ENDO/METABOLIC Flashcards
Epidemiology of T1DM in kids.
- What % have family hx?
- M vs F?
- Peak age?
F=M
Peak age between 5-15 years
20% have a family history of DM
S&S of DKA?
vomiting & abdo pain
dehydration
lethargy/drowsiness
confusion
Kussmaul respirations (deep sighing respirations)
smell of ketones
**DKA occurs in ~40% of children with new onset DM
Common S&S of T1DM in kids?
Weight loss
Polyuria, polyphagia, and polydipsia
**Polyuria may present as bed-wetting
Fatigue/tiredness
Polyuria is most consistent presenting concern, manifested as urinary frequency, nighttime polyuria, or secondary enuresis
Polyphagia and polydipsia are more commonly noticed when disease onsets in preschool years, when parents are able to monitor intake
Basic patho of T1DM?
Absolute insulin deficiency and impaired beta cell function.
Results from autoimmune destruction of the beta cells of the pancreas
Thought to be triggered by environmental factor (i..e, virus or toxin) in genetically susceptible individual
Management of DKA in kids is different because kids are have higher risk of ______
cerebral edema
A kid with a new diagnosis of Type 1 DM needs a strong interdisciplinary team. Who should this team include?
either a pediatric endocrinologist or pediatrician with diabetes expertise
dietician
diabetes nurse educator
social worker
mental health professional
What are the A1C, preprandial, and postprandial targets for a kid (<18 years) with Type 1 DM? (according to diabetes Canada)
A1C < or equal to 7.5
Fasting/preprandial PG: 4-8
2 hour postprandial PG: 5-10
**of course targets are more liberal in kids with issues with hypoglycemia or hypoglycemia unawareness
Mainstay of medical management of T1DM is?
Insulin
What is the “honeymoon period” in diabetes management in kids with T1DM, and how does insulin requirements change over time?
“Honeymoon period”
- up to 2 years after diagnosis
- target glycemic control and low insulin requirements; at the end of this period, may require more intensive management to continue to meet glycemic targets
Insulin requirements may increase in adolescents (sexual maturation process occurs in the setting of relative insulin resistance)- insulin requirements may increase to 1.5- 2 U/ kg during adolescence and then return to prepubertal levels at the end of teenage years.
What are the 2 main ways that insulin is given to kids with T1DM?
Two methods of intensive diabetes management have been used:
1) basal-bolus regimens (long-acting basal insulin analogues and rapid-acting bolus insulin analogues)
2) continuous subcutaneous insulin infusion (CSII) therapy
**Cribsiders stresses that you should start with basal-bolus for new diagnosis because patient needs to learn this system. If you start with pump and it malfunctions, they won’t know how to manage with basal-bolus unless they have this practice.
T/F Increased frequency of glucose monitoring for those with T1DM is associated with improved clinical outcomes
True :) Self-monitoring frequently is ESSENTIAL
(continuous glucose control is associated with less hypoglycemia)
What is the “closed loop” system of insulin management in T1DM>?
The closed-loop pancreas system, also known as the artificial or bionic pancreas system couples the use of an insulin pump with infusion of 1 or more hormones (insulin +/- glucagon), a glucose sensor and an algorithm for glucose control.
The closed-loop system allows for decreasing excursions in blood glucose levels while reducing the overall burden of self-care.
Promising results in small studies, larger studies underway now.
T/F Children with T1DM need to restrict carbohydrate intake and need a special diet unlike other kids
False!
Children with diabetes should follow a healthy diet as recommended for children without diabetes in Eating Well with Canada’s Food Guide
Nutrition therapy should be individualized (based on the child’s nutritional needs, eating habits, lifestyle, ability and interest) and must ensure normal growth and development without compromising glycemic control. T
**cribsiders also reinforces this…. the kid doesn’t need to restrict foods necessarily. They just need to be able to give themselves adequate insulin to manage the extra carbs, etc
How do kids/parents know how much bolus insulin to give the child with T1DM after eating?
