Diabetes mellitus type 2 in children and adolescents

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[+]Updated 2018 Mar 21 06:28 PM (ET)
Topic Editor Kim A. Carmichael, MD, FACPRecommendations Editor Allen Shaughnessy, PharmD,
M Med Ed, FCCPDeputy Editor William Aird, MD
Overview and Recommendations
BackgroundDiabetes mellitus type 2 is an endocrine disorder characterized by variable degrees of
insulin resistance and deficiency, resulting hyperglycemia and complications such as cardiovascular
disease, nephropathy, and retinopathy.Type 2 diabetes may be asymptomatic or may present
with symptoms typical of hyperglycemia such as polyuria, polydipsia, and polyphagia.Previously,
type 2 diabetes was uncommon in children, but prevalence is increasing, likely due to increasing
childhood obesity; consider targeted screening of overweight children with additional familial,
demographic, or clinical risk factors (such as acanthosis nigricans, hypertension, dyslipidemia, or
polycystic ovary syndrome) (Weak recommendation).
EvaluationPerform blood testing to diagnose diabetes (Strong recommendation).Diagnostic
criteria for diabetes is any of:fasting plasma glucose ≥ 126 mg/dL (7 mmol/L) (after no caloric intake
for ≥ 8 hours)symptoms of hyperglycemia with random plasma glucose ≥ 200 mg/dL (11.1 mmol/L)2-
hour plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during a 75 g oral glucose tolerance testHbA1c ≥
6.5% (HbA1c may not be accurate for diagnosis with pregnancy, hemoglobinopathy, certain
anemias, or abnormal erythrocyte loss or replacement)Repeat testing for confirmation in absence
of unequivocal hyperglycemia.If clinical findings alone are insufficient to differentiate between
diabetes type 1 and type 2, consider blood tests for autoantibodies and C-peptide (Weak
recommendation); results consistent with a diagnosis of type 2 diabetes include:absence of islet
cell, insulin, and glutamic acid decarboxylase autoantibodiesincreased C-peptide
levelConsider additional testing and evaluation at or soon after diagnosis with type 2 diabetes,
including:fasting lipid profileliver transaminasesspot urine albumin-to-creatinine ratiodilated eye
exam to detect retinopathy
ManagementIndividualize glycemic goals (Strong recommendation); generally recommended target
in children is HbA1c < 7% or 7.5% (Weak recommendation).Consider individualized lipid goals and
blood pressure goals; generally recommended targets in children with type 2 diabetes are low-
density lipoprotein (LDL) cholesterol < 100 mg/dL (2.6 mmol/L) and blood pressure < 95th percentile
for age (Weak recommendation).Provide support for dietary management, maintaining physical
activity, and diabetes self-management education (Strong recommendation).Prescribe glucose-
lowering medications (Strong recommendation).Metformin is the first-line drug of choice for type 2
diabetes (Strong recommendation); it is the only oral glucose-lowering agent labeled for use in
children with type 2 diabetes.Start with 250 mg twice daily.Increase by 500 mg/day every 1-2 weeks,
up to 1 g twice daily.Insulin is the first-line drug of choice in children and adolescents with glucose
≥ 250 mg/dL (13.9 mmol/L), HbA1c > 9%, ketosis, diabetic ketoacidosis, or if the diagnosis is not
clearly type 2 diabetes (Strong recommendation).Consider an angiotensin-converting enzyme
(ACE) inhibitor for blood pressure ≥ 95th percentile or persistent microalbuminuria.Consider
a statin for LDL cholesterol > 130 mg/dL (3.4 mmol/L).Consider fibrates or niacin in children > 10
years old with triglycerides > 700-1,000 mg/dL (7.9-11.3 mmol/L).Provide follow-up monitoring;
consider:HbA1c every 3 months (Weak recommendation)urine albumin excretion annually (Weak
recommendation)specialist retinal exam annually (consider every 2 years if normal exam) (Weak
recommendation)fasting lipid profile every 2 years (Weak recommendation)
