Endocrine System and Glucose Metabolism

• Module II covers Endocrine Disorders Part 1.

The Endocrine System

• The nervous and endocrine systems are major controllers of homeostasis.
• The endocrine system consists of glands that secrete hormones to maintain homeostasis.
• A hormone is a chemical messenger released in response to a change in the body's internal environment.
• Hormones enter the bloodstream after secretion from endocrine glands and are transported throughout the body.
• The primary endocrine glands include:
  • Hypothalamus
  • Pituitary
  • Thyroid
  • Adrenal
  • Parathyroid
  • Pancreas
  • Ovary/Testes
  • Pineal
  • Thymus
• Hormonal balance is kept within a narrow range, and excessive or insufficient hormone levels can lead to significant physiological changes.
• Negative feedback regulates hormonal processes.
• Medications can mimic or block hormone effects to address communication issues or disease states.

Normal Regulation of Blood Glucose

• Glucose, or "blood sugar," is the body's primary energy source.
• Glucose is supplied to bloodstream through diet and normal fasting levels for people without diabetes mellitus (DM) range between 70-110 mg/dL.
• The pancreas releases hormones to regulate blood glucose levels.
• Insulin reduces blood glucose levels.
• Glucagon increases blood glucose levels.
• Insulin is released from beta cells in the pancreas and it is needed to allow glucose entry into cells.
• Insulin secretion is triggered by glucose in the blood and incretins (GIP, GLP-1).
• Insulin promotes the storage of glucose in the liver as glycogen.
• Intestinal glucose triggers the release of incretins.
• Incretins cause the pancreas to release insulin, facilitating glucose entry into cells.
• Amylin is co-secreted with insulin from beta cells.
• Amylin plays a role in glycemic regulation by:
  • Inhibiting glucagon secretion
  • Slowing gastric emptying
  • Promoting satiety to prevent post-prandial spikes in blood glucose
• After carbohydrates are consumed, glucose enters the bloodstream and the small intestine releases incretins which causes:
  • Beta cells in the pancreas to release insulin and amylin
  • Insulin presence allows glucose into cells
  • Amylin promotes satiety, slows gastric emptying, and stops glucagon secretion
• Glucagon increases levels of glucose in blood:
  • It is released from alpha cells in pancreas
  • It can be increased through the process of glycogenolysis
  • Glycogenolysis occurs in the liver, stored glycogen is broken down, and glucose is released into the bloodstream
  • It can be increased through the process of gluconeogenesis
  • Gluconeogenesis occurs in the liver, fats and proteins are turned into endogenous glucose
  • Ketones increase in free fatty acids in blood and ketones in the urine due to breakdown of lipids

Diabetes Mellitus

• Diabetes mellitus impairs the body's ability to produce or respond to insulin, leading to elevated glucose levels in blood and urine.
• Diabetes can lead to acute and chronic complications.
• Glucose intolerance disorders include:
  • Type 1 diabetes mellitus (T1DM)
  • Type 2 diabetes mellitus (T2DM)
  • Gestational diabetes

Comparing Type 1 & 2 Diabetes

• Type 1 Diabetes Mellitus:
  • Etiology: Autoimmune process
  • Primary pathology: Loss of pancreatic beta cells secretion of insulin
  • Age of onset: Usually childhood or adolescents
  • Speed of onset: Abrupt
  • Prevalence: 5-10%
  • Treatment: Insulin replacement is mandatory with strict dietary control
  • Blood glucose: Levels fluctuate widely in response to infection, exercise, and changes in insulin dose and caloric intake
  • Body composition: Usually thin and undernourished at diagnosis
  • Ketosis: Common, especially if insulin dose is too low
• Type 2 Diabetes Mellitus:
  • Etiology: Genetics, lifestyle
  • Primary pathology: Insulin resistance, loss of incretin effect, beta cell dysfunction
  • Age of onset: Usually > 40 years
  • Speed of onset: Gradual
  • Prevalence: 90-95%
  • Treatment: Oral anti-diabetic, non-insulin injectable, or insulin in combination with reduced calorie diet and exercise
  • Blood glucose: More stable than in Type I
  • Body composition: Frequently obese
  • Ketosis: Uncommon
• T1DM manifests more abruptly and may present with diabetic ketoacidosis (DKA).
• T2DM has a gradual onset.
• Hallmark diabetes symptoms: Polyuria, polydipsia, and polyphagia
• Other symptoms include fatigue, vision changes, non-healing sores, frequent infections, and peripheral neuropathy.

