Etiology Of Hyperglycemia Research Articles

The Long Noncoding RNA Paupar Modulates PAX6 Regulatory Activities to Promote Alpha Cell Development and Function

Many studies have highlighted the role of dysregulated glucagon secretion in the etiology of hyperglycemia and diabetes. Accordingly, understanding the mechanisms underlying pancreatic islet α cell development and function has important implications for the discovery of new therapies for diabetes. In this study, comparative transcriptome analyses between embryonic mouse pancreas and adult mouse islets identified several pancreatic lncRNAs that lie in close proximity to essential pancreatic transcription factors, including the Pax6-associated lncRNA Paupar. We demonstrate that Paupar is enriched in glucagon-producing α cells where it promotes the alternative splicing of Pax6 to an isoform required for activation of essential α cell genes. Consistently, deletion of Paupar in mice resulted in dysregulation of PAX6 α cell target genes and corresponding α cell dysfunction, including blunted glucagon secretion. These findings illustrate a distinct mechanism by which a pancreatic lncRNA can coordinate glucose homeostasis by cell-specific regulation of a broadly expressed transcription factor.

Etiology of hyperglycemia in critically ill children and the impact of organ dysfunction.

Objective:This study aimed to study the incidence of stress hyperglycemia in critically ill children and to investigate the etiological basis of the hyperglycemia based on homeostasis model assessment.Methods:This was a prospective cohort study in one of the pediatric intensive care units of Cairo University, including 60 critically ill children and 21 healthy controls. Serum blood glucose, insulin, and C-peptide levels were measured within 24 hours of admission. Homeostasis model assessment was used to assess β-cell function and insulin sensitivity.Results:Hyperglycemia was estimated in 70% of patients. Blood glucose values ≥ 180mg/dL were associated with a poor outcome. Blood glucose levels were positively correlated with Pediatric Risk for Mortality (PRISM III) score and number of organ dysfunctions (p = 0.019 and p = 0.022, respectively), while insulin levels were negatively correlated with number of organ dysfunctions (r = -0.33, p = 0.01). Homeostasis model assessment revealed that 26 (43.3%) of the critically ill patients had low β-cell function, and 18 (30%) had low insulin sensitivity. Combined pathology was detected in 2 (3.3%) patients only. Low β-cell function was significantly associated with the presence of multi-organ dysfunction; respiratory, cardiovascular, and hematological dysfunctions; and the presence of sepsis.Conclusions:β-Cell dysfunction appeared to be prevalent in our cohort and was associated with multi-organ dysfunction.

Association of non‐diabetic hyperglycemia with autonomic shift in acute ischaemic stroke

The etiology of hyperglycemia in acute stroke remains controversial. It is unclear whether hyperglycemia arises as an epiphenomenon of stroke or as a reflection of underlying diabetes. Autonomic shift to sympathetic overactivity has been repeatedly observed in acute stroke. We hypothesize that hyperglycemia in acute stroke relates to autonomic imbalance and that the respective deleterious effects on stroke outcome may be cross-linked. A total of 75 non-diabetic patients with ischaemic stroke were included in a prospective study. Glucose levels at admission, fasting glucose, and glucose profiles were recorded. Autonomic function was quantified by the assessment of spontaneous baroreflex sensitivity (BRS) using a cross-correlation method. Demographic and clinical data including stroke volumes and admission National Institute of Heath Stroke Scale scores were included into the analysis. Functional outcome at 90 days was assessed using the modified Rankin Scale. Hyperglycemia was correlated with decreased BRS independent of stroke severity or volume (r = -0.46, P < 0.001). In two separate regression models, glucose levels and BRS independently predicted unfavorable outcome at 3 months (OR = 1.06, CI = 1.02-1.11, P = 0.004 and OR = 0.75, CI = 0.56-0.99, P = 0.04). However, combining the models, only glucose levels (OR = 1.06, CI = 1.02-1.11, P = 0.004) remained independent predictor of outcome at 3 months. We observed an association between hyperglycemia and decreased BRS in non-diabetic patients, suggesting that hyperglycemic reaction in acute stroke may reflect stroke-related autonomic changes. Moreover, outcome effects of autonomic changes and hyperglycemia seem to be interdependent, putatively having the sympatho-vagal imbalance as common underlying mechanism. The possible therapeutic relevance of this finding warrants further studies.

A woman with severe lupus nephritis and difficult to control diabetes mellitus

A woman with severe lupus nephritis and difficult to control diabetes mellitus

A.S.P.E.N. Clinical Guidelines: Nutrition Support of the Critically Ill Child

careful selection of the appropriate mode of feeding and monitoring the success of the feeding strategy. The use of specific nutrients, which possess a drug-like effect on the immune or inflammatory state during critical illness, continues to be an exciting area of investigation. The lack of systematic research and clinical trials on various aspects of nutrition support in the PICU is striking and makes it challenging to compile evidence based practice guidelines. There is an urgent need to conduct well-designed, multicenter trials in this area of clinical practice. The extrapolation of data from adult critical care literature is not desirable and many of the interventions proposed in adults will have to undergo systematic examination and careful study in critically ill children prior to their application in this population. In the following sections, we will discuss some of the key aspects of nutrition support therapy in the PICU; examine the literature and provide best practice guidelines based on evidence from PICU patients, where available. While some PICU popu lations include neonates, A.S.P.E.N. Clinical Guidelines for neonates will be published as a separate series.

Hyperglycemia in stressed small premature neonates

The metabolic responses to a constant glucose infusion were measured in 30 premature infants, 700 to 1,550 gm. The study included 18 stressed premature infants who needed assisted ventilation, and 12 control premature infants. Metabolic measurements were similar in both groups in the cord and preinfusion samples. In the first postinfusion sample, glucose, cortisol, and glycerol values were higher in stressed than in control premature infants. Hyperglycemia was seen in 13 of stressed and in only one of control premature infants. Stressed infants who became hyperglycemic in the first postinfusion sample were then compared to stressed euglycemic infants. Insulin levels were higher, glycerol levels similar, but cortisol levels lower in stressed hyperglycemic than in stressed euglycemic premature infants. The etiology of hyperglycemia in stressed premature infants cannot be attributed to hypoinsulinemia or to hypercortisolemia, and is not associated with increased glycerol levels. There was no difference in mortality between stressed hyperglycemia and stressed euglycemic infants; stress, rather than hyperglycemia, was related to mortality.