Pediatric Versus Adult-onset Type 1 Diabetes Mellitus: Are They Different?Chapter 1
Type 1 diabetes mellitus (T1DM) is a chronic organ-specific autoimmune disorder resulting from a destruction of pancreatic β-cells by activated T-cells. While T1DM is most common form of diabetes in children and adolescents and young adults in Caucasians, it may present at any age group including adults. In fact, a larger proportion of patients with T1DM are diagnosed as adults than in childhood. While the basic etiology and pathophysiology of T1DM, i.e., destructive insulitis remains the same in childhood and adult T1DM, their clinical presentation and prognosis may differ somewhat. The diagnosis of T1DM may often be missed in adults and patients may be managed as T2DM for many years with suboptimal control. This is because there is a wide range of presentation of autoimmune diabetes in adults ranging from a presentation with short duration of hyperglycemic symptoms, markedly elevated glucose and ketoacidosis to that indistinguishable from T2DM and diagnosed only by presence of islet antibodies [known as latent autoimmune diabetes in adults (LADA)]. These latter patients have lower β-cell reserve and earlier requirement of insulin compared to patients with T2DM.
PREVALENCE AND INCIDENCE
While the prevalence and incidence of childhood-onset T1DM is well documented, information for T1DM in adults is available. This is partly due to the fact that it is difficult to diagnose T1DM in adults, due to their variable presentation and lack of routine islet antibody testing. A meta-analysis suggests that the incidence of T1DM is lower in adults than children and declines with increasing age.1 For unknown reasons T1DM in adults is more common in males, compared with the female preponderance in early-onset T1DM.
PATHOGENESIS AND ETIOLOGY
Adult T1DM patients have a lower frequency of different islet antibodies including insulin antibodies. Adult patients also have a lower frequency of high risk human leukocyte antigen (HLA)-DR and DQ alleles when compared with those with childhood-onset T1DM.2
In contrast to T1DM in children and adolescents, the illness in adults has a more variable presentation. Even among patients with classical features of T1DM, clinical features differ somewhat between those with onset less than 20 years and at an older age. The latter have a longer duration of symptoms prior to their diagnosis, decreased metabolic decompensation at diagnosis, higher body mass index (BMI), and greater C-peptide levels, suggesting a lower level of β-cell autoimmune destruction.
The prognosis of T1DM in children and adults may differ. While mortality is higher in T1DM in all age groups when compared with the general population, it is improving in patients with childhood T1DM but not in those with adult-onset disease. Mortality due to chronic complications of diabetes has decreased in early-onset patients but not in adult-onset subjects.
LATENT AUTOIMMUNE DIABETES IN ADULTS
This refers to an autoimmune form of diabetes presenting in adults with a clinical presentation which is similar to T2DM and not requiring insulin for at least 6 months from the time of diagnosis.3 The diagnosis can be made only by the detection of antibodies against islet antigens. The most frequent antibody is against antiglutamic acid decarboxylase (GAD), which is found in 5–10% of patients with T2DM in different Western series. The frequency of the GAD antibody in adults is higher in populations where T1DM is more frequent, such as in Scandinavians. Patients with LADA share HLA and other susceptibility antigens with T1DM, as well as genetic similarities with T2DM, though the strength of the associations may vary. As a group, patients with LADA have lower mean age at onset, lower BMI, higher HbA1c, lower C-peptide, and an earlier requirement of insulin for treatment when compared with T2DM patients without islet antibodies.
The frequency of LADA in different racial groups is lower than in European Caucasians. In Indians, two large studies have reported a low frequency of LADA among patients of North Indian ancestry, between 2%.4 This may be related to differences in HLA or other susceptibility antigens.
- Diaz-Valencia PA, Bougnères P, Valleron AJ. Global epidemiology of type 1 diabetes in young adults and adults: a systematic review. BMC Public Health. 2015; 15: 255.
- Karlajainen J, Salmela P, Ilonen J, Surcel HM, Knip M. A comparison of childhood and adult type 1 diabetes. N Engl J Med. 1989; 320 (140): 881–6.
- Laugesen E, Østergaard JA, Leslie RD, Danish Diabetes Academy Workshop and Workshop Speakers. Latent autoimmune diabetes of adults: current knowledge and uncertainty. Diabet Med. 2015; 32 (7): 843–52.
- Sachan A, Zaidi G, Sahu RP Agrawal S, Colman PG, Bhatia E. Low prevalence of latent autoimmune diabetes in adults in northern India. Diabet Med. 2014; 32 (6): 810–3.