Delayed-Onset Transient Hyperinsulinism in Infants with Very Low and Extremely Low Birth Weights: A Cohort Study.

We describe 16 infants born preterm with birth weights <1500 g and transient hyperinsulinism. The onset of hyperinsulinism was delayed and often coincident with clinical stabilization. We hypothesize that postnatal stress caused by prematurity and associated problems may contribute to development of delayed-onset transient hyperinsulinism.

Hypoglycemia post bariatric surgery: drugs with different mechanisms of action to treat a unique disorder.

Postprandial hypoglycemia (PPH) is a complex and multifactorial complication of bariatric surgery (BS). PPH may cause severe symptoms or be asymptomatic. The treatment of this condition requires dietary changes, but severe cases require drug therapy. The number of therapeutic options is limited and are often associated with adverse side effects. Different classes of drugs have been used and tested, but the resolution of PPH remains a challenge for physicians and patients. In this review, we gathered articles on PPH after BS from PubMed searches (2001 to 2022) and focused on the main drugs tested for the treatment of this condition, such as acarbose, somatostatin analogues, type 2 sodium-glucose cotransporter inhibitors, calcium channel blockers, and liraglutide. Avexitide and glucagon pump are two new therapeutic options that have been recently tested. For the search, the terms "postbariatric hypoglycemia," "bariatric surgery," and "late dumping syndrome" were used. PPH after BS is a frequent condition that should always be evaluated after BS. Treatment should be individualized and the available therapeutic options may be useful based on the condition's pathophysiology.

[Prognostic value of hospital hypoglycemia]. / Valor pronóstico de la hipoglucemia hospitalaria.

BACKGROUND: Hospital hypoglycemia (HH) is an important problem since it is linked to hospital death, prolonged stay and higher costs, both in people with and without diabetes, in the critical area and general ward, especially in cases of severe hypoglycemia. The objective of our work was to compare hospital mortality, transfer to the critical area and hospitalization periods in adults with HH according to its severity. METHODS: We conducted a retrospective cohort of adults hospitalized with hypoglycemia at the Hospital Italiano de Buenos Aires between 2013 and 2018. Three groups of hypoglycemia were defined: mild (glycemia between 70 and 54 mg/dl), severe (glycemia < 54 mg/dl and = 40 mg/dl) and critical (glycemia < 40mg/dl). RESULTS: A total of 5994 patients had HH, the majority presented mild hypoglycemia (72%). Severe and critical hypoglycemia, compared with mild hypoglycemia, were associated with higher mortality: OR 2.6 (95%CI 2.2-3.1) and 4.2 (95%CI 3.5-5.0) respectively; and increased hospitalization in critical care areas: OR 1.6 (95%CI 1.4-1.9) and 3.2 (95%CI 2.6-4.0) respectively. There were no differences in length of stay. DISCUSSION: This information provides, in our country, evidence on the prognostic value of hypoglycemia, whose greater severity is associated with increased hospitalization in critical areas and higher hospital mortality.

Introducción: La hipoglucemia hospitalaria (HH) es un problema importante ya que se vincula a muerte hospitalaria, estadía prolongada y mayores costos, en personas con y sin diabetes, en área crítica y sala general, sobre todo en los casos de hipoglucemia grave. El objetivo de nuestro trabajo fue comparar la mortalidad hospitalaria, pase a área crítica y tiempo de internación en adultos con HH, según la gravedad de la misma. Métodos: Se realizó un estudio de cohorte retrospectiva en pacientes adultos internados con hipoglucemia en el Hospital Italiano de Buenos Aires entre 2013 y 2018. Se definieron tres grupos de hipoglucemia: leve (glucemia entre 70 y 54 mg/dl), grave (glucemia < 54 mg/dl = 40 mg/dl) y crítica (glucemia < 40mg/dl). Resultados: Un total de 5994 pacientes tuvieron HH, la mayoría presentó hipoglucemia leve (72%). La hipoglucemia grave y la crítica, comparadas con la hipoglucemia leve se asociaron a una mayor mortalidad: OR 2.6 (IC95% 2.2-3.1) y 4.2 (IC95% 3.5-5.0) respectivamente; y a mayor internación en áreas de cuidados críticos: OR 1.6 (IC95% 1.4-1.9) y 3.2 (IC95% 2.6-4.0) respectivamente. No hubo diferencias en el tiempo de internación. Discusión: Esta información aporta evidencia en nuestro país, sobre el valor pronóstico de la hipoglucemia, cuya mayor gravedad se asocia a mayor internación en áreas críticas y mayor mortalidad hospitalaria.

