviews

JF - Cochrane Database of Systematic Reviews

SN - 1361-6137

IS - 3

M1 - CD006165

ER -