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The insulin resistance syndrome, pre diabetes and obesity Shlomit Shalitin Institute for Endocrinology and Diabetes, Schneider Children s Medical Center of Israel ... – PowerPoint PPT presentation

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Title: Objective:


1
The insulin resistance syndrome, pre diabetes
and obesity Shlomit Shalitin Institute for
Endocrinology and Diabetes, Schneider Childrens
Medical Center of Israel Petah Tiqva, and
Sackler Faculty of Medicine, Tel Aviv University,
Tel Aviv, Israel
2
Prevalence of Childhood Obesity
  • The prevalence of obesity in adolescence in the
    USA is 10-25
  • Obesity prevalence in the USA among adolescents
    increased by 20 in the last decade

3
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4
Risks of Obesity
  • Sudden death is more common in those who are
    naturally fat than in the lean Hipocrates
  • BMIs in excess of 28 kg/m² are associated with a
    3- 4-fold increase in risk of hypertension,
    dyslipidemia, insulin resistance (IR) and type 2
    diabetes.

5
Global Projections for the DiabetesEpidemic
2003-2025 (millions)
38.2 44.2 16
Europe
North America
Asia
25.0 39.7 59
81.8 156.1 91
Middle East
18.2 35.9 97
Africa
13.6 26.9 98
South Central America
10.4 19.7 88
Oceania
1.1 1.7 59
WORLD 2003 189 million 2025 324
million Increase 72
6
  • Type 2 diabetes mellitus in the young population
  • The prevalence of type 2 diabetes in the young
  • population is increasing throughout the world
  • wherever childhood obesity is becoming more
  • prevalent
  • The risk of type 2 diabetes increases with the
  • degree and duration of obesity and with a
  • more central distribution of
  • body fat.

7
Genetics and Environment in obesity IR and type
2 diabetes
8
Insulin resistance (IR)
  • IR is defined as an impaired ability of plasma
    insulin at usual concentrations to adequately
    promote peripheral glucose disposal, suppress
    hepatic glucose, and inhibit VLDL output.
  • IR can be inferred on clinical evidence and
    confirmed by insulin and glucose measurements
    made by fasting insulin/glucose screening, OGTT,
    and insulin/glucose clamp studies.

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10
The metabolic syndrome
  • Diagnosis is made if 3 of the following
    criteria are met
  • Obesity (BMI z score 2, adjusted for age
    gender).
  • Hypertension (values gt95th percentile for age
    gender).
  • Dyslipidemia (triglyceride gt95th percentile,
    HDL
  • cholesterollt 5th percentile, adjusted for age
    gender).
  • Insulin resistance, IGT or type 2 diabetes.
  • Hepatic steatosis
  • Hyperandrogenism /PCO
  • Acanthosis nigricans, striae
  • Pseudoacromegaly, low IGFBP-1
  • Increased CRP, TNFa levels

11
NEJM June 3 2004
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13
CLINICAL STUDY Type 2 diabetes and
impaired glucose tolerance in European children
and adolescents with obesity-a problem that is no
longer restricted to minority groups Wiegand S
et al, Paediatric Endocrinology, Charit?
Children's Hospital Humboldt University Berlin
Germany Eur J Endocrinol 2004
14
Insulin resistance and impaired glucose
tolerance in obese children and adolescents
referred to a tertiary care center in Israel S
Shalitin, M Abrahami, P Lilos, M Phillip
  • Aim To establish the prevalence of IR and IGT and
    their determinants in obese children and
    adolescents.
  • Methods The group study included 234 patients
    (BMI 95th percentile for age sex) 22
    patients (BMI 85th-95th percentile for age
    sex) aged 5-22 ys who had been referred between
    1997-2003.
  • Fasting blood samples were obtained for
    evaluation of glucose, insulin and lipid profile.
  • Estimates of insulin resistance (HOMA-IR),
    insulin sensitivity (QUICKI, GF/IF) and ß- cell
    function (HOMAB) were derived from fasting
    measurements.
  • An OGTT was performed in 192 patients to
    determine the presence of IGT.

