Diabetes Mellitus Overview

Diabetes Mellitus (DM)

• Disorder of carbohydrate metabolism characterized by high blood glucose levels
• Body cannot produce or properly utilize insulin
• Contributes to increased morbidity and mortality
• Increases the risk of CVD, renal damage, peripheral vascular disease, neurological disorders, blindness and amputation

Four Major Categories of DM

• Type 1 DM (T1DM):     - Characterized by a lack of insulin production     - Beta cells of pancreas are destroyed     - Requires insulin treatment
• Type 2 DM (T2DM):     - Represents 90% of cases     - Characterized by insulin resistance
• Gestational DM (GDM):     - Develops during pregnancy due to hormone-induced insulin resistance     - Can lead to macrosomia (large babies)
• Other:     - Caused by factors like pancreatitis, cystic fibrosis, or neonatal conditions

Epidemiology of DM

• Affects over 30 million individuals in the US
• Prevalence increasing parallel to obesity rates and sedentary lifestyles
• Prevalence increases with age
• DM is a polygenic disorder with environmental triggers

Etiology of DM

• Type 1 DM:     - Autoimmune destruction of beta cells     - Antibodies present     - No insulin production by the body
• Type 2 DM:     - More gradual onset     - Insulin resistance     - Insulin is produced but not utilized effectively     - Associated with sedentary behavior and obesity

Insulin and Carbohydrate Ingestion

• Insulin:     - Produced by beta cells     - Facilitates glucose movement from blood to cells
• Carbohydrate ingestion:     - Simultaneous rise and fall of blood glucose and insulin levels     - Insulin levels rise in response to the increase in blood glucose

Insulin Facilitates Glucose Uptake

• Insulin promotes glucose uptake in:     - Muscle: Glycogenesis (glucose storage)     - Liver: Glycogenesis and gluconeogenesis (glucose production)     - Adipose tissue: Reduced lipolysis (fat breakdown)

Carbohydrate Metabolism Overview

• Glucose is used for energy, glycogen storage, and lipid (fat) synthesis
• Glycogenesis: Glucose to glycogen (storage) in liver and muscle
• Glycogenolysis: Glycogen to glucose (release) when blood glucose is low
• Gluconeogenesis: Non-carbohydrate sources like amino acids and glycerol are converted to glucose in the liver and kidneys

Ketone Formation and Diabetic Ketoacidosis (DKA)

• DKA primarily occurs in Type 1 DM
• Ketones are produced when glucose cannot be utilized for energy
• Accumulation of ketones can lead to metabolic acidosis (DKA)

Blood Glucose Levels

• Normal Blood Glucose: 70–100 mg/dL (fasting)
• Hypoglycemia: BG < 70 mg/dL
• Impaired Glucose Tolerance (IGT) / "Prediabetes": Fasting BG: 100–125 mg/dL
• Diabetes: Fasting BG: >126 mg/dL
• Postprandial BG:     - Glucose levels after eating     - > 200 mg/dL indicates diabetes

Role of Insulin

• Insulin: An anabolic hormone that facilitates glucose uptake and utilization
• Hyperinsulinism: Elevated insulin levels which may occur in early T2DM, attempting to overcome insulin resistance
• Hypoglycemia: Too much insulin leads to low blood glucose levels

Other Glucose-Regulating Hormones

• Glucagon: Released by alpha cells of the pancreas; raises blood glucose (injectable form for severe hypoglycemia)
• Somatostatin: Released by delta cells of pancreas; diminishes insulin and glucagon secretion, slows GI activity
• Incretins: GI hormone that stimulates insulin release and slows GI motility (includes GLP-1 and GIP)
• Cortisol: Released by adrenal cortex; a steroid hormone that increases blood glucose

Glucose-Regulating Signals from Pancreas

• Pancreatic cells release hormones (like insulin and glucagon) in response to blood glucose levels

T1DM: Pathological Mechanism

• Autoimmune destruction of beta cells mediated by T-cells
• Genetic predisposition
• Initial presentation is often DKA
• Symptoms: Polyuria (increased urination), polydipsia (increased thirst), polyphagia (increased hunger)

