BG Regulation
Type 1 Diabetes Mellitus: 5-10% of the diabetic population
Cause: autoimmune response (most common), genetics, virus
Insulin production: Do not produce insulin; requires exogenous insulin.
**Beta cell destruction
Increase in lipolysis: Leads to increased circulating free fatty acids and ketones in the liver.
Thin/wasting physical appearance
Circulating Hormones: Insulin low/absent, glucagon level is high but can be suppressed
Age of onset: Most often develops before age 30, typically non-obese.
Frequently develops ketoacidosis.
Type 2 Diabetes Mellitus: 90-95% of the diabetic population
Lifestyle factors: Often associated with obesity, sedentary lifestyle, and older age.
Insulin production: Rarely develops acidosis or ketosis unless poorly controlled.
**lack of insulin or insulin resistance
Android obesity (abdominal fat), HHS (NOT ketones like with DKA, but mostly just dehydration)
Circulating Hormones: Insulin normal/high, glucagon is high/resistant to suppression
Treatment options: Managed with oral hypoglycemic agents, exercise, and dietary therapy.
Complications of Diabetes
Microvascular Complications:
Retinopathy: Damage to the retina leading to vision problems.
Nephropathy: Kidney damage leading to renal failure.
Motor neuropathy
Autonomic neuropathy causing symptoms such as:
Orthostatic hypotension
Labile blood pressure
Erectile dysfunction
Loss of skin integrity
Abnormal vascular reflexes
Resting tachycardia
Exercise intolerance
Constipation
gastroparesis
Diarrhea
Impaired neurovascular response
Hypoglycemic autonomic failure
Sensory neuropathy causing symptoms such as:
paresthesias
numbness
burning sensation
Macrovascular Complications:
Coronary artery disease: Reduced blood flow to the heart.
Peripheral vascular disease: Poor circulation in limbs.
Cerebrovascular disease: Increased risk of stroke.
Other Complications:
Increased risk of infections
Cataracts
Stiff joint syndrome (difficulty intubating)
Glaucoma
Poor wound healing
Metabolic Response to Surgery
Surgical Stress Response:
Surgery produces a catabolic stress response (even though anesthesia is provided).
Causes release of catecholamines and glucocorticoids.
Alpha-2 receptors in the pancreas reduce insulin secretion.
General anesthesia elicits a stronger stress response compared to regional anesthesia (less blockage)
Requires monitoring of blood glucose levels throughout the intraoperative period.
Suggested monitoring frequency: Every 30-60 minutes if actively treating hyperglycemia
Some literature suggests every 2 hours.
Goals for HYPERglycemia: Varies, often treated at blood glucose of 200 mg/dL or greater with a target range of 100-175 mg/dL.
**According to Prodigy, elective surgery should be postponed if BG is acutely increased >400
Goals for HYPOglycemia: Treat when blood glucose is 60 mg/dL or less.
**Hypoglycemia is the #1 risk with DM1 during surgery
Insulin Characteristics and Functions
Composed of 51 amino acids, synthesized in beta cells of the islets of Langerhans in response to increased serum glucose levels.
Regulation of Insulin Release: Glucose acts as a critical regulator; levels greater than 100 mg/dL rapidly stimulate insulin release.
Functions:
Increases glucose uptake and usage in fat and muscle.
Inhibits gluconeogenesis and glycogenesis in the liver.
Process of secretion:
Under normal physiological conditions, the pancreas secretes 1 U/hr into the portal circulation.
After meals, insulin output increases 5-10 times
totaling to a daily secretion of approximately 40 U.
**Beta2 and parasympathetic stimulation increases insulin secretion.
**Alpha2 stimulation inhibits insulin secretion.
Therapeutic Uses of Insulin
Main Applications:
Treatment of Diabetes Mellitus.
IV insulin for managing diabetic ketoacidosis.
Management of gestational diabetes.
Treatment of hyperkalemia by promoting potassium uptake.
Assisting in diagnosing growth hormone (GH) deficiency.
