ADDITION-PRO Study Research Articles

The association between sleep duration and detailed measures of obesity: A cross sectional analysis in the ADDITION-PRO study.

Sleep duration is associated with BMI and waist circumference. However, less is known about whether sleep duration affects different measurements of obesity differently. To investigate the association between sleep duration and different measures of obesity. In this cross-sectional analysis 1309, Danish, older adults (55% men) completed at least 3days of wearing a combined accelerometer and heart rate-monitor for assessing sleep duration (hours/night) within self-reported usual bedtime. Participants underwent anthropometry and ultrasonography to assess BMI, waist circumference, visceral fat, subcutaneous fat, and fat percentage. Linear regression analyses examined the associations between sleep duration and obesity-related outcomes. Sleep duration was inversely associated with all obesity-related outcomes, except visceral-/subcutaneous-fat-ratio. After multivariate adjustment the magnitude of associations became stronger and statistically significant for all outcomes except visceral-/subcutaneous-fat-ratio, and subcutaneous fat in women. The associations with BMI and waist circumference demonstrated the strongest associations, when comparing standardized regression coefficients. Shorter sleep duration were associated with higher obesity across all outcomes except visceral-/subcutaneous-fat-ratio. No specifically salient associations with local or central obesity were observed. Results suggest that poor sleep duration and obesity correlate, however, further research is needed to conclude on beneficial effects of sleep duration regarding health and weight loss.

Health‐related quality of life for normal glycaemia, prediabetes and type 2 diabetes mellitus: Cross‐sectional analysis of the ADDITION‐PRO study

AimsWe estimated and compared health‐related quality of life for individuals with normal glucose tolerance, prediabetes and diabetes.MethodsParticipants in the ADDITION‐PRO study, Denmark, who attended a health assessment between 2009 and 2011, and who completed the 3‐level EuroQoL 5‐dimensions (EQ‐5D‐3L) questionnaire were included. For the present study, they were classified as normal glucose tolerance, prediabetes and diabetes (screen‐detected and known) using the 2019 American Diabetes Association criteria. Prediabetes was defined as impaired fasting glucose, impaired glucose tolerance or HbA1c between 5.7–6.4% (39–47 mmol/mol). EQ‐5D‐3L data were converted into utility scores using Danish and UK values, where ‘1’ equals full health and ‘0’ equals death. Regression models estimated the association between utility and the different glucose health states.ResultsThe mean EQ‐5D‐3L score in the sample population was 0.86 ± 0.17 (median 0.85, interquartile range 0.76 to 1) using UK values. Almost half of the sample (48%) reported full health with an EQ‐5D score of ‘1’. Individuals with known diabetes reported the lowest EQ‐5D‐3L utility scores (0.81 ± 0.20), followed by individuals with screen‐detected diabetes (0.85 ± 0.19), prediabetes (0.86 ± 0.17) and normal glucose tolerance (0.90 ± 0.15). The differences were statistically significant for normal glucose and known diabetes relative to prediabetes, after adjusting for sex, age, smoking, BMI and physical activity. These findings also held using Danish values albeit the differences were of smaller magnitude.ConclusionsHaving prediabetes and diabetes was significantly associated with lower health‐related quality of life relative to normal glucose tolerance. Our estimates will be useful to inform the value of interventions to prevent diabetes or prediabetes.

Role of fasting duration and weekday in incretin and glucose regulation

Fasting duration has been associated with lower fasting blood glucose levels, but higher 2-h post-load levels, and research has indicated an adverse effect of 'weekend behavior' on human metabolism. We investigated associations of fasting duration and weekday of examination with glucose, insulin, glucagon and incretin responses to an oral glucose tolerance test (OGTT). This cross-sectional study is based on data from the ADDITION-PRO study, where 2082 individuals attended a health examination including an OGTT. Linear regression analysis was applied to study the associations of overnight fasting duration and day of the week with glucose, insulin, glucagon, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) responses to an OGTT. We found that a 1 h longer fasting duration was associated with 1.7% (95% CI: 0.8,2.5) higher 2-h glucose levels, as well as a 3.0% (95% CI: 1.3,4.7) higher GIP and 2.3% (95% CI: 0.3,4.4) higher GLP-1 response. Fasting insulin levels were 20.6% (95% CI: 11.2,30.7) higher on Mondays compared to the other weekdays, with similar fasting glucose levels (1.7%, 95% CI: 0.0,3.4). In this study, longer overnight fasting duration was associated with a worsening of glucose tolerance and increased incretin response to oral glucose. We found higher fasting insulin levels on Mondays compared to the other days of the week, potentially indicating a worsened glucose regulation after the weekend.

