Mortality trends among people with type 1 and type 2 diabetes in Australia: 1997-2010

OBJECTIVE: With improvements in cardiovascular disease (CVD) rates among people with diabetes, mortality rates may also be changing. However, these trends may be influenced by coding practices of CVD-related deaths on death certificates. We analyzed trends of mortality over 13 years in people with diabetes and quantified the potential misclassification of CVD mortality according to current coding methods. RESEARCH DESIGN AND METHODS: A total of 1,136,617 Australians with diabetes registered on the National Diabetes Services Scheme between 1997 and 2010 were linked to the National Death Index. Excess mortality relative to the Australian population was reported as standardized mortality ratios (SMRs). Potential misclassification of CVD mortality was determined by coding CVD according to underlying cause of death (COD) and then after consideration of both the underlying and other causes listed in part I of the death certificate. RESULTS: For type 1 diabetes, the SMR decreased in males from 4.20 in 1997 to 3.08 in 2010 (Ptrend < 0.001) and from 3.92 to 3.46 in females (Ptrend < 0.01). For type 2 diabetes, the SMR decreased in males from 1.40 to 1.21 (Ptrend < 0.001) and from 1.56 to 1.22 in females (Ptrend < 0.001). CVD deaths decreased from 35.6 to 31.2% and from 31.5 to 27.2% in males and females with type 1 diabetes, respectively (Ptrend < 0.001 for both sexes). For type 2 diabetes, CVD decreased from 44.5 to 29.2% in males and from 45.5 to 31.6% in females (Ptrend < 0.001 for both sexes). Using traditional coding methods, ∼38 and 26% of CVD deaths are underestimated in type 1 diabetes and type 2 diabetes, respectively. CONCLUSIONS: All-cause and CVD mortality has decreased in diabetes. However, the total CVD mortality burden is underestimated when only underlying COD is considered. This has important ramifications for understanding mortality patterns in diabetes.

Diabetes distress among adolescents with type 1 diabetes: a systematic review

Diabetes distress (DD) refers to the negative emotions arising from living with diabetes and the burden of self-management. Among adults, the prevalence and significance of DD are well established, but this is not the case among adolescents. This systematic review investigated among adolescents with type 1 diabetes: the prevalence of DD; demographic, clinical, behavioral and psychosocial correlates of DD and interventions that reduce DD. Consistent with adult studies, around one third of adolescents experience elevated DD and this is frequently associated with suboptimal glycemic control, low self-efficacy and reduced self-care. Three measures of DD have been developed specifically for adolescents, as those designed for adults may not be sufficiently sensitive to adolescent concerns. Interventions reducing DD in the short term include strategies such as cognitive restructuring, goal setting and problem solving. Further work is needed to investigate sustainability of effect. Rigorous research is needed to progress this field among adolescents.

Diabetes MILES - Australia (Management and Impact for Long-Term Empowerment and Success) : methods and sample characteristics of a national survey of the psychological aspects of living with type 1 or type 2 diabetes in Australian adults

Background Successful management of diabetes requires attention to the behavioural, psychological and social aspects of this progressive condition. The Diabetes MILES (Management and Impact for Long-term Empowerment and Success) Study is an international collaborative. Diabetes MILES-Australia, the first Diabetes MILES initiative to be undertaken, was a national survey of adults living with type 1 or type 2 diabetes in Australia. The aim of this study was to gather data that will provide insights into how Australians manage their diabetes, the support they receive and the impact of diabetes on their lives, as well as to use the data to validate new diabetes outcome measures.

Methods The survey was designed to include a core set of self-report measures, as well as modules specific to diabetes type or management regimens. Other measures or items were included in only half of the surveys. Cognitive debriefing interviews with 20 participants ensured the survey content was relevant and easily understood. In July 2011, the survey was posted to 15,000 adults (aged 18-70 years) with type 1 or type 2 diabetes selected randomly from the National Diabetes Services Scheme (NDSS) database. An online version of the survey was advertised nationally. A total of 3,338 eligible Australians took part; most (70.4%) completed the postal survey. Respondents of both diabetes types and genders, and of all ages, were adequately represented in both the postal and online survey sub-samples. More people with type 2 diabetes than type 1 diabetes took part in Diabetes MILES-Australia (58.8% versus 41.2%). Most respondents spoke English as their main language, were married/in a de facto relationship, had at least a high school education, were occupied in paid work, had an annual household income > $AUS40,000, and lived in metropolitan areas.