Insulin Types
Very Rapid-Acting:
5-15 min onset, 45-75 min peak, 2-4 hour duration
Used for postprandial plasma insulin concentration profile similar to normal physiological insulin secretion
Administer SQ immediately before or after eating
Benefits: Decreases postprandial hyperglycemia and less risk of hypoglycemia compared to regular insulin
EX:
Lispro (Humalog): Onset 5-15 min, peak 45-75 min, duration 2-4 h.
Insulin aspart (Novolog)
Glulisine (Apidra)
Rapid-Acting:
Onset 30 min, peak 2-4 h, duration 6-8 h.
Can be given SQ or IV (rarely IM)
1-5 Units IV in preop is typical
**This is the only type of insulin that can be given IV!!
Preferred for the treatment of abrupt onset hyperglycemia or DKA
EX:
Regular Insulin (Humulin R, Novolin R)
Clear solution
Intermediate-Acting:
Onset 2 h, peak 4-12 h, duration 18-28 h.
Given SQ 2-3 times per day to provide glycemic control between meals and during the night
Absorption is delayed bc the the insulin is conjugated with protamine (0.005 mg protamine per unit of insulin)
Allergic reactions may occur
EX:
NPH (Humulin N, Novolin N)
Stands for Neutral protamine hagedron
Cloudy suspension and must be agitated before administration
Long-Acting:
Prolonged duration of action up to 24 hours
SQ only once or twice daily, often given at bedtime to provide basal insulin for 24 hours with less nocturnal hypoglycemia
Cannot mix with other insulins
Clear solutions
EX:
Detemir (Levemir): Onset 2 h, peak 3-9 h, duration 6-24 h.
Glargine (Lantus): Onset 1.5 h, NO peak, duration 20-24+ h.
Ultra Long-Acting:
Onset 2 h, no peak, duration 40+ h.
EX:
Degludec
Not available in the USA
Complications of Insulin Treatment
Hypoglycemia: Blood sugar < 70 mg/dL.
Symptoms: Confusion, seizures, coma, brain damage, and death.
**Prodigy also says lacrimation, NOT hypotension
Treatment:
Fast-acting oral sugar in awake patients (e.g., glucose tablets, orange juice)
IV glucose or parental glucagon if swallowing or gag reflex is impaired (e.g., 50-100 mL of 50% glucose solution or 0.5-1 mg Glucagon IV/SQ)
**Hypoglycemia may be difficult to identify under anesthesia as SNS stimulation is masked
Lipohypertrophy: Fat atrophy at the injection site of insulin.
Lipodystrophy: fat accumulates at the site of insulin injection
Allergic Reactions: Hypersensitivity reactions Includes swelling, erythema, and rarely urticaria.
Chronic NPH exposure: May stimulate antibody production to protamine.
Hypokalemia: Insulin promotes potassium entry into cells, lowering serum potassium levels.
Insulin Resistance: When daily insulin requirement exceeds 100 U/day due to antibodies or target cell dysfunction, often during stressful times.
Drug Interactions:
Counteracting Drugs to the hypoglycemic effect of insulin:
Epinephrine (inhibits secretion of insulin and stimulates glycogenolysis)
glucagon
Adrenocorticotropic hormone
Estrogens IN THE LIVER
**Will still increase BG levels
Enhancing Effects to the hypoglycemic effect of insulin:
MOAIs (more potentiation than direct hypoglycemic effect like the other drugs listed below)
Salicylates
Tetracycline
Chloramphenicol
Phenylbutazone
BBs (prolong or alter symptoms of hypoglycemia rather than directly decreasing BG levels)
**Will further decrease BG levels
Oral Hypoglycemic Agents
Biguanides (e.g., Metformin):
Mechanism: Inhibit gluconeogenesis and glycogenolysis in the liver and decreases peripheral insulin resistance.
First-line treatment for Type 2 Diabetes
Also used in cases of polycystic ovary disease, nonalcoholic fatty liver disease, and premature puberty
Key facts:
Does NOT cause hypoglycemia;
Risk of lactic acidosis, so avoid in patients with liver/renal disease, CHF, or acute MI
discontinue prior to extensive surgeries or procedures with IV contrast dye
May cause Vitamin B12 deficiency
Sulfonylureas (e.g., Glyburide, Glipizide, Glimepridine):
Mechanism: Stimulates insulin secretion from pancreatic beta cells by inhibiting ATP-sensitive K+ channels (aka, sulfonylurea receptor-1), which then causes Ca2+ influx and thus promoting insulin granule storage release.
