Oral Glucose Administration Research Articles

Ipomoea batatas and Agarics blazei ameliorate diabetic disorders with therapeutic antioxidant potential in streptozotocin-induced diabetic rats

Ipomoea batatas, Agaricus blazei and Smallanthus sonchifolius are known to favorably influence diabetes mellitus. To clarify their antidiabetic efficacy and hypoglycemic mechanisms, we treated streptozotocin-induced diabetic rats with daily oral feeding of powdered Ipomoea batatas (5 g kg−1 d−1), Agaricus blazei (1 g kg−1 d−1) or Smallanthus sonchifolius (4 g kg−1 d−1) for 2 months. Treatments with Ipomoea batatas or Agaricus blazei, but not Smallanthus sonchifolius, significantly suppressed the increases of fasting plasma glucose and hemoglobin A1c levels, and restored body weight loss during diabetes. Serum insulin levels after oral glucose administration tests increased along the treatments of Ipomoea batatas or Agaricus blazei. Moreover, Ipomoea batatas and Agaricus blazei reduced superoxide production from leukocytes and vascular homogenates, serum 8-oxo-2'-deoxyguanosine, and vascular nitrotyrosine formation of diabetic rats to comparable levels of normal control animals. Stress- and inflammation-related p38 mitogen-activated protein kinase activity and tumor necrosis factor-α production of diabetic rats were significantly depressed by Ipomoea batatas administration. Histological examination also exhibited improvement of pancreatic β-cells mass after treatments with Ipomoea batatas or Agaricus blazei. These results suggest that hypoglycemic effects of Ipomoea batatas or Agaricus blazei result from their suppression of oxidative stress and proinflammatory cytokine production followed by improvement of pancreatic β-cells mass.

Exercise-Induced Hypoglycemic Hemiplegia in a Child with Type 1 Diabetes: A Rare Find with Multiple Potential Causative Mechanisms

A 10-year-old boy known to have type 1 diabetes presented to the emergency department with history of sudden onset of right-sided hemiplegia after exercise. He did not respond to oral glucose administration, but had an almost immediate resolution of symptoms with intravenous bolus of dextrose. Hemiplegic hypoglycemia is a rare complication in diabetic children, mostly affects the right side of the body, and is rarely recurrent. Children have normal brain imaging and angiography testing, and electroencephalogram may show slow-wave activity. The recovery takes place within 24 hours, and the prognosis is excellent with no focal neurological deficits noted. Our patient responded within minutes to intravenous dextrose, which is unusual and has not been reported previously. The mechanisms leading to development of hypoglycemic hemiplegia are unclear, but may involve effects of hypoglycemia on intracellular signaling pathways or molecules on motor neurons, as recent studies have shown normal brain cell glucose uptake and metabolism in hypoglycemia. While hypoglycemic hemiplegia is rare, it is a frightening experience to caregivers, and efforts should concentrate on its prevention by preventing hypoglycemia.

Effects of heat exposure on Akt/S6K1 signaling and expression of genes related to protein and energy metabolism in chicken (Gallus gallus) pectoralis major muscle

In order to improve understanding of the heat-induced changes in muscle growth, we determined the expression of genes related to protein and energy metabolism in the pectoralis major muscle of chickens. We also explored the protein kinase B (PKB also called Akt)/p70 S6 kinase (S6K1)/S6 pathway that mediates anabolic signals thereby regulating metabolism and hypertrophic/atrophic balance. Four-week-old chickens were exposed to 32 or 22 degrees C for 1 week. Chickens from both groups were then fasted for 16 h or left fed, and submitted to an oral administration of glucose-arginine to induce an anabolic response (30-min treatment) or left untreated. High ambient temperature and the associated decrease in feed intake modified the expression of certain energy-related genes (e.g. -40% for PGC-1alpha) and protein metabolism (e.g. about +80% for atrogin-1), but the expression of several muscle metabolism-related genes considered here was unchanged. The capacity for muscle protein synthesis, i.e. RNA/protein ratio, was reduced in warm conditions (approximately -20%). Slightly lower activation of S6 induced by glucose-arginine treatment was found at 32 degrees C compared to 22 degrees C, which might indicate somewhat lower efficiency of mRNA translation. Analysis of glucose/insulin balance suggested changes in glucose metabolism under heat exposure. However, this remains to be characterized.

