Youth-onset type 2 diabetes (T2D) is increasing around the globe. The increased disease burden of youth-onset T2D portends substantial consequences for the health outcomes of young people and for health care systems. The pathophysiology of this condition is characterized by insulin resistance and initial insulin hypersecretion +/- an inherent insulin secretory defect, with progressive loss of stimulated insulin secretion leading to pancreatic β-cell failure. Research studies focusing on youth-onset T2D have illuminated key differences for youth- versus adult-onset T2D, with youth having more profound insulin resistance and quicker progression to loss of sufficient insulin secretion to maintain euglycemia. Therapies targeted to improve both insulin resistance and, importantly, maintain sufficient insulin secretory function over the lifespan in youth-onset T2D are needed.

This paper presents the case of a 22-year-old woman who was hospitalized multiple times with episodes of psychosis co-occurring with hyperglycemia. Her psychosis was characterized by auditory hallucinations, visual hallucinations, and disorganized speech and behavior. The patient has a prior medical history of type 1 diabetes mellitus (T1DM) and Graves\' disease and was non-adherent to diabetic diet and medications. The patient is a Somalian refugee who moved to the United States (US) a year ago. We explore the relatively unique observation of hyperglycemia-induced psychosis in the patient, specifically in the context of autoimmune disorders. We also discuss some of the complexities associated with the cultural aspects of mental health and diabetes management in refugee communities and their implications in clinical practice.

OBJECTIVE: To investigate the effect of hyperglycemia and empagliflozin on cardiorenal injury and inflammation in patients with uncomplicated type 1 diabetes (T1D).
METHODS: Serum cardiac (sST2, Gal-3, cTnT), kidney injury (KIM-1, NGAL), inflammatory (sTNFR1, sTNFR2), and hemodynamic (NT-proBNP, EPO) markers were assessed post-hoc in two separate T1D cohorts. The glycemic clamp trial (NCT02344602) evaluated 49 adults with T1D and 27 controls under euglycemic and acute hyperglycemic conditions. The crossover BETWEEN trial (NCT02632747) investigated empagliflozin 25 mg plus ramipril for 4 weeks compared to placebo-ramipril for 4 weeks in 30 adults with T1D.
RESULTS: In the glycemic clamp study, hyperglycemia acutely increased levels of NT-proBNP (p = 0.0003) and sTNFR2 (p = 0.003). BETWEEN participants treated with empagliflozin exhibited a paradoxical subacute rise in NT-proBNP (p = 0.0147) compared to placebo, independent of hematocrit. Individuals with higher baseline levels of sST2 and sTNFR1 had greater empagliflozin-associated reductions in systolic blood pressure and greater activation of renin-angiotensin-aldosterone system (RAAS) mediators, whereas those with higher baseline levels of KIM-1 and sTNFR1 had greater glomerular filtration rate (GFR) dip.
CONCLUSIONS: The protective mechanisms of SGLT2 inhibition on blood pressure, RAAS activation, and renal hemodynamics are apparent in the subset of people with uncomplicated T1D with adverse cardiorenal and inflammatory markers.

OBJECTIVE: In-hospital dysglycemia is associated with adverse outcomes. Identifying patients at risk of in-hospital dysglycemia early on admission may improve patient outcomes.
METHODS: We analysed 117 inpatients admitted with pneumonia and type 2 diabetes monitored by continuous glucose monitoring. We assessed potential risk factors for in-hospital dysglycemia and adverse clinical outcomes.
RESULTS: Time in range (3.9-10.0 mmol/l) decreased by 2.9 %-points [95 % CI 0.7-5.0] per 5 mmol/mol [2.6 %] increase in admission haemoglobin A1c, 16.2 %-points if admission diabetes therapy included insulin therapy [95 % CI 2.9-29.5], and 2.4 %-points [95 % CI 0.3-4.6] per increase in the Charlson Comorbidity Index (CCI) (integer, as a measure of severity and amount of comorbidities). Thirty-day readmission rate increased with an IRR of 1.24 [95 % CI 1.06-1.45] per increase in CCI. In-hospital mortality risk increased with an OR of 1.41 [95 % CI 1.07-1.87] per increase in Early Warning Score (EWS) (integer, as a measure of acute illness) at admission.
CONCLUSIONS: Dysglycemia among hospitalised patients with pneumonia and type 2 diabetes was associated with high haemoglobin A1c, insulin treatment before admission, and the amount and severity of comorbidities (i.e., CCI). Thirty-day readmission rate increased with high CCI. The risk of in-hospital mortality increased with the degree of acute illness (i.e., high EWS) at admission. Clinical outcomes were independent of chronic glycemic status, i.e. HbA1c, and in-hospital glycemic status.