T2DM: Pathological Mechanism

• Insulin resistance with increased insulin levels
• Molecular mechanisms: Oxidative stress, inflammation, insulin receptor mutation, mitochondrial dysfunction
• Associated with metabolic syndrome (HTN, dyslipidemia, hyperinsulinism, central obesity)
• Hyperosmolar Hyperglycemic State (HHS): Hyperglycemia with dehydration, usually occurs in type 2 DM and progresses slowly

Gestational Diabetes Mellitus (GDM)

• Develops during pregnancy due to pregnancy-induced insulin resistance
• Complications: Fetal defects, premature delivery, newborn hypoglycemia, macrosomia
• Screening: 2nd trimester oral glucose tolerance test (OGTT)
• GDM typically resolves after delivery but can increase the risk of T2DM

Diabetes Tests

• Blood Glucose: Fasting and random blood glucose measurements
• Oral Glucose Tolerance Test (OGTT): 75g glucose ingested, blood sugar is measured
• Glycated Hemoglobin (A1c): Indicates average blood sugar levels over 3 months
• eAG: Average blood glucose over the last few months
• Islet Cell Autoantibodies (ICAs): Present in T1DM
• C-Peptide Test: Measures endogenous insulin production, helps differentiate between T1DM and T2DM

Diabetes Tests: Urinalysis

• Glucosuria: Elevated blood glucose levels lead to glucose in urine
• Ketonuria: Ketones in urine are associated with DKA and increased ketone production

Complications of DM

• Both acute and long-term complications
• Acute: Hypoglycemia, hyperglycemia, DKA (T1DM), HHS (T2DM)
• Long-term systemic: Blindness, kidney failure, neuropathy, cardiovascular disease, amputation

Hypoglycemia

• Blood Glucose less than 70 mg/dL
• Causes:     - Excessive exogenous insulin     - Inadequate food intake     - Excessive physical activity     - Infection, illness, drug interaction
• Compensatory response: Activation of the sympathetic nervous system: Sweating, hunger, dizziness, headache, heart palpitations, confusion
• Management:     - Rapid acting carbohydrates (15 grams)     - Avoid fats (delay glucose absorption)     - If BG >70 mg/dL, provide a meal or snack     - IV glucose or subcutaneous glucagon injection
• Repeated hypoglycemia can blunt the compensatory response, potentially leading to autonomic neuropathy

Somogyi Effect and Dawn Phenomenon

• Somogyi Effect:     - Morning hyperglycemia due to hypoglycemia during sleep often caused by excessive insulin dosage     - Adjust insulin dosage
• Dawn Phenomenon:     - Morning hyperglycemia without hypoglycemia during sleep     - Adjust medication, exercise, and eating patterns

Classic Signs of Diabetes Mellitus

• Polydipsia (increased thirst): High blood glucose increases plasma osmolarity, leading to fluid shifts and dehydration, stimulating thirst
• Polyphagia (increased hunger): Cells cannot utilize glucose effectively due to lack of insulin, increasing appetite
• Polyuria (increased urination): Increased renal glucose filtration and osmotic diuresis lead to increased urination

Fluid Shifts and Glucose in Urine

• Glucose and fluid are excreted in urine due to the kidney's inability to reabsorb them efficiently

Additional Signs of DM

• Blurred vision: Glucose accumulation in aqueous fluid alters light refraction
• Fluid/Electrolyte Imbalance:     - Intracellular (ICF) to extracellular fluid (ECF ) shifts can lead to dilutional hyponatremia     - Electrolyte shifts: Potassium (K+) shifts out of cells

Diabetic Ketoacidosis (DKA)

• Occurs when insulin is lacking (primarily in T1DM)
• Insulin prevents lipolysis and ketone formation
• Ketone buildup leads to metabolic acidosis (DKA)
• Diagnostic criteria:     - BG > 250 mg/dL     - pH < 7.3     - HCO3− < 18 mEq/L     - Blood osmolarity > 20 mOsm/L
• Presentation: Nausea, vomiting, abdominal pain, deep rapid breathing (Kussmaul breathing), fruity breath odor

Hyperosmolar Hyperglycemic State (HHS)

