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Type 2 Diabetes in Youth Francine Ratner Kaufman, M.D.

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Presentation on theme: "Type 2 Diabetes in Youth Francine Ratner Kaufman, M.D."— Presentation transcript:

1 Type 2 Diabetes in Youth Francine Ratner Kaufman, M.D.
Distinguished Professor of Pediatrics The Keck School of Medicine of USC Head, Center for Diabetes and Endocrinology Childrens Hospital Los Angeles

2 What Do We Know About Type 2 Diabetes in Youth?
Question What Do We Know About Type 2 Diabetes in Youth?

3 Prevalence of Diabetes and IFG in US Adolescents – NHANES 1999-2002
Type 2 Diabetes 0.5% of adolescents have diabetes 71% type 1 and 29% type 2 Determined by insulin use vs no insulin use 39,005 US teens with T2D Impaired Fasting Glucose 11% had IFG 2,769,736 teens with IFG Diabetes Increased 41% from 4.9 to 6.9/1000 from 1997 to adults Duncan, Arch Pediatr Adolesc Med 2006;160:523; Geiss, Am J Prevent Med 2006;30:371

4 Is it an epidemic? The incidence is increasing and probably underestimated Population based estimates indicate an ~10-fold increase in incident cases over the past years 8% to 43% of all new cases of diabetes in the United States depending on ethnicity The SEARCH Trial What about prevalence?? Bloomgarden ZT. Diabetes Care. 2004;27: Centers for Disease Control. Diabetes Fact Sheet. 2005

5 Controversies as to the Nature of this Epidemic
Difficult to recruit for the TODAY trial 13 centers across the country Presence of antibodies The SEARCH Trial 19,000 new patients with T1D 4,100 new patients with T2D Type 1a + Ab FCP < 0.8 ng/ml Type 2 - Ab FCP > 2.9 ng/ml Hybrid

6 Diabetes Trends Among Adults in the US BRFSS 1990, 1995 and 2001

7 Is Type 2 Diabetes An Epidemic? Little Rock, Cincinnati, San Antonio
35 30 25 20 % with type 2 15 10 5 87 88 89 90 91 92 93 94 95 96 Ten-fold increase 0.7 vs 7.2/100000 8% to 43% of all new cases of diabetes in youth in US depending on ethnicity J Pediatr 136: , 2000

8 Question Is the Presentation the Same as in Adults?
Does not appear to be preceded by long asymptomatic period Do not find undiagnosed cases on screening

9 Natural History of Type 2 Diabetes
Complications Genetic susceptibility Environmental factors Onset of diabetes Disability PRE Obesity Insulin resistance Ongoing hyperglycemia Death Risk for Disease Metabolic Syndrome Blindness Renal failure CHD Amputation Atherosclerosis Hyperglycemia Hypertension Retinopathy Nephropathy Neuropathy

10 Pre-diabetes (IGT) and T2D
Overweight Sample IGT T2D Paulsen et al, 1968 66 multi-ethnic youth (4-16 years) 17% 6% Weninger et al, 1980 15 subjects 33% 0% Sinha et al, 2002 55 multi-ethnic youth (>95th %ile) 25% 112 multi-ethnic teens (>95th %ile) 21% 4% Goran et al, 2004 150 Hispanic +FH (8-13 years >85th %ile) 28% IGT = Impaired Glucose Tolerance



13 OGTT Feasibility Study Pre-diabetes and Diabetes by ADA Cut-offs
Fasting glucose 2-hour glucose Normal (< 140) Pre-diabetes ( ) Diabetes ( 200) (< 100) 57.6% 0.2% 0.0% ( ) 39.7% 2.0% 0.1% ( 126) 0.4%

14 Type 2 Diabetes ? Curve for Youth B-cell Function (%)
Progressive Pancreatic B-cell Failure Prevention and Early Treatment UKPDS Data B-cell Function (%) ? Curve for Youth Years from Clinical Diagnosis

15 Occurs at the time of intense insulin resistance due to puberty
Question Is the Pathophysiology the Same as in Adults? Associated with significant ß-cell failure as well as insulin resistance Occurs at the time of intense insulin resistance due to puberty

16 Polycystic ovary syndrome
Type 2 Diabetes Prediabetes Beta Cell Defect Beta Cell Defect Age Puberty Obesity BP, Lipids Insulin Resistance Genetics Ethnicity Sedentary Lifestyle Gender – Girls Polycystic ovary syndrome

17 Insulin Resistance Beta Cell Defect Type 2 Diabetes Prediabetes
Autoimmunity Genetic Defect Beta Cell Defect Fat cell toxicity Intrauterine IUGR, DM Glucose toxicity Insulin Resistance

18 What distinguishes type 1 from type 2 diabetes in youth?
Question What distinguishes type 1 from type 2 diabetes in youth?

