Biology subjects

Brage, S.

Publications and source records attributed to Brage, S..

3 recordsLinked to original sources

bioRxiv2018

Magnetic resonance spectroscopy analysis of intramyocellular lipid composition in lipodystrophic patients and athletes

ContextParadoxically, intramyocellular lipid (IMCL) accumulation has been linked to both insulin-resistant and to insulin-sensitive (athletes) states. The composition of this lipid store is unknown in these states.\n\nDesign and MethodsWe used a recently validated and potentially widely applicable 1H magnetic resonance spectroscopy method to compare the compositional saturation index (CH2:CH3 ratio) and concentration independent of composition (CH3) of intramyocellular lipid in the soleus and tibialis anterior muscles of 16 female insulin-resistant lipodystrophic patients with that of age- and gender-matched athletes (n=14) and healthy controls (n = 41).\n\nMain OutcomeIMCL compositional saturation index (CH2:CH3 ratio).\n\nResultsThe IMCL CH2:CH3 ratio was significantly higher in both muscles of the lipodystrophic patients compared with age- and gender-matched controls but not compared to athletes. IMCL CH2:CH3 was dependent on IMCL concentration in the controls and after adjusting the composition index for quantity (CH2:CH3adj) was able to distinguish patients from athletes. With groups pooled, this CH2:CH3adj marker had the strongest relation to insulin resistance (HOMA-IR) compared to other measures of lipid concentration and composition, especially in the soleus muscle. Contrary to the athletes paradox, IMCL in athletes was similar in tibialis anterior (p>0.05) and significantly lower in the soleus (p < 0.004) compared to both controls and patients.\n\nConclusionsThe IMCL saturation index adjusted for quantity, which likely reflects accumulation of saturated IMCL, is more closely associated with insulin resistance than concentration alone.

biochemistry↗

bioRxiv2018

Estimating energy expenditure from wrist and thigh accelerometry in free-living adults: a doubly labelled water study

BackgroundMany large studies have implemented wrist or thigh accelerometry to capture physical activity, but the accuracy of these measurements to infer Activity Energy Expenditure (AEE) and consequently Total Energy Expenditure (TEE) has not been demonstrated. The purpose of this study was to assess the validity of acceleration intensity at wrist and thigh sites as estimates of AEE and TEE under free-living conditions using a gold-standard criterion.\n\nMethodsMeasurements for 193 UK adults (105 men, 88 women, aged 40-66 years, BMI 20.4-36.6 kg{middle dot}m-2) were collected with triaxial accelerometers worn on the dominant wrist, non-dominant wrist and thigh in free-living conditions for 9-14 days. In a subsample (50 men, 50 women) TEE was simultaneously assessed with doubly labelled water (DLW). AEE was estimated from non-dominant wrist using an established estimation model, and novel models were derived for dominant wrist and thigh in the non-DLW subsample. Agreement with both AEE and TEE from DLW was evaluated by mean bias, Root Mean Squared Error (RMSE) and Pearson correlation.\n\nResultsMean TEE and AEE derived from DLW was 11.6 (2.3) MJ{middle dot}day-1 and 49.8 (16.3) kJ{middle dot}day-1{middle dot}kg-1. Dominant and non-dominant wrist acceleration were highly correlated in free-living (r=0.93), but less so with thigh (r=0.73 and 0.66, respectively). Estimates of AEE were 48.6 (11.8) kJ{middle dot}day-1{middle dot}kg-1 from dominant wrist, 48.6 (12.3) from non-dominant wrist, and 46.0 (10.1) from thigh; these agreed strongly with AEE (RMSE ~12.2 kJ{middle dot}day-1{middle dot}kg-1, r ~0.71) with small mean biases at the population level (~6%). Only the thigh estimate bias was statistically significantly different from the criterion. When combining these AEE estimates with estimated REE, agreement was stronger with the criterion (RMSE ~1.0 MJ{middle dot}day-1, r ~0.90). Conclusions: In UK adults, acceleration measured at either wrist or thigh can be used to estimate population levels of AEE and TEE in free-living conditions with high precision.

epidemiology↗

bioRxiv2018

Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: an overview of the data from the epidemiological studies within the IMI DIRECT Consortium

Abstract/SummaryO_ST_ABSBackground and aimsC_ST_ABSUnderstanding the aetiology, clinical presentation and prognosis of type 2 diabetes (T2D) and optimizing its treatment might be facilitated by biomarkers that help predict a persons susceptibility to the risk factors that cause diabetes or its complications, or response to treatment. The IMI DIRECT (Diabetes Research on Patient Stratification) Study is a European Union (EU) Innovative Medicines Initiative (IMI) project that seeks to test these hypotheses in two recently established epidemiological cohorts. Here, we describe the characteristics of these cohorts at baseline and at the first main follow-up examination (18-months).\n\nMaterials and methodsFrom a sampling-frame of 24,682 European-ancestry adults in whom detailed health information was available, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm and enrolled into a prospective cohort study (n=2127) undertaken at four study centres across Europe (Cohort 1: prediabetes). We also recruited people from clinical registries with recently diagnosed T2D (n=789) into a second cohort study (Cohort 2: diabetes). The two cohorts were studied in parallel with matched protocols. Endogenous insulin secretion and insulin sensitivity were modelled from frequently sampled 75g oral glucose tolerance (OGTT) in Cohort 1 and with mixed-meal tolerance tests (MMTT) in Cohort 2. Additional metabolic biochemistry was determined using blood samples taken when fasted and during the tolerance tests. Body composition was assessed using MRI and lifestyle measures through self-report and objective methods.\n\nResultsUsing ADA-2011 glycaemic categories, 33% (n=693) of Cohort 1 (prediabetes) had normal glucose regulation (NGR), and 67% (n=1419) had impaired glucose regulation (IGR). 76% of the cohort was male, age=62(6.2) years; BMI=27.9(4.0) kg/m2; fasting glucose=5.7(0.6) mmol/l; 2-hr glucose=5.9(1.6) mmol/l [mean(SD)]. At follow-up, 18.6(1.4) months after baseline, fasting glucose=5.8(0.6) mmol/l; 2-hr OGTT glucose=6.1(1.7) mmol/l [mean(SD)]. In Cohort 2 (diabetes): 65% (n=508) were lifestyle treated (LS) and 35% (n=271) were lifestyle + metformin treated (LS+MET). 58% of the cohort was male, age=62(8.1) years; BMI=30.5(5.0) kg/m2; fasting glucose=7.2(1.4)mmol/l; 2-hr glucose=8.6(2.8) mmol/l [mean(SD)]. At follow-up, 18.2(0.6) months after baseline, fasting glucose=7.8(1.8) mmol/l; 2-hr MMTT glucose=9.5(3.3) mmol/l [mean(SD)].\n\nConclusionThe epidemiological IMI DIRECT cohorts are the most intensely characterised prospective studies of glycaemic deterioration to date. Data from these cohorts help illustrate the heterogeneous characteristics of people at risk of or with T2D, highlighting the rationale for biomarker stratification of the disease - the primary objective of the IMI DIRECT consortium.\n\nAbbreviations

epidemiology↗