Carbohydrate counting!
This seems like the most common management strategy
- They count the carbs in the meal and this determines how many units of insulin they receive
“Carbohydrate counting is a commonly used method of matching insulin to carbohydrate intake that allows increased flexibility in diet, although fat and protein content also influence postprandial glucose levels.” - diabetes Canada
If this is not an option, they can also take preprandial BGs to determine bolus dose (like we do with adults in the hospital)
Severe hypoglycemia in the home should be treated with?
Glucagon
- In children, the use of mini-doses of glucagon has been shown to be useful in the home management of mild or impending hypoglycemia associated with inability or refusal to take oral carbohydrate
What is the most common causes of DKA in a child with established T1DM?
failing to take insulin or poor sick-day management.
What does sick day management look like in T1DM?
Sick-day management includes more frequent SMBG, ketone measurement during hyperglycemia and adjustment of insulin dose in response to monitoring
**This does NOT mean they stop taking their insulin!
In a kid with newly diagnosed T1DM, you want to consider screening for other autoimmune conditions. What might this include?
1) Thyroid issues: Serum TSH level + thyroid peroxidase antibodies
2) Celiac disease: Tissue transglutaminase + immunoglobulin A levels
3) adrenal insufficiency (8 AM serum cortisol and serum sodium and potassium) if unexplained recurrent hypoglycemia
Consider IBD if symptoms…
**Diabetes Canada outlines this nicely.
What is the deal with pancreatic autoantibodies and diagnosis of T1DM? Do all patients with T1DM test positive for these tests?
Measuring pacreatic autoantibodies:
autoantibodies against GAD65 (glutamic acid decarboxylase 65), IA2 (the 40K fragment of tyrosine phosphatase), insulin, and ZnT8 (zinc transporter 8)
Most patients with T1DM have one or more of the above pancreatic autoantibodies, indicating autoimmune destruction of pancreatic beta cells; this is sometimes referred to as type 1A diabetes. A minority of patients with clinical features of T1DM have no detectable autoantibodies and are categorized as having type 1B diabetes
Conversely, up to 30% of individuals with clinical characteristics of T2DM have positive autoantibodies and may have a slowly progressive type of autoimmune diabetes
What is C-peptide and how do we use it to differentiate between T1DM and T2DM?
The pancreas releases C-peptide when it makes insulin…so if the pancreas isn’t producing insulin (as in T1DM), you will see low C-peptide levels (even if the patient is receiving exogenous insulin)
We measure these levels for children with clinical characteristics that raise the possibility of T2DM. In a newly diagnosed patient, these tests should be performed after the child has recovered from the initial hyperglycemic stress because insulin and C-peptide levels may be suppressed by severe hyperglycemia (glucose toxicity) and acute illness.
In children with T1DM, levels of fasting insulin and C-peptide are inappropriately low relative to the concomitant plasma glucose concentration (ie, low or in the normal range despite hyperglycemia). By contrast, high fasting insulin and C-peptide levels suggest T2DM.
Why is it important to talk to young uterus-havers with T1DM about contraception?
Unplanned pregnancies should be avoided, as pregnancy in adolescent females with type 1 diabetes with suboptimal metabolic control may result in higher risks of maternal and fetal complications than in older women with type 1 diabetes who are already at increased risk compared to the general population
What psychological conditions are increased in kids with T1DM?
significant risks for psychological problems including: diabetes distress (104), depression (105), anxiety (105), eating disorders and externalizing disorders
**10%of adolescent females with type 1 diabetes meet the Diagnostic and Statistical Manual of Mental Disorders (4th Edition) criteria for eating disorders compared to 4% of their age-matched peers without diabetes
Eating disorders should be suspected in those adolescent and young adult females who are unable to achieve and maintain metabolic targets, especially when insulin omission is suspected
Differentiate T1 and T2 DM in terms of patho (think insulin)
T1DM = insulin deficiency (d/t autoimmune destruction of the beta cells in pancreas)
T2DM = insulin resistance with relative insulin deficiency (impaired beta cell function but NOT AUTOIMMUNITY)
Which types of insulin are rapid acting and what are their onset & duration
Lispro, aspart, glulisine
Onset within 15 mins
Duration < or equal to 5 hours
Which insulin is short acting and what is the onset & duration?