β-Conglycinin Lowers Very-Low-Density Lipoprotein-Triglyceride Levels by Increasing Adiponectin and Insulin Sensitivity in Rats

The relationship between insulin sensitivity and the plasma triglyceride-lowering effect induced by beta-conglycinin was investigated. Male Wistar rats (19 weeks old) were fed diets containing casein, soy protein isolate, or beta-conglycinin for 4 weeks. In oral glucose administration, the beta-conglycinin-fed rats showed a significant decrease in the area under the glucose curve (0-60 min) as compared with the casein-fed rats. The hypoglycemic effect was significantly higher in the beta-conglycinin-fed rats than in the casein-fed rats at 30 min after intraperitoneal insulin injection. The liver sterol regulatory element-binding-protein-1 mRNA expression level was significantly lower and the plasma adiponectin concentration was significantly higher in the beta-conglycinin-fed rats than in the casein-fed rats. The hypotriglyceridemic effect of beta-conglycinin depended on a significant decrease in the concentration of very-low-density-lipoprotein triglycerides. These results indicate that beta-conglycinin increases adiponectin levels and improves glucose tolerance. The ability of beta-conglycinin to lower plasma lipid levels might be due to increased insulin sensitivity of the liver.

Effect Of Glucose Intake On Blood Glucose And Tissue Glycogen Levels In Hypoxia Exposed Rats

PURPOSE: This study was aimed to examine the effect of glucose intake on blood glucose and heart, liver and skeletal muscle glycogen levels with 14% normobaric systemic hypoxia exposure in rats. METHODS: Eighty SD rats were divided into 10 groups such as, fasting hypoxia 0 min (FH-0, n=8), fasting hypoxia 30 min (FH-30, n=8), fasting hypoxia 60 min (FH-60, n=8), fasting hypoxia 120 min (FH-120, n=8), fasting hypoxia 240 min (FH-240, n=8), oral glucose hypoxia 0 min (GH-0, n=8), oral glucose hypoxia 30 min (GH-30, n=8), oral glucose hypoxia 60 min (GH-60, n=8), oral glucose hypoxia 120 min (GH-120, n=8), and oral glucose hypoxia 240 min (GH-240, n=8). RESULTS: The blood glucose concentration was significantly increased in fasting hypoxia 30 min compared to FH-0 min (FH-0 = 67.67±5.28 mg/dl<FH-30 = 83.86±2.93 mg/dl). No effect on red, white gastrocnemius muscles and liver glycogen levels in the fasting hypoxia group at all time points. However, heart glycogen levels were significantly (p<0.05) increased in fasting hypoxia group after 30min (FH-30=41.86±3.07 μmol/g) and 240min (FH-240=40.48±1.40 μmol/g) when compared to zero min (FH-0 32.26±2.84 μmol/g). After oral glucose administration red gastrocnemius and heart glycogen levels were significantly increased at 240min (GH-0=31.03±4.74 μmol/g < GH-240=44.87±1.10 μmol/g; GH-0=34.36±2.44 μmol/g < GH-240=58.63±6.16 μmol/g, respectively), but no effect in white gastrocnemius muscle glycogen levels. Liver glycogen levels were increased at 60, 120 and 240min (GF-60=75.92±8.51 μmol/g, GF-120=88.32±12.99 μmol/g, GF-240=96.99±12.81 μmol/g) after oral glucose intake compared that of zero min. CONCLUSIONS: Hypoxia under fasting condition increase heart glycogen levels. Hypoxia along with oral glucose intake induces liver glycogen response faster than heart and oxidative red gastrocnemius muscle, but no effect on white gastrocnemius muscle.