Discussion A potential limitation of the study is the under-representation of respondents from culturally and linguistically diverse backgrounds (including Aboriginal and Torres Strait Islander origin). Diabetes MILES-Australia represents a major achievement in the study of diabetes in Australia, where for the first time, the focus is on psychosocial and behavioural aspects of this condition at a national level.

Structured type 1 diabetes education delivered in routine care in Australia reduces diabetes-related emergencies and severe diabetes-related distress: the OzDAFNE program

AIMS: To evaluate structured type 1 diabetes education delivered in routine practice throughout Australia.

METHODS: Participants attended a five-day training program in insulin dose adjustment and carbohydrate counting between April 2007 and February 2012. Using an uncontrolled before-and-after study design, we investigated: HbA1c (% and mmol/mol); severe hypoglycaemia; diabetes ketoacidosis (DKA) requiring hospitalisation, and diabetes-related distress (Problem Areas in Diabetes scale; PAID), weight (kg); body mass index. Data were collected pre-training and 6-18 months post-training. Change in outcome scores were examined overall as well as between groups stratified by baseline HbA1c quartiles. Data are mean±SD or % (n).

RESULTS: 506 participants had data eligible for analysis. From baseline to follow-up, significant reductions were observed in the proportion of participants reporting at least one severe hypoglycaemic event (24.7% (n=123) vs 12.1% (n=59), p<0.001); and severe diabetes-related distress (29.3% (n=145) vs 12.6% (n=60), p<0.001). DKA requiring hospitalisation in the past year reduced from 4.1% (n=20) to 1.2% (n=6). For those with above target baseline HbA1c there was a small, statistically significant improvement (n=418, 8.4±1.1% (69±12mmol/mol) to 8.2±1.1% (66±12mmol/mol). HbA1c improvement was clinically significant among those in the highest baseline quartile (n=122, 9.7±1.1% (82±11mmol/mol) to 9.0±1.2% (75±13mmol/mol), p<0.001).

CONCLUSIONS: The proportion of participants reporting severe hypoglycaemia, DKA and severe diabetes-related distress was at least halved, and HbA1c reduced by 0.7% (7mmol/mol) among those with highest baseline levels. Structured type 1 diabetes education delivered in routine practice offers clinically important benefits for those with greatest clinical need.

Improved skeletal muscle oxidative enzyme activity and restoration of PGC-1α and PPARß/δ gene expression upon rosiglitazone treatment in obese patients with type 2 diabetes mellitus

Objective: To examine whether rosiglitazone alters gene expression of some key genes involved in mitochondrial biogenesis and oxidative capacity in skeletal muscle of type 2 diabetic patients, and whether this is associated with alterations in skeletal muscle oxidative capacity and lipid content.

Design: Skeletal muscle gene expression, mitochondrial protein content, oxidative capacity and lipid accumulation were measured in muscle biopsies obtained from diabetic patients, before and after 8 weeks of rosiglitazone treatment, and matched controls. Furthermore, whole-body insulin sensitivity and substrate utilization were assessed.

Subjects: Ten obese type 2 diabetic patients and 10 obese normoglycemic controls matched for age and BMI.

Methods: Gene expression and mitochondrial protein content of complexes I–V of the respiratory chain were measured by quantitative polymerase chain reaction and Western blotting, respectively. Histochemical staining was used to quantify lipid accumulation and complex II succinate dehydrogenase (SDH) activity. Insulin sensitivity and substrate utilization were measured during a hyperinsulinemic–euglycemic clamp with indirect calorimetry.