Role of fasting duration and weekday in incretin and glucose regulation.

Fasting duration has been associated with lower fasting blood glucose levels, but higher 2-h post-load levels, and research has indicated an adverse effect of ‘weekend behavior’ on human metabolism. We investigated associations of fasting duration and weekday of examination with glucose, insulin, glucagon and incretin responses to an oral glucose tolerance test (OGTT). This cross-sectional study is based on data from the ADDITION-PRO study, where 2082 individuals attended a health examination including an OGTT. Linear regression analysis was applied to study the associations of overnight fasting duration and day of the week with glucose, insulin, glucagon, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) responses to an OGTT. We found that a 1 h longer fasting duration was associated with 1.7% (95% CI: 0.8,2.5) higher 2-h glucose levels, as well as a 3.0% (95% CI: 1.3,4.7) higher GIP and 2.3% (95% CI: 0.3,4.4) higher GLP-1 response. Fasting insulin levels were 20.6% (95% CI: 11.2,30.7) higher on Mondays compared to the other weekdays, with similar fasting glucose levels (1.7%, 95% CI: 0.0,3.4). In this study, longer overnight fasting duration was associated with a worsening of glucose tolerance and increased incretin response to oral glucose. We found higher fasting insulin levels on Mondays compared to the other days of the week, potentially indicating a worsened glucose regulation after the weekend.

The role of physical activity in the development of first cardiovascular disease event: a tree-structured survival analysis of the Danish ADDITION-PRO cohort

BackgroundAmbiguity exists in relation to the role of physical activity (PA) for cardiovascular disease (CVD) risk reduction. We examined the interplay between PA dimensions and more conventional CVD risk factors to assess which PA dimensions were associated with the first CVD event and whether subgroup differences exist.MethodsA total of 1449 individuals [median age 65.8 (IQR: 61.2, 70.7) years] with low to high risk of type 2 diabetes and free from CVD from the Danish ADDITION-PRO study were included for survival analysis. PA was measured by individually calibrated heart rate and movement sensing for 7 consecutive days. The associations of different PA dimensions (PA energy expenditure, time spent in light-, moderate- and vigorous intensity PA), sedentary time and other conventional CVD risk factors with the first CVD event were examined by tree-structured survival analysis. Baseline information was linked to data on the first CVD event (ischemic heart disease, ischemic stroke, heart failure, atrial flutter/fibrillation and atherosclerotic disease) and mortality obtained from Danish registers.ResultsDuring a median follow-up time of 5.5 (IQR: 5.1–6.1) years, a total of 201 individuals (13.9%) developed CVD. Overall CVD incidence rate was 2.6/100 person-years. PA energy expenditure above 43 kJ/kg/day was associated with lower rates of CVD events among participants ≤ 70 years and with HbA1c ≤ 5.7% (39 mmol/mol), systolic blood pressure ≤ 156 mmHg and albumin creatinine ratio ≤ 70 (incidence rates 0.0–0.8/100 person-years).ConclusionsAny type of PA resulting in increased PA energy expenditure may over time be the best prevention strategy to uphold reduced risk of CVD.

Physical Activity Dimensions Associated with Impaired Glucose Metabolism.