Antenatal oral glucose-tolerance test values and pregnancy outcomes

AbstractObjectiveThe aim of the present study was to explore the impact of individual blood glucose values (n = 4; i.e. fasting and 1, 2 and 3 h following oral glucose administration) obtained during antenatal oral glucose-tolerance testing, together with two different sets of criteria used for diagnosis of gestational diabetes mellitus (GDM) — Carpenter and Coustan Criteria (CCC) and National Diabetes Data Group (NDDG) criteria — in predicting pregnancy outcomes and maternal insulin need.SettingAl Ain Hospital, United Arab Emirates.MethodThis observational uncontrolled cohort study gained its study subjects from a randomised, controlled, longitudinal, prospective clinical trial performed at Al Ain Hospital, Al Ain, United Arab Emirates. The eligible population was made up of all women (n = 720) who participated in an early screening programme for GDM. Those who had a positive oral glucose-tolerance test (OGTT) based on CCC were included in the study (n = 165). All recruited women with GDM were followed from time of recruitment to 6months postpartum. The sources of information used were maternal and neonatal medical records and laboratory findings for women both antenatally and postnatally.ResultsThe maternal and neonatal outcomes indicated that the number of abnormally elevated antenatal OGTT values obtained during the diagnosis of GDM was significantly correlated with development of a number of pregnancy complications. Data analysis also indicated that the number of abnormal diagnostic antenatal OGTT values using CCC was significantly correlated with development of postpartum diabetes mellitus (P = 0.044) within 6months of delivery. The number of abnormal OGTT values significantly contributed to insulin need during the index pregnancy (P &amp;lt; 0.05). The CCC approach was more sensitive than the NDDG methodology for predicting the onset of GDM and a number of the associated complications.ConclusionsThe study highlighted the importance of abnormal values for antenatal OGTT in identifying the need for insulin management in women with GDM.

Insulin Inhibits and Oral Sucrose Increases Neointimal Growth after Arterial Injury in Rats

Background/Aims: In our previous studies, rats on insulin treatment (5 U/day) and oral glucose to avoid hypoglycemia had reduced neointimal growth after arterial injury. However, plasma glucose in the insulin-treated rats was lower than normal and the effect of oral glucose remained undetermined. In this study, the effects of normoglycemic hyperinsulinemia and oral glucose or sucrose were investigated in the same model. Methods: Rats were divided into 6 groups: (1) control implants and tap water; (2) insulin implants (5 U/day) and oral glucose + i.p. glucose to avoid any glucose lowering; (3) insulin implants (4 U/day) and oral glucose; (4) insulin implants (4 U/day) and oral sucrose; (5) control implants and oral glucose, and (6) control implants and oral sucrose. Results: Insulin treatment at both doses reduced neointimal area (p < 0.001) 14 days after injury in rats receiving oral glucose but not in those receiving oral sucrose. Oral glucose, without insulin, had no effect on neointimal formation, whereas oral sucrose increased neointimal growth (p < 0.05). Oral sucrose (p < 0.05) but not oral glucose decreased insulin sensitivity measured with hyperinsulinemic clamps. Conclusions: (1) Insulin decreases neointimal growth after arterial injury independent of glucose-lowering or oral glucose administration and (2) oral sucrose per se affects neointimal growth.

Prevención del Dolor en Recién Nacidos de Término: Estudio Aleatorizado Sobre Tres Métodos

ABSTRACT Pain prevention in term neonates: randomised trial for three methods Introduction: Every newborn infant is screened for hypothyroidism and phenilketonuria by blood sampling, during the first week of life, but there is not a simple and efficient method to reduce pain during the procedure. Objectives: Prospective randomized trial, to assess if the administration of oral glucose, paracetamol or EMLA, given individually, can reduce the pain caused in newborns by heel prick, in an outpatient setting. Methods: Double-blind study in which seventy six healthy newborns at term were randomly assigned to receive placebo, oral glucose, EMLA in the heel, or oral paracetamol. Heel prick was performed to get a blood sample, and pain was measured by two independent observers, using two scales (NIPS and PIPP). Results: NIPS <4: placebo (9/19 = 47%), glucose (16/19 = 84%), paracetamol (8/19 = 42% and EMLA (12/19 = 63%); PIPP < 8: placebo (9/19 = 47%), oral glucose (12/19 = 63%), paracetamol (5/19 = 26%) and EMLA (8/19 = 42%). With the use of oral glucose we found RAR: 0.37 (IC 95% 0.09-0.64), RRR: 44% (IC 95% 6-67%), NNT: 2.7 (IC 95% 1.5-11).

