Diabetes%20mellitus%20(pediatric) Diagnosis
Diagnosis
Type 1 Diabetes Mellitus (DM)
- Occurs in children usually between 7-15 years old, but may present at any age
Immune-mediated
- Caused by absolute deficiency of insulin secretion due to autoimmune destruction of pancreatic islet beta cells
- Both genetic susceptibility & environmental factors contribute to the pathogenesis of this type
- Associated w/ other autoimmune diseases (eg Graves’ disease, thyroiditis, celiac disease, multiple sclerosis & Addison’s disease)
Idiopathic
- Manifests as alternating episodic ketoacidosis & insulin deficiency
- No β-cell autoimmunity & human leukocyte antigen (HLA) association present
- Treatment w/ Insulin replacement is flexible
Diagnosis
- Clinical presentation can vary from polyuria, polydipsia, polyphagia, weight loss to severe dehydration, shock & diabetic ketoacidosis (DKA)
- Most important clue is an inappropriate polyuria in any child w/ dehydration, poor weight, or “the flu”
- Hyperglycemia, glycosuria, ketonemia & ketonuria occurs w/ the classic symptoms
- Can be diagnosed if polyuria, polydipsia, polyphagia, weight loss are present & fasting plasma glucose (FPG) concentration is ≥126 mg/dL (7.0 mmol/L) &/or random plasma glucose is ≥200 mg/dL (11.1 mmol/L)
- Once hyperglycemia is confirmed, evaluate for presence of DKA & manage accordingly
Type 2 Diabetes Mellitus (DM)
- Patients who have insulin resistance & relative insulin deficiency
- Many causes including genetic defects
- Aggravated by environmental factors (eg low physical activity or hypercaloric lipid-rich diet)
- Insulin treatment is not usually needed until disease progresses
- Usually seen in obese children, not insulin dependent & infrequently develop ketosis
- History of polyuria & polydipsia is relatively uncommon
- When DKA occurs, it is associated w/ the stress of another illness eg severe infection & may resolve when the stressful illness resolves
- Most patients remain asymptomatic for month to year as symptoms of hyperglycemia are not as dramatic as the polyuria & weight loss accompanying Type 1 DM
- Often seek medical care because of excessive weight gain & fatigue as a result of insulin resistance &/or incidental finding of glycosuria during routine physical exam
- Prolonged hyperglycemia may be accompanied, in time, by microvascular & macrovascular complications
Screening guidelines adapted from the American Diabetes Association 2016
- Age of 10 years or at onset of puberty if puberty occurs at a younger age
- Overweight, defined by body mass index (BMI) >85th percentile for age & gender, weight for age >85th percentile, or weight >120% of ideal for height plus any 2 of the following risk factors:
- Family history of Type 2 DM in 1st- or 2nd-degree relative
- Race/ethnicity (Native American, Asian American, Black, Hispanic, or Asian/Pacific Islander)
- Signs of insulin resistance or conditions associated w/ insulin resistance [eg acanthosis nigricans, hypertension, dyslipidemia, polycystic ovarian syndrome (PCOS), or small-for-gestational-age birth weight]
- Maternal DM/gestational DM
- Frequency of testing: every 3 years
- FPG is recommended as the primary screening test for Type 2 DM because of decreased cost & greater convenience
- 2-hour oral glucose tolerance test (OGTT) is recommended as a secondary test
- Clinical judgment should be used to test for Type 2 DM in high-risk patients who do not meet these guidelines
Diagnosis
- Can be diagnosed if polyuria, polydipsia, polyphagia, wt loss are present & FPG concentration is ≥126 mg/dL (7.0 mmol/L) &/or casual plasma glucose is ≥200 mg/dL (11.1 mmol/L)
- Clinical manifestations of Type 2 DM:
- Obese (BMI >95th percentile for age & gender) or overweight (BMI ≥85th-94th percentile for age & gender)
- Normal - elevated C-peptide & insulin levels
- Absence of autoantibodies to insulin, islet cell, &/or glutamic acid decarboxylase
- Signs of insulin resistance
- Acanthosis nigricans
- Dyslipidemia
- Hypertension
- PCOS
Other Specific Types of Diabetes Mellitus (DM)
Diabetes secondary to genetic defects of beta-cell function
- Neonatal DM
- Hyperglycemia that occurs in the first 6 months of life
- Insulin is required for initial treatment
- May be transient w/o recurrence, transient w/ recurrence after 7-20 years or permanent
Transient Neonatal DM
