Endocrinology 7 - Diabetes - About 6% (3.5 - 5 million) of our population has a form of diabetes Diabetes Mellitus - All have the characteristic of high glucose levels (>7mmol/mol) - Collection of the conditions of glucose homeostasis o Type 1 o Type 2 o Type 3c " Some form of damage to the pancreas thus the B-cells islets o MODY " Maturity onset diabetes of the young Genetic mutation o Gestational diabetes o T2DMY o Others - 10% of NHS budget (total budget is 124B a year) o Is going to bankrupt the NHS - The treatments are all around manipulating hormones - Shortens lifespan/accelerates ageing Diagnosis: - Check the blood glucose levels - FBG - fasting blood glucose o >7mmol/mol = diabetes - OGTT - oral glucose tolerance test o If blood glucose is >11mmol/mol = diabetes - Newer test - HbA!c o Glucose binds irreversible to Hb in erythrocytes forming HbA1c " Binds non-enzymatically to the Alc " Binds to the n-terminal of the beta chain o Higher the glucose the more glycation will occur of the A1c portion o Erythrocytes circulate the body for around 90 - 120 days o If you measure the amount of the glycation of the Hb, gives you an indication of the last three months o Normal HbA!c = < 42mmol/mol o Diabetes HbAlc = 48mmol/mol History: First described in Ebers Papyrus - o Only a few diabetes described Normal Glucose Homeostasis - Insulin is the key hormone o Glucagon and somatostatin - Post-Prandially (after eating)
- Leads to the oxidation of the glucose by glucokin ase - Lead to more ATP, which closes K+ channels Which changes the voltage across the membra - o Stimulates insulin secretion o Glucose is absorbed through the walls of GI tract via SGLT1 · SGLT1 - sodium - glucose transporter o Glucose levels in the blood will rise o Passively diffuse across the membrane of the pancreatic cells through GLUT o Once insulin enters the blood and binds to the insulin receptors on other cells Changes the rate at which they take glucose out of the blood o To the liver, it reduces the rate at which it releases glucose from its stores o Glucose is stored as metabolites - anabolism - Fasted o Glucose levels o Insulin secretion stops to a smaller level (never stops) o Glucagon is released from the pancreatic alpha cells · Opposes the effects of insulin " Causes glucose to be released from the liver Insulin repression of glucose release lessens - catabolism o Post-meal Fasting state Hormonal regulation by glucagon, epinephrine or glucocorticoids Hormonal control by insulin Gut Muscle Glycogen - Glucose Muscle Amino acids - Protein Liver Glycogen Glucose Triglycerides Blood glucose Liver Amino acids Glucose - Glycogen Fatty acids · Ketone bodies Adipose Nerve and Triglycerides + Glucose other tissues Adipose Fatty acids -Triglycerides Insulin Secretion Produced by pancreatic cells - 51 aa peptide hormone - transcribed from the insulin gene as a prepro hormones