Cost-efficacy of surgically induced weight loss for the management of type 2 diabetes : a randomized controlled trial

OBJECTIVE -- To determine the within-trial cost-efficacy of surgical therapy relative to conventional therapy for achieving remission of recently diagnosed type 2 diabetes in class I and II obese patients.

RESEARCH DESIGN AND METHODS -- Efficacy results were derived from a 2-year randomized controlled trial. A health sector perspective was adopted, and within-trial intervention costs included gastric banding surgery, mitigation of complications, outpatient medical consultations, medical investigations, pathology, weight loss therapies, and medication. Resource use was measured based on data drawn from a trial database and patient medical records and valued based on private hospital costs and government schedules in 2006 Australian dollars (AUD). An incremental cost-effectiveness analysis was undertaken.

RESULTS -- Mean 2-year intervention costs per patient were 13,400 AUD for surgical therapy and 3,400 AUD for conventional therapy, with laparoscopic adjustable gastric band (LAGB) surgery accounting for 85% of the difference. Outpatient medical consultation costs were three times higher for surgical patients, whereas medication costs were 1.5 times higher for conventional patients. The cost differences were primarily in the first 6 months of the trial. Relative to conventional therapy, the incremental cost-effectiveness ratio for surgical therapy was 16,600 AUD per case of diabetes remitted (currency exchange: 1 AUD = 0.74 USD).

CONCLUSIONS -- Surgical therapy appears to be a cost-effective option for managing type 2 diabetes in class I and II obese patients.

Oxygen (O2) kinetics during early recovery from peak exercise in patients with type 2 diabetes

Aims To examine the oxygen (O₂) kinetics during early recovery from peak exercise in patients with Type 2 diabetes and to examine whether oxygen O₂ recovery is associated with fasting glucose and HbA_1c in this population.

Methods Eighty-nine participants (52 men) aged 51.8 ± 7.1 years (mean ± sd) were divided into three groups: normal weight (BMI ≤ 25.0 kg/m²), overweight/obese without diabetes (BMI ≥ 26 kg/m²) and overweight/obese with Type 2 diabetes. Participants were assessed for their aerobic power (VO_2peak) on a cycle ergometer, provided a fasting blood sample and underwent a series of anthropometric measurements. Early recovery period was measured for 60 s from cessation of exercise and expressed as percentage of VO_2peak (higher percentage represents slower recovery).

Results No significant differences were observed for age between the three study groups. Both the overweight/obese groups without diabetes and with Type 2 diabetes had higher BMI than the normal weight group, with no significant differences between overweight/obese participants without diabetes and those with diabetes. Participants with Type 2 diabetes had lower VO_2peak than overweight/obese participants without diabetes and normal weight individuals (19.6 ± 4.8, 22.6 ± 5.4 and 25.7 ± 5.3 ml kg^&minus;1 min^&minus;1, respectively, <i>P <i> 0.004 for overall trends). Participants with Type 2 diabetes also had slower recovery in oxygen O₂ kinetics after exercise, compared with both normal weight and overweight/obese individuals without diabetes (56.5 ± 7.7, 49.2 ± 7.2, 47.7 ± 7.4%, <i>P <i> 0.004 for overall trends). Multiple regression analysis revealed that percentage of oxygen O₂ recovery was a stronger predictor than VO_2peak, BMI or age for fasting glucose and HbA_1c.

Conclusions Patients with Type 2 diabetes have lower VO_2peak and prolonged oxygen O₂ recovery from peak exercise. However, only prolonged oxygen O₂ recovery was associated with fasting glucose and HbA_1c.

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, &sim;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.

Methodological comparisons of heart rate variability analysis in patients with type 2 diabetes and angiotensin converting enzyme polymorphism

Angiotensin converting enzyme (ACE) polymorphism has been shown to be important in hypertension progression and also in diabetes complications, especially associated with heart disease. Heart rate variability (HRV) is an established measure for classification of autonomic function regulating heart rate, based on the interbeat interval time series derived from a raw ECG recording. Results of this paper show that the length (number of interbeat intervals) and preprocessing of the tachogram affect the HRV analysis outcome. The comparison was based on tachogram lengths of 250, 300, 350, and 400 RR-intervals and five preprocessing approaches. An automated adaptive preprocessing method for the heart rate biosignal and tachogram length of 400 interbeat intervals provided the best classification. HRV results differed for the Type 2 Diabetes Mellitus (T2DM) group between the I/I genotype and the I/D and D/D genotypes, whereas for controls there was no significant difference in HRV between genotypes. Selecting an appropriate length of recording and automated preprocessing has confirmed that there is an effect of ACE polymorphism including the I/I genotype and that I/I should not be combined with I/D genotype in determining the extent of autonomic modulation of the heart rate.

