On the basis of the patient's personal and family history together with his presentation, the likely diagnosis is latent autoimmune diabetes in adults (LADA). LADA is characterized by beta-cell loss and insulin resistance. This slowly evolving form of autoimmune diabetes comprises 2%-12% of all patients with adult-onset diabetes. Patients with LADA present with evidence of autoimmunity and varying C-peptide levels, which decrease more slowly in this subgroup than in patients with type 1 diabetes (T1D). They also have immunogenic markers associated with T1D, primarily anti-glutamic acid decarboxylase (GAD) antibodies.
Patients with LADA are often misdiagnosed as having T2D. The clinical picture of LADA overlaps with that of T2D, with patients being insulin resistant and often overweight. In addition, presenting symptoms of LADA — excessive thirst, blurred vision, and high blood glucose — are also seen in T2D. Although LADA is technically classified as T1D, some groups posit that the condition exists on a spectrum between T1D and T2D. Compared with patients with T2D, those with LADA are generally younger at diagnosis (often in their 30s), have lower BMI, and report a personal or family history of autoimmune diseases, such as the patient in this quiz. Throughout the disease course, individuals with LADA show a reduced frequency of metabolic syndrome compared with those with T2D.
Key to diagnosis is the absence of insulin requirement for at least 6 months. Anti-GAD antibodies are the most sensitive marker for LADA; other autoantibodies that occur less frequently include ICA, IA-2A, ZnT8A, and tetraspanin 7 autoantibodies. With a paucity of large-scale clinical trials in LADA, current treatment strategies are not based on consensus guidelines, though an expert panel has published management recommendations. Category 1 patients (defined as a C-peptide level < 0.3 nmol/L) are treated with intensive insulin therapy. The recommendation for category 2 patients (defined as C-peptide values ≥ 0.3 and ≤ 0.7 nmol/L) is a modified American Diabetes Association/European Association for the Study of Diabetes algorithm for T2D. However, patients with category 2 LADA may need to initiate insulin therapy earlier to combat beta-cell failure (ostensibly because LADA is an autoimmune disease beta-cell function declines much faster than in T2D). For category 3 patients (defined as C-peptide values > 0.7 nmol/L), treatment decisions are made in response to changing C-peptide levels.
Romesh K. Khardori, MD, PhD, Professor, Department of Internal Medicine, Division of Diabetes, Endocrine, and Metabolic Disorders, Eastern Virginia Medical School; EVMS Medical Group, Norfolk, Virginia.
Romesh K. Khardori, MD, PhD, has disclosed no relevant financial relationships.