PAL: Diabetes & Diabetic Ketoacidosis

David Zorko MD Candidate 2016 University of Ottawa

ObjectivesPathophysiology, clinical presentation, and management of new onset

Type 1 Diabetes (T1DM) in children

Pathophysiology, clinical presentation, and management of diabetic ketoacidosis (DKA) in children

Illness management of hyperglycemia and hypoglycemia in children.

Clinical Case – Nick JID: 9M CC: Thirsty

HPI:- 2 weeks of increasing thirst, and parents feel his water intake is exceeding what he needs - Teachers have complained that he requires frequent trips to the bathroom and that he complains of being hungry, though eating all his lunch.- He has wet the bed once a week

FHx: Nil

What is your top DDx?

Diabetes.

Q: Type 1 or Type 2?

Type 1.

Type 1 DiabetesAutoimmune destruction of pancreatic beta cells

Decreased insulin production and hyperglycemia S/S evident when 80% of beta cell function is lost

Multifactorial Genetics Trigger

Autoimmunity Genetic Susceptibility Trigger

Autoantibodies include:- Islet cell autoAb- Insulin autoAb- Glutamic Acid Decarboxylase autoAb

- HLA DR3 and/or DR4- 90-95% of dx T1DM carry the susceptible genotype, but only 5% of people with these genotypes develop T1DM

- Seasonal: birth month Nov-Feb less risk than Apr-Jul- Viruses: Coxsackie B4- Nutritional: nitrites and nitrosamines (smoked salmon – Finland!), caffeine, cow’s milk, wheat gluten

Presentation of T1DM1. “Classic” Presentation

Polyuria/nocturia Polydypsia Polyphagia, weight loss

2. Diabetic Ketoacidosis Same classic symptoms that become more severe Progression to N/V, abdominal pain, hyperpnea Severe symptoms include drowsiness, lethargy, and obtundation

3. Incidental Finding No classic symptoms Glucosuria, hyperglycemia

Clinical Case – Nick JQ: What would you like to do for Nick at this time? (Choose one)

a) CBC, electrolytes, BUN, and creatinine b) Random plasma glucosec) Fasting plasma glucosed) Venous blood gase) Urine ketonesf) Urine glucoseg) HbA1c

Clinical Case – Nick JQ: What would you like to do for Nick at this time? (Choose one)

a) CBC, electrolytes, BUN, and creatinine b) Random plasma glucosec) Fasting plasma glucosed) Venous blood gase) Urine ketonesf) Urine glucoseg) HbA1c

Nick’s random BG is 14.0 mmol/L.

InvestigationsHow do we diagnose

diabetes? Most commonly used are

FPG and RPG

Test Result

FPG*No caloric intake for at least 8hrs

≥7.0 mmol/L

Random PG* ≥11.1 mmol/L

2hr PG in a 75g OGTT ≥11.1 mmol/L

HbA1c ≥ 6.5%

Given Nick has a random plasma glucose of 14.0 mmol/L, what is the next best management step?a) A repeat confirmatory test must be done (preferably the same as intial), prior to treatment.b) Treatment can be initiated today.

InvestigationsGiven Nick has a random plasma glucose of 14.0 mmol/L, what is the next best management step?a) A repeat confirmatory test must be done (preferably the same as intial), prior to treatment.b) Treatment can be initiated today.

Remember Nick is demonstrating the key symptoms of polyuria, polydypsia, and polyphagia. So he is symptomatic…

If asymptomatic, a repeat confirmatory test must be done (preferably the same as initial).

If symptomatic, diagnosis can be made and begin treatment.

Clinical Case – Nick JHow should Nick’s diabetes be managed?

Multidisciplinary team (pediatric endocrinologist, nurse educator, dietician, social worker, child life specialist, mental health professional)

Education

Nutrition

Glucose monitoring

Insulin

Insulin RegimenA) Multiple Dose Injections (MDI) BID/TID

B) Continuous Subcutaneous Insulin Infusion (CSII)

NR NR

NPH NPH

NR: NovorapidNPH

Insulin RegimenNick and his family opt for a basal-bolus regimen of NPH and Novorapid.

What are his glycemic targets?

Age HbA1c Fasting/Preprandial PG 2hr Postprandial PG

<6yo < 8% 6-10 mmol/L N/A

6-12yo ≤ 7.5% 4-10 mmol/L N/A

13-18yo ≤ 7% 4-7 mmol/L 5-10 mmol/L

Clinical Case – Nick JNick’s in the ED!

ID: 13M CC: Nauseous and BG 24.

