Diabetes Medicina interna

Diabetes Mellitus

• GLUT 4 in adipose tissue, GLUT 2 in pancreas membranes
• Glucose increases after a meal. Glucokinase and hexokinase convert glucose to glucose-6-phosphate
• ATP dependent K+ channels depolarize pancreatic beta cells
• The activation of Ca2+ channels trigger insulin release via the Golgi apparatus, rough endoplasmic reticulum, and vesicles
• Muscle and adipose tissue regulate glucose
• GLUT4 in the cytoplasm is activated by insulin to take up glucose
• Type 2 diabetes (DM2) with BMI > 28: Insulin resistance with reduced insulin receptors and decreased insulin production (requires 3-4x insulin to achieve the same effect as before).
• Type 1 diabetes: onset <20, autoimmune destruction of pancreatic beta cells
• Type 2 diabetes: onset ≥40, often related to obesity, insulin resistance, and decreased insulin production.
• Maturity-onset diabetes of the young (MODY): adequate beta cell number but impaired insulin secretion
• MODY types (2,1,3): represent defects in glucokinase and hepatocyte nuclear factor 4α (FNH4α) or hepatocyte nuclear factor 1α (FNH1α)
• Glucotoxicity: increases with raised glucose levels
• Treatment: Sulfonylureas, for example Glimepiride, Glibenclamide, Glicasida, and their dosage, are generally taken before meals to reduce glucose levels
• Incretins (GIP and GLP-1) secreted in the small intestine, in response to food ingestion, increase insulin secretion, and inhibit postprandial glucagon secretion.
• Exenatide, Semaglutide, Liraglutida, Tirzepatide are incretin-based therapies increase insulin and reduce glucose levels but may associated with weight loss

Other aspects

• DPP-4 inhibitors: block the enzyme DPP-4 that degrades incretins which prolongs incretin effects
• Sitagliptin, Vildagliptin, Saxagliptin are DPP-4 inhibitors
• Biguanides (Metformin): used for lowering basal glucose levels, typically taken at night to lower overnight glucose surges, not suitable for patients with Glomerular Filtration Rate (GFR) <30. Available only in oral formulations.
• Thiazolidinediones (Pioglitazone and Rosiglitazone): improve insulin sensitivity and lower blood lipid levels. Adverse effect: risk of bone fracture
• SGLT2 inhibitors (Empagliflozin, Canagliflozin, Dapaglifozin): cause glucosuria by blocking glucose reabsorption in the kidneys. This is potentially helpful in patients with heart failure and risk of cardiovascular events. Adverse effect: risk of urinary tract infections.
• Dosage for different drugs is listed.

Este cuestionario aborda la fisiología relacionada con la diabetes mellitus, incluyendo el papel de GLUT 4 y GLUT 2, y la respuesta del cuerpo al aumento de glucosa después de las comidas. También se exploran los diferentes tipos de diabetes, como la tipo 1, tipo 2 y diabetes de inicio en la madurez (MODY). Perfecto para estudiantes de medicina o interesados en temas de salud.