Objectively measured light-intensity physical activity is independently associated with 2-H plasma glucose

Objective: We examined the associations of objectively measured sedentary time, light-intensity physical activity, and moderate- to vigorous-intensity activity with fasting and 2-h postchallenge plasma glucose in Australian adults.

Research Design and Methods: A total of 67 men and 106 women (mean age ± SD 53.3 ± 11.9 years) without diagnosed diabetes were recruited from the 2004–2005 Australian Diabetes, Obesity, and Lifestyle (AusDiab) study. Physical activity was measured by Actigraph  accelerometers worn during waking hours for 7 consecutive days and summarized as sedentary time (accelerometer counts/min <100; average hours/day), light-intensity (counts/min 100-1951), and moderate- to vigorous-intensity (counts/min ≥1,952). An oral glucose tolerance test was used to ascertain 2-h plasma glucose and fasting plasma glucose.

Results: After adjustment for confounders (including waist circumference), sedentary time was positively associated with 2-h plasma glucose (b = 0.29, 95% CI 0.11–0.48, P = 0.002); light-intensity activity time (b = –0.25, –0.45 to –0.06, P = 0.012) and moderate- to vigorous-intensity activity time (b = –1.07, –1.77 to –0.37, P = 0.003) were negatively associated. Light-intensity activity remained significantly associated with 2-h plasma glucose following further adjustment for moderate- to vigorous-intensity activity (b = –0.22, –0.42 to –0.03, P = 0.023). Associations of all activity measures with fasting plasma glucose were nonsignificant (P > 0.05).

Conclusions: These data provide the first objective evidence that light-intensity physical activity is beneficially associated with blood glucose and that sedentary time is unfavorably associated with blood glucose. These objective data support previous findings from studies using self-report measures, and suggest that substituting light-intensity activity for television viewing or other sedentary time may be a practical and achievable preventive strategy to reduce the risk of type 2 diabetes and cardiovascular disease.

Effects of chronic treatment with arabose on glucose and lipid metabolism in obese diabetic wistar rats

Aims: The effect of chronic treatment with acarbose on fasting plasma glucose, insulin, triglyceride, cholesterol and free fatty acid (FFA) concentrations, as well as on the glucose and insulin excursions during oral glucose tolerance test (OGTT), in obese diabetic Wistar (WDF) rats was investigated. Methods: Forty-five mature male WDF rats were randomly distributed to one of the three treatment groups (no acarbose, 20 mg and 40 mg of acarbose/100 g of chow, respectively). After 3.5, 7.5 and 11.5 months, animals were tested for glucose tolerance by means of an OGTT, and their respective metabolic profiles were determined. Control determinations were done in obese and age-matched lean animals before the start of the trial. Results: The WDF rats exhibit higher body weight and fasting blood glucose, insulin, triglyceride and cholesterol concentrations compared to lean animals. Moreover, they show marked glucose intolerance as indicated by the glucose and insulin excursions during OGTT. Interestingly, in both treated and untreated animals, a reversion of the hyperglycaemic state as well as an improvement of the glucose tolerance is observed. However, whereas in the group receiving no acarbose this is accounted for by dramatic increases in fasting plasma insulin concentrations and insulin secretion during OGTT (as indicated by the ΔInsulin area), in rats treated with acarbose the reversion of the diabetic state takes place without increments in hormone concentration. In addition, rats treated with acarbose for 3.5 and 7.5 months show lower plasma triglyceride and FFA concentrations, and the same was observed for cholesterol at the highest dosage of the drug. Conclusions: Chronic treatment with acarbose of WDF rats improves the glycaemic and lipidic control as well as the glucose tolerance, with a lower demand of pancreatic insulin than in untreated rats. This data suggests that the long-term modulation of glucose and insulin excursions after meals improves the insulin sensitivity in this rat strain.

Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance. The Australian Diabetes, Obesity and Lifestyle Study (AusDiab)

Background--Diabetes mellitus increases the risk of cardiovascular disease (CVD) and all-cause mortality. The relationship between milder elevations of blood glucose and mortality is less clear. This study investigated whether impaired fasting glucose and impaired glucose tolerance, as well as diabetes mellitus, increase the risk of all-cause and CVD mortality.

