Diabetes Mellitus Med Path PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Diabetes Mellitus Dr. Muirne Spooner Senior Clinical Lecturer And Dr. Clive Kilgallen Consultant Pathologist  LEARNING OUTCOMES 1. Define Diabetes Mellitus 2. Compare & contrast the pathophysiology of...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Diabetes Mellitus Dr. Muirne Spooner Senior Clinical Lecturer And Dr. Clive Kilgallen Consultant Pathologist  LEARNING OUTCOMES 1. Define Diabetes Mellitus 2. Compare & contrast the pathophysiology of type 1 & type 2 diabetes 3. Discuss the principles of diagnosis & classification of diabetes 4. List the cardinal symptoms & signs of diabetes 5. Identify the risk factors for the rising prevalence of Type 2 Diabetes 6. Recognize the importance of prevention & early intervention in the management of type 2 diabetes 7. Outline the overarching principles of investigation & management of diabetes 8. Evaluate the implications of diabetes, including the impact on quality of life & healthcare costs 9. Identify the role of interdisciplinary care in the management of diabetes  PATIENT MF A 22-year-old male presents to A&E with 2-3 months worsening polyuria, polydipsia, fatigue & unintentional weight loss of 4 kg This is despite him drinking ~2 L of soda & fruit punch daily He is 175 cm in height & weighs 66 kg (BMI 21.5 kg/m 2) He has no family history of diabetes mellitus. His mother has hypothyroidism His plasma glucose is 26 mmol/L (4-7.8 mmol/L) What is the diagnosis?  WHAT IS DIABETES MELLITUS? Chronic disease Several distinct types. Main ones are: – Type 1 Diabetes (T1D) characterized by insulin deficiency (10% of the cases) – Type 2 Diabetes (T2D) characterized by insulin resistance (90% of the cases) Glucose levels in the body increase (i.e.- hyperglycaemia) Glucose will non-enzymatically glycosylate protein & cause pathology Long term complications & increase in mortality Burden of morbidity Significant resource use HEALTH IMPACT OF THE DISEASE 5th leading Life expectancy cause of death 5 to 10 yr Renal failure* Cardiovascular Diabetes disease 2X to 4X Blindness* Amputation* Nerve damage in 60-70% of patients * Diabetes is the no. 1 cause of renal failure, new cases of blindness, and nontraumatic amputations PREVALENCE https://idf.org/about-diabetes/facts-figures/ PREVALENCE https://idf.org/about-diabetes/facts-figures/  TYPE 1 DIABETES (T1D) Autoimmune process- body’s immune system attacks the insulin producing beta-cells of the pancreas -> body produces very little or no insulin Under the microscope (in this order) 1. Lymphocytes will come in an attack beta cells (insulitis) 2. Beta cells will die 3. This area will heal with fibrosis -> fibrotic islet  CAUSES Not fully understood Likely combination of genetic susceptibility (conferred by many genes) & an environmental trigger such as a viral infection Occurs most frequently in children & young adults  PATHOGENESIS OF T1D Image result for insulin secretion in beta cells PANCREAS  ℬ-CELL HISTOLOGY Normal Control T1D Red stains for insulin, beta cells Brown stains for glucagon, alpha cells  ENDOCRINE PANCREAS 1-3 million microscopic units – the islets of Langerhans which constitute 2% of total pancreas 3 most important cell types of the islets are: Beta: constitute 60-80% of the cells & contain insulin Alpha: 20-30% of the cells & produces glucagon Delta: secretes somatostatin which suppresses insulin & glucagon secretion  INSULIN A peptide hormone secreted by β-cells in the pancreatic islets of Langerhans Key anabolic hormone critical for glucose uptake & utilization, lipid & protein synthesis, & an essential growth factor for normal development Intact insulin function requires: Islet β-cell mass Insulin synthesis Glucose-dependent insulin secretion Insulin signaling at target cells A lack of insulin, or the inability of cells to respond to it, leads to high levels of blood glucose (hyperglycaemia) IMPORTANCE OF BETA CELL  NORMAL INSULIN METABOLISM The major regulator of insulin secretion is glucose which acts both directly & by augmenting the action of other insulin secretagogues: – including intestinal hormones such as glucagon–like peptide 1 (GLP-1) & certain amino acids (leucine & arginine) A rise in the blood glucose levels, causes an immediate release of insulin, that is stored in the beta-cell granules. If the secretory stimulus persists, a delayed response follows, which involves active synthesis of insulin (the constitutive pathway)  FUNCTIONS OF INSULIN Insulin is a major anabolic hormone. It is necessary for: – Transmembrane transport of glucose & amino acids – Glycogen formation in the liver & skeletal muscles – Glucose conversion to triglycerides – Nucleic acid synthesis – Protein synthesis Its principal metabolic function is to increase the rate of glucose transport into certain cells in the body. These are the striated muscle cells, including myocardial cells, fibroblasts, & fat cells, representing collectively about 2/3 of the entire bodyweight  CLASSIFICATION OF DIABETES MELLITUS Type 2 diabetes (~90% of cases) Type 1 diabetes (~10% of cases) Type 1a: autoimmune (majority of cases) Type 1b: non-autoimmune Gestational Diabetes (pre-cursor of T2D) Other specific types – Latent Autoimmune Diabetes of Adulthood (LADA) – Monogenic Diabetes Heterogeneous group of disorders characterized mainly by pancreatic beta cell dysfunction Accounts for 1-2% of diabetes Autosomal dominant inheritance – Diabetes secondary to other conditions (endocrinopathies- Cushing's, Acromegaly, drug-induced) – Primary pancreatic disease (e.g., cystic fibrosis, pancreatitis, pancreatectomy, pancreatic trauma)  T1D VS T2D Type 1 Diabetes Type 2 Diabetes Absolute insulin deficiency Insulin resistance with relative insulin deficiency Abrupt onset of hyperglycemia and propensity for the Hyperglycemia develops development of DKA gradually with progressive decline in beta-cell function Lifelong insulin injection (i.e., initially silent) required Can be treated with oral Associated with auto medications antibodies Associated with increasing age Predominant type of diabetes & obesity diagnosed in individuals