Paraneoplastic Syndromes in Hepatocellular Carcinoma, Epidemiology, and Survival: A Retrospective Seven Years Study.

Background and Objectives: Liver cancer poses a significant global health threat, ranking among the top three causes of cancer-related deaths. Patients with hepatocellular carcinoma (HCC) often present with symptoms associated with neoplasms or unusual clinical features such as paraneoplastic syndromes (PNS), including hypoglycemia, hypercholesterolemia, thrombocytosis, and erythrocytosis. Our study aimed to investigate the prevalence, clinical characteristics, and survival outcomes associated with PNS in HCC patients and assess each PNS's impact on patient survival. Materials and Methods: We conducted a retrospective analysis of PNS clinical features and survival among consecutive HCC patients diagnosed at our department over seven years, comparing them with HCC patients without PNS. The study involved a retrospective data evaluation from 378 patients diagnosed with HCC between January 2016 and October 2023. Results: We obtained a PNS prevalence of 25.7%, with paraneoplastic hypercholesterolemia at 10.9%, hypoglycemia at 6.9%, erythrocytosis at 4.5%, and thrombocytosis at 3.4%. Patients with PNS tended to be younger and predominantly male. Multivariate analysis revealed a strong correlation between PNS and levels of alpha-fetoprotein and tumor size, with diabetes also showing a significant statistical association (p < 0.05). Subgroup analysis based on specific paraneoplastic syndromes demonstrated shorter survival in patients with PNS, albeit without significant statistical differences, except for hypoglycemia (p < 0.0001). Matched analysis indicated a shorter survival rate for patients with PNS, although no significant statistical differences were observed. Conclusions: PNS are frequently observed in HCC cases and are associated with unfavorable prognoses and decreased survival rates due to their correlation with increased tumor burdens. However, they do not independently predict poor survival. The impact of individual PNS on HCC prognosis varies.

Binge eating symptomatology in adolescents with polycystic ovary syndrome.

Several factors may contribute to binge eating behaviors in PCOS. However, findings are contradictory and studies in the adolescence are limited. We aimed to evaluate the eating attitudes of adolescents with PCOS and the possible etiological factors underlying the association between PCOS and binge eating symptomology. Between 2019 and 2022, 46 newly diagnosed adolescents with PCOS and 56 controls matched for age and BMI z-score were included. The Eating Disorder Examination Questionnaire, Three Factor Eating Questionnaire-R18, and a questionnaire assessing postprandial reactive hypoglycemia symptom severity were given. Binge eating symptomology, in terms of over, uncontrolled, and emotional eating, were more prevalent in the PCOS group. Uncontrolled, emotional, and binge eating were positively correlated with postprandial reactive hypoglycemia symptom score. Overeating was also associated with clinical hyperandrogenism. Improving the disease outcome and reducing the future complications requires early recognition and management of emotional and uncontrolled eating behaviors in adolescents with PCOS.

Diabetes Mellitus Following Resection of a Hepatocellular Carcinoma in a Dog Presented with Hypoglycemia.

A 5 yr old male neutered Labradoodle presented for an episode of acute collapse. Point-of-care blood work showed hypoglycemia and abdominal ultrasonography revealed a liver mass arising from the caudate liver lobe. The dog underwent a partial liver lobectomy, and histopathology confirmed a fully resected hepatocellular carcinoma. Blood glucose levels normalized initially after surgery, but 1 wk later, the patient was diagnosed with diabetes mellitus based on the development of polyuria, polydipsia, hyperglycemia, and glucosuria. Appropriate treatment with insulin was initiated, and 1 yr following the diagnosis, the dog was still requiring administration of insulin twice daily. This case describes the uncommon development of diabetes mellitus in a dog following surgical resection of a hepatocellular carcinoma initially associated with hypoglycemia. Although very unusual, this should be considered as a potential complication of surgical treatment of such tumors, and affected patients may require long-term medical management.

Remission of type 2 diabetes: always more questions, but enough answers for action.

