Paternally expressed gene 3 (Pw1/Peg3) promotes sexual dimorphism in metabolism and behavior

The paternally expressed gene 3 (Pw1/Peg3) is a mammalian-specific parentally imprinted gene expressed in stem/progenitor cells of the brain and endocrine tissues. Here, we compared phenotypic characteristics in Pw1/Peg3 deficient male and female mice. Our findings indicate that Pw1/Peg3 is a key player for the determination of sexual dimorphism in metabolism and behavior. Mice carrying a paternally inherited Pw1/Peg3 mutant allele manifested postnatal deficits in GH/IGF dependent growth before weaning, sex steroid dependent masculinization during puberty, and insulin dependent fat accumulation in adulthood. As a result, Pw1/Peg3 deficient mice develop a sex-dependent global shift of body metabolism towards accelerated adiposity, diabetic-like insulin resistance, and fatty liver. Furthermore, Pw1/Peg3 deficient males displayed reduced social dominance and competitiveness concomitant with alterations in the vasopressinergic architecture in the brain. This study demonstrates that Pw1/Peg3 provides an epigenetic context that promotes male-specific characteristics through sex steroid pathways during postnatal development.

Fetal adrenal cortex function in pregnancy, complicated by maternal insulin-dependent diabetes mellitus

Fetal adrenal cortex glucocorticoid andfetal hypophysial adrenocorticotropic function in normal pregnancy and pregnancy, complicated with maternal insulin dependent diabetes mellitus were examined in the present study. Statistically significant feta l hypercortisolemia was observed in pregnancies, complicated by insulin-dependent diabetes mellitus. Correlations between vascular complications o f maternal insulin-dependent diabetes mellitus and fetal cortisol andACTG levels were revealed during the investigation. Severe vascular lesions o f maternal diabetes have been associated with delayed feta l lung maturity. Fetal pulmonary maturity was significantly associated with fe ta l cortisol levels.

Diabetes status and postoperative complications for patients receiving open rotator cuff repair

Background Diabetic patients are known to have poor wound healing and worse outcomes following surgeries. The purpose of this study is to evaluate diabetes status and complications for patients receiving open rotator cuff repair. Methods Patients undergoing open rotator cuff repair from 2006 to 2018 were identified in a national database. Patients were stratified into 3 cohorts: no diabetes mellitus, non-insulin dependent diabetes mellitus (NIDDM), and insulin dependent diabetes mellitus (IDDM). Differences in demographics, comorbidities, and complications were assessed with the use of bivariate and multivariate analyses. Results Of 7678 total patients undergoing open rotator cuff repair, 6256 patients (81.5%) had no diabetes, 975 (12.7%) had NIDDM, and 447 (5.8%) had IDDM. Bivariate analyses revealed that IDDM patients had increased risk of mortality, extended length of stay, and readmission compared to non-diabetic patients ( p < 0.05 for all). IDDM patients had higher risks of major complications and readmission relative to NIDDM patients ( p < 0.05 for both). On multivariate analysis, there were no differences in any postoperative complications between the non-diabetic, NIDDM, and IDDM groups. Discussion Diabetes does not affect postoperative complications following open rotator cuff repairs. Physicians should be aware of this finding and counsel their patients appropriately. Level of Evidence: III

Methemoglobinaemia in Diabetic Ketoacidosis Patient

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked genetic disorder. Case Presentation: In this paper, we report a case of a 41-years-old male patient with non-insulin-dependent diabetes and a family history of G6PD deficiency never known to have any previous hemolytic episodes, presented as a case of diabetic ketoacidosis with features of hemolytic anemia due to G6PD deficiency manifesting as methemoglobinemia and anemia. Conclusion: Our patient successfully managed with ascorbic acid and red blood cell transfusion. Clinicians should, therefore, be aware of the possibility of this uncommon association between diabetic ketoacidosis, G6PD deficiency, and methemoglobinemia which may be present in patients with G6PD deficiency and severe hemolysis.

