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FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh...

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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 Diabetes University College Hospital London and University College London Hospitals Children and Young Peoples Diabetes Service
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Page 1: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

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

Page 2: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

Barabasi A. N Engl J Med 2007;357:404-407

Complex Networks of Direct Relevance to Network MedicineNETWORKS AND DISEASE

Page 3: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

CHANGES

Biological

Psychological

Social

Body ShapeAppearance Function

Personal Identity Sexual Identity

Thinking PatternFamiliesPeers Outside World

Page 4: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

• 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 !!!

Page 5: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

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)

Page 6: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.
Page 7: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

HUMAN GROWTH CURVES

Page 8: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

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)

Page 9: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

CYCLICITY OF POSTNATAL GROWTH

Page 10: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

GH AND IGF-1 AXIS

GHRH SS

GH

IGF-1

Page 11: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

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

Page 12: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

GH SECRETION DURING PUBERTY

Girls Boys

Breast Stage Testicular Volume (mls)

Page 13: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

GH SECRETION DURING PUBERTY

Pre-Pubertal Pubertal

Page 14: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

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

- + - + - +

Page 15: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

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

Page 16: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

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

Page 17: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

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

Page 18: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

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

Page 19: FRIENDS FOR LIFE 2012 UPS AND DOWNS OF GROWTH What they dont tell you about puberty PC Hindmarsh London Centre for Paediatric Endocrinology and Diabetes.

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