Comprehensive Overview of Diabetes Mellitus and Thyroid Disorders: Pathophysiology, Diagnosis, and Treatment

Comprehensive Overview of Diabetes Mellitus and Thyroid Disorders: Pathophysiology, Diagnosis, and Treatment

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  Diabetes mellitus andThyroid Ms. Sakshi Bajaj Associate Professor ( Pharmacology) Global Research Institute Of Pharmacy
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  • Diabetes mellitus(DM) also known as simply diabetes, is a group of metabolic diseases in which there are high blood sugar levels over a prolonged period . • Symptoms • frequent urination, increased thirst, and increased hunger. Untreated, diabetes can cause many complications. • Acute complications include diabetic ketoacidosis and nonketotic hyperosmolar coma. • Types of DM: There are three main types of diabetes mellitus: • Type 1 DM results from the body's failure to produce enough insulin. This form was previously referred to as "insulin- dependent diabetes mellitus" (IDDM) or "juvenile diabetes". The cause is unknown. • Type 2 DM begins with insulin resistance, a condition in which cells fail to respond to insulin properly. As the disease progresses a lack of insulin may also develop. This form was previously referred to as "non insulin-dependent diabetes mellitus" (NIDDM) or "adult-onset diabetes". • The primary cause is excessive body weight and not enough exercise. Gestational diabetes, is the third main form and occurs when pregnant women without a previous history of diabetes develop a high blood glucose level. Prevention and treatment involves a healthy diet, physical exercise, not using tobacco, and being a normal body weight. Blood pressure control and proper foot care are also important for people with the disease. • Type 1 diabetes must be managed with insulin injections. Type 2 diabetes may be treated with medications with or without insulin. Insulin and some oral medications can cause low blood sugar. Diabetes mellitus
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  Risk factors The developmentof type 2 diabetes has been linked to several risk factors. Unmodifiable risk factors: include advancing population age, family history, and diabetes genetic variables in some ethnic groups. The most common risk factors for the rising diabetes epidemiology, are variables linked to poor food, inactivity, and smoking, Sedentary life style ,which typically result in being overweight, dyslipidaemia, high blood pressure, and impaired glucose tolerance. Diabetes development is influenced by environmental factors, including low socioeconomic position, physical living conditions, stress levels, and exposure to mercury and arsenic . Diabetes mellitus is diagnosed by measuring blood glucose levels or HbA1c (glycated hemoglobin). The commonly used diagnostic tests are: Fasting Plasma Glucose (FPG): Diabetes is diagnosed if the fasting blood glucose level is ≥126 mg/dL (7.0 mmol/L). Oral Glucose Tolerance Test (OGTT): Diabetes is diagnosed if the 2-hour plasma glucose level is ≥200 mg/dL (11.1 mmol/L) after consuming a glucose solution. HbA1c Test: An HbA1c value of ≥6.5% indicates diabetes. This test reflects the average blood glucose level over the previous 2–3 months. Random Plasma Glucose (RPG): A random blood glucose level ≥200 mg/dL (11.1 mmol/L) along with typical symptoms of hyperglycemia (such as excessive thirst, frequent urination, and unexplained weight loss) is also diagnostic of diabetes. Diagnosis
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  Complication of Diabetesmellitus Pathophysiology of Diabetes Mellitus • Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia (high blood glucose levels) resulting from impaired insulin secretion, insulin resistance, or both. Insulin, a hormone produced by the β-cells of the pancreas, is essential for maintaining normal blood glucose levels by promoting glucose uptake into cells and regulating carbohydrate, fat, and protein metabolism. Normal Glucose Regulation After a meal, blood glucose levels rise, stimulating pancreatic β-cells to release insulin. Insulin facilitates the uptake of glucose into muscle and adipose tissues, promotes glycogen synthesis in the liver, and suppresses glucose production by the liver, thereby maintaining normal blood glucose levels. Pathophysiology of Type 1 Diabetes Mellitus Type 1 diabetes mellitus is caused by autoimmune destruction of pancreatic β-cells, leading to an absolute deficiency of insulin. The lack of insulin prevents glucose from entering cells, resulting in elevated blood glucose levels. Since cells cannot utilize glucose for energy, the body breaks down fats and proteins, producing ketone bodies that may lead to diabetic ketoacidosis (DKA) if untreated. Pathophysiology of Type 2 Diabetes Mellitus Type 2 diabetes mellitus develops due to insulin resistance and progressive β-cell dysfunction. Initially, body tissues such as skeletal muscle, liver, and adipose tissue become less responsive to insulin. To compensate, the pancreas secretes more insulin (hyperinsulinemia). Over time, β-cells become exhausted, insulin secretion decreases, and persistent hyperglycemia develops. Metabolic Changes in Diabetes Mellitus • Carbohydrate metabolism: Reduced glucose uptake by peripheral tissues and increased hepatic glucose production cause hyperglycemia. • Fat metabolism: Increased breakdown of fats (lipolysis) raises free fatty acid levels, leading to ketone body formation, especially in type 1 diabetes. • Protein metabolism: Increased protein breakdown results in muscle wasting and weight loss. • .
