Endocrine Lecture 2: DM1

What is type 1 diabetes mellitus?

Insulin deficiency following destruction of the insulin-producing pancreatic beta cells.

Which age group does T1DM most commonly occur in?

Children and adolescents (but it can occur in adults).

Why is adult-onset T1DM often missed?

Misclassification is common - many who develop T1DM after age 30 are initially treated for T2DM.

At what two age ranges does T1DM onset peak?

Ages 4-6 and ages 10-14.

What percentage of T1DM cases present before age 10?

45%.

What percentage of T1DM cases are diagnosed in adulthood?

25%.

Which group of children has the highest rates of T1DM?

Non-Hispanic white children.

What are the three categories of risk factors for T1DM? (select all that apply)

1. Genetic 2. Environmental 3. Autoimmune

What is the twin concordance rate for T1DM?

40% (if one twin has it, there is a 40% chance the other will).

What percentage of T1DM susceptibility is attributed to the HLA gene?

50%.

Which HLA genotypes are present in 90% of children with T1DM? (select all that apply)

1. DR4-DQ8 2. DR3-DQ2

Which viruses are environmental triggers for T1DM? (select all that apply)

1. Coxsackie 2. Rubella 3. Mumps

How do viruses trigger T1DM?

They trigger an autoimmune response in susceptible people - they may contain molecules resembling a beta-cell protein, nullifying self-tolerance.

Which perinatal factors increase T1DM risk? (select all that apply)

1. Maternal age >25 2. Preeclampsia 3. Neonatal respiratory disease 4. Jaundice 5. ABO blood group incompatibility

How does cow's milk relate to T1DM risk?

Early introduction and high consumption in childhood increase the risk of T1DM.

What percentage of new-onset T1DM patients have antibodies to islet cell proteins?

80%.

Which immune cells and mediators drive beta-cell destruction in T1DM?

Activated T-lymphocytes and inflammatory cytokines.

Which pancreatic islet cells are spared in T1DM? (select all that apply)

1. Alpha cells 2. Delta cells

What are the 3 initial presentations of T1DM? (select all that apply)

1. Classic new onset 2. Diabetic ketoacidosis (DKA) 3. Incidental discovery (asymptomatic)

What is the most common initial presentation of T1DM?

Classic new onset - polydipsia, polyuria, weight loss with hyperglycemia and ketonemia/ketonuria.

What is the second most common presentation of T1DM?

Diabetic ketoacidosis (DKA).

What is the least common presentation of T1DM?

Asymptomatic / incidental discovery - children with a close family member with T1DM who are being closely monitored.

What is the most common childhood presentation of T1DM?

Hyperglycemia without acidosis.

What are the 4 Ts of type 1 diabetes? (select all that apply)

1. Thirsty 2. Tired 3. Thinner 4. Toilet

Above what serum glucose does urinary glucose excretion increase?

>180 mg/dL.

What causes polyuria in T1DM?

Glucose exceeds the kidney's ability to reabsorb it, spills into the urine, and water follows (osmotic diuresis).

How can polyuria present in children with T1DM? (select all that apply)

1. Nocturia 2. Bedwetting 3. Daytime incontinence 4. Increased frequency 5. Extremely wet diapers

What causes polydipsia in T1DM?

Enhanced thirst from increased serum osmolality (hyperglycemia and hypovolemia).

Which dehydration exam findings may be present in new-onset T1DM? (select all that apply)

1. Decreased skin turgor 2. Dry mucous membranes

What causes weight loss in T1DM?

Hypovolemia and increased catabolism - insulin deficiency impairs skeletal muscle glucose use and increases fat and muscle breakdown.

What is the mean duration of symptoms before a new T1DM patient seeks care?

10 days.

What percentage of new T1DM patients have polyuria and polydipsia?

90%.

What percentage of new T1DM patients have weight loss?

About 50%.

In which young children should you keep a high suspicion for T1DM?

Children seen for dehydration, abdominal pain, or fatigue - especially nonverbal children who can't communicate thirst.

What causes blurred vision in T1DM?

