Institute of Metabolic Science

Cambridge, United Kingdom

Institute of Metabolic Science

Cambridge, United Kingdom
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Buijsse B.,German Institute of Human Nutrition | Simmons R.K.,Institute of Metabolic Science | Griffin S.J.,Institute of Metabolic Science | Schulze M.B.,German Institute of Human Nutrition
Epidemiologic Reviews | Year: 2011

Trials have demonstrated the preventability of type 2 diabetes through lifestyle modifications or drugs in people with impaired glucose tolerance. However, alternative ways of identifying people at risk of developing diabetes are required. Multivariate risk scores have been developed for this purpose. This article examines the evidence for performance of diabetes risk scores in adults by 1) systematically reviewing the literature on available scores and 2) their validation in external populations; and 3) exploring methodological issues surrounding the development, validation, and comparison of risk scores. Risk scores show overall good discriminatory ability in populations for whom they were developed. However, discriminatory performance is more heterogeneous and generally weaker in external populations, which suggests that risk scores may need to be validated within the population in which they are intended to be used. Whether risk scores enable accurate estimation of absolute risk remains unknown; thus, care is needed when using scores to communicate absolute diabetes risk to individuals. Several risk scores predict diabetes risk based on routine noninvasive measures or on data from questionnaires. Biochemical measures, in particular fasting plasma glucose, can improve prediction of such models. On the other hand, usefulness of genetic profiling currently appears limited. © 2011 The Author.

News Article | October 5, 2016

Most people find high fat, high sugar foods particularly appetizing. This can lead to eating more calories than we need and can contribute to weight gain. But what influences food choice? The taste, appearance, smell and texture of food are all important, but biology may also play an important role. Previous studies in mice have shown that disruption of a particular pathway in the brain involving the melanocortin-4 receptor (MC4R) can lead to mice eating a lot more fat. Unusually, these mice eat a lot less sugar. However, the relevance of these findings to eating behavior in people has been unclear until now. In a study published today in the journal Nature Communications, researchers at the University of Cambridge gave participants an all-you-can-eat buffet of chicken korma – a popular type of curry – with three options manipulated to look and taste the same, but in which the fat content provided 20% (low), 40% (medium) and 60% (high) of the calories. They tested lean people, obese people, and people who were obese because they have a defect in a gene called MC4R. After taking a small taster of each meal, people were allowed to eat freely from the three kormas. They could not tell the difference between the foods and were unaware that the fat content varied. The researchers found that, although there was no overall difference in the amount of food eaten between the groups, individuals with defective MC4R ate almost double the amount of high fat korma than lean individuals ate (95 percent more) and 65 percent more than obese individuals. In a second arm of the study, people were given Eton mess, a dessert that includes a mixture of strawberries, whipped cream and broken meringue. Again, there were three options from which participants could freely choose, with sugar content providing 8 percent (low), 26 percent (medium) and 54 percent (high) of calorific content, but with the fat content fixed. Participants could choose freely which ones to eat. Lean and obese individuals said they liked the high sugar Eton mess more than the other two desserts. However, paradoxically, individuals with defective MC4R liked the high sugar dessert less than their lean and obese counterparts and in fact, ate significantly less of all three desserts compared to the other two groups. One in 100 obese people have a defect in the MC4R gene which makes them more likely to put on weight. The researchers think that for these individuals, the fact that the MC4R pathway is not working may lead to them preferring high fat food without realizing it and therefore contribute to their weight problem. There are many other genes that increase the risk of gaining weight and the impact of these genes on eating behavior needs to be studied in the future. Professor Sadaf Farooqi from the Wellcome Trust–Medical Research Council Institute of Metabolic Science at the University of Cambridge, who led the research team, says: “Our work shows that even if you tightly control the appearance and taste of food, our brains can detect the nutrient content. Most of the time we eat foods that are both high in fat and high in sugar. By carefully testing these nutrients separately in this study, and by testing a relatively rare group of people with the defective MC4R gene, we were able to show that specific brain pathways can modulate food preference.” Professor Farooqi and colleagues think that humans and animals may have evolved pathways in the brain that modulate the preference for high fat food in order to cope with times of famine. “When there is not much food around, we need energy that can be stored and accessed when needed: fat delivers twice as many calories per gram as carbohydrates or protein and can be readily stored in our bodies,” she explains. “As such, having a pathway that tells you to eat more fat at the expense of sugar, which we can only store to a limited extent in the body, would be a very useful way of defending against starvation.” The research was supported by the Wellcome Trust, the National Institute for Health Research Cambridge Biomedical Research Centre, the Bernard Wolfe Health Neuroscience Fund and the European Research Council, as well the European Union’s Seventh Framework Programme.

