Obesity and Hyperinsulinemia in HIV Positive Children

1
Obesity and Hyperinsulinemia in HIV Positive
Children

• Robert M. Lawrence, MD
• 16th Annual HIV Conference
• Florida/Caribbean AETC

2
(No Transcript)
3
(No Transcript)
4
Disclosure of Financial Relationships

• This speaker has no significant financial
  relationships with commercial entities to
  disclose.

The Florida/Caribbean AETC is supported in large
part by the Health Resources and Services
Administration (HRSA), HIV/AIDS Bureau (HAB).
DHHS-HAB Grant No. 2 H4A HA 00049-04-00.
This slide set has been peer-reviewed to ensure
that there are no conflicts of interest
represented in the presentation.
5
(No Transcript)
6
Definition

• To determine childhood obesity we need to
• calculate the Body Mass Index (BMI)
• BMI Weight (kg)
• Height x Height (m2)
• or
• Weight (pounds) x 703
• Height x Height (inches2)

7
DEFINITIONS

• Based on Body Mass Index (BMI)
• Children
• At risk for overweight (previously overweight)
• BMI ? 85th percentile and for age and sex.
• Overweight (previously obese)
• BMI ? 95th percentile for age and sex.

8


9
Insulin Resistance

• No consensus on definition of insulin resistance.
• Normal range for assays vary between different
  institutions, therefore it is difficult to arrive
  at a consensus for a cutoff.
• Gold standard euglycemic hyperinsulinemic clamp
• More practical measures
• - Elevated fasting insulin (20 µIU/ml)
• - Indices that combine fasting insulin and
  glucose have been shown to correlate well with
  gold standard
• Fasting glucose to insulin ratio 4.
• QUICKI (1/log fasting insulin log fasting
  glucose)
• Keep in mind that a normal fasting insulin does
  not rule out
• insulin resistance and in a high-risk child it
  may indicate
• ?-cell failure.

10
ADA Diagnostic Criteriafor Pre-Diabetes and Type
2 Diabetes

• Pre-diabetes
• -Impaired Fasting Glucose (IFG) 100 and mg/dl
• -Impaired Glucose Tolerance (IGT) 2-hour blood
  glucose during OGTT 140 and
• Diabetes
• -Fasting blood glucose 126 mg/dl
• -2-hour blood glucose during OGTT 200 mg/dl
• -Random blood glucose 200 mg/dl associated with
• symptoms of polydypsia, polyuria and/or weight
  loss.
• Note HgbA1C is not a diagnostic criteria for
  diabetes

11
INSULIN RESISTANCE
Genetics
Obesity
Hyperinsulinemia Normal Glucose
Tolerance (Compensated Insulin Resistance)
Glucotoxicity Lipotoxicity
?-cell failure
Impaired Fasting Glucose/ Impaired Glucose
Tolerance (PRE-DIABETES)
TYPE 2 DIABETES
M. Huerta, MD
12
Atherosclerosis Begins in Childhood

• The Pathological Determinants of Atherosclerosis
  in Youth Study was the first one to show that
  fatty streaks were present in the intima of large
  arteries in adolescents.
• Using high resolution vascular ultrasound
  techniques, changes in carotid intima-media
  thickness have been shown in children with type 1
  diabetes and hypercholesterolemia compared with
  controls.

13
Cardiovascular Risk in Childhood Obesity

• The Bogalusa Heart Study showed that 60 of
  overweight children (BMI 95th percentile for
  age and sex) have at least one cardiovascular
  risk factor such as
• - hyperinsulinemia
• - hypertension
• - hyperlipidemia
• Berenson GS, et. al. Association between
  multiple cardiovascular risk factors and
  atherosclerosis in children and young adults.
  New England Journal of Medicine 1998 338
  1650-1656.

