Manifestations of type 2 diabetes in corneal endothelial cell density, corneal thickness and intraocular pressure

We sought to evaluate central corneal thickness (CCT), corneal endothelial cell density (ECD) and intraocular pressure (IOP) in patients with type 2 diabetes mellitus (DM) and to associate potential differences with diabetes duration and treatment modality in a prospective, randomized study. We measured ECD, CCT and IOP of 125 patients with type 2 DM (mean age 57.1¡11.5 years) and compared them with 90 age-matched controls. Measured parameters were analyzed for association with diabetes duration and glucose control modalities (insulin injection or oral medication) while controlling for age. In the diabetic group, the mean ECD (2511¡252 cells/mm2), mean CCT (539.7¡33.6 mm) and mean IOP (18.3¡2.5 mmHg) varied significantly from those the control group [ECD: 2713¡132 cells/mm2 (P,0.0001), CCT: 525.0¡45.3 mm (P50.003) and IOP: 16.7¡1.8 mmHg (P,0.0001)]. ECD was significantly reduced by about 32 cell/mm2 for diabetics with duration of .10 years when compared with those with duration of ,10 years (P,0.05). CCT was thicker and IOP was higher for diabetics with duration of .10 years than those with duration of ,10 years (P.0.05). None of the measured parameters was significantly associated with diabetes duration and treatment modality (P.0.05). In conclusion, subjects with type 2 DM exhibit significant changes in ECD, IOP and CCT, which, however, are not correlated with disease duration or if the patients receive on insulin injection or oral medications.

Using mobile technology to motivate adolescents with type 1 diabetes mellitus: A systematic review of recent literature

Introduction Behavioural interventions have been shown to improve outcomes in patients with type 1 diabetes mellitus (T1DM). There are a small number of studies that suggest text-messages (TM), native mobile applications (NMAs), and other mobile tools may be useful platforms for delivering behavioural interventions to adolescents. Aim The aim of this study was to explore, by way of a systematic review of available literature, (a) the outcomes of interventions using mobile technology for youth with T1DM and (b) what mobile technologies, functional design elements and aesthetic design elements have the best evidence to support their use. Methods A search of six online databases returned 196 unique results, of which 13 met the inclusion criteria. Results Four studies were randomised controlled trials (RCTs), and all others prospective cohort studies. TM (10) was the most common intervention technology, while NMAs were used in four studies. The most common outcome measured was HbA1c (9); however, only three studies showed a significant decrease. Similarly, the results reported for other outcome measures were mixed. The studies included in this review suggest that interventions which have data collection and clinician support functionality may be more effective in improving adherence and glycaemic control, but more evidence is needed. Further, the evidence base supporting the use of NMAs in T1DM management for adolescents is weak, with most studies adopting TM as the intervention tool. Overall, the studies lack adequate descriptions of their methodology, and better quality studies are required to inform future intervention design.

Australian patients using a cardiac-diabetes web-based intervention program: Contributions to person-centered clinical practice

Rationale, aims and objectives: Patients with both cardiac disease and diabetes have poorer health outcomes than patients with only one chronic condition. While evidence indicates that internet based interventions may improve health outcomes for patients with a chronic disease, there is no literature on internet programs specific to cardiac patients with comorbid diabetes. Therefore this study aimed to develop a specific web-based program, then to explore patients’ perspectives on the usefulness of a new program. Methods: The interpretive approach using semi-structured interviews on a purposive sample of eligible patients with type 2 diabetes and a cardiac condition in a metropolitan hospital in Brisbane, Australia. Thematic analysis was undertaken to describe the perceived usefulness of a newly developed Heart2heart webpage. Results: Themes identified included confidence in hospital health professionals and reliance on doctors to manage conditions. Patients found the webpage useful for managing their conditions at home. Conclusions: The new Heart2heart webpage provided a positive and useful resource. Further research on to determine the potential influence of this resource on patients’ self-management behaviours is paramount. Implications for practice include using multimedia strategies for providing information to patients’ comorbidities of cardiac disease and type 2 diabetes, and further development on enhancement of such strategies

Conformational epitopes on the diabetes autoantigen GAD65 identified by peptide phage display and molecular modeling