Metabolized in the liver to active and inactive metabolites which are primarily excreted renally
Key facts:
Highly protein bound to albumin, 98%
Highest Risk of hypoglycemia, even more than insulin-induced hypoglycemia
contraindicated in sulfa allergies
Can cross the placenta and produce fetal hypoglycemia
Increases cardiac morbidity d/t closing of ATP Potassium channels, which then inhibits ischemic myocardial preconditioning
D/c 24-48 hours before surgery in high risk patients
Specific Characteristics:
Glyburide: stimulates insulin secretion over a 24 hour period (after a morning oral dose)
Standard drug used with a long half life
Peak levels 3 hours after doses
Increases insulin sensitivity and inhibits production of glucose by the liver
Mild diuretic effect
Metabolized in the liver with metabolites excreted equally in feces and urine
Glipizide: Stimulates insulin secretion over a 12 hour period (after a morning dose)
Short acting
Peak levels 1 hour after dose
Increases glucose uptake and suppresses glucose output by liver
Mild diuretic effect
Metabolized in liver with inactive metabolites excreted in the urine
Rapid clearance reduces potential for long lasting hypoglycemia
Glimepiride: decreases BG levels by stimulating insulin release from pancreas; may decrease hepatic glucose production
Thiazolidinediones (e.g., Rosiglitazone, Pioglitazone):
Mechanism: Decrease insulin resistance/hepatic glucose production in skeletal muscle, liver, and adipose tissue via Proliferator activator receptors
Only used for DM2, mainly as an add-on to metformin
Characteristics:
Decreases HbA1C by 1-5%
Clinical effect takes 4-12 weeks
Also decreases triglycerides and increases HDL levels
Risk of weight gain from increased ECF (may cause HF)
Contraindicated in liver failure.
Dipeptidyl-Peptidase-4 (DPP-4) Inhibitors (e.g., Saxagliptin, Linagliptin, Aloglipitin, Vidaglipitin, Sitaglipitin):
DPP-4 is an enzyme that degrades incretin hormones
Mechanism: Promotes glycemic control by enhancing secretion of incretin hormones, stimulating glucose dependent insulin release, and suppressing postprandial glucagon release
Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitors (e.g., Canagliflozin, Empagliflozin, Dapaglifozin):
Mechanism: Inhibiting filtered glucose reabsorption in kidneys, which then leads to glucosuria.
**Aka, increased renal glucose excretion
Used for DM2
Regular renal function assessment is required.
May cause hypotension, AKI, genital fungal infections, UTIs, and diuresis
**Aka, hypovolemia and periop DKA
Glucagon-like Peptide-1 (GLP-1) Agonists (e.g., Liraglutide, Ozempic, Wegovy):
Mechanism: Increase insulin secretion and decrease glucagon release postprandially. DELAYS GASTRIC EMPTYING.
S/e:
GI disturbances (e.g., n/v, constipation, diarrhea)
Increased risk of pancreatitis and thyroid cancer.
Most GLPs do not produce hypoglycemia unless combined with other meds
**Recommendation:
Daily dosing, consider holding day of procedure
Weekly dosing, consider holding a week before procedure
Assess GERD symptoms, use POCUS if appropriate, proceed with RSI if full stomach suspected
Management Rules for Surgery:
Long-acting basal insulin (Glargine/Detemir): Give the full dose the night before or morning of surgery if the patient does not have a history of hypoglycemia and their basal/prandial ratio is roughly 50/50. If they have a history of morning hypoglycemia, reduce the dose by 25%.
Intermediate-acting (NPH): Give the full dose the night before (or reduce by 25% if missing a nighttime meal). Reduce the morning dose by 50%.
Prandial (Mealtime) Insulin: Completely stop rapid/short-acting mealtime insulin on the morning of surgery.
Maintenance Fluids: If blood glucose is < 200 mg/dL, infuse D5 1/2 NS at 50-75 mL/hr to prevent hypoglycemia and starvation ketosis