Effects of Moderate Intensity Physical Training in Neonatal Alloxan- Administered Rats

Newborn rats (6 days old) received alloxan intraperitoneally (A= 250 mg/kg b.w). Rats injected with vehicle (citrate buffer) were used as controls (C). After weaning, half of the animals were submitted to 1 hour/day, 5 days/week swimming and with supporting overload of 5% b.w. At 28 days, no signi fi cant differences were found among the groups in fasting glycemia and insulinemia. At 60 days, the fasting glycemia (30 min after oral glucose administration) was higher in alloxan than in controls groups and lower in the alloxan group submitted to training than in the correspondent sedentary group. The glucose tolerance of the alloxan rats was reduced in comparison to controls, both at 28 and 60 days, since the area under the blood glucose curve during the OGTT was higher in the alloxan than in the control. No difference was found among the groups both at 28 and 60 days in the HOMA index. However, a slight reduction was observed in the values of the trained groups suggesting slightly increased insulin sensitivity in the animals. These results suggest that this diabetes mellitus animal model presents interesting characteristics for the study of the role of the physical exercise in diabetes outcome.

豚へのグルコース経口給与が血漿グレリン濃度に及ぼす影響

グレリンは28個のアミノ酸残基からなるペプチドで，摂食行動とエネルギー代謝調節に関与すると考えられている。豚におけるグレリンの分泌調節機序については現在までのところ明らかにされていない。本研究では，豚へのグルコースの経口投与がグレリン分泌に及ぼす影響を検討した。6頭の交雑種（LWD）去勢雄豚に，グルコースを0，1，2および4g/kgBWの用量で経口投与した。グルコース投与後に頻回の採血を行い，血漿グレリン，インスリンおよびグルコース濃度を測定した。その結果，血漿グレリン濃度はグルコースの投与量に依存して低下した。この血漿グレリン濃度の低下は，血漿グルコースおよびインスリン濃度の上昇に伴って起こり，血漿グレリンとグルコース（相関係数r＝－0.69，P＜0.01）およびインスリン（相関係数r＝－0.59，P＜0.01）の間に負の相関がみられた。以上の結果から，豚ではグレリンの分泌抑制機序の一部に血漿グルコースあるいはインスリンの上昇が関与する可能性が示唆された。

Transient Salt Wasting in POMC-deficiency due to Infection Induced Stress

Obesity is a multifactorial disorder influenced by genetic, behavioral, environmental and cultural factors. A twelve month old male patient was admitted to the hospital because of malaise, irritability, disquietness and obesity. His BMI was 19.8 kg/m (2) and BMI SDS was 1.38. Mental development was normal, and motor skills were mildly delayed most probably due to his obesity. His physical examination was totally normal except obesity and red hair. A history of hypoglycemia on the fourth day of life, which resolved after oral glucose administration, was reported. The child had been hyperphagic from the first weeks of life and had aggressive behavior when food was denied. The body weight of the patient increased dramatically during the first year of life. Based on the clinical features and laboratory findings (the overgrowth syndrome, red hair, hypoglycemia and hypocortisolism) the patient was diagnosed as POMC deficiency and the diagnosis was confirmed by genetic studies. Hypoglycemia and apnea episodes ceased as he was put on hydrocortisone but he developed relative mineralocorticoid deficiency during a urinary tract infection. In POMC deficiency, relative mineralocorticoid deficiency should be in mind in episodes of severe stress and therapy should be initiated.

Hydroxypropylated Tapioca Starch Retards the Development of Insulin Resistance in KKAy Mice, a Type 2 Diabetes Model, Fed a High‐Fat Diet

