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Maturity-onset diabetes of young ‘MODY’ type 6 is a rare form of monogenic diabetes caused by mutations in neuronal differentiation 1 (NEUROD1). Clinical features vary in a large spectrum in terms of age and body mass index (BMI) at diagnosis. Here, we reported the youngest patient with a NEUROD1 variant to the best of our knowledge. A 2.1-year-old girl was referred to pediatric endocrinology clinic for elevated fasting BG (104 mg/dL) which was detected at another center where she had been evaluated for loss of appetite. Her maternal aunt and uncle had been diagnosed with type 2 diabetes mellitus (DM) at the age of 40 and 45 years; they were obese (BMI: 30.2 and 30.6 kg/m2). At the age of 3.7 years old, she was hospitalized for buccal cellulitis and plasma glucose concentration was 239 mg/dL at admission. Targeted next-generation sequencing (NGS) was performed considering the stress induced hyperglycemia without serious illness, negative islet cell antibodies and insulin autoantibodies, age at the presentation, and family history of DM. NGS analysis revealed a previously reported heterozygous missense variant in NEUROD1. Segregation studies showed that the identified variant was inherited from her 44-year-old mother with a BMI of 27.2 kg/m2 and a normal oral glucose tolerance test. Heterozygous NEUROD1 mutations cause low-penetrant diabetes that is heterogeneous in terms of clinical features as some patients fulfill the classic MODY definition and others are mimicking type 2 DM. Clinical manifestations and family history should be carefully evaluated in patients with stress induced hyperglycemia to identify candidate cases for molecular testing, and proper follow-up should be initiated in affected individuals.

Maturity-onset diabetes of young ‘MODY’ type 6 is a rare form of monogenic diabetes caused by mutations in neuronal differentiation 1 (NEUROD1). Clinical features vary in a large spectrum in terms of age and body mass index (BMI) at diagnosis. Here, we reported the youngest patient with a NEUROD1 variant to the best of our knowledge. A 2.1-year-old girl was referred to pediatric endocrinology clinic for elevated fasting BG (104 mg/dL) which was detected at another center where she had been evaluated for loss of appetite. Her maternal aunt and uncle had been diagnosed with type 2 diabetes mellitus (DM) at the age of 40 and 45 years; they were obese (BMI: 30.2 and 30.6 kg/m² ). At the age of 3.7 years old, she was hospitalized for buccal cellulitis and plasma glucose concentration was 239 mg/dL at admission. Targeted next-generation sequencing (NGS) was performed considering the stress induced hyperglycemia without serious illness, negative islet cell antibodies and insulin autoantibodies, age at the presentation, and family history of DM. NGS analysis revealed a previously reported heterozygous missense variant in NEUROD1. Segregation studies showed that the identified variant was inherited from her 44-year-old mother with a BMI of 27.2 kg/m² and a normal oral glucose tolerance test. Heterozygous NEUROD1 mutations cause low-penetrant diabetes that is heterogeneous in terms of clinical features as some patients fulfill the classic MODY definition and others are mimicking type 2 DM. Clinical manifestations and family history should be carefully evaluated in patients with stress induced hyperglycemia to identify candidate cases for molecular testing, and proper follow-up should be initiated in affected individuals. [ABSTRACT FROM AUTHOR]

