Data-driven metabolic subtypes predict future adverse events in individuals with type 1 diabetes

Aims/hypothesis Previously, we proposed that data-driven metabolic subtypes predict mortality in type 1 diabetes. Here, we analysed new clinical endpoints and revisited the subtypes after 7 years of additional follow-up. Methods Finnish individuals with type 1 diabetes (2059 men and 1924 women, insulin treatment before 35 years of age) were recruited by the national multicentre FinnDiane Study Group. The participants were assigned one of six metabolic subtypes according to a previously published self-organising map from 2008. Subtype-specific all-cause and cardiovascular mortality rates in the FinnDiane cohort were compared with registry data from the entire Finnish population. The rates of incident diabetic kidney disease and cardiovascular endpoints were estimated based on hospital records. Results The advanced kidney disease subtype was associated with the highest incidence of kidney disease progression (67.5% per decade, p <0.001), ischaemic heart disease (26.4% per decade, p <0.001) and all-cause mortality (41.5% per decade, p <0.001). Across all subtypes, mortality rates were lower in women compared with men, but standardised mortality ratios (SMRs) were higher in women. SMRs were indistinguishable between the original study period (19942007) and the new period (2008-2014). The metabolic syndrome subtype predicted cardiovascular deaths (SMR 11.0 for men, SMR 23.4 for women, p <0.001), and women with the high HDL-cholesterol subtype were also at high cardiovascular risk (SMR 16.3, p <0.001). Men with the low-cholesterol or good glycaemic control subtype showed no excess mortality. Conclusions/interpretation Data-driven multivariable metabolic subtypes predicted the divergence of complication burden across multiple clinical endpoints simultaneously. In particular, men with the metabolic syndrome and women with high HDL-cholesterol should be recognised as important subgroups in interventional studies and public health guidelines on type 1 diabetes.Peer reviewe

Patients with type 1 diabetes show signs of vascular dysfunction in response to multiple high-fat meals

Peer reviewe

Oxygen deteriorates arterial function in type 1 diabetes

Aims Although oxygen is commonly used to treat various medical conditions, it has recently been shown to worsen vascular function (arterial stiffness) in healthy volunteers and even more in patients in whom vascular function might already be impaired. The effects of oxygen on arterial function in patients with type 1 diabetes (T1D) are unknown, although such patients display disturbed vascular function already at rest. Therefore, we tested whether short-term oxygen administration may alter the arterial function in patients with T1D. Methods We estimated arterial stiffness by augmentation index (AIx) and the pulse wave velocity equivalent (SI-DVP) in 98 patients with T1D and 49 age-and sex-matched controls at baseline and during hyperoxia by obtaining continuous noninvasive finger pressure waveforms using a recently validated method. Results AIx and SI-DVP increased in patients (P <0.05) but not in controls in response to hyperoxia. The increase in AIx (P = 0.05), systolic (P <0.05), and diastolic (P <0.05) blood pressure was higher in the patients than in the controls. Conclusions Short-term oxygen administration deteriorates arterial function in patients with T1D compared to non-diabetic control subjects. Since disturbed arterial function plays a major role in the development of diabetic complications, these findings may be of clinical relevance.Peer reviewe

Molecular Insights on Successful Reconstitution of Freeze-Dried Nanofibrillated Cellulose Hydrogel

The diversity and safety of nanofibrillated cellulose (NFC) hydrogels have gained a vast amount of interest at the pharmaceutical site in recent years. Moreover, this biomaterial has a high potential to be utilized as a protective matrix during the freeze-drying of heat-sensitive pharmaceuticals and biologics to increase their properties for long-term storing at room temperature and transportation. Since freeze-drying and subsequent reconstitution have not been optimized for this biomaterial, we must find a wider understanding of the process itself as well as the molecular level interactions between the NFC hydrogel and the most suitable lyoprotectants. Herein we optimized the reconstitution of the freeze-dried NFC hydrogel by considering critical quality attributes required to ensure the success of the process and gained insights of the obtained experimental data by simulating the effects of the used lyoprotectants on water and NFC. We discovered the correlation between the measured characteristics and molecular dynamics simulations and obtained successful freeze-drying and subsequent reconstitution of NFC hydrogel with the presence of 300 mM of sucrose. These findings demonstrated the possibility of using the simulations together with the experimental measurements to obtain a more comprehensive way to design a successful freeze-drying process, which could be utilized in future pharmaceutical applications.Peer reviewe

Attempted suicide among immigrants in European countries: an international perspective

This study compares the frequencies of attempted suicide among immigrants and their hosts, between different immigrant groups, and between immigrants and their countries of origin. The material, 27,048 persons, including 4,160 immigrants, was obtained from the WHO/EURO Multicentre Study on Suicidal Behaviour, the largest available European database, and was collected in a standardised manner from 11 European centres in 1989-2003. Person-based suicide-attempt rates (SARs) were calculated for each group. The larger immigrant groups were studied at each centre and compared across centres. Completed-suicide rates of their countries of origin were compared to the SARs of the immigrant groups using rank correlations. 27 of 56 immigrant groups studied showed significantly higher, and only four groups significantly lower SARs than their hosts. Immigrant groups tended to have similar rates across different centres. Moreover, positive correlation between the immigrant SAR and the country-of-origin suicide rate was found. However, Chileans, Iranians, Moroccans, and Turks displayed high SARs as immigrants despite low suicide rates in the home countries. The similarity of most immigrant groups' SARs across centres, and the correlation with suicidality in the countries of origin suggest a strong continuity that can be interpreted in either cultural or genetic terms. However, the generally higher rates among immigrants compared to host populations and the similarity of the rates of foreign-born and those immigrants who retained the citizenship of their country of origin point to difficulties in the acculturation and integration process. The positive correlation found between attempted and completed suicide rates suggests that the two are related, a fact with strong implications for suicide prevention