T1DM vs T2DM Diabetes

Diabetes: T1DM vs T2DM

• Type 1 Diabetes involves the autoimmune destruction of insulin-producing beta cells in the pancreas
• Type 2 Diabetes involves insulin resistance and eventual pancreatic beta cell dysfunction
• Onset of Type 1 Diabetes typically occurs in childhood or adolescence
• Onset of Type 2 Diabetes typically occurs in adulthood but is increasingly seen in children
• Those with Type 1 Diabetes always require insulin
• Those with Type 2 Diabetes do not always require insulin, sometimes it can be managed with diet, exercise, and medication
• Risk factors for Type 1 Diabetes include family history and genetic predisposition
• Risk factors for Type 2 Diabetes include obesity, sedentary lifestyle, family history, and poor diet
• Symptoms for both types are similar but Type 2 Diabetes may develop more gradually
• Symptoms include frequent urination, extreme thirst, weight loss, fatigue, increased appetite, and blurred vision
• Treatment for Type 1 Diabetes is insulin therapy, glucose monitoring, and a healthy diet
• Treatment for Type 2 Diabetes is lifestyle changes, oral medications, and sometimes insulin
• Type 1 Diabetes is not preventable
• Type 2 Diabetes is often preventable with healthy lifestyle choices

Hormones and Diabetes

• Insulin, produced by the pancreas, helps the body use sugar (glucose) from food for energy
• In Type 1 Diabetes, the body's immune system attacks the beta cells in the pancreas, which produce insulin
• In Type 2 Diabetes, the body may produce insulin, but it is not enough, or the cells become resistant to its effect, leading to decreased sugar metabolism and increased blood sugar levels

Pathophysiology of Insulin Resistance in T2DM

• Cells become less responsive to insulin
• Elevated blood sugar levels occur because glucose cannot be efficiently taken up by cells
• Eventually, the pancreas overproduces insulin and subsequently fails

Ketoacidosis in T1DM and HHNK (HHNC) in T2DM:

• In T1DM, the body cannot use sugar for energy due to lack of insulin and burns fat instead, producing acidic ketones, leading to ketoacidosis
• High blood sugar has no way to move from extracellular to intracellular
• In T2DM, extremely high blood sugar levels lead to severe dehydration and a buildup of solutes in the blood, known as HHNK (hyperosmolar nonketotic coma), triggered by illness, infection, or medication

Lack of Insulin

• Lack of insulin causes glucose to build up in the bloodstream instead of going into the cells, resulting in hyperglycemia
• The body is unable to use glucose as a form of energy
• This leads to symptoms of Type 1 DM

Polycystic Ovary syndrome

• The exact cause is unknown but is believed to begin in utero due to congenital dysfunction.
• Comorbidities: obesity, insulin resistance, Type 2 DM, anxiety, and depression

Amenorrhea

• Primary amenorrhea is caused by hormonal dysregulation, specifically elevated androgen levels and disruptions in the hypothalamic-pituitary-gonadal (HPG) axis
• Secondary amenorrhea is caused by hormonal imbalances, specifically hyperandrogenism, leading to anovulation and disruption of the menstrual cycle

Metabolic Syndrome and Obesity: Common Lab Values

• Elevated triglycerides exist
• Elevated fasting glucose exists
• Elevated blood pressure and waist circumference exists
• Decreased HDL-C exists

Role of Insulin in Metabolic Syndrome

• Glucose uptake is reduced due to insulin resistance, leading to hyperglycemia, hyperinsulinemia, and systemic metabolic disturbances

Complications of Metabolic Syndrome

• There is an increased risk for type 2 DM, cardiovascular disease, MASLD, and MASH