19 Type 1 Versus type 2 Diabetes in youth?
T1DM T2DM Weight 20% may be overweight / obese Virtually all BMI > 85%th percentile Course Rapid From DPT-1 can be indolent Indolent Virtually none found on screening DKA 35%-40% Ketonuria (33%) Mild DKA (5%-25%) Relative with DM 5% with T1DM Up to 30% may have with T2DM FH of T2 2-3Xs in person with T1 74%-100% - 1st –2nd degree with T2DM Comorbid Thyroid, adrenal, vitiligo, celiac Increase in polycystic ovary syndrome Acanthosis nigricans C-peptide C-peptide can be preserved at DX Normal or increased Antibody Ethnicity 85% Whites predominate 15% (reported as high as 30%) NA, AA, HA, Asian, Pacific Islander Kaufman,Endocrinol Meta Clinics N Am, 34; : 2005

20 Differentiation Between Type 1 and 2
48 with type 2 vs 39 with type 1 Type 2 Ethnicity, 1st degree relative, BMI>24, +C-peptide, acanthosis Type 2 Type 1 DKA 33% 53% C-peptide ug/l ug/l Abs 8.1% ICA 30% GAD 35%IAA 85% have islet autoimmunity Hathout et al Pediatrics 107e102,June,2001

21 Question How Does Type 2 Present in Youth?
Is it asymptomatic or symptomatic in youth?

22 Diagnosis with Type 2 Fagot-Campagna et al J Pediatr 2000
Mean Age years Girls > Boys :1 Obese BMI >85th % Minority Groups 94% Strong Family History % Acanthosis Nigricans % Diagnosis made by Symptoms, not Screening HbA1c % Weight loss % Glucose in urine 95% Ketosis % DKA %

23 Question What Are Treatment Targets in Youth with Type 2 Diabetes?
Are they the same as in adults?

24 TREATMENT GOALS Glucose control, HbA1c <7%
Goals (Diabetes Care, 2000) FG PP Bed A1c <7.0 TREATMENT GOALS Glucose control, HbA1c <7% Eliminate symptoms of hyperglycemia Maintenance of reasonable body weight Improve cardiovascular risk factors Reduce microvascular complications Improvement in physical and emotional well-being

25 Treatment Issues Self-monitoring of blood glucose
Fasting and postprandial Frequency depends on regimen Medical Nutrition Therapy Diabetes Education Involves family Direct family supervision produces better glycemic control outcomes1 Lifestyle Coaching Preconception counseling Immunizations Dental care Smoking and alcohol counseling 1. Bradshaw, J Pediatr Endocrinol Meta 15, 2002 2. Pediatrics 112:2003 Prevention and treatment of type 2 diabetes in children with special emphasis on Native American Youth

26 What are the Treatment Regimens for Youth?
Question What are the Treatment Regimens for Youth?

27 GLP

28 Start with insulin and diet, exercise
Diagnosis BG 250 mg/dL or 12 mmol/L Asymptomatic Start with insulin and diet, exercise Diet and exercise <7% <7% Monthly review, A1C q3mo Add metformin Attempt to wean insulin >7% Add metformin >7% Add insulin, TZD, sulfonylurea >7% Add 3rd agent TZD = thiazolidinedione Silverstein JH, Rosenbloom AL. J Pediatr Endcrinol Metab. 2000;13 Suppl 6:

29 LWPES Survey 130 Clinical Practices
48% treated with insulin alone 2 injections 44% with oral agents 71% metformin 46% sulfonylurea 9% TZD 4% meglitinide 8% lifestyle