Physical activity (PA) is important in the prevention of Type 2 diabetes, yet little is known about the role of specific dimensions of PA, including sedentary time in subgroups at risk for impaired glucose metabolism (IGM). We applied a data-driven decision tool to identify dimensions of PA associated with IGM across age, sex, and body mass index (BMI) groups. This cross-sectional study included 1501 individuals (mean (SD) age, 65.6 (6.8) yr) at high risk for Type 2 diabetes from the ADDITION-PRO study. PA was measured by an individually calibrated combined accelerometer and heart rate monitor worn for 7 d. PA energy expenditure, time spent in different activity intensities, bout duration, and sedentary time were considered determinants of IGM together with age, sex, and BMI. Decision tree analysis was applied to identify subgroup-specific dimensions of PA associated with IGM. IGM was based on oral glucose tolerance test results and defined as a fasting plasma glucose level of ≥6.1 mmol·L and/or a 2-h plasma glucose level of ≥7.8 mmol·L. Among overweight (BMI ≥25 kg·m) men, accumulating less than 30 min·d of moderate-to-vigorous PA was associated with IGM, whereas among overweight women, sedentary time was associated with IGM. Among individuals older than 53 yr with normal weight (BMI <25 kg·m), time spent in light PA was associated with IGM. None of the dimensions of PA were associated with IGM among individuals ≤53 yr of age with normal weight. We identified subgroups in which different activity dimensions were associated with IGM. Methodology and results from this study may suggest a preliminary step toward the goal of tailoring and targeting PA interventions aimed at Type 2 diabetes prevention.

Glucose-Dependent Insulinotropic Polypeptide Is Associated With Lower Low-Density Lipoprotein But Unhealthy Fat Distribution, Independent of Insulin: The ADDITION-PRO Study.

Glucose-dependent insulinotropic polypeptide (GIP) may increase lipid clearance by stimulating lipid uptake. However, given that GIP promotes release of insulin by the pancreas and insulin is anti-lipolytic, the effect may be indirect. In this study we examined the association between GIP and lipid metabolism in individuals with low to high risk of type 2 diabetes and assessed whether the associations were modified by or mediated through insulin. Analyses were based on the Danish cross-sectional ADDITION-PRO study (n = 1405). Lipid metabolism was measured by fasting plasma lipids and obesity including abdominal fat distribution assessed by ultrasonography. GIP and insulin were measured during an oral glucose tolerance test (0, 30 and 120 min). Linear regression analysis was used to study the associations between GIP, plasma lipids, and obesity measures. A doubling in fasting GIP levels was associated with lower low-density lipoprotein in both men (mean [95% CI] -0.10 mmol/l [-0.18--0.03]) and women (-0.14 mmol/l [-0.23--0.04]) and with higher high-density lipoprotein in women (0.06 mmol/l [-0.02-0.10]). In men, a doubling in stimulated GIP was associated with 0.13 cm less 0.01-0.25 sc fat but with more visceral abdominal fat (0.45 cm [0.12-0.78]) and higher waist-hip ratio (0.011 [0.004-0.019]). Contrary to what was previously thought, GIP may be associated with improved low-density lipoprotein clearance but with an unhealthy fat distribution independent of insulin. The effect of GIP on obesity measures was substantially different between men and women. The potential effect of GIP on visceral and sc adipose tissue physiology warrants further examination.

Physical activity energy expenditure vs cardiorespiratory fitness level in impaired glucose metabolism.

Little is known about the relative roles of physical activity energy expenditure (PAEE) and cardiorespiratory fitness (CRF) as determinants of glucose regulation. The aim of this study was to examine the associations of PAEE and CRF with markers of glucose metabolism, and to test the hypothesis that CRF modifies the association between PAEE and glucose metabolism. We analysed cross-sectional data from 755 adults from the Danish ADDITION-PRO study. On the basis of OGTT results, participants without known diabetes were classified as having normal glucose tolerance, isolated impaired fasting glycaemia (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG + IGT or screen-detected diabetes mellitus. Markers of insulin sensitivity and beta cell function were determined. PAEE was measured using a combined heart rate and movement sensor. CRF (maximal oxygen uptake) was estimated using a submaximal 8 min step test. The associations were examined by linear regression analysis. Results were adjusted for relevant confounders. PAEE and CRF were reduced in individuals with i-IGT, combined IFG + IGT and screen-detected diabetes mellitus, but were not significantly different in individuals with i-IFG compared with those with normal glucose tolerance. When adjusting CRF for PAEE and vice versa, PAEE and CRF were both associated with lower fasting and 2 h insulin and higher peripheral insulin sensitivity. CRF was additionally associated with lower fasting and 2 h glucose and higher insulin sensitivity and beta cell function. There was no interaction between CRF and PAEE for any markers of glucose metabolism. Only CRF, not PAEE, appears to be independently associated with plasma glucose levels and beta cell function, suggesting that CRF may be particularly important for glycaemic control.