Regular
Onset within 30 mins
Duartion 5- 8 hours
Which insulins are long acting.
Onset and duration?
Glargine, detemir, degludec
Onset varies from 1 hr to 2.5 hrs
Duration varies, typically 20-24 hours
Are girls or boys more likely to be diagnosed with T2DM?
Girls
T2DM is Highly heritable- ________% of children/ youth with T2DM also have a FDR or second degree relative who also have T2DM
90%!
Non-genetic risk factors for T2DM in kids?
obesity, PCOS, exposure to diabetes in utero, HTN, dyslipidemia, NAFLD, atypical antipsychotics.
Preventative measures for T2DM?
breastfeeding
efforts to improve sleep quality and quantity
decreased sedentary and increased physical activity, reduced screen time, reduces sugar- sweetened beverage consumption
Clinical presentation of T2DM in kids?
Can present with DKA or HHS
Weight loss is less common than T1DM (T2DM strongly associated with obesity/ BMI >95 percentile)
Polyuria, polyphagia, polydipsia
More often ID on screening UA
Acanthosis nigricans
Diagnosis of T2DM in kids - how do we test? Is A1C enough? When is 2hr OGTT recommended?
Recommended screening: FPG (can also do OGTT, A1C (>6%)). Note: A1C should not be relied upon as the sole diagnostic test to screen for T2DM, but rather used in combination with FBG and/or 2 hour OGTT.
“we recommend using a combination of A1C and fasting or random blood glucose to screen for type 2 diabetes in children and youth with risk factors. A 2-hour OGTT may be considered as an initial screening test in children and youth with 3 or more risk factors and should be done in those in whom there is a discrepancy between the A1C and fasting or random blood glucose results.”
Testing for DM autoantibodies should be considered in all peds patients with T2DM, as 10-20% are autoantibody positive, suggesting they actually have T1DM with insulin deficiency (and are at risk for other autoimmune conditions)
In addition, the absence of islet autoantibodies may be useful in supporting the diagnosis of type 2 diabetes
Target A1C for most kids with T2DM
≤7.0%.
Key aspects of treating adolescents with T2DM
treatment programs for adolescents with type 2 diabetes need to address the lifestyle and health habits of the entire family, emphasizing healthy eating and physical activity, and promoting smoking prevention/cessation strategies.
In adolescent females with type 2 diabetes, proactive contraceptive counselling to avoid pregnancy is warranted given the high rates of congenital anomalies reported in this population
When might insulin be initiated in kids at time of diagnosis with T2DM?
Insulin is required in those with severe metabolic decompensation at diagnosis (e.g. DKA, A1C ≥9.0%, symptoms of severe hyperglycemia) but may be successfully weaned once glycemic targets are achieved
Once-a-day basal insulin is often effective in attaining metabolic control
Unless acidosis is present, metformin should generally be started at the same time as insulin
What screening needs to be done at diagnosis & yearly for kids with T2 diabetes?
neuropathy, retinopathy, nephropathy, dyslipidemia, HTN (plus at every visit), NAFLD, PCOS, OSA, depression, and binge eating
T/F all of the same antihyperglycemic meds that are used in adults are also used in pediatrics
Wrongo bongo!
None of the noninsulin antihyperglycemic agents have been approved by Health Canada for use in children
….However there are increasing data about the safety or efficacy of certain noninsulin antihyperglycemic agents in the pediatric population (metformin, glimepiride etc)
Who is at higher risk of diabetes microvascular and CVD complications: kids with T1 or T2 DM?