Hildebrand M.,Norwegian School of Sport Sciences | Van Hees V.T.,Newcastle University | Hansen B.H.,Norwegian School of Sport Sciences | Ekelund U.,Norwegian School of Sport Sciences | Ekelund U.,Institute of Metabolic Science
Medicine and Science in Sports and Exercise | Year: 2014

PURPOSE: The study aims were to compare raw triaxial accelerometer output from ActiGraph GT3X+ (AG) and GENEActiv (GA) placed on the hip and the wrist and to develop regression equations for estimating energy expenditure. METHODS: Thirty children (7-11 yr) and 30 adults (18-65 yr) completed eight activities (ranging from lying to running) while wearing one AG and one GA on the hip and the wrist. Oxygen consumption (V̇O2) was measured with indirect calorimetry. Analysis involved the use of ANOVA to examine the effect of activity, brand, and placement on the acceleration values, intraclass correlation coefficient to evaluate the agreement between the two brands and placements, and linear regression to establish intensity thresholds. RESULTS: A significant difference in acceleration values between the hip and the wrist placement was found (P < 0.001). The output from the wrist placement was, in general, higher compared with that from the hip. There was no main effect of monitor brand in adults (P < 0.12) and children (P < 0.73), and the intraclass correlation coefficient showed a strong agreement (0.96-0.99). However, a three-way interaction and systematic error between the brands was found in children. Acceleration from both brands and placements showed a strong correlation with V̇O2. The intensity classification accuracy of the developed thresholds for both brands and placements was, in general, higher for adults compared with that for children and was greater for sedentary/light (93%-97%), and vigorous activities (68%-92%) than that for moderate activities (33%-59%). CONCLUSIONS: Accelerometer outputs from AG and GA seem comparable when attached to the same body location in adults, whereas inconsistent differences are apparent between the two brands and placements in children, hence limiting the comparability between brands in this age group. © 2014 by the American College of Sports Medicine.

Wallin A.,Karolinska Institutet | Di Giuseppe D.,Karolinska Institutet | Orsini N.,Karolinska Institutet | Patel P.S.,Institute of Metabolic Science | And 2 more authors.
Diabetes Care | Year: 2012

OBJECTIVE - The evidence on the association between fish consumption, dietary long-chain n-3 fatty acids, and risk of type 2 diabetes is inconsistent. We therefore performed a systematic review and meta-analysis of the available prospective evidence. RESEARCH DESIGN AND METHODS - Studies were identified by searching the PubMed and EMBASE databases through 15 December 2011 and by reviewing the reference lists of retrieved articles. Prospective studies were included if they reported relative risk (RR) estimates with 95% CIs for the association between fish consumption and/or dietary long-chain n-3 fatty acids and incidence of type 2 diabetes. A dose-response random-effects model was used to combine study-specific RRs. Potential sources of heterogeneity were explored by prespecified stratifications. RESULTS - Sixteen studies involving 527,441 participants and 24,082 diabetes cases were included. Considerable statistical heterogeneity in the overall summary estimates was partly explained by geographical differences. For each serving perweek increment in fish consumption, the RRs (95% CIs) of type 2 diabetes were 1.05 (1.02-1.09), 1.03 (0.96-1.11), and 0.98 (0.97-1.00) combining U.S., European, and Asian/Australian studies, respectively. For each 0.30 g per day increment in long-chain n-3 fatty acids, the corresponding summary estimates were 1.17 (1.09-1.26), 0.98 (0.70-1.37), and 0.90 (0.82-0.98). CONCLUSIONS - Results from this meta-analysis indicate differences between geographical regions in observed associations of fish consumption and dietary intake of long-chain n-3 fatty acids with risk of type 2 diabetes. In consideration of the heterogeneous results, the relationship warrants further investigation. Meanwhile, current public health recommendations on fish consumption should be upheld unchanged. © 2012 by the American Diabetes Association.