14
Effect of Childhood Cardiovascular Risk Markers
in Adulthood

• Cardiovascular risk factors present during
  childhood, such as elevated LDL-C, elevated
  systolic blood pressure and higher BMI are
  associated with
• - increased carotid intima media thickness
• - increased risk for CVD
• - increased risk for all-cause and CVD-related
  mortality in adulthood.

Gunnell D. Am J Clin Nutr 1998 67 1111-1118
15
Prevalence of Overweight Children in US
Hedley et al, NHANES JAMA 2912847, 2004
16
Association between BMI in
Childhood and Adulthood

• Bogalusa Heart Study
• 2617 subjects (2-17 years old) re-examined at
  18-37 years old with a mean follow-up of 17 years
• Of 186 overweight children (BMI 95th) 77
  (144) were obese as adults.
• Only 7 of 1317 normal weight children became
  obese adults.

Freedman DS et al, Pediatrics 2001, 108712-718.
17
Why our Children Obese?

• Their parents are obese.
• Fast Food consumption has increased.
• Increased consumption of junk food and soft
  drinks in schools.
• Less physical activity.
• Increased TV viewing and computer time.
• Food advertising directed at children.

18
Pediatric Type 2 Diabetes

• Florida Among 682 patients with newly diagnosed
  diabetes seen at 3 university diabetes centers
  the proportion of type 2 diabetes increased from
  8.7 in 1994 to 19 in 1998.
• Cincinnati, OH from 1000 children 0-19 years of
  age with new onset diabetes
• - 1982-1992 2-4 had type 2 diabetes
• - 1994 16 had type 2 diabetes
• (33 of those between 10-19 years of age)

Macaluso CJ et al, Pub Health Rep.
2002117373-9. Pinhas-Hamiel et al, J Pediatr
128608-15.
19
Pediatric Type 2 Diabetes

• More prevalent in minority children including
  African-Americans, Hispanic-Americans and
  Native-Americans.
• It represents up to 46 of all new cases of
  pediatric diabetes in communities with large
  minority populations.

20
Prevalence of Pre-Diabetes in Children and
Adolescents

• In children and adolescents with BMI 95th
  percentile
• Impaired Glucose Tolerance (pre-diabetes) was
  found in
• - 25 of obese children age 4-10y
• - 21 of obese adolescents age 11-18y
• Asymptomatic type 2 diabetes was found in 4 of
  obese adolescents
• Fasting glucose failed to identify those children
  with impaired glucose tolerance.
• Sinha R, et al. New England Journal of
  Medicine 2002 346 802-810.

21
Prevalence of Pre-Diabetes in Children and
Adolescents

• In obese Hispanic adolescents with BMI 85th
  percentile and a family history of type 2
  diabetes, 28 have IGT based on 2-hour glucose
  by OGTT.
• (Goran M, JCEM 2003 88 1417-1427)

22
Prevalence of Impaired Fasting Glucose (IFG)

• 1999-2000 NHANES data
• 915 adolescents 12 to 19 years of age
• Overall prevalence of IFG 7
• - Trend for IFG to be more prevalent in boys
  (10) than in girls (4).
• In those with BMI 95th percentile prevalence
  of IFG was 17.8
• - Racial differences
• Mexican Americans 13
• Non-Hispanic whites 7
• Non-Hispanic blacks 4.2

Williams DE. Pediatrics 2005 116 1122-1126.
23
Prevalence of Impaired Fasting Glucose

• In a cohort of 8th Grade Students (50 Hispanic,
  23 AA)
• IFG was found in 40.5 (n1643)
• IGT was found in 2.3 (n1128)
• STOPP-T2D Study Group. Diabetes Care 2006 29
  212-217
• Study in the Princeton School District (n2500)
• IFG was found in 7.5 of students 9-20 years of
  age.
• 0.08 had type 2 diabetes.

Dolan LM. J Pediatrics 2005 146 751-758.
24
Why is it important to identify Impaired Glucose
Tolerance (IGT)?