- Onset in the 1st week of life & persists for several weeks to months before spontaneous resolution
- Occurs most often in infants who are small for gestational age
- Characterized by hyperglycemia & pronounced glycosuria, resulting in severe dehydration & sometimes, metabolic acidosis but w/ minimal or no ketonemia or ketonuria
- Insulin responses to glucose or Tolbutamide are low to absent; basal plasma insulin concentrations are normal
- After spontaneous recovery, the insulin responses to these same stimuli are brisk & normal, implying a functional delay in beta-cell maturation w/ spontaneous resolution
- Occurrence of the syndrome in consecutive siblings has been reported
- Abnormalities of chromosome 6 are common in transient neonatal DM
- Administration of insulin is mandatory during the active phase of neonatal DM
- 1-2 U/kg/day of an intermediate-acting insulin in 2 divided doses results in dramatic improvement, accelerated growth & weight gain
- May attempt reducing the dose as soon as recurrent hypoglycemia manifests
Permanent Neonatal DM
- DM in the newborn period may be permanent if associated w/ pancreatic agenesis
- Studies revealed that almost one-half of neonatal DM patients had permanent diabetes, one third had transient diabetes & about one fourth had transient diabetes that recurred when they were 7-20 years old
- Affected twin & families w/ >1 affected infant have been reported
- May initially present as euglycemic & w/in the 1st month of life
- Maturity-onset diabetes of the young (MODY)
- A primary defect in insulin secretion characterized by early onset between 9 & 25 years of age, absence of ketosis & autosomal dominant inheritance
- Should be considered if:
- Diagnosed w/ diabetes in the first 6 months of life
- Family members w/ type 2 DM but w/ uncommon presentation
- Mild fasting hyperglycemia (100-150 mg/dL or 5.5-8.5 mmol/L) but young & nonobese
- Absent diabetes-associated autoantibodies & w/ atypical presentation of type 2 DM
- Some patients respond to diet therapy, exercise &/or oral antidiabetic agents; others may require insulin therapy
- Mitochondrial DNA mutation
Genetic defects in insulin action
- Type A insulin resistance
- Leprechaunism
- Rabson-Mendenhall syndrome
- Lipoatrophic diabetes
Exocrine pancreatic diseases
- Pancreatitis
- Pancreatic trauma that may require pancreatectomy
- Neoplasia
- Cystic fibrosis
- Hemochromatosis
- Fibrocalculous pancreatopathy
- Pancreatic resection
Endocrinopathies
- Acromegaly
- Cushing’s syndrome
- Glucagonoma
- Pheochromocytoma
- Hyperthyroidism
- Somatostatinoma
- Aldosteronoma
Uncommon forms of immune-mediated diabetes mellitus (DM)
- “Stiff-man” syndrome
- Anti-insulin receptor antibodies
- Autoimmune polyendocrine syndrome deficiencies I & II
Drug- or chemical-induced
- Glucocorticoids
- Thyroid hormones
- Diazoxide
- Beta-adrenergic agonists
- Nicotinic acid
- Thiazides
- Dilantin
- Alpha-interferon
- Pentamidine
- Rodenticide (eg Vacor)
Genetic syndromes
- Down syndrome
- Klinefelter’s syndrome
- Turner syndrome
- Wolfram syndrome
- Friedreich’s ataxia
- Huntington’s chorea
- Laurence-Moon-Biedl syndrome
- Myotonic dystrophy
- Porphyria
- Prader-Willi syndrome
Infections
- Congenital rubella
- Cytomegalovirus
Classification
Type 1 Diabetes Mellitus (DM)
- Beta-cell destruction which leads to complete insulin deficiency
- May be immune-mediated or idiopathic
- Most common endocrine metabolic disorder of childhood & adolescence
- Occurs more commonly in children 7-15 years, but may occur at any age
Type 2 Diabetes Mellitus (DM)
- Patients who have insulin resistance & relative insulin deficiency
- Insulin treatment is not usually needed until disease progresses
- Many causes including genetic defects
Other specific types of Diabetes Mellitus (DM)
- Uncommon causes; underlying cause or disease is identified
- Eg genetic defects, drug use, pancreatic disease, chemical exposure, other diseases, etc
Neonatal Dibaetes Mellitus (DM)
- Hyperglycemia that occurs in the first 6 months of life
- Insulin is required for initial treatment
- May be transient w/o recurrence, transient w/ recurrence after 7-20 years or permanent
Evaluation
Should include but is not limited to the following:
- Exclusion of secondary causes
Growth impairment
- Evaluate height & weight based on growth chart every clinic visit.
