Physiology of Insulin and Glucose Regulation

Diabetes Mellitus Overview

• Diabetes mellitus is a condition characterized by an abnormality in blood glucose regulation, linked to an absolute deficiency in insulin or resistance to insulin's actions.
• Key features include decreased insulin secretion and/or insulin insensitivity (target cell resistance).
• The condition is characterized by hyperglycemia.
• Different types of diabetes exist, including Type 1, Type 2, and Gestational diabetes.

Pancreas Anatomy

• The pancreas has two main functions: exocrine and endocrine.
• Exocrine cells produce digestive enzymes and bicarbonate that are released into the duodenum.
• Endocrine cells, located in the islets of Langerhans, secrete hormones like insulin and glucagon to regulate blood glucose levels.

Glucose Metabolism Terms

• Gluconeogenesis: The creation of glucose from non-carbohydrate sources (proteins, glycerol, or lactate).
• Glycogenesis: The creation of glycogen, a carbohydrate easily converted to glucose.
• Glycolysis: The breakdown of glucose within a cell to release energy in the form of ATP.
• Glycogenolysis: The breakdown of glycogen into simple glucose.

Glucose-Regulating Hormones

• Insulin: Produced by beta cells in the pancreas, insulin promotes glucose uptake by cells and its storage as glycogen, fat and protein. It also inhibits gluconeogenesis and promotes protein synthesis, leading to lower blood glucose levels.
• Glucagon: Produced by alpha cells in the pancreas when glucose levels fall, glucagon stimulates the release of glucose into the bloodstream and glycogen breakdown(glycogenolysis).

Insulin-Stimulated Glucose Uptake

• Insulin stimulates glucose transporters to relocate to cell membranes, allowing glucose entry into cells.
• Insulin promotes the storage of glucose as glycogen, lipids and protein.
• Insulin will also stimulate glucose breakdown for energy (glycolysis) in the cell.

Insulin Main Actions

• Insulin promotes glucose uptake and storage.
• Insulin prevents fat breakdown and glycogen breakdown.
• Insulin inhibits gluconeogenesis and stimulates protein synthesis.

Type 1 Diabetes Mellitus

• Characterized by the complete loss of insulin production by the pancreatic beta cells.
• Typically develops in younger people (often under 25, but can occur later).
• Further divided into immune-mediated and idiopathic (non-immune) types.

Type 1A & 1B Diabetes Mellitus

• Type 1A diabetes is an autoimmune disorder with genetic factors and environmental triggers leading to immune system attack on beta cells.
• Type 1B diabetes has no evidence of autoimmunity; the cause of beta cell destruction is unknown.

Type 2 Diabetes Mellitus

• Often develops in adulthood (typically over 25).
• Characterized by insulin resistance and impaired insulin secretion by beta cells.
• Risk factors include age, obesity, and family history, and acquired environmental factors.

Type 2 Diabetes Mellitus - Pathogenesis

• Insulin resistance, increased glucose production by the liver, and impaired insulin secretion by pancreatic beta cells are key factors.
• Reduction in beta cell mass, increased apoptosis, and glucotoxicity/lipotoxicity contribute.

Metabolic Syndrome and Insulin Resistance

• Features include abdominal obesity, hyperglycemia, hypertension, and hyperlipidemia.

Role of Adipose Tissue in Type 2 DM

• Increased levels of free fatty acids (FFAs) lead to pancreatic beta cell dysfunction (lipotoxicity).
• FFAs hinder glucose uptake and glycogen storage, reducing the body's sensitivity to insulin and contributing to hyperglycemia.

Gestational Diabetes Mellitus (GDM)

• Any degree of glucose intolerance that begins during pregnancy.
• Risk factors include glycosuria, family history of type 2 diabetes, obesity, and prior history of gestational diabetes.
• The placenta produces hormones that interfere with insulin function and lead to higher glucose levels.

Gestational Diabetes Screening

• Risk assessment for all pregnant women during the first prenatal visit.
• High-risk women undergo glucose testing performed ASAP, while others undergo the oral glucose tolerance test (OGTT) at 24-28 weeks.

Fetal Abnormalities in GDM

• Potential complications include macrosomia, hypoglycemia, hypocalcemia, polycythemia, and hyperbilirubinemia.

Treatment of Gestational Diabetes

• Close observation of both the mother and fetus, including glucose monitoring, fetal growth measurements, and monitoring for fetal distress.
• Dietary modifications, and if necessary, insulin therapy.

Maternal Follow-up from Gestational Diabetes

• Ongoing follow-up after delivery to identify potential type 2 diabetes.
• Patients are screened through a 2-hour OGTT with a 75g glucose load.
• Prognosis suggests a 50% chance of developing type 2 diabetes in the 5-10 following years.

Clinical Manifestations of Diabetes

• Three common clinical manifestations known as the "three polys": polyuria (increased urination), polydipsia (increased thirst), and polyphagia (increased hunger).
• Further clinical manifestations include weight loss, blurred vision, paresthesias, fatigue, weakness, and chronic infections.

