Health service utilization and related costs attributable to diabetes.

AIMS: To estimate the health service use and direct healthcare costs attributable to diabetes using best available data and methods. METHODS: A nationally representative sample of adults aged ≥50 years was analysed (n=8107). Health service use in the previous 12 months included the number of general practitioner visits, outpatient department visits, hospital admissions, and accident and emergency department attendances. Multivariable negative binomial regression was used to estimate the associations between diabetes and frequency of visits. Average marginal effects were applied to unit costs for each health service and extrapolated to the total population, calculating the incremental costs associated with diabetes. RESULTS: The prevalence of diabetes was 8.0% (95% CI: 7.4, 8.6). In fully adjusted models, diabetes was associated with additional health service use. Compared to those without diabetes, people with diabetes have, on average, 1.49 (95% CI: 1.10, 1.88) additional general practitioner visits annually. Diabetes was associated with an 87% increase in outpatient visits, a 52% increase in hospital admissions and a 33% increase in accident and emergency department attendances (P<0.001). The incremental cost of this additional service use, nationally, is an estimated €88,894,421 annually, with hospital admissions accounting for 67% of these costs. CONCLUSION: Using robust methods, we identified substantially increased service use attributable to diabetes across the health system. Our findings highlight the urgent need to invest in the prevention and management of diabetes.

Trends in blindness due to diabetic retinopathy among adults aged 18-69years over a decade in Ireland.

AIMS: To describe trends in the incidence of visual impairment and blindness due to diabetic retinopathy among adults aged 18-69years in Ireland between 2004 and 2013. METHODS: Data on visual impairment due to diabetic retinopathy in adults aged 18-69years or over who are registered with the National Council for the Blind of Ireland, (2004-2013) were analysed. Annual incidence rates were calculated for the adult population and the population with diagnosed diabetes. Poisson regression was used to test for changes in rates over time. The relative, attributable and population risk of blindness and visual impairment due to diabetic retinopathy were calculated for 2013. RESULTS: Over the decade, the prevalence of diagnosed diabetes increased from 2.1% to 3.6%. Among people with diagnosed diabetes, the incidence of visual impairment due to diabetic retinopathy increased from 6.4 (95% CI 2.4-13.9) per 100,000 in 2004 to 11.7 (95% CI 5.9-21.0) per 100,000 in 2013. The incidence of blindness due to diabetic retinopathy varied from 31.9 per 100,000 (95% CI 21.6-45.7) in 2004 to 14.9 per 100,000 (95% CI 8.2-25.1) in 2013. CONCLUSIONS: Our findings indicate the need for increased attention to preventive measures for microvascular complications among adults with diabetes in Ireland. Retinopathy screening has been standardised in Ireland, these findings provide useful baseline statistics to monitor the impact of this population-based screening programme.

Evaluating the implementation of a national clinical programme for diabetes to standardise and improve services: a realist evaluation protocol.

BACKGROUND: Over the last three decades in response to the growing burden of diabetes, countries worldwide have developed national and regional multifaceted programmes to improve the monitoring and management of diabetes and to enhance the coordination of care within and across settings. In Ireland in 2010, against a backdrop of limited dedicated strategic planning and engrained variation in the type and level of diabetes care, a national programme was established to standardise and improve care for people with diabetes in Ireland, known as the National Diabetes Programme (NDP). The NDP comprises a range of organisational and service delivery changes to support evidence-based practices and policies. This realist evaluation protocol sets out the approach that will be used to identify and explain which aspects of the programme are working, for whom and in what circumstances to produce the outcomes intended. METHODS/DESIGN: This mixed method realist evaluation will develop theories about the relationship between the context, mechanisms and outcomes of the diabetes programme. In stage 1, to identify the official programme theories, documentary analysis and qualitative interviews were conducted with national stakeholders involved in the design, development and management of the programme. In stage 2, as part of a multiple case study design with one case per administrative region in the health system, qualitative interviews are being conducted with frontline staff and service users to explore their responses to, and reasoning about, the programme's resources (mechanisms). Finally, administrative data will be used to examine intermediate implementation outcomes such as service uptake, acceptability, and fidelity to models of care. DISCUSSION: This evaluation is using the principles of realist evaluation to examine the implementation of a national programme to standardise and improve services for people with diabetes in Ireland. The concurrence of implementation and evaluation has enabled us to produce formative feedback for the NDP while also supporting the refinement and revision of initial theories about how the programme is being implemented in the dynamic and unstable context of the Irish healthcare system.