The concept of type 2 diabetes remission is evolving rapidly, and gaining wide public and professional interest, following demonstration that with substantial intentional weight loss almost nine in ten people with type 2 diabetes can reduce their HbA1c level below the diagnostic criterion (48 mmol/mol [6.5%]) without glucose-lowering medications, and improve all features of the metabolic syndrome. Pursuing nomoglycaemia with older drugs was dangerous because of the risk of side effects and hypoglycaemia, so the conventional treatment target was an HbA1c concentration of 53 mmol/mol (7%), meaning that diabetes was still present and allowing disease progression. Newer agents may achieve a normal HbA1c safely and, by analogy with treatments that send cancers or inflammatory diseases into remission, this might also be considered remission. However, although modern glucagon-like peptide-1 receptor agonists and related medications are highly effective for weight loss and glycaemic improvement, and generally safe, many people do not want to take drugs indefinitely, and their cost means that they are not available across much of the world. Therefore, there are strong reasons to explore and research dietary approaches for the treatment of type 2 diabetes. All interventions that achieve sustained weight loss of >10-15 kg improve HbA1c, potentially resulting in remission if sufficient beta cell capacity can be preserved or restored, which occurs with loss of the ectopic fat in liver and pancreas that is found with type 2 diabetes. Remission is most likely with type 2 diabetes of short duration, lower HbA1c and a low requirement for glucose-lowering medications. Relapse is likely with weight regain and among those with a poor beta cell reserve. On current evidence, effective weight management should be provided to all people with type 2 diabetes as soon as possible after diagnosis (or even earlier, at the stage of prediabetes, defined in Europe, Australasia, Canada [and most of the world] as ≥42 and <48 mmol/mol [≥6.0 and <6.5%], and in the USA as HbA1c ≥39 and <48 mmol/mol [≥5.7 and <6.5%]). Raising awareness among people with type 2 diabetes and their healthcare providers that remission is possible will enable earlier intervention. Weight loss of >10 kg and remission lasting 1-2 years may also delay vascular complications, although more evidence is needed. The greatest challenge for research is to improve long-term weight loss maintenance, defining cost-effective approaches tailored to the preferences and needs of people living with type 2 diabetes.

Perioperative Glycemic Management in Cardiac Surgery: A Narrative Review.

Diabetes and hyperglycemic events in cardiac surgical patients are associated with postoperative morbidity and mortality. The causes of dysglycemia, the abnormal fluctuations in blood glucose concentrations, in the perioperative period include surgical stress, surgical techniques, medications administered perioperatively, and patient factors. Both hyperglycemia and hypoglycemia lead to poor outcomes after cardiac surgery. While trying to control blood glucose concentration tightly for better postoperative outcomes, hypoglycemia is the main adverse event. Currently, there is no definite consensus on the optimum perioperative blood glucose concentration to be maintained in cardiac surgical patients. This review provides an overview of perioperative glucose homeostasis, the pathophysiology of dysglycemia, factors that affect glycemic control in cardiac surgery, and current practices for glycemic control in cardiac surgery.

Hypoglycaemia in adrenal insufficiency.

Adrenal insufficiency encompasses a group of congenital and acquired disorders that lead to inadequate steroid production by the adrenal glands, mainly glucocorticoids, mineralocorticoids and androgens. These may be associated with other hormone deficiencies. Adrenal insufficiency may be primary, affecting the adrenal gland's ability to produce cortisol directly; secondary, affecting the pituitary gland's ability to produce adrenocorticotrophic hormone (ACTH); or tertiary, affecting corticotrophin-releasing hormone (CRH) production at the level of the hypothalamus. Congenital causes of adrenal insufficiency include the subtypes of Congenital Adrenal Hyperplasia, Adrenal Hypoplasia, genetic causes of Isolated ACTH deficiency or Combined Pituitary Hormone Deficiencies, usually caused by mutations in essential transcription factors. The most commonly inherited primary cause of adrenal insufficiency is Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency; with the classical form affecting 1 in 10,000 to 15,000 cases per year. Acquired causes of adrenal insufficiency can be subtyped into autoimmune (Addison's Disease), traumatic (including haemorrhage or infarction), infective (e.g. Tuberculosis), infiltrative (e.g. neuroblastoma) and iatrogenic. Iatrogenic acquired causes include the use of prolonged exogenous steroids and post-surgical causes, such as the excision of a hypothalamic-pituitary tumour or adrenalectomy. Clinical features of adrenal insufficiency vary with age and with aetiology. They are often non-specific and may sometimes become apparent only in times of illness. Features range from those related to hypoglycaemia such as drowsiness, collapse, jitteriness, hypothermia and seizures. Features may also include signs of hypotension such as significant electrolyte imbalances and shock. Recognition of hypoglycaemia as a symptom of adrenal insufficiency is important to prevent treatable causes of sudden deaths. Cortisol has a key role in glucose homeostasis, particularly in the counter-regulatory mechanisms to prevent hypoglycaemia in times of biological stress. Affected neonates particularly appear susceptible to the compromise of these counter-regulatory mechanisms but it is recognised that affected older children and adults remain at risk of hypoglycaemia. In this review, we summarise the pathogenesis of hypoglycaemia in the context of adrenal insufficiency. We further explore the clinical features of hypoglycaemia based on different age groups and the burden of the disease, focusing on hypoglycaemic-related events in the various aetiologies of adrenal insufficiency. Finally, we sum up strategies from published literature for improved recognition and early prevention of hypoglycaemia in adrenal insufficiency, such as the use of continuous glucose monitoring or modifying glucocorticoid replacement.

