Autoimmune diabetes, but not type 2 diabetes, was strongly and gender neutrally associated with an increased prevalence of hypo- and hyperthyroidism and the presence of thyroid peroxidase antibodies. Increased surveillance for hypothyroidism appears not necessary in patients with type 2 diabetes.
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.
Relationships between circulating immune mediators (cytokines, chemokines and growth factors) and a beta cell destructive autoimmune process in adult-onset type 1 diabetes are poorly elucidated. We measured serum levels of immune mediators in type 1 diabetic patients in the context of ongoing deterioration of endogenous insulin secretion. Levels of 27 immune mediators were measured in 34 GADA (glutamic acid decarboxylase antibodies) positive type 1 diabetic patients, aged 27.4 ± 1.2 years at a mean of 7 weeks after diagnosis (designated 0 month) and 6 months later. Endogenous insulin secretion was assessed by C-peptide glucagon stimulation tests during 12 months. Additional data (for baseline analysis) was obtained in 9 GADA positive type 1 diabetic subjects and in 43 non-diabetic age- and sex-matched subjects. In general, the levels of immune mediators displayed large inter- but small intra-individual differences with only minor changes observed between measurements at 0 month and at 6 months. Levels of the majority of immune mediators were strongly and positively correlated to each other not only in the diabetic, but also in the non-diabetic subjects. Body weight (BMI) was positively associated with levels of IL-1 ra, IL-2, IL-4, IL-6, IL-17, Basic FGF, GCSF, IFN gamma and MIP-1 alpha. Adjustment for BMI removed most associations to C-peptide. When adjusted for BMI, levels at 0 month for Basic FGF and MIP-1 alpha were inversely associated with the percentage decline in stimulated C-peptide from 0 to 12 months (nominally p < 0.05). We conclude that associations between different immune mediators are strikingly but not exclusively tied in autoimmune diabetes. BMI is a major confounder in the analysis of associations to autoimmunity. Associations of beta cell decline to individual immune mediators need confirmation in further studies.
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