The prevalence of Type 2 diabetes and related complications in a nationally representative sample of adults aged 50 and over in the Republic of Ireland.

AIM: To investigate the prevalence of diagnosed Type 2 diabetes and its related complications in a nationally representative sample of older adults in the Republic of Ireland. METHODS: Cross-sectional analysis of a population-based sample of adults aged ≥ 50 years from the first wave of The Irish Longitudinal Study on Ageing (TILDA), (2009-2011). Diagnosed Type 2 diabetes prevalence was estimated by self-report or the use of oral hypoglycaemic agents. The prevalence of microvascular and macrovascular complications was determined by self-report. RESULTS: Diagnosed Type 2 diabetes prevalence was 8.4% [95% confidence interval (CI): 7.8-9.0%] and was higher among men [10.3% (95% CI: 9.4-11.2%)] than women [6.6% (95% CI: 5.9-7.5%)]; P ≤ 0.001. Among participants with diagnosed Type 2 diabetes, the overall prevalence of microvascular complications was 26.0% (95% CI: 22.4-30.0%) with no evidence of gender-specific differences (P = 0.7). The overall prevalence of macrovascular complications was 15.1% (95% CI: 12.2-18.4%) and was higher among men [17.8% (95% CI: 14.3-23.1%)] than women [11.4% (95% CI: 7.7-16.4%)]; P ≤ 0.001. CONCLUSIONS: In the absence of a national diabetes register, these findings provide a robust estimate of the national prevalence of diagnosed Type 2 diabetes and level of complications among adults aged 50 years and over in Ireland.

Microvariation at the human D1S80 locus.

The minisatellite locus D1S80, (location: 1p35-p36) GenBank sequence accession # D28507), is a variable number of tandem repeat (VNTR) locus with a 16 base pair repeat size. The sequence of the predominant core repeat region and variants of the D1S80 locus were determined to ascertain whether sequence variation or size variation is the cause of altered migration of some D1S80 alleles. A total of 23 alleles from 14 individuals, previously typed based on the number of repeats (i.e. nominal alleles) for the D1S80 locus, were selected for sequence analysis. The individuals were from African American, Caucasian, and Hispanic databases. From these, 18 different repeat unit sequences were observed and arbitrarily designated A-R. Structural relationships between the alleles became more apparent when the arrays of repeat units were divided into common motifs or super-repeat domains. Six motifs ranging from 3 to 9 repeat units were identified. Several of the alleles included repeat arrays which were too diverse to predict an evolutionary relationship, however, there are two general repeat motif arrays and each has some relationship with either the 18 or the 24 repeat allele. The D1S80 allelic polymorphism is primarily due to variation in the number of repeat units and to sequence variation among repeats, however, it can not be ruled out that some rare alleles may be due to insertions or deletions.

Hinf I/Tsp509 I and BsoF I polymorphisms in the flanking regions of the human VNTR locus D1S80.

The minisatellite locus D1S80 (1p35-p36), is a highly polymorphic VNTR that also contains a Hinf I polymorphism in the 5' flanking region. Our data suggest that the Hinf I polymorphism is a G > T transversion 58 bases downstream from the forward primer. This G > T transversion also creates a Tsp509 I restriction site. Additionally, a G > C transversion polymorphism was identified in the 3' flanking region by the creation of a BsoF I restriction site immediately adjacent to the repeat region.

Allozyme variability and relatedness in six crayfish species.

A total of twenty-six allozyme loci were assayed in six crayfish species. Estimated mean heterozygosity was low (5.5 percent) for all species in comparison with the invertebrate average. The specific values, however, ranged from 2.9 percent to 8.3 percent. These crayfish estimates are consistent with estimates for other decapods where low heterozygosity is the rule. The consistency of low heterozygosity estimates in the order Decapoda suggests that its explanation may include both order specific differences such as low mutation or intracistronic recombination rates and species specific differences. A dendrogram, constructed using Nei's D, is in agreement with the morphological clustering.

Genetic load in natural populations: is it compatible with the hypothesis that many polymorphisms are maintained by natural selection?

Recent studies of genetically controlled enzyme variation lead to an estimation that at least 30 to 60% of the structural genes are polymorphic in natural populations of many vertebrate and invertebrate species. Some authors have argued that a substantial proportion of these polymorphisms cannot be maintained by natural selection because this would result in an unbearable genetic load. If many polymorphisms are maintained by heterotic natural selection, individuals with much greater than average proportion of homozygous loci should have very low fitness. We have measured in Drosophila melanogaster the fitness of flies homozygous for a complete chromosome relative to normal wild flies. A total of 37 chromosomes from a natural population have been tested using 92 experimental populations. The mean fitness of homozygous flies is 0.12 for second chromosomes, and 0.13 for third chromosomes. These estimates are compatible with the hypothesis that many (more than one thousand) loci are maintained by heterotic selection in natural populations of D. melanogaster.

