MacKenzi Hillard May 4 2011 aka What to do with Fasting Labs The Obesity Epidemic The prevalence of obesity in adolescents has tripled since 1980 31 of children are overweight and 17 are obese ID: 686087
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Slide1
Laboratory analysis of the obese child – recommendations and discussion
MacKenzi
Hillard
May 4, 2011Slide2
aka: What to do with “Fasting Labs”Slide3
The Obesity EpidemicThe prevalence of obesity in adolescents has tripled since 1980
31% of children are overweight and 17% are obeseSlide4
The ConcernObesity is associated with numerous medical comorbidities:
Elevated blood pressure
Dyslipidemia
Impaired glucose tolerance / Type 2 DM
Non-alcoholic fatty liver diseaseSlide5
From: Singhal V, Schwenk WF, and Kumar S. Evaluation and management of childhood and adolescent obesity. Mayo Clin Proc 2007; 82(10): 1258-1264.Slide6
Objectives
Discuss the role of the primary care physician to identify obese children with three common comorbidities - altered glucose tolerance, NAFLD and dyslipidemia.
Discuss the appropriate utilization and interpretation of laboratory screening tests and subsequent management.Slide7
Question #1You are seeing an obese 14 year old female patient. Her mother asks you to test her for diabetes because it runs in the family. You order a fasting blood glucose and it is 120. You tell her mother:Slide8
Answers #1
Your daughter’s labs are normal.
Your daughter has impaired glucose tolerance.
Your daughter has diabetes.
Your daughter has prediabetes.Slide9
Altered glucose toleranceInsulin resistance and altered glucose metabolism is a component of the metabolic syndromeSlide10
Altered glucose tolerance
Prediabetes
Impaired fasting glucose
(IFG)
fasting glucose 100-125 mg/
dL
Impaired glucose tolerance (IGT)
plasma glucose after 2 hr oral glucose tolerance test (OGTT) is 140-199 mg/
dL
Type 2 DM
Fasting glucose >126 mg/
dL
plasma glucose after OGTT > 200 mg/
dL
Two random plasma glucose values >200Slide11
Altered glucose tolerance
10-30% of obese children have
prediabetes
45% convert to normal glucose tolerance over 2 years
20% convert to type 2 DM
Goal of screening is to detect these at-risk patients and intervene before disease progressesSlide12
Who should be screened?
The American Diabetes Association recommends obtaining a
fasting plasma glucose
in any obese individual who has 2 additional risk factors ….
Family history
Ethnicity: African-American, American Indian, Hispanic, Pacific-Islander
Signs of insulin resistance or of conditions associated with insulin resistance:
acanthosis
, PCOS, SGA, HTN,
dyslipidemia
Mother with GDM in pregnancy
… beginning at age 10 or at the onset of puberty and repeating every 3 yearsSlide13
Fasting plasma glucoseEasy to obtain, easily reproducible, relatively inexpensive
Problem: only identifies a portion of patients who are prediabetic.Slide14
Impaired fasting glucose vs. impaired glucose tolerance
FG alone only has a 21% sensitivity to detect IGT
Tsai
J
et al
, Horm Res Paediatr
2010Slide15
Who should get an oral glucose tolerance test?
OGTT is not recommended for a first line screen
Inconvenient
Not readily reproducible
No specific recommendations exist for when to order an OGTT in an obese child
Consider when fasting glucose is normal and you have a high suspicion for a pre-diabetic state (PCOS, strong family history)Slide16
Hemoglobin A1creflects average blood sugar over the previous 3 monthsSlide17
What about using HbA1c as a screening test?
HbA1C has been looked at as a predictor of impaired glucose tolerance
Cut-off of 5.5% has the best combined sensitivity (85.7%) and specificity (56.9%) for IGT
However, low specificity means that other tests will still be indicated to make a diagnosis so not currently recommended as a screen Slide18
Screening for hyperinsulinemia
Fasting insulin levels have been historically used as a marker of insulin resistanceSlide19
Screening for hyperinsulinemia
A few problems ….
Insulin levels normally rise in puberty while insulin sensitivity decreases to facilitate rapid growth
Fasting insulin levels
do not
correlate well with the euglycemic hyperinsulinemic clamp measure of insulin sensitivity (gold standard)
Correlation of 0.42 at age 13 and 0.29 at age 15Slide20
Screening for hyperinsulinemia
Fasting insulin levels should not be routinely obtained and applied to clinical decision makingSlide21
Management of altered glucose tolerance by the PCP
Prediabetes
: goal of treatment is to slow the progression to diabetes
1.
lifestyle modification:
Weight loss + physical activitySlide22
Management of altered glucose tolerance by the PCP
2.
metformin
has been shown to slow the progression from
prediabetes
-> diabetes in adults
may initiate treatment at diagnosis of altered glucose tolerance or wait 3-6 months to see effects of lifestyle changesSlide23
Risk of Diabetes
Diabetes Prevention Program Research Group. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study.
The Lancet
2009.
374
(9702): 1677-1686Slide24
Management
T2 DM
lifestyle modification
metformin
Consider referral to endocrinology
(especially if HbA1c is >8)
insulin if neededSlide25
Summary
The ADA recommends obtaining a fasting blood glucose as an initial screen.
This test will miss some patients who might have IGT on an OGTT –> obtain an OGTT if you have additional concerns.
Fasting insulin levels and HbA1C are not recommended as screening tests.