• Data from adults studies has shown that
• IGT is associated with the development of
  microvascular diabetic complications.
• IGT is associated with 2- to 5-fold increased
  risk for cardiovascular disease and increased
  all-cause and cardiovascular disease-related
  mortality.

25
Pre-diabetes and CV risk factors

• Adolescents with IFG also had
• higher total and LDL-cholesterol
• higher triglycerides
• lower HDL-cholesterol
• higher systolic blood pressure
• Than those with normal fasting glucose.

Williams DE. Pediatrics 2005 116 1122-1126.
26
Can we do anything to break the link?
Childhood Obesity
Atherosclerosis
Type 2 Diabetes
27
What about Obesity in HIV Positive Children?

• Fat Maldistribution and Body Habitus Changes
• Lipodystrophy
• Lipohypertrophy
• Lipoatrophy
• Hyperlipidemia

Guidelines for the Use of Antiretroviral Agents
in Pediatric HIV Infection Supplement III -
Pediatric Adverse Drug Effects, October 26, 2006
28
Lipodystrophy in HIV Children

• Changes in body fat distribution
• This has been reported in 1, 10, 18, 29 and
  33 of HIV-infected children treated with ARVs!!
• This is either loss of subcutaneous fat
  (peripheral fat wasting/lipoatrophy) or
  deposition of fat tissue subcutaneously or in
  visceral stores or a mixture of the two.

29
Lipohypertrophy (central fat accumulation)

• Dorsocervical fat accumulation buffalo hump
• Increased visceral adipose tissue (VAT)
• Increased abdominal girth
• Increased waist-to-hip ratio
• Breast enlargement

30
Definition / Measurementof Lipohypertrophy

• Trunk/arm skinfold ratio 2 standard deviations
  from the mean.
• DEXA scan identified increase in trunk/total fat
  or trunk/limb fat ratio.
• Clinical findings alone.
• MRI or CT measured increase in intra-abdominal
  adipose tissue (IAT) single-slice measurements
  for calculation of total, visceral, or
  subcutaneoustissue (TAT, VAT, or SAT)
• Bioelectric Impedance Analysis (BIA)

31
Proposed Causes of Fat Maldistribution in HIV

• Lipoatrophy PI use and NRTIs (d4T, ddI)
• Very low plasma leptin concentrations
• Low plasma adiponectin levels
• Alterations in mitochrondial function - due to
  NRTIs d4t, ddI, ddC
• Lipohypertrophy insulin resistance, PI use,
  elevated cholesterol or triglycerides

Adverse Drug Events from Guidelines for Pediatric
HIV October 26, 2006
32
Assessment and Monitoringof Lipodystrophy

• No current recommended routine
• Anthropometric measurements waist
  circumference, waist-to-hip ratio, triceps skin
  fold thickness
• Single-slice MRI or CT scan for TAT, VAT and SAT
• Bioelectric Impedance Analysis
• DEXA Scanning

Adverse Drug Events from Guidelines for Pediatric
HIV October 26, 2006
33
Treatment ofFat Maldistribution Syndrome

• Multiple potential causes - ? Multiplepotential
  treatments ?
• Lack of standard definitions of the
  differentabnormalities
• Switching antiretrovirals may help in prevention
  or treatment no studies in children.
• Diet, exercise, insulin-sensitizing medications
  or lipid-lowering agents - there are no studies
  in children

Adverse Drug Events from Guidelines for Pediatric
HIV October 26, 2006
34
Insulin Resistance andHyperglycemia

• Insulin resistance without fasting hyperglycemia
• Asymptomatic fasting hyperglycemia
• New-onset diabetes mellitus
• Exacerbation of pre-existing DM
• All of these have been reported in patients
  treated with ARV therapy.

Adverse Drug Events from Guidelines for Pediatric
HIV October 26, 2006
35
HIV Positive Children

• Insulin resistance and increased free fatty acids
  often occur with fat maldistribution syndromes
  related to PI or d4T containing regimens.
• New onset clinical diabetes rarely occurs in
  children or adolescents treated with PIs.