HPI:- This morning, BG measured 24. - Felt nauseous and didn’t want to eat so he didn’t take any insulin.- At lunchtime, glucometer measured “high.”- Shortly after, Vx x2 and went to ED.

PMHx- Type 1 Diabetes (dx at 9yo)

Clinical Case – Nick JReview of Systems:

- No fever or chills.- No diarrhea. No cough. No dysuria. - No sick contacts.- Able to take sips of water. Hasn’t eaten anything since the morning. - Diffuse abdominal pain.

Clinical Case – Nick JWhat are you most worried about?

Diabetic Ketoacidosis

What else would you like to learn about in the history?

Clinical Case – More HistoryPrevious DKA?

2 other episodes of DKA within the last year

Glycemic control? Initially good glycemic control HbA1c elevated past 2 years (10-14%)

Current insulin regimen? NPH 34u + Novorapid 14u before breakfast 12u Novorapid at supper 18u NPH at bedtime Sliding scale for adjustment of Novorapid

Clinical Case – More History Social Hx:

Home: Parents divorced 2 years ago. Lives with mom and 3 brothers (Kevin, Joe, Frankie). Mom’s had to work some extended hours to make ends meet.

Education: Just finished Gr 7. Likes music and drama. Now that school’s out for summer, he sleeps in a lot and doesn’t take his AM insulin.

Activities: Plays guitar, sings and writes his own songs. Has a band with Kevin and Joe and like all bands, they hope to rule the pop world.

Diet: Past 2 years he’s had to do his own carb counting, but admits that he usually forgets and only does it when prompted to by mom.

Rest of HEADSS non-contributory

Clinical Case – PEx Vitals on assessment: T 37.1 oral; HR 120bpm; BP 98/60; RR 45; SpO2 100% RA

Growth parameters: (see growth chart)

GENERAL: Lethargic and grimacing in pain. Answers some questions. Opens eyes spontaneously.

HEENT: Dry MM and lips. Pupils round and reactive, but sluggish. Normal TM x2. Normal oropharynx and tongue. Fruity breath. No cervical LNs. Neck supple, full ROM.

CVS: Normal S1 and S2 (phys split). There is a soft I-II/VI SEM heard best over LUSB, best in full exhalation. PPP. Central capillary refill is 3s.

RESP: Mildly increased WOB, breathing deeply. GAEB. Vesicular. No adventitia. No accessory muscle use. No retractions.

ABDO: Mild tenderness diffusely on palpation. No guarding. No rebound. +BS diffusely. No HSM. No masses

EXT: No rashes. No joint swelling/effusion. No petechiae/purpura.

Sick or Not Sick?Clinically, which features on assessment worry you?

a) Recent insulin omission b) A “high” glucometer readingc) His systolic murmurd) His abdominal tendernesse) His vital signsf) His GCSg) His hydration statush) His music careeri) His growth chartj) His respiratory distress

Sick or Not Sick?Clinically, which features on assessment worry you?

a) Recent insulin omission b) A “high” glucometer readingc) His systolic murmurd) His abdominal tendernesse) His vital signsf) His GCSg) His hydration statush) His music careeri) His growth chartj) His respiratory distress

Is he sick or not sick?

Diabetic Ketoacidosis (DKA): Pathophysiology

Insulin

Counter-Regulatory Hormones

GlucagonCatecholaminesCortisolGH

HyperglycemiaKetone Production

Osmotic diuresisHypovolemia

Acidosis

Gluconeogenesis Lipolysis

Glycogenolysis Glycosis

DKA: Triggers

Ischemia

Infection

Intra-abdo process Pregnancy

Pancreatitis

Insulin Deficiency

Excess Counter-Regulatory Hormones

New diagnosis

Omission and non-compliance

Inadequate dose (poor sick-day dosing)

Pump failure

DKA: Initial Investigations

What investigations would you like to order? (Choose 6)

a) CBCb) Electrolytesc) BUN, Crd) Random plasma glucosee) TSH and thyroid antibodiesf) HbA1cg) Arterial blood gash) Venous blood gas

h) Serum ketonesi) Urine ketonesj) CV monitoringk) ECG l) Chest XRm) Abdominal USn) Head CTo) STAT surgical consult

DKA: Initial Investigations

What investigations would you like to order? (Choose 6)

a) CBCb) Electrolytesc) BUN, Crd) Random plasma glucosee) TSH and thyroid antibodiesf) HbA1cg) Arterial blood gash) Venous blood gas

h) Serum ketones i) Urine ketonesj) CV monitoringk) ECG l) Chest XRm) Abdominal USn) Head CTo) STAT surgical consult

Clinical Case – Nick’s Labs

You’ve put Nick on a cardiac monitor. His labs are back!