Resolution of dysglycaemia after treatment of monoclonal gammopathy of endocrine significance.

In very rare cases of monoclonal gammopathy, insulin-binding paraprotein can cause disabling hypoglycaemia. We report a 67-year-old man re-evaluated for hyperinsulinaemic hypoglycaemia that persisted despite distal pancreatectomy. He had no medical history of diabetes mellitus or autoimmune disease but was being monitored for an IgG kappa monoclonal gammopathy of undetermined significance. On glucose tolerance testing, hyperglycaemia occurred at 60 min (glucose 216 mg/dL) and hypoglycaemia at 300 min (52 mg/dL) concurrent with an apparent plasma insulin concentration of 52 850 pmol/L on immunoassay. Laboratory investigation revealed an IgG2 kappa with very high binding capacity but low affinity (Kd 1.43 × 10-6 mol/L) for insulin. The monoclonal gammopathy was restaged as smouldering myeloma not warranting plasma cell-directed therapy from a haematological standpoint. Plasma exchange reduced paraprotein levels and improved fasting capillary glucose concentrations. Lenalidomide was used to treat disabling hypoglycaemia, successfully depleting paraprotein and leading to resolution of symptoms.

The oral disposition index calculated from a meal tolerance test is a crucial indicator for evaluating differential normalization of postprandial glucose and triglyceride excursions in morbidly obese patients after laparoscopic sleeve gastrectomy.

To determine the normalization of postprandial blood glucose (PG) and triglyceride (TG) excursions in 30 morbidly obese patients with or without diabetes mellitus (DM) 1-year after they underwent a laparoscopic sleeve gastrectomy (LSG) vs. their pre-surgery data, we administered the 75-g oral glucose tolerance test (OGTT) and a meal tolerance test (MTT) using a 75-g glucose-equivalent carbohydrate- and fat-containing meal. The results were as follows; (i) Postoperative body-weight reduction was associated with DM remission and reduced multiple cardiometabolic risks. (ii) OGTT data showing postprandial hyper-insulinemic hypoglycemia in many post-surgery patients were associated with overdiagnosis of improved glucose tolerance. However, postoperative MTT data without hypoglycemia showed no improvement in the glucose tolerance vs. pre-surgery data. (iii) The disposition index (DI) i.e., [Matsuda index] × (Glucose-induced insulin secretion) was progressively worsened from normal glucose tolerance to DM patients after LSG. These post-surgery DI values measured by the MTT were correlated with 2h-plasma glucose levels and were not normalized in DM patients. (iv) The baseline, 2h-TG, and an increase in 2h-TG values above baseline were correlated with the insulin resistance index, DI, or HbA1c; These TG values were normalized post-LSG. In conclusion, the glucose tolerance curve measured by the MTT was not normalized in T2DM patients, which was associated with impaired normalization of the DI values in those patients 1-year after the LSG. However, the baseline TG and a fat-induced 2h-TG values were normalized postoperatively. The MTT can be used to assess normalization in postprandial glucose and TG excursions after LSG.

Mitophagy disorder mediates cardiac deterioration induced by severe hypoglycemia in diabetic mice.

