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