Blood glucose: 35mmol/L

VBG: 7.11 / 32 / 79 / 10

Na 137 K 5.0 Cl 99 BUN 7.0

Urine ketones: 3+

What is his anion gap?

Interpret his blood gas.

Are you worried about is pO2 of 79?

DKA: Diagnosis

CLINICAL Thirst/polydipsia, polyuria

Abdominal pain, N/V

Decreased LOC, profound weakness

Tachypnea, Kussmaul respiration

Ketotic breath

Dehydration

CHEMICAL Hyperglycemia

BG >11.1mmol/L, but usually >15mmol/L

Metabolic acidosis pH <7.35, bicarb <15

Increased anion gap AG >12

Positive ketones Urine (or serum)

DKA Zebras!

POTASSIUM

Insulin deficiency shifts K out of cells, and osmotic diuresis removes K from the body.

May appear as low, normal, or high, but total body K is ALWAYS LOW!

This has management implications! Need to replace K as soon as K is in normal range.

SODIUM

Looks low or normal, but that’s due to osmotic diuresis and may in fact be normal or high, respectively.

For each 10mM increase in glucose >10, Na should decrease by 3.

Nick’s serum sodium is actually 145mmol!

Clinical Case – Nick JHow would you manage Nick at this time? (Choose all that are correct)

a) Place him on a cardiac monitor.b) Frequently monitor for headache.c) Bolus IV NS for his dehydration.d) Maintenance IV NS for his dehydration.e) Bolus insulin, then start IV insulin infusion.f) Start IV insulin infusion.g) Give him 1 amp of NaHCO3 because he is acidotic.h) Monitor his glucose hourly.i) Transfer him to the PICU.

Clinical Case – Nick JHow would you manage Nick at this time? (Choose all that are correct)

a) Place him on a cardiac monitor.b) Frequently monitor for headache.c) Bolus IV NS for his dehydration.d) Maintenance IV NS for his dehydration.e) Bolus insulin, then start IV insulin infusion.f) Start IV insulin infusion.g) Give him 1 amp of NaHCO3 because he is acidotic.h) Monitor his glucose hourly.i) Transfer him to the PICU.

DKA: Management Issues Fluids

Key point: Majority of kids in DKA are 5-10% dehydrated Plan:

DO NOT BOLUS! (If hypotensive, not more than 10cc/kg NS) Normal saline at maintenance rate + 10% deficit (over 48hrs) +/- KCl. Add glucose when BG <15 mmol/L (D5 ½NS or D10 ½NS)

Insulin Key point: The glucose will correct faster than the ketosis/acidosis, but do not

stop insulin infusion until acidosis/AG corrected Plan:

DO NOT BOLUS! 0.1U/kg/hr of Humulin R or Novolin T, starting 1-2 hours after fluids. Decrease glucose at a rate of 5mmol/L/hr. Glucoscans q1hr until normal. Once the acidosis/AG corrected, transition to SC insulin.

DKA: Management IssuesMonitoring

Plan: Cardiorespiratory monitoring, sat monitoring, vitals q1hr. Accurate ins and outs q2-4hr. Glucoscans q1hr until glucose in normal range, then q2hr. VBG, electrolytes, BUN/Cr, urine ketons, serum osmolality q4hr.

Bicarbonate Plan:

Don’t use it.

Cerebral edema What?

DKA: Cerebral EdemaRisk Factors

Patient: age <5yo, new-onset diabetes, severe dehydration Lab: initial pH <7.1, high BUN, initial corrected Na >145mmol/L Tx: bicarbonate use, failure of serum Na to rise during tx, rapid

administration of hypotonic fluids, early IV insulin infusion (within first hour of fluids)

Beware of: headache, irritability or altered behaviour, drowsiness, decreasing LOC, vomiting

Suspected cerebral edema is a medical emergency! Contact ICU.

Clinical Case – Nick JHow could Nick have prevented himself from going into DKA when his morning BG was 24?

HyperglycemiaWhen a child is ill, insulin management

changes (a little): Measure BG and urine ketones q2-4hrs NEVER MISS AN INSULIN DOSE When BG >14mmol/L, give supplemental

fast-acting insulin q4hrs as needed Based on total daily dose of insulin and

ketones (small/moderate/large) Call Diabetes Team for help

Clinical Case – Nick JNick omitted his insulin today because he wasn’t eating, and was worried that if he would run “low” if he gave himself his daily insulin dose.

What could Nick have done to prevent lows in his illness?

HypoglycemiaTry to follow the meal plan as close as

possible

If unable to eat, sip on sugar-containing fluids (juice) while also drinking lots of water

Call Diabetes Team for help

Fin.