Related SummariesDiabetes (list of topics)Obesity in children and adolescents
General Information
Descriptionendocrine disorder characterized by hyperglycemia(1, 4)occurs due to(1, 4)resistance to
insulin actioninadequate compensatory or total insulin secretory responseprevalence is increasing
with increasing obesity in children and adolescents(1)chronic hyperglycemia of diabetes can lead to
multiorgan damage, resulting in renal, neurologic, cardiovascular, and other serious
complications(7)
Also calleddiabetes mellitus type IItype 2 diabetestype II diabetesnon-insulin-dependent diabetes
mellitus (NIDDM)insulin-resistant diabetes is preferred term when diabetes no longer controlled with
oral agents because insulin-dependent diabetes mellitus (IDDM) implies diabetes mellitus type 1
Definitionsdiabetes diagnosed if any of(7)fasting plasma glucose ≥ 126 mg/dL (7 mmol/L) (no caloric
intake for ≥ 8 hours)random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) with symptoms of
hyperglycemia (such as polyuria, polydipsia, blurred vision) or hyperglycemic crisis2-hour plasma
glucose ≥ 200 mg/dL (11.1 mmol/L) during 75 g oral glucose tolerance testHbA1c ≥
6.5%prediabetes diagnosed if any of(6)fasting plasma glucose 110-125 mg/dL (6.1-6.9 mmol/L)
using World Health Organization (WHO) criteria, or 100-125 mg/dL (5.6-6.9 mmol/L) using American
Diabetes Association (ADA) criteria2-hour plasma glucose 140-199 mg/dL (7.8-11 mmol/L) during
75 g oral glucose tolerance testHbA1c 5.7%-6.4% (using ADA criteria)childhood diabetes mellitus
type 2 defined as disease in child who usually(2)is overweight (body mass index 85th-94th percentile
for age and gender) or obese (> 95th percentile for age and gender)has strong family history of type
2 diabetesdemonstrates insulin resistance (including clinical evidence of polycystic ovary
syndrome, acanthosis nigricans, dyslipidemia, or nonalcoholic fatty liver disease)lacks evidence for
diabetic autoimmunity (negative for autoantibodies typically associated with diabetes mellitus type
1)
TypesAmerican Diabetes Association (ADA) classifications of diabetes(7)type 1 diabetes (beta-cell
destruction, usually leading to absolute insulin deficiency)immune-mediatedidiopathictype 2
diabetes (varying degrees of insulin resistance and insulin deficiency)other specific typesgenetic
defects of beta-cell functionmaturity-onset diabetes of the young (MODY)6 genetic loci on different
chromosomes have been identified (MODY1 through MODY6)may also occur with mutations in
mitochondrial DNAgenetic defects in insulin action - includes type A insulin resistance,
leprechaunism, Rabson-Mendenhall syndrome, lipoatrophic diabetesdiseases of exocrine pancreas
- includes pancreatitis, trauma, infection, neoplasia, cystic fibrosis,hemochromatosis, fibrocalculous
pancreatopathy, pancreatectomyendocrinopathies - includes acromegaly, aldosteronoma, Cushing
syndrome, glucagonoma, hyperthyroidism, pheochromocytoma, somatostatinomadrug- or
chemical-induced diabetesinfections - congenital rubella, other viruses have been
implicateduncommon forms of immune-mediated diabetesstiff-man syndrome (autoimmune
disorder of central nervous system, usually with high titers of glutamic acid decarboxylase [GAD]
autoantibodies)anti-insulin receptor antibodies (previously called type B insulin resistance)other
genetic syndromes sometimes associated with diabetes - includes Down syndrome, Klinefelter
syndrome, Turner syndrome, Wolfram syndrome, Friedreich ataxia, Huntington disease, Laurence-
Moon-Biedl syndrome, myotonic dystrophy, porphyria, Prader-Willi syndromegestational diabetes
mellitusmaturity-onset diabetes of the young (MODY)rare, autosomal dominant transmission, onset
usually before age 25 years, normal or high insulin levels, mild hyperglycemia6 subtypes based on