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  Development of DiabeticComplications • Chronic hyperglycemia causes several biochemical changes that damage blood vessels and nerves: • Increased formation of Advanced Glycation End Products (AGEs). • Activation of the polyol pathway, causing sorbitol accumulation. • Increased oxidative stress due to excessive production of reactive oxygen species (ROS). • Activation of protein kinase C (PKC) and inflammatory pathways. • These changes lead to endothelial dysfunction, inflammation, and tissue damage, resulting in: • Microvascular complications: Diabetic retinopathy, nephropathy, and neuropathy. • Macrovascular complications: Coronary artery disease, stroke, and peripheral arterial disease
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  Major Pathways Involvedin Diabetic Complications 1. Advanced Glycation End Products (AGEs) Pathway Persistent high blood glucose causes glucose to bind non-enzymatically to proteins, lipids, and DNA, forming Advanced Glycation End Products (AGEs). AGEs make blood vessels stiff, increase inflammation and oxidative stress, and damage the eyes, kidneys, nerves, and heart. 2. Polyol Pathway Excess glucose is converted into sorbitol by the enzyme aldose reductase. Sorbitol accumulates inside cells, causing osmotic stress and reducing antioxidant levels, which leads to nerve, retinal, and kidney damage. 3. Protein Kinase C (PKC) Pathway High glucose increases the production of diacylglycerol (DAG), which activates Protein Kinase C (PKC). PKC causes abnormal blood vessel function, increased vascular permeability, inflammation, and reduced blood flow, contributing to diabetic complications. 4. Hexosamine Pathway When glucose levels are high, excess glucose enters the hexosamine pathway, leading to abnormal modification of proteins and altered gene expression. This increases inflammation and fibrosis, contributing to vascular and kidney damage. 5. Oxidative Stress Pathway Hyperglycemia increases the production of reactive oxygen species (ROS). Excess ROS damages cellular proteins, lipids, and DNA, resulting in endothelial dysfunction and accelerating diabetic complications. 6. Inflammatory Pathway • Chronic hyperglycemia activates inflammatory mediators such as TNF-α, IL-6, and NF-κB. Persistent inflammation damages blood vessels and tissues, worsening insulin resistance and promoting diabetic complications.
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  Pharmacological treatment Drug ClassExamples Main Action Biguanides Metformin ↓ Hepatic glucose production, ↑ insulin sensitivity Sulfonylureas Glimepiride, Gliclazide Stimulate insulin secretion Meglitinides Repaglinide Short-acting insulin secretagogue Thiazolidinediones (TZDs) Pioglitazone Improve insulin sensitivity α-Glucosidase Inhibitors Acarbose Delay carbohydrate absorption DPP-4 Inhibitors Sitagliptin, Linagliptin Increase incretin levels → ↑ insulin secretion SGLT2 Inhibitors Empagliflozin, Dapagliflozin Increase urinary glucose excretion GLP-1 Receptor Agonists Semaglutide, Liraglutide ↑ Insulin, ↓ glucagon, promote weight loss Insulin Lispro, Regular, Glargine Replaces insulin deficiency and lowers blood glucose
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  Thyroid Gland Synthesis ofThyroid Hormones Iodide uptake by thyroid cells. Oxidation of iodide. Iodination of tyrosine residues. Formation of T3 and T4. Storage in thyroglobulin. Release into circulation. Butterfly-shaped endocrine gland located in the neck. Produces: Thyroxine (T4) Triiodothyronine (T3) Calcitonin Regulated by the hypothalamic–pituitary–thyroid (HPT) axis
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  Functions of ThyroidHormones • Regulate basal metabolic rate (BMR). • Increase oxygen consumption. • Promote growth and development. • Regulate carbohydrate, fat, and protein metabolism. • Maintain cardiovascular and nervous system functions. Hypothyroidism Definition Hypothyroidism is a disorder in which the thyroid gland produces insufficient amounts of T3 and T4 hormones, leading to a reduction in the body's metabolic rate. Causes Hashimoto's thyroiditis (most common) Iodine deficiency Thyroid surgery (thyroidectomy) Radioactive iodine therapy Congenital hypothyroidism Drugs (e.g., lithium, amiodarone) Risk Factors Female gender Age >60 years Autoimmune diseases Family history Previous thyroid surgery
