Prevention of type 2 diabetes in a primary health care setting interim results from the Greater Green Triangle (GGT) Diabetes Prevention Project

Although clinical trials have shown that lifestyle modifications reduce the risk of type 2 diabetes, translating lessons from trials to primary care remains a challenge. The aim of the study was to evaluate efficacy and feasibility of primary care-based diabetes prevention model with modest resource requirements in rural Australia. Three hundred and eleven subjects with at least a moderate risk of type 2 diabetes participated in a combined dietary and physical activity intervention. Clinical measurements and fasting blood samples were taken at the baseline and after intervention. After 3 months intervention, total (change −3.5%, p < 0.001) and LDL cholesterol (−4.8%, p < 0.001) plasma levels as well as body mass index (−2.5%, p < 0.001), weight (−2.5%, p < 0.001), and waist (−1.6%, p < 0.001) and hip (−2.7%, p < 0.001) circumferences reduced significantly. A borderline reduction was found in triglyceride levels (−4.8%, p = 0.058) while no changes were observed in HDL cholesterol (+0.6%, p = 0.525), glucose (+0.06%, p = 0.386), or systolic (−0.98%, p = 0.095) or diastolic (−1.06%, p = 0.134) blood pressure levels. In conclusion, a lifestyle intervention improved health outcomes – especially obesity and blood lipids – in a population at high risk of developing type 2 diabetes. Our results suggest that the present model is effective and feasible to carry out in primary care settings.

Young women with diabetes: using internet communication to create stability during life transitions

Aims and objectives. The aim of the current study was to explore and describe the strategies young women with Type 1 diabetes used to manage transitions in their lives. This paper will describe one aspect of the findings of how women with Type 1 diabetes used the Internet to interact with other people with diabetes and create stability in their lives.

Background. Individuals living with diabetes develop a range of different strategies to create stability in their lives and enhance their well-being. Changing social and emotional conditions during life transitions have a major impact on diabetes management. Although the literature indicates that strategies enabling the individuals to cope with transitions are important, they remain under-researched.

Design. Using grounded theory, interviews were conducted with 20 women with Type 1 diabetes. Constant comparative data analysis was used to analyse the data and develop an understanding of how young women with Type 1 diabetes used the Internet to create stability in their lives.

Findings. The findings revealed that the women valued their autonomy and being in control of when and to whom they reveal their diabetic status, especially during life transitions and at times of uncertainty. However, during these times they also required health and social information and interacting with other people. One of the women's main strategies in managing transitions was to use Internet chat lines as a way of obtaining information and communicating with others. This strategy gave women a sense of autonomy, enabled them to maintain their anonymity and interact with other people on their own terms.

Conclusions. Having meaningful personal interactions, social support and being able to connect with others were fundamental to the women's well being. Most importantly, preserving autonomy and anonymity during such interactions were integral to the way the women with Type 1 diabetes managed life transitions.

Relevance to clinical practice. Health professionals need to explore and incorporate Internet communication process or anonymous help lines into their practice as a way to assist people manage their diabetes.

Association of television viewing with fasting and 2-h postchallenge plasma glucose levels in adults without diagnosed diabetes

OBJECTIVE—We examined the associations of television viewing time with fasting plasma glucose (FPG) and 2-h postchallenge plasma glucose (2-h PG) levels in Australian adults.

RESEARCH DESIGN AND METHODS—A total of 8,357 adults aged >35 years who were free from diagnosed diabetes and who attended a population-based cross-sectional study (Australian Diabetes, Obesity and Lifestyle Study [AusDiab]) were evaluated. Measures of FPG and 2-h PG were obtained from an oral glucose tolerance test. Self-reported television viewing time (in the previous week) was assessed using an interviewer-administered questionnaire. Homeostasis model assessment (HOMA) of insulin sensitivity (HOMA-%S) and ß-cell function (HOMA-%B) were calculated based on fasting glucose and insulin concentrations.

