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 University College Hospital London and University College London Hospitals Children and Young Peoples Diabetes Service

2. Barabasi A. N Engl J Med 2007;357:404-407 Complex Networks of Direct Relevance to Network Medicine NETWORKS AND DISEASE

3. CHANGES Biological Psychological Social Body Shape Appearance Function Personal Identity Sexual Identity Thinking Pattern Families Peers Outside World

4. 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 dont fancy yours !!! Independence/autonomy Experimenting & bullet proof !!!

5. 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)

7. HUMAN GROWTH CURVES

8. CHILDHOOD AND PUBERTAL GROWTH

9. CYCLICITY OF POSTNATAL GROWTH

10. GH AND IGF-1 AXIS GHRH SS GH IGF-1

11. GHRH AND SS INTERACT TO GENERATE GH RELEASE GH GHRH SS Effect of Estradiol + = 2 – 3 Fold Increase in GH Secretion

12. GH SECRETION DURING PUBERTY Girls Boys Breast Stage Testicular Volume (mls)

13. GH SECRETION DURING PUBERTY Pre-Pubertal Pubertal

14. EFFECT OF ALTERING SEX STEROID ENVIRONMENT ON GH SECRETION Flutamide Tamoxifen Oxandrolone - + - + - +

15. DERIVATIVES FROM OGTT DATASETS Fasting insulin (mU/l) Liver insulin resistance Muscle insulin resistance HOMA-R Prepubertal (n=22) 6.7 ± 1.1149 ± 202.3 ± 0.41.4 ± 0.2 Pubertal (n=23) 12.4 ± 1.4 224 ± 251.3 ± 0.52.6 ± 0.3 p0.0020.02NS0.003

16. 24 hr INSULIN PROFILES IN CHILDREN

17. COMPARISON OF PHYSIOLOGICAL CHANGES IN INSULIN SECRETION WITH INSULIN PUMP THERAPY 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

18. 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