| 1. |
- Acerini, Carlo L., et al.
(författare)
-
Optimizing Patient Management and Adherence for children receiving Growth Hormone
- 2017
-
Ingår i: Frontiers in Endocrinology. - : FRONTIERS MEDIA SA. - 1664-2392. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Poor adherence with growth hormone (GH) therapy has been associated with worse clinical outcomes, which in children relates specifically to their linear growth and loss of quality of life. The "360 degrees GH in Europe" meeting, held in Lisbon, Portugal, in June 2016 and funded by Merck KGaA (Germany), examined many aspects of GH diseases. The three sessions, entitled "Short Stature Diagnosis and Referral," "Optimizing Patient Management," and "Managing Transition," each benefited from three guest speaker presentations, followed by an open discussion and are reported as a manuscript, authored by the speakers. Reported here is a summary of the proceedings of the second session, which reviewed the determinants of GH therapy response, factors affecting GH therapy adherence and the development of innovative technologies to improve GH treatment in children. Response to GH therapy varies widely, particularly in regard to the underlying diagnosis, although there is little consensus on the definition of a poor response. If the growth response is seen to be less than expected, the possible reasons should be discussed with patients and their parents, including compliance with the therapy regimen. Understanding and addressing the multiple factors that influence adherence, in order to optimize GH therapy, requires a multi-disciplinary approach. Because therapy continues over many years, various healthcare professionals will be involved at different periods of the patients journey. The role of the injection device for GH therapy, frequent monitoring of response, and patient support are all important for maintaining adherence. New injection devices are incorporating electronic technologies for automated monitoring and recording of clinically relevant information on injections. Study results are indicating that such devices can at least maintain GH adherence; however, acceptance of novel devices needs to be assessed and there remains an on-going need for innovations.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Ahlin, Sofie, 1985, et al.
(författare)
-
Metabolite Changes After Metabolic Surgery – Associations to Parameters Reflecting Glucose Homeostasis and Lipid Levels
- 2021
-
Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To test the hypothesis that adipose tissue gene expression patterns would be affected by metabolic surgery and we aimed to identify genes and metabolic pathways as well as metabolites correlating with metabolic changes following metabolic surgery. Materials and Methods: This observational study was conducted at the Obesity Unit at the Catholic University Hospital of the Sacred Heart in Rome, Italy. Fifteen patients, of which six patients underwent Roux-en-Y gastric bypass and nine patients underwent biliopancreatic diversion, were included. The participants underwent an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Small polar metabolites were analyzed with a two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS). Gene expression analysis of genes related to metabolism of amino acids and fatty acids were analyzed in subcutaneous adipose tissue. All procedures were performed at study start and at follow-up (after 185.3 ± 72.9 days). Results: Twelve metabolites were significantly changed after metabolic surgery. Six metabolites were identified as 3-indoleacetic acid, 2-hydroxybutyric acid, valine, glutamic acid, 4-hydroxybenzeneacetic acid and alpha-tocopherol. The branched chain amino acids displayed a significant decrease together with a decrease in BCAT1 adipose tissue mRNA levels. Changes in the identified metabolites were associated to changes in lipid, insulin and glucose levels. Conclusions: Our study has identified metabolites and metabolic pathways that are altered by metabolic surgery and may be used as biomarkers for metabolic improvement. Copyright © 2021 Ahlin, Cefalo, Bondia-Pons, Trošt, Capristo, Marini, Romero, Zorzano, Gastaldelli, Mingrone and Nolan.
|
|
| 5. |
|
|
| 6. |
- Ahmad, Shafqat, et al.