Adverse Drug Events from Guidelines for Pediatric
HIV October 26, 2006 Arpadi et al, J Acquir
Immune Defic Syndr 2001. 2730-34. Jaquet et al.
AIDS 2000. 142123-28.
36
HIV Positive Children

• HIV-infected children, even without ARVs, have
  demonstrated growth delay and been shown to have
  resistance to IGF-1, GH and insulin.

Geffner ME et al. Pediatr Res, 1993. 3466-72.
37
Recommendations for Monitoring Glucose
Metabolism

• Educate children and families about symptoms of
  diabetes and risk factors for cardiovascular
  disease.
• For children with fat maldistribution or with
  risk factors for type 2 diabetes fasting blood
  glucose measurments oral glucose tolerance
  testing may identify children with fasting
  hyperglycemia or insulin resistance

Adverse Drug Events from Guidelines for Pediatric
HIV October 26, 2006
38
AAP/ADA Recommendations for Screening for Type 2
Diabetes

• Use fasting glucose to screen children with BMI
  85th
• percentile and who have at least 2 of the
  following risk
• factors
• Family history of type 2 diabetes in first or
  second degree relatives.
• High risk ethnicity (American Indian, African
  American, Hispanic, Asian/Pacific Islander)
• Clinical signs of insulin resistance acanthosis,
  hypertension, dyslipidemia or polycystic ovary
  syndrome.
• Start at age 10 years or at onset of puberty ,
  whichever
• occurs first. Repeat test every 2 years.

39
Screening for Type 2 Diabetes

• All children and adolescents with BMI 85th
  percentile should be screened with a fasting
  insulin and glucose.
• Recommend OGTT in
• - children with fasting glucose 100 mg/dL
  but less than 200 mg/dL
• - children with HgbA1C between 5.5 and 7.

40
How does this relate to HIV?

• Infection
• Inflammation mediators and markers
• Lipid metabolism
• Insulin resistance

41
Role of Adipose Tissue in the Development of Type
2 Diabetes

• Adipose tissue is an endocrine organ.
• ADIPOKINES are proteins derived from
• adipocyte and stromal cells of adipose tissue
  that
• have local, paracrine and endocrine functions.
• Adiponectin protective effect against insulin
• resistance and atherogenesis.
• Adiponectin levels are reduced in obesity.

42
Role of Adipose Tissue in the Development of Type
2 Diabetes

• Leptin acts in the hypothalamus to suppress
  appetite and increase energy expenditure. Also
  decreases fat content in liver and skeletal
  muscle, therefore improving insulin sensitivity.
  Leptin levels are elevated in obesity, obesity
  considered a state of leptin resistance.
• Resistin elevated in obesity. Proposed as the
  link between obesity and insulin resistance.

43

ROLE OF INFLAMMATION IN THE DEVELOPMENT OF TYPE 2
DIABETES AND ATHEROSCLEROSIS
ADIPOCYTES

Hepatic Synthesis of Acute Phase Response
Proteins C Reactive Protein, PAI-1, fibrinogen,
etc.
Insulin Resistance
Type 2 Diabetes
Atherosclerosis
44
EARLY EVENTS IN ATHEROGENESIS
Rolling
Adhesion
Migration
monocyte
Blood flow
Endothelial cell in vessel wall
45

Adipokines Modulate the Inflammatory
Cascade Leading to Insulin Resistance and
Atherosclerosis
ADIPOCYTES

Activation of Pro-Inflammatory Cascade
Endothelial Activation
Monocyte Activation
Insulin Resistance
46
Diabetes Prevention Program

• The Diabetes Prevention Program demonstrated
  the feasibility of preventing type 2 diabetes in
  adults with impaired glucose tolerance.
• Intensive lifestyle intervention resulted in
  58 decrease in incidence of type 2 diabetes vs.
  31 with metformin.
• Only 7 weight loss was required to achieve
  this goal.