The hypoglycemic and antidiabetic effect of hydroxypropyl tapioca starch (HPTS, degree of substitution = 0.180) was investigated in male KKAy mice. Mice were fed a purified high-fat (20%) diet without or with HPTS (5% or 10%) for 33 d. Gelatinized tapioca starch (TS) was used as a reference. Fasting blood glucose concentrations, days 14 and 28, were significantly lower in the 10% HPTS group compared with the reference. In an oral glucose tolerance test (OGTT), day 28, blood glucose concentrations in the 5% HPTS group, at 60, 90, and 120 min, and in the 10% HPTS group, at 30, 60, and 90 min after oral administration of glucose, were significantly lower compared with the reference. The area under the glucose curve (AUC) for glucose in both HPTS groups was significantly lower compared with the reference. Energy intake was significantly lower in the 10% HPTS group compared with the reference. At the end of the experiment, adiponectin concentrations were significantly higher in the 10% HPTS group compared with the reference. A homeostasis model assessment of insulin resistance (HOMA-IR) tended to be lower in the 10% HPTS group compared with the reference, whereas a quantitative insulin sensitivity check index (QUICKI) was significantly higher in both HPTS groups compared with the reference. These results show that HPTS retards the development of insulin resistance in KKAy mice fed a high-fat diet.

Resolution of type 2 diabetes following gastric bypass surgery: involvement of gut-derived glucagon and glucagonotropic signalling?

Certain types of bariatric surgical procedures have proved not only to be effective with regard to treating obesity, but they also seem to be associated with endocrine changes which independently of weight loss give rise to remission of type 2 diabetes. Currently, it is speculated that surgical re-routing of nutrients triggers changes in the release of gastrointestine-derived hormones, which in turn cause amelioration of the diabetic state. The 'hindgut hypothesis' states that surgical re-routing of nutrients to the distal part of the small intestine results in increased secretion and concomitant glucose-lowering effects of glucagon-like peptide-1, whereas the 'foregut hypothesis' emphasises that surgical bypass of the foregut prevents the release of a hitherto unidentified nutrient-induced diabetogenic signal in susceptible individuals. Recent studies have shown that in patients with type 2 diabetes, glucagon is differentially secreted in response to oral and i.v. glucose, respectively, with lack of suppression (and initial net secretion) during oral glucose administration and a perfectly normal suppression during isoglycaemic i.v. glucose administration. These findings could point towards a role for glucagon or gut-derived glucagonotropic signalling as putative diabetogenic signals of the foregut hypothesis. In the present paper the hypotheses describing the glucose-lowering mechanisms of bariatric surgical procedures sharing the common feature of a bypass of the duodenum and the proximal jejunum are outlined and a possible role for glucagon in these is proposed.

Bile Acids Have the Gall to Function as Hormones

In this issue of Cell Metabolism, Thomas et al. (2009) show that specific activation of the bile-acid-activated G protein-coupled receptor TGR5 improves pancreatic and hepatic function and impairs the development of obesity following administration of a high-fat diet.

Pancreatic beta cell function in polycystic ovary syndrome: its relationship to body weight, serum testosterone and serum prolactin levels.

Circulating levels of insulin and C-peptide in response to oral glucose administration (75 g) were measured in 25 PCOS patients (13 were obese and 12 non-obese) without acanthosis nigricans and in 12 non-obese normal cycling women of similar age. Fasting levels of insulin and C-peptide as well as the sums of their levels in response to glucose were significantly greater in PCO patients than in controls despite similar glucose responses. Obese PCO patients had greater basal levels, maximum increments and sums of insulin and C-peptide levels than non-obese PCO patients and controls. PCO patients with increased basal total testosterone levels had significantly greater mean fasting insulin levels (p less than 0.005) than those with normal testosterone levels but their responses to glucose were not significantly different. Hyperprolactinaemic PCO patients had neither basal level nor sums of insulin and C-peptide levels in response to glucose greater than normoprolactinaemic PCO patients. In all PCO patients BMI correlated significantly with insulin (p less than 0.05) and C-peptide levels (p less than 0.001). Total serum testosterone levels correlated significantly with fasting levels and the sum of C-peptide levels in response to glucose. The correlations of total serum testosterone levels with fasting and the sum of insulin levels in response to glucose were also positive but not significant. These results clearly indicate that in PCOS there is a significant degree of hyperinsulinaemia which is mainly related to obesity.