Methods and Results--In 1999 to 2000, glucose tolerance status was determined in 10 428 participants of the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). After a median follow-up of 5.2 years, 298 deaths occurred (88 CVD deaths). Compared with those with normal glucose tolerance, the adjusted all-cause mortality hazard ratios (HRs) and 95% confidence intervals (CIs) for known diabetes mellitus and newly diagnosed diabetes mellitus were 2.3 (1.6 to 3.2) and 1.3 (0.9 to 2.0), respectively. The risk of death was also increased in those with impaired fasting glucose (HR 1.6, 95% CI 1.0 to 2.4) and impaired glucose tolerance (HR 1.5, 95% CI 1.1 to 2.0). Sixty-five percent of all those who died of CVD had known diabetes mellitus, newly diagnosed diabetes mellitus, impaired fasting glucose, or impaired glucose tolerance at baseline. Known diabetes mellitus (HR 2.6, 95% CI 1.4 to 4.7) and impaired fasting glucose (HR 2.5, 95% CI 1.2 to 5.1) were independent predictors for CVD mortality after adjustment for age, sex, and other traditional CVD risk factors, but impaired glucose tolerance was not (HR 1.2, 95% CI 0.7 to 2.2).

Conclusions--This study emphasizes the strong association between abnormal glucose metabolism and mortality, and it suggests that this condition contributes to a large number of CVD deaths in the general population. CVD prevention may be warranted in people with all categories of abnormal glucose metabolism.

Beneficial associations of physical activity with 2-h, but not fasting, blood glucose in Australian adults

OBJECTIVE--We examined the associations of physical activity with fasting plasma glucose (FPG) and with 2-h postload plasma glucose (2-h PG) in men and women with low, moderate, and high waist circumference.

RESEARCH DESIGN AND METHODS--The Australian Diabetes, Obesity and Lifestyle (AusDiab) study provided data on a population-based cross-sectional sample of 4,108 men and 5,106 women aged [greater than or equal to] 25 years without known diabetes or health conditions that could affect physical activity. FPG and 2-h PG were obtained from an oral glucose tolerance test. Self-reported physical activity level was defined according to the current public health guidelines as active ([greater than or equal to] 150 min/week across five or more sessions) or inactive (<150 min/week and/or less than five sessions). Sex-specific quintiles of physical activity time were used to ascertain dose response.

RESULTS--Being physically active and total physical activity time were independently and negatively associated with 2-h PG. When physical activity level was considered within each waist circumference category, 2-h PG was significantly lower in active high-waist circumference women ([beta] -0.30 [95% CI -0.59 to -0.01], P = 0.044) and active low-waist circumference men ([beta] -0.25 [-0.49 to -0.02], P = 0.036) compared with their inactive counterparts. Considered across physical activity and waist circumference categories, 2-h PG levels were not significantly different between active moderate-waist circumference participants and active low-waist circumference participants. Associations between physical activity and FPG were nonsignificant.

CONCLUSIONS--There are important differences between 2-h PG and FPG related to physical activity. It appears that 2-h PG is more sensitive to the beneficial effects of physical activity, and these benefits occur across the waist circumference spectrum.

Association between impaired glucose metabolism and quality of life

Aims
We examined the association of quality of life with glucose tolerance status in an Australian population to determine the stage in the development of diabetes that quality of life is impaired.

Methods
The Australian Diabetes, Obesity and Lifestyle study (AusDiab) was a population-based study of 11,247 people from randomly selected areas of Australia. As part of the study, participants underwent an oral glucose tolerance test and completed the SF-36 quality of life questionnaire.

Results
Previously diagnosed diabetes was associated with a significantly greater risk of being in the lowest quartile of each dimension of the SF-36 scale (except for mental health) and this association was only partially attenuated by adjustment for age, sex, body mass index (BMI), physical activity and treatment for hypertension and lipid abnormalities (adjusted odds ratios [95% CI]: bodily pain, 1.51 [1.18–1.94]; general health, 2.20 [1.64–2.95]; physical functioning, 1.50 [1.10–2.05]; role limitation (emotional), 1.43 [1.07–1.91]; role limitation (physical), 1.57 [1.13–2.18]; social functioning, 1.93 [1.46–2.54] and vitality, 2.24 [1.56–3.22]. Among those with newly diagnosed diabetes (NDM) and impaired glucose tolerance (IGT), there was also evidence of reduced quality of life on some dimensions of the SF-36 scale (NDM, general health, physical functioning and role limitation (physical); IGT, physical functioning and social functioning) after adjustment for confounders.

Conclusion
These findings show that diabetes is associated with a reduced quality of life and that this is evident in the early stage of the disease, particularly in relation to the ability to perform physical activities.