47
Metformin Therapy in Obese Adolescents
Effect of Metformin 500 mg po BID for 6 months
(n29)
Change in BMI metformin -1.3 vs. placebo
2.3
Freemark M. Pharmacologic Approaches to the
Prevention of Type 2 Diabetes in High Risk
Pediatric Patients. J Clin Endocrinol Metab
2003 88 3-13
48
Metformin Plus Diet in Obese Adolescents

• Data are means (SE). pt-test.

Kay JP et. al. Beneficial effects of
metformin in normoglycemic morbidly obese
adolescents. Metabolism 2001 50 1457-1461.
49
Metformin Therapy for Insulin Resistance

• Randomized crossover clinical trial of metformin
  1000 mg po BID
• vs. placebo for 6 months in 22 adolescents with
  insulin resistance
• defined by FGIR 4.5 or presence of acanthosis.
• Variable Treatment Effect p-value
• Weight (kg) -4.35 0.02
• BMI (kg/m2) -1.26 0.002
• BMI z-score
  -0.12 0.005
• Fasting insulin -2.2 0.011
• Fasting glucose -0.2 0.048
• Insulin sensitivity (Si)
  0.17 0.506
• Percentage of body fat (DEXA) -0.67
  0.062

50
Effect of Metformin on BMI z-score
51
Effect of Metformin on Insulin Sensitivity
52
Metformin Therapy for Pre-Diabetes

• Not enough efficacy data in children and
  adolescents.
• Use only for children with pre-diabetes after a
  3- to 6-month trial of lifestyle changes.
• Do OGTT before using for treatment of insulin
  resistance or weight loss.
• Dose
• -Metformin 500 mg BID x 2 weeks, then 850 mg
  BID.
• -Glucophage XR 500 mg po for 1 week, then
• 1000 mg po for 1 week, then 1500 mg po.
• Duration 6-12 months while implementing
  lifestyle changes.

53
Metformin Therapy for Pre-Diabetes

• Approved for use in children 10 years of age.
• Do not use if liver enzymes 3 times the upper
  limit of normal or kidney failure.
• Most common side effects (25-50 of patients)
  gastrointestinal (nausea or diarrhea), usually
  transient.
• Must take metformin after meals to increase
  absorption and minimize side effects.

54
Six-Month Clinical Trial Comparing the effect of
Metformin vs. Lifestyle Modification on the risk
for Type 2 Diabetes and Atherosclerosis in Obese
Children
55
Criteria for Enrollment

• Children 10-18 years of age
• BMI 85th percentile
• Healthy except for mild allergic rhinitis or
  asthma
• Not using chronic medications other than
  non-steroidal medications for allergic rhinitis
  or asthma.

56
Prevention of Pediatric Type 2 Diabetes

• Studies to Treat or Prevent Pediatric Type 2
  Diabetes (STOPP-T2D)
• Comparing the effect of
• - metformin alone vs.
• - metformin plus rosiglitazone vs.
• - metformin plus lifesytle modification
• on the prevention of type 2 diabetes in
• overweight children.

57
Obesity and Hyperinsulinemia inHIV Positive
Children and Adolescents

• Watch out for these problems
• Establish clear definitions and criteria for the
  different syndromes or conditions.
• Develop studies to evaluate and treat these
  conditions in HIV positive children and
  adolescents.
• Involve your pediatric endocrinologists.

58
(No Transcript)
59
(No Transcript)
60
(No Transcript)
61
(No Transcript)
62
(No Transcript)
63
Diagnostic Criteria

• Normal Borderline
  Elevated
• Total ? 200
• Cholesterol
• (mg/dL)
• LDL
• Cholesterol
• (mg/dL)
• HDL- 40 35-39
• Cholesterol
• (mg/dL)
• Triglycerides 200
• (mg/dL)

64
Hypertension

• Measure blood pressure manually with a cuff of
  appropriate size.
• Use tables to determine SBP and DBP percentiles
  according to height, age and gender.
• Identify those with
• Borderline hypertension SBP or DBP 90th and
  
• Hypertension SBP or DBP 95th percentile.