Heil D.P.,Montana State University | Brage S.,Institute of Metabolic Science | Rothney M.P.,General Electric
Medicine and Science in Sports and Exercise | Year: 2012

Although the measurement of physical activity with wearable monitors may be considered objective, consensus guidelines for collecting and processing these objective data are lacking. This article presents an algorithm embodying best practice recommendations for collecting, processing, and reporting physical activity data routinely collected with accelerometry-based activity monitors. This algorithm is proposed as a linear series of seven steps within three successive phases. The Precollection Phase includes two steps. Step 1 defines the population of interest, the type and intensity of physical activity behaviors to be targeted, and the preferred outcome variables, and identifies the epoch duration. In Step 2, the activity monitor is selected, and decisions about how long and where on the body the monitor is to be worn are made. The Data Collection Phase, Step 3, consists of collecting and processing activity monitor data and is dependent on decisions made previously. The Postcollection Phase consists of four steps. Step 4 involves quality and quantity control checks of the activity monitor data. In Step 5, the raw data are transformed into physiologically meaningful units using a calibration algorithm. Step 6 involves summarizing these data according to the target behavior. In Step 7, physical activity outcome variables based on time, energy expenditure, or movement type are generated. Best practice recommendations include the full disclosure of each step within the algorithm when reporting monitor-derived physical activity outcome variables in the research literature. As such, those reading and publishing within the research literature, as well as future users, will have the best chance for understanding the interactions between study methodology and activity monitor selection, as well as the best possibility for relating their own monitor-derived physical activity outcome variables to the research literature.

Williams R.M.,University of Cambridge | Ong K.K.,Institute of Metabolic Science | Dunger D.B.,University of Cambridge
Molecular and Cellular Endocrinology | Year: 2013

PCOS has reasonably well defined clinical, biochemical and radiological features in adult women, but in the adolescent population, some of these features may overlap with normal puberty leading to difficulties in making a diagnosis. In addition, the rising prevalence of obesity in the paediatric population may compound insulin resistance in girls predisposed to ovarian hyperandrogenism leading to younger age of presentation and more severe phenotype. It is important to distinguish between normal puberty and true ovarian hyperandrogenism, as well as excluding other causes of androgen excess such as adrenal tumours or non classical congenital adrenal hyperplasia. The long term co-morbidities associated with ovarian hyperandrogenism presenting during adolescence are not well defined but there is likely to be increased cardiovascular risk. There are little data on intervention in the adolescent population and studies in adult women often focus on ovulation and fertility which are less of a concern to adolescents. Current options include insulin sensitisation with metformin, anti androgens, or the oral contraceptive pill, with each girl being treated on an individual basis. There is a requirement for establishment of normative data in adolescence, in conjunction with physiological phenotyping in order to elucidate potential mechanisms thus informing potential intervention. © 2013 Elsevier Ireland Ltd.

Ahmadi-Abhari S.,University of Cambridge | Kaptoge S.,University of Cambridge | Luben R.N.,University of Cambridge | Wareham N.J.,Institute of Metabolic science | Khaw K.-T.,University of Cambridge
American Journal of Epidemiology | Year: 2014

Chronic obstructive pulmonary disease is known to be associated with systemic inflammation. We examined the longitudinal association of C-reactive protein (CRP) and lung function in a cohort of 18,110 men and women from the European Prospective Investigation Into Cancer in Norfolk who were 40-79 years of age at baseline (recruited in 1993-1997) and followed-up through 2011. We assessed lung function by measuring forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) at baseline, 4 years, and 13 years. Serum CRP levels were measured using a high-sensitivity assay at baseline and the 13-year follow up. Cross-sectional and longitudinal associations of loge-CRP and lung function were examined using multivariable linear mixed models. In the cross-sectional analysis, 1-standard-deviation increase in baseline loge-CRP (about 3-fold higher CRP on the original milligrams per liter scale) was associated with a-86.3 mL (95% confidence interval:-93.9,-78.6) reduction in FEV1. In longitudinal analysis, a 1-standard-deviation increase in loge-CRP over 13 years was also associated with a-64.0 mL (95% confidence interval:-72.1,-55.8) decline in FEV1 over the same period. The associations were similar for FVC and persisted among lifetime never-smokers. Baseline CRP levels were not predictive of the rate of change in FEV1 or FVC over time. In the present study, we found longitudinal observational evidence that suggested that increases in systemic inflammation are associated with declines in lung function. © 2013 The Author.

