Clinical profile and risk factors of symptomatic and asymptomatic hypoglycemia in neonates admitted to NICU in a tertiary care center: A cross-sectional study

Objective:To investigate the clinical profile and risk factors of symptomatic and asymptomatic hypoglycemia in neonates admitted to a neonatal intensive care unit in a tertiary care center.Methods:The prospective observational study was conducted in a tertiary care center in the Specialty Department of Pediatric.196 Newborn babies with blood glucose levels<45 mg/dL were examined with a simple random sampling method between December 2019 and November 2021.Maternal and neonatal risk factors and clinical signs were recorded and compared between symptomatic and asymptomatic cases.Results:The proportion of symptomatic hypoglycemia neonates born to gestational diabetes mellitus mothers was significantly higher(23.4%vs.8.4%)(P<0.05).Small for gestational age,low birth weight,respiratory distress syndrome,hypothermia,and endocrine disorders were risk factors.The death rate in asymptomatic hypoglycemia neonates was significantly higher(58%vs.39%)(P<0.05).Conclusions:The study indicates that maternal gestational diabetes mellitus is associated with symptomatic hypoglycemia and asymptomatic hypoglycemia is associated with neonatal mortality.It is important to take vigilance and timely interventions to address associated symptoms,particularly poor feeding,in the management of neonatal hypoglycemia.

Efficacy of Raw Corn Starch in Insulinoma-Related Hypoglycemia:A Promising Supportive Therapy

Objective To investigate the efficacy of raw corn starch(RCS)in clinical management of insulinoma-induced hypoglycemia.Methods We retrospectively collected clinical data of insulinoma patients who received RCS-supplemented diet preoperatively,and analyzed the therapeutic effects of the RCS intervention on blood glucose control,weight change,and its adverse events.Results The study population consisted of 24 cases of insulinoma patients,7 males and 17 females,aged 46.08±14.15 years.Before RCS-supplemented diet,all patients had frequent hypoglycemic episodes(2.51±3.88 times/week),concurrent with neuroglycopenia(in 83.3% of patients)and autonomic manifestations(in 75.0% of patients),with the median fasting blood glucose(FBG)of 2.70(interquartile range[IQR]:2.50-2.90)mmol/L.The patients'weight increased by 0.38(IQR:0.05-0.65)kg per month,with 8(33.3%)cases developing overweight and 7(29.2%)cases developing obesity.All patients maintained the RCS-supplemented diet until they underwent tumor resection(23 cases)and transarterial chemoembolization for liver metastases(1 case).For 19 patients receiving RCS throughout the day,the median FBG within one week of nutritional management was 4.30(IQR:3.30-5.70)mmol/L,which was a significant increase compared to pre-nutritional level[2.25(IQR:1.60-2.90)mmol/L;P<0.001].Of them,10 patients receiving RCS throughout the day for over four weeks had sustained improvement in FBG compared to pre-treatment[3.20(IQR:2.60-3.95)mmol/L vs.2.15(IQR:1.83-2.33)mmol/L;P<0.001].Five patients who received RCS only at night also had a significant increase in FBG within one week of nutritional management[3.50(IQR:2.50-3.65)mmol/L vs.2.20(IQR:1.80-2.60)mmol/L;P<0.001],but only one patient who continued to receive RCS for over four weeks did not have a significant improvement in FBG.No improvement in weight gain was observed upon RCS supplementation.Mild diarrhea(2 cases)and flatulence(1 case)occurred,and were relieved by reduction of RCS dose.Conclusion The RCS-supplemented diet is effective in controlling insulinoma-induced hypoglycemia.

Successful management of severe hypoglycemia induced by total parenteral nutrition in patients with hepatocellular injury: Three cases reports

BACKGROUND Glucose imbalance is common in total parenteral nutrition(TPN).Hypoglycemia seems to be less frequent than hyperglycemia,but it influences the clinical outcome to a greater extent.Therefore,it should be effectively prevented and treated.However,there is no relevant report on how to treat hypoglycemia caused by TPN in patients with liver cell injury.CASE SUMMARY We present three patients with liver cell injury who developed severe hypo-glycemia during or after TPN infusion.The causes of severe hypoglycemia and glucose-raising strategies were discussed.According to the physiological charac-teristics of the hepatocellular injury,the ratio of nutrition components prescribed in TPN was appropriately adjusted for the three cases.We simultaneously reduced the dose of insulin and fat emulsion,and increased the dose of glucose in TPN.The blood glucose level was restored to normal range and clinical symptoms were eliminated.CONCLUSION When hypoglycemia occurs during or after TPN in patients with hepatocellular injury,physicians need to simultaneously reduce insulin and fat emulsion,and increase glucose,and correct severe hypoglycemia in time to reduce its adverse consequences.

