The Research on Perioperative Blood Glucose and Insulin Levels of Patients with Single Insulinoma

Background The blood glucose level is an important biochemical parameter for evaluating the resection effectiveness of insulinomas. However, whether other biochemical parameters have better evaluating ability remains unclear. The current study aims to compare the evaluating capability of blood glucose and insulin levels at several aspects, such as the accuracy and response time. Methods Between September 2017 and July 2018, 21 insulinoma patients with single tumor who underwent surgical resection were enrolled. Peripheral venous blood samples were assayed for blood glucose and insulin levels on the day of surgery and at 30 minutes, 60 minutes, 1 day, and 7 days after surgery. The evaluating abilities of blood glucose and insulin levels for resection effectiveness were recorded and compared. Results The evaluating performance of the insulin level was better than that of the blood glucose level (100% for 21 patients vs 82.4% for 17 patients), as well as the response time ( p<0.0001). Furthermore, the insulin level was not effected by intravenous glucose infusion compared to the blood glucose level. Conclusions Comparing with blood glucose level, insulin level is a better parameter for evaluating resection effectiveness of insulinomas with faster response and regardless of perioperative intravenous glucose infusion.

The glucose infusion rate of parenteral nutrition in the first week of life in preterm infants: an observational study

Background Most preterm infants require a continuous glucose infusion in the early postnatal period due to the interruption of the transplacental glucose supply after birth to promote better neurodevelopmental outcomes. Aims To investigate the glucose infusion rate (GIR) on parenteral nutrition (PN) in the first week of life administered in preterm infants and its effect on neonatal morbidity and mortality. Methods This study included 97 infants aged < 37 gestational weeks and weighed < 2500 g at birth. Infants recruited in this study were classified into 3 groups based on the GIR usage in parenteral nutrition as follows: GIR usage of 5- < 7 g/kg/day (Group I), GIR usage of 7–13 g/kg/day (Group II), and GIR usage of > 13–15 g/kg/day (Group III). Univariate and multivariate logistic regression analyzes were carried out to investigate whether the GIR usage in the three groups was associated with selected neonatal morbidities and mortality. Neonatal morbidities analyzed included respiratory distress syndrome (RDS), necrotizing enterocolitis, sepsis, retinopathy of prematurity, pulmonary hypertension, hypoglycemia, and hyperglycemia. Result Of 97 preterm infants included, 51.5% infants had a gestational age of 34- < 37 weeks, and 54.6% infants had a birth weight of 1500- < 2500 g. The multivariate logistic regression analysis showed that the GIR usage of 5- < 7 g/kg/day was an independent variable that significantly increased the risk of hypoglycemia (Adjusted Odds Ratio [AOR] = 4.000, 95% Confidence Interval [CI] = 1.384–11.565, P = 0.010) and reduced the risk of sepsis (AOR = 0.096, 95% CI = 0.012–0.757, P = 0.026). The GIR usage in all three groups did not increase the risk of mortality. For neonatal morbidity analyzed in this study, RDS (AOR = 5.404, 95%CI = 1.421–20.548, P = 0.013) was an independent risk factor of mortality. Conclusion The GIR usage of < 7 g/kg/day in PN in the first week of life administered to preterm infants was an independent variable in increasing hypoglycemia, but in contrast, reducing the risk of sepsis.

Two Weeks High Glucose is Enough to Induce Liver and Gut Lesion

Background:High glucose is critical for diabetes.But in which way it induces diabetes, and which organ trigger the formation of diabetes are not clear.The goal of this study is to see if there is a risk of acquiring diabetic symptoms following a 2 weeks short infusion of 2g/kg/day and dietary 2.5g/kg/day in SD rats on various body organs.Methods：Twelve weeks old SD rats were randomly divided into control group,high glucose infusion group(IHG,infusion 2g/kg/day) and oral high glucose group OHG,dietary 2.5g/kg/day).Fasten blood sugar,TNF-a and IL-6 were measured. Intestine and liver samples were collected for pathological examination.Feces of rats were collected for gut microbiota tests.Results：The results indicated that short time high glucose induced hyperglycemia lasted for at least 2 weeks after ceasing of high glucose.It increased serum levels of IL-6 and TNF-a obviously.It led to jejunum mucosa injury, obvious steatosis of hepatocytes, and disturbed the balance of gut microbiota.OHG led to swelling and necrosis of individual intestinal villi.IHG led to necrosis and disappearence of cells in the upper layer of intestinal mucosa.The lesion was confined to the mucosa.Conclusions:Short time high glucose induced lesion in liver and intestine,disturbed the balance of gut microbiota and consequently induced inflammation and triggered diabetes.

