IDDM Lecture 5 PDF

DIABETES MELLITUS in Children (IDDM) Lecture 5 Department of Pediatrics Prof Malak Shaheen Objectives at the end of this lecture, you will be able to Describe the mechanisms of hyperglycemia and DKA Perform an initial assessment on a child who is exper...

DIABETES MELLITUS in Children (IDDM) Lecture 5 Department of Pediatrics Prof Malak Shaheen Objectives at the end of this lecture, you will be able to Describe the mechanisms of hyperglycemia and DKA Perform an initial assessment on a child who is experiencing hyperglycemia and DBA Develop an effective management plan Definition of DM  A syndrome of disturbed energy homeostasis caused by a deficiency of insulin or of its action  an abnormal metabolism of CHO, fat, protein. Regulation of Plasma Glucose Level  Pathophysìology — Type 1 DM is characterized by an absolute deficiency of insulin due to immune- mediated destruction of the pancreatic B-cells —In rare cases the B-cell destruction is not due to immune mediated reaction (idiopathic type 1 DM)  tnsuhn seer ated into bloodshe am Bla ad capillar y Insulin Insulin- producing producing cells cells destroyed  Diabetes: Warning Signs International Society for Pediatric and Adolescent Diabetes Diagnosis oł Diabetes Mellitus Diagnosing diabetes Classification  Diabetes is heterogeneous group of disorders.  Three major forms of Diabetes and several forms of carbohydrate intolerance have been identified which are: 1. Type I diabetes: (juvenile-onset diabetes) 2. Type II diabetes: (Adult-onset diabetes, maturity onset diabetes (MOD) or stable diabetes) 3. Secondary Diabetes.  Type I diabetes (juvenile-onset diabetes)  Characterized by severe insulinopenic & dependence on exogenous insulin to prevent ketosis and to preserve life.  Also termed insulin dependent diabetes mellitus (IDDM).  Onset occurs in childhood. It may come at any age.  Associated with certain histocompatibility antigen (HLA) B8, B15, DR3 & DR4.  There is circulating antibodies to cytoplasmic & cell surface components of islet cells and antibodies to insulin.  Type II diabetes (Adult-onset diabetes, maturity onset diabetes (MOD) or stable diabetes)  Not insulin dependent, therefore termed non-insulin dependent diabetes mellitus (NIDDM).  Serum concentration of insulin may be normal or moderately ↓.  Onset occurs after age of 40. It is rare in childhood & adolescence.  Usually occurs in obese individuals. There appears to be adequate secretion of insulin, but there is also resistance to it.  There is strong family history of Type II diabetes (a pattern suggestive of dominant inheritance). This pattern of diabetes is termed MODY (Monogenic diabetes).  No association with human leukocyte antigen (HLA), autoimmunity and/or islet cell antibodies.  Secondary Diabetes  Diabetes secondary to: 1.Exocrine pancreatic disease as cystic fibrosis. 2. Endocrine disease other than pancreatic disease as Cushing syndrome & ingestion of certain drugs or poisons. 3.Certain genetic syndromes including those with abnormality of the insulin receptor are included.  No association with HLA autoimmunity or islet cell antibodies.  Type I Diabetes Mellitus (IDDM, Juvenile-onset diabetes)  Epidemiology  Males & females are almost equally affected.  Peak of presentation occurs at 2 age groups; at 5- 7 yrs & at puberty.  Seasonal and cyclic variation occurs ► More in autumn & winter ms.  Incidence ↑ in children with congenital rubella. These associations with viral infections suggest a potential role for viruses as direct or indirect triggering mechanisms in the etiology of diabetes.  Prevalence is about 0.2 - 1.2 in a 1000 in Egypt & all over the world. Etiology and Pathogenesis A. Genetic factors: Prevalence of Type I diabetes occurs among persons with such disorders as Addison’s disease, Hashimoto's thyroiditis & pernicious anemia. These conditions together with type I diabetes are associated with ↑ frequency of HLA, in particular HLAB8, B15, DR3 & DR4.  Etiology and Pathogenesis B. Environmental factors: Viral infections: Triggering factors as mumps, rubella and coxackie virus B4 may act by directly destroying B cells, by persistence B cell as slow viral infections, or by triggering a wide spread immune response to several endocrine tissues. Dietary factors: Early exposure to cow’s milk may be a factor in triggering diabetes. Thus explaining the reported lower incidence of diabetes among breast fed infants. Seasonal factors: as DM occur more in autumn & winter, which may be related to occurrence of mumps or other viral infection. Chemicals: some drugs as alloxan are directly toxic to B-cell. Etiology and Pathogenesis - As there is sharply ↓ secretion of insulin. Failure of pancreatic B-cell function points to the autoimmune destruction of pancreatic islets, which could be due to interaction between both genetic & environmental factors. - Some 80 - 90% of newly diagnosed patients with IDDM have islet cell antibodies (ICA) directed at cell surface of cytoplasmic determinants. In their islet cells, the prevalence of these antibodies decreases with the duration of established disease. - 30 - 40% may have spontaneous anti-insulin antibodies at initial diagnosis. Etiology and Pathogenesis  Clinical manifestations I. The classic presentation of diabetes in children is a history of: a) Polyuria. b) Polydipsia. c) Polyphagia. d) Weight loss. A clue to existence of polyuria may be the onset of enuresis in a previously toilet trained child. II. Lethargy, weakness & weight loss (in spite of ↑ dietary intake). III. Pyogenic skin infection and monilial vaginitis.  Clinical manifestations IV. Ketoacidosis may be the initial presentation in 30% of cases of IDDM ► vomiting, polyuria & dehydration. In severe cases ► Kussmaul respiration. An odour of acetone on the breath is present. Abdominal pain or rigidity may be also present & may mimic appendicitis. Cerebral obtundation and ultimately coma ensue. Lab. Findings They include: * Glucosuria. * Ketonuria. * Hyperglycemia. * Ketonemia. * Metabolic acidosis. * Leucocytosis. * Non specific elevation of serum amylase.  Diagnosis I- History. II- Random blood glucose. Clinical history: * Clinical symptoms. * Diabetic ketoacidosis in 30% of cases at diagnosis. * Clinical course