Gestational Diabetes

• Gestational diabetes involves insulin resistance with onset during pregnancy in 1-10% of pregnancies in the US which closely resembles Type 2 DM (T2DM).
• Placental hormones and weight gain during pregnancy most likely precipitate gestational diabetes.
• Risk factors include:
• Obesity
• Previous history of gestational diabetes
• Previous offspring weighing more than 9 lb. at birth
• Presence of glycosuria
• Family history of T2DM
• Complications include:
• Infant: metabolic abnormalities, stillbirth, macrosomia, and neonatal hypoglycemia
• Mother: development of T2DM or insulin resistance later in life
• Management includes:
  • Dietary counseling
  • Exercise
  • Blood glucose/ketone monitoring, and insulin may be needed

Evaluating Blood Glucose Levels

• Hemoglobin A1c:
  • Reflects blood glucose control over the lifespan of the red blood cells (90-120 days range)
  • It is not affected by short-term variations in blood glucose.
  • Diagnostic value: ≥ 6.5%
• Fasting Plasma Glucose (FPG), where FPG= no caloric intake for ≥ 8 hours:
  • Diagnostic value: ≥ 126 mg/dL
• Two-hour Plasma Glucose During an Oral Glucose Tolerance Test (OGTT) using 75g glucose water:
  • Diagnostic value: ≥ 200 mg/dL
• Random Plasma Glucose
  • In patients with classic symptoms of hyperglycemia
  • Diagnostic value: ≥ 200 mg/dL
• Glycemic control recommendations for diabetic patients:
  • HgbA1c < 7%
  • Elderly or patients with a history of severe hypoglycemia may have a goal of < 8%
  • Fasting Plasma Glucose
  • Outpatient = 80-130mg/dL
  • Hospital = 140-180 mg/dL
  • Post-prandial (1-2 hours after a meal) < 180 mg/dL
• Blood pressure recommendations for diabetic patients:
  • < 130/80 mmHg or < 140/90 mmHg
• Lipid recommendations for diabetic patients:
  • Total Cholesterol < 200 mg/dL
  • LDL < 100 mg/dL
  • HDL > 60 mg/dL
  • Triglycerides < 150 mg/dL
• Protein in urine recommendation for diabetic patients:
  • The kidney may leak small amounts of albumin into urine because of damage.
  • Albumin to creatinine ratio level goal is <30 mcg/mg (for random collection).
• Tight goals prevent chronic and acute complications like:
  • Hypoglycemia
  • Diabetic ketoacidosis (DKA)
  • Hyperglycemic hyperosmolar nonketotic syndrome (HHS)
  • Micro and macrovascular complications

Chronic Diabetes Complications

• Microvascular damage:
  • Basement membrane of capillaries thickens, reducing blood flow in narrow vessels.
  • Destruction of small vessels contributes to kidney damage (nephropathy), blindness (retinopathy), and neuropathies
• Macrovascular Disease:
• Complications result from sustained hyperglycemia and altered lipid metabolism often causing atherosclerosis that affect:
• Brain- Cerebrovascular disease, Transient ischemic attack and Cerebrovascular accident
• Heart- Coronary artery disease, Myocardial infarction and Congestive heart failure
• Extremities- Peripheral vascular disease causes Ulceration, Gangrene and Amputation

Treatment of Diabetes Mellitus

• Cornerstone of Therapy for DM include:
  • Nutrition
  • Physical Activity
  • Self Monitoring of Glucose
  • Education
  • Medications
• Medication treatment options include:
  • Oral Medications for DM
  • Non-insulin injectables
  • Insulin
• Oral medications are useful for T2DM patients not controlled with lifestyle modifications Patients with long standing T2DM may need medications or insulin alone if HA1c remains high
• Types of oral medication available for DM include:
  • Biguanide
  • Sulfonylureas
  • Thiazolidinediones (TZDs)
  • α-glucosidase inhibitors
  • DPP-4 inhibitors
  • SGLT-2 inhibitors
• Monitoring should include glycemic, blood pressure, lipid and renal goals
• The goal of medications is to increase the utilization of glucose through
  • Increasing insulin and amylin secretion by the pancreas
  • Slowing glucose absorption and increasing incretin effect from intestines
  • Inhibiting gluconeogenesis in the liver
  • Increasing glucose excretion through urine by the kidneys
  • Enhancing insulin sensitivity of skeletal and adipose tissues

