Childhood-onset Insulin-dependent Diabetes Research Articles

Reliability and validity of the Wolfram Unified Rating Scale (WURS)

BackgroundWolfram syndrome (WFS) is a rare, neurodegenerative disease that typically presents with childhood onset insulin dependent diabetes mellitus, followed by optic atrophy, diabetes insipidus, deafness, and neurological and psychiatric dysfunction. There is no cure for the disease, but recent advances in research have improved understanding of the disease course. Measuring disease severity and progression with reliable and validated tools is a prerequisite for clinical trials of any new intervention for neurodegenerative conditions. To this end, we developed the Wolfram Unified Rating Scale (WURS) to measure the severity and individual variability of WFS symptoms. The aim of this study is to develop and test the reliability and validity of the Wolfram Unified Rating Scale (WURS).MethodsA rating scale of disease severity in WFS was developed by modifying a standardized assessment for another neurodegenerative condition (Batten disease). WFS experts scored the representativeness of WURS items for the disease. The WURS was administered to 13 individuals with WFS (6-25 years of age). Motor, balance, mood and quality of life were also evaluated with standard instruments. Inter-rater reliability, internal consistency reliability, concurrent, predictive and content validity of the WURS were calculated.ResultsThe WURS had high inter-rater reliability (ICCs>.93), moderate to high internal consistency reliability (Cronbach’s α = 0.78-0.91) and demonstrated good concurrent and predictive validity. There were significant correlations between the WURS Physical Assessment and motor and balance tests (rs>.67, p<.03), between the WURS Behavioral Scale and reports of mood and behavior (rs>.76, p<.04) and between WURS Total scores and quality of life (rs=-.86, p=.001). The WURS demonstrated acceptable content validity (Scale-Content Validity Index=0.83).ConclusionsThese preliminary findings demonstrate that the WURS has acceptable reliability and validity and captures individual differences in disease severity in children and young adults with WFS.

Divergent trends in the incidence of end‐stage renal disease due to Type 1 and Type 2 diabetes in Europe, Canada and Australia during 1998–2002

To describe the variation in geographical distribution of end-stage renal disease (ESRD) due to Type 1 and Type 2 diabetes, and to calculate recent trends in incidence in predominantly white populations. Estimation of age- and sex-standardized incidence of ESRD by type of diabetes, and temporal trends, in population-based data for persons aged 30-44, 45-54 or 55-64 years newly treated for ESRD during 1998-2002 in eight countries or regions of Europe, and Non-Indigenous Canadians and Australians. The incidence of ESRD due to Type 1 diabetes at age 30-44 years correlated with published rates of childhood-onset insulin dependent diabetes mellitus (P = 0.0025). ESRD due to Type 2 diabetes was uncommon before 45 years of age; in older persons, the highest rates (in Canada and Austria) were five times the lowest rates (in Norway and the Basque region). Rates of ESRD due to Type 1 diabetes fell, per year, by 6.4%[95% confidence interval (CI): 2.1-10.6%) in persons aged 30-44 years, and by 7.7% (95% CI: 2.4-12.7%] in those aged 45-54 years. In contrast, rates of ESRD due to Type 2 diabetes increased annually by 16% (95% CI: 5-28%) in the 30-44-year age group, 11% (95% CI: 6-16%) at 45-54 years, and 9% (95% CI: 5-14%) at 55-64 years. Modern prevention has reduced progression of nephropathy to ESRD due to Type 1 diabetes, but the continuing rise of ESRD due to Type 2 diabetes represents a failure of current disease control measures that has serious public health implications.

Incidence, prevalence, and mortality of insulin-dependent (type 1) diabetes mellitus in Lithuanian children during 1983-98.

Our purpose is to analyze interrelations of the incidence, prevalence and mortality of childhood-onset insulin-dependent diabetes mellitus (type 1) in Lithuania. Incidence and prevalence rates were based on the national type 1 diabetes register during 1983-98. The cohort study was performed to evaluate the standardized mortality ratios. The average incidence of type 1 diabetes during the 16-yr study period was 7.36 per 100,000/yr. For both males and females the highest incidence of type 1 diabetes was recorded in the 10-14 yr age group. The regression-based linear trends of the increase in incidence in various age groups and the annual percentage change for both genders was 2.05 (p = 0.0039) and the greatest regression slope is observed for both genders in the 10-14 yr age group. Regression-based linear trends in type 1 diabetes prevalence indicate an even growth in all age groups (3.47; p = 0.001), although the annual percentage change is most prominent in the 5-9 yr age group for girls (4.95%/yr) and in the 10-14 yr age group for boys (4.06%/yr). The standardized mortality ratio of all-cause mortality in people with diabetes is higher than in the common population 7.71 (p < 0.0001). The standard mortality ratio for all causes increases with longer diabetes duration. The significant increasing trend of incidence and prevalence during 1983-98 is observed. The annual percentage change is similar. The young patients with type 1 diabetes have a higher mortality risk.

