Endocrine System 2

The Pancreas

Islets of Langerhans (beta cells) produce and co-secrete insulin and amylin

Insulin: released in response to elevation in serum glucose

1. Promotes uptake and metabolism of glucose by cells

2. Promotes uptake of amino acids by muscle tissue: anabolic growth hormone

3. Inhibits release of glucose by liver & breakdown/release of fats: restores euglycemia

Amylin: peptide hormone, balances effect of insulin by slowing gastric emptying, inhibiting glucagon secretion and enhancing feeling of satiety

Glucagon and Insulin

Glucagon

• Produced by the alpha cells of the islets of Langerhans in the pancreas

• Maintains blood glucose between meals and during fasting

• Main action: Increase blood glucose

• Initiates glycogenolysis (breakdown of glycogen) as a means of raising blood glucose

• Glucagon secretion is regulated by blood glucose

Insulin

• Produced by the beta cells of the islets of Langerhans in the pancreas

• Promotes glucose uptake by target cells and provides for glucose storage as glycogen

• Prevents fat and glycogen breakdown

• Inhibits gluconeogenesis and increases protein synthesis

Action of Insulin & Glucagon on Glucose

Insulin

• Increases glucose transport into skeletal muscle and adipose tissue

• Increases glycogen synthesis

• Decreases gluconeogenesis

Glucagon (treats hypoglycemia)

• Promotes glycogen breakdown

• Increases gluconeogenesis

Diabetes Mellitus

Characterized by imbalance between insulin availability & need

Type 1 (5%)

• Usually autoimmune, can also be genetic w/env components

• Complete absence of insulin, unable to produce

• Must have exogenous insulin injected

Type 2 (most common)

• Usually related to obesity, can also be genetic w/env components

• May still be able to produce insulin, but not enough

• Cannot properly metabolize carbs with endogenous insulin

• Can be treated with oral agents

Other

• Gestational

• Prediabetes

• Secondary Diabetes: something else going on that prevents function of pancreas. Ex. pancreatitis

Blood Tests for Diabetics

Fasting blood glucose test (6-8hrs)

• Target 80-130 mg/dL (ADA)

Capillary blood tests and self-monitoring of capillary blood glucose levels after meals

• Target <180 mg/dL (ADA)

Glycated hemoglobin testing (HbA1c) (how well controlled glucose been past few months)

• Target <7% (ADA)

Continuous glucose monitoring (CGM)

Diabetes Mellitus- the 3 polys

• Polyuria

• Polydipsia

• Polyphagia

Diabetes Impacts

• Leading cause of

• End-stage renal disease

• Adult blindness

• Non-traumatic lower limb amputations

Major contributing factor

• heart disease

• Stroke

Diabetes Mellitus Type I

Causes

• Loss of beta cell function

• Could be iatrogenic

• Could be genetic

• Could be autoimmune

• Almost always multifactorial

Clinical manifestation

• Absolute insulin deficiency

Diabetes Mellitus 2

Causes

• Impaired beta cell function

• Peripheral insulin resistance

• Increased hepatic glucose production

Clinical manifestation

• Insulin resistance and reduced insulin production

• Often preceded by prediabetes

Vascular Complications

• Result from thickening of vessel membranes in capillaries and arterioles

• Response to chronic hyperglycemia

• Specific to diabetes (unlike macrovascular)

• Peripheral vascular disease

  • Kidneys: nephropathy

  • Eyes: retinopathy

Diabetic Peripheral Neuropathy

Autonomic issues

• Can affect nearly all body systems

Complications

• Gastroparesis

• Delayed gastric emptying

• Sexual function

• Neurogenic bladder

• Cardiovascular abnormalities-postural hypotension, resting tachycardia, and painless MI

Pancreatic Disorders (oral hypoglycemics): sulfonylureas: glipizide & glyburide

sulfonylureas:

glipizide (Glucotrol) & glyburide (Glynase)

MOA

• Causes beta cells within the pancreas to secrete insulin

• Must have a functioning pancreas to work

• This reduces glucose output from liver

• May increase insulin sensitivity in tissues

Therapeutic Use

• Type 2 DM

Adverse Drug Reactions

• Hypoglycemia (safety alert!)