Genetic variation in natural populations of five Drosophila species and the hypothesis of the selective neutrality of protein polymorphisms.

We have studied genetic variation at 30-32 loci coding for enzymes in natural populations of five species of Drosophila. The average proportion of heterozygous loci per individual is 17.7 +/- 0.4%. The average proportion of polymorphic loci per population is 69.2 +/- 2.6% or 49.8 +/- 2.2%, depending on what criterion of polymorphism is used. The following generalizations are advanced: (1) The amount of genetic polymorphism varies considerably from locus to locus. (2) At a given locus, populations of the same species are very similar in the amount and pattern of genetic variation. (3) However, at some loci large differences sometimes occur between local populations of the same species. (4) The amount of variation at a given locus is approximately the same in all five species. (5) When different species are compared, the pattern of the variation is either essentially identical or totally different at a majority of loci. We have tested the hypothesis that protein polymorphisms are selectively neutral by examining four predictions derived from the hypothesis. Our results are at variance with every one of the predictions. We have measured the amount of genetic differentiation, D, between taxa of various degrees of evolutionary divergence. The average value of D is 0.033 for local populations, 0.228 for subspecies, 0.226 for semispecies, 0.538 for sibling species, and 1.214 for morphologically distinguishable species. Our results indicate that a substantial degree of genetic differentiation (22.8 allelic substitutions for every 100 loci) occurs between allopatric populations that have diverged to the point where they might become different species if they were to become sympatric. However, very little additional genetic change is required for the development of complete reproductive isolation. After the speciation process is completed, species continue to diverge genetically from each other.

Genetic differentiation within and between species of the Drosophila willistoni group.

We describe allelic variation at 28 loci in six Caribbean populations of four sympatric species of Drosophila. Within any one species the allelic frequencies are very similar from population to population, although there is evidence of local as well as regional genetic differentiation. The genetic distance is greater between populations from different islands than between populations of the same island. When the allelic frequencies are compared between different species, a remarkable pattern appears. In any pair of species nearly half of the loci have essentially identical allelic frequencies, while nearly the other half of the loci have different alleles and in different frequencies. The loci with nearly identical allelic frequencies are different when different pairs of species are compared. The patterns of allelic variation within and between species are inconsistent with the hypothesis that the variation is adaptively neutral. Migration or mutation cannot explain the patterns of genetic variation, either. Balancing natural selection is the main process maintaining protein polymorphisms in natural populations.

Sex chromosome translocations in the evolution of reproductive isolation.

Haldane's rule states that in organisms with differentiated sex chromosomes, hybrid sterility or inviability is generally expressed more frequently in the heterogametic sex. This observation has been variously explained as due to either genic or chromosomal imbalance. The fixation probabilities and mean times to fixation of sex-chromosome translocations of the type necessary to explain Haldane's rule on the basis of chromosomal imbalance have been estimated in small populations of Drosophila melanogaster. The fixation probability of an X chromosome carrying the long arm of the Y(X.Y(L)) is approximately 30% greater than expected under the assumption of no selection. No fitness differences associated with the attached Y(L) segment were detected. The fixation probability of a deficient Y chromosome is 300% greater than expected when the X chromosome contains the deleted portion of the Y. It is suggested that sex-chromosome translocations may play a role in the establishment of reproductive isolation.

Enzyme variability in the Drosophila willistoni group. IV. Genic variation in natural populations of Drosophila willistoni.

We describe allelic variation at 28 gene loci in natural populations of D. willistoni. Seventy samples were studied from localities extending from Mexico and Florida, through Central America, the West Indies, and tropical South America, down to South Brazil. At least several hundred, and often several thousand, genomes were sampled for each locus. We have discovered a great deal of genetic variation. On the average, 58% loci are polymorphic in a given population. (A locus is considered polymorphic when the frequency of the most common allele is no greater than 0.95). An individual fly is heterozygous, on the average, at 18.4% loci.-Concerning the pattern of the variation, the most remarkable finding is the similarity of the configuration of allelic frequencies from locality to locality throughout the distribution of the species. Our observations support the conclusion that balancing natural selection is the major factor responsible for the considerable genetic variation observed in D. willistoni.