Reliability and Observer Dependence of Signs of Neonatal Hypoglycemia.

OBJECTIVES: To evaluate, using video documentation, the sensitivity, specificity, and interobserver reliability of visualizable signs of neonatal hypoglycemia at different glucose concentrations in neonates. STUDY DESIGN: In a prospective cohort study of 145 neonates with and without risk factors for hypoglycemia, 430 videos were recorded before blood glucose measurements and analyzed by 10 blinded investigators of different professions. The primary outcome measures were sensitivity and specificity for clinical detection of hypoglycemia. RESULTS: The overall sensitivity to detect low blood glucose (<55 mg/dL [<3.1 mmol/L]) based on signs was 30%, and the specificity was 82%. Significantly more investigators suspected hypoglycemia while viewing videos of infants with blood glucose levels of 46-54 mg/dL (2.6-3.0 mmol/L) and 30-45 mg/dL (1.7-2.5 mmol/L) compared with ≥55 mg/dL (≥3.1 mmol/L) (29 ± 3% and 31 ± 4% vs 18 ± 1%; P = .001; P = .007). After 48 hours of life, significantly more investigators suspected hypoglycemia in videos of infants with blood glucose levels of ≤45 mg/dL (≤2.5 mmol/L) compared with blood glucose levels of >45 mg/dL (>2.5 mmol/L) (28.9 ± 8.1% vs 10.9 ± 1.8%; P = .007). For blood glucose levels 30-45 mg/dL (1.7-2.5 mmol/L), sensitivity varied widely between investigators, ranging from 5% to 62%. Three hypoglycemic episodes <30 mg/dL (<1.7 mmol/L) were only partially recognized. CONCLUSIONS: Clinical observation of signs is neither sensitive nor specific to detect neonatal hypoglycemia, and there are large interobserver differences. Thus, guidelines on neonatal hypoglycemia should reconsider whether distinguishing between asymptomatic and symptomatic hypoglycemia provides useful information for the management of neonatal hypoglycemia, because it may pose a risk for systematic under-recognition and undertreatment, leading to an increased risk for neurodevelopmental impairment. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00021500 www.drks.de/drks_web/setLocale_EN.do.

Study on the changes of blood glucose in hemodialysis patients with diabetes.

OBJECTIVE: The aims of this study were to observe the regularity of blood glucose changes in hemodialysis patients with diabetes, time of onset of hypoglycemia and blood glucose level during dialysis, and to explore the sensitive early warning indicators of hypoglycemia in dialysis patients. BACKGROUND: Diabetes patients have a high incidence of hypoglycemia during hemodialysis. METHODS: A total of 124 maintenance hemodialysis patients with diabetes were selected for this study. Before dialysis, one, two, and three h after dialysis, and when hypoglycemia symptoms occurred, the blood glucose changes were monitored, the blood glucose drop range was observed when hypoglycemia symptoms occurred, and the correlation between the two was analyzed. RESULTS: After the start of the dialysis, the patient's blood glucose showed a downward trend. The symptoms of hypoglycemia were most obvious within one-two hours, with an incidence rate of 57.9%. When the blood glucose drop percentage reached 37.7%, the specificity and sensitivity of early warning hypoglycemia symptoms were 84.6 and 73%, respectively. CONCLUSIONS: For hemodialysis patients with diabetes, attention should be paid to the symptoms of hypoglycemia during dialysis, and blood glucose should be monitored before dialysis and after 1-2 h of dialysis. If the blood glucose drop percentage is greater than 37.7%, the timely measures should be taken.

Study on the changes of blood glucose in hemodialysis patients with diabetes

SUMMARY OBJECTIVE: The aims of this study were to observe the regularity of blood glucose changes in hemodialysis patients with diabetes, time of onset of hypoglycemia and blood glucose level during dialysis, and to explore the sensitive early warning indicators of hypoglycemia in dialysis patients. BACKGROUND: Diabetes patients have a high incidence of hypoglycemia during hemodialysis. METHODS: A total of 124 maintenance hemodialysis patients with diabetes were selected for this study. Before dialysis, one, two, and three h after dialysis, and when hypoglycemia symptoms occurred, the blood glucose changes were monitored, the blood glucose drop range was observed when hypoglycemia symptoms occurred, and the correlation between the two was analyzed. RESULTS: After the start of the dialysis, the patient's blood glucose showed a downward trend. The symptoms of hypoglycemia were most obvious within one-two hours, with an incidence rate of 57.9%. When the blood glucose drop percentage reached 37.7%, the specificity and sensitivity of early warning hypoglycemia symptoms were 84.6 and 73%, respectively. CONCLUSIONS: For hemodialysis patients with diabetes, attention should be paid to the symptoms of hypoglycemia during dialysis, and blood glucose should be monitored before dialysis and after 1-2 h of dialysis. If the blood glucose drop percentage is greater than 37.7%, the timely measures should be taken.