6 different gene mutationsMODY 1 - defect in hepatocyte nuclear factor 4-alpha, a transcription
factor; most commonly treated with oral hypoglycemic agent or insulinMODY 2 - defect in
glucokinase, a glycolytic enzyme; most commonly treated with diet and exercise; heterozygous
mutations present with hyperglycemia (but < 50% with diabetes), and usually responsive to
dietMODY 3 - defect in hepatocyte nuclear factor 1-alpha, a transcription factor; most commonly
treated with oral hypoglycemic agent or insulinpatients with MODY 3 have much greater response
to sulfonylurea than response to metformin or response in patients with type 2 diabetes, based on
randomized trial of 36 patients (Lancet 2003 Oct 18;362(9392):1275EBSCOhost Full Text)MODY 4
- defect in insulin promoter factor 1, a transcription factor; most commonly treated with oral
hypoglycemic agent or insulin in heterozygous variant; homozygous form presents in neonates with
pancreatic agenesis and requires insulinMODY 5 - defect in hepatocyte nuclear factor 1-beta, a
transcription factor; most commonly treated with insulinseries of 13 patients with 8 novel hepatocyte
nuclear factor 1-beta mutations can be found in Ann Intern Med 2004 Apr 6;140(7):510EBSCOhost
Full TextMODY 6 - defect in neurogenic differentiation factor 1, a transcription factor also called
beta-cell E-box transactivator 2; most commonly treated with insulinReference - Endocr Rev 2008
May;29(3):254MODY also called monogenic diabetes (International Diabetes Federation [IDF] 2011
PDF)review of diagnosis and management of MODY can be found in BMJ 2011 Oct 19;343:d6044
Epidemiology
Who is most affectedobese and sedentary children and adolescents ≥ 10 years old(2)4%-8% of
children with type 2 diabetes may present at < 10 years old (Expert Rev Cardiovasc Ther 2010
Mar;8(3):393)female predominance(1)Native Americans, Blacks, Hispanics, and Asian-Pacific
Islanders(4)
Incidence/Prevalenceincreasing incidence over time, but ethnic variation and undiagnosed type 2
diabetes make it difficult to determine actual incidence(4)increase in incidence of type 1 diabetes
over 2002-2012 more pronounced in some minority ethnic children and adolescentsbased on
population-based cohort study of 4,900,000 children and adolescents in United States in 2002-
2012overall incidence rate of diabetes type 1 increased from 19.5 per 100,000 in 2002-2003 to 21.7
per 100,000 in 2011-2012annual adjusted rate of increase in incidence4.2% in Hispanic children
and adolescents (p < 0.001 vs. non-Hispanic white children and adolescents)2.2% in non-Hispanic
black children and adolescents1.2% in non-Hispanic white children and adolescentsReference - N
Engl J Med 2017 Apr 13;376(15):1419, editorial can be found in N Engl J Med 2017 Apr
13;376(15):1473incidence per 100,000 children and adolescents based on ethnicity
Incidence per 100,000 in United States:EthnicityAges 1-14 YearsAges 15-19 YearsNon-Hispanic
Caucasian35.6African American22.319.4Hispanic8.917Asian/Pacific Islander11.822.7American
Indian25.322.7

Incidence per 100,000 in Canada:EthnicityChildren < 18 Years

OldCaucasian0.54Aboriginal23.2African/Caribbean7.7Asian1.9
Incidence per 100,000 in United Kingdom:EthnicityChildren < 17 Years
OldCaucasian0.35African3.9South Asian1.25
Reference - Expert Rev Cardiovasc Ther 2010 Mar;8(3):393
Incidence per 100,000 in New Zealand:EthnicityChildren < 15 Years
OldEuropean0.1Maori3.4Pacifica3.4Asian/Middle Eastern/Latin American/African0.6
Reference - Pediatr Diabetes 2012 Jun;13(4):294prevalence of type 2 diabetes in children and
adolescents in United States in 2009based on population-based cross-sectional study of 1,800,000
children and adolescents aged 10-19 years in United States in 2009prevalence of newly diagnosed
type 2 diabetes per 1,000 persons0.46 overall (95% CI 0.43-0.49)0.17 in whites (95% CI 0.15-
0.2)1.06 in blacks (95% CI 0.93-1.22)0.79 in Hispanics (95% CI 0.7-0.88)1.2 in American Indians