Severe hypoglycemia is closely related to adverse cardiovascular outcomes in patients with diabetes; however, the specific mechanism remains unclear. We previously found that severe hypoglycemia aggravated myocardial injury and cardiac dysfunction in diabetic mice, and that the mechanism of damage was related to mitochondrial oxidative stress and dysfunction. Based on the key regulatory role of mitophagy in mitochondrial quality control, this study aimed to further explore whether the myocardial damage caused by severe hypoglycemia is related to insufficient mitophagy and to clarify their underlying regulatory relationship. After severe hypoglycemia, mitochondrial reactive oxygen species increased, mitochondrial membrane potential and ATP content decreased, and pathological mitochondrial damage was aggravated in the myocardium of diabetic mice. This was accompanied by decreased mitochondrial biosynthesis, increased fusion, and downregulated PTEN-induced kinase 1 (PINK1)/Parkin-dependent mitophagy. Treating diabetic mice with the mitophagy activator and polyphenol metabolite urolithin A activated PINK1/Parkin-dependent mitophagy, reduced myocardial oxidative stress and mitochondrial damage associated with severe hypoglycemia, improved mitochondrial function, alleviated myocardial damage, and ultimately improved cardiac function. Thus, we provide insight into the prevention and treatment of diabetic myocardial injury caused by hypoglycemia to reduce adverse cardiovascular outcomes in patients with diabetes.

Hypoglycemia risk with inappropriate dosing of glucose-lowering drugs in patients with chronic kidney disease: a retrospective cohort study.

The incidence rates and consequences of inappropriate dosing of glucose-lowering drugs remain limited in patients with chronic kidney disease (CKD). A retrospective cohort study was conducted to estimate the frequency of inappropriate dosing of glucose-lowering drugs and to evaluate the subsequent risk of hypoglycemia in outpatients with an estimated glomerular filtration rate (eGFR) of < 50 mL/min/1.73 m2. Outpatient visits were divided according to whether the prescription of glucose-lowering drugs included dose adjustment according to eGFR or not. A total of 89,628 outpatient visits were included, 29.3% of which received inappropriate dosing. The incidence rates of the composite of all hypoglycemia were 76.71 and 48.51 events per 10,000 person-months in the inappropriate dosing group and in appropriate dosing group, respectively. After multivariate adjustment, inappropriate dosing was found to lead to an increased risk of composite of all hypoglycemia (hazard ratio 1.52, 95% confidence interval 1.34, 1.73). In the subgroup analysis, there were no significant changes in the risk of hypoglycemia regardless of renal function (eGFR < 30 vs. 30-50 mL/min/1.73 m2). In conclusion, inappropriate dosing of glucose-lowering drugs in patients with CKD is common and associated with a higher risk of hypoglycemia.

Pathophysiology and Management of Glycemic Alterations before and after Surgery for Pheochromocytoma and Paraganglioma.

Glycemic alterations are frequent in patients with pheochromocytoma and paraganglioma (PPGL), but the real incidence of secondary diabetes mellitus (DM) is uncertain, because prospective multicenter studies on this topic are lacking in the literature. The main pathophysiological mechanisms of glucose homeostasis alterations in PPGL, related to catecholamine hypersecretion, are impaired insulin and glucagon-like peptide type 1 (GLP-1) secretion and increased insulin resistance. Moreover, it has been reported that different pathways leading to glucose intolerance may be related to the secretory phenotype of the chromaffin tumor. Predictive factors for the development of glucose intolerance in PPGL patients are a higher age at diagnosis, the need for a higher number of anti-hypertensive drugs, and the presence of secreting neoplasms. Tumor resection is strongly related to the resolution of DM in PPGL patients, with a significant improvement of glycemic control in most cases. We can hypothesize a different personalized therapeutic approach based on the secretory phenotype. The adrenergic phenotype is more closely related to reduced insulin secretion, so insulin therapy may be required. On the other hand, the noradrenergic phenotype mainly acts by increasing insulin resistance and, therefore, insulin-sensitizing antidiabetic agents can find a greater application. Regarding GLP-1 receptor agonists, the data suggest a possible promising therapeutic effect, based on the assumption that GLP-1 secretion is impaired in patients with PPGL. The principal predictors of remission of glycemic alterations after surgery for PPGL are a lower preoperative body mass index (BMI), a larger tumor, higher preoperative catecholamine levels, and a shorter duration of the disease (under three years). Otherwise, after resection of PPGL, hypoglycemia can occur as the result of an excessive rebound of preoperative hyperinsulinemia. It is a rare, but potentially severe complication reported in a lot of case reports and a few small retrospective studies. Higher 24-h urinary metanephrine levels, longer operative times and larger tumors are predictive factors for hypoglycemia in this setting. In conclusion, alterations of carbohydrate metabolism are clinically relevant manifestations of PPGL before and after surgery, but there is the need to conduct multicenter prospective studies to obtain an adequate sample size, and to allow the creation of shared strategies for the clinical management of these potentially severe manifestations of PPGL.