Abstract Background Stress induced hyperglycemia (SIH) is common among patients with ST-elevation myocardial infarction (STEMI), even in patients without diabetes mellitus. However, evidence regarding its role on the angiographic outcomes and the prognosis of patients presenting with STEMI is scarce. Methods This study included 309 consecutively enrolled STEMI patients undergoing primary percutaneous coronary intervention (pPCI). Patients were diagnosed with SIH if blood glucose on admission was > 140 mg/dl. Also, patients had to fast for at least 8 hours before blood sampling. The objective was to assess whether SIH was associated with major adverse cardiovascular and cerebrovascular (MACCE) events and explore its relationship with angiographic predictors of worse prognosis such as poor initial TIMI flow, intracoronary thrombus burden, distal embolization, and presence of residual thrombus after pPCI. Results SIH in diabetic and non-diabetic patients was associated with a higher incidence of LTB (aOR = 2.171, 95% CI 1.27–3.71), distal embolization (aOR = 2.71, 95% CI 1.51–4.86), and pre-procedural TIMI flow grade = 0 (aOR = 2.69, 95% CI 1.43–5.04) after adjusting for relevant clinical variables. Importantly, during a median follow-up of 1.7 years STEMI patients with SIH with or without diabetes experienced increased occurrence of MACCE both in univariate (HR = 1.92, 95% CI 1.19–3.01) and multivariate analysis (aHR = 1.802, 95% CI 1.01–3.21). Conclusions SIH in STEMI patients with or without diabetes was independently associated with increased MACCE. This could be attributed to the fact that SIH was strongly correlated with poor pre-procedural TIMI flow, LTB, and distal embolization. Large clinical trials need to validate SIH as an independent predictor of adverse angiographic and clinical outcomes to provide optimal individualized care for patients with STEMI.

Background: Hyperglycemia is a common finding which is associated with increased mortality and morbidity among critically ill patients. There is currently no evidence that melatonin could improve stress induced hyperglycemia (SIH). In this study, we evaluated the effect of melatonin on blood sugar and insulin resistance (IR) in critically-ill patients. Methods: 104 critically-ill patients with SIH divided into two groups, receiving melatonin (6 mg BD for 3 days) or placebo. Changes of blood sugar, IR indices including homeostasis model assessment for insulin resistance and homeostasis model assessment adiponectin (HOMA-AD) ratios, Glasgow coma scale (GCS) were evaluated on the 4th day of melatonin prescription. On the 7Th day of study, changes of ventilator dependency and delirium were considered. Mortality and intensive care unit (ICU) stay were also compared between groups. Results: On day 4, patients in the melatonin group had significantly lower blood glucose and HMOA-IR level compared with the placebo group (P=0.04 and P=0.03, respectively) whereas HOMA-AD level did not differ significantly from placebo group (p>0.2). Also, we did not observe any significant difference in GCS level at this time between groups (p>0.2). On day 7, melatonin could not improve ventilator dependency and delirium significantly (p>0.2) and also could not reduce mortality and ICU stay in comparison with placebo (p>0.2, P=0.2, respectively). Conclusion: Melatonin supplementation showed positive effect on blood sugar and somehow insulin resistance whereas it could not improve ICU complications.

Background: Stress induced hyperglycemia (SIH) is common among patients with ST-elevation myocardial infarction (STEMI), even in patients without diabetes mellitus. However, evidence regarding its role on the angiographic outcomes and the prognosis of patients presenting with STEMI is scarce. Methods: This study included 309 consecutively enrolled STEMI patients undergoing primary percutaneous coronary intervention (pPCI). Patients were diagnosed with SIH if blood glucose on admission was > 140 mg/dl. Also, patients had to fast for at least 8 hours before blood sampling. The objective was to assess whether SIH was associated with major adverse cardiovascular and cerebrovascular (MACCE) events and explore its relationship with angiographic predictors of worse prognosis such as poor initial TIMI flow, intracoronary thrombus burden, distal embolization, and presence of residual thrombus after pPCI. Results: SIH in diabetic and non-diabetic patients was associated with a higher incidence of LTB (aOR = 2.171, 95% CI 1.27–3.71), distal embolization (aOR = 2.71, 95% CI 1.51–4.86), and pre-procedural TIMI flow grade = 0 (aOR = 2.69, 95% CI 1.43–5.04) after adjusting for relevant clinical variables. Importantly, during a median follow-up of 1.7 years STEMI patients with SIH with or without diabetes experienced increased occurrence of MACCE both in univariate (HR = 1.92, 95% CI 1.19–3.01) and multivariate analysis (aHR = 1.802, 95% CI 1.01–3.21). Conclusions: SIH in STEMI patients with or without diabetes was independently associated with increased MACCE. This could be attributed to the fact that SIH was strongly correlated with poor pre-procedural TIMI flow, LTB, and distal embolization. Large clinical trials need to validate SIH as an independent predictor of adverse angiographic and clinical outcomes to provide optimal individualized care for patients with STEMI. [ABSTRACT FROM AUTHOR]

