Autoimmune Diabetes Not Requiring Insulin at Diagnosis (Latent Autoimmune Diabetes of the Adult)

Abstract

Type 1 diabetes is caused by the immune-mediated destruction of islet insulin-secreting β-cells. This chronic destructive process is associated with both cellular and humoral immune changes in the peripheral blood that can be detected months or even years before the onset of clinical diabetes. Throughout this prediabetic period, metabolic changes, including altered glucose tolerance and reduced insulin secretion, deteriorate at variable rates and eventually result in clinical diabetes. A fraction of individuals with humoral immunological changes have clinical diabetes that initially is not insulin-requiring. The onset of diabetes in these patients is usually in adult life, and because their diabetes is at least initially not insulin-requiring, they appear clinically to be affected by type 2 diabetes. Such patients probably have the same disease process as patients with type 1 diabetes in that they have similar HLA genetic susceptibility as well as autoantibodies to islet antigens, low insulin secretion, and a higher rate of progression to insulin dependency. These patients are defined as being affected by an autoimmune type of diabetes not requiring insulin at diagnosis, which is also named latent autoimmune diabetes of the adult (LADA). Special attention should be paid to diagnose such patients because therapy may influence the speed of progression toward insulin dependency, and in this respect, efforts should be made to protect residual C-peptide secretion. LADA can serve as a model for designing new strategies for prevention of type 1 diabetes but also as a target group for prevention in its own right.

The addition of metformin and glucagon-like peptide-1 receptor agonist or dipeptidyl-peptidase-4 inhibitor to insulin for latent autoimmune diabetes in adults

“…The addition of sitagliptin (50 mg/day) induced more insulin secretion (52.9 μg/day), however, could not suppress her appetite completely. Therefore, we switched from sitagliptin to exenatide (10 μg/day), which remarkably suppressed her appetite and also significantly reduced daily insulin requirement (from 42 units/day to 16 units/day), and maintained intrinsic insulin secretion (51.2 μg/day).There are no studies that evaluated metformin in patients with LADA, possibly due to potential risk for the development of lactic acidosis by metformin in patients who progress toward insulin dependency [2]. We used metformin with insulin, which improved blood glucose and increased intrinsic insulin secretion without the development of lactic acidosis.…”

“…There are no studies that evaluated metformin in patients with LADA, possibly due to potential risk for the development of lactic acidosis by metformin in patients who progress toward insulin dependency [2]. We used metformin with insulin, which improved blood glucose and increased intrinsic insulin secretion without the development of lactic acidosis.…”

Evaluation of Two Nonisotopic Immunoassays for Determination of Glutamic Acid Decarboxylase and Tyrosine Phosphatase Autoantibodies in Serum

“…RBAs, although cumbersome and requiring use of 35 S, reportedly provide more precise results and higher diagnostic sensitivity and specificity than ELISAs (2)(3)(4).…”

“…Autoantibodies against ␤-cells can be detected before clinical onset of DM1 (2,3 ) and can help to distinguish type 2 diabetes mellitus (DM2) from latent autoimmune diabetes of the adult (LADA) (4 ), which may represent one-half of cases of autoimmune diabetes (1 ). The major autoantibodies in DM1 are against islet cells, insulin, a protein tyrosine phosphatase-like protein (IA-2), and the 65-kDa isoform of glutamic acid decarboxylase (GAD65) (1 ).…”

Anti-CD38 autoantibodies: Characterisation in new-onset Type I diabetes and latent autoimmune diabetes of the adult (LADA) and comparison with other islet autoantibodies

“…Although these markers are mainly found in Type I diabetic patients, a subgroup of patients routinely classified as Type II was also found to show high prevalences of ICA and anti-GAD, but not of anti-IA-2 aAbs. These patients have later been classified as having a slow progressive form of Type I diabetes, defined as Latent Autoimmune Diabetes of the Adult (LADA) [12,13,18,19,20,21,22].…”