RESULTS—After adjustment for confounders and physical activity time, time spent watching television in women was positively associated with 2-h PG, log fasting insulin, and log HOMA-%B and inversely associated with log HOMA-%S (P < 0.05) but not with FPG. No significant associations were observed with glycemic measures in men. The ß-coefficients across categories of average hours spent watching television per day (<1.0, 1.0–1.9, 2.0–2.9, 3.0–3.9, and ≥4.0) for 2-h PG in women were 0 (reference), 0.009, 0.047, 0.473, and 0.501, respectively (P for trend = 0.02).

CONCLUSIONS—Our findings highlight the unique deleterious relationship of sedentary behavior (indicated by television viewing time) and glycemic measures independent of physical activity time and adiposity status. These relationships differed according to sex and type of glucose measurement, with the 2-h PG measure being more strongly associated with television viewing. The findings suggest an important role for reducing sedentary behavior in the prevention of type 2 diabetes and cardiovascular disease, especially in women.

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

Introduction to diabetes

This chapter contains sections titled:

* Incidence and prevalence of diabetes
* Overview of diabetes
* Management strategies
* Management targets and regimens
* Short-term complications
* Long-term complications
* Psychological aspects
* Diabetes management requires integrated approaches
* People with diabetes' needs, capacities and resources
* Health professionals' needs
* Integration - is it possible?
* Complementary therapies
* Summary
* References

Overweight and obesity in Australia: the 1999-2000 Australian Diabetes, Obesity and Lifestyle Study (AusDiab)

Objective:
To measure the prevalence of obesity in Australian adults and to examine the associations of obesity with socioeconomic and lifestyle factors.

Design:
AusDiab, a cross-sectional study conducted between May 1999 and December 2000, involved participants from 42 randomly selected districts throughout Australia.

Participants:
Of 20 347 eligible people aged > 25 years who completed a household interview, 11 247 attended the physical examination at local survey sites (response rate, 55%).

Main outcome measures:
Overweight and obesity defined by body mass index (BMI; kg/m2) and waist circumference (cm); sociodemographic factors (including smoking, physical activity and television viewing time).

Results:
The prevalence of overweight and obesity (BMI > 25.0 kg/m2; waist circumference > 80.0 cm [women] or > 94.0 cm [men]) in both sexes was almost 60%, defined by either BMI or waist circumference. The prevalence of obesity was 2.5 times higher than in 1980. Using waist circumference, the prevalence of obesity was higher in women than men (34.1% v 26.8%; P < 0.01). Lower educational status, higher television viewing time and lower physical activity time were each strongly associated with obesity, with television viewing time showing a stronger relationship than physical activity time.

Conclusions:
The prevalence of obesity in Australia has more than doubled in the past 20 years. Strong positive associations between obesity and each of television viewing time and lower physical activity time confirm the influence of sedentary lifestyles on obesity, and underline the potential benefits of reducing sedentary behaviour, as well as increasing physical activity, to curb the obesity epidemic.

Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the third national health and nutrition examination survey

OBJECTIVE— To determine the association between serum 25-hydroxyvitamin D (25OHD) and diabetes risk and whether it varies by ethnicity.
RESEARCH DESIGN AND METHODS— We performed an analysis of data from participants who attended the morning examination of the Third National Health and Nutrition Examination Survey (1988–1994), a cross-sectional survey of a nationally representative sample of the U.S. population. Serum levels of 25OHD, which reflect vitamin D status, were available from 6,228 people (2,766 non-Hispanic whites, 1,736 non-Hispanic blacks, and 1,726 Mexican Americans) aged ≥20 years with fasting and/or 2-h plasma glucose and serum insulin measurements.
RESULTS— Adjusting for sex, age, BMI, leisure activity, and quarter of year, ethnicityspecific odds ratios (ORs) for diabetes (fasting glucose ≥7.0 mmol/l) varied inversely across quartiles of 25OHD in a dose-dependent pattern (OR 0.25 [95% CI 0.11– 0.60] for non-Hispanic whites and 0.17 [0.08–0.37] for Mexican Americans) in the highest vitamin D quartile (25OHD ≥81.0 nmol/l) compared with the lowest 25OHD (≥43.9 nmol/l). This inverse association
was not observed in non-Hispanic blacks. Homeostasis model assessment of insulin resistance (loge) was inversely associated with serum 25OHD in Mexican Americans (P ≥ 0.0024) and non-Hispanic whites (P≥0.058) but not non-Hispanic blacks (P≥0.93), adjusting for confounders.
CONCLUSIONS— These results show an inverse association between vitamin D status and diabetes, possibly involving insulin resistance, in non-Hispanic whites and Mexican Americans. The lack of an inverse association in non-Hispanic blacks may reflect decreased sensitivity to vitamin D and/or related hormones such as the parathyroid hormone.