Backgrounds: Emerging evidence suggests that stress hyperglycemia ratio (SHR), an index of relative stress hyperglycemia, is of great prognostic value in acute myocardial infarction (AMI), but current evidence is limited in elderly patients. In this study, we aimed to assess whether SHR is associated with in-hospital outcomes in elderly patients with AMI.Methods: In this retrospective study, patients who were aged over 75 years and diagnosed with AMI were consecutively enrolled from 2015, January 1st to 2019, December 31th. Admission blood glucose and glycosylated hemoglobin (HbA1C) during the index hospitalization were used to calculate SHR. Restricted quadratic splines, receiver-operating curves, and logistic regression were performed to evaluate the association between SHR and in-hospital outcomes, including in-hospital all-cause death and in-hospital major adverse cardiac and cerebrovascular events (MACCEs) defined as a composite of all-cause death, cardiogenic shock, reinfarction, mechanical complications of MI, stroke, and major bleeding.Results: A total of 341 subjects were included in this study. Higher SHR levels were observed in patients who had MACCEs (n = 69) or death (n = 44) during hospitalization. Compared with a SHR value below 1.25, a high SHR was independently associated with in-hospital MACCEs (odds ratio [OR]: 2.945, 95% confidence interval [CI]: 1.626–5.334, P < 0.001) and all-cause death (OR: 2.871 95% CI: 1.428–5.772, P = 0.003) in univariate and multivariate logisitic analysis. This relationship increased with SHR levels based on a non-linear dose-response curve. In contrast, admission glucose was only associated with clinical outcomes in univariate analysis. In subgroup analysis, high SHR was significantly predictive of worse in-hospital clinical outcomes in non-diabetic patients (MACCEs: 2.716 [1.281–5.762], P = 0.009; all-cause death: 2.394 [1.040–5.507], P = 0.040), but the association was not significant in diabetic patients.Conclusion: SHR might serve as a simple and independent indicator of adverse in-hospital outcomes in elderly patients with AMI, especially in non-diabetic population.

Elevation of glucose level in response to acute coronary syndrome (ACS) has been recognized as stress induced hyperglycemia (SIH). Plenty of clinical studies have documented that SIH occurs very common in patients hospitalized with ACS, even in those without previously known diabetes mellitus. The association between elevated blood glucose levels with adverse outcome in the ACS setting is well-established. Yet, the precise definition of SIH in the context of ACS remains controversial, bringing confusions about clinical management strategy. Several randomized trials aimed to evaluate the effect of insulin-based therapy on outcomes of ACS patients failed to demonstrate a consistent benefit of intensive glucose control. Mechanisms underlying detrimental effects of SIH on patients with ACS are undetermined, oxidative stress might play an important role in the upstream pathways leading to subsequent harmful effects on cardiovascular system. This review aims to discuss various definitions of SIH and their values in predicting adverse outcome in the context of ACS, as well as the effect of intensive glucose control on clinical outcome. Finally, a glimpse of the underlying mechanisms is briefly discussed.