(författare)
-
Gene Lifestyle Interactions With Relation to Obesity, Cardiometabolic, and Cardiovascular Traits Among South Asians
- 2019
-
Ingår i: Frontiers in Endocrinology. - : FRONTIERS MEDIA SA. - 1664-2392. ; 10
-
Forskningsöversikt (refereegranskat)abstract
- The rapid rise of obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) during the last few decades among South Asians has been largely attributed to a major shift in lifestyles including physical inactivity, unhealthy dietary patterns, and an overall pattern of sedentary lifestyle. Genetic predisposition to these cardiometabolic risk factors may have interacted with these obesogenic environments in determining the higher cardiometabolic disease prevalence. Based on the premise that gene-environment interactions cause obesity and cardiometabolic diseases, we systematically searched the literature and considered the knowledge gaps that future studies might ful fill. We identified only seven published studies that focused specifically on gene-environment interactions for cardiometabolic traits in South Asians, most of which were limited by relatively small sample and lack of replication. Some studies reported that the differences in metabolic response to higher physical activity and low caloric diet might be modified by genetic risk related to these cardiometabolic traits. Although studies on gene lifestyle interactions in cardiometabolic traits report significant interactions, future studies must focus on more precise assessment of lifestyle factors, investigation of a larger set of genetic variants and the application of powerful statistical methods to facilitate translatable approaches. Future studies should also be integrated with findings both using mechanistic studies through laboratory settings and randomized clinical trials for clinical outcomes.
|
|
| 7. |
- Ahrén, Bo
(författare)
-
DPP-4 inhibition and the path to clinical proof
- 2019
-
Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 10:JUN
-
Tidskriftsartikel (refereegranskat)abstract
- In the 1990s it was discovered that the enzyme dipeptidyl peptidase-4 (DPP-4) inactivates the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). DPP-4 inhibition results in raised levels of the two incretin hormones which in turn result in lowering of circulating glucose through stimulation of insulin secretion and inhibition of glucagon secretion. Since then, several small orally available molecules have been developed with DPP-4 inhibitory action. Early studies in the 1990s showed that the DPP-4 inhibitors improve glycemia in animals. Subsequent clinical studies during the 2000s showed a glucose-lowering action of DPP-4 inhibitors also in human subjects with type 2 diabetes. This action was seen when DPP-4 inhibitors were used both as monotherapy and as add-on to other therapies, i.e., metformin, sulfonylureas, tiazolidinediones or exogenous insulin. The DPP-4 inhibitors were also found to have a low risk of adverse events, including hypoglycemia. Five of the DPP-4 inhibitors (sitagliptin, vildagliptin, alogliptin, saxagliptin and linagliptin) were approved by regulatory authorities and entered the market between 2006 and 2013. DPP-4 inhibitors have thereafter undergone long-term cardiovascular outcome trials, showing non-inferiority for risk of major acute cardiovascular endpoints. Also the risk of other potential adverse events is low in these long-term studies. DPP-4 inhibitors are at present included in guidelines as a glucose-lowering concept both as monotherapy and in combination therapies. This article summarizes the development of the DPP-4 inhibition concept from its early stages in the 1990s. The article underscores that the development has its basis in scientific studies on pathophysiology of type 2 diabetes and the importance of targeting the islet dysfunction, that the development has been made possible through academic science in collaboration with the research-oriented pharmaceutical industry, and that the development of a novel concept takes time and requires focused efforts, persistence and long-term perserverance.
|
|
| 8. |
- Ahrén, Bo, et al.