Hígado agudo graso del embarazo: reporte de caso / Acute fatty liver of pregnancy: case report

El hígado graso del embarazo es una patología poco frecuente en la especialidad obstétrica, cuyo diagnóstico se realiza basado en los criterios de Swansea, muchas veces es un diagnóstico que se realiza por exclusión; usualmente se presenta entre las semanas 30 y 35 del embarazo, y la cura definitiva se realiza con la interrupción expedita del mismo; con una tasa de recuperación casi del 100% si se realiza la interrupción oportuna y una tasa de mortalidad materno fetal actual del 10%. Es importante estar atentos a la ganancia ponderal de la embarazada durante el control prenatal, la epigastralgia, y los signos clínicos asociados a hipoglicemia(AU)

Fatty liver of pregnancy is a rare pathology in obstetrics, whose diagnosis is made based on the Swansea criteria, many times it is a diagnosis that is made by exclusion; It usually occurs between weeks 30 and 35, and the definitive cure is carried out with the expeditious interruption of pregnancy; with a recovery rate of almost 100% if timely interruption is made and a current maternal-fetal mortality rate of 10%. It is important to be attentive to the weight gain of the pregnant woman during prenatal control, epigastric pain, and clinical signs associated with hypoglycemia

A Graded Approach to Intravenous Dextrose for Neonatal Hypoglycemia Decreases Blood Glucose Variability, Time in the Neonatal Intensive Care Unit, and Cost of Stay.

OBJECTIVE: To determine associations between a graded approach to intravenous (IV) dextrose treatment for neonatal hypoglycemia and changes in blood glucose (BG), length of stay (LOS), and cost of care. STUDY DESIGN: Retrospective cohort study of 277 infants born at ≥35 weeks of gestation in an urban academic delivery hospital, comparing the change in BG after IV dextrose initiation, neonatal intensive care unit (NICU) LOS, and cost of care in epochs before and after a hospital protocol change. During epoch 1, all infants who needed IV dextrose for hypoglycemia were given a bolus and started on IV dextrose at 60 mL/kg/day. During epoch 2, infants received IV dextrose at 30 or 60 mL/kg/day based on the degree of hypoglycemia. Differences in BG outcomes, LOS, and cost of hospital care between epochs were compared using adjusted median regression. RESULTS: In epoch 2, the median (IQR) rise in BG after initiating IV dextrose (19 [10, 31] mg/dL) was significantly lower than in epoch 1 (24 [14,37] mg/dL; adjusted ß = -6.0 mg/dL, 95% CI -11.2, -0.8). Time to normoglycemia did not differ significantly between epochs. NICU days decreased from a median (IQR) of 4.5 (2.1, 11.0) to 3.0 (1.5, 6.5) (adjusted ß = -1.9, 95% CI -3.0, -0.7). Costs associated with NICU hospitalization decreased from a median (IQR) $14 030 ($5847, $30 753) to $8470 ($5650, $19 019) (adjusted ß = -$4417, 95% CI -$571, -$8263) after guideline implementation. CONCLUSIONS: A graded approach to IV dextrose was associated with decreased BG lability and length and cost of NICU stay for infants with neonatal hypoglycemia.

Alternative Cerebral Fuels in the First Five Days in Healthy Term Infants: The Glucose in Well Babies (GLOW) Study.