The hyperosmolar state's effect on the lens and vitreous humor.

Which infection is a relatively common presenting symptom of T1DM in young children and girls?

Perineal candidiasis.

Besides the classic triad, what other signs and symptoms can occur in T1DM? (select all that apply)

1. Blurred vision 2. Cataracts 3. Perineal candidiasis 4. Repeated infections 5. Abdominal pain

What should a targeted history for suspected T1DM include? (select all that apply)

1. Age of onset/duration 2. Weight trajectory 3. Medication review (drug-induced hyperglycemia)

Which skin finding is usually ABSENT in T1DM but present in T2DM?

Acanthosis nigricans.

What is the differential diagnosis for suspected T1DM? (select all that apply)

1. Type 2 DM 2. Diabetes insipidus 3. UTI 4. Hyperthyroidism 5. Medication-induced hyperglycemia

How does diabetes insipidus differ from T1DM?

Polyuria/polydipsia with dilute urine but NORMAL glucose.

Which features suggest hyperthyroidism rather than T1DM?

Weight loss, polyphagia, and heat intolerance.

What fasting plasma glucose diagnoses diabetes?

>126 mg/dL on more than one occasion.

What random venous plasma glucose diagnoses diabetes?

>200 mg/dL in a patient with classic hyperglycemia symptoms.

What 2-hour OGTT result diagnoses diabetes?

Plasma glucose >200 mg/dL 2 hours after a 1.75 g/kg glucose load.

What HbA1c diagnoses diabetes?

>6.5% (should be confirmed by another measure of hyperglycemia).

Which clinical features favor T1DM over T2DM? (select all that apply)

1. Weight loss 2. Less excess body weight 3. Age

Which clinical features favor T2DM over T1DM in children? (select all that apply)

1. BMI >=95th percentile for age/sex 2. Age >10 3. Insulin resistance 4. Acanthosis nigricans 5. HTN 6. Dyslipidemia 7. Positive family history

Which antibodies are in the pancreatic autoantibody panel? (select all that apply)

1. GAD65 (glutamic acid decarboxylase 65) 2. IA2 3. Insulin 4. ZnT8

When are insulin and C-peptide levels checked in children?

When T2DM is suspected.

How are insulin and C-peptide levels in T1DM vs T2DM?

Low in T1DM, elevated in T2DM.

What can falsely suppress insulin and C-peptide levels?

Severe hyperglycemia (glucose toxicity) and acute illness - so draw them once glucose is under control.

How does ketosis at onset compare in T1DM vs T2DM?

Common in T1DM; only 5-10% in T2DM.

How strongly is HLA-DR3/4 associated with T1DM vs T2DM?

Strong association in T1DM; no association in T2DM.

How common is obesity in T1DM vs T2DM?

T1DM 20-25% overweight; T2DM >80% obese.

How common is acanthosis nigricans in T1DM vs T2DM?

T1DM 12%; T2DM 50-90%.

What is the HbA1c goal in T1DM when tight control is not indicated?

<=7% (individualized to reduce hypoglycemia risk).

How often should HbA1c be tested in T1DM?

Every 3-6 months.

What is the blood glucose target range in T1DM?

70-180 mg/dL.

What blood glucose levels define severe hypoglycemia and severe hyperglycemia to avoid?

Severe hypoglycemia <54 mg/dL; severe hyperglycemia >250 mg/dL.

How often should a T1DM patient check blood glucose by fingerstick?

4x/day (before meals and at bedtime), and more as needed (illness, exercise, hypoglycemia).

What is the time-in-range goal on continuous glucose monitoring?

70% of the time in range 70-180 mg/dL.

Who should be offered continuous glucose monitoring?

All patients with T1DM.

What is the standard of care treatment for T1DM?

Intensive insulin therapy (lifelong).

What two components must every T1DM insulin regimen include? (select all that apply)

1. Basal (long-acting) insulin 2. Mealtime boluses of rapid, ultra-rapid, or short-acting insulin

Which outcomes are reduced by early aggressive T1DM therapy? (select all that apply)

1. Microvascular disease (retinopathy, nephropathy, neuropathy) 2. Cardiovascular disease 3. Mortality

What is the most commonly used long-acting (basal) insulin?

