Type 1 diabetes Year 4 Paediatrics Notes OmpathStudy

Type 1 diabetes Year 4 · Paediatrics Collection: 4TH YEAR ALL NOTES / PAEDS / PAEDS 4.3 / Munge / ENDOCRINOLOGY -- Slide 1 Type 1 Diabetes Dr Rose Munge Slide 2 Diabetes mellitus (DM) is a common, chronic, metabolic disease characterized by hyperglycemia as a cardinal biochemical feature.\nThe major forms of diabetes are differentiated by insulin deficiency vs insulin resistance:\ntype 1 diabetes mellitus (T1DM ) results from deficiency of insulin secretion because of pancreatic β-cell damage;\ntype 2 diabetes mellitus (T2DM) is a consequence of insulin resistance occurring at the level of skeletal muscle, liver, and adipose tissue, with various degrees of β-cell impairment.\nT1DM is the most common endocrine-metabolic disorder of childhood and adolescence, with important consequences for physical and emotional development. Slide 3 DM is not a single entity but rather a heterogeneous group of disorders in which there are distinct genetic patterns as well as other etiologic and pathophysiologic mechanisms that lead to impairment of glucose tolerance through deficient insulin production or action.\n4 categories: type 1 diabetes, type 2 diabetes, other specific types, and gestational diabetes. Slide 4 Type 1 Diabetes Mellitus Characterized by low or absent levels of endogenously produced insulin and by dependence on exogenous insulin to prevent development of ketoacidosis, an acute life-threatening complication of T1DM. The natural history includes 4 distinct stages:\n(1) preclinical β-cell autoimmunity with progressive defect of insulin secretion\n(2) onset of clinical diabetes\n(3) transient remission honeymoon period (4) established diabetes during which there may occur acute and/or chronic complications and decreased life expectancy.\nThe onset occurs predominantly in childhood, with a median age of 7-15 yr, but it may present at any age. The incidence of T1DM has steadily increased in nearly all parts of the world. Slide 5 T1DM is characterized by autoimmune destruction of pancreatic islet β-cells.\nBoth genetic susceptibility and environmental factors contribute to the pathogenesis.\nSusceptibility to T1DM is genetically controlled by alleles of the major histocompatibility complex (MHC) class II genes expressing human leukocyte antigens (HLAs).\nAutoantibodies to β-cell antigens including islet cell cytoplasm (ICA), insulin autoantibody (IAA), glutamic acid decarboxylase (GADA), islet antigen 2 (IA- 2A, formerly ICA512), and zinc transporter 8 (ZnT8A) are detected in serum from affected subjects.\nThese can be detected months to years prior to clinical onset of T1DM. Slide 6 In some children and adolescents with apparent T1DM, the β- cell destruction is not immune mediated.\nThis subtype of diabetes occurs in patients of African or Asian origin and is distinct from known causes of β-cell destruction such as drugs or chemicals, viruses, mitochondrial gene defects, pancreatectomy, and ionizing radiation.\nThese individuals may have ketoacidosis, but they have extensive periods of remission with variable insulin deficiency, similar to patients with T2DM.\nPatients with T1DM require lifelong treatment with insulin. Slide 7 Type 2 Diabetes Mellitus T2DM develops as a result of insulin resistance and progressive non-autoimmune β-cell failure.\nWhile T2DM has long been the most prevalent form of diabetes in adults, the dramatic rise in childhood obesity has led to a markedly increased incidence of this disease in children and adolescents. Pediatric T2DM may account for up to 80% of the new cases of diabetes in high-risk populations. Childhood onset T2DM differs from adult disease in that it is associated with a more rapid decline in β-cell function and the earlier development of T2DM related complications. Slide 8 The presentation of T2DM is typically more insidious than that with T1DM.\nChildren with T2DM often seek medical care because of excessive weight gain and fatigue as a result of insulin resistance and/or the incidental finding of glycosuria during routine physical examination.\nA history of polyuria and polydipsia is not always a cardinal clinical feature in these patients.\nAcanthosis nigricans (dark pigmentation of skin creases in the nape of the neck especially), a sign of insulin resistance, is present in the majority of patients with T2DM and is accompanied by a relative hyperinsulinemia at the time of the diagnosis.\nHealthy lifestyle interventions and treatment with metformin remain the cornerstones of T2DM treatment in children and adolescents; however, insulin therapy is often required to control hyperglycemia. There is a strong heritable component to T2DM, although the genetic basis remains poorly understood. Slide 9 Other Specific Types of Diabetes Monogenic Diabetes The term monogenic diabetes is used to refer to a heterogeneous group of single gene disorders resulting in impaired insulin secretion.\nThis category encompasses maturity-onset diabetes of the young (MODY) as well as transien