Diabetes mellitus and the risk of depressive and anxiety disorders in Australian women: A longitudinal study

Background Longitudinal studies examining the risk of depressive and anxiety disorders associated with diabetes are limited. This study examined the association between diabetes and the risk of depressive and anxiety disorders in Australian women using longitudinal data. Methods Datawere froma sample of women who were part of anAustralian pregnancy and birth cohort study. Data comprised self-reported diabetes mellitus and the subsequent reporting of depressive and anxiety disorders. Mood disorders were assessed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, obtained from participants using Composite International Diagnostic Interview (CIDI)-Auto (WHO WMH-CIDI CAPI, version 21.1.3). Multiple regression models with adjustment for important covariates were used. Results Women with diabetes had a higher lifetime prevalence of any depressive and/or anxiety disorder than women without diabetes. About 3 in 10 women with diabetes experienced a lifetime event of any depressive disorder, while 1 in 2 women with diabetes experienced a lifetime event of any anxiety disorder. In prospective analyses, diabetes was only significantly associated with a 30-day episode of any anxiety disorder (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.09–2.15). In the case of lifetime disorders, diabetes was significantly associated with any depressive disorder (OR 1.37, 95% CI 1.03–1.84), major depressive disorder (OR 1.36, 95% CI 1.01–1.85), and posttraumatic stress disorder (OR 1.42, 95% CI 1.01–2.02). Conclusions The findings suggest that the presence of diabetes is a significant risk factor for women experiencing current anxiety disorders. However, in the case of depression, the association with diabetes only held for women who had experienced past episodes, there was no association with current depression. This suggests that the evidence is not strong enough to support a direct effect of diabetes as a cause of mood disorders.

Evaluation of a mobile phone image-based dietary assessment method in adults with type 2 diabetes

Photographic and image-based dietary records have limited evidence evaluating their performance and use among adults with a chronic disease. This study evaluated the performance of a mobile phone image-based dietary record, the Nutricam Dietary Assessment Method (NuDAM), in adults with type 2 diabetes mellitus (T2DM). Criterion validity was determined by comparing energy intake (EI) with total energy expenditure (TEE) measured by the doubly-labelled water technique. Relative validity was established by comparison to a weighed food record (WFR). Inter-rater reliability was assessed by comparing estimates of intake from three dietitians. Ten adults (6 males, age=61.2±6.9 years, BMI=31.0±4.5 kg/m2) participated. Compared to TEE, mean EI was under-reported using both methods, with a mean ratio of EI:TEE 0.76±0.20 for the NuDAM and 0.76±0.17 for the WFR. There was moderate to high correlations between the NuDAM and WFR for energy (r=0.57), carbohydrate (r=0.63, p<0.05), protein (r=0.78, p<0.01) and alcohol (rs=0.85, p<0.01), with a weaker relationship for fat (r=0.24). Agreement between dietitians for nutrient intake for the 3-day NuDAM (ICC = 0.77-0.99) was marginally lower when compared with the 3-day WFR (ICC=0.82-0.99). All subjects preferred using the NuDAM and were willing to use it again for longer recording periods.

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.

Multifocal electroretinogram responses in Nepalese diabetic patients without retinopathy

Purpose To determine neuroretinal function with multifocal electroretinogram (mfERG) in diabetic subjects without retinopathy. Methods Multifocal electroretinogram (mfERG) was performed in 18 eyes of 18 diabetic subjects without retinopathy and 17 eyes of 17 age and gender-matched healthy control participants. Among 18 diabetic subjects, two had type 1 and 16 had type 2 diabetes. MfERG responses were averaged by the retinal areas of six concentric rings and four quadrants, and 103 retinal locations; N1–P1 amplitude and P1-implicit time were analysed. Results Average mfERG N1–P1 amplitude (in nv/deg2) of 103 retinal locations was 56.3 ± 17.2 (mean ± SD) in type 1 diabetic subjects, 47.2 ± 9.3 in type 2 diabetic subjects and 71.5 ± 12.7 in controls. Average P1-implicit time (in ms) was 43.0 ± 1.3 in type 1 diabetic subjects, 43.9 ± 2.3 in type 2 diabetic subjects and 41.9 ± 2.1 in controls. There was significant reduction in average N1–P1 amplitude and delay in P1-implicit time in type 2 diabetic subjects in comparison to controls. mfERG amplitude did not show any significant correlation with diabetes duration and blood sugar level. However, implicit time showed a positive correlation with diabetes duration in type 2 diabetic subjects with diabetes duration ≥5 years. Conclusions This is the first study in a Nepalese population with diabetes using multifocal electroretinography. We present novel findings that mfERG N1–P1 amplitude is markedly reduced along with delay in P1-implicit time in type 2 diabetic subjects without retinopathy. These findings indicate that there might be significant dysfunction of inner retina before the development of diabetic retinopathy in the study population, which have higher prevalence of diabetes than the global estimate and uncontrolled blood sugar level.

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.

Genome-wide association study for sight-threatening diabetic retinopathy reveals association with genetic variation near the GRB2 gene

Aims/hypothesis Diabetic retinopathy is a serious complication of diabetes mellitus and can lead to blindness. A genetic component, in addition to traditional risk factors, has been well described although strong genetic factors have not yet been identified. Here, we aimed to identify novel genetic risk factors for sight-threatening diabetic retinopathy using a genome-wide association study. Methods Retinopathy was assessed in white Australians with type 2 diabetes mellitus. Genome-wide association analysis was conducted for comparison of cases of sight-threatening diabetic retinopathy (n = 336) with diabetic controls with no retinopathy (n = 508). Top ranking single nucleotide polymorphisms were typed in a type 2 diabetes replication cohort, a type 1 diabetes cohort and an Indian type 2 cohort. A mouse model of proliferative retinopathy was used to assess differential expression of the nearby candidate gene GRB2 by immunohistochemistry and quantitative western blot. Results The top ranked variant was rs3805931 with p = 2.66 × 10−7, but no association was found in the replication cohort. Only rs9896052 (p = 6.55 × 10−5) was associated with sight-threatening diabetic retinopathy in both the type 2 (p = 0.035) and the type 1 (p = 0.041) replication cohorts, as well as in the Indian cohort (p = 0.016). The study-wide meta-analysis reached genome-wide significance (p = 4.15 × 10−8). The GRB2 gene is located downstream of this variant and a mouse model of retinopathy showed increased GRB2 expression in the retina. Conclusions/interpretation Genetic variation near GRB2 on chromosome 17q25.1 is associated with sight-threatening diabetic retinopathy. Several genes in this region are promising candidates and in particular GRB2 is upregulated during retinal stress and neovascularisation.