The Association of HLA-class I Antigens and Class II Genotypes with Childhood-onset Insulin-Dependent Diabetes Mellitus in Japanese

The Association of HLA-class I Antigens and Class II Genotypes with Childhood-onset Insulin-Dependent Diabetes Mellitus in Japanese

Incidence of childhood diabetes mellitus in Yorkshire, northern England, is associated with nitrate in drinking water: an ecological analysis

The relationship between the incidence of childhood-onset insulin-dependent diabetes mellitus and levels of nitrate in drinking water in the former Yorkshire Regional Health Authority was investigated by means of an ecological analysis. A population-based register contributed 1797 0-16-year-olds diagnosed with diabetes between 1978 and 1994. Nitrate data were based on 9330 samples of drinking water tested between 1990 and 1995 in 148 water supply zones, for which 1991 census small area statistics were taken on population density, ethnicity and socio-economic status. Diabetes incidence was positively associated with raised mean nitrate levels with a standardised incidence ratio of 115 in zones with greater than 14.85 mg.1-1 (chi2 = 26.81, 1 df, p < 0.001). Significant negative trends were found between standardised incidence ratios and proportion of non-whites in the population (chi2 = 33.57, 1 df, p < 0.001), childhood population density (chi2 = 30.81, 1 df, p < 0.001) and the Townsend deprivation score (chi2 = 33.89, 1 df, p < 0.001). Poisson regression modelling, adjusting for the other factors, showed a significant increase in relative incidence rate ratio from a baseline of 1 at nitrate levels below 3.22 mg.1-1 to 1.27 (95% confidence interval 1.09, 1.48) for mean nitrate levels above 14.85 mg.1-1. An association between higher nitrate levels in domestic drinking water and incidence of childhood diabetes has been demonstrated. This was not explained by the ethnic composition of the population, population density or socioeconomic status. Nitrate in drinking water may be a precursor of chemicals which are toxic to the pancreas.

Incidence trends in childhood onset IDDM in four countries around the Baltic sea during 1983-1992.

We present secular trends of childhood onset insulin-dependent diabetes mellitus (IDDM) in Finland, Estonia, Latvia and Lithuania during the period of 1983-1992. Incidence data were obtained from the national IDDM registries. The average age-standardized incidence per 100,000/year was 35.0 in Finland, followed by 10.2 in Estonia, 7.1 in Lithuania and 6.5 in Latvia. A male excess in incidence was recorded in Finland (1.15) and Latvia (1.01). In all countries, the highest age-specific risk of IDDM was observed in the 11-13 year age range. The large difference in incidence between Finland and other Baltic countries was see even in 1-2 year-old children. During the 10-year study period overall changes in incidence of IDDM were relatively small in these four countries. The incidence increased in Finland and Lithuania on average by 1% and 1.4% per year, respectively. A statistically significant increase was recorded only in 0-4 year old children in Finland, at 5.6% per year. In Estonia, an 8.3% increase in this age group, however, was not statistically significant. The different trends in the age-group specific incidence rates were confirmed in Finland. In conclusion, from 1983 to 1992 the incidence of childhood onset IDDM was increasingly in Finland and Lithuania, while in Latvia and Estonia it was stable. There are still great differences in IDDM incidence between the countries around the Baltic Sea.

Intrauterine growth pattern and risk of childhood onset insulin dependent (type I) diabetes: population based case-control study.

To investigate whether prenatal growth affects the risk of development of childhood onset insulin dependent (type I) diabetes mellitus. Population based case-control study. Data from a nationwide childhood diabetes case register were linked with data from the nationwide Swedish Medical Birth Registry. Data from a total of 4584 diabetic children born after 1973 and diagnosed with diabetes from 1978 to 1992 were studied. For each child with insulin dependent diabetes three control children were randomly selected from among all infants born in the same year and at the same hospital as the proband. Birth weight, gestation, maternal age and parity, number of previous spontaneous abortions, and sex specific birth weight by gestational week expressed as multiples of the standard deviation (SD). There was a clear trend in the odds ratio for childhood onset diabetes according to SD of birth weight. The odds ratio (95% confidence interval) for small for gestational age after stratification for maternal age, parity, smoking habits, and maternal diabetes was 0.81 (0.65 to 0.99) and for large for gestational age after similar stratification was 1.20 (1.02 to 1.42). Intrauterine conditions that affect prenatal growth seem also to affect the risk of development of childhood diabetes in the way previously described for postnatal growth: a poor growth decreases and an excess growth increases the risk. The mechanism for this association is unclear.