Persistent acidosis and chronic kidney disease in a patient with type 1 glycogen storage disease.

Type 1 glycogen storage disease (GSDI) is a rare autosomal recessive disorder caused by glucose-6-phosphatase (G6Pase) deficiency. We discuss a case of a 29-year-old gentleman who had GSDI with metabolic complications of hypoglycemia, hypertriglyceridemia, hyperuricemia, and short stature. He also suffered from advanced chronic kidney disease, nephrotic range proteinuria, and hepatic adenomas. He presented with acute pneumonia and refractory metabolic acidosis despite treatment with isotonic bicarbonate infusion, reversal of hypoglycemia, and lactic acidosis. He eventually required kidney replacement therapy. The case report highlights the multiple contributing mechanisms and challenges to managing refractory metabolic acidosis in a patient with GSDI. Important considerations for dialysis initiation, decision for long-term dialysis modality and kidney transplantation for patients with GSDI are also discussed in this case report.

Treatment of Severe Hyperglycemia in Patients Without Diabetes After Colorectal Surgery.

Background: Several studies have suggested that intravenous insulin therapy for post-operative hyperglycemia improves outcomes after colorectal surgery. Despite the potential benefit, there is a reluctance to use this approach in patients without diabetes mellitus because of an unproven benefit and the potential for hypoglycemia. In this study, we examined whether sliding-scale insulin is sufficient to improve outcomes or if stricter glucose control is necessary. Patients and Methods: Of 1,064 consecutive colorectal surgery patients between August 2016 and December 2021, 478 patients without diabetes mellitus had an average of 6.4 ± 3.1 glucose samples taken within 48 hours after surgery. Sixty-six percent of patients with severe hyperglycemia (glucose ≥180 mg/dL) received sliding-scale insulin. Complication rates and effects of insulin were examined. Results: Severe hyperglycemia was associated with a higher total infection rate (p < 0.002), National Healthcare Safety Network-reported infections (NHSN; p < 0.026), total complications (p < 0.001), and length of stay (LOS; p < 0.000). Sliding-scale insulin did not lower the risk of infection or other complications. Hypoglycemia (glucose <70 mg/dL) occurred in 3.5% of patients, but was not related to insulin use, and was predictable with clinical variables: albumin (p < 0.032), operative duration (p < 0.012), and average post-operative glucose (p < 0.002; area under the curve [AUC], 0.86). Conclusions: Our data confirm that severe post-operative hyperglycemia in patients without diabetes mellitus after colorectal surgery is associated with complications. Sliding-scale insulin was safe but not effective. Treatment before severe hyperglycemia is reached, not after its occurrence, may be beneficial.

Caffeine-Supplemented Diet Prevents Fatigue-Like Behavior in Tumor-Bearing Mice.

Caffeine is a widely consumed stimulant, known for its positive effects on physical and mental performance. These effects are potentially beneficial for ameliorating cancer-related fatigue, which affects the quality of life of patients with cancer. This study aimed to determine the anti-fatigue and antitumor effects of caffeine in tumor-bearing mice. BALB/c mice were intravenously injected with C26 colon carcinoma cells and fed with normal or 0.05% caffeine-supplemented diet. Fatigue-like behavior was assessed by running performance using a treadmill test. Lung, blood, liver, muscle, and epididymal adipose tissue samples were collected on day 13 and examined. The antitumor effect of caffeine was assessed using subcutaneous tumor-bearing mice fed with 0.05% caffeine-supplemented diet, and the tumor volume was measured. C26 tumor-bearing mice showed fatigue-like behavior associated with hypoglycemia, depleted liver glycogen and non-esterified fatty acid (NEFA) levels. C26 tumor-bearing mice fed with 0.05% caffeine-supplemented diet showed improved running performance associated with restored NEFA levels. However, exacerbated hypoglycemia and liver glycogen levels after caffeine consumption may be due to tumor-induced catabolic signals, as the tumor volume was not affected. Collectively, caffeine may exert anti-fatigue effects through enhanced lipolysis leading to restored NEFA levels, which can be used as an alternative energy source.

HIF-1α accumulation in response to transient hypoglycemia may worsen diabetic eye disease.

