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Investigating optimal β-cell-preserving treatment in latent autoimmune diabetes in adults : Results from a 21-month randomized trial

Hals, Ingrid K.; Fiskvik Fleiner, Hanne; Reimers, Nina; Astor, Marianne C.; Filipsson, Karin LU ; Ma, Zuheng; Grill, Valdemar and Björklund, Anneli (2019) In Diabetes, Obesity and Metabolism
Abstract

Aims: To compare outcomes of glucagon-stimulated C-peptide tests (GSCTs) in people with latent autoimmune diabetes in adults (LADA) after a 21-month intervention with either insulin or the dipeptidyl peptidase-4 inhibitor sitagliptin. Research design and methods: We included 64 glutamic acid decarboxylase (GAD) antibody-positive individuals, who were diagnosed with diabetes <3 years before the study, aged 30 to 70 years, and without clinical need for insulin treatment. We stratified participants by age and body mass index (BMI) and evaluated β-cell function by GSCT after a 48-hour temporary withdrawal of study medication. Results: Age at randomization (mean 53 years), BMI (mean 27 kg/m2) and metabolic markers were similar... (More)

Aims: To compare outcomes of glucagon-stimulated C-peptide tests (GSCTs) in people with latent autoimmune diabetes in adults (LADA) after a 21-month intervention with either insulin or the dipeptidyl peptidase-4 inhibitor sitagliptin. Research design and methods: We included 64 glutamic acid decarboxylase (GAD) antibody-positive individuals, who were diagnosed with diabetes <3 years before the study, aged 30 to 70 years, and without clinical need for insulin treatment. We stratified participants by age and body mass index (BMI) and evaluated β-cell function by GSCT after a 48-hour temporary withdrawal of study medication. Results: Age at randomization (mean 53 years), BMI (mean 27 kg/m2) and metabolic markers were similar between treatment arms. Glycated haemoglobin concentrations during intervention did not differ between arms. Fasting C-peptide concentrations after the intervention were similar, as were stimulated C-peptide levels (0.82 ± 0.63 nmol/L after insulin, 0.82 ± 0.46 nmol/L after sitagliptin; nonsignificant). Autoimmunity in the study population (estimated from GAD antibody titres and positivity/no positivity for zinc transporter 8 and islet antigen 2 antibodies) affected the evolution of the GSCT results significantly, which deteriorated in participants with high but not in those with low autoimmunity. Adjustment using analysis of covariance for the degree of autoimmunity did not alter the findings of no difference between treatment arms. Conclusions: β-cell function after intervention was similar in patients with insulin- and sitagliptin-treated LADA, regardless of the strength of autoimmunity. Further, participants with low levels of GAD antibodies did not experience progressive deterioration of β-cell function over a 21-month period. Taken together, these findings could be useful for clinicians' choices of treatment in people with LADA.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
clinical trial, insulin therapy, LADA, latent autoimmune diabetes in adults, randomized trial, sitagliptin, β-cell function
in
Diabetes, Obesity and Metabolism
publisher
Wiley-Blackwell
external identifiers
  • scopus:85067901718
ISSN
1462-8902
DOI
10.1111/dom.13797
language
English
LU publication?
yes
id
67f7e12d-f026-47c7-9331-ab40a093a012
date added to LUP
2019-07-05 12:57:34
date last changed
2019-07-30 05:06:07
@article{67f7e12d-f026-47c7-9331-ab40a093a012,
  abstract     = {<p>Aims: To compare outcomes of glucagon-stimulated C-peptide tests (GSCTs) in people with latent autoimmune diabetes in adults (LADA) after a 21-month intervention with either insulin or the dipeptidyl peptidase-4 inhibitor sitagliptin. Research design and methods: We included 64 glutamic acid decarboxylase (GAD) antibody-positive individuals, who were diagnosed with diabetes &lt;3 years before the study, aged 30 to 70 years, and without clinical need for insulin treatment. We stratified participants by age and body mass index (BMI) and evaluated β-cell function by GSCT after a 48-hour temporary withdrawal of study medication. Results: Age at randomization (mean 53 years), BMI (mean 27 kg/m<sup>2</sup>) and metabolic markers were similar between treatment arms. Glycated haemoglobin concentrations during intervention did not differ between arms. Fasting C-peptide concentrations after the intervention were similar, as were stimulated C-peptide levels (0.82 ± 0.63 nmol/L after insulin, 0.82 ± 0.46 nmol/L after sitagliptin; nonsignificant). Autoimmunity in the study population (estimated from GAD antibody titres and positivity/no positivity for zinc transporter 8 and islet antigen 2 antibodies) affected the evolution of the GSCT results significantly, which deteriorated in participants with high but not in those with low autoimmunity. Adjustment using analysis of covariance for the degree of autoimmunity did not alter the findings of no difference between treatment arms. Conclusions: β-cell function after intervention was similar in patients with insulin- and sitagliptin-treated LADA, regardless of the strength of autoimmunity. Further, participants with low levels of GAD antibodies did not experience progressive deterioration of β-cell function over a 21-month period. Taken together, these findings could be useful for clinicians' choices of treatment in people with LADA.</p>},
  author       = {Hals, Ingrid K. and Fiskvik Fleiner, Hanne and Reimers, Nina and Astor, Marianne C. and Filipsson, Karin and Ma, Zuheng and Grill, Valdemar and Björklund, Anneli},
  issn         = {1462-8902},
  keyword      = {clinical trial,insulin therapy,LADA,latent autoimmune diabetes in adults,randomized trial,sitagliptin,β-cell function},
  language     = {eng},
  month        = {05},
  publisher    = {Wiley-Blackwell},
  series       = {Diabetes, Obesity and Metabolism},
  title        = {Investigating optimal β-cell-preserving treatment in latent autoimmune diabetes in adults : Results from a 21-month randomized trial},
  url          = {http://dx.doi.org/10.1111/dom.13797},
  year         = {2019},
}