Insulin glargine.

What is the duration of action and dosing frequency of insulin glargine U-100?

Up to 24 hours; once daily.

Which insulin is ultra long-acting (>42 hours)?

Insulin degludec.

Which basal insulin has been shown to reduce DKA risk in patients with recurrent DKA?

Insulin degludec.

Which long-acting insulin is no longer available in the US?

Insulin detemir.

Which basal insulins have no peak? (select all that apply)

1. Insulin glargine U-100 2. Insulin glargine U-300 3. Insulin degludec

What is the main advantage of NPH as basal therapy?

It is less costly.

What is the approximate duration of action of NPH?

About 12 hours (14-24 hr range on the insulin table).

Why is NPH used infrequently in high-resource settings? (select all that apply)

1. Requires twice-daily dosing for 24-hour coverage 2. Requires consistent timing and carbohydrate intake to prevent hypo/hyperglycemia

When is NPH taken?

At breakfast and bedtime.

What is the short-acting insulin?

Regular insulin.

When must regular insulin be injected relative to a meal?

30 minutes before the meal.

Why does regular insulin carry a higher risk of hypoglycemia a few hours after dosing?

Its duration exceeds the duration of the post-meal glucose rise.

What are the onset, peak, and duration of regular insulin?

Onset 30-60 min; peak 2-4 hr; duration 5-8 hr.

Which insulins are rapid-acting? (select all that apply)

1. Insulin aspart 2. Insulin lispro 3. Insulin glulisine

What is the main advantage of rapid-acting insulin over regular insulin?

It can be taken right before mealtime.

In T1DM, what advantages does rapid-acting insulin have over regular insulin? (select all that apply)

1. Lower hypoglycemia 2. Better A1c

What is a disadvantage of rapid-acting insulin compared with regular insulin?

More expensive.

What are the onset, peak, and duration of rapid-acting insulin (aspart/lispro)?

Onset 10-15 min; peak 1-3 hr; duration 3-5 hr.

How often should fixed-ratio premixed insulin be prescribed in T1DM?

Almost never.

Why are premixed insulins avoided in T1DM?

Intensive regimens require frequent adjustment of the pre-meal bolus insulin.

When could premixed insulin be considered in T1DM?

In patients who cannot comply with an intensive regimen.

Should an insulin vial currently in use be refrigerated, and when does it expire?

No - refrigerate only vials NOT in use; a vial in use is kept unrefrigerated and expires in 28 days (potency lost if used >30 days).

What should a patient inspect an insulin vial for before use? (select all that apply)

1. Clumping 2. Frosting 3. Precipitation 4. Change in clarity or color

What needle safety rules should insulin users follow? (select all that apply)

1. Do not share syringes or reuse needles 2. Do not recap, bend, or break the needle 3. Dispose in a puncture-resistant container

What is the most common adverse effect of insulin?

Hypoglycemia.

What is lipoatrophy?

Loss of subcutaneous fat at injection sites, leaving a depression in the skin.

What is lipohypertrophy?

Swelling or firm nodules at insulin injection sites.

What are the adverse effects of insulin? (select all that apply)

1. Hypoglycemia 2. Injection site reactions (lipoatrophy, lipohypertrophy) 3. Weight gain

In MDI, what does the basal insulin cover?

Fasting/overnight glucose needs.

Why are rapid-acting insulins used for mealtime boluses?

Rapid onset and shorter duration cover mealtime glucose excursions while minimizing post-meal hypoglycemia.

What type of insulin is used in an insulin pump (CSII)?

Rapid-acting insulin only, delivered continuously.

What are the advantages of an insulin pump (CSII)? (select all that apply)

1. Flexible dosing 2. Continual adjustments 3. Smaller dose delivery (0.05 units)

Why can an insulin pump increase DKA risk?

Mechanical failure interrupts insulin delivery.