Fractures

• Classified by pattern, extent, or skin involvement.
• Open Fracture: Bone pierces the skin creating an open wound, e.g., Compound fracture.
• Closed Fracture: Bone doesn't pierce the skin, e.g., Simple fracture with or without external injury.
• Complete Fracture: Bone is broken into two or more distinct pieces, e.g., Transverse (straight across) or Oblique (at an angle).
• Incomplete Fracture: Bone is partially broken but remains intact on one side.
• Seen mostly in children
• Example: Greenstick (bone is bent so that only the outer curve of the bend is broken) or Buckle (Torus) (one side of bone compresses and buckles)

Stages of Bone Healing:

• Inflammation (Days 1-7): Immediately after fracture with bleeding and inflammation at the fracture site
  • Release of inflammatory mediators (cytokines, prostaglandins)
  • Recruitment of immune cells (neutrophils, macrophages)
  • Preparation for tissue repair
• Bone Production (Repair) (Days 7-21): Fibroblast and chondrocytes proliferate forming granulations and soft callus
  • Angiogenesis occurs for nutrient supply
  • Early stabilization of fracture site
• Hard Callus Formation (2-6 weeks): Osteoblasts deposit woven bone
• Soft callus replaced with hard mineralized callus where fracture site gains more stability
• Bone Remodeling: Newly formed bone is remodeled, and the fracture callus is replaced with strong, organized bone tissue (Lasts for years)
  • Woven bone replaced by lamellar bone
  • Osteoclasts resorb excess bone, osteoblasts form new bone
  • Bone structure and strength are restored

Phases of Bone Remodeling

• Activation: Bone cells are activated, and osteoclasts are recruited to the bone surface
• Resorption: Osteoclasts break down old bone tissue by removing the mineralized matrix
• Reversal: Mononuclear cells are recruited to the bone surface, preparing it for the formation phase
• Formation: Osteoblasts synthesize and deposit new bone matrix, filling the space left by the resorbed bone
• Quiescence: Newly formed bone is covered by bone lining cells, keeping the bone surface inactive until the next remodeling cycle is initiated

Bone Reabsorption vs Resorption

• Bone Reabsorption: Absorbing something again, not the initial breakdown of tissue
• Bone Resorption: Physiological process where bone tissue is broken down and released into the bloodstream (bone is lost)

Osteoblast vs. Osteoclast:

• Osteoblast: Bone formation
• Osteoclasts: Bone reabsorption
• Osteocytes: Regulate mineralization and bone turnover
• Chondrocytes: Form cartilage in soft callus phase

Osteopenia and Osteoporosis

• Osteopenia: Condition characterized by lower-than-average bone density
• Osteoporosis: Metabolic bone disorder characterized by decreased bone density and strength and increased fracture risk
  • Primarily affects post-menopausal women and the elderly

Pathophysiology of Osteoporosis

• The rate of bone resorption exceeds bone formation

Causes of Osteoporosis

• Low dietary calcium

Risk Factors for Osteoporosis

• Age, being female, menopause, genetic predisposition, calcium and vitamin D deficiency, certain medications (glucocorticoids, anticonvulsants, PPI's, SSRI's, chemo meds, loop diuretics)

Interpretation of DEXA (T-scores):

• Normal: T-score greater than -1.0
• Osteoporosis: T-score less than -2.5
• Osteopenia: T-score between -1.0 and -2.5

Osteoarthritis

• Most common form of arthritis
• Key Features: cartilage degeneration, subchondral bone changes, and synovitis
• Cause: Primarily due to mechanical stress and aging, leading to cartilage breakdown -Imbalance in cartilage degeneration and repair -Chronic low-grade inflammation
• Common Affected Joints: knees, hips, and spine (neck and lower back), which are weight-bearing joints

Rheumatoid Arthritis

• Cause: Autoimmune with unknown triggers
• Most Affected Joint Area: Synovium (lining of joints)
• Joints Affected: small joints, wrists, MCPs, PIPs

Lab Tests for Rheumatoid Arthritis

• Positive rheumatoid factor
• Present anti-CCP antibodies (anti-cyclic citrullinated)
• Elevated ESR & CRP
• Anemia of chronic disease