- See Growth Charts in MIMS Pediatrics
- Monitor thyroid-stimualting hormone (TSH) levels at diagnosis, every 1-2 years & w/ occurrence of abnormal growth rate
- Evaluate for celiac disease w/ unsatisfactory weight gain
Diabetic ketoacidosis (DKA)
- Hyperglycemia, accumulation of ketone bodies & metabolic disease due to insulin deficiency
- Type 1 DM patients may initially present w/ DKA at diagnosis
- Obtain capillary glucose in children w/ excessive thirst, polyuria, abrupt unexplained weight loss, excessive tiredness, reduced level of consciousness, N/V, abdominal pain, hyperventilation, & appears dehydrated
- May also be caused by missed Insulin doses
- Monitor venous pH, central venous & intra-arterial pressure
- Mild DKA: Venous pH 7.2-7.3 & <15-18 mmoL/L bicarbonate
- Moderate DKA: Venous pH 7.1-7.2 & <10-15 mmoL/L bicarbonate
- Severe DKA: Venous pH <7.1 & <10 mmoL/L bicarbonate
- Monitor heart rate (HR), respiratory rate (RR), blood pressure (BP), neurologic status, fluid input & output, evidence of hyper- or hypokalemia
- Monitor capillary glucose hourly
- Perform laboratory tests on electrolytes, blood glucose & blood gases every 2-4 hours
Hypoglycemia
- Blood glucose <3.9 mmol/L (70 mg/dL) causing cognitive impairment
- Cognitive impairment may be more pronounced in patients <5 years
- May occur more frequently in those w/ lower HbA1C levels, history of hypoglycemia, use of high Insulin doses, younger children, male gender
- May be mild, moderate or severe
- Mild hypoglycemia: Sweating, pallor, palpitations, tremors, mild symptoms of neutropenia
- Moderate hypoglycemia: Aggressiveness, drowsiness, confusion associated w/ neuroglycopenia; autonomic symptoms
- Severe hypoglycemia: Altered states of consciousness, coma, seizures
- Determine frequency of hypoglycemia every clinic visit
- Assess for unawareness of hypoglycemia & assess blood glucose
Nephropathy
- Microalbuminuria is the primary manifestation of diabetic nephropathy
- At the development of microalbuminuria, nephropathy may still be reversible
- Poor glycemic control, smoking, family history of essential hypertension & cardiovascular disease (CVD) are associated w/ the development of nephropathy
- Screen for microalbuminuria annually once the patient starts puberty or is ≥10 years & had DM for 5 years
- More frequent testing is indicated w/ increased values
- Confirmed elevated albumin-to-creatinine ratio (ACR) (>30 mg/g) consists of 2 out of 3 specimens obtained from separate days over a 6-months interval after treatment initiation for hypo/hyperglycemia & BP for age
- Timed overnight or a 24-hours analysis w/ elevated albumin excretion rate (AER) of 20-199 mcg/minute may also be used
- Exercise, smoking & menstruation may affect results, confirm on another day
- Obtain baseline estimated glomerular filtration rate (eGFR) measurement & repeat based on patient’s age, clinical status, duration of disease & treatment history
- Exclude non-DM related causes upon confirmation of diagnosis
- Monitor microalbumin excretion every 3-6 months
Hypertension
- Common comorbidity of DM
- Determine BP every clinic visit & evaluate for parental hypertension which is a major risk
- ≥95th percentile of systolic or diastolic BP for age, gender & height percentile measured on at least 3 separate days is definitive of hypertension
- “High-normal” BP is >90th but <95th percentile of systolic or diastolic BP for age, gender & height percentile measured on at least 3 separate days
- Exclude non-DM related causes upon confirmation of diagnosis
- Evaluate renal functional status by urinalysis, serum creatinine (Cr) & blood urea nitrogen (BUN)
- Obtain urinary albumin excretion if not obtained w/in previous 6 months
Dyslipidemia
- Elevated plasma lipid concentration, smoking, hypertension, obesity, family history of heart disease & DM contribute to the development of atherosclerosis