T2
Youth with type 2 diabetes appear to be at significantly higher risk of developing earlier and severe microvascular and cardiovascular (CV) disease compared to youth with type 1 diabetes
Name many many risk factors that predispose children to hypoglycemia (specifically mentioned in ILOs)
Young age- food intake, activity, adherence to treatment schedules are less predictable in younger kids
“Tight” glycemic control (i.e., A1C lower than 7.5)
Type of insulin regimen- fixed dose regiments (fixed injection schedule) results in more hypoglycemia than intensive regiments (basal insulin with intermittent boluses of rapid acting insulin to cover food intake) or continuous sub cut insulin infusion (pumps)
Missed snacks or meals.
Inconsistent carb intake
Exercise- increases body’s sensitivity to insulin
Alcohol ingestion (acutely increases insulin sensitivity!)
Acute illness with nausea/ vomiting/ anorexia (due to decreased intake) (note- hyperglycemia can also result in acute illness due to peripheral insulin resistance)
Lower SES
Psych disorders
Co-existing autoimmune diseases (i.e., autoimmune thyroiditis, celiac, addison’s)
What can you do to prevent risk of hypoglycemia with exercise?
- Monitor BG before/ during/ after vigorous activity
- Consume snack before/ during time of increased activity
- Reduce the last insulin dose before activity
- Reduce the basal rate of the insulin pump for the duration of the exercise and a variable period after
Are hyper and hypothyroidism congenital or acquired in kids?
Can be either
Congenital hyperthyroidism aka
Neonatal Grave’s disease (not to be mistaken with plain old Grave’s, which is acquired hyperthyroidism)
Typically caused by transplacental transfer of TSH receptor antibody
Presentation of baby with congenital hyperthyroidism?
-Maternal history of thyroid pathology and management
-Low birthweight, IUGR, premature birth, tachycardia, irritability, triangular facies, hepatosplenomegaly, goiter, flushing, sweating
How is congenital hyperthyroidism diagnosed in neonates?
TSH receptor antibodies during 3rd trimester or in the cord blood
-Neonatal TSH, T3, free T4
Tx of hyperthyroidism in kids?
Methimazole and beta blocker (ex. Propranolol)
Graves (acquired hyperthyroidism) - is it more common in girls or boys?
Girls
Graves disease most commonly occurs in early-adolescent girls
Thought to be linked to estrogen…
Presentation of Graves in kids
-Presentation may be vague and include hyperactivity or slowness and fatigue
-Distractibility, poor school performance and all the adult hyperthyroid symptoms
-May have goiter and mild ophthalmopathy
T/F The diagnosis of Grave’s disease in kids is the same as in adults
True!
What is the most common abnormality of thyroid function in kids?)
Acquired hypothyroidism, most often autoimmune thyroiditis (just like adults)
S&S of acquired hypothyroidism in kids?
-Declining height growth/short stature
-Delayed pubertal development
-Altered school performance
-Normal hypo-thy S/S: sluggishness, cold intolerance, brittle hair, goiter, et
Diagnosis of acquired hypothyroidism in kids?
Same as adults
Management of acquired hypothyroidism in kids
Levothyroxine (like adults!)
Weight based dosing depends on age
May not require continued therapy for milder cases once full growth and development achieved
Are all kids screening for congenital hypothyroidism?
Yes, they should be!
-Repeat screening at 2 weeks old for high-risk infants (preterm, SGA, NICU, specimen collection <24h from birth, multiple births)
-Confirm abnormal screen with venipuncture
Causes of congenital hypothyroidism?
-Permanent or transient
-Categorized into:
Primary (85% dysgenesis, 15% thyroid gland disorder)
Secondary/central (pituitary/hypothalamic disorder)
Peripheral (deficits in TH transport, metabolism or action)
How will TSH and T3 look in kids with primary vs secondary congenital hypothyroidism
Primary CH = inc TSH, dec T4
Secondary CH = dec TSH, dec T4
How do fresh babies with congenital hypothyroidism present?