30 A1c at CHLA 2005 Diabetes Type Type 1 n=1534 Type 2 n=276 A1c %
Age years Duration years Visit Number

31 T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.
Intensive Therapy for Diabetes: Reduction in Incidence of Complications T1DM DCCT T2DM Kumamoto UKPDS A1C 9%  7% 8%  7% Retinopathy 63% 69% 17%–21% Nephropathy 54% 70% 24%–33% Neuropathy 60% 58% Cardiovascular disease 41%* 52* 16%* Review Data T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus. *Not statistically significant due to small number of events. †Showed statistical significance in subsequent epidemiologic analysis. DCCT Research Group. N Engl J Med. 1993;329: ; Ohkubo Y, et al. Diabetes Res Clin Pract. 1995;28: ; UKPDS 33: Lancet. 1998;352: ; Stratton IM, et al. Brit Med J. 2000;321:

32 Long term outcome Pima Indians - diagnosed < 20 years of age
22% had microalbuminuria at diagnosis Increased to 60% at years of age Indigenous Canadians- mean age 23 yrs, 9 yrs duration of diabetes HbA1c 10.9% 67% poor glycemic control 45% hypertension requiring treatment 35% microalbuminuria (6% required dialysis) 38% pregnancy loss 9% mortality Arslanian S. Hormone Res 2002; 57 Suppl 1: Dean., Diabetes 2002;51(Suppl 2):A24.

33 Uncontrolled diabetes
Amputations Loss of Sensations Heart disease and strokes Blindness Uncontrolled diabetes can lead to… Death Kidney failure

34 An Answer The Today Trial?

35 Studies to Treat Or Prevent Pediatric Type 2 Diabetes STOPP-T2D
Funded by National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health

To compare the efficacy of 3 treatment regimens Metformin Metformin + lifestyle Metformin + TZD On Time to Treatment Failure and on Glycemic Control TODAY

37 Primary Outcomes Treatment goal Treatment failure
HbA1c < 6% (glycemic control) Treatment failure HbA1c  8.0% over 6 consecutive months OR Inability to wean from temporary insulin therapy due to metabolic decompensation

38 Outcome Measures Glycemia Insulin sensitivity and secretion
HbA1c, fasting and postprandial glucose by home monitoring Insulin sensitivity and secretion OGTT, HOMA, QUICKI, proinsulin, C-peptide Body composition BMI, DEXA, waist circumference, abdominal height Fitness and physical activity PDPAR, PWC 170, accelerometer

39 Outcome Measures (continued)
Nutrition food frequency questionnaire Cardiovascular disease risk BP, lipids, inflammatory markers, coagulation factors Microvascular complications microalbuminuria, neuropathy Quality of life Cost

40 Inclusion Criteria Age 10 to 17 years
Duration of diabetes < 2 years BMI  85th percentile Adult involved in the daily activities of the child agrees to participate in the intervention Absence of pancreatic autoimmunity Fasting C-peptide > 0.6 mmol/L Fluency in English or Spanish

41 National Diabetes Education Program’s Tip Sheets for Kids with Type 2
                         In terms of publications, these colorful tip sheets provide basic information about type 2 diabetes and encourage young people to take steps to manage the disease for a long and healthy life. Written in simple language, the tip sheets are helpful for anyone who has type 2 diabetes and their loved ones. Topics include: What is Diabetes? Be Active. Stay at a Healthy Weight. Eat Healthy Foods. These tip sheets also are available online on the NDEP website. Additional tip sheets are in development covering dealing with diabetes and diabetes prevention. What is Diabetes? Be Active Stay at a Healthy Weight Eat Healthy Foods

42 Helping the Student with Diabetes Succeed
The school guide is called Helping the Student with Diabetes Succeed. A Guide for School Personnel. NDEP took on this project because of reports from NDEP partner organizations and their constituents of the lack of awareness and knowledge on how to manage kids with diabetes during the school day and the discrimination against children with diabetes in the school setting. Numerous NDEP partners joined NDEP to create and pretest the school guide.

43 Conclusion Increased incidence Difficult to distinguish from type 1
Occurs at the time of intense insulin resistance due to puberty Does not appear to be preceded by long asymptomatic period More insulin deficiency and requirement for exogenous insulin early Safety and efficacy of therapeutic agents Rapid progression of co-morbidities and complications

44 Thank you

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