case study

• Organ which plays role in Homeostasis of blood sugar is Pancreas• Location of pancreas in body – with organ system• Anatomical location – Exocrine part – opens pancreatic duct – releasing pancreatic juices inDuodenum – Alkaline in nature -to buffer acidic chyme.• Types of pancreatic cells• Relationship of islets and blood capillaries – In Hormone release
• Pancreas – Two parts - Exocrine and Endocrine• Pancreatic cells and their function• Role of pancreatic cells in regulation of blood glucose – by α and β cells of islets• Role of insulin –• in maintaining – lowering blood sugar• Storage in Liver and muscles
• Humoral Control - blood glucose regulation is a primary example of humoral control, where changes in blood levels ofnon-hormone chemicals (like glucose) trigger the release or inhibition of hormones (like insulin and glucagon) tomaintain homeostasis
• Glucose cannot diffuse across the cell membrane : needs transporter• Glucose entry (mostly via GLUT-2 transporter) in pancreatic beta cells• Glucose metabolised –↑ATP• KATP channel inhibition → depolarisation• Ca2+ entry to cell; insulin secretion byexocytosisMechanism of Insulin release by β cellsRate limitingNote:- Sulfonylureas drugs stimulates insulin secretion by binding to the ATP-sensitive potassium channels.
• Insulin action on target cells: muscle & fat• Insulin binds to the receptor on the plasma membrane.• Increased mobilisation of GLUT4 glucose transporters from inside the cytoplasm to the cell surface• Glucose transport into the cell where it will be stored as triglycerides (adipocytes) or glycogen (striated muscle).• Suppresses gluconeogenesis
• Pathophysiology of High blood glucose• Reason for Diabetes Mellitus▪ Decrease insulin receptor numbers▪ Decrease insulin sensitivity• Type I and Type II• How to differentiate clinically?• Pharmacological management of Type I and Type II DM
• Diabetes mellitusIs a complex of polygenic metabolic disorders defined byhyperglycemia (plasma fasting level of glucose > 70 mmol/l) and characterizedby relative or absolute deficiency of insulin secretion and/or insulin resistance with consequentderanged metabolism of carbohydrates, fats and proteins
• Type 1 Diabetes ( autoimmune b-cell destruction) Insulin-dependent DM (IDDM)With type 1 diabetes, beta cells produce little or no insulin. Without enough insulin, glucose builds up in thebloodstream instead of going into the cells. This buildup of glucose in the blood is called hyperglycaemia.• Type 2 Diabetes (defects in insulin secretion or action) Non-Insulin-Dependent DM (NIDDM)▪ Gestational diabetes mellitus▪ MODY
• Low C peptide indicates insulin deficiency (usuallyfrom type I diabetes), which means that the patient will need lifelong insulin treatment.
• High C peptide shows that the patient is producing some insulin and could have another form of diabetes- type II that could be controlled by lifestyle change and tablets.
• Honeymoon Period in patients with new onset of DM1 who do not haveDKA, the beta cell mass has not been completely destroyed.• The remaining functional beta cells seem to recover with insulin treatment, and they are again able to produce insulin.• When this occurs, insulin requirements decrease, and there is a period of stable blood glucose control, often with nearly normal glucose concentrations.• This phase of the disease, known as the honeymoon period, usually starts in the first weeks of therapy and usually continues for a few months at most, but can last 2 years
• Summary - Type I DM and C-peptide for diagnosis

  A) genetic factors

  B) environmental factors

  C) immunilogical factors

  D) dietary factors

  
• Rationale for 3Ps (Polytriad)• Autoantibodies- destroyed β cells• This high blood sugar produces the classical symptoms of• polyuria (frequent urination)- Osmotic diuresis• polydipsia (increased thirst) and• polyphagia (increased hunger).• Explanation of each symptom
• elation of blood glucose measurement with HbA1c and RBCs?• Diabetes is caused by an absolute or functional lack of insulin, which leads to increasedglucose levels outside the cell.• High concentrations of glucose can increase the glycation of common proteins such ashaemoglobin, forming Haemoglobin A1c (HbA1c).• However, it is important to note that HbA1c is neither considered dysfunctional nor harmful.• Haemoglobin A1c (HbA1c) is known to correlate with blood glucose levels over the lifetimeof the red blood cell, which is approximately 120 days.
• Advantage to perform this test and role in management ?• Although red cell survival may show subtle differences between diabetes patients andnondiabetes patients which could be considered, the fundamental understanding is thatblood glucose levels determine HbA1c levels, and this underpins the value of HbA1c as thecurrent gold standard for clinical monitoring of diabetes.
• Diagnosis - diabetes • Urine dip stick• Blood test- Fasting blood sugar• HbA1c test
• Assess the effects ofHyperglycaemia on body function• Hyperglycaemia• Long standing -can lead to health problems that affect the eyes, kidneys, nerves and heart.• increased thirst and a dry mouth.• needing to pee frequently.• tiredness.• blurred vision.• unintentional weight loss.• recurrent infections,• such as thrush,• bladder infections (cystitis) and• skin infections
• insulin infusion pumps+ real time continuous glucose monitoring
• Management (Rx)• Type –I DM• Acute management• Long term healthy lifestyle maintenance• Let’s do Pharmacological management using vevox questions
• Management (Rx)❑Type 1• Only Rx choice -Treated with injection insulin❑Type 2• Lifestyle modificationo Diet▪ Low carb to decrease glucose load▪ Low calorie diet – to decrease fat store and restore insulin productiono Exercise – stimulate Glut4 movements• Oral HypoGlycaemic Agents (OHGA)• Injection Insulin
• Reason for fainting in Hyperglycemia• High blood sugar levels (hyperglycaemia) can cause polyuria, which in turn can lead todehydration by passing too much fluid out of the body in an attempt to remove excessglucose. With low levels of water in the body, the brain may struggle to function correctlyand cause light headedness
• Clinical Consequences (Clinical aspects of Diabetic ketoacidosis- DKA)• Hyperglycaemia associated with DKA results in polyuria and ultimately volume depletionwhich may lead to hypotension and associated tachycardia.• Release of large amounts of ketoacids give the patient's breath a characteristic fruityodour and can affect acid-base homeostasis, resulting in metabolic acidosis.• Intense abdominal pain, nausea, and vomiting are also associated with DKA. If not treatedpromptly, patients with DKA can progress to coma within hours todays.
• Hyperglycaemia• Long standing -can lead to health problems that affect the eyes, kidneys, nerves and heart.• increased thirst and a dry mouth.• needing to pee frequently.• tiredness.• blurred vision.• unintentional weight loss.• recurrent infections,• such as thrush,• bladder infections (cystitis) and• skin infections
• Hypoglycaemia• is usually a side effect of treatment with blood-sugar-lowering medication.• problems with central nervous system.• Early symptoms include weakness, light-headedness, and dizziness.• Headaches can occur from a lack of glucose, especially if you have diabetes.• You may also feel signs of stress, such as nervousness, anxiety, and irritability.Assess the effects ofHypoglycaemia on body function