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Obesity at Onset of T1D: It has also been suggested that the typical presentation 
with T1D has changed over time, and that youth with T1D are more obese at 
diagnosis.  Libman and colleagues 
(69)
 examined the prevalence of overweight or 
obesity among black and white children with newly diagnosed T1D in Pittsburgh over 
two periods: 1979-1989 and 1990-1998.  The prevalence of overweight or obesity 
increased from 12.6% to 36.8%.  Similarly, the prevalence of overweight among 
SEARCH youth with T1D was higher than among those without diabetes (22.1% vs. 
16.1%, P <0.05) 
(23)
.  
The “accelerator hypothesis” postulates that obesity-associated insulin resistance 
accelerates the disease process of T1D.  The marker is an earlier age at onset of T1D 
associated with increased BMI 
(70)
.  Prospective data from population-based studies in 
Europe 
(71)
 and the U.S. 
(72)
 have shown that children who develop T1D have faster 
growth trajectories before onset of autoimmunity 
(72)
 and diagnosis of diabetes 
(71, 72)
.  
Several studies have demonstrated an inverse association between age at T1D 
diagnosis and childhood BMI 
(73, 74)
.  The SEARCH study reported that a higher BMI 
was associated with a younger age at diagnosis only in youth with substantially 
reduced β-cell function at diagnosis 
(16)
, suggesting that obesity may operate after 
initiation of autoimmunity by accelerating the β-cell decline, thus leading to an earlier 
T1D diagnosis.  The Australian Baby Diab Study recently reported that weight gain 
early in life independently predicts development of islet autoimmunity 
(75)
.  These 
combined findings suggest that obesity may both trigger the autoimmune process as 
well as accelerate β-cell loss after autoimmunity development.  By collecting data on 
height, weight and other markers of insulin resistance at onset of T1D, SEARCH will 
answer questions related to temporal trends in clinical presentation, providing 
important clues to etiological research. 

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Section 4A - Study Objectives/Background and Significance (Phase 3 - 11/2010) 
Section 4A - Page 10 
 Registry 
Study
 
 
4.2.4.
 
Type 2 Diabetes 
T2D has been traditionally viewed as an adult disease, with risk increasing with 
advancing age.  An increasing proportion of youth with apparent T2D has been reported 
in the last two decades, especially in minority populations 
(76, 77)
.  The epidemiology of 
T2D in youth is yet unclear, due to its relative rarity, the unclear clinical and 
epidemiological definition, and the small number of appropriate, population-based 
studies.  Therefore, the true magnitude of T2D in youth may be under- or overestimated, 
depending on the study setting (clinic versus population-based), characteristics of 
populations under study, and definitions used.  
SEARCH for Diabetes in youth is the first population-based study to provide 
comprehensive estimates of T2D incidence in youth according to race/ethnicity.  Overall, 
T2D was relatively infrequent, except among 10-14 and 15-19 year old minority groups 
(17.0 to 49.4 per 100,000/year) 
(5)
.  Consistent with previous reports 
(78, 79)
, SEARCH 
demonstrated that T2D contributes considerably to the overall diabetes incidence among 
minority youth age ≥ 10 years of age.  
Many studies rely on data collected from diabetes clinics.  A strength of such studies is 
that assignment of diabetes type is likely to be more accurate (though not always 
uniform) than in population-based studies.  However, a clinic population may not 
accurately represent the general population.  
Several clinic-based studies reported an increased incidence of T2D.  For example, T2D 
incidence rates reportedly rose by 9%/year from 1985-94, based on medical records of 
735 AA and Latino children with insulin-treated diabetes in Chicago 
(80)
.  The incidence 
was higher in AA than Latinos (15.2 vs. 10.7/100,000/year), with a female predominance.  
Similarly, among 1027 consecutive patients attending a Cincinnati diabetes clinic 
(81)
, 
T2D incidence increased by 10-fold, from 0.7/100,000/year in 1982 to 7.2/100,000/year 
in 1994.  Onset was typically around puberty, the majority were AA, and the female: 
male ratio was 1.7:1.  Among 569 adolescents presenting to a Florida diabetes clinic 
between 1994 and 1998 (82), the proportion of new cases with T2D rose from 9.4% to 
20%.  In Arkansas, new-onset non-T1D increased fivefold in youth aged 8-21 between 
1990 and 1995) 
(79)
.   
Similarly, a study in Thailand 
(83)
 reported a rise in the proportion with T2D referred to a 
diabetes clinic from 5% to 17% during 1997 to 1999.  Another study of 0- to 16-year-olds 
from U.K. identified 67 cases of T2D (defined as diabetes with elevated insulin or FCP 
levels and/or the absence of DA) during the period 2004-2005 
(84)
.  The U.K. T2D 
incidence was 0.53/100,000/year and was higher in blacks and South Asians compared to 
whites.  A study from the only pediatric diabetes clinic serving approximately 2 million 
Australians, documented a rise in the incidence of T2D among youth aged 0-17 years 
(85)
.  

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Section 4A - Study Objectives/Background and Significance (Phase 3 - 11/2010) 
Section 4A - Page 11 
 Registry 
Study
 
 
Between 1990 and 2002, average annual rises were 23% in the indigenous, and 31% in 
the non-indigenous population. 
With the exception of SEARCH, only a limited number of population-based studies of 
childhood T2D exist.  Most have been conducted in American Indians and Native 
Canadians 
(78, 86 - 87)
 and showed high prevalence of T2D.  While there is evidence 
supporting an increasing incidence and prevalence of T2D among youth, it is possible 
that this rise is mainly a feature of high-risk ethnic groups.  Well-designed studies of 
youth in Germany, Austria, France and the U.K 
(88 - 90)
 all indicate that T2D remains a 
rarity in these populations, accounting for only 1-2% of all diabetes cases.  A survey of 
all children with diabetes from 177 U.K. pediatric diabetes centers found that <1% of all 
cases were due to T2D 
(91)
.  A single center in France 
(89)
 reported that only 2% of 382 
children (aged 1-16) with diabetes had T2D.  Using an Austrian national register, Rami et 
al 
(92)
 found that T2D represented only 1.5% of all newly diagnosed cases of diabetes 
under the age of 15 from 1999-2001.  In contrast, while the SEARCH data 
(5)
 support the 
notion that T2D in youth is predominantly occurring in high risk ethnic groups, T2D 
accounts for 14.9% of all diabetes cases among NHW adolescents age 10 years and older.  
Although differences in obesity rates between U.S. and European youth are likely 
contributors, the full explanation for these discrepancies remains uncertain and deserves 
further study.  By continuing to ascertain prospectively newly diagnosed diabetes cases, 
SEARCH will be in the unique position to estimate trends in the incidence of T2D among 
US youth by age-group, sex and race/ethnicity. 
4.3.
 
PUBLIC HEALTH SURVEILLANCE OF DIABETES IN YOUTH 
4.3.1.