15
Clinical characteristics of obese children and
adolescents
Total (n256) n () Girls )n147) n () Boys (n109) n () Characteristics
54 (21) 81 (31.6) 9 (3.5) 37 (25.2) 42 (28.6) 7 (4.8) 17 (15.6) 39 (35.8) 2 (1.8) Family history of type 2 diabetes or gestational diabetes (GDM) Diabetes in Parents Diabetes is 2nd degree relative (s) GDM
145 (56.6) 9 (62.6) 53 (48.6) Acanthosis nigricans
Obesity Complications
18 (7) 129 (50.3) 10 (3.9) 5 (1.9) 16 (6.3) 42 (32.8) 3 (1.2) 9 (6.1) 72 (49) 4 (2.7) 5 (3.4) 5 (3.4) 42 (32.8) 2 (1.4) 9 (8.3) 57 (52) 6 (5.5) 11 (10.1) 1 (0.9) Hypertension Dyslipidemia Fatty liver Pseudotumor cerebri Sleep apnea Hyperandrogenism/PCO Depression
16
Clinical laboratory characteristics of obese
children and adolescents
Girls (n147) Mean SD Boys (n109) Mean SD Characteristics
13.8 3.7 13.0 3.3 Age (years)
32.7 7.0 32.2 5.5 BMI (kg/m²)
3.2 1.4 3.5 1.4 BMI SDS
176.8 36 169.7 30.5 Total cholesterol (mg/dL)
104 27.9 103.6 29.6 LDL- cholesterol (mg/dL)
45.4 11.1 42.7 9.3 HDL- cholesterol (mg/dL)
130.3 61 122.4 61 Triglycerides (mg/dL)
17
Clinical laboratory characteristics of obese
children and adolescents (cont.)
Normal range Mean SD Girls (n147) Mean SD Boys (n109) Mean SD Characteristics
60-100 85.2 8.8 87.0 9.4 Glucose fasting (mg/dL)
lt20 21.0 16.0 21.3 20.8 Insulin fasting (µU/mL)
lt 140 116.8 27 109.1 24.3 Glucose 120' (on OGTT) (mg/dL)
134.4 96.6 89 74.7 Insulin 120' (on OGTT) (µU/mL)
lt5.8 5.5 0.3 5.5 0.4 HbA1C ()
lt2.0 4.5 4.4 4.8 5.3 HOMA-IR
gt0.339 0.319 0.029 0.322 0.033 QUICKI
5.9 4.8 6.8 4.8 GF/IF
378.2 317.3 330.2 281.5 HOMA- B
18
Characteristics of obese children and adolescents
with normal or impaired glucose tolerance
p Value Impaired glucose tolerance (n26) Normal glucose tolerance (n165) Characteristics
NS 10 16 67 98 GenderBoysGirls
NS 14.0 2.8 13.65 3.47 Age (years)
NS 33.9 5.3 32.6 6.7 BMI
NS 3.48 1.27 3.28 1.46 BMI-SDS
lt0.05 89.2 10.6 85.9 6.5 Fasting glucose (mg/dL)
NS 23.2 16.2 19.4 15.0 Insulin fasting (µU/mL)
lt0.001 210.8 128.1 101.2 74.03 Insulin 120' (in OGTT) (µU/mL)
19
Characteristics of obese children and adolescents
with normal or impaired glucose tolerance
p Value Impaired glucose tolerance (n26) Normal glucose tolerance (n165) Characteristics
NS 5.4 5.0 4.1 3.4 HOMA-IR
0.062 4.9 2.1 6.7 5.0 GF/IF
lt0.05 0.309 0.022 0.323 0.031 QUICKI
NS 333.5 174.7 332.9 300.4 HOMA- B
NS 181.9 29.6 172.3 34.1 Total Cholesterol (mg/dL)
NS 103.6 23.9 105.2 29.7 LDL- cholesterol (mg/dL)
NS 46.6 13.3 44.5 10.1 HDL- cholesterol (mg/dL)
0.002 156.9 68.9 117.4 53.1 Triglycerides (mg/dL)
20
Results
  • Insulin resistance was detected in 81.2 of the
    patients, IGT in 13.5, and silent diabetes in
    one adolescent girl.
  • GF/IF QUICKI decreased significantly during
    puberty (plt0.005).
  • Insulin resistance insulin sensitivity indexes
    were not associated with ethnicity, presence of
    acanthosis nigricans or type 2 diabetes in
    family.
  • Only 2 patients with IGT also had impaired
    fasting glucose.

21
Conclusions
  • Insulin resistance is highly prevalent in obese
    children and adolescents.
  • Neither fasting blood glucose or insulin levels
    nor HOMA-IR or HOMA-B are effective in the
    screening of IGT.
  • As there are no predictive cut-point values of
    insulin resistance or insulin sensitivity indexes
    for IGT, an OGTT is required in all subjects at
    high risk.
  • Improving insulin resistance may be crucial in
    the prevention of both type 2 diabetes and
    premature cardiovascular disease in this at-risk
    population.

22
ADA recommendations for screening for type 2
diabetes in youth
  • BMIgt 85th percentile for age and gender
  • Any 2 or more of the following risk factors
  • Family history of type 2 diabetes in first or
  • second-degree relative
  • Member of a high risk ethnicity
  • Signs of insulin resistance acanthosis
  • nigricans, hypertension, dyslipidemia, or
    PCOs.
  • Screening should include a fasting plasma glucose
    (Begin testing at 10 years old or at onset of
    puberty).

23
  • As IR is the precursor of type 2 diabetes, and IR
    begins in childhood, then the earlier an
    intervention can be initiated in the natural
    history of the disease, the more effective it
    will be to prevent or delay progression to
    diabetes.
  • Modest weight reductions of 5-10 significantly
    decrease the risk of complications of IR.

24
Prevention and treatment
  • Family based behavioral interventions for obese
    children have been associated with reductions in
    cholesterol, increases in HDL, and reductions in
    IR. Pasquali R, JCEM 1989.
  • There are reports that with appropriate changes
    in lifestyle (diet physical activity) and
    weight reduction progression from IGT to diabetes
    can be delayed or prevented. Tuomilehro J et al.
    N Engl J Med, 2001.

25
Prevention and treatment
  • The STOP-NIDDM trial has shown that
    pharmacological
  • intervention with Acarbose in adult patients with
    IGT
  • can reduce the progression to type 2 diabetes by
    25.
  • This trial also demonstrated that Acarbose
    increases
  • the probability that IGT will revert to normal
    glucose
  • tolerance over time.Chiasson-JL et al. Lancet,
    2002.

26
Prevention and treatment
27
  • Thank you
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