Western diet-induced ultrastructural changes in mouse pancreatic acinar cells

Mouse models of diet-induced type 2 diabetes mellitus provide powerful tools for studying the structural and physiological changes that are related to the disease progression. In this study, diabetic-like glucose dysregulation was induced in mice by feeding them a western diet, and light and transmission electron microscopy were used to study the ultrastructural changes in the pancreatic acinar cells. Acinar necrosis and vacuolization of the cytoplasm were the most prominent features. Furthermore, we observed intracellular and extracellular accumulation of lipid compounds in the form of lipid droplets, structural enlargement of the cisternae of the rough endoplasmic reticulum (RER), and altered mitochondrial morphology, with mitochondria lacking the typical organization of the inner membrane. Last, autophagic structures, i.e., autophagosomes, autolysosomes, and residual bodies, were abundant within the acinar cells of western diet-fed mice, and the autolysosomes contained lipids and material of varying electron density. While diets inducing obesity and type 2 diabetes are clearly associated with structural changes and dysfunction of the endocrine pancreas, we here demonstrate the strong effect of dietary intervention on the structure of acinar cells in the exocrine part of the organ before detectable changes in plasma amylase activity, which may help us better understand the development of non-alcoholic fatty pancreas disease and its association with endo- and exocrine dysfunction

Application of Transmission Electron Microscopy to Detect Changes in Pancreas Physiology

Insulin resistance in key target organs and beta cell dysfunction due to gluco- and lipotoxicity, are the two main factors driving type 2 diabetes mellitus pathogenesis. Recently, it has been suggested that ectopic fat deposition in the pancreas, named non-alcoholic fatty pancreas disease, occurs in metabolic syndrome, and may play an etiological role in islet dysfunction and damage the exocrine pancreas, increasing its susceptibility to pancreatitis and pancreatic cancer. In this chapter, we present transmission electron microscopy (TEM) as a valuable method to detect early changes in the ultrastructure of pancreatic cells during the development of the metabolic syndrome in mice fed with a western diet (WD). Mice fed with a WD develop pathological ultrastructural alterations in the exocrine and endocrine cells. We demonstrate how to use image segmentation methods and ultrastructural morphometry to analyze and quantify structural changes in cellular organelles and evaluate the presence of lipid droplets, autophagic structures, and vacuolization. Since ultrastructural lesions can be detected early during the progression of the metabolic syndrome, are in many aspects subtle, and by far precede cell apoptosis, necrosis, fat infiltration, and overt functional changes, TEM is not only a suitable but probably the crucial method for detecting early pancreas dysfunction

Attachment in close relationships and glycemic outcomes in children with type 1 diabetes

Background: Our aim was to determine whether child attachment to parents, parent attachment style, and morning cortisol levels were related to diabetes outcomes measured by average glycated hemoglobin (HbA1c), HbA1c variability over 4 years and time in range (TIR) in children with type 1 diabetes (T1D). Research design and methods: 101 children with T1D and one of their parents were assessed at baseline for child attachment (Child Attachment InterviewCAI) and parent attachment (Relationship Structures QuestionnaireECR-RS). Serum samples were collected for cortisol measurements before the interviews. HbA1c levels were measured during a 4-year follow-up period at regular 3-monthly visits, and data for TIR were exported from blood glucose measuring devices. Multivariate linear regression models were constructed to identify independent predictors of glycemic outcomes. Results: More girls than boys exhibited secure attachment to their mothers. The results of the regression models showed that securely attached girls (CAI) had higher average HbA1c than did insecurely attached girls (B = -0.64, p = 0.03). In boys, the more insecure the parent\u27s attachment style, the worse the child\u27s glycemic outcome: the higher the average Hb1Ac (B = 0.51, p = 0.005), the higher the HbA1c variability (B = 0.017, p = 0.011), and the lower the TIR (B = -8.543, p = 0.002). Conclusions: Attachment in close relationships is associated with glycemic outcomes in children with T1D, and we observed significant differences between sexes. A sex- and attachment-specific approach is recommended when treating children with less favorable glycemic outcomes. Special attention and tailored support should be offered to securely attached girls in transferring responsibility for diabetes care and at least to male children of insecurely attached parents to prevent suboptimal glycemic control. Further studies in larger samples and more daily cortisol measurements may help us better understand the links between stress response, attachment and T1D

To ventilate or not to ventilate during bystander CPR — A EuReCa TWO analysis

Background: Survival after out-of-hospital cardiac arrest (OHCA) is still low. For every minute without resuscitation the likelihood of survival decreases. One critical step is initiation of immediate, high quality cardiopulmonary resuscitation (CPR). The aim of this subgroup analysis of data collected for the European Registry of Cardiac Arrest Study number 2 (EuReCa TWO) was to investigate the association between OHCA survival and two types of bystander CPR namely: chest compression only CPR (CConly) and CPR with chest compressions and ventilations (FullCPR). Method: In this subgroup analysis of EuReCa TWO, all patients who received bystander CPR were included. Outcomes were return of spontaneous circulation and survival to 30-days or hospital discharge. A multilevel binary logistic regression analysis with survival as the dependent variable was performed. Results: A total of 5884 patients were included in the analysis, varying between countries from 21 to 1444. Survival was 320 (8%) in the CConly group and 174 (13%) in the FullCPR group. After adjustment for age, sex, location, rhythm, cause, time to scene, witnessed collapse and country, patients who received FullCPR had a significantly higher survival rate when compared to those who received CConly (adjusted odds ration 1.46, 95% confidence interval 1.17–1.83). Conclusion: In this analysis, FullCPR was associated with higher survival compared to CConly. Guidelines should continue to emphasise the importance of compressions and ventilations during resuscitation for patients who suffer OHCA and CPR courses should continue to teach both