Oral Medications for DM

• Drug Class: Biguanide
  • Prototype: Metformin
  • Use: T2DM
  • Mechanism of Action:
    • Enhances glucose uptake by tissues by increasing insulin sensitivity
    • Decreases gluconeogenesis
    • Decreases amount of glucose absorbed from intestines
  • Route: Oral
  • Adverse Effects: Diarrhea, nausea, vomiting, lactic acidosis, and vitamin B12 deficiency
  • Administer with food!
  • Monitor and provide B12 supplementation if needed
  • Avoid in patients with lactic acidosis
  • Hold medication if lactic acidosis occurs and contact provider
• Drug Interactions:
  • Avoid iodine contrast media
  • Hold metformin 48 hours before contrast is administered and can resume when kidney function is acceptable
  • Alcohol can increase risk of lactic acidosis
• Considerations: Best initial T2DM treatment and no hypoglycemia or weight gain
• Drug Class: Sulfonylurea
  • Prototype: Glipizide
  • Use: T2DM
  • Mechanism of action: Stimulates insulin secretion from pancreas by binding to pancreatic beta receptors
  • Route: Oral
  • Adverse effects: hypoglycemia and weight gain
  • Drug interactions: alcohol can cause a disulfiram reaction (intense nausea and vomiting)
  • Nursing considerations: take 30 minutes prior to breakfast, hold if patient is not eating, monitor for hypoglycemia
• Drug Class: Thiazolidinediones (TZDs)
  • Prototype: Pioglitazone
  • Use: T2DM
  • Mechanism of Action: activates PPAR-gamma gene to increase insulin sensitivity while decreasing liver gluconeogenesis
  • Route: Oral
  • Adverse Effects: fluid retention, heart failure, may increase LDL levels, hepatotoxicity, risk of bone fractures, may cause ovulation
  • Drug interactions: use with insulin can increase fluid retention
  • Nursing considerations: take once daily, monitor for fluid status, liver function, and cholesterol levels
• Drug Class: Alpha-glucosidase inhibitor
  • Prototype: Acarbose
  • T2DM; targets post prandial glucose -Blocks enzymes in the small intestine that are responsible for breaking down carbohydrates slowing digestion and thus, absorption of glucose from food
  • Route: Oral
  • Adverse Effects: Abdominal distention, cramping, hyperactive bowel sounds, diarrhea, excessive flatulence, decreased iron absorption->anemia, and potential hepatotoxicity
  • Clinical Considerations: Take with the first bite of food of each meal, dont give to patients with GI issues, Monitor CBC (anemia) and liver function, may not be effective on a low carb diet
• Drug Class: DPP-4 Inhibitors
  • Prototype: Sitagliptin
  • Use: T2DM
  • Mechanism of Action: Inhibits dipeptidyl peptidase-4 (DPP-4), which decreases the breakdown of incretins resulting in insulin production and a greater response to glucose.
  • Nursing consideration: Is generally well tolerated. It should be taken once daily.
• Drug Class: SGLT-2 Inhibitor
  • Prototype: Canagliflozin
  • Use: T1DM or T2DM, targets post prandial glucose levels
  • Mechanism of Action: Inhibits sodium-glucose co-transporter in the proximal renal tubule which facilitates more glucose excretion in urine
  • Route: Oral
  • Adverse Effects: Infections like cystitis and candida, polyuria, increased dizziness, risk for hypotension and hypovolemia
  • Clinical Consideration: Take once daily with or without food; rise slowly and report dizziness; monitor renal function, volume status, blood pressure