Management of asymptomatic hypoglycemia with 40% oral dextrose gel in near term at-risk infants to reduce intensive care need and promote breastfeeding

Background Neonatal hypoglycemia is a common disorder especially in at-risk infants and it can be associated with poor long-term neurological outcomes. Several therapeutic interventions are suggested, from the implementation of breastfeeding to the glucose intravenous administration. Oral dextrose gel massaged into the infant’s inner cheek is a recent treatment option of asymptomatic hypoglycemia, after which oral feeding is encouraged. This approach seems to reduce the admission of infants to neonatal intensive care unit (NICU) so favouring maternal bonding and breastfeeding success at discharge. Methods In our ward, we prospectively compared a group of near-term neonates, (Gr2, n = 308) at risk for hypoglycemia, treated with an innovative protocol based on the addition of 40% oral dextrose gel (Destrogel, Orsana®,Italy) administered by massaging gums and cheek with historical matching newborns (Gr1, n = 389) treated with a formerly used protocol, as control group. The primary outcome was occurrence of NICU admission and the requirement of intravenous glucose administration; while discharge with full breastfeeding was the secondary outcome. Results In Gr1, 39/389 (10%) infants presented with asymptomatic hypoglycemia, 19/39 were transferred to the NICU, and 14/39 required intravenous glucose treatment. In Gr2, among the 30/308 infants with asymptomatic hypoglycemia managed according to the new protocol, 3/30 were transferred to the NICU and received intravenous glucose infusion. The mean duration of hospitalization respectively was 6.43 (± 6.36) and 3.73 ± 1.53 days (p < 0.001). At discharge, 7.7% of the infants in Gr1 and 30% of the infants in Gr2 were exclusively breastfed (p = 0.02). Considering Gr1 vs Gr2, the number of patients that were transferred to NICU was 19 (48.7%) vs 3 (10%) (p = 0.001) and the number of infants that needed intravenous glucose infusion was 14 (35.9%) vs 3 (10%) (p = 0.01), respectively. Conclusions In our population of near term infants, the introduction of 40% oral dextrose gel to the protocol, helped in the safe management of asymptomatic hypoglycemia and, at the same time, implemented breastfeeding.

Similar pharmacokinetics and pharmacodynamics of a new biosimilar and reference insulin aspart in healthy Chinese males

Insulin aspart (IAsp) is one of the main therapies used to control blood glucose after a meal. This study aimed to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of 2 rapid-acting IAsp products: a new IAsp biosimilar (RD10046) and NovoRapid. In a single-center, randomized, single-dose, 2-period, crossover, euglycemic clamp study (registry number: CTR20180517, registration date: 2018-05-30), healthy Chinese males were randomized to receive 0.2 U/kg of the IAsp biosimilar RD10046 and NovoRapid under fasted conditions on two separate occasions. PK and PD were assessed for up to 10 h. Of the 30 randomized subjects, all 30 completed both treatment periods. The PK (area under the curve [AUC] of total IAsp; maximum observed IAsp concentration [Cmax]) and PD (maximum glucose infusion rate [GIRmax]; total glucose infusion during the clamp [AUCGIR,0–10h]) were similar between the new IAsp biosimilar RD10046 and NovoRapid. In all cases, the 90% CIs for the ratios of the geometric means were completely contained in the prespecified acceptance limits of 0.80–1.25. No hypoglycemic events, allergic reactions, or local injection adverse reactions occurred in this trial. We concluded that the studied IAsp biosimilar (RD10046) was bioequivalent to NovoRapid.