OBJECTIVE: This review explores the emerging evidence regarding pathogenesis, future trajectories, treatment options, and phenotypes of youth-onset type 2 diabetes (T2D).
RESULTS: Youth-onset T2D is increasing in incidence and prevalence worldwide, disproportionately affecting First Nations communities, socioeconomically disadvantaged youth, and people of colour. Youth-onset T2D differs in pathogenesis to later-onset T2D and progresses more rapidly. It is associated with more complications, and these occur earlier. While there are limited licensed treatment options available, the available medications also appear to have a poorer response in youth with T2D. Multiple interacting factors likely contribute to this rising prevalence, as well as the increased severity of the condition, including structural inequities, increasing obesity and sedentary lifestyles, and intergenerational transmission from in-utero exposure to maternal hyperglycemia and obesity. Youth-onset T2D is also associated with stigma and poorer mental health, and these impact clinical management. There is an urgent need to develop effective interventions to prevent youth-onset T2D and enhance engagement of affected youth. It is also critical to better understand the differing phenotypes of youth-onset T2D, to effectively target treatments, and to address intergenerational transmission in high-risk populations.

BACKGROUND: The comorbidities of ischemic heart disease (IHD) and diabetes mellitus (DM) compromise the protection of the diabetic heart from ischemia/reperfusion (I/R) injury. We hypothesized that manipulation of reperfusion injury salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways might protect the diabetic heart, and intervention of these pathways could be a new avenue for potentially protecting the diabetic heart.
METHODS: All hearts were subjected to 30-min ischemia and 30-min reperfusion. During reperfusion, hearts were exposed to molecules proven to protect the heart from I/R injury. The hemodynamic data were collected using suitable software. The infarct size, troponin T levels, and protein levels in hearts were evaluated.
RESULTS: Both cyclosporine-A and nitric oxide donor (SNAP) infusion at reperfusion protected 4-week diabetic hearts from I/R injury. However, 6-week diabetic hearts were protected only by SNAP, but not cyclosporin-A. These treatments significantly (p < 0.05) improved cardiac hemodynamics and decreased infarct size.
CONCLUSIONS: The administration of SNAP to diabetic hearts protected both 4- and 6-week diabetic hearts; however, cyclosporine-A protected only the 4-week diabetic hearts. The eNOS/GLUT-4 pathway executed the SNAP-mediated cardioprotection.

BACKGROUND: Postoperative hyperglycemia is associated with morbidity and mortality in non-diabetic surgical patients. However, there is limited information on the extent and factors associated with postoperative hyperglycemia. This study assessed the magnitude and associated factors of postoperative hyperglycemia among non-diabetic adult patients who underwent elective surgery at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.
METHODS: A facility-based cross-sectional study was conducted among 412 adult patients who underwent elective surgery at University of Gondar Comprehensive Specialized Hospital from April 14 to June 30, 2022 All consecutive postoperative non-diabetic elective surgical patients who were admitted to PACU during the data collection period and who fulfilled inclusion criteria were included in the study until the intended minimum sample size was achieved. And data were collected through interviews using a pretested semi-structured questionnaire. Postoperative hyperglycemia was defined as a blood glucose level of ≥ 140 mg/dl. Multivariable logistic regression was performed to identify the association between postoperative hyperglycemia and independent variables. Variables with a p-value less than 0.05 and a 95% confidence interval (CI) were considered statistically significant.
RESULTS: A total of 405 patients\' data were evaluated with a response rate of 98.3%. The median (IQR) age was 40 (28-52) years. The prevalence of postoperative hyperglycemia was 34.1% (95% CI: 29.4-39.0). Factors significantly associated with postoperative hyperglycemia included being overweight (AOR = 5.45, 95% CI: 2.46-12.0), American Society of Anesthesiologists (ASA) classification II and III (AOR = 2.37, 95% CI: 1.17-4.79), postoperative low body temperature (AOR = 0.18, 95% CI: 0.069-0.48), blood loss ≥ 500 ml (AOR = 2.33, 95% CI: 1.27-4.27), long duration of surgery, mild pain (AOR = 5.17, 95% CI: 1.32-20.4), and moderate pain (AOR = 7.63, 95% CI: 1.811-32.20).
CONCLUSIONS: One-third of the study participants had postoperative hyperglycemia. Weight, ASA classification, postoperative body temperature, duration of surgery, intraoperative blood loss, and postoperative pain were identified as a modifiable risk factors. Maintaining normal body temperature throughout the procedure, treating postoperative pain, and monitoring and controlling blood glucose level in patients at risk of hyperglycemia is crucial.

