Endocrinol Metab.  2018 Jun;33(2):147-159. 10.3803/EnM.2018.33.2.147.

Latent Autoimmune Diabetes in Adults: Current Status and New Horizons

• Pozzilli P
• Pieralice

• KMID: 2420481
• DOI: http://doi.org/10.3803/EnM.2018.33.2.147

Abstract

Autoimmune diabetes is a heterogeneous disease which can arise at any age. Subjects with adult-onset autoimmune diabetes who do not necessitate insulin-therapy for at least 6 months after diagnosis are demarcated as having latent autoimmune diabetes in adults (LADA). This condition is more heterogeneous than young-onset autoimmune diabetes and shares clinical and metabolic characteristics with both type 2 and type 1 diabetes. Patients with LADA are considered by having highly variable β-cell destruction, different degrees of insulin resistance and heterogeneous titre and pattern of islet autoantibody, suggesting different pathophysiological pathways partially explaining the heterogeneous phenotypes of LADA. To date the heterogeneity of LADA does not allow to establish a priori treatment algorithm and no specific guidelines for LADA therapy are available. These subjects are mostly treated as affected by type 2 diabetes, a factor that might lead to the progression to insulin-dependency quickly. A personalised medicine approach is necessary to attain optimal metabolic control and preserve β-cell function to decrease the risk of long-term diabetes complications. Recent data concerning the use of oral antidiabetic agents as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists indicate up-and-coming results in term of protect C-peptide levels and improving glycaemic control. This review summarises current knowledge on LADA, emphasising controversies regarding its pathophysiology and clinical features. Moreover, we discuss data available about novel therapeutic approaches that can be considered for prevention of β-cell loss in LADA.

Keyword

Islet cell; Autoantibodies; Diabetes mellitus, type 1; Diabetes mellitus, type 2; C-peptide; B-cell function; Insulin; Insulin resistance; Latent autoimmune diabetes in adults

MeSH Terms

Adult*
Autoantibodies
C-Peptide
Diabetes Complications
Diabetes Mellitus, Type 1*
Diabetes Mellitus, Type 2
Diagnosis
Dipeptidyl-Peptidase IV Inhibitors
Glucagon-Like Peptide 1
Humans
Hypoglycemic Agents
Insulin
Insulin Resistance
Islets of Langerhans
Phenotype
Population Characteristics
Autoantibodies
C-Peptide
Dipeptidyl-Peptidase IV Inhibitors
Glucagon-Like Peptide 1
Hypoglycemic Agents
Insulin

Figure

• 

  Fig. 1 Pathogenetic features and their relation to define diabetes. T1DM, type 1 diabetes mellitus; LADA, latent autoimmune diabetes in adults; T2DM, type 2 diabetes mellitus [32].

• 

  Fig. 2 Potential pathological pathways of latent autoimmune diabetes in adults (LADA). Modified from Buzzetti et al., with permission from Springer Nature [13]. TCF7L2, transcription factor 7 like 2; HLA, human leukocyte antigen; INS VNTR, insulin variable number tandem repeat; PTPN22, protein tyrosine phosphatase nonreceptor 22; GADA, glutamic acid decarboxylase autoantibody; IA-2A, protein tyrosine phosphatase IA-2.

• 

  Fig. 3 Algorithm for diagnosis and therapy of latent autoimmune diabetes in adults (LADA). BMI, body mass index; T2DM, type 2 diabetes mellitus; GADA, glutamic acid decarboxylase autoantibody; DPP-4, dipeptidyl peptidase 4.

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