The analysis of variation of risk for a given disease in space and time is a key issue in descriptive epidemiology. When the data are scarce, maximum likelihood estimates of the area-specific risk and of its linear time-trend can be seriously affected by random variation. In this paper, we propose a Bayesian model in which both area-specific intercept and trend are modelled as random effects and correlation between them is allowed for. This model is an extension of that originally proposed for disease mapping. It is illustrated by the analysis of the cumulative prevalence of insulin dependent diabetes mellitus as observed at the military examination of 18-year-old conscripts born in Sardinia during the period 1936-1971. Data concerning the genetic differentiation of the Sardinian population are used to interpret the results.

OBJECTIVE -To determine the incidence of retinopathy and the relative importance of its risk factors in type 1 diabetes. RESEARCH DESIGN AND METHODS-This is a 7.3-year follow-up of 764 of 1,215 (63%) people with type 1 diabetes across Europe, aged 15-60 years at baseline with no retinopathy (the EURODIAB Prospective Complications Study). Retinal photographs were taken at baseline and follow-up and risk factors were assessed to a standard protocol.RESULTS -Retinopathy incidence was 56% (429/764, 95% CI 52-59%). Key risk factors included diabetes duration and glycemic control. We found no evidence of a threshold effect for HbA 1c on retinopathy incidence. Univariate associations were observed between incidence and albumin excretion rate, cholesterol, triglyceride, fibrinogen, von Willebrand factor, ␥-glutamyltransferase, waist-to-hip ratio, and insulin dose. No associations were observed for blood pressure, cardiovascular disease, or smoking. Independent risk factors, as assessed by standardized regression effects, were HbA 1c (1.93, P = 0.0001), duration (1.32, P = 0.008), waist-to-hip ratio (1.32, P = 0.01), and fasting triglyceride (1.24, P = 0.04).CONCLUSIONS -Retinopathy incidence in type 1 diabetes remains high. Key risk factors include diabetes duration and glycemic control, with no evidence of a threshold for the latter. Other independent risk factors, such as waist-to-hip ratio and triglyceride levels, both markers of insulin resistance, were strongly related to incidence.

OBJECTIVEZinc transporter 8 (ZnT8) is an islet β-cell secretory granule membrane protein recently identified as an autoantibody antigen in type 1 diabetes. The aim of this study was to determine the prevalence and role of antibodies to ZnT8 (ZnT8As) in adult-onset diabetes.RESEARCH DESIGN AND METHODSZnT8As were measured by a radioimmunoprecipitation assay using recombinant ZnT8 COOH-terminal or NH2-terminal proteins in 193 patients with adult-onset autoimmune diabetes having antibodies to either GAD (GADAs) or IA-2 (IA-2As) and in 1,056 antibody-negative patients with type 2 diabetes from the Non Insulin Requiring Autoimmune Diabetes (NIRAD) study.RESULTSZnT8As-COOH were detected in 18.6% patients with autoimmune diabetes and 1.4% with type 2 diabetes. ZnT8As-NH2 were rare. ZnT8As were associated with younger age and a high GADA titer. The use of GADAs, IA-2As, and ZnT8As in combination allowed a stratification of clinical phenotype, with younger age of onset of diabetes and characteristics of more severe insulin deficiency (higher fasting glucose and A1C, lower BMI, total cholesterol, and triglycerides) in patients with all three markers, with progressive attenuation in patients with two, one, and no antibodies (all Ptrend < 0.001). Autoantibody titers, association with high-risk HLA genotypes, and prevalence of thyroid peroxidase antibodies followed the same trend (all P < 0.001).CONCLUSIONSZnT8As are detectable in a proportion of patients with adult-onset autoimmune diabetes and seem to be a valuable marker to differentiate clinical phenotypes.

Aims/hypothesis. This prospective study examined the epidemiology of Type 1 diabetes in young adults in Europe. Methods. We ascertained incident cases of Type 1 diabetes in the 15 to 29 years (both inclusive) age group throughout Europe over a period of 2 years. Diabetes registries in nine countries, in which incidence rates for Type 1 diabetes in the 0 to 14 age group were available, took part. Incidence rates were estimated per 100000 person years and standardised for sex and age. Cumulative incidences per 1000 from birth to age 30 were estimated. Heterogeneity between centres was tested with a Poisson regression model. Results. A total of 2112 diabetes cases were ascertained in 1996 and 1997, of which 61.4% were considered to be Type 1 diabetes. Completeness of ascertainment varied from 70 to 90%. Standardised incidence varied from 4.8 per 100000 person years to 13.4 per 100000 person years. The male-female ratio was estimated to be one or more, and in the 25 to 29 age group 1.5 or more in all countries. Cumulative incidences for males and females indicate that the former exceeds the latter from age 24. In the two centres with highest childhood incidence, this applied already from 14 years of age. Conclusions/interpretation. The incidence of Type 1 diabetes in adults is lower than in children and the range of incidence is also reduced, with a less than threefold variation in adults, against an eightfold variation in children. There is a male excess in incidence, especially in the age group 25 to 29 years.

