Heterogeneity in glucose response curves during an oral glucose tolerance test and associated cardiometabolic risk

We aimed to examine heterogeneity in glucose response curves during an oral glucose tolerance test with multiple measurements and to compare cardiometabolic risk profiles between identified glucose response curve groups. We analyzed data from 1,267 individuals without diabetes from five studies in Denmark, the Netherlands and the USA. Each study included between 5 and 11 measurements at different time points during a 2-h oral glucose tolerance test, resulting in 9,602 plasma glucose measurements. Latent class trajectories with a cubic specification for time were fitted to identify different patterns of plasma glucose change during the oral glucose tolerance test. Cardiometabolic risk factor profiles were compared between the identified groups. Using latent class trajectory analysis, five glucose response curves were identified. Despite similar fasting and 2-h values, glucose peaks and peak times varied greatly between groups, ranging from 7-12 mmol/L, and 35-70 min. The group with the lowest and earliest plasma glucose peak had the lowest estimated cardiovascular risk, while the group with the most delayed plasma glucose peak and the highest 2-h value had the highest estimated risk. One group, with normal fasting and 2-h values, exhibited an unusual profile, with the highest glucose peak and the highest proportion of smokers and men. The heterogeneity in glucose response curves and the distinct cardiometabolic risk profiles may reflect different underlying physiologies. Our results warrant more detailed studies to identify the source of the heterogeneity across the different phenotypes and whether these differences play a role in the development of type 2 diabetes and cardiovascular disease

Carbon nanotubes allow capture of krypton, barium and lead for multichannel biological X-ray fluorescence imaging

The desire to study biology in situ has been aided by many imaging techniques. Among these, X-ray fluorescence (XRF) mapping permits observation of elemental distributions in a multichannel manner. However, XRF imaging is underused, in part, because of the difficulty in interpreting maps without an underlying cellular ‘blueprint’; this could be supplied using contrast agents. Carbon nanotubes (CNTs) can be filled with a wide range of inorganic materials, and thus can be used as ‘contrast agents’ if biologically absent elements are encapsulated. Here we show that sealed single-walled CNTs filled with lead, barium and even krypton can be produced, and externally decorated with peptides to provide affinity for sub-cellular targets. The agents are able to highlight specific organelles in multiplexed XRF mapping, and are, in principle, a general and versatile tool for this, and other modes of biological imaging

Quantifying defects in graphene via Raman spectroscopy at different excitation energies.

We present a Raman study of Ar(+)-bombarded graphene samples with increasing ion doses. This allows us to have a controlled, increasing, amount of defects. We find that the ratio between the D and G peak intensities, for a given defect density, strongly depends on the laser excitation energy. We quantify this effect and present a simple equation for the determination of the point defect density in graphene via Raman spectroscopy for any visible excitation energy. We note that, for all excitations, the D to G intensity ratio reaches a maximum for an interdefect distance ∼3 nm. Thus, a given ratio could correspond to two different defect densities, above or below the maximum. The analysis of the G peak width and its dispersion with excitation energy solves this ambiguity

Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes: a longitudinal analysis from the Whitehall II cohort study

AIMS/HYPOTHESIS: South Asian individuals have reduced insulin sensitivity and increased risk of type 2 diabetes compared with white individuals. Temporal changes in glycaemic traits during middle age suggest that impaired insulin secretion is a particular feature of diabetes development among South Asians. We therefore aimed to examine ethnic differences in early changes in glucose metabolism prior to incident type 2 diabetes. METHODS: In a prospective British occupational cohort, subject to 5 yearly clinical examinations, we examined ethnic differences in trajectories of fasting plasma glucose (FPG), 2 h post-load plasma glucose (2hPG), fasting serum insulin (FSI), 2 h post-load serum insulin (2hSI), HOMA of insulin sensitivity (HOMA2-S) and secretion (HOMA2-B), and the Gutt insulin sensitivity index (ISI0,120) among 120 South Asian and 867 white participants who developed diabetes during follow-up (1991-2013). We fitted cubic mixed-effects models to longitudinal data with adjustment for a wide range of covariates. RESULTS: Compared with white individuals, South Asians had a faster increase in FPG before diagnosis (slope difference 0.22 mmol/l per decade; 95% CI 0.02, 0.42; p = 0.03) and a higher FPG level at diagnosis (0.27 mmol/l; 95% CI 0.06, 0.48; p = 0.01). They also had higher FSI and 2hSI levels before and at diabetes diagnosis. South Asians had a faster decline and lower HOMA2-S (log e -transformed) at diagnosis compared with white individuals (0.33; 95% CI 0.21, 0.46; p < 0.001). HOMA2-B increased in both ethnic groups until 7 years before diagnosis and then declined; the initial increase was faster in white individuals. ISI0,120 declined steeply in both groups before diagnosis; levels were lower among South Asians before and at diagnosis. There were no ethnic differences in 2hPG trajectories. CONCLUSIONS/INTERPRETATION: We observed different trajectories of plasma glucose, insulin sensitivity and secretion prior to diabetes diagnosis in South Asian and white individuals. This might be due to ethnic differences in the natural history of diabetes. South Asian individuals experienced a more rapid decrease in insulin sensitivity and faster increases in FPG compared with white individuals. These findings suggest more marked disturbance in beta cell compensation prior to diabetes diagnosis in South Asian individuals