• Nausea, Diarrhea

Interventions

• Monitor for s/sx of hypoglycemia

• Monitory for persistent N/V

• Monitor CBC (if N/V persists)

Client Instructions

• Always carry snacks

• Wear medical alert bracelet

• If feeling hypoglycemic, check BG

• Take orally 30 min prior to meals!!! MUST HAVE FOOD!!!

Contraindications

• Pregnancy& Breastfeeding

• (insulin is preferable in pregnancy and lactation)

• DKA

Drug Interactions

• Alcohol! – may experience (N/V/ palpitations, flushing)

• Alcohol, NSAIDs, Salicylates may increase hypoglycemic effects (dizziness, weakness, tremors, malaise, sweating, tiredness, irritability, confused, gait, speech)

Precautions

• Renal or hepatic dysfunction

• Adrenal or pituitary insufficiency due to increased risk for hypoglycemia (low cortisol)

Pancreatic Disorders (oral hypoglycemics): Meglitinides/ antidiabetic: repaglinide & nateglinide

Meglitinides/ antidiabetic:

repaglinide (Prandin) & nateglinide (Starlix)

MOA

• Causes beta cells within the pancreas to secrete insulin

• Must have a functioning pancreas to work

• This reduces glucose output from liver

• May increase insulin sensitivity in tissues

• *similar to sulfonylureas, so if the patient doesn’t respond to those, they likely won’t respond to meglitinides

• different half life compared to sulfonylureas

Therapeutic Use

• Type 2 Diabetes Mellitus

Adverse Drug Reactions

• Hypoglycemia (safety alert!)

• Nausea, Diarrhea

Interventions

• Monitor for s/sx of hypoglycemia

• Monitory for persistent N/V

• Monitor CBC (if N/V persists)

Client Instructions

• Always carry snacks

• Wear medical alert bracelet

• If feeling hypoglycemic, check BG

• Take orally 30 min or less prior to meals (fast acting!): Kinda emergent. HAVE TRAY IN ROOM

Contraindications

• DKA

Drug Interactions

• Gemfibrozil (Lopid)

• Alcohol and rifampin may decrease hypoglycemic effects

Precautions

• Renal or hepatic dysfunction especially in older adults

• Individuals with other endocrine disorders

Pancreatic Disorders (oral hypoglycemics): Biguanides: metformin (Glucophage)

Biguanides: metformin (Glucophage)

MOA

• Decreases absorption of glucose from the intestines

• Decreases glucoses output from liver

• Increases insulin sensitivity in tissues

• does not promote secretion of insulin!!! Less risk of hypoglycemic event from dumping

• *Can be combined with other hypoglycemics (often Sulfonylureas and meglitinides) especially since it does not impact insulin secretion

Therapeutic Use

• Type 2 diabetes mellitus

Adverse Drug Reactions

• Lactic acidosis (rare): muscle ache, urine output change

• Nausea and vomiting

• Diarrhea eventually resolves

• Metallic tasting med: GI tapers over time

• Vitamin deficiencies (folic acid/B12)

Interventions

• Monitory for persistent N/V/D

• Monitor I/O

• Monitor for lactic acidosis

• Supplement folic acid/B12 PRN

Client Instructions

• Avoid alcohol

• Report weakness, hyperventilation

• May cause weight loss

• Take twice a day am/pm

• If ER form, take once a day (don’t chew or crush ER form)

Contraindications

• DKA

• Renal Insufficiency (eGFR < 30)

• hepatic insufficiency

• Hx of Recent MI or CHF

• COPD

• Alcoholism

Drug Interactions

• Alcohol increases risk for lactic acidosis

• CONTRAST must stop 2 days before procedure and do not resume until 48 hr after

  • very bad on kidneys and buildup can occur, leading to lactic acidosis

Precautions

• Diarrhea

• Gastroparesis

• Hyperthyroidism

• Older adults

• Pituitary insufficiency

Pancreatic Disorders (oral hypoglycemics): Thiazolidinediones or glitazones: pioglitazone & rosiglitazone

Thiazolidinediones or glitazones:

pioglitazone (Actos) & rosiglitazone (Avandia)

MOA

• Increases insulin sensitivity in tissues (via PPAR gamma receptors)

• Therefore, it requires insulin, so may need to be given in combination with insulin or medications that stimulate the pancreas to release insulin

Therapeutic Use

• Type 2 Diabetes Mellitus (with or without medication therapy with insulin or sulfonylureas)

Adverse Drug Reactions

• Fluid Retention!