65
Metabolic Syndrome

• NHANES definition
• 3 or more of the following criteria
• Fasting triglycerides 100 mg/dL
• HDL
• Fasting glucose 110 mg/dL
• Waist circumference 75th percentile for age and
  gender
• SBP 90th percentile for age, gender and height

De Ferranti SD, et al. Circulation 2004
1102494-2497.
66
Metabolic Syndrome- NHANES III

• From 1960 adolescents 12 to 19 years old
• Two thirds (63) had at least one metabolic
  abnormality
• 1 in 10 had Metabolic Syndrome
• Among overweight adolescents (BMI 85th
  percentile) One third (31.2) had metabolic
  syndrome
• De Ferranti SD, et al. Circulation 2004
  1102494-2497.

67
Childhood Obesity Treatment Programs

• Dr. Epsteins program Buffalo, NY
• Subjects
• Children 6-12 years old
• - Diet Traffic Light Diet providing 900-1200
  calories per day.
• - Weekly family treatment sessions with a
  counselor for 8-16 weeks, followed by monthly
  meetings for 6-12 months
• Plus participation in separate child and
  parent group sessions.
• Results
• Decrease of 10-20 in percent overweight at
  the end of intervention.
• Decrease of 8-15 in percent overweight
  maintained at 5-year-and10-year- follow-up.

Epstein LH. Health Pscyhology 1994 13373-383.
68
Effect of Baseline BMI Percentile on Percent
change in BMI z-score

• At 6 months
• For all subjects (66/300) - 4.4 5
• Subjects with BMI
• - 8.09 6.75
• vs.
• Subjects with BMI ? 99th percentile
• - 3.07 3.8.
• (p0.0012)

69
Progression from Pre-Diabetes to Diabetes in
Adults

• - Rate of conversion from pre-diabetes to type 2
  diabetes is 7 per year.
• - Transition is a gradual phenomenon that occurs
  over
• 5-10 years
• - An International Diabetes Federation consensus
  workshop concluded that more than 60 of people
  who developed diabetes had either IGT or IFG
  within the 5-year period preceding diagnosis of
  diabetes.
• - In Dutch adults, 38 of those with IFG and
  32.4 of those with IGT develop diabetes over a
  6-year period.

70
Progression from Pre-Diabetes to Diabetes in
Adolescents

• 117 obese children and adolescents who had OGTT a
  baseline and 2 years later
• At baseline 84 had NGT and 33 had IGT
• After 2 years
• 8 IGT subjects developed T2D (24.2)
• 15 IGT subjects reverted to NGT (45.5)
• 10 IGT subjects remained IGT (30.3)
• Best predictors of development of T2D
• Severe obesity (BMI 97th percentile) and
  persistent weight gain
• African-American race

Weiss R. et al. Diabetes Care 2005 28902-909
71
Diagnostic Criteria

• Normal Borderline
  Elevated
• Total
• Cholesterol
• LDL
• Cholesterol
• HDL- 40 35-39
• Cholesterol
• Triglycerides 200

72
Bordeline LDL

• LDL between 110 and 129 mg/dL
• Discuss cardiovascular risk factors
• Begin Step-One Diet (saturated fat calories, total cholesterol
• Other dietary changes
• - increase soluble fiber consumption (10-25
  grs/day or age plus 5 grs/day)
• - encourage intake of plant sterols and
  stanols (e.g. Benachol margarine)
• Weight reduction if overweight
• Increase physical activity
• Reevaluate status in 1 year

73
Elevated LDL

• LDL 130 mg/dL
• Evaluate secondary causes hypothyroidism,
  nephrotic syndrome
• Evaluate for familial disorders screen family
  members
• Begin Step-Two diet (saturated fat calories, total cholesterol should be done in consultation with a registered
  dietitian.
• Effect of diet on LDL-C variable, may
  decrease from 8 to 24.