• Hyperglycemia: Inability to facilitate glucose uptake, contributing to increased blood sugar
• Hyperosmolarity: Elevated blood glucose leads to osmotic diuresis and dehydration
• Clinical progression: Can develop slowly over days to weeks
• Presentation: Weakness, dehydration, tachycardia, thready pulse, confusion, coma
• Causes: Infection, trauma, non-compliance with DM management
• Treatment: Fluids (first) followed by insulin

Long-Term Complications of DM

• Arteriosclerosis (damaged blood vessels): Hyperglycemia damages endothelial cells, leading to plaque formation
• Peripheral angiopathy (poor circulation): Damage to blood vessels in the extremities
• Diabetic retinopathy (damaged eye vessels): Can lead to blindness
• Diabetic neuropathy (nerve damage): Affects nerves, particularly in the feet, causing numbness, tingling, and pain
• Autonomic neuropathy: Disrupts autonomic nervous system function
• Diabetic nephropathy (kidney damage): Can lead to kidney failure
• Poor wound healing: Reduced blood flow and high sugar levels impair the healing process
• Immunosuppression: Weakened immune response

DM and Atherosclerosis

• Increases risk of acute cardiac events (MI)
• Atherosclerosis affects both large and small arteries
• Hyperglycemia leads to oxidative stress, contributing to vascular damage

DM and Peripheral Neuropathy

• Distal, symmetric polyneuropathy: Damage to neural arteries begins in the feet, progresses upwards
• Effects: Burning, tingling, impaired sensation, pain perception, motor weakness, gait abnormalities, charcot joints

DM and Autonomic Neuropathy

• Affects various systems:     - Cardiac: Tachycardia, hypotension     - GI: Gastroparesis, gastric emptying abnormalities, anorexia, nausea, bowel dysfunction     - Urinary: Increased UTI risk     - Reproductive: Erectile dysfunction     - Temperature regulation: Decreased sweating, hyperthermia, dry skin     - Glycemic control: Hypoglycemia, impaired awareness of warning signs

DM and Susceptibility to Infection

• Impaired WBC function increases the risk of infections like staphylococcus aureus and candida (yeast)
• High glucose levels alter vaginal pH, promoting candida proliferation

DM and Amputation

• Leading cause of non-traumatic limb amputations
• Peripheral neuropathy, poor circulation, and immune suppression increase infection risk, potentially leading to gangrene and amputation

DM and Foot Care

• Regular foot examination is essential for early detection of injuries, ulcers, and infections

DM and Retinopathy/Blindness

• Leading cause of blindness in adults
• Retinal circulatory damage: Microaneurysms, macular edema, "cotton wool spots" (infarcted areas)
• Proliferative retinopathy: New vessel growth, fragile and prone to rupture, retinal detachment
• Regular eye exams are crucial

DM and Nephropathy

• Can lead to renal failure
• Damage to glomerular capillaries leading to microalbuminuria (protein in the urine)
• Thickening of the glomerular basement membrane due to glycosylation
• Activation of the RAAS (renin-angiotensin-aldosterone system) exacerbates blood pressure issues

DM and Dermatological Changes

• Prolonged wound healing and ulcer formation
• Diabetic skin spots: Hyperpigmented areas
• Acanthosis nigricans: Tiny, hyperpigmented macular lesions
• Lipoatrophy: Can occur at insulin injection sites

DM and Psychological Resistance

• Depression is more common in individuals with DM
• Guilt, discouragement, self-blame
• Anxiety regarding disease management
• Denial and non-compliance
• Psychological insulin resistance: Refusal to comply with insulin management

DM and Eating Disorders

• Young women with T1DM are at risk for eating disorders
• Insulin purging: Restricting or skipping insulin to stimulate lipolysis and weight loss
• Suspect eating disorder in patients with:     - Recurrent DKA     - Chronically poor glycemic control

DM Treatment Overview

• Blood glucose control: Both hyperglycemia and hypoglycemia need to be managed
• Glycemic control: Primary treatment goal to minimize the risk of complications
• Reduce CVD risk: Lipid panels, LDL < 60 mg/dL, Trigylcerides under control