(författare)
-
The Insulin Response to Oral Glucose in GIP and GLP-1 Receptor Knockout Mice : Review of the Literature and Stepwise Glucose Dose Response Studies in Female Mice
- 2021
-
Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- A key factor for the insulin response to oral glucose is the pro-glucagon derived incretin hormone glucagon-like peptide-1 (GLP-1), together with the companion incretin hormone, glucose-dependent insulinotropic polypeptide (GIP). Studies in GIP and GLP-1 receptor knockout (KO) mice have been undertaken in several studies to examine this role of the incretin hormones. In the present study, we reviewed the literature on glucose and insulin responses to oral glucose in these mice. We found six publications with such studies reporting results of thirteen separate study arms. The results were not straightforward, since glucose intolerance in GIP or GLP-1 receptor KO mice were reported only in eight of the arms, whereas normal glucose tolerance was reported in five arms. A general potential weakness of the published study is that each of them have examined effects of only one single dose of glucose. In a previous study in mice with genetic deletion of both GLP-1 and GIP receptors we showed that these mice have impaired insulin response to oral glucose after large but not small glucose loads, suggesting that the relevance of the incretin hormones may be dependent on the glucose load. To further test this hypothesis, we have now performed a stepwise glucose administration through a gastric tube (from zero to 125mg) in model experiments in anesthetized female wildtype, GLP-1 receptor KO and GIP receptor KO mice. We show that GIP receptor KO mice exhibit glucose intolerance in the presence of impaired insulin response after 100 and 125 mg glucose, but not after lower doses of glucose. In contrast, GLP-1 receptor KO mice have normal glucose tolerance after all glucose loads, in the presence of a compensatory increase in the insulin response. Therefore, based on these results and the literature survey, we suggest that GIP and GLP-1 receptor KO mice retain normal glucose tolerance after oral glucose, except after large glucose loads in GIP receptor KO mice, and we also show an adaptive mechanism in GLP-1 receptor KO mice, which needs to be further examined.
|
|
| 9. |
- Akkuratova, N, et al.
(författare)
-
Developmental heterogeneity of embryonic neuroendocrine chromaffin cells and their maturation dynamics
- 2022
-
Ingår i: Frontiers in endocrinology. - : Frontiers Media SA. - 1664-2392. ; 13, s. 1020000-
-
Tidskriftsartikel (refereegranskat)abstract
- During embryonic development, nerve-associated Schwann cell precursors (SCPs) give rise to chromaffin cells of the adrenal gland via the “bridge” transient stage, according to recent functional experiments and single cell data from humans and mice. However, currently existing data do not resolve the finest heterogeneity of developing chromaffin populations. Here we took advantage of deep SmartSeq2 transcriptomic sequencing to expand our collection of individual cells from the developing murine sympatho-adrenal anlage and uncover the microheterogeneity of embryonic chromaffin cells and their corresponding developmental paths. We discovered that SCPs on the splachnic nerve show a high degree of microheterogeneity corresponding to early biases towards either Schwann or chromaffin terminal fates. Furthermore, we found that a post-”bridge” population of developing chromaffin cells gives rise to persisting oxygen-sensing chromaffin cells and the two terminal populations (adrenergic and noradrenergic) via diverging differentiation paths. Taken together, we provide a thorough identification of novel markers of adrenergic and noradrenergic populations in developing adrenal glands and report novel differentiation paths leading to them.
|
|
| 10. |
- Alanentalo, Tomas, et al.
(författare)
-
Mesoscopic Optical Imaging of the Pancreas : Revisiting Pancreatic Anatomy and Pathophysiology
- 2021
-
Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 12
-
Forskningsöversikt (refereegranskat)abstract
- The exocrine-endocrine multipart organization of the pancreas makes it an exceedingly challenging organ to analyze, quantitatively and spatially. Both in rodents and humans, estimates of the pancreatic cellular composition, including beta-cell mass, has been largely relying on the extrapolation of 2D stereological data originating from limited sample volumes. Alternatively, they have been obtained by low resolution non-invasive imaging techniques providing little detail regarding the anatomical organization of the pancreas and its cellular and/or molecular make up. In this mini-review, the state of the art and the future potential of currently existing and emerging high-resolution optical imaging techniques working in the mm-cm range with μm resolution, here referred to as mesoscopic imaging approaches, will be discussed regarding their contribution toward a better understanding of pancreatic anatomy both in normal conditions and in the diabetic setting. In particular, optical projection tomography (OPT) and light sheet fluorescence microscopy (LSFM) imaging of the pancreas and their associated tissue processing and computational analysis protocols will be discussed in the light of their current capabilities and future potential to obtain more detailed 3D-spatial, quantitative, and molecular information of the pancreas.
|
|
