DSA13 - Type 1 Diabetes Mellitus, Hypoglycemia, and DKA

Type 1 Diabetes Mellitus (T1DM)

Define Condition:

Disorder of glucose homeostasis characterized by autoimmune destruction of the insulin-producing pancreatic beta cells, which progressively leads to insulin deficiency and resultant hyperglycemia

-Hx:

> Usually in PEDS

> More in CAUCASIANS

> PMHx OR FHx of Autoimmune Disease

-Sx/PE:

> Polyuria

> Polydipsia

> Wt Loss (worsen over course of 3-6 wks)

-Dx:

1) Make Dx of DM

> Fasting glucose > 126 mg/dL

> HbA1c > 6.5%

> Random plasma glucose > 200 + Sx of Hyperglycemia

> 2 hr glucose on Oral Glucose Tolerance Test (OGTT) > 200 mg/dL

2) Determine Type

> Insulin = LOW

> C-Peptide = LOW

-Tx:

> Insulin (permanent; reproduce production of healthy pancreas)

>> Injections (multiple daily) = One Long + One Rapid (to mimic normal endogenous insulin in normal individual)

>>> Long acting (Giargine, Detemir) = active for 24 hrs w/ low but consistent amount of insulin concentration; to meet basal metabolic needs

>>> Rapid acting (Lispro, Aspart) = active for 4 hrs w/ "peaked" effect; several times a day to cover extra requirement from meals

>> Insulin pump (continuous rapid-acting) = for basal metabolic needs + deliver bolus (for meal coverage or high BS)

> Home blood glucose monitoring

>> Morning

>> Before Meals

>> Before Bedtime

> Attention to diet

>> Less concentrated sweets

>> Less snacking/grazing

> Healthy exercise

>> Increases sensitivity to insulin --> Lower BS

> Screening/Checkups

>> Checking HbA1c at every visit (avg BS over last 3 months)

>> Retinal Exam (Diabetic Retinopathy)

>> Urine Albumin:Cr (Diabetic Nephropathy)

>> Lipids (CVD)

-Prog (UnTx): DKA

Diabetic Ketoacidosis (DKA)

Define Condition:

When pts w/ DM get TO LITTLE INSULIN (when body is markedly insulin deficient)

-Hx: More in T1DM (can occur in T2DM)

> Usually at NEW ONSET of T1DM (30%)

> More often, PT NONCOMPLIANCE to INSULIN

> Some pt's need more Insulin in Illness

-Path:

> Low Insulin --> Hyperglycemia --> Glycosuria ==> Increased Urine Output (Osmotic Diuresis) ==> DEHYDRATION + MORE URINE POTASSIUM EXCRETION

> Low Insulin --> Less use of Glucose for cellular metabolism --> Fat Store breakdown for energy (MORE LIPOLYSIS) --> MORE KETONES (B-hydroxybutyrate and acetoacetate) ==> ACIDOTIC BLOOD

-Sx/PE:

Gen DM

> Polyuria

> Polydipsia

> Wt Loss

Concerning

> Kussmaul breathing (Deep, labored breathing - compensatory to metabolic acidosis)

> Fruity breath (exhaled ketones)

> Nausea/Vomiting + Abdominal Pain

> AMS

-Dx:

Labs

> Glucose = HIGH

> Ketones = HIGH

> pH = LOW (HIGH H+, Low HCO3-)

> Potassium = Normal OR High, despite Inc Urine Excretion (Serum Acidosis = More exchange of K+ from cells; will DROP when Insulin & Fluids are given b/c K+ moves back into cells = TOTAL BODY POTASSIUM IS LOW)

-Tx:

> Insulin (Continuous IV)

> Rehydration (Aggressive IV Fluids - twice as large as standard rate)

> Electrolyte replacement, if needed - POTASSIUM once it drops

-Prog:

> Resolve w/n 24 hrs

> CEREBRAL EDEMA

> Cause of Death in 10% of those w/ T1DM

> Diabetes

> Serum Ketones (measuring the serum B-hydroxybutyrate concentration)

> Acidosis (pH < 7.3, HCO3- < 18)

What are the 3 criteria needed to Dx DKA?

DKA-induced Cerebral Edema

Define Condition:

Complication of DKA

-Hx: Responsible for most DKA-related deaths

-Path: Hyperosmolarity in serum, then in cells after equilibration --> Tx w/ IV Insulin & Fluids ==> Serum Osmolarity DROPS RAPIDLY ==> Rapid Osmolarity-mediated shift of water into brain cells = NEURONAL DAMAGE

-Sx/PE:

Gen DM

> Polyuria

> Polydipsia

> Wt Loss

Gen DKA

> Kussmaul breathing (Deep, labored breathing - compensatory to metabolic acidosis)

> Fruity breath (exhaled ketones)

> Nausea/Vomiting + Abdominal Pain

CONCERNING

> AMS

> Abnormal response to painful stimuli

> Abnormal response to Light

-Dx:

> Clinical Presentation

> CT = CONFIRM!