The major diabetes autoantigen, glutamic acid decarboxylase (GAD65), contains a region of sequence similarity, including six identical residues PEVKEK, to the P2C protein of coxsackie B virus, suggesting that cross-reactivity between coxsackie B virus and GAD65 can initiate autoimmune diabetes. We used the human islet cell mAbs MICA3 and MICA4 to identify the Ab epitopes of GAD65 by screening phage-displayed random peptide libraries. The identified peptide sequences could be mapped to a homology model of the pyridoxal phosphate (PLP) binding domain of GAD65. For MICA3, a surface loop containing the sequence PEVKEK and two adjacent exposed helixes were identified in the PLP binding domain as well as a region of the C terminus of GAD65 that has previously been identified as critical for MICA3 binding. To confirm that the loop containing tile PEVKEK sequence contributes to the MICA3 epitope, this loop was deleted by mutagenesis. This reduced binding of MICA3 by 70%. Peptide sequences selected using MICA4 were rich in basic or hydroxyl-containing amino acids, and the surface of the GAD65 PLP-binding domain surrounding Lys358, which is known to be critical for MICA4 binding, was likewise rich in these amino acids. Also, the two phage most reactive width MICA4 encoded the motif VALxG, and the reverse of this sequence, LAV, was located in this same region. Thus, we have defined the MICA3 and MICA4 epitopes on GAD65 using the combination of phage display, molecular modeling, and mutagenesis and have provided compelling evidence for the involvement of the PEVKEK loop in the MICA3 epitope.

After 10 years of clinical trials with liraglutide, do we know whether it is beneficial in diabetes?

Type 2 diabetes remains an escalating world-wide problem, despite a range of treatments. The revelation that insulin secretion is under the control of a gut hormone, glucagon-like peptide 1 (GLP-1), led to a new paradigm in the management of type 2 diabetes. Liraglutide is a long acting GLP-1 receptor agonist used in the treatment of type 2 diabetes. The review considers the clinical trials with liraglutide. There are many comparator trials between liraglutide and other medicines for the treatment of type 2 diabetes, and these trials have shown that liraglutide lowers HbA1c and body weight, and is well tolerated. A large cardiovascular safety trial with liraglutide is presently being undertaken. After 10 years of clinical trials with liraglutide, we do not know whether liraglutide has cardiovascular safety in subjects with type 2 diabetes and high cardiovascular risk. Although this is not a requirement for registration by the Food and Drug Administration (FDA), in my opinion, they should reconsider this. We also do not presently know whether liraglutide has any beneficial effects on clinical cardiovascular outcomes.

Adherence to insulin treatment in diabetes: Can it be improved?

Insulin is used in all subjects with Type 1 diabetes, and when Type 2 diabetes is not controlled by oral anti-diabetic medicines, insulin is also used in Type 2 diabetes. However, despite this use, there is still increased mortality and morbidity in subjects with diabetes, compared to subjects without diabetes. One of the factors, which may be involved in this increased mortality and morbidity in subjects with diabetes, is nonadherence to insulin. Nonadherence rates to insulin are in the range20-38%, and many factors contribute to the nonadherence. The major aim of the review was to determine whether interventions to improve adherence to insulin do actually improve adherence to insulin. Most studies have shown that adherence to insulin was improved by changing from the vial-and-syringe approach to prefilled insulin pens, but not all studies have shown that this translated into better glycemic control and clinical outcomes. The results of studies using automatic telephone messages to improve adherence to insulin to date are inconclusive. There is limited and variable evidence that an intervention by a nurse/educator, which discusses adherence to medicines, does improve adherence to insulin. In contrast, there is little or no evidence that an extra intervention by a doctor or an intervention by a pharmacist, which discusses adherence to insulin, does actually improve the measured adherence to insulin. In conclusion, rather than assuming that an intervention by a health professional discussing adherence to insulin actually improves adherence to insulin, long-term studies investigating this are required.

Evaluation of physical activity among adults with diabetes mellitus from Sri Lanka

We evaluated the patterns of physical activity (PA) and the prevalence of physical inactivity among Sri Lankan adults with diabetes mellitus. Data were collected as part of a wider cross-sectional national study on diabetes in Sri Lanka. PA during the past week was assessed using the short version of the IPAQ. Overall prevalence of physical inactivity was 13.9%. Females (3091 ± 2119) had a significantly higher mean weekly total MET minutes than males (2506 ± 2084) (p < 0.01). Inactivity of those residing in urban (17.2%) areas was higher than rural (12.6%) in all adults. Participants from Moor ethnicity were more inactive compared to others. Adults who were physically active had significantly low waist and hip circumferences, BMI and systolic blood pressure.

