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FRIENDS FOR LIFE 2012
UPS AND DOWNS OF GROWTH
What they don’t tell you about puberty
PC Hindmarsh
London Centre for Paediatric Endocrinology and DiabetesUniversity College Hospital London
andUniversity College London Hospitals
Children and Young Peoples Diabetes Service
Barabasi A. N Engl J Med 2007;357:404-407
Complex Networks of Direct Relevance to Network MedicineNETWORKS AND DISEASE
CHANGES
Biological
Psychological
Social
Body ShapeAppearance Function
Personal Identity Sexual Identity
Thinking PatternFamiliesPeers Outside World
• Biological and sexual maturation• what have I got and does it work ?• Personal identity• who (or where) am I ?
• Intimate relationships with an appropriate peer • don’t fancy yours !!!
• Independence/autonomy
• Experimenting & bullet proof !!!
JOB DESCRIPTION
• To go out without letting people know where you are going
• Not tell your parents when you are coming back
• Experiment with alcohol and other mind altering substances
• Believe you are invincible• Know that you are right• Independence (Goldilocks principle)
HUMAN GROWTH CURVES
CHILDHOOD AND PUBERTAL GROWTH
0
50
100
150
200
250
B1 B2/3 B4/5
Pubertal Stage
Su
m o
f G
H p
uls
es (
mU
/l)
CYCLICITY OF POSTNATAL GROWTH
GH AND IGF-1 AXIS
GHRH SS
GH
IGF-1
GHRH AND SS INTERACT TO GENERATE GH RELEASE
-1
0
1
2
3
4
5
6
GH
GHRH
SS
Effect of Estradiol
+ =
2 – 3 Fold
Increase in
GH Secretion
GH SECRETION DURING PUBERTY
Girls Boys
Breast Stage Testicular Volume (mls)
GH SECRETION DURING PUBERTY
Pre-Pubertal Pubertal
EFFECT OF ALTERING SEX STEROID ENVIRONMENT ON GH SECRETION
0
1
2
3
4
5
6
7
8
9
10M
ean
GH
(m
U/l
)Flutamide Tamoxifen Oxandrolone
- + - + - +
DERIVATIVES FROM OGTT DATASETS
Fasting insulin (mU/l)
Liver insulin
resistance
Muscle insulin
resistance
HOMA-R
Prepubertal (n=22)
6.7 ± 1.1 149 ± 20 2.3 ± 0.4 1.4 ± 0.2
Pubertal (n=23)
12.4 ± 1.4
224 ± 25 1.3 ± 0.5 2.6 ± 0.3
p 0.002 0.02 NS 0.003
24 hr INSULIN PROFILES IN CHILDREN
0
10
20
30
40
50
60
70
0 3 6 9 12 15 18 21
Clock Time (mins)
Ser
um
In
suli
n (
mU
/l)
Pre-pubertal
Pubertal
COMPARISON OF PHYSIOLOGICAL CHANGES IN INSULIN SECRETION WITH INSULIN PUMP THERAPY
0
5
10
15
20
25
30
35
40
45
Background Day Time
Ser
um
Insu
lin (
mU
/l)
Pre-Pubertal
Pubertal
0.00 5.00 10.00 15.00 20.00
Age
0.00
2.00
4.00
6.00
8.00
10.00
"Insulin S
ensitiv
ity"
0.00 5.00 10.00 15.00 20.00
Age
0.20
0.40
0.60
0.80
1.00
1.20
Insu
lin D
ose
(U
nits/
kg)
0.00 5.00 10.00 15.00 20.00
Age
0.00
20.00
40.00
60.00
80.00
% B
asal
So for Puberty:
1. Individuals become more insulin insensitive so overall insulin dose needs to be increased from 0.9 to 1.5 U/kg/day
2. The total daily dose should be divided into roughly 40 – 50% delivered as the background insulin
3. Because of the degree of insulin insensitivity hypoglycaemia is unlikely to be a problem at least in the early stages of the pubertal growth spurt
4) Insulin regimens in patients with type 1 diabetes mellitus need to parallel these physiological changes.
1) The pubertal growth spurt arises from the effects of estradiol on GH secretion.
SUMMARY
2) GH reduces tissue sensitivity to insulin
3) Background and food related insulin secretion increases 2-3 fold