Results: Skeletal-muscle mRNA of PGC-1a and PPARb/d – but not of other genes involved in glucose, fat and oxidative metabolism – was significantly lower in diabetic patients (Po0.01). Rosiglitazone significantly increased PGC-1a (B2.2-fold, Po0.01) and PPARb/d (B2.6-fold, Po0.01), in parallel with an increase in insulin sensitivity, SDH activity and metabolic flexibility (Po0.01). Surprisingly, none of the measured mitochondrial proteins was reduced in type 2 diabetic patients, nor affected by rosiglitazone treatment. No alterations were seen in muscular fat accumulation upon treatment.

Conclusion: These results suggest that the insulin-sensitizing effect of rosiglitazone may involve an effect on muscular oxidative capacity, via PGC-1a and PPARb/d, independent of mitochondrial protein content and/or changes in intramyocellular lipid.

Severe hypoglycaemia in type 1 diabetes mellitus: underlying drivers and potential strategies for successful prevention

Hypoglycaemia remains an over-riding factor limiting optimal glycaemic control in type 1 diabetes. Severe hypoglycaemia is prevalent in almost half of those with long-duration diabetes and is one of the most feared diabetes-related complications. In this review, we present an overview of the increasing body of literature seeking to elucidate the underlying pathophysiology of severe hypoglycaemia and the limited evidence behind the strategies employed to prevent episodes. Drivers of severe hypoglycaemia including impaired counter-regulation, hypoglycaemia-associated autonomic failure, psychosocial and behavioural factors and neuroimaging correlates are discussed. Treatment strategies encompassing structured education, insulin analogue regimens, continuous subcutaneous insulin infusion pumps, continuous glucose sensing and beta-cell replacement therapies have been employed, yet there is little randomized controlled trial evidence demonstrating effectiveness of new technologies in reducing severe hypoglycaemia. Optimally designed interventional trials evaluating these existing technologies and using modern methods of teaching patients flexible insulin use within structured education programmes with the specific goal of preventing severe hypoglycaemia are required. Individuals at high risk need to be monitored with meticulous collection of data on awareness, as well as frequency and severity of all hypoglycaemic episodes.

Aerobic exercise and resistance training for the management of type 2 diabetes mellitus

BACKGROUND
Implementation of a structured physical exercise program can improve glycemic control in patients with type 2 diabetes mellitus.

OBJECTIVE
To evaluate the efficacy of aerobic exercise and resistance training (either alone or in combination) in the management of type 2 diabetes mellitus.

DESIGN AND INTERVENTION
DARE (Diabetes Aerobic and Resistance Exercise) was a 26-week, single-center, parallel-group, randomized, controlled trial of patients with type 2 diabetes mellitus of >6 months' duration. Participants were aged 39-70 years with a baseline [HbA.sub.1c] level 6.6-9.9%. Exclusion criteria included current insulin therapy, regular exercise regime and blood pressure >160/95 mmHg. All participants underwent a 4-week run-in period that comprised 12 sessions of combined aerobic exercise and resistance training; participants who attended [greater than or equal to] 10 sessions were eligible to enter the study. Eligible participants were randomly allocated to one of four groups: aerobic exercise alone; resistance training alone; combined aerobic exercise and resistance training; and no intervention (control group). Exercise was performed three times weekly. The aerobic exercise group progressed from 15-20 min on a treadmill or bicycle ergometer per session at 60% of the maximum heart rate to 45 min per session at 75% of the maximum heart rate. The resistance training group performed 7 different exercises on weight machines per 45 min session, and progressed to 2-3 sets of each exercise at the maximum weight that could be lifted 7-9 times. The combined exercise group performed the full aerobic exercise program plus the full resistance training program. Participants in the control group reverted to their pre-study exercise levels.

OUTCOME MEASURES
The primary outcome measure was the change in [HbA.sub.1c] from baseline. Secondary outcome measures included changes in blood pressure, lipid profile, and body composition.

RESULTS
A total of 251 participants were eligible for intervention. The median session attendance was 80% (aerobic exercise), 85% (resistance training) and 86% (combined exercise). When compared with the control group, the HbA1c levels were reduced by 0.50% in the aerobic exercise group (P = 0.007) and by 0.38% in the resistance training group (P = 0.038). The combined exercise group had an additional reduction of 0.46% when compared with the aerobic exercise group (P = 0.014) and of 0.59% when compared with the resistance training group (P = 0.001). Decreases in [HbA.sub.1c] levels were greatest for participants with a baseline [HbA.sub.1c] level = 7.5% (P <0.001). For participants with a baseline level [HbA.sub.1c] <7.5%, significant improvements in glycemic control were observed in the combined exercise group only (P = 0.002). Changes in blood pressure and lipid profiles did not differ between the groups. By contrast, participation in a structured exercise program improved body composition.

