β Cell transcription factors such as forkhead box protein O1 (FoxO1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), pancreatic and duodenal homeobox 1, and neuronal differentiation 1, are dysfunctional in type 2 diabetes mellitus (T2DM). Posttransplant diabetes mellitus resembles T2DM and reflects interaction between pretransplant insulin resistance and immunosuppressants, mainly calcineurin inhibitors (CNIs). We evaluated the effect of tacrolimus (TAC), cyclosporine A (CsA), and metabolic stressors (glucose plus palmitate) on insulinoma β cells in vitro and in pancreata of obese and lean Zucker rats. Cells were cultured for 5 days with 100 μM palmitate and 22 mM glucose; CsA (250 ng/mL) or TAC (15 ng/mL) were added in the last 48 h. Glucose plus palmitate increased nuclear FoxO1 and decreased nuclear MafA. TAC in addition to glucose plus palmitate magnified these changes in nuclear factors, whereas CsA did not. In addition to glucose plus palmitate, both drugs reduced insulin content, and TAC also affected insulin secretion. TAC withdrawal or conversion to CsA restored these changes. Similar results were observed in pancreata of obese animals on CNIs. TAC and CsA, in addition to glucose plus palmitate, induced comparable inhibition of calcineurin and nuclear factor of activated T cells (NFAT); therefore, TAC potentiates glucolipotoxicity in β cells, possibly by sharing common pathways of β cell dysfunction. TAC-induced β cell dysfunction is potentially reversible. Inhibition of the calcineurin–NFAT pathway may contribute to the diabetogenic effect of CNIs but does not explain the stronger effect of TAC compared with CsA.

Background—: Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor ( LDLR ), apolipoprotein B ( APOB ), proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), and LDL protein receptor adaptor 1 ( LDLRAP1 ). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition. Here, we aimed to characterize HoFH in Spain. Methods and Results—: Data were collected from the Spanish Dyslipidemia Registry of the Spanish Atherosclerosis Society and from all molecular diagnoses performed for familial hypercholesterolemia in Spain between 1996 and 2015 (n=16 751). Clinical data included baseline lipid levels and atherosclerotic cardiovascular disease events. A total of 97 subjects were identified as having HoFH—of whom, 47 were true homozygous (1 for APOB , 5 for LDLRAP1 , and 41 for LDLR ), 45 compound heterozygous for LDLR , 3 double heterozygous for LDLR and PSCK9 , and 2 double heterozygous for LDLR and APOB . No PSCK9 homozygous cases were identified. Two variants in LDLR were identified in 4.8% of the molecular studies. Over 50% of patients did not meet the classical HoFH diagnosis criteria. The estimated HoFH prevalence was 1:450 000. Compared with compound heterozygous cases, true homozygous cases showed more aggressive phenotypes with higher LDL-C and more atherosclerotic cardiovascular disease events. Conclusions—: HoFH frequency in Spain was higher than expected. Clinical criteria would underestimate the actual prevalence of individuals with genetic HoFH, highlighting the importance of genetic analysis to improve familial hypercholesterolemia diagnosis accuracy.

Maternal diabetes is associated with an increased risk of complications for the mother and her offspring. The latter have an increased risk of foetal macrosomia, hypoglycaemia, respiratory distress syndrome, preterm delivery, malformations and mortality but also of life-long development of obesity and diabetes. Epigenetics have been proposed as an explanation for this long-term risk, and microRNAs (miRNAs) may play a role, both in short- and long-term outcomes. Gestation is associated with increasing maternal insulin resistance, as well as β-cell expansion, to account for the increased insulin needs and studies performed in pregnant rats support a role of miRNAs in this expansion. Furthermore, several miRNAs are involved in pancreatic embryonic development. On the other hand, maternal diabetes is associated with changes in miRNA both in maternal and in foetal tissues. This review aims to summarise the existing knowledge on miRNAs in gestational and pre-gestational diabetes, both as diagnostic biomarkers and as mechanistic players, in the development of gestational diabetes itself and also of short- and long-term complications for the mother and her offspring.

Background: Portable blood glucose meters (PBGMs) allow easy glucose measurements. As animal-specific PBGMs are not available everywhere, those for humans are widely used. Objectives: To assess the accuracy and precision of 9 PBGMs in canine whole blood (WB) and plasma, based on the ISO 15197:2013. Animals: Fifty-nine client-owned dogs attending the Veterinary Teaching Hospital. Methods: Analytical evaluation of 100 blood samples was performed for accuracy and 23 for precision (glucose 29–579 mg/dL) following ISO recommendations. A PBGM was considered accurate if 95% of the measurements were within ±15 mg/dL from the reference when glucose was <100 mg/dL and within ±15% when it was ≥100 mg/dL, and if 99% of them were within zones A and B in error grid analysis (EG). A hexokinase-based analyzer was used as reference. Ninety samples were assessed for hematocrit interferences. Results: Accuracy requirements were not fulfilled by any PBGM in WB (74% of measurements within the limits for the most accurate) and by 1 only in plasma. However, the EG analysis in WB was passed by 6 PBGM and by all in plasma. The most accurate were also the most precise, with coefficients of variation <5% in WB and <3% in plasma. Hematocrit correlated with bias against the reference method in 4 PBGM (r = −0.243 − [−0.371]; P < .021). Conclusions and Clinical Importance: This disparity among PBGM suggests that meters approved for humans need to be evaluated before use in other species.