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Stoffers, D.

Publications and source records attributed to Stoffers, D..

2 recordsLinked to original sources

Insomnia subtypes have differentiating deviations in brain structural connectivity

ObjectiveInsomnia disorder is the most common sleep disorder. A better understanding of insomnia-related deviations in the brain could inspire better treatment. Insufficiently recognized heterogeneity within the insomnia population could obscure involved brain circuits. The present study investigated whether structural brain connectivity deviations differ between recently discovered and validated insomnia subtypes. MethodsStructural and diffusion weighted 3-Tesla MRI data of four independent studies were harmonized. The sample consisted of 73 controls without sleep complaints and 204 participants with insomnia grouped into five subtypes based on their fingerprint of personality and mood traits assessed with the Insomnia Type Questionnaire. Linear regression correcting for age, sex, and brain volume evaluated group differences in structural connectivity strength, indicated by fractional anisotropy and mean diffusivity, and evaluated within two different atlases. ResultsInsomnia subtypes showed differentiating profiles of deviating structural connectivity which moreover concentrated in different functional networks. Permutation testing against randomly drawn heterogeneous subsamples indicated significant specificity of deviation profiles in four of the five subtypes: highly distressed (p=0.019), moderately distressed reward insensitive (p=0.014), slightly distressed low reactive (p=0.006) and slightly distressed high reactive (p=0.006). ConclusionsOur results provide a first indication that different insomnia subtypes exhibit distinct profiles of deviations in structural brain connectivity. Subtyping of insomnia could be essential for a better understanding of brain mechanisms that contribute to insomnia vulnerability.

neuroscience↗

Alpha cell dysfunction in early type 1 diabetes

Multiple islet autoantibodies (AAb) predict type 1 diabetes (T1D) and hyperglycemia within 10 years. By contrast, T1D develops in just [~]15% of single AAb+ (generally against glutamic acid decarboxylase, GADA+) individuals; hence the single GADA+ state may represent an early stage of T1D amenable to interventions. Here, we functionally, histologically, and molecularly phenotype human islets from non-diabetic, GADA+ and T1D donors. Similar to the few remaining beta cells in T1D islets, GADA+ donor islets demonstrated a preserved insulin secretory response. By contrast, alpha cell glucagon secretion was dysregulated in both T1D and GADA+ islets with impaired glucose suppression of glucagon secretion. Single cell RNA sequencing (scRNASeq) of GADA+ alpha cells revealed distinct abnormalities in glycolysis and oxidative phosphorylation pathways and a marked downregulation of PKIB, providing a molecular basis for the loss of glucose suppression and the increased effect of IBMX observed in GADA+ donor islets. The striking observation of a distinct early defect in alpha cell function that precedes beta cell loss in T1D suggests that not only overt disease, but also the progression to T1D itself, is bihormonal in nature.

physiology↗