The discovery of islet cell antibodies (ICAs) was the prelude to the understanding that type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease. The issue regarding whether or not the measurement of ICAs should be completely replaced by biochemical markers detecting islet autoantibodies (AAs) for the prediction of T1DM has been the subject of endless international debates. In light of this controversy, we assessed the current role of ICAs as a predictive marker for T1DM progression. We examined a cohort of 1484 first-degree relatives (FDRs) of T1DM probands from the Children's Hospital of Pittsburgh Registry. These relatives were consecutively enrolled between 1979 through 1984 and followed up to 22 yr. Serum obtained at the time of enrollment was assayed for ICAs, glutamic acid decarboxylase (GAD)65, insulin A (IA)-2 AA, and insulin AAs (IAAs). In FDRs who had ICAs in addition to GAD65 and IA-2 AAs, the cumulative risk of developing insulin-requiring diabetes was 80% at 6.7 yr of follow-up, whereas this risk in those with GAD65 and IA-2 AAs without ICAs was only 14% at 10 yr of follow-up (log rank: P < 0.00001). Cox regression analysis showed that diabetes risk was significantly associated with the presence of ICAs in both subjects with low titer and high titer GAD65 and IA-2 AAs. The addition of IAAs in GAD65 and IA-2 AA-positive relatives did not increase the cumulative risk for conversion to insulin-treated diabetes. We provide evidence that a subgroup of ICAs predicts a more rapid progression to insulin-requiring diabetes in GAD65 and IA-2 AA-positive relatives and should remain part of the assessment of T1DM risk for intervention trials. In addition, these findings provide impetus for efforts to identify a novel islet autoantigen(s) reactive with this ICA subset.

Pediatric DiabetesVolume 6, Issue 3 p. 119-121 Changing trends in epidemiology of type 1 diabetes mellitus throughout the world: how far have we come and where do we go from here* Ingrid M. Libman MD. PhD, Ingrid M. Libman MD. PhD Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA [email protected]Search for more papers by this authorRonald E. LaPorte PhD, Ronald E. LaPorte PhD Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA [email protected]Search for more papers by this author Ingrid M. Libman MD. PhD, Ingrid M. Libman MD. PhD Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA [email protected]Search for more papers by this authorRonald E. LaPorte PhD, Ronald E. LaPorte PhD Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA [email protected]Search for more papers by this author First published: 15 August 2005 https://doi.org/10.1111/j.1399-543X.2005.00119.xCitations: 11 * We have provided a set of slides concerning this editorial and these can be found at: http://www.pitt.edu/~super1/lecture/lec20501/index.htm Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References 1 http://www.-unix.oit.umass.edu/~abhu000/diabetes/index.html. 2 Rosner F, ed. Maimonides' Medical Writings. Haifa: Maimonides Research Institute,1984. 3 West KM. Epidemiology of Diabetes and its Vascular Lesions.New York: Elsevier,1978. 4 Karvonen M, Viik-Kajander M, Moltchanova E, Tuomilehto J, Libman I, Laporte R. Incidence of childhood type 1 diabetes worldwide. Diabetes Care 2000: 23: 1516–1526. 5 Eeurodiab Ace Study Group. Variation and trends in incidence of childhood diabetes in Europe. Lancet 2000: 355: 873–876. 6 Tuomilehto J, Karvonen M, Pitkaniemi J et al. Record-high incidence of type 1 (insulin-dependent) diabetes mellitus in Finnish children. Diabetologia1999: 42: 655–660. 7 Casu A, Pascutto C, Bernardinelli L, Songini M. Type 1 diabetes among Sardinian children is increasing: the Sardinian diabetes register for children aged 0–14 years (1989–1999). Diabetes Care 2004: 27: 1623–1629. 8 Yang Z, Wang K, Li T et al. Childhood diabetes in China. Enormous variation by place and ethnic group. 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Epidemiology of type 1 diabetes mellitus in Switzerland: steep rise in incidence in under 5 year old children in the past decade. Diabetologia 2001: 44: 286–289. 15 Haynes A, Bower C, Bulsara MK, Jones TW, Davis EA. Continued increase in the incidence of childhood type 1 diabetes in a population-based Australian sample (1985–2002). Diabetologia 2004: 47: 866–870. 16 Dokheel T, The Pittsburgh Diabetes Epidemiology Research Group. An epidemic of childhood diabetes in the United States? Evidence from Allegheny County, Pennsylvania. Diabetes Care 1993: 16: 1606–1611. 17 Libman IM, Laporte RE, Becker D, Dorman J, Drash A, Kuller L. Was there an epidemic of diabetes in nonwhite adolescents in Allegheny County, Pennsylvania.Diabetes Care 1998: 21: 1278–1281. 18 Dahlquist G, Ivarsson S, Lindberg B, Forsgren M. Maternal enteroviral infection during pregnancy as a risk factor for childhood IDDM. A population-based case-control study: Diabetes 1995: 44: 408–413. 19 Akerblom H, Vaarala O, Hyoty H, Ilonen J, Knip M. Environmental factors in the etiology of type 1 diabetes: Am J Med Genet 2002: 115: 18–29. 20 Hypponen E, Virtanen SM, Kenward MG, Knip M, Akerblom H. Obesity, increased linear growth and risk of type 1 diabetes in children: Diabetes Care 2002: 23: 1755–1760. 21 EURODIAB Substudy 2 Study Group. Rapid early growth is associated with increased risk of childhood type 1 diabetes in various European populations: Diabetes Care 2002: 25: 1755–1760. 22 Gale EAM. A missing link in the hygiene hypothesis?Diabetologia 2002: 45: 588–594. Citing Literature Volume6, Issue3September 2005Pages 119-121 ReferencesRelatedInformation