CONCLUSION
Although aerobic exercise or resistance training alone improved glycemic control, additional improvements were observed with the combined exercise regimen.

Patient-reported outcomes in trials of incretin-based therapies in patients with type 2 diabetes mellitus

Incretin-based therapies have a glucose-dependent mode of action that results in excellent glucose-lowering efficacy with very low risk of hypoglycaemia, and weight neutrality [dipeptidyl peptidase-4 (DPP-4) inhibitors] or weight loss [glucagon-like peptide-1 (GLP-1) receptor agonists], in people with type 2 diabetes mellitus (T2DM). Patient-reported outcomes (PROs) complement physician evaluations of efficacy and tolerability and offer insights into the subjective experience of using modern diabetes treatments. We conducted a systematic search of clinical trials of the GLP-1 receptor agonists liraglutide, exenatide and long-acting exenatide, one of which included the oral DPP-4 inhibitor sitagliptin as a comparator. No other PRO data for DPP-4 inhibitors were identified. This review summarizes PRO data from eight clinical trials, the majority of which used the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and/or Impact of Weight on Quality of Life-Lite (IWQOL-Lite) to evaluate patient experience. People with T2DM were highly satisfied with modern incretin-based therapies compared with traditional therapies. Treatment satisfaction (including perceptions of convenience and flexibility) was high and generally higher with GLP-1 agonists in association with their greater glucose-lowering efficacy and tendency to facilitate weight loss. Weight-related quality of life (QoL) also improved in people using incretin therapies. The glycaemic improvements achieved with GLP-1 receptor agonists, coupled with the low incidence of hypoglycaemia and ability to cause weight loss, seemed to offset potential concern about injections. It is plausible that superior patient-reported benefits found in clinical trials may translate into improved, clinically meaningful, long-term outcomes through increased treatment acceptability. Long-term, prospective data are needed to ascertain whether this is the case in practice.

Diabetes care provision: barriers, enablers and service needs of young adults with Type 1 diabetes from a region of social disadvantage

AIMS:
To determine the barriers to and enablers of engaging with specialist diabetes care and the service requirements of young adults with Type 1 diabetes mellitus from a low socio-economic, multicultural region.

METHODS:
A cross-sectional survey targeted 357 young adults with Type 1 diabetes, aged 18-30 years. Participants completed questions about barriers/enablers to accessing diabetes care and service preferences, self-reported HbA(1c), plus measures of diabetes-related distress (Problem Areas in Diabetes), depression/anxiety (Hospital Anxiety and Depression Scale), and illness perceptions (Brief Illness Perceptions Questionnaire).

RESULTS:
Eighty-six (24%) responses were received [55 (64%) female; mean ± sd age 24 ± 4 years; diabetes duration 12 ± 7 years; HbA(1c) 68 ± 16 mmol/mol (8.4 ± 1.5%)]. Logistical barriers to attending diabetes care were reported; for example, time constraints (30%), transportation (26%) and cost (21%). However, 'a previous unsatisfactory diabetes health experience' was cited as a barrier by 27%. Enablers were largely matched to overcoming these barriers. Over 90% preferred a multidisciplinary team environment, close to home, with after-hours appointment times. Forty per cent reported severe diabetes-related distress, 19% reported moderate-to-severe depressive symptoms and 50% reported moderate-to-severe anxiety.

CONCLUSIONS:
Among these young adults with Type 1 diabetes, glycaemic control was suboptimal and emotional distress common. They had identifiable logistical barriers to accessing and maintaining contact with diabetes care services, which can be addressed with flexible service provision. A substantial minority were discouraged by previous unsatisfactory experiences, suggesting health providers need to improve their interactions with young adults. This research will inform the design of life-stage-appropriate diabetes services targeting optimal engagement, access, attendance and ultimately improved healthcare outcomes in this vulnerable population.