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  Pathophysiology of Hypothyroidism •Thyroid gland damage or iodine deficiency ↓ Reduced T3 and T4 secretion ↓ Loss of negative feedback ↓ Increased TSH secretion ↓ Reduced basal metabolic rate ↓ Clinical manifestations Effects • Decreased energy production • Slowed metabolism • Reduced heart rate • Cold intolerance • Weight gain • Dry skin and hair loss • Constipation • Mental slowing
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  Clinical Features, Diagnosis& Treatment Symptoms • Fatigue • Weight gain • Cold intolerance • Puffy face • Dry skin • Constipation • Bradycardia • Depression Diagnosis • ↑ TSH • ↓ Free T4 • Anti-thyroid peroxidase (Anti-TPO) antibodies • Thyroid ultrasound (if required) Treatment • Levothyroxine (drug of choice) • Monitor TSH every 6–8 weeks initially • Adequate dietary iodine intake
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  Hyperthyroidism Definition Hyperthyroidism is adisorder in which the thyroid gland produces excessive amounts of T3 and T4 hormones, resulting in an increased metabolic rate. Causes • Graves' disease (most common) • Toxic multinodular goiter • Toxic adenoma • Thyroiditis Excess thyroid hormone intake • Risk Factors • Female gender • Family history • Autoimmune disorders • Smoking (Graves' disease)
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  Pathophysiology of Hyperthyroidism •Autoimmune stimulation (Graves' disease) or thyroid nodule ↓ Excess secretion of T3 and T4 ↓ Suppression of TSH ↓ Increased cellular metabolism ↓ Excess sympathetic activity ↓ Clinical manifestations • Effects • Increased basal metabolic rate • Increased heart rate • Weight loss • Heat intolerance • Tremors • Nervousness • Increased sweating • Muscle weakness
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  Clinical Features, Diagnosis& Treatment Symptoms • Weight loss • Increased appetite • Heat intolerance • Tachycardia • Tremors • Anxiety • Excessive sweating • Exophthalmos (Graves' disease) Diagnosis • ↓ TSH • ↑ Free T3 and T4 • Thyroid receptor antibodies (TRAb) • Radioactive iodine uptake scan • Thyroid ultrasound Treatment • Methimazole (first-line in most patients) • Propylthiouracil (PTU) (preferred in the first trimester of pregnancy and thyroid storm) • Propranolol for symptom control • Radioactive iodine therapy
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  • Goiter • Definition •Goiter is an abnormal enlargement of the thyroid gland. • Causes • Iodine deficiency • Graves' disease • Hashimoto's thyroiditis • Thyroid nodules • Symptoms • Neck swelling • Difficulty swallowing • Hoarseness • Breathing difficulty (large goiter) • Treatment • Depends on the cause: • Iodine supplementation • Levothyroxine • Antithyroid drugs • Surgery
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  Pregnancy as aRisk Factor for Thyroid Disorders • Increased thyroid hormone requirement during pregnancy • Higher iodine requirement for hormone synthesis • hCG stimulates the thyroid, causing temporary hyperthyroidism in some women • Immune changes increase the risk of postpartum thyroiditis • Untreated thyroid disorders may affect fetal growth and brain development Female gender (5–8 times more common than in males) Family history of thyroid disease Autoimmune diseases (e.g., Type 1 diabetes, rheumatoid arthritis) Iodine deficiency or excess Increasing age (especially >60 years) Radiation exposure to the head and neck Pregnancy and postpartum period Certain medications (e.g., lithium, amiodarone) Smoking (particularly associated with Graves' disease) Previous thyroid surgery or radioactive iodine therapy Risk factors
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  Effect of Lifestyleon Thyroid Health • Balanced iodine intake supports normal thyroid hormone production. • Healthy diet rich in selenium, zinc, and iron helps maintain thyroid function. • Regular exercise improves metabolism and helps maintain a healthy body weight. • Stress management may reduce the risk of thyroid dysfunction. • Adequate sleep supports normal hormone regulation. • Avoid smoking, as it increases the risk of Graves' disease and thyroid eye disease. • Limit excessive alcohol consumption to support overall endocrine health. • Regular health check-ups help in the early detection and management of thyroid disorders.
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  THANK YOU FF