(95% CI 0.96-1.51)estimated increase in type 2 diabetes from 2001 to 2009 was 30.5% (95% CI
17.3%-45.1%)Reference - JAMA 2014 May 7;311(17):1778incidence of type 2 diabetes in children
in United States from 2002 to 2003based on population-based SEARCH for Diabetes in Youth Study
of 2,435 children and adolescents < 20 years old with newly diagnosed diabetes in 2002-2003,
including 503 with type 2 diabetesestimated incidence per 100,000 person-years0 at ages 0-4
years0.8 at ages 5-9 years (highest 2.2 per 100,000 person-years in Asian/Pacific Islander
children)8.1 at ages 10-14 years (highest 25.3 per 100,000 person-years in American Indian
children)11.8 at ages 15-19 years (highest 49.4 per 100,000 person-years in American Indian
children)Reference - JAMA 2007 Jun 27;297(24):2716, correction can be found in JAMA 2007 Aug
8;298(6):627, editorial can be found in JAMA 2007 Jun 27;297(24):2760, full-text0.5% of
adolescents aged 12-19 years reported having diabetes in United States national survey 1999-2002,
71% with type 1 and 29% with type 2 diabetes (Arch Pediatr Adolesc Med 2006 May;160(5):523)
Likely risk factorssee also Risk factors for diabetes mellitus type 2obesity(1)up to 50% of obese
children and adolescents have insulin resistance10%-25% have glucose abnormalitiesimpaired
glucose tolerance associated with increased risk for developing type 2 diabetes within 2-3 years in
obese children and adolescentsbased on 2 prospective cohort studies128 obese white children
(mean age 13.5 years) with impaired glucose tolerance at baseline followed for mean 3.9 yearsrisk
factors for type 2 diabetes includedweight gainimpaired glucose tolerancebaseline age, gender,
body mass index, blood pressure, or fasting glucose levels were nonpredictiveReference - Exp Clin
Endocrinol Diabetes 2011 Mar;119(3):172117 obese children and adolescents with oral glucose
tolerance testing at baseline and about 2 years laterrisk factors for type 2 diabetes includedsevere
obesityimpaired glucose toleranceAfrican American heritagefasting glucose, insulin, and C-peptide
were nonpredictiveReference - Diabetes Care 2005 Apr;28(4):902 full-textfamily history of type 2
diabetes in first- or second-degree relatives reported in 74%-100% of children with type 2 diabetes
(Pediatrics 2000 Mar;105(3 Pt 1):671)
Possible risk factorspossible risk factors includeelevated body mass index or hypertension (systolic
blood pressure ≥ 95th percentile) during childhoodbeing born small for gestational age (intrauterine
growth restriction)excessive weight gain and fat disposition after premature or growth-restricted
birthbeing born large for gestational ageexcessive maternal weight gain in pregnancyearly
pubertylow socioeconomic statusadiposity rebound (transient change in body fat composition) < 5.5
years oldintrahepatic fat accumulationsmokingpaternal obesityReference - Curr Diab Rep 2012
Feb;12(1):88, Best Pract Res Clin Endocrinol Metab 2012 Oct;26(5):569, Curr Diab Rep 2012
Feb;12(1):82, Diabetes Care 2011 May;34 Suppl 2:S161maternal factors during fetal development
may contribute to insulin resistance and beta-cell abnormalitiesmaternal obesity and diabetes result
in excess nutrient delivery to fetus which may causebeta-cell hyperplasia and increased fetal
insulinincreased fetal fat depositionmaternal malnutrition, prematurity, and low birth weight result in
reduced nutrient delivery to fetus which may causebeta-call hypoplasia and reduced insulin
productionelevated glucocorticoids and catch-up fat dispositionReference - Curr Diab Rep 2012
Feb;12(1):82less physical activity and more electronic media use reported in children with diabetes
compared to healthy counterpartsbased on case-control study384 children and adolescents aged
10-20 years with diabetes type 1, 90 children with diabetes type 2, and 173 healthy children