Age of onset of obesity and risk of type 2 diabetes

OBJECTIVE: To compare a simple measure - age of onset of obesity - to an obese-years construct (a product of duration and magnitude of obesity) as risk factors for type 2 diabetes.

METHOD: Participants from the Framingham Heart Study who were not obese and did not have diabetes at baseline were included (n=4,320). The Akaike Information Criterion (AIC) was computed to compare four Cox proportional hazards models with incident diabetes as the outcome and: (i) obese-years; (ii) age of onset of obesity; (iii) body mass index (BMI); and (iv) age of onset of obesity plus magnitude of BMI combined, as exposures.

RESULTS: AIC indicated that the model with obese-years provided a more effective explanation of incidence of type 2 diabetes compared to the remaining three models. Models including age of onset of obesity plus BMI were not appreciably different from the model with BMI alone, except in those aged ≥60.

CONCLUSIONS: While obese-years was the optimal obesity construct to explain risk of type 2 diabetes, age of onset may be a useful, practical addition to current BMI in the elderly.

IMPLICATIONS: Where computation of obese-years is not possible or impractical, age of onset of obesity combined with BMI may provide a useful alternative.

The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes

Aims/hypothesis This study aimed to identify genes that are expressed in skeletal muscle, encode proteins with functional significance in mitochondria, and are associated with type 2 diabetes.
Methods We screened for differentially expressed genes in skeletal muscle of Psammomys obesus (Israeli sand rats), and prioritised these on the basis of genomic localisation and bioinformatics analysis for proteins with likely mitochondrial functions.
Results We identified a mitochondrial intramembrane protease, known as presenilins-associated rhomboid-like protein (PSARL) that is associated with insulin resistance and type 2 diabetes. Expression of PSARL was reduced in skeletal muscle of diabetic Psammomys obesus, and restored after exercise training to successfully treat the diabetes. PSARL gene expression in human skeletal muscle was correlated with insulin sensitivity as assessed by glucose disposal during a hyperinsulinaemic–euglycaemic clamp. In 1,031 human subjects, an amino acid substitution (Leu262Val) in PSARL was associated with increased plasma insulin concentration, a key risk factor for diabetes. Furthermore, this variant interacted strongly with age to affect insulin levels, accounting for 5% of the variation in plasma insulin in elderly subjects.
Conclusions/interpretation Variation in PSARL sequence and/or expression may be an important new risk factor for type 2 diabetes and other components of the metabolic syndrome.

Decreased expression of adipogenic genes in obese subjects with type 2 diabetes

Objective: Our objective was to delineate the potential role of adipogenesis in insulin resistance and type 2 diabetes. Obesity is characterized by an increase in adipose tissue mass resulting from enlargement of existing fat cells (hypertrophy) and/or from increased number of adipocytes (hyperplasia). The inability of the adipose tissue to recruit new fat cells may cause ectopic fat deposition and insulin resistance.

Research Methods and Procedures: We examined the expression of candidate genes involved in adipocyte proliferation and/or differentiation [ CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBPdelta, GATA domain-binding protein 3 (GATA3), C/EBPbeta, peroxisome proliferator-activated receptor (PPAR) gamma2, signal transducer and activator of transcription 5A (STAT5A), Wnt-10b, tumor necrosis factor alpha, sterol regulatory element-binding protein 1c (SREBP1c), 11 beta-hydroxysteroid dehydrogenase, PPARG angiopoietin-related protein (PGAR), insulin-like growth factor 1, PPARitalic gamma coactivator 1alpha, PPARitalic gamma coactivator 1beta, and PPARdelta] in subcutaneous adipose tissue from 42 obese individuals with type 2 diabetes and 25 non-diabetic subjects matched for age and obesity.

Results: Insulin sensitivity was measured by a 3-hour 80 mU/m2 per minute hyperinsulinemic glucose clamp (100 mg/dL). As expected, subjects with type 2 diabetes had lower glucose disposal (4.9 plusminus 1.9 vs. 7.5 plusminus 2.8 mg/min per kilogram fat-free mass; p < 0.001) and larger fat cells (0.90 plusminus 0.26 vs. 0.78 plusminus 0.17 mum; p = 0.04) as compared with obese control subjects. Three genes (SREBP1c, p < 0.01; STAT5A, p = 0.02; and PPARitalic gamma2, p = 0.02) had significantly lower expression in obese type 2 diabetics, whereas C/EBPbeta only tended to be lower (p = 0.07).