- Perform fasting lipid profile on >2 years prepubertal patients w/ Type 1 DM if w/ family history of hypercholesterolemia, CVD before 55 years
- Screen at puberty (≥10 years) if w/o mentioned family history
- Obtain fasting lipid profile in patients ≥10 years of age after glucose control has been achieved
- Repeat screening if low-density lipoprotein cholesterol (LDL-C) is borderline (100-129 mg/dL) or abnormal (≥130 mg/dL)
Retinopathy
- Has been reported w/ DM of 1-2 years duration
- Identify early & treat appropriately
- Hypertension, poor metabolic control, presence of albuminuria, dyslipidemia, smoking, longer duration of DM & pregnancy are associated w/ increased risk for retinopathy
- Refer patient to ophthalmologist w/ expertise in diabetic retinopathy & its risks in the pediatric patient
- Schedule regular ophthalmological screening w/ initial exam when the patient is ≥10 years or post-puberty onset & had DM for 3-5 years & annually from then on
- Patient planning pregnancy should have an ophthalmological exam prior to conception during the 1st trimester & at the recommendation of the ophthalmologist
Neuropathy
- Initial foot examination at the beginning of puberty & at least annually for protective sensation, pulses, skin integrity & treatable nail problems (eg ingrown toenails)
- Comprehensive foot exam should include inspection, dorsalis pedis & posterior tibial pulse palpation, patellar/ Achilles tendon reflex testing, & proprioception/vibration/monofilament sensation assessment
Thyroid disease
- Most common autoimmune disorder in Type 1 DM patients
- May be euthyroid, hypothyroid or hyperthyroid
- Screen for autoimmune thyroid disease at diagnosis & recheck TSH levels every 1-2 years for patients w/ normal TSH or if growth rate is abnormal
- See Growth Charts in MIMS Pediatrics
- Monitor for thyroid control after establishing metabolic control
- Measure thyroid autoantibodies & TSH
- Identify patients at increased risk of autoimmune thyroid disease w/ the presence of thyroid autoantibodies [antithyroid peroxidase (APO), & antithyroglobulin (TG)]
- Treat patients w/ elevated TSH levels
- Measure free T4 if TSH is abnormal
- Perform thyroid function test whenever thyroid dysfunction is suspected & if patient has thyromegaly
- Evaluate for hypothyroidism thoroughly & treat appropriately
Celiac disease
- Type 1 DM patients have high risk for celiac disease
- Immune-mediated damage to the mucosa of the small intestine due to ingestion of food w/ gluten (eg wheat, rye, barley & oats)
- Symptoms include diarrhea, weight loss or poor wt gain, growth failure, abdominal pain, chronic fatigue, irritability, inability to concentrate, malnutrition due to malabsorption & other GI problems
- Symptoms of DM patient w/ celiac disease include unpredictable blood glucose levels, unexplained hypoglycemia & deterioration in glycemic control
- Screen for celiac disease by testing for the presence of IgA autoantibodies to tissue transglutaminase (tTG) or deaminated gliadin antibodies, or endomysial autoantibody (EMA) assay
- Perform test upon diagnosis of type I DM & in children w/ 1st-degree relatives w/ celiac disease, growth failure, failure to gain weaight & gastroenterologic symptoms (diarrhea, flatulence, abdominal pain, signs of malabsorption), & those w/ frequent unexplained hypoglycemia or deteriorating glycemic control
- Confirm elevated tTG antibodies
- Interpret low to moderate tTG antibodies along w/ symptoms & repeat screening after 6-12 months
- Confirm positive Ab levels
- Recommend small bowel biopsy if patient has elevated tTG antibodies
- Refer patient to gastroenterologist once celiac disease is confirmed
- Recommend consultation w/ registered dietitian experienced w/ DM & celiac disease in pediatric patients