Effects of l-arginine supplementation on glucose and nitric oxide (NO) levels and activity of NO synthase in corticosterone-challenged broiler chickens ( Gallus gallus)

In the present study, three experiments were conducted to investigate the effect of oral supplementation of l-arginine (ARG) on the disposal of glucose in stressed-broiler chickens ( Gallus gallus domesticus). In all the three experiments, the broiler chickens were randomly subjected to one of the four treatments at the beginning of the experiments: oral administration of saline, glucose (2.0 g/kg body weight, BW), l-arginine (0.5 g/kg BW) or mixed solution (2.0 g glucose + 0.5 g arginine/kg BW). Immediately after the oral treatment, the experimental chickens were subcutaneously injected with corn oil (Experiment 1), corticosterone (CORT, 4 mg/kg BW, Experiment 2) or insulin (1 U/kg BW, Experiment 3), respectively. Blood samples were obtained at the beginning (0-h), 0.5-, 1- and 2-h time points after injection and the levels of plasma glucose, urate, nitric oxide (NO) and activity of NO synthase (NOS) were measured. The results showed that plasma NO levels and NOS activity were significantly suppressed while glucose and insulin concentrations were increased by CORT treatment. In contrast, insulin administration improved the circulating level of NO and activity of NOS. ARG supplementation could not improve the circulating levels of NO and NOS activity in CORT-challenged chickens and, in turn, the glucose disposal. The result suggests that NO is involved in insulin-mediated glucose transport in chickens, as well as that in mammals. The reduced circulating level of NO resulted from the suppressed activity of NOS rather than the reduced substrate concentration.

Glucagon-like peptide 1 (GLP-1) as a new therapeutic approach for type 2-diabetes.

Glucagon-like peptide 1 (GLP-1) is a physiological incretin hormone in normal humans explaining in part the augmented insulin response after oral versus intravenous glucose administration. In addition, GLP-1 also lowers glucagon concentrations, slows gastric emptying, stimulates (pro)insulin biosynthesis, reduces food intake upon intracerebroventricular administration in animals, and may, in addition, enhance insulin sensitivity. Therefore, GLP-1, in many aspects, opposes the Type 2-diabetic phenotype characterized by disturbed glucose-induced insulin secretory capacity, hyperglucagonaemia, moderate insulin deficiency, accelerated gastric emptying, overeating (obesity) and insulin resistance. The other incretin hormone, gastric inhibitory polypeptide (GIP), has lost almost all its activity in Type 2-diabetic patients. In contrast, GLP-1 glucose-dependently stimulates insulin secretion in diet- and sulfonylurea-treated Type 2-diabetic patients and also in patients under insulin therapy long after sulfonylurea secondary failure. Exogenous administration of GLP-1 ([7-37] or [7-36 amide]) in doses elevating plasma concentrations to approximately 3-4 fold physiological postprandial levels fully normalizes fasting hyperglycaemia in Type 2-diabetic patients. The half life of GLP-1 is too short to maintain therapeutic plasma levels for sufficient periods by subcutaneous injections. Current research activities aim at finding GLP-1 analogues with more suitable pharmacokinetic properties than the original peptide. Another approach could be the augmentation of endogenous release of GLP-1, which is abundant in L cells of the lower small intestine and the colon. Interference with sucrose digestion using alpha-glucosidase inhibition moves nutrients into distal parts of the gastrointestinal tract and, thereby, prolongs and augments GLP-1 release. Enprostil, a prostaglandin E2 analogue, fully suppresses GIP responses, while only marginally affecting insulin secretion and glucose tolerance after oral glucose, suggesting compensatory hypersecretion of additional insulinotropic peptides, possibly including GLP-1. Given the large amount of GLP-1 present in L cells, it appears worthwhile to look for more agents that could 'mobilize' this endogenous pool of the 'antidiabetogenic' gut hormone GLP-1.

Neonatal procedural pain exposure and pain management in ventilated preterm infants during the first 14 days of life.