Home-based resistance training is not sufficient to maintain improved glycemic control following supervised training in older individuals with type 2 diabetes

OBJECTIVE—To examine whether improvements in glycemic control and body composition resulting from 6 months of supervised high-intensity progressive resistance training could be maintained after an additional 6 months of home-based resistance training.

RESEARCH DESIGN AND METHODS—We performed a 12-month randomized controlled trial in 36 sedentary, overweight men and women with type 2 diabetes (aged 60–80 years) who were randomly assigned to moderate weight loss plus high-intensity progressive resistance training (RT&WL group) or moderate weight loss plus a control program (WL group). Supervised gymnasium-based training for 6 months was followed by an additional 6 months of home-based training. Glycemic control (HbA_1c), body composition, muscle strength, and metabolic syndrome abnormalities were assessed at 0, 3, 6, 9, and 12 months.

RESULTS—Compared with the WL group, HbA_1c decreased significantly more in the RT&WL group (–0.8%) during 6 months of supervised gymnasium-based training; however, this effect was not maintained after an additional 6 months of home-based training. In contrast, the greater increase in lean body mass (LBM) observed in the RT&WL group compared with the WL group (0.9 kg, P < 0.05) after the gymnasium-based training tended to be maintained after the home-based training (0.8 kg, P = 0.08). Similarly, the gymnasium-based increases in upper body and lower body muscle strength in the RT&WL group were maintained over the 12 months (P < 0.001). There were no between-group differences for changes in body weight, fat mass, fasting glucose, or insulin at 6 or 12 months.

CONCLUSIONS—In older adults with type 2 diabetes, home-based progressive resistance training was effective for maintaining the gymnasium-based improvements in muscle strength and LBM but not glycemic control. Reductions in adherence and exercise training volume and intensity seem to impede the effectiveness of home-based training for maintaining improved glycemic control.

Intranasal vaccination with proinsulin DNA induces regulatory CD4+ T cells that prevent experimental autoimmune diabetes

Insulin, an autoantigen in type 1 diabetes, when administered mucosally to diabetes-prone NOD mice induces regulatory T cells (T_reg) that protect against diabetes. Compared with protein, Ag encoded as DNA has potential advantages as a therapeutic agent. We found that intranasal vaccination of NOD mice with plasmid DNA encoding mouse proinsulin II-induced CD4⁺ T_reg that suppressed diabetes development, both after adoptive cotransfer with "diabetogenic" spleen cells and after transfer into NOD mice given cyclophosphamide to accelerate diabetes onset. In contrast to prototypic CD4⁺CD25⁺ T_reg, CD4⁺ T_reg induced by proinsulin DNA were both CD25⁺ and CD25^– and not defined by markers such as glucocorticoid-induced TNFR-related protein (GITR), CD103, or Foxp3. Intriguingly, despite induction of T_reg and reduced islet inflammation, diabetes incidence in proinsulin DNA-treated mice was unchanged. However, diabetes was prevented when DNA vaccination was performed under the cover of CD40 ligand blockade, known to prevent priming of CTL by mucosal Ag. Thus, intranasal vaccination with proinsulin DNA has therapeutic potential to prevent diabetes, as demonstrated by induction of protective T_reg, but further modifications are required to improve its efficacy, which could be compromised by concomitant induction of pathogenic immunity.