Discussion: This cross-sectional study supports the hypothesis that impaired expression of adipogenic genes may result in impaired adipogenesis, potentially leading to larger fat cells in subcutaneous adipose tissue and insulin resistance.

Medication knowledge and self-management by people with type 2 diabetes

Objective: To explore medication knowledge and self management practices of people with type 2 diabetes.

Design: A one-shot cross sectional study using in-depth interviews and participant observation.

Setting: Diabetes outpatient education centre of a university teaching hospital.

Subjects: People with type 2 diabetes, n=30, 17 males and 13 females, age range 33-84, from a range of ethnic groups.

Outcome measures: Ability to state name, main actions and when to take medicines. Performance of specific medication-related tasks; opening bottles and packs, breaking tablets in half, administering insulin, and testing blood glucose.

Results: Average medication use > or = 10 years. Respondents were taking 86 different medicines, mean 7 +/- 2.97 SD. Dose frequency included two, three and four times per day. All respondents had > or = 2 diabetic complications +/- other comorbidities. The majority (93%) were informed about how and when to take their medicines, but only 37% were given information about side effects and 17% were given all possible seven items of information. Younger respondents received more information than older respondents. Older respondents had difficulty opening bottles and breaking tablets in half. Twenty per cent regularly forgot to take their medicines. Increasing medication costs was one reason for stopping medicines or reducing the dose or dose interval. The majority tested their blood glucose but did not control test their meters and 33% placed used sharps directly into the rubbish.

Conclusion: Polypharmacy was common. Medication knowledge and self management were inadequate and could lead to adverse events.

Patient engagement and coaching for health: the PEACH study- a cluster randomised controlled trial using the telephone to coach people with type 2 diabetes to engage with their GPs to improve diabetes care: a study protocol.

Background
The PEACH study is based on an innovative 'telephone coaching' program that has been used effectively in a post cardiac event trial. This intervention will be tested in a General Practice setting in a pragmatic trial using existing Practice Nurses (PN) as coaches for people with type 2 diabetes (T2D). Actual clinical care often fails to achieve standards, that are based on evidence that self-management interventions (educational and psychological) and intensive pharmacotherapy improve diabetes control. Telephone coaching in our study focuses on both. This paper describes our study protocol, which aims to test whether goal focused telephone coaching in T2D can improve diabetes control and reduce the treatment gap between guideline based standards and actual clinical practice.
Methods/design
In a cluster randomised controlled trial, general practices employing Practice Nurses (PNs) are randomly allocated to an intervention or control group. We aim to recruit 546 patients with poorly controlled T2D (HbA1c >7.5%) from 42 General Practices that employ PNs in Melbourne, Australia. PNs from General Practices allocated to the intervention group will be trained in diabetes telephone coaching focusing on biochemical targets addressing both patient self-management and engaging patients to work with their General Practitioners (GPs) to intensify pharmacological treatment according to the study clinical protocol. Patients of intervention group practices will receive 8 telephone coaching sessions and one face-to-face coaching session from existing PNs over 18 months plus usual care and outcomes will be compared to the control group, who will only receive only usual care from their GPs. The primary outcome is HbA1c levels and secondary outcomes include cardiovascular disease risk factors, behavioral risk factors and process of care measures.
Discussion
Understanding how to achieve comprehensive treatment of T2D in a General Practice setting is the focus of the PEACH study. This study explores the potential role for PNs to help reduce the treatment and outcomes gap in people with T2D by using telephone coaching. The intervention, if found to be effective, has potential to be sustained and embedded within real world General Practice.

Young women with type 1 diabetes' management of turning points and transitions

The authors used grounded theory to explore and develop a substantive theory to explain how 20 young women with type 1 diabetes managed their lives when facing turning points and undergoing transitions. The women experienced a basic social problem: being in the grip of blood glucose levels (BGLs), which consisted of three categories: (a) the impact of being susceptible to fluctuating BGLs, (b) the responses of other people to the individual woman’s diabetes, and (c) the impact of the individual women’s diabetes on other people’s lives. The women used a basic social process to overcome the basic social problem by creating stability, which involved using three interconnected subprocesses: forming meaningful
relationships, enhancing attentiveness to blood glucose levels, and putting things in perspective. Insights into the processes and strategies used by the women have important implications for provision of care and service delivery.