Glucagon-like peptide-1 agonists:Role of the gut in hypoglycemia unawareness,and the rationale in type 1 diabetes

Type 1 diabetes is increasing and the majority of patients have poor glycemic control.Although advanced technology and nanoparticle use have greatly enhanced insulin delivery and glucose monitoring,weight gain and hypoglycemia remain major challenges and a constant source of concern for patients with type 1 diabetes.Type 1 diabetes shares some pathophysiology with type 2 diabetes,and an overlap has been reported.The above observation created great interest in glucagon-like peptide-1 receptor agonists(GLP-1)as adjuvants for type 1 diabetes.Previous trials confirmed the positive influence of GLP-1 agonists onβcell function.However,hypoglycemia unawareness and dysregulated glucagon response have been previously reported in patients with recurrent hypoglycemia using GLP-1 agonists.Jin et al found that the source of glucagon dysregulation due to GLP-1 agonists resides in the gut.Plausible explanations could be gut nervous system dysregulation or gut microbiota disruption.This review evaluates the potential of GLP-1 agonists in managing type 1 diabetes,particularly focusing on their impact on glycemic control,weight management,and glucagon dysregulation.We provide a broader insight into the problem of type 1 diabetes mellitus management in the light of recent findings and provide future research directions.

Role of intestinal glucagon-like peptide-1 in hypoglycemia response impairment in type 1 diabetes

This study critically examines the novel findings presented by Jin et al,which explores the role of intestinal glucagon-like peptide-1(GLP-1)in impaired counterregulatory responses to hypoglycemia in mice with type 1 diabetes.The study identifies intestinal GLP-1 as a significant determinant in the physiological responses to hypoglycemia,offering new insights into its potential implications for diabetes management.The editorial synthesizes these findings,discusses their relevance in the context of current diabetes research,and outlines potential avenues for future investigation of intestinal GLP-1 as a therapeutic target.This analysis underscores the need for continued research into the complex mechanisms underlying impaired hypoglycemia responses and highlights the potential of targeting intestinal GLP-1 pathways in therapeutic strategies for type 1 diabetes.

Relationship between hemoglobin glycation index and risk of hypoglycemia in type 2 diabetes with time-in-range in target

BACKGROUND In patients with type 2 diabetes mellitus(T2DM),the risk of hypoglycemia also occurs in at a time-in-range(TIR)of>70%.The hemoglobin glycation index(HGI)is considered the best single factor for predicting hypoglycemia,and offers new perspectives for the individualized treatment of patients with well-controlled blood glucose levels that are easily ignored in clinical settings.All participants underwent a 7-days continuous glucose monitoring(CGM)using a retrospective CGM system.We obtained glycemic variability indices using the CGM system.We defined HGI as laboratory hemoglobin A1c minus the glucose management indicator.Patients were categorized into low HGI(HGI<0.5)and high HGI groups(HGI≥0.5)according to HGI median(0.5).Logistic regression and receiver operating characteristic curve analyses were used to determine the risk factors for hypoglycemia.RESULTS We included 129 subjects with T2DM(54.84±12.56 years,46%male)in the study.Median TIR score was 90%.The high HGI group exhibited lower TIR and greater time below range with higher hemoglobin A1c than the low HGI group;this suggests more glycemic excursions and an increased incidence of hypoglycemia in the high HGI group.Multivariate analyses revealed that mean blood glucose,standard deviation of blood glucose and HGI were independent risk factors for hypoglycemia.Receiver operating characteristic curve analysis indicated that the HGI was the best predictor of hypoglycemia.In addition,the optimal cut-off points for HGI,mean blood glucose,and standard deviation of blood glucose in predicting hypoglycemia were 0.5%,7.2 mmol/L and 1.4 mmol/L respectively.CONCLUSION High HGI was significantly associated with greater glycemic excursions and increased hypoglycemia in patients with TIR>70%.Our findings indicate that HGI is a reliable predictor of hypoglycemia in this population.