Ventilated preterm infants are at high risk for procedural pain exposure. In Switzerland there is a lack of knowledge about the pain management in this highly vulnerable patient population. The aims of this study were to describe the type and frequency of procedures and to determine the amount of analgesia given to this patient group in two Swiss neonatal intensive care units. A retrospective cohort study was performed examining procedural exposure and pain management of a convenience sample of 120 ventilated preterm infants (mean age = 29.7 weeks of gestation) during the first 14 days of life after delivery and born between May 1st 2004 and March 31st 2006. The total number of procedures all the infants underwent was 38,626 indicating a mean of 22.9 general procedures performed per child and day. Overall, 75.6% of these procedures are considered to be painful. The most frequently performed procedure is manipulation on the CPAP prongs. Pain measurements were performed four to seven times per day. In all, 99.2% of the infants received either non-pharmacological and/or pharmacological agents and 70.8% received orally administered glucose as pre-emptive analgesia. Morphine was the most commonly used pharmacological agent. The number of procedures ventilated preterm infants are exposed to is disconcerting. Iatrogenic pain is a serious problem, particularly in preterm infants of low gestational age. The fact that nurses assessed pain on average four to seven times daily per infant indicates a commitment to exploring a painful state in a highly vulnerable patient population. In general, pharmacological pain management and the administration of oral glucose as a non-pharmacological pain relieving intervention appear to be adequate, but there may be deficiencies, particularly for extremely low birth weight infants born <28 weeks of gestation.

Neonatal procedural pain exposure and pain management in ventilated preterm infants during the first 14 days of life.

Ventilated preterm infants are at high risk for procedural pain exposure. In Switzerland there is a lack of knowledge about the pain management in this highly vulnerable patient population. The aims of this study were to describe the type and frequency of procedures and to determine the amount of analgesia given to this patient group in two Swiss neonatal intensive care units. A retrospective cohort study was performed examining procedural exposure and pain management of a convenience sample of 120 ventilated preterm infants (mean age = 29.7 weeks of gestation) during the first 14 days of life after delivery and born between May 1st 2004 and March 31st 2006. The total number of procedures all the infants underwent was 38,626 indicating a mean of 22.9 general procedures performed per child and day. Overall, 75.6% of these procedures are considered to be painful. The most frequently performed procedure is manipulation on the CPAP prongs. Pain measurements were performed four to seven times per day. In all, 99.2% of the infants received either non-pharmacological and/or pharmacological agents and 70.8% received orally administered glucose as pre-emptive analgesia. Morphine was the most commonly used pharmacological agent. The number of procedures ventilated preterm infants are exposed to is disconcerting. Iatrogenic pain is a serious problem, particularly in preterm infants of low gestational age. The fact that nurses assessed pain on average four to seven times daily per infant indicates a commitment to exploring a painful state in a highly vulnerable patient population. In general, pharmacological pain management and the administration of oral glucose as a non-pharmacological pain relieving intervention appear to be adequate, but there may be deficiencies, particularly for extremely low birth weight infants born <28 weeks of gestation.

Short-term Acute Hyperinsulinemia and Prothrombotic Factors in Subjects with Normal Glucose Tolerance

Some cytokines and proinflammatory mediators are considered markers of increased atherothrombotic risk. Few information is available on the effects of acute glucose and insulin variations on these markers of atherosclerosis. We assessed the acute effect of glucose and insulin on soluble CD40 ligand (sCD40L), IL-6, and P-selectin levels, evaluating their relationship with insulin sensitivity in normal glucose tolerance subjects (NGT). Twenty-four NGT subjects underwent a 3-h oral glucose tolerance test (OGTT) with measurements of sCD40L, IL-6, and P-selectin levels at 0, 90 and 180 min. Insulin sensitivity was assessed by the Oral Glucose Sensitivity Index (OGIS). To distinguish the role of glucose and insulin, eight subjects had the plasma glucose profile of the OGTT reproduced by a variable IV glucose infusion (ISO-G study) and nine underwent a euglycemic clamp. Lastly, a 3-h time-control (TC) study was performed in eleven subjects. A significant reduction of sCD40L was observed during OGTT and ISO-G study. This reduction was not due to time-related changes, since it was not observed in TC study. During the clamp, insulin induced a marked drop in sCD40L (from 4.89+/-1.34 to 1.60+/-0.29 ng/ml, p<0.05). In the pooled data from all studies, fasting sCD40L was indirectly related to LDL-cholesterol (r=-0.38; p=0.04), while IL-6 was directly related with BMI, fat mass, waist circumference, and P-selectin (p<0.05). sCD40L levels are downregulated during a short-term period of acute hyperinsulinemia, whether induced by oral or intravenous glucose administration or by insulin infusion, while it does not seem to affect P-selectin and IL-6.