Response to Comment on Færch et al. GLP-1 Response to Oral Glucose Is Reduced in Prediabetes, Screen-Detected Type 2 Diabetes, and Obesity and Influenced by Sex: The ADDITION-PRO Study. Diabetes 2015;64:2513–2525

We appreciate the comments from Theodorakis (1) in response to our findings of reduced glucagon-like peptide 1 (GLP-1) release in prediabetes, screen-detected type 2 diabetes, and obesity (2). Theodorakis suggests that participants with screen-detected diabetes in the ADDITION-PRO study may have had long-standing diabetes, which could then explain why findings on GLP-1 release in participants with type 2 diabetes in the ADDITION-PRO study and the Baltimore Longitudinal Study of Aging (BLSA) point in different directions. The ADDITION-PRO study performed in 2009–2011 was originally designed to quantify diabetes progression rates, examine early markers of micro- and macrovascular diabetes complications, and understand the related mechanisms …

Comment on Færch et al. GLP-1 Response to Oral Glucose Is Reduced in Prediabetes, Screen-Detected Type 2 Diabetes, and Obesity and Influenced by Sex: The ADDITION-PRO Study. Diabetes 2015;64:2513-2525.

On the basis of their Danish study population, Faerch et al. (1) concluded that glucagon-like peptide 1 (GLP-1) response to oral glucose tolerance testing (OGTT) was up to 25% impaired in prediabetes and screen-detected diabetes compared with normal glucose tolerance (NGT) and more pronounced in women than men. This finding supports the concept introduced more than two decades ago that a diminishing incretin effect is associated with the development of type 2 diabetes (T2DM), with early impaired GLP-1 release occurring before rather than after diabetes becomes clinically manifest. The authors cite the Baltimore Longitudinal Study of Aging (BLSA) …

Associations of objectively measured physical activity and abdominal fat distribution.

Visceral adipose tissue (VAT) and physical activity are both independent predictors of Type 2 diabetes. Physical activity and overall obesity are inversely associated with each other. Yet the nature of the association between objectively measured dimensions of physical activity and abdominal fat distribution has not been well characterized. We aimed to do so in a middle-age to elderly population at high risk of diabetes. A cross-sectional analysis of 1134 participants of the ADDITION-PRO study. VAT and subcutaneous adipose tissue (SAT) were assessed one-dimensionally by ultrasonography and physical activity with combined accelerometry and HR monitoring. Linear regression of physical activity energy expenditure (PAEE) and time spent in different physical activity intensity levels on VAT and SAT was performed. Median body mass index (BMI) was 26.6 kg·m and PAEE was 28.1 kJ·kg·d, with 18.9 h·d spent sedentary, 4.5 h·d in light-intensity physical activity, and 0.4 h·d in moderate-intensity physical activity. PAEE was significantly negatively associated with VAT, and in women, PAEE was also significantly negatively associated with SAT. The difference in VAT was -1.1 mm (95% confidence interval [CI] = -1.8 to -0.3) per 10-kJ·kg·d increment, and the corresponding difference in SAT for women was -0.6 mm (95% CI = -1.2 to -0.04) in models adjusted for age, sex, and waist circumference. Exchanging 1 h of light physical activity with moderate physical activity was significantly associated with VAT (-4.5 mm, 95% CI = -7.6 to -1.5). Exchanging one sedentary hour with light physical activity was significantly associated with both VAT (-0.9 mm, 95% CI = -0.1 to -1.8) and SAT (-0.4 mm, 95% CI = -0.0 to -0.7). In this population with low physical activity levels, cross-sectional findings indicate that increasing overall physical activity and decreasing time spent sedentary is important to avoid the accumulation of metabolically deleterious VAT.