assessed for 3-day activity recallchildren with diabetes type 1 or 2 reported lower physical activity
levels than healthy counterparts (p < 0.05)children with type 2 diabetes were 51% less likely to meet
national activity and electronic media use recommendations than children with type 1 diabetes (p =
0.017)lowest activity levels in male patients belonging to minority groupsReference - Pediatrics 2010
Jun;125(6):e1364
Associated conditionscomorbidities associated with type 2 diabetes
includedyslipidemiahypertriglyceridemia in 65% and low high-density lipoprotein cholesterol in 60%
of youths with type 2 diabetesbased on prospective cohort study of 2,096 children aged 0-19 years
with diabetesReference - SEARCH study (Diabetes Care 2006 Aug;29(8):1891 full-text)lipid
abnormalities occur in children and adolescents with type 2 diabetesbased on cross-sectional
study283 children and adolescents aged 10-19 years with type 2 diabetes mellituslipid abnormalities
includetotal cholesterol level > 240 mg/dL (6.2 mmol/L) in 33%low-density lipoprotein cholesterol >
160 mg/dL (4.1 mmol/L) in 24%triglyceride concentration > 150 mg/dL (1.7 mmol/L) in 29%high-
density lipoprotein cholesterol < 40 mg/dL (1 mmol/L) in 44%Reference - J Pediatr 2006
Sep;149(3):314cardiovascular abnormalitieshypertension (systolic or diastolic blood pressure
values ≥ 95 percentile) present in36% of youth with type 2 diabetes within 1.3 years of
diagnosis(3)23.7% of adolescents with type 2 diabetes mellitus in SEARCH for diabetes in youth
study (J Pediatr 2010 Aug;157(2):245.e1)children with type 2 diabetes may have reduced
cardiovascular function, indicated by(1)cardiac hypertrophyincreased aortic pulse wave
velocityadolescents with type 2 diabetes may have left ventricular hypertrophy and reduced exercise
capacitybased on prospective cohort study39 children and adolescents aged 12-19 years with
similar physical activity levels tested by hyperinsulinemic clamp for insulin resistance and measures
of oxygen consumption and cardiac functiontype 2 diabetes in 36%obesity in 33%leanness in
31%adolescents with type 2 diabetes had decreased maximal exercise capacity compared to obese
adolescents (p < 0.04) and lean adolescents (p < 0.0001)blood pressure similar in type 2 diabetes
and obese groups and significantly higher than lean group (p < 0.01)evidence of left ventricular
hypertrophy in 29% of adolescents with type 2 diabetesReference - J Clin Endocrinol Metab 2009
Oct;94(10):3687 full-textpsychosocial/emotional disorders(3, 6)anxiety
disordersdepressiondepression rate may be higher among adolescent boys with type 2 diabetes
than among boys with type 1 diabeteshigher levels of depressed mood in adolescents may be
associated with poor glycemic control and number of emergency department visitsdepressive
symptoms may be seen in 14.8% of adolescents with type 2 diabetes, but reported to be similar to
adolescents without type 2 diabetesbased on prospective cohort study of 704 children and
adolescents aged 10-17 years with type 2 diabetes for < 2 years and body mass index ≥ 85th
percentile who completed Children's Depression Inventory, or Beck Depression Inventory II and
Pediatric Quality of Life surveyReference - Diabetes Care 2011 Oct;34(10):2205 PDFdisordered
eating behaviorserious mental illness including schizophrenia and other thought disordersmetabolic
syndromeacanthosis nigricans (1, 4)nonalcoholic fatty liver disease (3)orthopedic problems such as
slipped capital femoral epiphysis or Blount disease(3)obstructive sleep apnea (3)HIV
infection(6)cancer of liver, pancreas, endometrium, colon/rectum, breast, or
bladder(6)fractures(6)periodontal disease(6)hearing impairment(6)pancreatitis(6)
Etiology and Pathogenesis
Causesmultifactorialgeneticmany gene mutations and polymorphisms have been linked to type 2
diabetesfamily history present in almost 90%Reference -