Background and Aim: Although large studies have demonstrated the association between hyperglycemia and adverse intensive care unit (ICU) outcomes, it is yet unclear which subset of patients benefi t from tight sugar control in ICU. Recent evidence suggests that stress induced hyperglycemia (SIH) and co-incidentally detected diabetes mellitus are different phenomena with different prognoses. Differentiating SIH from diabetic hyperglycemia is challenging in ICU settings. We followed a cohort of trauma patients admitted to a surgical intensive care unit (SICU) to evaluate if initial glycated hemoglobin A (HbA1c) level predicts the outcome of admission. Materials and Methods: A cohort of 120 consecutive admissions to SICU following trauma were recruited and admission blood sugar and HbA1c were measured. Outcomes were prospectively measured by blinded ICU doctors. A logistic regression model was developed to assess if HbA1c predicts poor outcomes in these settings. Results: Nearly 24% of the participants had HbA1c ≥ 6. Those with HbA1c ≥ 6 had 3.14 times greater risk of poor outcome at the end of hospital stay when compared to those with HbA1c < 6 and this risk increased to an odds ratio of 4.57 on adjusting for other significant predictors: Acute Physiology and Chronic Health Evaluation II, injury severity score, admission blood sugar and age at admission. Conclusions: Substantial proportion of trauma admissions has underlying diabetes. HbA1c, a measure of pre admission glycaemic status is an important predictor of ICU outcome in trauma patients. [ABSTRACT FROM AUTHOR]

Backgrounds: Emerging evidence suggests that stress hyperglycemia ratio (SHR), an index of relative stress hyperglycemia, is of great prognostic value in acute myocardial infarction (AMI), but current evidence is limited in elderly patients. In this study, we aimed to assess whether SHR is associated with in-hospital outcomes in elderly patients with AMI. Methods: In this retrospective study, patients who were aged over 75 years and diagnosed with AMI were consecutively enrolled from 2015, January 1st to 2019, December 31th. Admission blood glucose and glycosylated hemoglobin (HbA1C) during the index hospitalization were used to calculate SHR. Restricted quadratic splines, receiver-operating curves, and logistic regression were performed to evaluate the association between SHR and in-hospital outcomes, including in-hospital all-cause death and in-hospital major adverse cardiac and cerebrovascular events (MACCEs) defined as a composite of all-cause death, cardiogenic shock, reinfarction, mechanical complications of MI, stroke, and major bleeding. Results: A total of 341 subjects were included in this study. Higher SHR levels were observed in patients who had MACCEs ( n = 69) or death ( n = 44) during hospitalization. Compared with a SHR value below 1.25, a high SHR was independently associated with in-hospital MACCEs (odds ratio [OR]: 2.945, 95% confidence interval [CI]: 1.626-5.334, P < 0.001) and all-cause death (OR: 2.871 95% CI: 1.428-5.772, P = 0.003) in univariate and multivariate logisitic analysis. This relationship increased with SHR levels based on a non-linear dose-response curve. In contrast, admission glucose was only associated with clinical outcomes in univariate analysis. In subgroup analysis, high SHR was significantly predictive of worse in-hospital clinical outcomes in non-diabetic patients (MACCEs: 2.716 [1.281-5.762], P = 0.009; all-cause death: 2.394 [1.040-5.507], P = 0.040), but the association was not significant in diabetic patients. Conclusion: SHR might serve as a simple and independent indicator of adverse in-hospital outcomes in elderly patients with AMI, especially in non-diabetic population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Li, Wen, Wang, Zhou, Xue and He.)

Elevation of glucose level in response to acute coronary syndrome (ACS) has been recognized as stress induced hyperglycemia (SIH). Plenty of clinical studies have documented that SIH occurs very common in patients hospitalized with ACS, even in those without previously known diabetes mellitus. The association between elevated blood glucose levels with adverse outcome in the ACS setting is well-established. Yet, the precise definition of SIH in the context of ACS remains controversial, bringing confusions about clinical management strategy. Several randomized trials aimed to evaluate the effect of insulin-based therapy on outcomes of ACS patients failed to demonstrate a consistent benefit of intensive glucose control. Mechanisms underlying detrimental effects of SIH on patients with ACS are undetermined, oxidative stress might play an important role in the upstream pathways leading to subsequent harmful effects on cardiovascular system. This review aims to discuss various definitions of SIH and their values in predicting adverse outcome in the context of ACS, as well as the effect of intensive glucose control on clinical outcome. Finally, a glimpse of the underlying mechanisms is briefly discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Chen, Feng and He.)