Role of Physical Activity Energy Expenditure versus Estimated Fitness Level in Impaired Glucose Regulation

Physical activity and exercise are beneficial for glucose regulation, but little is known about the relative roles of physical activity energy expenditure (PAEE) versus cardiorespiratory fitness (CRF) in glucose regulation. PURPOSE: To examine the associations of PAEE and CRF with markers of glucose metabolism, and to test the hypothesis that CRF modifies the association between PAEE and glucose metabolism. METHODS: We analyzed cross-sectional data from the Danish ADDITION-PRO study, including 755 adults aged 45-80 y with low-to-high diabetes risk. All participants had a 75 g oral glucose tolerance test with venous glucose and insulin concentrations measured at 0, 30 and 120 min. Markers of insulin sensitivity and beta cell function were calculated. PAEE (kJ·kg−1·d−1) was measured using a combined heart rate and movement sensor. CRF (maximal oxygen uptake, ml O2·kg−1·min−1) was estimated using a sub-maximal 8-min step test. The associations were examined by linear regression analysis adjusted for age, sex, smoking status, alcohol intake, and waist circumference. Interaction between CRF and PAEE on glucose metabolism was examined. RESULTS: Both PAEE and CRF were lower in impaired glucose tolerance (median (IQR) PAEE: 26.6 (18.9;35.8); CRF: 27.9 (24.3;30.3); P≤0.004) and screen-detected diabetes (PAEE: 28.0 (19.8;36.8); CRF: 28.5 (26.1;30.9); P≤0.003), but unchanged in impaired fasting glucose (PAEE: 30.9 (22.5;41.4); CRF: 29.5 (26.2;32.8); P=0.488) as compared with normal glucose tolerant individuals (PAEE: 32.0 (23.1;44.5); CRF: 29.9 (26.8;34.2)). Both PAEE and CRF were associated with higher insulin sensitivity and beta cell function (P<0.05). When adjusting CRF for PAEE and vice versa, CRF was still associated with lower fasting and 2-hour glucose levels as well as higher insulin sensitivity and beta cell function, but PAEE was only significantly associated with higher insulin sensitivity. There was no interaction between CRF and PAEE on any markers of glucose metabolism (P≥0.05 for all). CONCLUSIONS: PAEE and CRF are both associated with insulin sensitivity, but only CRF is independently associated with blood glucose levels and beta cell function. These findings suggest that long-term accumulation of PAEE and/or the intensity of PAEE are particularly important for glucose regulation.

Associations between ultrasound measures of abdominal fat distribution and indices of glucose metabolism in a population at high risk of type 2 diabetes: the ADDITION-PRO study.

AimsVisceral adipose tissue measured by CT or MRI is strongly associated with an adverse metabolic risk profile. We assessed whether similar associations can be found with ultrasonography, by quantifying the strength of the relationship between different measures of obesity and indices of glucose metabolism in a population at high risk of type 2 diabetes.MethodsA cross-sectional analysis of 1342 participants of the ADDITION-PRO study. We measured visceral adipose tissue and subcutaneous adipose tissue with ultrasonography, anthropometrics and body fat percentage by bioelectrical impedance. Indices of glucose metabolism were derived from a three point oral glucose tolerance test. Linear regression of obesity measures on indices of glucose metabolism was performed.ResultsMean age was 66.2 years, BMI 26.9kg/m2, subcutaneous adipose tissue 2.5cm and visceral adipose tissue 8.0cm. All measures of obesity were positively associated with indicators of glycaemia and inversely associated with indicators of insulin sensitivity. Associations were of equivalent magnitude except for subcutaneous adipose tissue and the visceral/subcutaneous adipose tissue ratio, which showed weaker associations. One standard deviation difference in BMI, visceral adipose tissue, waist circumference, waist/height ratio and body fat percentage corresponded approximately to 0.2mmol/l higher fasting glucose, 0.7mmol/l higher 2-hr glucose, 0.06-0.1% higher HbA1c, 30 % lower HOMA index of insulin sensitivity, 20% lower Gutt’s index of insulin sensitivity, and 100 unit higher Stumvoll’s index of beta-cell function. After adjustment for waist circumference visceral adipose tissue was still significantly associated with glucose intolerance and insulin resistance, whereas there was a trend towards inverse or no associations with subcutaneous adipose tissue. After adjustment, a 1cm increase in visceral adipose tissue was associated with ~5% lower insulin sensitivity (p≤0.0004) and ~0.18mmol/l higher 2-hr glucose (p≤0.001).ConclusionVisceral and subcutaneous adipose tissue assessed by ultrasonography are significantly associated with glucose metabolism, even after adjustment for other measures of obesity.