-Tx: Mannitol (IV) or Hypertonic (3%) Saline (IV)

> Increase the serum osmolarity back to the high level, thereby removing the osmotic gradient that was driving excess free water into brain cells

> Give Insulin & IV Fluids at SLOWER RATE

Insulin-induced hypoglycemia

Define Condition:

D/t too much insulin

-Hx: Often in T1DM

-Path:

-Sx/PE:

Adrenergic Sx

> Tremors

> Palpitations

> Diaphoresis

Neuroglycopenic Sx

> Fatigue

> HA

> Drowsiness

> LOC

> Seziure

> Coma --> Death

-Dx:

Labs

> Glucose < 60 mg/dL

-Tx:

Mild/Moderate = Rapidly absorbable simple Carbs

Severe (NOT ALERT) = Glucagon (SQ, IV, IM, Nasal)

-Prog:

> Mild = Resolve

> Recurrent/Severe = Negative impact on brain development

> Severe = Cause of death in 10% of T1DM

Hypoglycemia (New Pt Presentation)

Define Condition:

Low Blood Glucose Concentration (< 60 mg/dL)

-Hx:

> Medications (Unintentional or Intentional)

> Insulinoma

> Prolonged Fasting

-Path:

-Sx/PE:

Adrenergic Sx

> Tremors

> Palpitations

> Diaphoresis

Neuroglycopenic Sx

> Fatigue

> HA

> Drowsiness

> LOC

> Seziure

> Coma --> Death

-Dx:

> Step 1 = Demonstrate Low BS (< 60 mg/dL) - should draw labs DURING Sx

> Step 2 = Find Cause of Low BS

> WHIPPLE'S TRIAD = Adrenergic/Neuroglycopenic Sx + Low Blood Glucose during Sx + Correction of Low BS --> Sx Stop

-Tx:

Medication-Induced Hypoglycemia

Define Cause of Hypoglycemia:

-Hx: Unintentional or Intentional Ingestion of...

> Diabetes = Insulin, Sulfonylureas, Meglitinides

> Non-Diabetes = PROPANOLOL, Pentamidine, Quinine, Indomethacin

-Sx/PE:

Adrenergic Sx

> Tremors

> Palpitations

> Diaphoresis

Neuroglycopenic Sx

> Fatigue

> HA

> Drowsiness

> LOC

> Seziure

> Coma --> Death

-Dx:

Labs

>> Blood Glucose = LOW (< 60 mg/dL)

>> Serum Insulin = HIGH

>> Serum C-Peptide = LOW (HIGH if Sulfonylrea Ingested b/c it release own insulin from pancreatic beta cell)

>> Serum b-hydroxybutyrate = LOW

-Tx: REMOVE AGENT

Insulinoma

Define Cause of Hypoglycemia:

Tumor of pancreatic beta cell --> excessive insulin secretion

-Hx:

> RARE

> Range = 18-80 y/o (Median = 50 y/o)

> 5-10% have MEN1 (of those w/ MEN1, 10% have this)

-Sx/PE:

Adrenergic Sx

> Tremors

> Palpitations

> Diaphoresis

Neuroglycopenic Sx

> Fatigue

> HA

> Drowsiness

> LOC

> Seziure

> Coma --> Death

-Dx:

Labs

>> Blood Glucose = LOW (< 60 mg/dL)

>> Serum Insulin = HIGH

>> Serum C-Peptide = HIGH

>> Serum b-hydroxybutyrate = LOW

Imaging (CONFIRM) = US, CT, MRI, PET Scan

-Tx: REMOVAL (Curative)

Prolonged Fasting

Define Cause of Hypoglycemia:

-Hx: Presents FASTER in those w/ lower stores of glycogen & fat (infants, toddlers, malnourished adults)

-Path: Takes longer normally b/c of stores

-Sx/PE:

-Dx:

Labs

>> Blood Glucose = LOW (< 60 mg/dL)

>> Serum Insulin = LOW

>> Serum C-Peptide = LOW

>> Serum b-hydroxybutyrate = HIGH

-Tx: Stop fasting for so long

Glucagonoma

Define Condition:

Rare neuroendocrine tumor of pancreatic alpha cell

-Hx:

> Very RARE

> Age = 40-50 y/o

> SPORADIC

> 10% in MEN1

-Sx/PE: (6 Ds)

> Dermatitis (Necrolytic migratory erythema = red, blistering, itchy, painful rash; fluctuates in severity; usually seen in genitals, buttocks, groin, and extremities)

> Diabetes [SECONDARY (antagonizes insulin by inducing hepatic glycogenolysis and gluconeogenesis)]

> DVT (Clotting factor release from alpha cell)

> Declining wt (Catabolic Hormone)

> Depression

> Diarrhea (Co-secretion of pancreatic enzymes)

-Dx:

Labs

> Fasting Glucagon > 1000 pg/mL (normal < 50)

Imaging = CT, MRI, PET scan

-Tx:

> Somatostatin (Octreotide)

> Surgical resection

> Chemo

Somatostatinoma

Define Condition:

Rare neuroendocrine tumors of delta cell origin that contain and sometimes secrete excessive amounts of its hormone

-Hx:

> VERY RARE

> Age Range = 25-85 y/o (Median = 50 y/o)

> Sometimes a/w...

>> MEN1 (1%)

>> NF1

-Sx/PE:

> Diabetes = stops insulin secretion

> Cholelithiasis = inhibits CCK (stops gallbladder contraction)

> Diarrhea & Steatorrhea = inhibits release of pancreatic digestive enzymes

> Hypochlorhydria/low gastric acid = decreases gastin secretion (leads to abdominal discomfort/indigestion)

-Dx:

Labs

> Serum Somato > x3 ULN

Abdominal Imaging

-Tx:

1) SURGICAL RESECTION

2) Chemo

LADA (latent autoimmune diabetes in adults) - aka Type 1.5 Diabetes [FOR BOARDS ONLY]

Define Condition:

Autoimmune destruction of pancreatic beta cells, but LATER in life & more slow than T1DM

-Hx:

> Usually Caucasian

> Usually > 30 y/o

-Path:

-Sx/PE: Less acute onset

> Polyuria

> Polydispia

> Wt Loss

-Tx: Diet/Exercise --> INSULIN later