Screening for type 2 diabetes and impaired glucose metabolism – the Australian experience

OBJECTIVE--To assess the Australian protocol for identifying undiagnosed type 2 diabetes and impaired glucose metabolism.

RESEARCH DESIGN AND METHODS--The Australian screening protocol recommends a stepped approach to detecting undiagnosed type 2 diabetes based on assessment of risk status, measurement of fasting plasma glucose (FPG) in individuals at risk, and further testing according to FPG. The performance of and variations to this protocol were assessed in a population-based sample of 10,508 Australians.

RESULTS--The protocol had a sensitivity of 79.9%, specificity of 79.9%, and a positive predictive value (PPV) of 13.7% for detecting undiagnosed type 2 diabetes and sensitivity of 51.9% and specificity of 86.7% for detecting impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). To achieve these diagnostic rates, 20.7% of the Australian adult population would require an oral glucose tolerance test (OGTT). Increasing the FPG cut point to 6.1 mmol/l (110 mg/dl) or using Hb[A.sub.1c], instead of FPG to determine the need for an OGTT in people with risk factors reduced sensitivity, increased specificity and PPV, and reduced the proportion requiring an OGTT. However, each of these protocol variations substantially reduced the detection of IGT or IFG.

CONCLUSIONS--The Australian screening protocol identified one new case of diabetes for every 32 people screened, with 4 of 10 people screened requiring FPG measurement and 1 in 5 requiring an OGTT. In addition, 1 in 11 people screened had IGT or IFG. Including Hb[A.sub.1c] measurement substantially reduced both the number requiring an OGTT and the detection of IGT or IFG.

Are barriers to physical activity similar for adults with and without abnormal glucose Metabolism?

Purpose The purpose of this study was to examine perceived barriers to physical activity among adults with and without abnormal glucose metabolism (AGM), and whether barriers varied according to physical activity status.
Methods The 1999 to 2000 Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) was a population-based cross-sectional study among adults aged ≥25 years. AGM was identified through an oral glucose tolerance test. The previous week’s physical activity and individual, social, and environmental barriers to physical activity were self-reported. Logistic regression analyses examined differences in barriers to physical activity between those with and without AGM, and for those with and without AGM who did and did not meet the minimum recommendation of 150 minutes/week of moderate-to-vigorous intensity physical activity.
Results Of the 7088 participants (47.5 ± 12.7 years; 46% male), 18.5% had AGM. Approximately 47.5% of those with AGM met the physical activity recommendation, compared to 54.7% of those without AGM (P < .001). Key barriers to physical activity included lack of time, other priorities, and being tired. Following adjustment for sociodemographic and behavioral factors, there were few differences in barriers to physical activity between those with and without AGM, even after stratifying according to physical activity.
Conclusions Adults with AGM report similar barriers to physical activity, as do those without AGM. Programs for those with AGM can therefore focus on the known generic adult-reported barriers to physical activity.

Angiotensin converting enzyme inhibition lowers body weight and improves glucose tolerance in C57BL/6J mice maintained on a high fat diet

The renin–angiotensin system (RAS) is functional within adipose tissue and angiotensin II, the active component of RAS, has been implicated in adipose tissue hypertrophy and insulin resistance. In this study, captopril, an angiotensin converting enzyme (ACE) inhibitor that prevents angiotensin II formation, was used to study the development of diet-induced obesity and insulin resistance in obesity prone C57BL/6J mice. The mice were fed a high fat diet (w/w 21% fat) and allowed access to either water or water with captopril added (0.2 mg/ml). Body weight was recorded weekly and water and food intake daily. Glucose tolerance was determined after 11–12 weeks. On completion of the study (after 16 weeks of treatment), the mice were killed and kidney, liver, epididymal fat and extensor digitorum longus muscle (EDL) were weighed. Blood samples were collected and plasma analysed for metabolites and hormones. Captopril treatment decreased body weight in the first 2 weeks of treatment. Food intake of captopril-treated mice was similar to control mice prior to weight loss and was decreased after weight loss. Glucose tolerance was improved in captopril-treated mice. Captopril-treated mice had less epididymal fat than control mice. Relative to body weight, captopril-treated mice had increased EDL weight. Relative to control mice, mice administered captopril had a higher plasma concentration of adiponectin and lower concentrations of leptin and non-esterified fatty acids (NEFA). The results indicate that captopril both induced weight loss and improved insulin sensitivity. Thus, captopril may eventually be used for the treatment of obesity and Type 2 diabetes.