Prevalence of retinopathy among adults with self-reported diabetes mellitus: the Sri Lanka diabetes and Cardiovascular Study

Background: At present there are no large scale nationally-representative studies from Sri Lanka on the prevalence and associations of Diabetic Retinopathy (DR). The present study aims to evaluate the prevalence and risk factors for DR in a community-based nationally-representative sample of adults with self-reported diabetes mellitus from Sri Lanka. Methods: A cross-sectional community-based national study among 5,000 adults (≥18 years) was conducted in Sri Lanka, using a multi-stage stratified cluster sampling technique. An interviewer-administered questionnaire was used to collect data. Ophthalmological evaluation of patients with ‘known’ diabetes (previously diagnosed at a government hospital or by a registered medical practitioner) was done using indirect ophthalmoscopy. A binary-logistic regression analysis was performed with ‘presence of DR’ as the dichotomous dependent variable and other independent covariates. Results: Crude prevalence of diabetes was 12.0%(n=536),of which 344 were patients with ‘known’ diabetes.Mean age was 56.4 ± 10.9 years and 37.3% were males. Prevalence of any degree of DR was 27.4% (Males-30.5%, Females-25.6%; p = 0.41). In patients with DR, majority had NPDR (93.4%), while 5.3% had maculopathy. Patients with DR had a significantly longer duration of diabetes than those without. In the binary-logistic regression analysis in all adults duration of diabetes (OR:1.07), current smoking (OR:1.67) and peripheral neuropathy (OR:1.72)all were significantly associated with DR. Conclusions: Nearly 1/3rd of Sri Lankan adults with self-reported diabetes are having retinopathy. DR was associated with diabetes duration, cigarette smoking and peripheral neuropathy. However, further prospective follow up studies are required to establish causality for identified risk factors

Living well with diabetes: 24-month outcomes from a randomized trial of telephone-delivered weight loss and physical activity intervention to improve glycemic control

OBJECTIVE: To evaluate the effectiveness of a telephone-delivered behavioral weight loss and physical activity intervention targeting Australian primary care patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Pragmatic randomized controlled trial of telephone counseling (n = 151) versus usual care (n = 151). Reported here are 18-month (end-of-intervention) and 24-month (maintenance) primary outcomes of weight, moderate-to-vigorous-intensity physical activity (MVPA; via accelerometer), and HbA1c level. Secondary outcomes include dietary energy intake and diet quality, waist circumference, lipid levels, and blood pressure. Data were analyzed via adjusted linear mixed models with multiple imputation of missing data. RESULTS: Relative to usual-care participants, telephone counseling participants achieved modest, but significant, improvements in weight loss (relative rate [RR] -1.42% of baseline body weight [95% CI -2.54 to -0.30% of baseline body weight]), MVPA (RR 1.42 [95% CI 1.06-1.90]), diet quality (2.72 [95% CI 0.55-4.89]), and waist circumference (-1.84 cm [95% CI -3.16 to -0.51 cm]), but not in HbA1c level (RR 0.99 [95% CI 0.96-1.02]), or other cardio-metabolic markers. None of the outcomes showed a significant change/deterioration over the maintenance period. However, only the intervention effect for MVPA remained statistically significant at 24 months. CONCLUSIONS: The modest improvements in weight loss and behavior change, but the lack of changes in cardio-metabolic markers, may limit the utility, scalability, and sustainability of such an approach.

Missing in space: An evaluation of imputation methods for missing data in spatial analysis of risk factors for type II diabetes

Background Spatial analysis is increasingly important for identifying modifiable geographic risk factors for disease. However, spatial health data from surveys are often incomplete, ranging from missing data for only a few variables, to missing data for many variables. For spatial analyses of health outcomes, selection of an appropriate imputation method is critical in order to produce the most accurate inferences. Methods We present a cross-validation approach to select between three imputation methods for health survey data with correlated lifestyle covariates, using as a case study, type II diabetes mellitus (DM II) risk across 71 Queensland Local Government Areas (LGAs). We compare the accuracy of mean imputation to imputation using multivariate normal and conditional autoregressive prior distributions. Results Choice of imputation method depends upon the application and is not necessarily the most complex method. Mean imputation was selected as the most accurate method in this application. Conclusions Selecting an appropriate imputation method for health survey data, after accounting for spatial correlation and correlation between covariates, allows more complete analysis of geographic risk factors for disease with more confidence in the results to inform public policy decision-making.