OBJECTIVEWe have previously reported differences in the prevalence of beta-cell autoantibodies (AAs) in black and white children with insulin-treated diabetes, suggesting that the disease pathogenesis may be more heterogeneous among racial groups than previously thought. To further explore this issue, we compared clinical, biochemical, and autoimmune characteristics at disease diagnosis and follow-up treatment in an expanded number of black and white children with and without the presence of AAs.RESEARCH DESIGN AND METHODSThe study cohort of 130 black children and adolescents, aged <19 years, diagnosed with diabetes and treated with insulin at time of diagnosis (January 1979 to December 1998) were matched with an equal number of white children by age at onset, sex, and year of diagnosis.RESULTSThe black children had a higher prevalence of obesity (43 vs. 11%) and acanthosis nigricans (21 vs. 1%) than white children and a lower prevalence of AAs. Compared with black children who had AAs, those with no AAs were older and had a higher prevalence of obesity, acanthosis nigricans, and parental diabetes. However, one of four of the black children with AAs was obese and/or had acanthosis nigricans. Among white children, the absence of AAs was not associated with any differences in terms of obesity or acanthosis nigricans compared with those with AAs. Similar to their black counterparts, white children without antibodies were older and had a higher prevalence of parental diabetes. Although treatment with an insulin sensitizer was used, insulin therapy was rarely discontinued on follow-up.CONCLUSIONSThese pediatric subjects, irrespective of autoimmunity, often showed characteristics associated with type 2 diabetes. These characteristics were more frequently displayed in black than in white children. Our data suggest that childhood diabetes may constitute a spectrum of pathogenic mechanisms that may overlap, including those typically associated with both type 1 and type 2 diabetes. This finding could have therapeutic implications.

OBJECTIVE To determine the incidence of IDDM in children aged < 20 years at diagnosis in Allegheny County, Pennsylvania, for the period from 1 January 1990 to 31 December 1994 and to compare the incidence between whites and nonwhites in the same area and for the same time period. RESEARCH DESIGN AND METHODS All new patients diagnosed between January 1990 and December 1994 who were aged < 20 years, on insulin, and residents of Allegheny County at diagnosis were identified from medical records of 23 hospitals in the Allegheny County area. To verify the completeness of the hospitals using the capture-recapture method, pediatricians and diabetologists were used as a secondary source. RESULTS A total number of 257 patients were identified. The overall age-standardized incidence rate was 16.7/100,000. Nonwhites had a slightly higher incidence (17.6/100,000) than whites (16.5/100,000). In the 15–19 years age-group, the incidence in nonwhites (30.4/100,000) was almost three times higher than that in white (11.2/100,000) and more than two times higher than that in the previous period (from 1985 to 1989) (13.8/100,000). CONCLUSIONS For the first time in the Allegheny County registry, and in any other registry, nonwhites showed a higher incidence of IDDM than whites. The high incidence in the 15–19 years age-group was responsible for this phenomenon. This epidemic of diabetes in adolescent nonwhites may be the result of a rising incidence of classical IDDM or another type of diabetes. Further studies using population-based registries are needed to determine whether this increase is being seen in other areas and other ethnic groups and to clarify the reasons for the increase in IDDM among blacks.

OBJECTIVE - To compare the frequency of islet cell antibodies (ICA) and antibodies to GAD65 and IA-2 (ICA512) between black and white children and adolescents at the diagnosis of IDDM in a large consecutive series of cases from Children's Hospital of Pittsburgh.RESEARCH DESIGN AND METHODS - ICA and antibodies to GAD65 and IA-2 were measured in 437 white and black children and adolescents who were diagnosed with IDDM at <19 years of age at Children's Hospital of Pittsburgh from January 1983 to December 1985, from January to December 1989, and from January 1996 to December 1997.RESULTS - The prevalence of ICA(H), GAD65, and IA-2 antibodies was significantly lower in blacks than whites at onset of the disease. In contrast, the prevalence of ICA(R) alone was higher in blacks. None of the antibodies were present in 12% of the blacks compared with 4% in whites. The same pattern was seen in both sexes. The prevalence of antibodies in white patients with onset of IDDM at <11 years of age was no different than in those who developed IDDM during adolescence. In contrast, black patients showed a significantly lower prevalence of almost all antibodies in the adolescent group.CONCLUSIONS - Black adolescents were more likely to not have antibodies, suggesting either that they have a nonautoimmune type of diabetes or that antibodies are not being detected by these assays.

When a disaster occurs, a major difficulty is knowing where to find accurate information, and how to help coordinate efforts to share accurate information in a quick and organized manner. The establishment of a global information network, that is in place before a disaster occurs, could link all the communication efforts for relief. We propose that a Global Health Unit for Disaster and Relief Coordination be set up as part of the Global Health Network, utilizing the Internet as its backbone. This Unit would establish the links for the disaster information mosaic.