Reading impairment after neonatal hypoglycemia with parietotemporo-occipital injury without cortical blindness:A case report

BACKGROUND Perinatal brain injury may lead to later neurodevelopmental disorders,whose outcomes may vary due to neuroplasticity in young children.Recent neuroimaging studies have shown that the left parietotemporal area(which includes the left inferior parietal lobe)is associated with phonological awareness and decoding skills,which are essential skills for reading acquisition in children.However,the literature on the effect of perinatal cerebral injury on the development of phonological awareness or decoding ability in childhood is limited.CASE SUMMARY We report the case of an 8-year-old boy who presented with reading difficulty following a perinatal injury in the parieto-temporal-occipital lobes.The patient was born at term and was treated for hypoglycemia and seizures during the neonatal period.Diffusion-weighted brain magnetic resonance imaging on postnatal day 4 revealed cortical and subcortical hyperintensities in the parieto-temporo-occipital lobe.At the age of 8 years,physical examination was unremarkable,aside from mild clumsiness.Despite occipital lobe injury,the patient had adequate visual acuity,normal eye movement,and no visual field defects.Full-scale intelligence quotient and verbal comprehension index on Wechsler Intelligence Scale for Children-Fourth Edition were 75 and 90,respectively.Further assessment revealed adequate recognition of Japanese Hiragana letters.However,he had significantly slower reading speed in the Hiragana reading test than control children.The phonological awareness test revealed significant errors(standard deviation+2.7)in the mora reversal task.CONCLUSION Patients with perinatal brain injuries in the parietotemporal area require attention and may benefit from additional reading instructions.

Recurrent ciprofloxacin induced hypoglycemia in a non-diabetic patient:A case report

BACKGROUND Fluoroquinolones are a class of broad-spectrum antimicrobials used for various bacterial infections.Frequent use of fluoroquinolones has been questioned due to severe associated adverse effects,including dysglycemia(hypoglycemia or hyperglycemia)due to an alternation in glucose metabolism.Recent clinical trials showed the association of poor clinical outcomes with hypoglycemia in critically ill patients without diabetes.Many predisposing factors worsen fluoroquinolone-induced hypoglycemia,including diabetes,concomitant medication use like sulfonylureas or insulin,renal disease,and the elderly.CASE SUMMARY We report a case of recurrent hypoglycemia after ciprofloxacin initiation for a 71-year-old,non-diabetic,critically ill patient despite the presence of total parenteral nutrition and nasogastric tube feeding.The adverse drug reaction probability(Naranjo)scale was completed with a probable adverse drug reaction.The hypoglycemia resolved entirely after ciprofloxacin discontinuation.CONCLUSION Although ciprofloxacin-induced hypoglycemia is rare,special consideration is needed for the elderly due to their higher susceptibility to adverse side effects.

Oral Glucose Combined with Short-Term Intravenous Nutrition for the Prevention of Hypoglycemia after Painless Endoscopic Gastric Polypectomy

Objective: To explore the application effect of oral glucose combined with short-term intravenous nutrition in preventing postoperative hypoglycemia after painless endoscopic gastric polyp resection, and to provide guidance for better management of patients undergoing such procedures. Methods: A total of 886 patients who underwent painless endoscopic gastric polyp resection in the Department of Gastroenterology, the First Affiliated Hospital of Yangtze University, from January 2020 to December 2021, were selected as the study subjects. According to the random number table method, they were divided into an experimental group and a control group, with 443 cases in each group. Patients in the control group were subjected to routine fasting and water restriction for 8 hours before surgery, and routine fasting for 24 hours after surgery. Short-term intravenous nutrition support was provided through fluid supplementation, and finger blood glucose levels were monitored at 1 hour, 4 hours, and 8 hours after completion of intravenous infusion, or when symptoms such as palpitations and cold sweats occurred. The experimental group received oral administration of 5% glucose solution (500 ml) 2 hours before surgery based on the procedures of the control group. The incidence of preoperative discomfort (hunger, thirst, and fatigue), residual gastric fluid volume, and postoperative hypoglycemia were compared between the two groups. Results: The incidence of postoperative blood glucose Conclusion: Based on the study population, oral glucose combined with short-term intravenous nutrition can effectively prevent the incidence of hypoglycemia in patients undergoing painless endoscopic gastric polyp resection. However, due to the limitations of a single-center study and a small number of cases, its feasibility needs to be further validated with more data from multi-center and large-sample cases.