The cost-effectiveness of the Dose Adjustment for Normal Eating (DAFNE) structured education programme: an update using the Sheffield Type 1 Diabetes policy model

AIMS: 
To estimate the cost-effectiveness of training in flexible intensive insulin therapy [as provided in the Dose Adjustment for Normal Eating (DAFNE) structured education programme] compared with no training for adults with Type 1 diabetes mellitus in the UK using the Sheffield Type 1 Diabetes Policy Model.

METHODS: 
The Sheffield Type 1 Diabetes Policy Model was used to simulate the development of long-term microvascular and macrovascular diabetes-related complications and the occurrence of diabetes-related adverse events in 5000 adults with Type 1 diabetes. Total costs and quality-adjusted life years were estimated from a National Health Service perspective over a lifetime horizon, discounted at a rate of 3.5%. The treatment effectiveness of DAFNE was modelled as a reduction in HbA1c that affected the risk of developing long-term diabetes-related complications. Probabilistic and structural sensitivity analyses were conducted.

RESULTS:
DAFNE resulted in greater life expectancy and reduced incidence of some diabetes-related complications compared with no DAFNE. DAFNE was found to generate an average of 0.0294 additional quality-adjusted life years for an additional cost of £426 per patient, leading to an incremental cost-effectiveness ratio of £14 400 compared with no DAFNE. There was a 54% probability that DAFNE would be cost-effective at a willingness-to-pay threshold of £20 000 per quality-adjusted life year.

CONCLUSIONS: 
The results of this study suggest that DAFNE is a cost-effective structured education programme for people with Type 1 diabetes and support its provision by the National Health Service in the UK.

Breastfeeding practices in women with type 1 diabetes: A discussion of the psychosocial factors and policies in Sweden and Australia.

Women with type 1 diabetes (T1DM) face many challenges during their pregnancy, birth and in the postnatal period, including breastfeeding initiation and continuation while maintaining stable glycaemic control. In both Sweden and Australia the rates of breastfeeding initiation are high. However, overall there is limited information about the breastfeeding practices of women with T1DM and the factors affecting them. Similarities in demographics, birth rates and health systems create bases for discussion.

'I'm not a druggie, I'm just a diabetic': a qualitative study of stigma from the perspective of adults with type 1 diabetes

While health-related stigma has been the subject of considerable research in other conditions (eg, HIV/AIDS, obesity), it has not received substantial attention in diabetes. Our aim was to explore perceptions and experiences of diabetes-related stigma from the perspective of adults with type 1 diabetes mellitus (T1DM).

Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral antidiabetic drugs that improve glycaemic control without causing weight gain or increasing hypoglycaemic risk in patients with type 2 diabetes mellitus (T2DM). The eight available DPP-4 inhibitors, including alogliptin, anagliptin, gemigliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin, and vildagliptin, are small molecules used orally with identical mechanism of action and similar safety profiles in patients with T2DM. DPP-4 inhibitors may be used as monotherapy or in double or triple combination with other oral glucose-lowering agents such as metformin, thiazolidinediones, or sulfonylureas. Although DPP-4 inhibitors have the same mode of action, they differ by some important pharmacokinetic and pharmacodynamic properties that may be clinically relevant in some patients. The main differences between the eight gliptins include: potency, target selectivity, oral bioavailability, elimination half-life, binding to plasma proteins, metabolic pathways, formation of active metabolite(s), main excretion routes, dosage adjustment for renal and liver insufficiency, and potential drug-drug interactions. The off-target inhibition of selective DPP-4 inhibitors is responsible for multiorgan toxicities such as immune dysfunction, impaired healing, and skin reactions. As a drug class, the DPP-4 inhibitors have become accepted in clinical practice due to their excellent tolerability profile, with a low risk of hypoglycaemia, a neutral effect on body weight, and once-daily dosing. It is unknown if DPP-4 inhibitors can prevent disease progression. More clinical studies are needed to validate the optimal regimens of DPP-4 inhibitors for the management of T2DM when their potential toxicities are closely monitored.