OBJECTIVES: To determine plasma lactate and beta-hydroxybutyrate (BHB) concentrations of healthy infants in the first 5 days and their relationships with glucose concentrations. STUDY DESIGN: Prospective masked observational study in Hamilton, New Zealand. Term, appropriately grown singletons had heel-prick blood samples, 4 in the first 24 hours then twice daily. RESULTS: In 67 infants, plasma lactate concentrations were higher in the first 12 hours (median, 20; range, 10-55 mg/dL [median, 2.2 mmol/L; range, 1.1-6.2 mmol/L]), decreasing to 12 mg/dL (range, 7-29 mg/dL [median, 1.4 mmol/L; range, 0.8-3.3 mmol/L]) after 48 hours. Plasma BHB concentrations were low in the first 12 hours (median, 0.9 mg/dL; range, 0.5-5.2 mg/dL [median, 0.1 mmol/L; range, 0.05-0.5 mmol/L]), peaked at 48-72 hours (median, 7.3 mg/dL; range, 1.0-25.0 mg/dL [median, 0.7 mmol/L; range, 0.05-2.4 mmol/L]), and decreased by 96 hours (median, 0.9 mg/dL; range, 0.5-16.7 mg/dL [median, 0.1 mmol/L; range, 0.05-1.6 mmol/L]). Compared with infants with plasma glucose concentrations above the median (median, 67 mg/dL [median, 3.7 mmol/L]), those with lower glucose had lower lactate concentrations in the first 12 hours and higher BHB concentrations between 24 and 96 hours. Lower interstitial glucose concentrations were also associated with higher plasma BHB concentrations, but only if the lower glucose lasted greater than 12 hours. Glucose contributed 72%-84% of the estimated potential adenosine triphosphate throughout the 5 days, with lactate contributing 25% on day 1 and BHB 7% on days 2-3. CONCLUSIONS: Lactate on day 1 and BHB on days 2-4 may contribute to cerebral fuels in healthy infants, but are unlikely to provide neuroprotection during early or acute hypoglycemia. TRIAL REGISTRATION: The Australian and New Zealand Clinical Trials Registry: ACTRN12615000986572.

Impact of Maternal HbA1c Levels ≤6% and Race in Nondiabetic Pregnancies on Birthweight and Early Neonatal Hypoglycemia.

OBJECTIVE: To evaluate whether pregnancy glycated hemoglobin (HbA1c) levels of ≤6% and maternal race impacts neonatal hypoglycemia and birthweight, and whether diabetes and beta blocker use during pregnancy additively impacts neonatal outcomes. STUDY DESIGN: Retrospective chart review of 4769 infants born at ≥34 weeks; 21 482 glucose measurements were assessed. Predefined groups were infants born to mothers without documented pregnancy conditions (group N), prenatal exposure of beta blockers (group B), diabetes (group D), or both (group DB). RESULTS: In group N, both in Caucasian (Caucasian, n = 1756; ß = 2.6, P < .001) and African American (n = 1872; ß = 2.2, P = .002) race, there was a direct relationship between pregnancy HbA1c levels and birthweight. HbA1c (aOR 1.8; 95% CI [1.3-2.5]) levels, maternal race, prematurity, cesarean delivery, and birth weight predicted hypoglycemia. Each 0.1% increase in HbA1c levels between 4.8 and 6 increased the odds of neonatal hypoglycemia by 6.4% in African American (ß 0.62, SE 0.22, P = .01) and by 12.0% in Caucasian (ß 1.13, SE 0.23 P < .001) population. The odds of neonatal hypoglycemia were 1.7 (group B), 2.1 (group D), and 3.1 (group DB) times higher compared with group N. CONCLUSIONS: Pregnancy HbA1c levels between 4.8% and 6.0% considered acceptable during pregnancy impacts neonatal hypoglycemia and birthweight especially in Caucasian race. A third trimester HbA1c >5.2 is a potential risk factor for neonatal hypoglycemia, especially in preterm infants. Although we report new findings on the relationship between maternal HbA1c levels and neonatal outcomes, a prospective study is required to validate our findings and determine "optimal" HbA1C levels during pregnancy.

Awareness of hypoglycemia and spectral analysis of heart rate variability in type 1 diabetes.

AIMS: To investigate the relationship of unawareness of hypoglycemia with spectral analysis of heart rate variability (HRV) and clinical variables in type 1 diabetes (T1D) individuals. METHODS: Participants with type 1 diabetes mellitus (type 1 diabetes) were prospectively assessed for hypoglycemia awareness using the Pedersen-Bjergaard method and were classified as normal hypoglycemia awareness, impaired hypoglycemia awareness and hypoglycemia unawareness. Indices of HRV in frequency domain were evaluated and Ewing tests were used for the diagnosis of cardiovascular autonomic neuropathy (CAN). RESULTS: Ninety-eight participants with T1D (mean age 26 years, average diabetes duration 13 years, and mean HbA1c 8.4%) were included in this study. The prevalence of hypoglycemia unawareness was 28%. No significant difference was observed on the prevalence of CAN among groups of different hypoglycemia awareness (p = 0.740). On regression analyses, abnormal results of HRV in frequency domain were not associated with unawareness of hypoglycemia. On univariable regression analysis, age, diabetes duration and estimated creatinine clearance were associated with unawareness of hypoglycemia. CONCLUSION: CAN as assessed by Ewing tests and spectral analysis of HRV is not associated with unawareness of hypoglycemia. There is association of age, diabetes duration and renal deficit with unawareness of hypoglycemia.