Oral Glucose Combined with Short-Term Intravenous Nutrition for the Prevention of Hypoglycemia after Endoscopic Colorectal Polypectomy

Objective: To investigate the effect of oral glucose combined with short-term intravenous nutrition on the prevention of hypoglycemia after endoscopic colorectal polypectomy and to provide guidance for better management of such patients. Methods: 860 patients who underwent endoscopic colorectal polypectomy for colorectal polyps in the Department of Gastroenterology of the First Affiliated Hospital of Yangtze University from January 2020 to December 2021 were selected for the study. The patients were divided into experimental and control groups according to the random number table method, with 430 patients in each group. In the control group, 3 L of polyethylene glycol electrolyte dispersion was used for preoperative intestinal preparation and postoperative fasting was performed routinely for 24 h. Short-term intravenous nutrition support was provided by rehydration, and finger blood glucose was monitored at 1, 4, and 8 h after intravenous infusion or when there were symptoms such as panic and cold sweat;in the experimental group, oral glucose intervention was implemented on the basis of the control group. The incidence of postoperative hypoglycemia, quality of bowel preparation, and tolerance of patients during bowel preparation were compared between the 2 groups. Results: The incidence of postoperative blood glucose Conclusion: Based on the present study population, oral glucose combined with short-term intravenous nutrition can effectively prevent the incidence of hypoglycemia in patients after endoscopic colorectal polypectomy;however, this was limited to a single-center study and the number of cases was small.

Fear of hypoglycemia,a game changer during physical activity in type 1 diabetes mellitus patients

Hypoglycemia limits optimal glycemic management of patients with type 1 diabetes mellitus(T1DM).Fear of hypoglycemia(FoH)is a significant psychosocial consequence that negatively impacts the willingness of T1DM patients to engage in and profit from the health benefits of regular physical activity(e.g.,cardiometabolic health,improved body composition,cardiovascular fitness,quality of life).Technological advances,improved insulin regimens,and a better understanding of the physiology of various types of exercise could help ameliorate FoH.This narrative review summarizes the available literature on FoH in children and adults and tools to avoid it.

Late-onset non-islet cell tumor hypoglycemia: A case report

BACKGROUND Hypoglycemia due to non-insulin-producing tumors is referred to as non-islet cell tumor hypoglycemia(NICTH).As NICTH is a rare lesion,the natural course of NICTH is not well understood.We report a case of NICTH that was observed 30 years before the onset of hypoglycemia.CASE SUMMARY A 50-year-old man was diagnosed with an abnormal right chest shadow during a routine X-ray examination,but no further examination was undertaken because the lesion appeared benign.Thirty years after the tumor discovery,the patient was admitted to the hospital with symptoms of severe hypoglycemia,which was diagnosed as NICTH based on a complete examination.The tumor was resected and found to be a solitary fibrous mass(15.6 cm×13.7 cm×10.4 cm);thereafter,the patient’s blood glucose levels normalized and he completely recovered.CONCLUSION NICTH can have an acute onset,even if the tumor has been present and asymptomatic over a long time period.

Beyond diabetes remission a step further: Post bariatric surgery hypoglycemia

Postbariatric hypoglycemia is a rare but increasingly recognized complication of bariatric surgery,with significant associated morbidity,and many patients often require multimodal treatment.A mixed meal challenge test is often helpful to diagnose this condition.This manuscript highlights the underlying mechanisms that lead to this condition and the novel emerging therapeutic targets that target these mechanisms.