UNASSIGNED: Acute Type A Aortic Dissection (AAAD) is one of the most life-threatening diseases, often associated with transient hyperglycemia induced by acute physiological stress. The impact of stress-induced hyperglycemia on the prognosis of ST-segment elevation myocardial infarction has been reported. However, the relationship between stress-induced hyperglycemia and the prognosis of AAAD patients remains uncertain.
UNASSIGNED: The clinical data of 456 patients with acute type A aortic dissection were retrospectively reviewed. Patients were divided into two groups based on their admission blood glucose. Cox model regression analysis was performed to assess the relationship between stress-induced hyperglycemia and the 30-day and 1-year mortality rates of these patients.
UNASSIGNED: Among the 456 patients, 149 cases (32.7%) had AAAD combined with stress-induced hyperglycemia (SIH). The results of the multifactor regression analysis of the Cox model indicated that hyperglycemia (RR = 1.505, 95% CI: 1.046-2.165, p = 0.028), aortic coarctation involving renal arteries (RR = 3.330, 95% CI: 2.237-4.957, p < 0.001), aortic coarctation involving superior mesenteric arteries (RR = 1.611, 95% CI: 1.056-2.455, p = 0.027), and aortic coarctation involving iliac arteries (RR = 2.034, 95% CI: 1.364-3.035, p = 0.001) were independent influences on 1-year postoperative mortality in AAAD patients.
UNASSIGNED: The current findings indicate that stress-induced hyperglycemia measured on admission is strongly associated with 1-year mortality in patients with AAAD. Furthermore, stress-induced hyperglycemia may be related to the severity of the condition in patients with AAAD.

BACKGROUND: One of the confounding factors in pancreatic cancer (PC) pathogenesis is hyperglycemia. The molecular mechanism by which high glucose (HG) influences PC severity is poorly understood. Our investigation delved into the impact of lncRNA highly upregulated in liver cancer (HULC) and its interaction with yes-associated protein (YAP) in regulating the fate of pancreatic ductal adenocarcinoma cells (PDAC) under HG-induced conditions. PDAC cells were cultured under normal or HG conditions. We thereafter measured the effect of HG on the viability of PDAC cells, their migration potential and drug resistance properties. The lncRNAs putatively dysregulated in PC and diabetes were shortlisted by bioinformatics analysis followed by wet lab validation of function.
RESULTS: HG led to enhanced proliferation and drug refractoriness in PDAC cells. HULC was identified as one of the major deregulated lncRNAs following bioinformatics analysis. HULC was found to regulate the expression of the potent transcriptional regulator - YAP through selective histone modifications at the YAP promoter. siRNA-mediated ablation of HULC resulted in a concurrent decrease in YAP transcriptional activity. Importantly, HULC and YAP were found to co-operatively regulate the cellular homeostatic process autophagy, thus inculcating drug resistance and proliferative potential in PDAC cells. Moreover, inhibition of autophagy or YAP led to a decrease in HULC levels, suggesting the existence of an inter-regulatory feedback loop.
CONCLUSIONS: We observed that HG triggers aggressive properties in PDAC cells. Mechanistically, up-regulation of lncRNA HULC resulted in activation of YAP and differential regulation of autophagy coupled to increased proliferation of PDAC cells.
CONCLUSIONS: Inhibition of HULC and YAP may represent a novel therapeutic strategy for PDAC. Furthermore, this study portrays the intricate molecular interplay between HULC, YAP and autophagy in PDAC pathogenesis.

Alpha-ketoglutarate (α-KG), an endogenous intermediate of the tricarboxylic acid cycle, is involved in a variety of cellular metabolic pathways. It serves as an energy donor, a precursor of amino acid biosynthesis, and an epigenetic regulator. α-KG plays physiological functions in immune regulation, oxidative stress, and anti-aging as well. In recent years, it has been reported that the level of α-KG in the body is closely associated with metabolic syndrome, including obesity, hyperglycemia, and other pathological factors. Exogenous supplementation of α-KG improves obesity, blood glucose levels, and cardiovascular disease risks associated with metabolic syndrome. Furthermore, α-KG regulates the common pathological mechanisms of metabolic syndrome, suggesting the potential application prospect of α-KG in metabolic syndrome. In order to provide a theoretical basis for further exploration of the application of α-KG in metabolic syndrome, we focused on α-KG and metabolic syndrome in this article and summarized the latest research progress in the role of α-KG in improving the pathological condition and disease progression of metabolic syndrome. For the next step, researchers may focus on the co-pathogenesis of metabolic syndrome and investigate whether α-KG can be used to achieve the therapeutic goal of \"homotherapy for heteropathy\" in the treatment of metabolic syndrome.