Is biochemical hypoglycemia necessary during an insulin tolerance test?

Objective The insulin tolerance test (ITT) has been accepted as the gold standard test for assessing the integrity of the growth hormone (GH) - insulin-like growth factor (IGF-1) axis and the hypothalamic-pituitary-adrenal (HPA) axis. The goal of the test is to achieve clinical and biochemical hypoglycemia at a blood glucose level ≤ 40 mg/dL to effectively and correctly assess the HPA and GH-IGF-1 axes. In this study, the GH and cortisol responses of patients who achieved and failed to achieve biochemical hypoglycemia during an ITT were compared. Subjects and methods One hundred thirty-five patients with pituitary disorders were included in the study. Samples for blood glucose levels were obtained after clear symptoms of clinical hypoglycemia developed. The patients were enrolled in the hypoglycemic and nonhypoglycemic groups according to whether their plasma glucose level ≤ 40 mg/dL or > 40 mg/dL during an ITT, and the groups were compared in terms of their GH and cortisol responses. Results The mean age, body mass index and waist circumference of the two patient groups were found to be similar. The mean blood glucose level was significantly lower in the hypoglycemic group than in the nonhypoglycemic group (19.3 and 52.0 mg/dL, respectively). When the two groups were compared in terms of peak cortisol and GH responses, no statistically significant differences were found. Conclusion The data presented suggest that clinically symptomatic hypoglycemia is as effective as biochemically confirmed hypoglycemia during an ITT. Arch Endocrinol Metab. 2020;64(1):82-8.

Is biochemical hypoglycemia necessary during an insulin tolerance test?

ABSTRACT Objective The insulin tolerance test (ITT) has been accepted as the gold standard test for assessing the integrity of the growth hormone (GH) - insulin-like growth factor (IGF-1) axis and the hypothalamic-pituitary-adrenal (HPA) axis. The goal of the test is to achieve clinical and biochemical hypoglycemia at a blood glucose level ≤ 40 mg/dL to effectively and correctly assess the HPA and GH-IGF-1 axes. In this study, the GH and cortisol responses of patients who achieved and failed to achieve biochemical hypoglycemia during an ITT were compared. Subjects and methods One hundred thirty-five patients with pituitary disorders were included in the study. Samples for blood glucose levels were obtained after clear symptoms of clinical hypoglycemia developed. The patients were enrolled in the hypoglycemic and nonhypoglycemic groups according to whether their plasma glucose level ≤ 40 mg/dL or > 40 mg/dL during an ITT, and the groups were compared in terms of their GH and cortisol responses. Results The mean age, body mass index and waist circumference of the two patient groups were found to be similar. The mean blood glucose level was significantly lower in the hypoglycemic group than in the nonhypoglycemic group (19.3 and 52.0 mg/dL, respectively). When the two groups were compared in terms of peak cortisol and GH responses, no statistically significant differences were found. Conclusion The data presented suggest that clinically symptomatic hypoglycemia is as effective as biochemically confirmed hypoglycemia during an ITT. Arch Endocrinol Metab. 2020;64(1):82-8

Glucose Homeostasis in Newborns: An Endocrinology Perspective.

Physiologic adaptations in the postnatal period, along with gradual establishment of enteral feeding, help maintain plasma glucose concentrations in the neonatal period. The definition of normal plasma glucose in the neonatal period has been a subject of debate because of a lack of evidence linking a set plasma or blood glucose concentration to clinical symptoms or predictors of short- and long-term outcomes. However, there is consensus that maintaining plasma glucose in the normal range for age is important to prevent immediate and long-term neurodevelopmental consequences of hypoglycemia or hyperglycemia. The specific management strategy for abnormal glucose levels in neonates depends on the underlying etiology, and interventions could include nutritional changes, medications, hormone therapy, or even surgery. Here, we will review the physiological processes that help maintain plasma glucose in newborns and discuss the approach to a newborn with disordered glucose homeostasis, with an emphasis on the endocrine basis of abnormal glucose homeostasis.