1	Diabetes in Young Women Francine R. Kaufman, M.D. Professor of Pediatrics The Keck School of Medicine of USC Head, Center for Diabetes and Endocrinology Childrens Hospital Los Angeles
2	Life Goes on …. Diabetes does not have to stop you That can only happen if you face your diabetes 24/7 Just do it If people react negatively They are uninformed – you need to educate them If they cannot be enlightened – you don’t need them Make it a positive – or at least a neutral
3	Points of Discussion Practical Strategies for Managing Diabetes Leaving Home – Taking Risks Colleges Life and Employment Dating - Marriage Pregnancy Avoiding Complications
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5	Glycemic Targets Glucose values are plasma (mg/mL)
6	HbA1c Statistics for CHLA 2003 Type 1: Diabetes > 1 year, followed > 1 year Enrolled in Long-term study – total n 1800
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8	Managing Diabetes In DCCT, intensively treated adolescents (13-17 yrs of age) manifested a greater absolute rate of severe hypoglycemia and higher mean HbA1_c levels. Why? Adolescents are faced with rapid physiological and psychological modifications with the onset of puberty which may destabilize glycemic control.
9	DCCT Results: Comparison of Adults Versus Adolescents
10	Insulin management Fixed dose regimens: requires scheduled meals and snacks and is not flexible enough for most lifestyles Basal: bolus regimens: Long-acting relatively peak free analogue with pre-food injection of rapid acting analogue useful only if child is willing to take frequent injections Insulin pumps being increasingly used in all age groups but child must be willing to wear the device
11	Relationship Between Number of Blood Glucose Determinations and A1C
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13	Metabolic Control and Quality of Life The study involved 20 centres in 17 countries in Europe, Japan and North America. Adolescents aged 10-18 yrs at each study centre were invited to participate. 2,101 adolescents were enrolled. Samples and information from 79% of all patients registered at the centres were obtained.
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18	Adolescent Issues Desire for peer acceptance Rebellion against authority Expectations of increasing responsibilities outside of home
19	Taking Risks Alcohol Drugs Driving Hiding diabetes – impacts on it all
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21	College Life Fun Food Friends Fraternity Focus
22	Keeping in Touch Stay with health care provider who knows you versus changing at college or before you go Email program Less frequent visits Stressors and stress reduction
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24	Dating When to tell about diabetes What to tell Where to find information How do you handle different responses MARRIAGE
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27	Prevalence of Diabetes in Pregnancy in the United States of America More than 135,000 GDM + 200,000 T2DM + 6,000 T1DM pregnancies annually
28	"Glucose" Glucose
29	Data At CHLA 225 Teens at Risk 5-6 pregnancies / year >50% interrupted or SAB 2-3 Live Births / year 1/3 Require Prolonged Hospitalization Last 3 years – no anomalies Overall increased rate of anomalies 6-12% compared to 2-3% - a 2-5 fold increase But this can be modified by pre-conception planning and meticulous diabetes control
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31	DCCT Results: Comparison of Adults Versus Adolescents
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33	Intensive Therapy for Diabetes: Reduction in Incidence of Complications
34	Recommendations For Treatment Of Retinopathy Annual screening should be done when the child is ≥ 10 years old and has diabetes for 3-5 years Questions: Is this early enough for a child with poorly controlled diabetes for longer than 3-5 years?
35	Recommendations For Microalbuminuria Testing Annual screening for urinary albumin should begin when Child is ≥ 10 yrs old DM of 5 years duration If urine albumin: creat ratio on spot urine is abnormal (30-299 mg/gm creatinine) Confirm with 2 additional urine specimens Obtain up: down urine specimen to rule out orthostatic proteinuria
36	Recommendations For Microalbuminuria Treatment ACE Inhibitors may reverse microalbuminuria or delay rate of progression to macro-albuminuria Treat BP aggressively Questions: Should these children all be referred to a nephrologist for evaluation and treatment? Should children with poorly controlled DM be evaluated sooner? Should children with HTN be evaluated sooner?