Tight glycemic control (TGC), the cornerstone of diabetic management, reduces the incidence and progression of diabetic microvascular disease. However, TGC can also lead to transient episodes of hypoglycemia, which have been associated with adverse outcomes in patients with diabetes. Here, we demonstrate that low glucose levels result in hypoxia-inducible factor (HIF)-1-dependent expression of the glucose transporter, Glut1, in retinal cells. Enhanced nuclear accumulation of HIF-1α was independent of its canonical post-translational stabilization but instead dependent on stimulation of its translation and nuclear localization. In the presence of hypoxia, this physiologic response to low glucose resulted in a marked increase in the secretion of the HIF-dependent vasoactive mediators that promote diabetic retinopathy. Our results provide a molecular explanation for how early glucose control, as well as glycemic variability (i.e., oscillating serum glucose levels), contributes to diabetic eye disease. These observations have important implications for optimizing glucose management in patients with diabetes.

Insulinoma as a cause of seizure-like activity and spontaneous hypoglycaemia.

A woman in her 60s presented to our hospital with recurrent episodes of confusion and double vision with spontaneous recovery to baseline within 10 min. Her initial workup was unremarkable, and she was diagnosed with complex partial seizures and commenced on levetiracetam. The following week, she re-presented with a recurrence of her symptoms, associated with spontaneous hypoglycaemia, with blood glucose levels of 1.9 mmol/L. She was found to have endogenously elevated serum insulin and C peptide levels, which were concomitantly associated with hypoglycaemia. An initial diagnosis of insulinoma was made and she was commenced on diazoxide. MRI and endoscopic ultrasound revealed 16 mm insulinoma in her uncinate process. She underwent surgical resection and remained symptom free at follow-up. This case highlights the importance of blood glucose measurements in patients presenting with neuroglycopenic symptoms and outlines the workup and management of insulinoma.

Counter-regulatory responses to postprandial hypoglycaemia in patients with post-bariatric hypoglycaemia vs surgical and non-surgical control individuals.

AIMS/HYPOTHESIS: Post-bariatric hypoglycaemia is an increasingly recognised complication of bariatric surgery, manifesting particularly after Roux-en-Y gastric bypass. While hyperinsulinaemia is an established pathophysiological feature, the role of counter-regulation remains unclear. We aimed to assess counter-regulatory hormones and glucose fluxes during insulin-induced postprandial hypoglycaemia in patients with post-bariatric hypoglycaemia after Roux-en-Y gastric bypass vs surgical and non-surgical control individuals. METHODS: In this case-control study, 32 adults belonging to four groups with comparable age, sex and BMI (patients with post-bariatric hypoglycaemia, Roux-en-Y gastric bypass, sleeve gastrectomy and non-surgical control individuals) underwent a postprandial hypoglycaemic clamp in our clinical research unit to reach the glycaemic target of 2.5 mmol/l 150-170 min after ingesting 15 g of glucose. Glucose fluxes were assessed during the postprandial and hypoglycaemic period using a dual-tracer approach. The primary outcome was the incremental AUC of glucagon during hypoglycaemia. Catecholamines, cortisol, growth hormone, pancreatic polypeptide and endogenous glucose production were also analysed during hypoglycaemia. RESULTS: The rate of glucose appearance after oral administration, as well as the rates of total glucose appearance and glucose disappearance, were higher in both Roux-en-Y gastric bypass groups vs the non-surgical control group in the early postprandial period (all p<0.05). During hypoglycaemia, glucagon exposure was significantly lower in all surgical groups vs the non-surgical control group (all p<0.01). Pancreatic polypeptide levels were significantly lower in patients with post-bariatric hypoglycaemia vs the non-surgical control group (median [IQR]: 24.7 [10.9, 38.7] pmol/l vs 238.7 [186.3, 288.9] pmol/l) (p=0.005). Other hormonal responses to hypoglycaemia and endogenous glucose production did not significantly differ between the groups. CONCLUSIONS/INTERPRETATION: The glucagon response to insulin-induced postprandial hypoglycaemia is lower in post-bariatric surgery individuals compared with non-surgical control individuals, irrespective of the surgical modality. No significant differences were found between patients with post-bariatric hypoglycaemia and surgical control individuals, suggesting that impaired counter-regulation is not a root cause of post-bariatric hypoglycaemia. TRIAL REGISTRATION: ClinicalTrials.gov NCT04334161.