Association of self-perceived body image with body mass index and type 2 diabetes—The ADDITION-PRO study

ObjectiveWeight loss is important for prevention of type 2 diabetes and an accurate self-perceived body image can promote weight reduction. We evaluated the association of self-perceived body image with body mass index (BMI) and type 2 diabetes. MethodsData from the Danish ADDITION-PRO cohort study (2009–2011) were used. A total of 2082 men and women attended a health examination including assessment of BMI, waist circumference, the Stunkard scale of self-perceived obesity and an oral glucose tolerance test for assessment of diabetes risk. ResultsMean (SD) age was 66.2 (6.9) years and 24% were obese (BMI ≥30kg/m2). However, only 7% of obese men and 11% of obese women perceived themselves as obese. Among obese women, for a given level of BMI and waist circumference, one unit higher self-perceived body image was associated with 52% (95% CI: 14–73) lower risk of having type 2 diabetes and 45% (95% CI: 12–65) lower risk of having pre-diabetes. Overweight, but not obese, men had a 35% (95% CI: 36–56) lower risk of type 2 diabetes per unit increase in body image. ConclusionsObese individuals seem to underestimate their body shape. However, having a realistic body image (higher self-perceived obesity) is independently associated with lower diabetes risk. Self-perceived body image might serve as a valuable tool for type 2 diabetes risk assessment.

GLP-1 Response to Oral Glucose Is Reduced in Prediabetes, Screen-Detected Type 2 Diabetes, and Obesity and Influenced by Sex: The ADDITION-PRO Study.

The role of glucose-stimulated release of GLP-1 in the development of obesity and type 2 diabetes is unclear. We assessed GLP-1 response to oral glucose in a large study population of lean and obese men and women with normal and impaired glucose regulation. Circulating concentrations of glucose, insulin, and GLP-1 during an oral glucose tolerance test (OGTT) were analyzed in individuals with normal glucose tolerance (NGT) (n = 774), prediabetes (n = 525), or screen-detected type 2 diabetes (n = 163) who attended the Danish ADDITION-PRO study (n = 1,462). Compared with individuals with NGT, women with prediabetes or type 2 diabetes had 25% lower GLP-1 response to an OGTT, and both men and women with prediabetes or type 2 diabetes had 16-21% lower 120-min GLP-1 concentrations independent of age and obesity. Obese and overweight individuals had up to 20% reduced GLP-1 response to oral glucose compared with normal weight individuals independent of glucose tolerance status. Higher GLP-1 responses were associated with better insulin sensitivity and β-cell function, older age, and lesser degree of obesity. Our findings indicate that a reduction in GLP-1 response to oral glucose occurs prior to the development of type 2 diabetes and obesity, which can have consequences for early prevention strategies for diabetes.

Relationship between insulin resistance and β-cell dysfunction in subphenotypes of prediabetes and type 2 diabetes.

There is little overlap between diabetes diagnosed by glycated hemoglobin (HbA1c) and blood glucose, and it is unclear which pathophysiological defects are captured when using HbA1c for diagnosis. We examined and compared the relationship between insulin sensitivity and β-cell function in different subphenotypes of prediabetes and type 2 diabetes (T2D). A cross-sectional analysis of the Danish ADDITION-PRO study was performed (n = 1713). Participants without known diabetes were classified into subgroups of prediabetes and T2D based on fasting or 2-hour glucose criteria or HbA1c. Insulin sensitivity and insulin release were determined from glucose and insulin concentrations during the oral glucose tolerance test, and disposition indices were calculated. Individuals with prediabetes or T2D diagnosed by fasting glucose had lower absolute insulin release (P ≤ .01) and higher insulin sensitivity in response to glucose intake (P ≤ .01) but a similar disposition index (P ≥ .36), compared with individuals with elevated 2-hour glucose concentrations. Individuals with HbA1c-defined T2D or prediabetes had a mixture of the pathophysiological defects observed in the glucose-defined subgroups, and individuals with normoglycemia by HbA1c had worse pathophysiological abnormalities than individuals with normoglycemia by the glucose criteria. On average, the diagnostic HbA1c criteria for diabetes and prediabetes identified individuals with a mixture of the pathophysiological characteristics found when using the glucose criteria, but the diversity and pathophysiology captured by the oral glucose tolerance test cannot be captured when applying the more simple HbA1c criteria. Whether the disease progression and prognosis will differ in individuals diagnosed by fasting glucose, 2-hour glucose, or HbA1c should be examined in longitudinal studies.