37	BP Recommendations Repeat with child sitting and relaxed on 2 more occasions HTN defined as BP≥ 95% for age, sex and height measured on at least 3 separate days High normal BP is ≥ 90% but < 95% Rule out non-diabetes causes
38	BP: When to Treat High normal BP Diet (limit salt) and exercise for 3-6 months If still high normal, treat with ACE inhibitor Consider adding ARBs if 90% on maximal doses Hypertension (confirmed) Treat with ACEI to achieve BP< 90% Questions Remaining: At what age to treat? At what level to treat?
39	Children with diabetes have increased muscle thickness & stiffness Carotid artery intima media thickness is significantly increased in youth with diabetes compared to controls matched for age and gender -correlated with LDL-C levels Brachial artery reactivity is decreased in children with diabetes compared to matched controls Radial artery tonometry → stiffer vessels in children with diabetes compared to BMI, age, sex matched controls
40	Cardiovascular Disease Risk Factors in Adolescents with Type 1 Diabetes Mellitus M.V. Karantza, S. Bababeygy, H.N. Hodis, W.J. Mack, C.-R. Liu, C.-H. Liu, and F.R. Kaufman Division of Endocrinology, Diabetes, and Metabolism, Childrens Hospital Los Angeles Supported by ADA Clinical Research Award 1-01-CR-06
41	Background Atherosclerosis is a Major Cause of Morbidity and Mortality in Patients with T1DM May be initiated early Accelerated by traditional CVD factors Hig blood pressure, dyslipidemia, cigarette smoking, obesity Inflammatory and prothrombotic factors
42	Background Previous Investigations Atherosclerosis assessed by IMT measurement 142 subjects with T1DM Mean age 16.0 ± 2.6 yr, mean T1DM duration 6.6 ± 7.9 yr 87 matched healthy subjects Results: Adolescents with T1DM had increased atherosclerosis compared to controls Risk factors for increased IMT included diabetic complications, and HDL and LDL/HDL ratio Krantz JS, et al, J Pediatr 2004;145: 452-457
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45	IMT vs Lipids in T1DM In males, IMT is significantly associated with Total Cholesterol (r=0.32, p<0.05) Apolipoprotein B (r=0.41, p<0.05) In females, IMT is negatively correlated with HDL (r=-0.30, p<0.05)
46	The Continuum Of Vascular Damage in T1DM Conventional CVD risk factors result in increased IMT and probably cause the initial endothelial dysfunction in our cohort of youth with T1DM The subsequent loss of normal endothelial homeostatic properties leading to a proinflammatory, proadhesive, and procoagulant endothelial surface is not yet present in our cohort Early treatment of modifiable risk factors could avert the chronic inflammatory process which, if unabated, will result in the advanced atherosclerotic plaque formation
47	Recommendations For Lipid Management When to test Pre-pubertal children >2 years old should have Fasting lipids at diagnosis if there is positive FH of increased lipids or early cv event (<50 males, < 60 females) If initial LDL-c < 100 mg/dl, repeat every 5 years If initial LDL-c > 100 mg/dl, begin therapeutic lifestyle change (TLC) Fasting lipids at puberty or at age 12 yrs if FH normal Pubertal children or > 12 years old should have fasting lipid profile done at time of diagnosis after BG control established
48	Recommendations For Lipid Management LDL-c > 100 mg/dl Step 2 diet (< 7% saturated fat, < 200 mg/d chol) Exercise 60 minutes daily Intensify efforts to normalize BG Repeat 3-6 months LDL-c >130 mg/dl & ≤ 160 mg/dl after 3-6 mos Consider treatment LDL-c > 160 mg/dl after 3-6 months Treat
49	Pittsburgh Epidemiology of Diabetes Complications Study 10 year follow up of patients with Type 1 diabetes diagnosed before age 17 Showed that increased LDL is an independent factor of microvascular disease, macrovascular disease, and mortality LDL 100-129 RR 5.3 LDL 130-159 RR 5.6 LDL >160 RR 12.1 (p<0.01 in all)
50	Unanswered Questions At what age should we begin medication to decrease lipids? Should we wait until glycemic control is achieved before initiation of lipid lowering medications At what level of LDL-c should we treat? Should we be monitoring hsCRP? What drugs should we use?
51	Life Goes on …. Diabetes does not have to stop you That can only happen if you face your diabetes 24/7 Just do it If people react negatively They are uninformed – you need to educate them If they cannot be enlightened – you don’t need them Make it a positive – or at least a neutral