Presentation
-Prolonged jaundice, feeding difficulty, constipation, umbilical hernia, macroglossia, large fontanelles, puffy face, swollen eyes, hypotonia
-May accompany congenital malformations (especially cardiac) and dysmorphic features
-Central associated with hypoglycemia, micropenis, undescended testes, DI
How is congenital hypothyroidism treated? What should the babe NOT recieve?
-Thyroid hormone replacement – normalize hormones within 2 weeks to avoid cognitive impairment
-Avoid soy-based formulas
Prognosis of congenital hypothyroidism.
What can it cause if untreated?
-Excellent if treatment started within 1-2 months of birth
-Treatment initiation after 3-6 months old can lead to permanent developmental delay, mild-profound disability, intellectual impairment, poor growth and hearing loss
PCOS Frequently first manifests in adolescents within ____ years of puberty
2
Cause of PCOS?
= a syndrome (not a disease), so are many possible etiologies
Cause unknown
Evidence it arises as a complex trait with contributions from both heritable and nonheritable intrauterine and extrauterine factors
_______ is common initial first complaint of teens with PCOS
Other key complaints in teens with PCOS?
Excessive, irregular menstrual bleeding = most common
Chief complaint in adolescents with PCOS may also be hirsutism, topical treatment-resistant acne, menstrual irregularities, acanthosis nigricans, and/or obesity
Can we use adult criteria for PCOS in kids/teens?
No, these criteria don’t work in this age because:
- anovulatory cycles, menstrual irregularities and acne vulgaris common and hirsutism is a developmental phase
- Testostone levels in teens is problematic
- Extent to which adolescent hyperandrogenism predicts adult hyperandrogenism is unclear
- Polycystic ovary morphology to adult standards is common in adolscents
Soooo then how do we diagnosis PCOS in kids/teens?
There is still debate about diagnostic criteria. Core criteria agreed upon (as below) but how each of these criteria is measured is not agreed upon.
It is agreed that adolescents with evidence of PCOS within one to two years after menarche should be assigned a provisional diagnosis of “at risk for PCOS” and treated symptomatically
CRITERIA (according to UTD):
- Abnormal menstrual pattern as evidence of ovulatory dysfunction
- abnormal for age or gynecologic age AND persistent symptoms for 1-2 years - Clinical and/or biochemical evidence of hyperandrogenism
- Hirsutism, especially if moderate to severe
- elevation of serum total or free testosterone
General S&S of PCOS in peds?
Heterogeneous condition – clinically and biochemically; often don’t have all features
Cutaneous signs of hyperandrogenism: hirsutism, moderate-severe acne
Menstrual irregularity: oligo- or amenorrhea, or irregular bleeding, heavy bleeding
Polycystic ovaries (one or both)
Obesity
Insulin resistance - leading to acanthosis nigricans and skin tags
Define hirsutism
abnormal amount of sexual hair that appears in a male pattern
T/F All patients with PCOS are obese
Wrongo bongo again.
1/2 of patients with PCOS are NOT obese
Treatment of PCOS?
Really depends on individual symptoms and goals/preferences
1st line:
usually COCs – will correct menstrual irregularities, acne, and hirsutism
Lifestyle modifications to help with obesity & insulin resistance
If hirsutism not controlled by COCs and cosmetic treatment, can add antiandrogen (spironolactone) and/or direct hair reduction therapy
Metformin can be helpful if weight loss doesn’t correct glucose tolerance or lipid abnormalities, or if ovulation is the primary goals
Acne help by: topicals, antibiotics, COCs, antiandrogens
Progestin in COCs is important because it inhibits endometrial proliferation, preventing hyperplasia
Complications of PCOS. What are they at increased risk for?
Those with PCOS have increased risk for metabolic syndrome, T2DM, obstructive sleep apnea, endometrial hyperplasia, and, possibly, CVD and endometrial carcinoma
Chronic anovulation increases the risk of developing endometrial hyperplasia, which is associated with endometrial carcinoma