• Hepatotoxicity: jaundice

• Increased serum lipid levels

• UTI

• Headaches

• Myalgia

Interventions

• Monitory for edema

• Monitor I/O

• Monitor serum lipids/triglycerides

• Liver enzyme surveillance

• Bone health

Client Instructions

• Do not take with food: changes absorption

• Can be given in combination with metformin, sulfonylureas or insulin

• Report swelling/weight gain

• Report jaundice

• Report urinary changes

Contraindications

• Cardiovascular disease (esp HTN, severe CHF)

• Active hepatic disease

• T1DM or hx of DKA

Drug Interactions

• With insulin, may increase risk of heart failure and edema

• Given with Lopid will increase hypoglycemic effects

Precautions

• Mild CHF

• Hepatic impairment

• May increase the risk of bladder cancer

Pancreatic Disorders (oral hypoglycemics): Gliptins: linagliptin & sitagliptin

Gliptins: linagliptin (Tradjenda) & sitagliptin (Januvia)

MOA

• Augments incretin production by inhibiting the enzyme that inactivates incretin hormone (DPP-4): ozempic is incretin mimetics

• As a result, promotes the release of insulin and decreases glucagon

Therapeutic Use

• Type 2 Diabetes Mellitus

Adverse Drug Reactions

• Upper respiratory infxn: fluid, edema

• Headache

• Pancreatitis: interacts w/ pancreas w incretin and insulin production

• Stevens-Johnson Syndrome (rare): immune response

• Angioedema

Interventions

• Monitor for respiratory infxn

• Monitor for s/sx pancreatitis

• Assess for SJS

• OTC pain meds for headache

Client Instructions

• Report s/sx of resp infection

• Report s/sx of pancreatitis

Contraindications

• Hypersensitivity

• Type 1 Diabetes

• DKA

Drug Interactions

• May increase digoxin levels

• If in combination with other antidiabetic meds, can increase the risk for hypoglycemia

Precautions

• Hemodialysis

• Moderate renal dysfunction

• History of pancreatitis

Pancreatic Disorders (injectable hypoglycemics): Incretin Mimetics: semaglutide, exenatide, tirzepatide

Incretin Mimetics:

semaglutide (Ozempic), exenatide (Byetta), tirzepatide (Mounjaro)

MOA

• Mimics the action of incretin (activates GLP-1 agonist receptors)

• Slows gastric emptying

• Stimulates the release of insulin

• Inhibits secretion of glucagon (reducing the amount of BG)

• Increases feelings of satiety/reduces appetite (tirzepatide is also GIP agonist)

Therapeutic Use

• T2DM – often used in combination with oral hypoglycemics if needed

Adverse Drug Reactions

• Hypoglycemia

• N/V/D

• Pancreatitis

• Renal Failure

• Severe hypersensitivity

Interventions

• Monitor for Hypoglycemia

• Monitor for persistent N/V/D

• Monitor carb intake

• Monitor for pancreatitis

Client Instructions

• Give SQ in thighs or abdomen

• Rotate sites!

• Always carry a carb snack

• May cause weight loss

Contraindications

• Severe renal impairment

• T1DM

• DKA

• Severe GI disease

• Pregnancy

• Children (except tirzepatide)

Drug Interactions

• Sulfonylureas increase the risk for hypoglycemia

• Oral med absorption slows,

• So take abx and oral contraceptives 1hr before taking incretin mimetics***

Precautions

• Thyroid carcinoma (black box)

• Moderate renal impairment

• Hx of pancreatitis

• Using insulin