The changing course of diabetic nephropathy: Low-density lipoprotein cholesterol and blood pressure correlate with regression of proteinuria

Diabetic nephropathy (DN) as manifested by persistent and clinically evident proteinuria, has long been considered an irreversible process that predicts a rapid decline in renal function. The observation of reversal of DN in several individuals enrolled in a prospective study of the natural course of diabetes complications challenged this view and led to the current investigation into the correlates of such regression of proteinuria. DN was defined as a median albumin excretion rate (AER) over 200 μg/min in two or three urine collections obtained at baseline, and again at 2 and 4 years of follow-up. Among 658 individuals with childhood-onset insulin-dependent diabetes mellitus (IDDM), 146 had DN at baseline. Nine subsequently died without renal failure, and 13 were lost to follow-up. Of the 124 subjects with at least survey follow-up data, 32 (24%) developed renal failure, and 78 of the remaining 92 provided full quantitative data. AER decreased by ≥10-fold into the microalbuminuric (20 to 200 μg/min) or normal range (<20 μg/min) in 7 of these individuals and are called “regressors of proteinuria.” Compared with the remaining 71 subjects, the strongest correlate of regression of proteinuria was an improvement in fasting plasma low-density lipoprotein cholesterol (LDL-C) in the 7 regressors ( P < 0.008). Improved glycemic control was not a significant predictor of improved AER. Five of the 7 individuals with improved AER had a baseline median AER below 500 μg/min. When the 7 regressors of proteinuria were combined with an additional 38 individuals who also experienced smaller decreases in median AER, such improvement was associated with a more favorable systolic (or diastolic) blood pressure (BP) change ( P < 0.01), and a decrease in plasma LDL-C level ( P = 0.01). These data suggest that proteinuria in DN may substantially regress in approximately 6% and improve in at least 34% of individuals with IDDM over a 4-year period, often in association with a decrease in plasma LDL-C concentration or stabilization or improvement in BP. Furthermore, the data suggest that the nonreversibility threshold for diabetic nephropathy may be higher (500 μg/min) than previously reported (200 μg/min).

Biomedical and Psychiatric Risk Factors for Retinopathy Among Children With IDDM

Illness duration and glycemic control influence the development of retinopathy in childhood-onset insulin-dependent diabetes mellitus (IDDM). Psychiatric disorders and sociodemographic factors also affect diabetes-related outcomes. However, biomedical and psychosocial factors have not been examined together in modeling the risk of retinopathy. We conducted a single-site prospective longitudinal study of 66 children (aged 8-13 years) newly diagnosed with IDDM. Repeated assessments served to derive psychiatric diagnoses. Poor glycemic control was defined as the upper 15th percentile of all HbA1 values. After a median follow-up of 10 years, severity of retinopathy was determined. It was modeled with a stepwise polychotomous regression procedure using antecedent biomedical and psychosocial variables. Young adults with childhood-onset IDDM were found to be at increased risk of retinopathy the longer they had IDDM, the more persistently they evidenced poor antecedent glycemic control, and the longer they suffered from depressive illness. These three factors operated individually and additively, with duration of IDDM conferring a baseline level of risk. In depressed patients (27%), depression onset antedated the detection of retinopathy generally by 7 years. Duration of childhood-onset IDDM confers a baseline level of risk of retinopathy irrespective of glycemic control; antecedent clinical depression is also a risk factor. Depression therefore may serve as a marker of vulnerability and help to identify a subgroup of patients at risk for complications. The findings raise the question whether timely treatment of depression could forestall diabetic retinopathy.

Eating Disorders and Maladaptive Dietary/Insulin Management among Youths with Childhood-Onset Insulin-Dependent Diabetes Mellitus

To determine the prevalence of DSM-III eating disorder and the conjoint symptoms of maladaptive dietary/insulin management (irrespective of eating disorder) and their psychiatric and biomedical correlates among youths with childhood-onset insulin-dependent diabetes mellitus (IDDM). Forty-four girls and 35 boys, 8 to 13 years old at IDDM onset, were repeatedly interviewed during an interval of up to 14 years (mean = 9 years) to ascertain psychiatric disorders and behaviors related to diabetes care. Metabolic control and IDDM-related hospitalizations also were monitored. By the mean age of approximately 21 years, 3.8% of the sample had DSM-III eating disorders and 11.4% had "eating problems," defined as the conjoint symptoms of severe dietary indiscretion and repeated insulin omission (irrespective of eating disorders). Youths with "eating problems" were nine times more likely to have had a psychiatric disorder than the rest of the patients, and they had a significantly higher rate of pervasive noncompliance with medical treatment. No between-group differences were found in metabolic control and rates of multiple hospitalizations. The diabetes-specific symptom-pair of serious dietary indiscretion and repeated insulin omission appears to identify youths who have had other problems as well. The association of eating problems with psychiatric disorders (other than eating disorders) suggests that a subgroup of diabetic youths have various difficulties in coping with the medical illness and require close monitoring and psychosocial intervention.

Effects of insulin-dependent diabetes on learning and memory efficiency in adults

Previous work with elderly adults with maturity-onset non-insulin-dependent diabetes has demonstrated the presence of significant learning and memory deficits which are correlated with the degree of chronic hyperglycemia. This study was conducted to examine learning and memory processes in a group of 82 younger adults (mean age = 33.4 years) with a long history (mean duration = 26.2 years) of childhood-onset insulin-dependent diabetes. Contrary to expectation, diabetic subjects performed as well as a group of 82 age- and SES-matched nondiabetic control subjects on all measures of learning and memory. On the other hand, they performed significantly worse on measures of psychomotor efficiency, with degree of chronic hyperglycemia being the best predictor of psychomotor slowing. These findings, together with earlier studies of elderly diabetic patients, suggest that specific neural systems within the aging brain may be differentially sensitive to the "toxic" effects of chronic hyperglycemia.