Area-level socioeconomic status and incidence of abnormal glucose metabolism : the Australian diabetes, obesity and lifestyle (AusDiab) study

OBJECTIVE--To examine the role of area-level socioeconomic status (SES) on the development of abnormal glucose metabolism (AGM) using national, population-based data.

RESEARCH DESIGN AND METHODS--The Australian Diabetes, Obesity and Lifestyle (AusDiab) study is a national, population-based, longitudinal study of adults aged [greater than or equal to] 25 years. A sample of 4,572 people provided complete baseline (1999 to 2000) and 5-year follow-up (2004 to 2005) data relevant for these analyses. Incident AGM was assessed using fasting plasma glucose and 2-h plasma glucose from oral glucose tolerance tests, and demographic, socioeconomic, and behavioral data were collected by interview and questionnaire. Area SES was defined using the Index of Relative Socioeconomic Disadvantage. Generalized linear mixed models were used to examine the relationship between area SES and incident AGM, with adjustment for covariates and correction for cluster design effects.

RESULTS--Area SES predicted the development of AGM, after adjustment for age, sex, and individual SES. People living in areas with the most disadvantage were significantly more likely to develop AGM, compared with those living in the least deprived areas (odds ratio 1.53; 95% CI 1.07-2.18). Health behaviors (in particular, physical activity) and central adiposity appeared to partially mediate this relationship.

CONCLUSIONS--Our findings suggest that characteristics of the physical, social, and economic aspects of local areas influence diabetes risk. Future research should focus on identifying the aspects of local environment that are associated with diabetes risk and how they might be modified.

Application of dynamic metabolomics to examine in vivo skeletal muscle glucose metabolism in the chronically high-fat fed mouse.

RATIONALE: Defects in muscle glucose metabolism are linked to type 2 diabetes. Mechanistic studies examining these defects rely on the use of high fat-fed rodent models and typically involve the determination of muscle glucose uptake under insulin-stimulated conditions. While insightful, they do not necessarily reflect the physiology of the postprandial state. In addition, most studies do not examine aspects of glucose metabolism beyond the uptake process. Here we present an approach to study rodent muscle glucose and intermediary metabolism under the dynamic and physiologically relevant setting of the oral glucose tolerance test (OGTT). METHODS AND RESULTS: In vivo muscle glucose and intermediary metabolism was investigated following oral administration of [U-(13)C] glucose. Quadriceps muscles were collected 15 and 60 min after glucose administration and metabolite flux profiling was determined by measuring (13)C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates via gas chromatography-mass spectrometry. While no dietary effects were noted in the glycolytic pathway, muscle from mice fed a high fat diet (HFD) exhibited a reduction in labelling in TCA intermediates. Interestingly, this appeared to be independent of alterations in flux through pyruvate dehydrogenase. In addition, our findings suggest that TCA cycle anaplerosis is negligible in muscle during an OGTT. CONCLUSIONS: Under the dynamic physiologically relevant conditions of the OGTT, skeletal muscle from HFD fed mice exhibits alterations in glucose metabolism at the level of the TCA cycle.

The effectiveness of a brief intervention using a pedometer and step-recording diary in promoting physical activity in people diagnosed with type 2 diabetes or impaired glucose tolerance

Issue addressed: To evaluate the effectiveness of a brief intervention using a pedometer and step-recording diary on promoting physical activity in people with type 2 diabetes or impaired glucose tolerance (IGT). Methods: People with type 2 diabetes or IGT who attended the Illawarra Diabetes Service were invited to participate. Participants in the intervention group received a pedometer and a diary to record their daily steps for a two-week period. Both the intervention and comparison group received advice on physical activity. Physical activity levels were measured using the Active Australia Survey at baseline, and at two and 20 weeks. Results: A total of 226 participants were recruited. At two-week follow-up the mean self-reported minutes of walking was significantly higher in the intervention group than the comparison group (223 minutes versus 164 minutes; p=0.01), as was the percentage of intervention participants achieving recommended levels of moderate-intensity physical activity (63.5% versus 41.8%, p=0.02) and the percentage of intervention participants achieving adequate levels of total physical activity (68.9% versus 48.0%, p=0.04). There were no differences between study groups for any physical activity measure at 20-week follow-up. Conclusions: A pedometer and a step-recording diary were useful tools to promote short-term increase in physical activity in people diagnosed with type 2 diabetes or IGT. Future studies need to examine whether a longer intervention, individualised physical activity counselling and support for achieving step goals could result in increasing physical activity over the long term.