Diabetes Mellitus PDF

Endocrinology Diabetes Mellitus Definition:  Chronic disorder characterized by impaired glucose metabolism → Hyperglycemia.  It is associated with secondary changes in multiple organs → Complications.  It is due to: Ins...

Endocrinology Diabetes Mellitus Definition:  Chronic disorder characterized by impaired glucose metabolism → Hyperglycemia.  It is associated with secondary changes in multiple organs → Complications.  It is due to: Insulin deficiency, Insulin resistance OR Both. NB: 1. Diabetes is the leading cause of: Non-traumatic lower limb amputation 2. Diabetes is the leading cause of: Adult blindness. 3. Diabetes is the leading cause of: ESRD 4. Diabetes is the leading cause of: Peripheral neuropathy Incidence:  Worldwide prevalence of diabetes mellitus. Global estimate is 463 million individuals with diabetes in 2019. Regional estimates of the number of individuals with diabetes (20- 79 years of age) are shown (2019). (Data from the IDF Diabetes Atlas, 9th ed. The International Diabetes Federation; 2019.)  Egypt is in the world' top 10 in terms of the highest number of people with diabetes (9 million in 2019) DR. NOAMAN GWELY 1  Endocrinology Diabetes Mellitus Hormonal regulation of blood glucose level: ↓ Blood Glucose ↑ Blood Glucose 1. Insulin 1. Glucagon 2. Amylin 2. Growth hormone 3. GLP-1 3. Cortisone 4. GIP 4. Catecholamine 5. Thyroxin [ Insulin ]  In β Cells of pancreas.  Proinsulin (precursor of insulin) is cleaved to insulin & C-peptide.  Blood C-peptide level is a marker of endogenous insulin secretion. DR. NOAMAN GWELY 2  Endocrinology Diabetes Mellitus  Insulin secretion is stimulated by an increase in blood glucose levels.  Glucose enters pancreatic B cells via GLUT2 transporters and is metabolized to generate ATP.  Intracellular ATP binds to and blocks ATP-sensitive K channels, increasing the intracellular K concentration and raising the membrane potential until depolarization occurs.  Voltage-gated Ca channels open in response to depolarization enters the pancreatic B cells.  Increased intracellular Ca concentration triggers the fusion of insulin- containing secretory granules to the cell membrane, resulting in exocytosis of insulin into the bloodstream.  CHO: ↓ Glucose level by :  ↓ Gluconeogenesis & Glycogenolysis (liver).  ↑Glycogenesis (liver &Ms).  Glucose Transport to Ms & fat using glucose transporters  Lipid: ↑ lipogenesis, ↓ lipolysis, ketogenesis  Protein: Potent anabolic effect through, facilitation of A.A. uptake.  Other: Intracellular K shift DR. NOAMAN GWELY 3  Endocrinology Diabetes Mellitus Insulin action. DR. NOAMAN GWELY 4  Endocrinology Diabetes Mellitus Glucose Transporters (Wide group of protein that facilitate transport of glucose through cell membrane) Insulin- Name Site Function dependent  Most human cells  Blood-brain barrier GLUT- 1  RBCS & CNS & Cornea NO  High affinity for glucose  Placenta & Fetal tissue  Transports all monosaccharides from the basolateral membrane of  Hepatocytes enterocytes into blood  Pancreatic cells  Glucose sensor GLUT -2  Kidneys  High capacity but low affinity for glucose (i.e, glucose only diffuses at NO  Small intestine high concentrations)  Bidirectional transporter: allows hepatocytes to uptake glucose for glycolysis and release glucose during gluconeogenesis  Most human cells  Blood-brain barrier GLUT -3 NO  CNS & Placenta  High affinity for glucose (i.e, glucose diffuses at low concentrations)  Plays a key role in regulating body glucose homeostasis  Adipose tissue  Insulin stimulates incorporation of GLUT4 (stored in vesicles) into  Striated muscle: GLUT -4 plasma membranes of cells for controlled glucose uptake and storage. Yes 1. Skeletal muscle  Physical exercise also induces the translocation of GLUT4 into the 2. Heart muscle plasma membrane of skeletal muscle, in an insulin-independent manner.  Only GLUT has.  rain, BCs, ntestine, ornea, idney, iver, slet cells, lacenta, permatocytes (insulin independent glucose uptake).  Specific insulin-independent glucose transporters: GLUT and GLUT For (Blood Brain Barrier) & GLUT transporter in directions & GLUT ( ive) is a ructose transporter. DR. NOAMAN GWELY 5