Peroxisome proliferator-activated receptor-γ coactivator-1 and insulin resistance: acute effect of fatty acids

Aims/hypothesis Peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1 (PPARGC1), a coactivator regulating the transcription of genes involved in oxidative metabolism, is downregulated in patients with type 2 diabetes and in their first-degree relatives. Whether this downregulation is a cause or effect of early aberrations in the development of insulin resistance, such as disturbances in fat metabolism, is unknown. We examined whether lipid-induced insulin resistance was associated with downregulation of expression of skeletal muscle genes involved in oxidative metabolism and mitochondrial biogenesis in humans.
Materials and methods Nine healthy lean male subjects underwent a 6-h hyperinsulinaemic–euglycaemic clamp with simultaneous infusion of either a lipid emulsion or glycerol as a control. Blood was sampled at regular time points and muscle biopsies were taken before and after every test. Intramuscular triacylglycerol (IMTG) content was determined by Oil Red O staining and gene expression was measured by quantitative PCR.
Results Lipid infusion resulted in a ∼2.7-fold increase in plasma NEFA levels and a 31±6% decrease in insulin sensitivity (p=0.001). The infusion of lipids resulted in a ∼1.6-fold increase in IMTG (p=0.02), whereas during the clamp with glycerol infusion IMTG tended to decrease to ∼53% of preinfusion levels (p=0.065). Lipid infusion decreased PPARGC1A, PPARGC1B and PPARA expression to ∼61, 77 and ∼52% of basal values respectively, whereas expression of uncoupling protein 3 was upregulated 1.8-fold (all p<0.05).
Conclusions/interpretation Acute elevation of plasma NEFA levels, leading to muscular fat accumulation and insulin resistance, downregulates PPARGC1A, PPARGC1B and PPARA expression, suggesting that the decrease in PPARGC1 expression observed in the (pre)diabetic state may be the result, rather than the cause of lipid-induced insulin resistance.

The subcellular fractionation properties and function of insulin receptor substrate-1 (IRS-1) are independent of cytoskeletal integrity

Efficient insulin action requires spatial and temporal coordination of signaling cascades. The prototypical insulin receptor substrate, IRS-1 plays a central role in insulin signaling. By subcellular fractionation IRS-1 is enriched in a particulate fraction, termed the high speed pellet (HSP), and its redistribution from this fraction is associated with signal attenuation and insulin resistance. Anecdotal evidence suggests the cytoskeleton may underpin the localization of IRS-1 to the HSP. In the present study we have taken a systematic approach to examine whether the cytoskeleton contributes to the subcellular fractionation properties and function of IRS-1. By standard microscopy or immunoprecipitation we were unable to detect evidence to support a specific interaction between IRS-1 and the major cytoskeletal components actin (microfilaments), vimentin (intermediate filaments), and tubulin (microtubules) in 3T3-L1 adipocytes or in CHO.IR.IRS-1 cells. Pharmacological disruption of microfilaments and microtubules, individually or in combination, was without effect on the subcellular distribution of IRS-1 or insulin-stimulated tyrosine phosphorylation in either cell type. Phosphorylation of Akt was modestly reduced (20–35%) in 3T3-L1 adipocytes but not in CHO.IR.IRS-1 cells. In cells lacking intermediate filaments (Vim^−/−) IRS-1 expression, distribution and insulin-stimulated phosphorylation appeared normal. Even after depolymerisation of microfilaments and microtubules, insulin-stimulated phosphorylation of IRS-1 and Akt were maintained in Vim^−/− cells. Taken together these data indicate that the characteristic subcellular fractionation properties and function of IRS-1 are unlikely to be mediated by cytoskeletal networks and that proximal insulin signaling does not require an intact cytoskeleton.

Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1, a novel neuronal protein that regulates energy balance

To identify genes involved in the central regulation of energy balance, we compared hypothalamic mRNA from lean and obese Psammomys obesus, a polygenic model of obesity, using differential display PCR. One mRNA transcript was observed to be elevated in obese, and obese diabetic, P. obesus compared with lean animals and was subsequently found to be increased 4-fold in the hypothalamus of lethal yellow agouti (Ay/a) mice, a murine model of obesity and diabetes. Intracerebroventricular infusion of antisense oligonucleotide targeted to this transcript selectively suppressed its hypothalamic mRNA levels and resulted in loss of body weight in both P. obesus and Sprague Dawley rats. Reductions in body weight were mediated by profoundly reduced food intake without a concomitant reduction in metabolic rate. Yeast two-hybrid screening, and confirmation in mammalian cells by bioluminescence resonance energy transfer analysis, demonstrated that the protein it encodes interacts with endophilins, mediators of synaptic vesicle recycling and receptor endocytosis in the brain. We therefore named this transcript Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 (SGIP1). SGIP1 encodes a large proline-rich protein that is expressed predominantly in the brain and is highly conserved between species. Together these data suggest that SGIP1 is an important and novel member of the group of neuronal molecules required for the regulation of energy homeostasis.