Associations between objectively measured physical activity energy expenditure and central haemodynamics. The ADDITION-PRO study

Associations between objectively measured physical activity energy expenditure and central haemodynamics. The ADDITION-PRO study

Reproducibility of ultrasonography for assessing abdominal fat distribution in a population at high risk of diabetes

Background:Visceral fat plays an important role in the development of metabolic disease independently of the effect of overall abdominal fat. Ultrasonography is an accessible method of accurately assessing abdominal fat distribution in epidemiological studies, but few details about the reproducibility of this method have been published.Objective:The aim of this study was to investigate the reproducibility of ultrasonography in the assessment of abdominal fat distribution in a population at high risk of type 2 diabetes.Design and Methods:Ultrasonography was used to estimate visceral and subcutaneous abdominal fat. Intra- and interobserver variation, short-term variation and variation between estimates in the fasting and non-fasting state were examined in three samples of 30, 33 and 23 participants from the ADDITION-PRO study. A variance components model was used to calculate intra- and interobserver variation, and Bland–Altman plots were drawn for all three substudies.Results:Coefficients of variation for intra- and interobserver variation were in the range 3.4–6.1%, except for interobserver variation for subcutaneous fat (9.5%). Short-term variation over a median of 35 days had a coefficient of variation of 15%. The effect of a meal was primarily on the visceral estimates and did not extend beyond the first postprandial hour. Non-fasting visceral estimates were larger than fasting estimates.Conclusion:Both visceral and subcutaneous fat can be estimated with ultrasonography with adequate intra- and interobserver reproducibility by clinical researchers with limited training, making it a feasible method of assessing abdominal fat distribution in epidemiological studies.

Protocol for ADDITION-PRO: a longitudinal cohort study of the cardiovascular experience of individuals at high risk for diabetes recruited from Danish primary care

BackgroundScreening programmes for type 2 diabetes inevitably find more individuals at high risk for diabetes than people with undiagnosed prevalent disease. While well established guidelines for the treatment of diabetes exist, less is known about treatment or prevention strategies for individuals found at high risk following screening. In order to make better use of the opportunities for primary prevention of diabetes and its complications among this high risk group, it is important to quantify diabetes progression rates and to examine the development of early markers of cardiovascular disease and microvascular diabetic complications. We also require a better understanding of the mechanisms that underlie and drive early changes in cardiometabolic physiology. The ADDITION-PRO study was designed to address these issues among individuals at different levels of diabetes risk recruited from Danish primary care.Methods/DesignADDITION-PRO is a population-based, longitudinal cohort study of individuals at high risk for diabetes. 16,136 eligible individuals were identified at high risk following participation in a stepwise screening programme in Danish general practice between 2001 and 2006. All individuals with impaired glucose regulation at screening, those who developed diabetes following screening, and a random sub-sample of those at lower levels of diabetes risk were invited to attend a follow-up health assessment in 2009–2011 (n = 4,188), of whom 2,082 (50%) attended. The health assessment included detailed measurement of anthropometry, body composition, biochemistry, physical activity and cardiovascular risk factors including aortic stiffness and central blood pressure. All ADDITION-PRO participants are being followed for incident cardiovascular disease and death.DiscussionThe ADDITION-PRO study is designed to increase understanding of cardiovascular risk and its underlying mechanisms among individuals at high risk of diabetes. Key features of this study include (i) a carefully characterised cohort at different levels of diabetes risk; (ii) detailed measurement of cardiovascular and metabolic risk factors; (iii) objective measurement of physical activity behaviour; and (iv) long-term follow-up of hard clinical outcomes including mortality and cardiovascular disease. Results will inform policy recommendations concerning cardiovascular risk reduction and treatment among individuals at high risk for diabetes. The detailed phenotyping of this cohort will also allow a number of research questions concerning early changes in cardiometabolic physiology to be addressed.