Non-Insulin Injectables for DM

• Drug Class: Amylin Mimetic
  • Prototype: Pramlintide
  • Use: T1DM and T2DM; targets post prandial glucose levels
  • Mechanism of Action: Mimics native peptide amylin to prolong gastric emptying time, reduces postprandial glucagon secretion, and reduces calorie intake
  • Route: Subcutaneous
  • Adverse Effects: Higher risk of Hypoglycemia in T1DM , nausea, vomiting, and reaction at injection site
    • If patient is on insulin then insulin dose must be decreased by 50%
  • Oral absorption is delayed so administer oral medications one hour before or two hours after each injection
• Drug Class: Incretin Mimetic
  • Prototype: Exenatide
  • Use: T2DM
  • Mechanism of Action: GLP-1 receptor agonist, stimulates glucose-dependent insulin secretion and increases glucose absorption
  • Route: Subcutaneous injection
  • Adverse Effects: Increased risk for thyroid cancer, GI upset, or pancreatitis
  • Nursing Considerations: don't use in patients with renal or GI issues, can administer other meds at separate times and keep it refrigerated until ready to use

Insulin

• Use: Glycemic control for T1DM, T2DM, and gestational DM
• Patients with T2DM may require when:
  • Oral medications, diet, and exercise are ineffective.
  • Severe renal or liver disease is present.
  • Experiencing severe stress.
• Mechanism of action: promotes cellular uptake of glucose, converts glucose to glycogen
• Adverse effect: hypoglycemia, hypokalemia
• Insulin types vary in onset, peak, and duration:
  • Rapid-Acting: has the fastest onset within 5 to 15 minutes, peak at 1-3 hours with a duration of 3-5 hours
  • Short Acting: has a onset within 30 to 60 minutes, peak at 2-4 hours, and duration of 5-7 hours
  • Intermediate Acting: has a onset within 1-2 hours, peak at 4-12 hours, duration of 18-24 hours
  • Long Acting: has a onset within 1-2 hours, is peakless and lasts for 24 hours
• Given SubQ and rotate injection sites to prevent lipohypertrophy or can be given IV in 0.9 % NS only
• Can be given through:
  • Basal/Bolus
  • Twice Daily Premixed
  • Just Basal insulin
  • Insulin pumps/patches or correction
• Drug Interactions:
  • Sulfonylureas, pramlintide and alcohol have additive hypoglycemic effects with concurrent use; monitor serum glucose levels and adjust medication doses accordingly.
  • Thiazide diuretics and glucocorticoids can raise blood glucose levels.
• Education for patients:
  • Proper diet and exercise
  • How to adjust insulin and appropriate insulin dosing to prevent hyper/hypoglycemia
  • What food and drinks should be eaten to adjust glucose
  • Appearance and mixing of types of insulin
  • Understanding insulin storage
  • When to seek medical advice: - Blood glucose > 250 mg/dL for 2 checks - Vomiting or diarrhea more than 6 hours - High fever more than 24 hours - moderate/high ketones for six or more hours

Managing Diabetes Mellitus Acute Complications

• Hypoglycemia:
  • Low blood glucose (<70 mg/dL).
  • Symptoms include shaking, sweating, rapid heartbeat, extreme hunger, confusion, and dizziness
  • Conscious patients: oral glucose using the 15/15 rule
    • Give 15-20 grams of oral glucose
    • Recheck blood glucose levels after 15 minutes and treat again if still hypoglycemic.
    • Eat something to prevent further hypoglycemia
  • Unconscious patients: parenteral route
    • Glucagon (intramuscular, subcutaneous, or intranasal)
    • Dextrose 50% intravenous
• Diabetic Ketoacidosis (DKA)
  • Common in T1DM.
  • Severe manifestation of insulin deficiency, evolving quickly
  • Results in hyperglycemia, dehydration, and ketoacidosis
  • Symptoms include polyuria, abdominal pain, polydipsia, Kaussmal respirations, nausea, vomiting, tachycardia, dehydration, hyponatremia, altered mental status and breath that smells fruity
  • Management
  • Fluid and electrolyte replacment
  • IV regular insulin therapy
    • Slowly stabilize blood glucose
    • Always check potassium levels before insulin, give supplement if potassium levels are less than 3.3
    • Once resolved, switch to subQ insulin with BG < 200 mg/dl and no acidosis
  • Correct severe acidosis
• Hyperosmolar Hyperglycemic Nonketotic State (HHS)
  • In patients with T2DM
  • Symptoms include:
    • Fatigue
    • Altered level of consciousness
  • Management
    • Careful rehydration
    • Monitor serum osmolality