Diabetes Mellitus Classification & Pathophysiology

Definition Diabetes Mellitus is a group of metabolic diseases characterized metabolic diseases characterized by high plasma levels of glucose resulting from defects in insulin secretion, insulin action, or both. Body is unable to metabolize carbohydrates, fats and proteins The Expert Committee On the Diagnosis and Classification of Diabetes Mellitus (2000 )

An Early definition “ a wonderful but not very frequent affliction among men, being a meltdown of the flesh and limbs into urine ….. life is short, offensive and distressing, thirst unquenchable, death inevitable” Aretaeus ( A.D) Aretaeus ( A.D) a Roman Physician a Roman Physician

Diabetes (siphon) Mellitus (sweet or honey-like )

Normal Blood Glucose 3.5 – 8 mmol/L

Classification  Type-1 –Autoimmune disease against ß cells in the pancreas. Possibly viral. Cells destroyed –Genetic predisposition – HLA genes  Type-2 –Insulin (high, normal or low) present but cannot be utilized (insulin resistance).  Other specific types (secondary )  Gestational  LADA (latent autoimmune diabetes in adults) – diabetes/expert-answers/lada-diabetes/faq diabetes/expert-answers/lada-diabetes/faq http:// diabetes/expert-answers/lada-diabetes/faq

Gestational diabetes  Placental hormones affect glucose tolerance  Carbohydrate intolerance  Insulin resistance  3-8% of pregnancies  At risk for eclampsia  BG levels normal post natal  Precautions to reduce risk

History of Insulin resources/history-of-diabetes.html resources/history-of-diabetes.html resources/history-of-diabetes.html

Diabetes (before )

Diabetes (after insulin)

Pathophysiology of Diabetes Mellitus Lewis : Pg 1183/1359

Type I Diabetes  Destruction of beta cells. No Insulin is produced produced  Often occurs suddenly and most commonly in persons under 30 most before 15 in persons under 30 most before 15  Accounts for up to 10% of persons with diabetes diabetes  Increase by 3% - 5% more frequently in children children  One of the most common childhood diseases in developed countries diseases in developed countries

Type 1 Pathophysiology  Autoimmune destruction of beta cells  Total absence of insulin production  Glutamic acid decarboxylase (GAD)antibodies islet cell and insulin autoantibodies islet cell and insulin autoantibodies  Unchecked glucose production by liver  Fasting hyperglycaemia and post - prandial hyperglycaemia post - prandial hyperglycaemia  Increased glycogenolysis, gluconeogenesis gluconeogenesis  Fat break-down – ketone bodies (DKA)

Type 1 Diabetes

Type 1 diabetes

Type 2 Diabetes  Most common type  Insulin produced is not effective “sluggish”  Insulin resistance  Impaired insulin secretion  Gradual – most often in people over 40  Controlled by diet, oral meds and in some cases insulin  Preventable

Type 2 Pathophysiology  Insulin resistance - decreased tissue sensitivity to insulin - insulin normally binds to receptors on cell surfaces and receptors on cell surfaces and initiates reactions. initiates reactions. - receptors unresponsive or insufficient or insufficient - decrease in Glut 4 transporters - glucose entry into cell impeded - unable to regulate glucose release by liver  Lewis 1185/ 1361

Type 2 Pathophysiology Type 2 Pathophysiology  Impaired Insulin secretion - beta cells cannot keep up with increased - beta cells cannot keep up with increased demand for insulin to overcome resistance demand for insulin to overcome resistance “fatigued” (compensatory overproduction) “fatigued” (compensatory overproduction) - decrease in production of insulin or insulin - decrease in production of insulin or insulin sluggish. sluggish.  Inappropriate glucose production by liver - haphazard not consistent with needs - haphazard not consistent with needs - leads to high fasting blood glucose - leads to high fasting blood glucose  Altered production of hormones and cytokines by adipose tissue (adipokines – adiponectin & leptin adipose tissue (adipokines – adiponectin & leptin - cause insulin resistance - cause insulin resistance

Acanthosis nigricans

Metabolic syndrome (syndrome X)  Increased risk of insulin resistance  Five components - increased glucose levels - increased glucose levels - elevated BP - elevated BP - abdominal obesity - abdominal obesity - high triglycerides - high triglycerides - low HDL’s - low HDL’s  Any 3 = Metabolic syndrome

Type 2 Diabetes

Pre-Diabetic Conditions  Relates to Type 2 Diabetes pathology  Between a normal state and the diabetic state. – IGT & IFG (Impaired)  Tests: - IGT if OGTT = 7.8 to 11.0 mmol/L - IFG if fasting glucose = 5.5 to 6.9 mmol /L  usually no symptoms

Insulin Dependent Type 2  Pre-diabetics with cellular resistance compensate by pumping out lots of insulin.  The hyper insulin state exhausts the beta cells and create less insulin.  Thus, the Type 2 to may also require insulin

Diabetes Overview