Issues in the provision of nursing care to people undergoing cardiac surgery who also have type 2 diabetes

There has been little investigation of the issues associated with caring for patients presenting for cardiac surgery with a comorbid diagnosis of diabetes although there is some evidence that the diabetes management is suboptimal. This study aimed to identify issues that patients and cardiac specialist nurses experience with the provision of inpatient services for people undergoing cardiac surgery who also have type 2 diabetes. A qualitative interpretive design, using individual interviews with patients and nurses, provided data about some of these issues. The study found that nurses had high levels of confidence in their cardiac care but little confidence in diabetes management. Patients described concerns about their diabetes care and treatment regimens. A 'typical journey' for a person with diabetes undergoing cardiac surgery was identified. The findings support the need to build increased capacity in specialist nurses to support diabetes care as a secondary diagnosis.

Plasma phospholipid and dietary fatty acids as predictors of type 2 diabetes: interpreting the role of linoleic acid 1-3

Background: Dietary fatty acids may be associated with diabetes but are difficult to measure accurately.

Objective: We aimed to investigate the associations of fatty acids in plasma and diet with diabetes incidence.

Design: This was a prospective case-cohort study of 3737 adults aged 36-72 y. Fatty acid intake (/kJ) and plasma phospholipid fatty acids (%) were measured at baseline, and diabetes incidence was assessed by self-report 4 y later. Logistic regression excluding (model 1) and including (model 2) body mass index and waist-hip ratio was used to calculate odds ratios (ORs) for plasma phospholipid and dietary fatty acids.

Results: In plasma phospholipid, positive associations with diabetes were seen for stearic acid [OR model 1, highest versus lowest quintile: 4.14 (95% CI: 2.65, 6.49), P for trend < 0.0001] and total saturated fatty acids [OR model 1: 3.76 (2.43, 5.81), P for trend < 0.0001], whereas an inverse association was seen for linoleic acid [OR model 1: 0.22 (0.14, 0.36), P for trend < 0.0001]. Dietary linoleic [OR model 1: 1.77 (1.19, 2.64), P for trend = 0.002], palmitic [OR model 1: 1.65 (1.12, 2.43), P for trend = 0.012], and stearic [OR model 1: 1.46 (1.00, 2.14), P for trend = 0.030] acids were positively associated with diabetes incidence before adjustment for body size. Within each quintile of linoleic acid intake, cases had lower baseline plasma phospholipid linoleic acid proportions than did controls.

Conclusions: Dietary saturated fat intake is inversely associated with diabetes risk. More research is required to determine whether linoleic acid is an appropriate dietary substitute.

Prevention of type 2 diabetes by lifestyle intervention in an Australian primary health care setting : Greater Green Triangle (GGT) Diabetes Prevention Project

Background
Randomised controlled trials demonstrate a 60% reduction in type 2 diabetes incidence through lifestyle modification programmes. The aim of this study is to determine whether such programmes are feasible in primary health care.

Methods
An intervention study including 237 individuals 40–75 years of age with moderate or high risk of developing type 2 diabetes. A structured group programme with six 90 minute sessions delivered during an eight month period by trained nurses in Australian primary health care in 2004–2006. Main outcome measures taken at baseline, three, and 12 months included weight, height, waist circumference, fasting plasma glucose and lipids, plasma glucose two hours after oral glucose challenge, blood pressure, measures of psychological distress and general health outcomes. To test differences between baseline and follow-up, paired t-tests and Wilcoxon rank sum tests were performed.

Results
At twelve months participants' mean weight reduced by 2.52 kg (95% confidence interval 1.85 to 3.19) and waist circumference by 4.17 cm (3.48 to 4.87). Mean fasting glucose reduced by 0.14 mmol/l (0.07 to 0.20), plasma glucose two hours after oral glucose challenge by 0.58 mmol/l (0.36 to 0.79), total cholesterol by 0.29 mmol/l (0.18 to 0.40), low density lipoprotein cholesterol by 0.25 mmol/l (0.16 to 0.34), triglycerides by 0.15 mmol/l (0.05 to 0.24) and diastolic blood pressure by 2.14 mmHg (0.94 to 3.33). Significant improvements were also found in most psychological measures.

Conclusion
This study provides evidence that a type 2 diabetes prevention programme using lifestyle intervention is feasible in primary health care settings, with reductions in risk factors approaching those observed in clinical trials.

Trial Number
Current Controlled Trials ISRCTN38031372