Effect of Recurrent Severe Hypoglycemia on Cognitive Performance in Adult Patients with Diabetes: A Meta-analysis

The purpose of this study was to investigate the existence and extent of cognitive impairment in adult diabetes mellitus（DM） patients with episodes of recurrent severe hypoglycemia, by using meta-analysis to synthesize data across studies. PubMed, EMBASE and Cochrane library search engines were used to identify studies on cognitive performance in DM patients with recurrent severe hypoglycemia.Random-effects meta-analysis was performed on seven eligible studies using an inverse-variance method. Effect sizes, which are the standardized differences between the experimental group and the control group, were calculated. Of the 853 studies, 7 studies met the inclusion criteria. Compared with control subjects, the adult DM patients with episodes of recurrent severe hypoglycemia demonstrated a significantly lowered performance on memory in both types of DM patients, and poor performance of processing speed in type 2 DM patients. There was no significant difference between adult DM patients with and those without severe hypoglycemia in other cognitive domains such as general intelligence,executive function, processing speed and psychomotor efficiency. Our results seem to confirm the hypothesis that cognitive dysfunction is characterized by worse memory and processing speed in adult DM patients with a history of recurrent severe hypoglycemia, whereas general intelligence, executive function,and psychomotor efficiency are spared.

Mechanisms of hypoglycemia unawareness and implications in diabetic patients

Hypoglycemia unawareness(HU) is defined at the onset of neuroglycopenia before the appearance of autonomic warning symptoms.It is a major limitation to achieving tight diabetes and reduced quality of life.HU occurs in approximately 40% of people with type 1 diabetesmellitus(T1DM) and with less frequency in T2 DM.Though the aetiology of HU is multifactorial,possible mechanisms include chronic exposure to low blood glucose,antecedent hypoglycaemia,recurrent severe hypoglycaemia and the failure of counter-regulatory hormones.Clinically it manifests as the inability to recognise impeding hypoglycaemia by symptoms,but the mechanisms and mediators remain largely unknown.Prevention and management of HU is complex,and can only be achieved by a multifactorial intervention of clinical care and structured patient education by the diabetes team.Less know regarding the impact of medications on the development or recognition of this condition in patients with diabetes.Several medications are thought to worsen or promote HU,whereas others may have an attenuating effect on the problem.This article reviews recent advances in how the brain senses and responds to hypoglycaemia,novel mechanisms by which people with insulin-treated diabetes develop HU and impaired counter-regulatory responses.The consequences that HU has on the person with diabetes and their family are also described.Finally,it examines the evidence for prevention and treatment of HU,and summarizes the effects of medications that may influence it.

Case report on an infant presenting with hypoglycemia,and milky serum

A 4-month-old male baby who presented in a moribund condition with seizures was found to have hepatomegaly,hypoglycemia and milky serum.Serum triglycerides were markedly elevated(3168 mg/dL) with cholesterol being 257 mg/dL and high density lipoprotein levels were low(19 mg/dL).The possibility of glycogen storage disease type Ⅰ was considered in the diagnosis.Infants with glycogen storage disease type Ⅰ may present like sepsis.The association of hepatomegaly, hypoglycemia and abnormal lipid profile stated above should alert the physician to consider glycogen storage disease type Ⅰ in the diagnosis.

Predictors of hypoglycemia in insulin-treated patients with type 2 diabetes mellitus in Basrah

AIM To measure the incidence and determinants(predictors) of hypoglycemia among patients with type 2 diabetes mellitus(T2DM) who were on insulin treatment for at least one year. METHODS The present study is an out-patients based inquiry about the risk and predictors of hypoglycemia among patients with T2DM seeking care at the Al-Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah over a period of 7 mo(from 15^(th) of April, 2013 to 15^(th) of October, 2013). The data used in the study were based on all detailed interview and selected laboratory investigations. A total of 336 patients could be included in the study.RESULTS The incidence of overall hypoglycemia among the studied patients was 75.3% within the last 3 mo preceding the interview. The incidence of hypoglycemia subtypes were 10.2% for severe hypoglycemia requiring medical assistance in the hospital, 44.36% for severe hypoglycemia treated at home by family; this includes both confirmed severe hypoglycemia with an incidence rate of 14.6% and unconfirmed severe hypoglycemia for which incidence rate was 29.76%. Regarding mild self-treated hypoglycemia, the incidence of confirmed mild hypoglycemia was 21.42%, for unconfirmed mildhypoglycemia the incidence rate was 50.0% and for total mild hypoglycemia, the incidence rate was 71.42%. The most important predictors of hypoglycemia were a peripheral residence, increasing knowledge of hypoglycemia symptoms, in availability and increasing frequency of self-monitoring blood glucose, the presence of peripheral neuropathy, higher diastolic blood pressure, and lower Hemoglobin A1c.CONCLUSION Hypoglycemia is very common among insulin-treated patients with T2DM in Basrah. It was possible to identify some important predictors of hypoglycemia.