‘” Hyper-Warburg“ Phenomenon - A Rare Complication

Background: Malignant cells rewire metabolism to promote growth and survival through fermentation of glucose to lactate known as Warburg phenomenon; this process occurs even in aerobic conditions. To produce enough ATP the cells must increase the rate of glucose uptake. We report a fatal case of severe hypoglycemia and progressive lactic acidosis in a patient with lymphoma thought to be from Hyper-Warburgism. Case: 57-year-old male with no past medical history presented with diarrhea, abdominal cramping, nausea, vomiting of 1-week duration. At presentation he was hemodynamically stable except for mild tachycardia. Biochemical evaluation showed normal renal function, glucose of 115 mg/dl, sodium of 126 mmol/dL, mild leukocytosis and anemia. CT scan of the abdomen and pelvis showed large retroperitoneal mesenteric portacaval and periportal nodes, biopsy of which revealed CD 30 + T- cell lymphoma. He was discharged with outpatient oncology follow up but re-presented within 1 week with weakness. He was noted to be hypoglycemic with a serum glucose of 55 mg/dl, which was corrected with D50. Laboratory work up showed anemia, mild leukocytosis. Lactic acid was elevated at 5 mmol/dl (0.5–2.2). Chest X ray showed increased peri-hilar markings and he was admitted for presumed sepsis secondary to community acquired pneumonia. Throughout the hospitalization he had persistent hypoglycemia with a serum glucose as low as 33 mg/dl but with only mild neurocognitive symptoms. He was started on a continuous glucose infusion up to 20 g/hr with no significant improvement of the hypoglycemia. He was started on stress dose steroids again without much improvement. Lab evaluation to rule out insulin mediated hypoglycemia was limited an IGF level 1.3 mcg/ml (3.4–6.9), insulin level 2.4 uIU/ml (2.5- 25) with a corresponding serum glucose of 119 mg/dl. He had negative urine and blood cultures. Lactate level continued to increase throughout the hospitalization to as high as 11.3 mmol/dl with the continuous glucose infusion. He unfortunately suffered a cardiac arrest and passed away. Discussion: Warburg phenomenon is an adaptive form of metabolism where malignant cells utilize glucose via the glycolytic pathway irrespective of the oxygen content. This process requires increased glucose uptake to sustain energy production and, in some cases, can result in clinically asymptomatic hypoglycemia and concurrent lactic acidosis. Infusions of dextrose are thought to ‘feed’ the cycle. This severe complication is very rare and associated more commonly with lymphoproliferative disorders as demonstrated in this case. Hypoglycemia and lactic acidosis has been shown to improve only after institution of chemotherapy for treatment of the underlying malignancy. It is important to maintain a high index of suspicion as this cause of hypoglycemia has important therapeutic implications.

Determining insulin sensitivity from glucose tolerance tests in Iberian and landrace pigs

As insulin sensitivity may help to explain divergences in growth and body composition between native and modern breeds, metabolic responses to glucose infusion were measured using an intra-arterial glucose tolerance test (IAGTT). Iberian (n = 4) and Landrace (n = 5) barrows (47.0 ± 1.2 kg body weight (BW)), fitted with a permanent carotid artery catheter were injected with glucose (500 mg/kg BW) and blood samples collected at -10, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120 and 180 min following glucose infusion. Plasma samples were analysed for insulin, glucose, lactate, triglycerides, cholesterol, creatinine, albumin and urea. Insulin sensitivity indices were calculated and analysed. Mean plasma glucose, creatinine and cholesterol concentrations were lower (P < 0.01) in Iberian (14, 68 and 22%, respectively) than in Landrace pigs during the IAGTT. However, mean plasma insulin, lactate, triglycerides and urea concentrations were greater (P < 0.001) in Iberian (50, 35, 18 and 23%, respectively) than in Landrace pigs. Iberian pigs had larger area under the curve (AUC) of insulin (P < 0.05) or tended to a greater AUC of lactate (P < 0.10), and a smaller (P < 0.05) AUC for glucose 0-60 min compared with Landrace pigs. Indices for estimating insulin sensitivity in fasting conditions indicated improved β-cell function in Iberian compared with Landrace pigs, but no difference (P > 0.10) in calculated insulin sensitivity index was found after IAGTT between breeds. A time response (P < 0.05) was obtained for insulin, glucose and lactate so that maximum concentration was achieved at 10 and 15 min post-infusion for insulin (Iberian and Landrace pigs, respectively), immediately post-infusion for glucose, and 20 min post-infusion for lactate, decreasing thereafter until basal levels. There was no time effect for the rest of metabolites evaluated. In conclusion, growing Iberian pigs challenged with an IAGTT showed changes in biochemical parameters and insulin response that may indicate an early stage of insulin resistance.