Advise lifestyle changes and consider starting
metformin
in obese children with
prediabetes
.Slide26
Question #2You obtain a hepatic panel on a 15 year old obese male patient. His ALT measures 110 u/L and his AST is 100 u/L. He has no previous labs on record and is asymptomatic. There is no family history of liver disease. You advise which of the following?Slide27
Answer #2
Counsel on lifestyle changes and repeat a hepatic panel with other labs in 2 years.
Counsel on lifestyle changes and repeat labs in 3 months.
Obtain a liver ultrasound.
Refer immediately to GI.Slide28
Non-alcoholic fatty liver disease
The most common liver disease among adolescents in North America
Autopsies suggest a prevalence of 9.8% in American children, 38% of obese children
Male predominance (2:1)
More prevalent in Hispanics and Asians, less prevalent in African-AmericansSlide29
Non-alcoholic fatty liver diseaseStrongly associated with other components of the metabolic syndrome, particularly insulin resistance and increased visceral fatSlide30
Non-alcoholic fatty liver disease
A
Steatosis
- triglyceride deposition in
hepatocytes
(reversible)
B
Steatohepatitis
(NASH)
- inflammation and fibrosis (may be irreversible)
Increased fibrosis, cirrhosis
Characterized by accumulation of triglycerides in hepatocytes
From : Takahashi Y, Fuckusato T. Pediatric non-alcoholic fatty liver disease: emphasis on histology.
World Journal of Histology
2010. 16(42). 5280-5285Slide31
NAFLD – what’s the risk
Children with NAFL have a 13.8 times greater risk of dying or requiring liver transplant in 20 years after diagnosis
Children diagnosed with NAFLD
From: Fieldstein AE et al. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years.
Gut
2009 58: 1538-1544Slide32
NAFLD – clinical signs
Initial presentation:
Asymptomatic with ALTSlide33
NAFLD – screening
Recommendation is to measure
transaminases
on all obese children, especially those with other components of metabolic syndrome
No consistent recommendations for timing of initiation or frequency of screening
ALT > 2x normal that persists for > 3 months suggests the diagnosisSlide34
NAFLD – a diagnosis of exclusion
Need to rule-out
hepatitis B and C
autoimmune hepatitisWilson’s disease
alpha-1 antitrypsin deficiency
drug-induced liver injurySlide35
NAFLD – interpreting results
Consider checking a
ceruloplasmin
in any patient with elevated
transaminases
and screen for
autoimmune hepatitis in females with a family history
before waiting for repeat labs.
Obtain a full CMP with PT/INR to evaluate liver function when labs are repeatedSlide36
NAFLD – interpreting results
Transaminase
measurement is the only acceptable screening test, but realize …
not extremely sensitive - 23% of patients with evidence of NAFLD on biopsy have normal ALT
Liver biopsy is gold standard of diagnosis to assess the degree of
steatosis
, inflammation and/or fibrosis
Expensive, invasive – not recommended for routine screeningSlide37
NAFLD – further evaluation
Ultrasound may reveal an enlarged,
echogenic
liver but is not always needed
Patients with suspected NAFLD should be referred to and followed by GI Slide38
NAFLD - management
Address the metabolic
comorbidities
OBESITY : Diet/Lifestyle modification
Moderate weight loss can decrease the
transaminitis
and inflammation but does not consistently reverse fibrosis
INSULIN RESISTANCE:
Metformin
may help to reduce
transaminitis
?
ANTIOXIDANT THERAPY – Vitamin ESlide39
SummaryNAFLD is common and often asymptomatic.All obese patients should have transaminases measured as a screening test.
If initial screen is abnormal, r/o Wilson’s and autoimmune hepatitis in at risk patients, then repeat a CMP with INR in 3 months.
Recommend lifestyle changes, consider GI referral.Slide40
Question #3 Which is the most common lipid abnormality in obese children …Slide41
Answer #3
Elevated total cholesterol
Elevated LDL
Low HDL
Elevated triglyceridesSlide42
Dyslipidemia
Elevated LDL and triglycerides and a low HDL increase risk for CVD
Atherosclerosis begins
in childhood
42% of obese youth
24% elevated triglycerides
20% have low HDL
14.2 % have high LDLSlide43
Dyslipidemia
Metabolic syndrome
HDL < 50 (women)
or <40 (men)
Triglycerides > 150Slide44
Dyslipidemia – AAP screening recommendations
Screen pediatric patients with a fasting lipid profile who have any of the following risk factors:
family history of
dyslipidemia
overweight or obesity
hypertension
diabetes
mellitus
cigarette smoking
Begin screening between ages 2 and 10, repeat every 3-5 yearsSlide45
Dyspidemia - management
Low HDL or elevated triglycerides
-> weight management and increased physical activity
Consider pharmacologic treatment for
LDL >190 (or >160 if multiple risk factors)
with initial goal <160
Statins
Fish Oil
Plant SterolsSlide46
Conclusions
The initial laboratory evaluation of the obese child who is developmentally normal and growing (too) well should include a fasting glucose, a hepatic panel, and a lipid panel.
There is a room for a great deal of inter-provider variability in the interpretation of these results and selection of subsequent tests.
Lifestyle changes are the answer to just about everything.Slide47
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NJ, Francis CS,
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Diabetes Prevention Program Research Group. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study.
The Lancet
2009.
374
(9702). 1677-1686.
Executive Summary – Standards of medical care in diabetes – 2009.
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Fieldstein AE et al. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut 2009 58: 1538-1544.
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Fuckusato
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