Causative anti-diabetic drugs and the underlying clinical factors for hypoglycemia in patients with diabetes

Recent clinical trials indicated that the intensive glycemic control do not reduce cardiovascular disease mortality among diabetic patients, challenging a significance of the strict glycemic control in diabetes management. Furthermore, retrospective analysis of the Action to Control Cardiovascular Risk in Diabetes study demonstrated a significant association betweenhypoglycemia and mortality. Here, we systematically reviewed the drug-induced hypoglycemia, and also the underlying clinical factors for hypoglycemia in patients with diabetes. The sulfonylurea use is significantly associated with severe hypoglycemia in patients with type 2 diabetes. The use of biguanide(approximately 45%-76%) and thiazolidinediones(approximately 15%-34%) are also highly associated with the development of severe hypoglycemia. In patients treated with insulin, the intensified insulin therapy is more frequently associated with severe hypoglycemia than the conventional insulin therapy and continuous subcutaneous insulin infusion. Among the underlying clinical factors for development of severe hypoglycemia, low socioeconomic status, aging, longer duration of diabetes, high Hb A1 c and low body mass index, comorbidities are precipitating factors for severe hypoglycemia. Poor cognitive and mental functions are also associated with severe hypoglycemia.

Hypoglycemia in diabetes:An update on pathophysiology,treatment,and prevention

Hypoglycemia is a common complication in patients with diabetes,mainly in those treated with insulin,sulfonylurea,or glinide.Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia.Episodes of hypoglycemia are associated with physical and psychological morbidity.The fear of hypoglycemia constitutes a barrier that impairs the patient’s ability to reach good glycemic control.To prevent hypoglycemia,much effort must be invested in patient education regarding risk factors,warning signs,and treatment of hypoglycemia at an early stage,together with setting personalized goals for glycemic control.In this review,we present a comprehensive update on the treatment and prevention of hypoglycemia in type 1 and type 2 diabetic patients.

EFFECTS OF ACUTE HYPOGLYCEMIA ON THE OREXIN SYSTEM IN RAT

Objective To evaluate the effects of acute glucose level changes on expression of prepro-orexin, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) mRNA in rat hypothalamus tissue and pancreatic islets cells. Methods Thirty adult male Wistar rats were randomly divided into three equal groups (n = 10). The acute hypoglycemia rat model was induced by a single subcutaneous injection of insulin. Twenty acute hypoglycemia rats were divided into group B and group C. Group B was allowed to eat freely, while group C was food-deprived. Control rats were injected the same volume of saline. The effect of glucose levels (2.8 mmol/L and 8.3 mmol/L) on pancreatic islet cell orexin system was detected in pancreas islet cell cultured in vitro. The expression of prepro-orexin and OXR mRNA was examined in rat hypothalamus tissue and pancreatic islets cell cultured in vitro using reverse transcription-polymerase chain reaction (RT-PCR). Results Expression of orexin mRNA increased about 150% for the food-deprived hypoglycemia rats in comparison with control group (P < 0.01), whereas expression of OX1R mRNA decreased up to 30% (P < 0.01). However, expression of OX2R mRNA was unchanged in comparison with control group. In vitro, after incubation with 2.8 mmol/L glucose for 6 hours, the expression of prepro-orexin mRNA increased 2 times in rat pancreas islet cells in comparison with 8.3 mmol/L glucose group (P < 0.01). But the expression of OX1R mRNA was not sensitive to acute glucose fluctuation.Conclusions Orexin in rat hypothalamus is stimulated by decline in blood glucose and inhibited by signals related to feeding. Moreover, glucose plays a role in modulating the gene expression of prepro-orexin in rat pancreatic islet cells.