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Objective: The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up. Methods: This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression. Results: During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes (P!0.0001 for both). A BMI of %25 kg/m 2 and IA-2 IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P!0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P!0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P!0.0001, ORZ6.95). Conclusions: High GADA titer, BMI % 25, ZnT8 and IA-2 IC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients.

OBJECTIVE -The Sardinian type 1 diabetes register represented the basis to determine the most recent trends and the age distribution of type 1 diabetes incidence among Sardinians Ͻ15 years of age during 1989 . Part of the data (1989 has been already published by the EURODIAB Group with a lower completeness of ascertainment (87%). The geographical distribution of type 1 diabetes risk was also investigated. RESEARCH DESIGN AND METHODS -The new cases of type 1 diabetes in children aged 0 -14 years in Sardinia were prospectively registered from 1989 to 1999 according to the EURODIAB ACE criteria. The completeness of ascertainment calculated applying the capturerecapture method was 91%. Standardized incidence rates and 95% CI were calculated assuming the Poisson distribution. Trend of type 1 diabetes incidence was analyzed using the Poisson regression model. Maps of the geographical distribution of type 1 diabetes risk for the whole time period and separately for 1989 -1994 and 1995-1999 were produced applying a Bayesian method.RESULTS -A total of 1,214 type 1 diabetic patients were registered yielding to an overall age-and sex-standardized incidence rate of 38.8/100,000 (95% CI 36.7-41.1). There was a male excess with an overall male-to-female ratio of 1.4 (1.3-1.8). The increase of incidence during the 11 years analyzed was statistically significant (P ϭ 0.002) with a yearly increasing rate of 2.8% (1.0 -4.7). No evidence of an effect of age and sex on this trend has been found. The geographical distribution of type 1 diabetes relative risk (RR) showed that the highest risk areas are located in the southern and central-eastern part of the island and the lowest risk in the northeastern part, even if most of these differences were not statistically significant. This geographical distribution seemed to remain mainly the same between 1989 -1994 and 1995-1999. CONCLUSIONS -The homogeneity of diabetes risk and the increase of incidence over the age-groups in the Sardinian population stress the role of an environmental factor uniformly distributed among the genetically high-risk Sardinians.

OBJECTIVE -The Registry for Type 1 Diabetes Mellitus in Italy (RIDI) Study Group was established to coordinate the registries of type 1 diabetes in Italy. This report is based on 3,606 children younger than 15 years diagnosed with type 1 diabetes and prospectively registered during 1990 -1999 by nine centers, covering Ͼ35% of the Italian population.RESEARCH DESIGN AND METHODS -Registries were pooled in four geographic macro-areas: north, central, south, and insular. The completeness of registration was assessed by the capture-recapture method. Poisson regression analysis was used to evaluate temporal trend in incidence.RESULTS -Large variations in incidence were confirmed not only between Sardegna and the mainland but also among peninsular areas. In Sardegna, there was an excess of boys (the boy-to-girl incidence ratio was 1.4). The overall incidence showed average increases of 3.6% (P Ͻ 0.001) and 3.7% (P Ͻ 0.001) per year in peninsular Italy and in Sardegna, respectively. Significant increases in incidence rates were found in boys aged 10 -14 years (6.7%, 95% CI 0.5-13.3) and in girls aged 5-9 years (6.6%, 0.5-13.1) living in the southern area. The incidence rate also increased in boys aged 10 -14 years (5.0%, 0.3-10) and in girls aged 0 -4 years (4.9%, 0.8 -9.1) living in Sardegna.CONCLUSIONS -Italy is a country with large geographical variations in incidence rates of type 1 diabetes. However, the rates are evenly increasing both in the mainland and Sardegna, suggesting that similar environmental factors are operating over populations that have different genetic backgrounds.