- Screen periodically in patients negative for celiac disease
Psychiatric disorders
- DM is a risk factor for psychiatric disorders (eg depression, generalized anxiety disorders) in adolescent patients
- An increasing number of adolescents newly diagnosed w/ DM considers suicide
- Screen patients ≥10 years annually for depression
- Screen for psychiatric disorders in patients w/ difficulties in achieving treatment goals & w/ recurrent DKA
- Patients w/ DKA are more likely to develop psychiatric disorders
Eating disorders
- Associated w/ DM in adolescent patients
- Patients w/ eating disorders are at risk for poor metabolic control & recurrent hospitalization
- Mental health professional should screen for eating disorders w/ failure in treatment goals especially if patient is underweight
History
Early in the evaluation of a new patient w/ diabetes mellitus (DM), it is important to distinguish between Type 1 & Type 2 DM to optimize therapy
- Past &/or current DM characteristics including age of onset, diagnosis, management & treatment
- Previous or ongoing infection(s)
- Growth records
- Family history of DM & cardiovascular disease (CVD)
- History of DM-related complications
- Medications, nutritional status, eating patterns & exercise history
- Tobacco, alcohol use & drug history
- Sexual activity & contraceptive use
- Risk factors for atherosclerosis
- Glycosylated hemoglobin (HbA1c) history
- History of hypoglycemia
- History of diabetic ketoacidosis (DKA)
- History of gestational diabetes or macrosomia
- History of other disorders (eg endocrine, eating & mood disorders)
Physical Examination
- Height & weight, calculate body mass index (BMI), measure waist circumference
- Blood pressure (BP) measurement
- Hand & foot examination, & evaluation of pulses by palpation w/ auscultation
- Funduscopic, oral, abdominal examination
- Cardiac & thyroid examination
- Skin examination for acanthosis nigricans
- Neurological examination
- Evaluate signs of puberty/physical development
Laboratory Tests
- If there is suspicion or any evidence of diabetes ketoacidosis (DKA), include:
- Serum glucose
- Electrolytes
- Arterial or venous pH
- Serum or urine ketones
- HbA1c
- Fasting lipid profile [total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) & triglycerides (TG)]
- Test for microalbuminuria
- Thyroid antibodies
- Liver function test
- Genetic testing - if presentation is atypical & w/ family history of monogenic diabetes
Screening
Diagnostic criteria for diabetes mellitus (DM) adapted from the American Diabetes Association 2016
Any of the following:
- HbA1c >6.5% (48 mmol/mol)
- Done in a National Glycohemoglobin Standardization Program (NGSP)-certified method traceable to the Diabetes Control & Complications Trial (DCCT) reference assay
- Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L)
- Fasting is defined as no caloric intake for at least 8 hours
- 2-hours plasma glucose of ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test (OGTT)
- Perform test as described by the World Health Organization (WHO), using a glucose load of 75 g anhydrous glucose dissolved in water or 1.75 g /kg body weight if weight is <40 lbs (18 kg)
- OGTT is not recommended for routine clinical use, but may be required in the evaluation of patients when diabetes is still suspected despite a normal FPG
- Symptoms of polyuria, polydipsia & unexplained wt loss w/ random plasma glucose ≥200 mg/dL (11.1 mmol/L)
- Random is defined as any time of day w/o regard to time since last meal
If typical hyperglycemic symptoms are not present, a repeat test should be done on a different day to confirm diagnosis
- Confirm diagnosis if FPG ≥126 mg/dL or 2-hours plasma glucose of ≥200 mg/dL or random glucose of ≥200 mg/ dL in high-risk patient screened for DM