Diabetes management in patients receiving palliative care

A literature review revealed no evidence-based guidelines specific to managing diabetes in the context of palliative care. The purpose of the current project was to describe the management practices of doctors and nurses caring for people with diabetes and advanced disease. Palliative care doctors, palliative care nurses, endocrinologists, and diabetes nurse educators participated in this study. A two-phase project was undertaken: 1) two focus groups, and 2) a cross-sectional survey using a self-completed questionnaire. The focus group and questionnaire data identified that doctors and nurses used a range of practices and blood glucose testing frequencies to control blood glucose based on experience and not according to a robust evidence base. Implications for practice include the importance of collaboration between diabetes and palliative care specialists, and the need to develop clinical management guidelines.

Early detection of emotional and behavioural problems in children with diabetes: the validity of the child health questionnaire as a screening instrument

Aims: To assess the validity of the Child Health Questionnaire (CHQ) as a screening tool for detecting 'at risk' emotional and behavioural  maladjustment in children with diabetes, using the Behaviour Assessment System for Children (BASC) as a gold standard measure. Methods: CHQ and BASC were administered to 103 parents of children with Type 1 diabetes, aged 7–12 years. Sub-scales of the two measures were compared using Pearson's bivariate correlations. CHQ sensitivity and specificity cut-points were optimized against the BASC borderline category using receiver operating characteristic curves. Results: The BASC Externalizing Problems scale correlated strongly with CHQ Behaviour, Global Behaviour, Mental Health, Family Activities and Family Cohesion scales (r-values −0.68, −0.54, −0.51, −0.59, and −0.42, respectively). BASC Internalizing Problems scale correlated strongly with CHQ Behaviour, Mental Health and Family Cohesion scales (r-values −0.40, −0.43 and −0.45, respectively). Using receiver operating characteristic curve analysis, the CHQ Mental Health scale most effectively identified children classified as borderline on the BASC Internalizing Problems scale (sensitivity 87%, specificity 78%), while the CHQ Global Behaviour scale most effectively identified children classified as borderline on the BASC Externalizing Problems scale (sensitivity 73%, specificity 82%). Conclusions: Significant correlations were seen between the CHQ Global Behaviour and Mental Health scales and the BASC Externalizing and Internalizing scales, respectively. Sequential use of the CHQ, as a screening tool, followed by an established mental health measure such as the BASC, may help identify children with diabetes 'at risk' for chronic maladjustment and poor health outcomes.

Predicting the grade of disability 1 year after stroke following rehabilitation

The purpose of this study was to identify predictors of grades of disability at least 1 year after stroke rehabilitation therapy. We recruited stroke patients from the inpatient rehabilitation department of a university hospital. The degree of disability was graded using the disability evaluation at least 1 year after stroke onset. Functional ability was evaluated using the Functional Independence Measure instrument on admission, on discharge from the inpatient rehabilitation program, and at the 6-month follow-up visit after discharge. Major sociodemographic, medical, and rehabilitative factors were also collected during the hospitalization period. Of the 109 patients surveyed, 64 (58.7%) had severe or very severe grades of disability. The correlates of severe or very severe disability in logistic regression analyses were bilaterally affected (odds ratio, OR, 10.8), impaired orientation (OR, 3.6), and poorer functional ability at discharge (OR, 7.6). Based on the significant predictors identified, the logistic regression model correctly classified severe or very severe disability in 68.0% of subjects. The higher frequency of severe or very severe disability in this study may have been due to the relatively more severely affected stroke patient population in the inpatient rehabilitation service and the use of unique disability evaluation criteria. These results may provide information useful in planning continuous rehabilitation care and setting relevant socio-welfare policies for stroke victims.