Gout

• Primary Cause: Monosodium urate crystal (MSU) deposition in joints, a result of hyperuricemia (high uric acid levels in the blood)
• Manifestation: Acute gout attacks with rapid onset of severe pain, redness, and swelling
• Common sites: 1st metatarsophalangeal joint (Podagra)
• Chronic tophaceous gout: Presence of tophi (deposits of MSU crystals)
• Renal complications: Uric acid nephropathy, nephrolithiasis

Lab Values to Look for with Gout:

• Elevated serum uric acid
• Presence of MSU crystals under polarized light
• Increased inflammatory markers ESR, CRP
• Normal or elevated WBC during acute attacks

Disorders of Adrenal Glands

• Primary Disorders Originate directly within the adrenal glands
• Secondary Disorders Originate in the pituitary gland
• The pituitary gland signals the adrenal glands to produce hormones

Cushing's

• Cause: Problem with adrenal glands hypersecreting, usually due to the pituitary hypersecreting ACTH
• Complications: Hypertension, depression, infection, muscle weakness, MI, blood clots, osteoporosis, hyperglycemia, lower sex drive

Addison's

• Cause: Autoimmune attack on the adrenal cortex
• Complications: Severe abdominal pain, extreme weakness, hypotension, kidney failure, shock

Adrenal Excess vs. Adrenal Insufficiency

• Adrenal Excess (Cushing's Syndrome):*
• Hormone levels: Excess cortisol
• Primary cause: Excessive ACTH or adrenal tumors
• Symptoms: Weight gain, moon face, purple striae, muscle weakness
• Blood pressure: Hypertension
• Electrolyte imbalance: Hypokalemia
• Treatment: Tumor removal, medication to reduce cortisol
• Adrenal Insufficiency (Addison's Disease):*
• Hormone levels: Deficient cortisol & aldosterone
• Primary cause: Adrenal cortex damage (autoimmune, infection)
• Symptoms: Fatigue, weight loss, hyperpigmentation
• Blood pressure: Hypotension
• Electrolyte imbalance: Hyponatremia, hyperkalemia
• Treatment: Hormone replacement therapy

Thyroid Hormones

• Regulate weight, energy levels, internal temperature, skin, hair, nail growth, metabolism
• Increase metabolic rate, protein synthesis, heart function, heat production and nervous system activity

Triiodothyronine (T3)

• Active form of thyroid hormone
• Regulates metabolism, growth, and energy production
• Produced in the thyroid gland and from the conversion of T4 in peripheral tissues
• More potent than T4
• Shorter half-life than T4, is metabolized and eliminated from the body more quickly

Thyroxine (T4)

• Breaks down to T3 inside body tissues
• Primary thyroid hormone secreted by the thyroid gland
• Prohormone, and it is not directly active in the body
• Converted into T3 in peripheral tissues (liver and kidneys)
• Longer half-life than T3 and will stay in the bloodstream for a longer period

Hyperthyroidism vs. Hypothyroidism

• Primary Hyperthyroidism: Excessive thyroid hormones produced by the thyroid gland
• Primary Hypothyroidism: Insufficient thyroid hormones produced
• Secondary Hyperthyroidism: Excessive thyroid hormone due to stimulation from the pituitary gland or hypothalamus
• Secondary Hypothyroidism: Insufficient thyroid hormone production because the pituitary gland isn't functioning properly

Hyperthyroidism (Metabolism, Excitability Increased):

• Weight loss despite of increased appetite
• Rapid or irregular heartbeat
• Nervous, irritable and trouble sleeping

Hypothyroidism (Metabolism, Excitability Decreased):

• Weight gain
• Slowed heart rate
• Fatigue, depression, or trouble tolerating cold
• Enlargement in the neck, called a goiter

Hypothalamus-Pituitary-Thyroid (HPT) Axis: Feedback Inhibition

• Hypothalamus releases TRH, stimulating the Pituitary to release TSH, which in turn stimulates the Thyroid to produce T3 and T4
• This is to maintain a balance