Rational for the "Polys"

• Diabetes is characterized as “starvation in the midst of plenty” due to the body's inability to utilize excess glucose.
• This leads to hyperglycemia, which in turn causes increased urination, thirst, hunger, and weight loss.

Diagnostic Tests for Diabetes

• Diagnosis confirmed by specific lab tests that measure blood glucose levels.
• Tests included fasting plasma glucose, casual blood glucose testing, oral glucose tolerance test(OGTT), capillary blood glucose, and glycosylated hemoglobin (HbA1c).

Diabetes Management

• Glycemic control is the primary goal in type 1 and 2 diabetes management to avoid complications.
• Treatment involves dietary modifications, regular exercise, and the use of medications.
• Antidiabetic agents include both oral and injectable types depending on type of diabetes.

Insulin Therapy

• Insulin is administered via injection or infusion to mimic the body's natural insulin secretion patterns.
• Different types of insulin exist based on duration and peak of action, allowing for tailored treatment approaches.

Acute Complications of Diabetes

• Diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and hypoglycemia are life-threatening complications that require immediate intervention.

Diabetic Ketoacidosis (DKA)

• DKA is marked by a lack of insulin, resulting in accelerated breakdown of energy sources like fats and proteins. This rapid breakdown produces ketones causing metabolic acidosis.
• Symptoms include fruity breath odor, elevated heart rate, and rapid respiration (Kussmaul respirations).

DKA Manifestations

• Symptoms typically include a fruity-smelling breath due to acetone, elevated heart rate and rapid respirations, increased rate and depth of respirations(Kussmaul's).

DKA Treatment Goals

• Improve circulatory volume and tissue perfusion, decrease blood glucose, correct acidosis, and correct electrolyte imbalance via IV fluids, insulin infusion, and potassium supplementation.

Hypoglycemia

• Hypoglycemia results from excess insulin in the blood, leading to abnormally low blood glucose levels.
• Potential causes include errors in insulin dosage, missed meals, increased exercise, medication changes, and altered insulin injection sites.

Clinical Manifestations of Hypoglycemia

• Symptoms include altered cerebral function (headache, difficulty problem-solving, altered behavior, and seizures), and activation of the autonomic nervous system (hunger, anxiety, tachycardia, and sweating).

Treatment of Hypoglycemia

• Treatment involves immediate administration of 15–20 g of simple carbohydrates, and for unconscious patients, glucose via intramuscular or subcutaneous glucagon injection.

Chronic Complications of Diabetes

• Chronic complications result from prolonged elevated blood glucose levels, potentially leading to problems such as microvascular (neuropathy, nephropathy, retinopathy) and macrovascular complications (coronary artery disease, cerebrovascular disease, peripheral vascular disease).

Diabetic Foot Ulcers

• Diabetic foot ulcers result from neuropathy and/or vascular insufficiency, leading to constant trauma to the feet, difficulty sensing pain from injury, poor weight-bearing, and impaired immune response to infection.

Pathology of Infections

• Infections are impacted by sensory deficits and vascular insufficiency resulting in impairment of healing, and neurogenic bladder.

Diabetes and Illness (Infection)

• Diabetes management during illness or infection may require adjustments in insulin regimens or medication dosage, increased blood glucose monitoring, and regular eating habits and fluid intake.

Diabetic Nephropathy

• Diabetic nephropathy involves kidney lesions and chronic kidney disease, particularly due to glomerular changes that can lead to kidney enlargement and increased nephron work.
• Hypertension accelerates disease progression and often leads to end-stage renal disease (ESRD).

Diabetic Retinopathy

• Diabetic retinopathy is the leading cause of acquired blindness due to abnormal retinal vascular function. Risk factors include poor glycemic control, hypertension, and hyperlipidemia.
• Treatment often involves regular eye exams and, where appropriate, laser photocoagulation.

Macrovascular Complications

• Macrovascular complications include diseases like coronary artery disease (CAD), cerebrovascular disease (Stroke), and peripheral vascular disease (PVD). These are 2 to 4 times more common in people with diabetes.
• Risk factors for these diseases also include obesity, hypertension, hyperglycemia, hyperlipidemia, altered platelet function, and systemic inflammation

Treatment for Diabetic Nephropathy

• Management focuses on strict glycemic control, blood pressure (<130/80), reduction in proteinuria (with ACE inhibitors, or protein restriction), smoking cessation, and, if necessary, dialysis.

Treatment for Diabetic Retinopathy

• Management involves regular dilated eye exams and laser photocoagulation to treat proliferative lesions. Growth factor antagonists also play a role in treatment.

Treatment for Macrovascular Complications

• Management involves aggressive management of cardiovascular risk factors. Treatment includes smoking cessation, managing hypertension, controlling lipids, managing diabetes, and, if appropriate, antiplatelet agents.

This quiz explores the roles of insulin and glucagon in blood glucose regulation, particularly during fasting and starvation. It also covers aspects of Metabolic Syndrome, Gestational Diabetes, and the impact of free fatty acids in diabetes management. Test your knowledge on hormonal interactions and their physiological implications!