Duodenal mucosal resurfacing with GLP-1 receptor agonism increases postprandial unconjugated bile acid in patients with insulin-dependent type 2 diabetes

Introduction: Duodenal Mucosal Resurfacing (DMR) is a new endoscopic ablation technique aimed at improving glycemia and metabolic control in patients with type 2 diabetes mellitus (T2DM). DMR appears to improve insulin resistance, which is the root cause of T2DM, but its mechanism of action is largely unknown. Bile acids function as intestinal signalling molecules in glucose and energy metabolism via the activation of farnesoid X receptor and secondary signalling (e.g. via fibroblast growth factor 19[FGF19]), and are linked to metabolic health. Methods: We investigated the effect of DMR and GLP-1 on postprandial bile acid responses in 16 patients with insulin-dependent T2DM, using mixed meal tests performed at baseline and six months after the DMR procedure. Results: The combination treatment allowed discontinuation of insulin treatment in 11/16 (69%) of patients while improving glycaemic and metabolic health. We found increased postprandial unconjugated bile acid responses (all p<0.05), an overall increased secondary bile acid response (p=0.036) and a higher 12α-hydroxylated:non12α-hydroxylated ratio (p<0.001). Total bile acid concentrations were unaffected by the intervention. Postprandial FGF19 and 7-alpha-hydroxy-4-cholesten-3-one (C4) concentrations decreased post-intervention (both p<0.01). Conclusion and discussion: Our study demonstrates that DMR with GLP-1 modulates the postprandial bile acid response. The alterations in postprandial bile acid responses may be the result of changes in the microbiome, ileal bile acid uptake and improved insulin sensitivity. Controlled studies are needed to elucidate the mechanism linking the combination treatment to metabolic health and bile acids.

CANDIED: A Pan-Canadian Cohort of Immune Checkpoint Inhibitor-Induced Insulin-Dependent Diabetes Mellitus

Immune checkpoint inhibitor (ICI)-induced insulin-dependent diabetes mellitus (IDDM) is a rare but potentially fatal immune-related adverse event (irAE). In this multicentre retrospective cohort study, we describe the characteristics of ICI-induced IDDM in patients treated across five Canadian cancer centres, as well as their tumor response rates and survival. In 34 patients identified, 25 (74%) were male and 19 (56%) had melanoma. All patients received anti-programed death 1 (anti-PD1) or anti-programmed death ligand-1 (anti-PD-L1)-based therapy. From ICI initiation, median time to onset of IDDM was 2.4 months (95% CI 1.1–3.6). Patients treated with anti-PD1/PD-L1 in combination with an anti-cytotoxic T lymphocyte antigen 4 antibody developed IDDM earlier compared with patients on monotherapy (1.4 vs. 3.9 months, p = 0.05). Diabetic ketoacidosis occurred in 21 (62%) patients. Amongst 30 patients evaluable for response, 10 (33%) had a complete response and another 10 (33%) had a partial response. Median overall survival was not reached (95% CI NE; median follow-up 31.7 months). All patients remained insulin-dependent at the end of follow-up. We observed that ICI-induced IDDM is an irreversible irAE and may be associated with a high response rate and prolonged survival.

The Effect of Longitudinal Gastric Resection in Morbid Obesity Surgery on the Course of Insulin-Dependent Diabetes and Gastroesophageal Reflux Disease

Longitudinal resection of the stomach is a relatively new type of gastroplasty within the framework of bariatric surgery, which is gaining popularity worldwide today not only as a method of getting rid of excess subcutaneous fat, but also from a range of serious chronic diseases together. The potential of longitudinal gastric resection turned out to be promising, and if the first performed longitudinal gastric resection in 1988 was only a restrictive stage of biliopancreotic bypass surgery, then since the 2000s, laparoscopic longitudinal resection has been started as a deliberately first stage in patients with morbid obesity with high operational risk. To date, longitudinal gastric resection has become increasingly used in particularly difficult cases in the form of independent surgical intervention, for example, in the elderly, teenagers, people with cirrhosis of the liver and other severe pathologies. At the initial stages of the formation of this type of treatment, different surgeons did not have a common opinion on many issues related to the technique of this operation. And therefore, to date, the data on the longitudinal resection of the stomach of many years ago are contradictory. They do not create a holistic view of the effectiveness of surgical intervention, especially in the long term. According to IFSO (The International Federation for the Surgery of Obesity and Metabolic Disorders) data, in 2012, longitudinal gastric resection accounted for 27.8% of all bariatric operations, which even then overtook the gastric banding operation in terms of the number of operations. Over the past 20 years, a little more than 250 thousand such operations have been performed worldwide, and the frequency of performing longitudinal gastric resection increases every year. The purpose of this article is to reveal the statistics of the effectiveness of longitudinal gastric resection.