[Preterm with Macroglossia and Persistent Hypoglycemia - Beckwith-Wiedemann Syndrome]. / Frühgeborenes mit Makroglossie und persistierender Hypoglykämie ­ Beckwith-Wiedemann-Syndrom.

Beckwith-Wiedemann syndrome (BWS) is a genetic disease with phenotypic variability and the following signs: macroglossia, asymmetry, lateralised overgrowth, overgrowth of the internal organs, abdominal wall defects, neonatal hypoglycemia and increased risk of embryonic tumours. The prevalence is reported as being between 1 in 10,000 and 1 in 21,000 live births. The disease is caused by molecular changes in gene clusters on the short arm of chromosome 11 region P15.5. We present the case of a female, born preterm at 32 0/7 weeks. A UPD(11)pat-mutation was diagnosed postnatally. The particular feature of her case was an early tongue reduction surgery which was necessary because of drinking and breathing difficulties. Long-lasting hypoglycemia was difficult to treat.

Effects of Intensive Blood Glucose Control on Surgical Site Infection for Liver Transplant Recipients: A Randomized Controlled Trial.

BACKGROUND: The evidence supporting intensive blood glucose control to prevent surgical site infections (SSIs) among liver transplant recipients is insufficient. We aimed to assess the effects of postoperative intensive blood glucose control (IBGC) against standard blood glucose control (SBGC) on the incidence of SSIs among adult liver transplant recipients. METHODS: We performed a randomized controlled trial (ClinicalTrials.gov identifier NCT03474666). The IBGC target was 80 to 130 mg/dL, and the SBGC target was below 180 mg/dL. Analyses were made on an intention-to-treat basis. RESULTS: Of the 41 recipients enrolled onto the trial, 20 were randomly allocated to the IBGC group and 21 to the SBGC group. There were no significant differences in SSIs among recipients allocated to either group (relative risk [RR], 0.78; 95% confidence interval [CI], 0.21-2.88; P = .69). Mean (SD) blood glucose levels were significantly lower in the IBGC group in the 24-hour period after surgery (145.0 [20.7] mg/dL and 230.2 [51.6] mg/dL; P = .001). While there were fewer episodes of hypoglycemia in the IBGC group, this was not statistically significant. There were no episodes of severe hypoglycemia in either group. Hyperglycemia and severe hyperglycemia were significantly more frequent in the SBGC group (RR, 0.70; 95% CI, 0.52-0.93; P = .001 and RR, 0.07; 95% CI, 0.01-0.48; P = .001, respectively). Length of hospital stay was significantly shorter for recipients in the IBGC group (13.1 [5.5] days vs 19.3 [12.1] days; P = .04). CONCLUSIONS: Although this small trial did not find intensive control reduced SSI, it was associated with lower blood glucose levels, fewer episodes of hyperglycemia and severe hyperglycemia, and shorter length of hospital stay.

Mito-TEMPO, a Mitochondria-Targeted Antioxidant, Improves Cognitive Dysfunction due to Hypoglycemia: an Association with Reduced Pericyte Loss and Blood-Brain Barrier Leakage.

Hypoglycemia is associated with cognitive dysfunction, but the exact mechanisms have not been elucidated. Our previous study found that severe hypoglycemia could lead to cognitive dysfunction in a type 1 diabetes (T1D) mouse model. Thus, the aim of this study was to further investigate whether the mechanism of severe hypoglycemia leading to cognitive dysfunction is related to oxidative stress-mediated pericyte loss and blood-brain barrier (BBB) leakage. A streptozotocin T1D model (150 mg/kg, one-time intraperitoneal injection), using male C57BL/6J mice, was used to induce hypoglycemia. Brain tissue was extracted to examine for neuronal damage, permeability of BBB was investigated through Evans blue staining and electron microscopy, reactive oxygen species and adenosine triphosphate in brain tissue were assayed, and the functional changes of pericytes were determined. Cognitive function was tested using Morris water maze. Also, an in vitro glucose deprivation model was constructed. The results showed that BBB leakage after hypoglycemia is associated with excessive activation of oxidative stress and mitochondrial dysfunction due to glucose deprivation/reperfusion. Interventions using the mitochondria-targeted antioxidant Mito-TEMPO in both in vivo and in vitro models reduced mitochondrial oxidative stress, decreased pericyte loss and apoptosis, and attenuated BBB leakage and neuronal damage, ultimately leading to improved cognitive function.