Thyroid Function Tests:

• Associated Conditions: Graves', Central Hyperthyroidism, Hashimoto's, Hypothyroidism
• Hypothyroidism: low TSH, high T4/T3 and thyroid-stimulating antibodies.
• Hyperthyroidism (Graves'): elevated free T4 and FT3 levels, normal or elevated TSH
• Hashimoto's: high levels of TPOAb (thyroid antibodies)
• Central Hyperthyroidism: elevated TSH

Graves' Disease

• No clear cause, but is the most common cause of hyperthyroidism
• Autoimmune disorder where the immune system mistakenly attacks the thyroid gland, causing it to overproduce thyroid hormones
• Results in Hyperthyroidism (too much thyroid hormone)
• Risks: women over men, genetic predisposition, environmental triggers, stress, smoking, infections

Hashimoto's

• No clear cause (autoimmune) Autoimmune disorder where the immune system attacks and damages the thyroid gland, leading to a gradual decrease in its ability to produce thyroid hormone
• Results in Hypothyroidism (Not enough thyroid hormone)
• Risk : women more likely than men especially women who have ever been pregnant before.

Graves' Disease vs. Hashimoto's:

• Graves' disease causes hyperthyroidism (overactive thyroid), while Hashimoto's causes hypothyroidism (underactive thyroid)

Pituitary Gland:

Hormones Secreted:

• Anterior pituitary releases all target hormones
• Posterior pituitary releases only ADH and oxytocin

Role of Growth Hormone:

• Excessive GH and IGF-1: Gigantism in a child, acromegaly in an adult
• Deficiency: Dwarfism

Hypopituitarism:

• Insufficient production of pituitary hormones
• Deficiencies exist with GH (somatropin), FSH/LH, TSH, ACTH, ADH, and GH (Growth hormone-pediatric)

Causes

Conditions exist affecting hormone production of the pituitary gland (most common is a pituitary adenoma (Tumor)) & hypothalamus

• Pituitary: Condition affecting the hormone production of the pituitary gland itself (most common is a pituitary adenoma (Tumor))
• Hypothalamic: conditions affecting the hypothalamus, the brain region that controls pituitary function, leading to a disruption in the signals that tell the pituitary to release hormones.
• Sheehan's syndrome: Postpartum pituitary gland necrosis. Caused by vasospasm of the hypothalamic portal vessels which can lead to the death of the pituitary gland.

HPA Axis: Hormonal Control via Negative Feedback

• Negative feedback systems use the hormone to signal the body to reduce further release when levels are too high, maintaining balance and preventing overproduction

Chronic vs. Acute Stress

• Differentiate between chronic stress and acute stress and the hormones that control the body's reaction

Chronic Stress

• Prolonged feeling of pressure and overwhelm that can last for weeks or months
• Cause: related to Life events, environment, work, or relationships

Acute Stress

• A sever but temporary psychological response to a traumatic or surprising event <1month
• Cause: related to Exposure to a traumatic event

Hormones Involved in Stress Response:

• Cortisol: Increases glucose production, suppresses inflammation, regulates BP, enhances memory and cognitive function, mobilizes fat stores, regulates metabolism, controls sleep-wake cycle -Mood is impacted
  • Targets: Hypothalamus Pituitary gland, Adrenal gland, Liver and Pancreas
• Epinephrine: Prepares the body for "fight or flight"
  • Targets: Heart, Lungs and Liver
• Norepinephrine: Mobilizes the body for action, regulates BP, enhances glucose release, increases muscle contraction, modulates mood, regulates sleep-wake cycle, and suppresses the immune response. -Targets: Lungs and brain

Adrenal Gland

• Adrenal gland is the difference in the adrenal gland during the stress response
• Adrenal medulla: Plays a crucial role in the body's stress response by secreting catecholamines and secretes Epi/NorEpi
• Adrenal cortex: Produces steroid hormones such as Cortisol, aldosterone, and Adrenal androgens (DHEA)