Diabetes in South Asians

Economic, dietary and other lifestyle transitions have been occurring rapidly in most South Asian countries, making their populations more vulnerable to developing Type 2 diabetes and cardiovascular diseases. Recent data show an increasing prevalence of Type 2 diabetes in urban areas as well as in semi-urban and rural areas, inclusive of people belonging to middle and low socio-economic strata. Prime determinants for Type 2 diabetes in South Asians include physical inactivity, imbalanced diets, abdominal obesity, excess hepatic fat and, possibly, adverse perinatal and early life nutrition and intra-country migration. It is reported that Type 2 diabetes affects South Asians a decade earlier and some complications, for example nephropathy, are more prevalent and progressive than in other races. Further, prevalence of pre-diabetes is high, and so is conversion to diabetes, while more than 50% of those who are affected remain undiagnosed. Attitudes, cultural differences and religious and social beliefs pose barriers in effective prevention and management of Type 2 diabetes in South Asians. Inadequate resources, insufficient healthcare budgets, lack of medical reimbursement and socio-economic factors contribute to the cost of diabetes management. The challenge is to develop new translational strategies, which are pragmatic, cost-effective and scalable and can be adopted by the South Asian countries with limited resources. The key areas that need focus are: generation of awareness, prioritizing health care for vulnerable subgroups (children, women, pregnant women and the underprivileged), screening of high-risk groups, maximum coverage of the population with essential medicines, and strengthening primary care. An effective national diabetes control programme in each South Asian country should be formulated, with these issues in mind.

Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes

Vitamin D is synthesised in the skin through the action of UVB radiation (sunlight), and 25-hydroxy vitamin D (25OHD) measured in serum as a marker of vitamin D status. Several studies, mostly conducted in high latitudes, have shown an association between type 1 diabetes mellitus (T1DM) and low serum 25OHD. We conducted a case-control study to determine whether, in a sub-tropical environment with abundant sunlight (latitude 27.5°S), children with T1DM have lower serum vitamin D than children without diabetes. Fifty-six children with T1DM (14 newly diagnosed) and 46 unrelated control children participated in the study. Serum 25OHD, 1,25-dihydroxy vitamin D (1,25(OH)2D) and selected biochemical indices were measured. Vitamin D receptor (VDR) polymorphisms Taq1, Fok1, and Apa1 were genotyped. Fitzpatrick skin classification, self-reported daily hours of outdoor exposure, and mean UV index over the 35d prior to blood collection were recorded. Serum 25OHD was lower in children with T1DM (n=56) than in controls (n=46) [mean (95%CI)=78.7 (71.8-85.6) nmol/L vs. 91.4 (83.5-98.7) nmol/L, p=0.02]. T1DM children had lower self-reported outdoor exposure and mean UV exposure, but no significant difference in distribution of VDR polymorphisms. 25OHD remained lower in children with T1DM after covariate adjustment. Children newly diagnosed with T1DM had lower 1,25(OH)2D [median (IQR)=89 (68-122) pmol/L] than controls [121 (108-159) pmol/L, p=0.03], or children with established diabetes [137 (113-153) pmol/L, p=0.01]. Children with T1DM have lower 25OHD than controls, even in an environment of abundant sunlight. Whether low vitamin D is a risk factor or consequence of T1DM is unknown. © 2012 John Wiley & Sons A/S.

Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes

Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 P×-9, odds ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin. © 2011 Nature America, Inc. All rights reserved.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

Is there a relationship between screening for diabetes related foot complications and limb amputation?

Background From the conservative estimates of registrants with the National Diabetes Supply Scheme, we will be soon passing 1.1 Million Australians affected by all types of diabetes. The diabetes complications of foot ulceration and amputation are costly to all. These costs can be reduced with appropriate prevention strategies, starting with identifying people at risk through primary care diabetic foot screening. Yet levels of diabetic foot screening in Australia are difficult to quantify. This presentation aims to report on foot screening rates as recorded in existing academic literature, national health surveys and national database reports. Methods Literature searches included diabetic foot screening that occurred in the primary care setting for populations over 2000 people from 2002 to 2014. Searches were performed using Medline and CINAHL as well as internet searches of Organisations for Economic Co-operation and Development (OECD) countries health databases. The focus is on type 1 and type 2 diabetes in adults, and not gestational diabetes or children. The two primary outcome measures were foot -screening rates as a percentage of adult diabetic population and major lower limb amputation incidence rates from standardised OECD data. Results The most recent and accurate level for Australian population review was in the AUSDIAB (Australian Diabetes and lifestyle survey) from 2004. This survey reported screening in primary care to be as low as 50%. Countries such as the United Kingdom and United States of America have much higher reported rates of foot screening (67-86%) recorded using national databases and web based initiatives that involve patients and clinicians. By comparison major amputation rates for Australia were similar to the United Kingdom at 6.5 versus 5.1 per 100,000 population, but dis-similar to the United States of America at 17 per 100,000 population. Conclusions Australian rates of diabetic foot screening in primary care centres is ambiguous. There is no direct relationship between foot screening levels in a primary care environment and major lower limb amputation, based on national health survey's and OECD data. Uptake of national registers, incentives and web-based systems improve levels of diabetic foot assessment, which are the first steps to a healthier diabetic population.