Ahmadi-Abhari S.,University of Cambridge | Luben R.N.,University of Cambridge | Wareham N.J.,Institute of Metabolic science | Khaw K.-T.,Addenbrookes Hospital
European Journal of Epidemiology | Year: 2013

There is strong evidence from observational studies suggesting serum C-reactive protein (CRP) is associated with cardiovascular and all-cause mortality. However, less is known about whether there are differences in the association of CRP with all-cause or cause specific mortality by sex, smoking, body mass index (BMI), or physical activity. We aimed to investigate these interactions and also investigate and compare the association of CRP and other inflammation markers (i.e., fibrinogen and leukocyte count) with all-cause and cause-specific mortality. Men and women aged 40-79 were recruited in 1993-1997 in the EPIC-Norfolk cohort study. A total of 16,850 participants with high-sensitivity assayed CRP data who had no known cancer, myocardial infarction and stroke at baseline were entered in the analysis to test the association of CRP, fibrinogen and leukocyte count with risk of all-cause and cause specific mortality. A total of, 2,603 all-cause deaths (1,452 in men) including 823 cardiovascular and 1,035 cancer deaths, were observed after 231,000 person-years of follow-up (median 14.3 years). CRP was positively associated with risk of all-cause, cardiovascular, and non-cancer non-cardiovascular mortality independent of established risk factors. The hazard ratio of all-cause mortality (95 % CI) for participants with CRP in the range of 3-10 and >10 mg/l (vs. <0.5 mg/l) was 1.56 (1.26-1.93) and 1.87 (1.43-2.43) respectively in men and 1.34 (1.07-1.68) and 1.98 (1.50-2.63) in women. The association was less positively graded in women with the increased risk being significant only at higher levels of the CRP distribution. The association persisted in never smokers and did not vary by levels of BMI or physical activity. Although fibrinogen and leukocyte count were also positively associated with mortality risk, only CRP remained a significant predictor of mortality when the inflammation markers were adjusted for one another in multivariable models. Serum CRP levels were a long-term predictor of risk of cardiovascular and non-cardiovascular mortality independent of known risk factors, fibrinogen, and leukocyte count. © 2013 Springer Science+Business Media Dordrecht.

Simmons R.K.,Institute of Metabolic Science | Echouffo-Tcheugui J.B.,Institute of Metabolic Science | Griffin S.J.,Institute of Metabolic Science
Diabetes, Obesity and Metabolism | Year: 2010

A growing body of evidence on diabetes screening has been published during the last 10 years. Type 2 diabetes meets many but not all of the criteria for screening. Concerns about potential harms of screening have largely been resolved. Screening identifies a high-risk population with the potential to gain from widely available interventions. However, in spite of the findings of modelling studies, the size of the benefit of earlier initiation of treatment and the overall cost-effectiveness remains uncertain, in contrast to other screening programmes (such as for abdominal aortic aneurysms) that are yet to be fully implemented. There is also uncertainty about optimal specifications and implementation of a screening programme, and further work to complete concerning development and delivery of individual- and population-level preventive strategies. While there is growing evidence of the net benefit of earlier detection of individuals with prevalent but undiagnosed diabetes, there remains limited justification for a policy of universal population-based screening for type 2 diabetes at the present time. Data from ongoing studies should inform the key assumptions in existing modelling studies and further reduce uncertainty. © 2010 Blackwell Publishing Ltd.

Green A.Q.,Ipswich Hospital National Health Service Trust | Krishnan S.,Ipswich Hospital National Health Service Trust | Finucane F.M.,Institute of Metabolic Science | Rayman G.,Ipswich Hospital National Health Service Trust
Diabetes Care | Year: 2010

OBJECTIVE - This study explored the importance of glycemic burden compared with features of the metabolic syndrome in the pathogenesis of diabetic neuropathy by comparing C-fiber function in people with type 1 diabetes to that in people with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS - The axon reflex-elicited flare areas (LDI-flares) were measured with a laser Doppler imager (LDI) in age-, height-, and BMI-matched groups with IGT (n = 14) and type 1 diabetes (n = 16) and in healthy control subjects (n = 16). RESULTS - The flare area was reduced in the IGT group compared with the control (2.78 ± 1.1 vs. 5.23 ± 1.7 cm2, P = 0.0001) and type 1 diabetic (5.16 ± 2.3 cm2, P = 0.002) groups, whereas the flare area was similar in the type 1 diabetic and control groups. CONCLUSIONS - This technique suggests that small-fiber neuropathy is a feature of IGT. The absence of similar small-fiber neuropathy in those with longstanding type 1 diabetes suggests that glycemia may not be the major determinant of small-fiber neuropathy in IGT. © 2010 by the American Diabetes Association.

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