Familial hypercholesterolemia (FH) is a genetic disease characterized by high low-density lipoprotein (LDL) cholesterol (LDL-c) concentrations that increase cardiovascular risk and cause premature death. The most frequent cause of the disease is a mutation in the LDL receptor (LDLR) gene. Diabetes is also associated with an increased risk of cardiovascular disease and mortality. People with FH seem to be protected from developing diabetes, whereas cholesterol-lowering treatments such as statins are associated with an increased risk of the disease. One of the hypotheses to explain this is based on the toxicity of LDL particles on insulin-secreting pancreatic β-cells, and their uptake by the latter, mediated by the LDLR. A healthy lifestyle and a relatively low body mass index in people with FH have also been proposed as explanations. Its association with superimposed diabetes modifies the phenotype of FH, both regarding the lipid profile and cardiovascular risk. However, findings regarding the association and interplay between these two diseases are conflicting. The present review summarizes the existing evidence and discusses knowledge gaps on the matter.

The ThyPRO questionnaire is the most widely used tool for measuring quality of life in patients with benign thyroid diseases. The purpose of this study was to adapt and validate a Spanish translation of the ThyPRO and its abbreviated version (ThyPRO-39). Adaptation to the Spanish language was performed using the forward-backward translation method, followed by a pretesting study on five representative patients. The final questionnaire (ThyPROes) was administered to 155 patients with thyroid disorders recruited in a tertiary Spanish hospital. Psychometric properties were evaluated by multitrait scaling and estimation of internal consistency reliability (Cronbach's alpha coefficient). Data from a previous sample of 902 Danish patients were used to analyze differential item functioning (DIF) between the Spanish and the original Danish versions of the questionnaire using ordinal logistic regression. Three of 85 items in ThyPROes and four of the 39 items in ThyPRO-39es lacked convergent validity, while lack of discriminant validity was found for in nine and 14 items of each version respectively. Cronbach's alpha was >0.7 for 12 of 13 scales in the ThyPRO and 10 of 12 scales in the ThyPRO-39es. Eight items in the ThyPROes were flagged with DIF (one with non-uniform DIF), as were two items in the ThyPRO-39es. DIF magnitude was small (explained variance in the item score <3%) in most cases, with a minor impact on scale scores. The Spanish versions of the ThyPRO and ThyPRO-39 show acceptable psychometric properties and good cross-lingual validity, and are suitable for use in clinical studies.

Plasma triglyceride levels are a strong cardiovascular risk marker. However, triglyceride–lowering therapies have not demonstrated a reduction in cardiovascular events, suggesting that triglycerides may serve as surrogate markers for other atherogenic mechanisms. The aim is to investigate the role of triglycerides in derangements of the global lipoprotein profile, as assessed by ¹H–NMR spectroscopy. Serum lipoprotein profiles were analyzed in patients with metabolic alterations attending the Lipid Unit of a University hospital (n = 822). Lipoprotein particle number, size, and composition were evaluated and visualized through a graphic representation of a lipoprotein network analysis referred to lipid silhouette in patients sorted by triglyceride quartiles. Profound alterations in lipoprotein quantity and composition were associated with incremental triglyceride concentrations independently on the presence of diabetes or obesity, including a significantly increased number of VLDL and smaller LDL particles, and higher remnant cholesterol, representing up to 30% of all cholesterol in quartile 4. It was also a significant triglyceride enrichment of LDL and HDL particles. Triglycerides are not merely components of atherogenic dyslipidemia; they are a key driver of the overall changes and are strongly associated with a proatherogenic plasma lipoprotein profile. Visualization of these alterations provides supplementary insights to support cardiovascular prevention strategies.

The p.(Tyr400_Phe402del) mutation in the LDL receptor (LDLR) gene is the most frequent cause of familial hypercholesterolaemia (FH) in Gran Canaria. The aim of this study was to determine the age and origin of this prevalent founder mutation and to explore its functional consequences. For this purpose, we obtained the haplotypic information of 14 microsatellite loci surrounding the mutation in one homozygous individual and 11 unrelated heterozygous family trios. Eight different mutation carrier haplotypes were identified, which were estimated to originate from a common ancestral haplotype 387 (110–1572) years ago. This estimation suggests that this mutation happened after the Spanish colonisation of the Canary Islands, which took place during the fifteenth century. Comprehensive functional studies of this mutation showed that the expressed LDL receptor was retained in the endoplasmic reticulum, preventing its migration to the cell surface, thus allowing us to classify this LDLR mutation as a class 2a, defective, pathogenic variant.