74
Pharmacologic Intervention

• Consider pharmacologic intervention if after
  3 months of dietary intervention, LDL remains
  elevated
• LDL 190, or
• LDL 160 in children with strong family
  history of premature CAD (males
• or at least 2 cardiovascular risk factors
• - low HDL
• - smoking
• - obesity
• - hypertension
• - diabetes

75
Pharmacologic Therapy

• Statins (HMG CoA reductase inhibitors)
• Mechanism of action inhibit cholesterol
  synthesis in the liver. Reduce LDL-C by 21 to
  45.
• - Several studies have now shown the safety
  and efficacy of statin therapy in children and
  adolescents as young as 4 years of age.
• - use in children ? 10 years of age may use
  at younger age in familial hypercholesterolemia.
• - monitor liver functions tests at baseline
  and every 3 months
• - discontinue if muscle pain occurs
• - consider oral contraceptive use in sexually
  active adolescent females

76
Pharmacologic Therapy

• Ezetimibe (Zetia)
• Mechanism of Action Prevents absorption of
• cholesterol and plant sterols at the brush border
  of the
• small intestine.
• Decreases LDL-C by 18 in adults.
• Recommended as adjunctive to statin therapy in
  order to avoid using higher doses of statins
  which may be associated with higher incidence of
  side effects.

77
Low HDL-Cholesterol

• Diet low in saturated fats
• Increase consumption of healthy fats (fish,
  almonds, avocado)
• Increase physical activity
• Weight reduction
• Avoid smoking

78
Treatment of Elevated Triglycerides

• Weight reduction
• Increase physical activity.
• Dietary interventions
• - decrease consumption of fat and simple
  sugars
• - increase intake of omega-3 fatty acids
  (fish oil and flaxseed oil)
• Maximize glycemic control in patients with
  diabetes.

79
Treatment of Elevated Triglycerides

• Consider pharmacologic therapy if triglycerides
  400 mg/dL after 3 months of dietary intervention.
  Concern about risk to develop pancreatitis.
• Usually requires pharmacologic therapy and a very
  low fat diet (

80
Pharmacologic Treatment

• Fibric Acid derivatives
• Gemfibrozil, fenofibrate and clofibrate
• Niacin
• High-dose statins

81
Criteria for Referral to Pediatric Endocrine
Lipid/Type 2 Diabetes Clinic

• Pre-diabetes
• IGT 2-hour blood sugar in OGTT 140mg/dL and 200 mg/dL.
• IFG Fasting blood sugar 100 and (if asymptomatic, please obtain OGTT prior to
  referral to further evaluate for type 2 diabetes)
  
• If HgbA1C 5.5 and asymptomatic, please obtain an OGTT to determine
  glucose tolerance.

82
Criteria for Referral to Pediatric Endocrine
Lipid/Type 2 Diabetes Clinic

• 2) Lipid disorders that require pharmacologic
  therapy
• - Familial hypercholesterolemia
• - LDL 160
• - Triglycerides 400
• 3) Other lipid abnormalities that will benefit
  from dietary intervention
• - LDL 130
• - Triglycerides 200 and
• - HDL

83
Criteria for Referral to Pediatric Endocrine
Lipid/Type 2 Diabetes Clinic

• Patient with diabetes diagnosed by ADA criteria
  will
• be seen in new onset type 2 diabetes clinic
• - Symptomatic with blood sugar 200 mg/dL.
• - 2-hour blood sugar in OGTT 200 mg/dL
• - Fasting blood sugar 126 mg/dL in at least 2
  separate occasions.
• For those with HgbA1C 7 who do not meet any
• of the above criteria, please obtain OGTT prior
  to
• referral for complete evaluation of glucose
  tolerance .