The occurrence of low insulin response to glucose infusion in children

Summary Insulin response to glucose infusion was studied in 42 children with a normal intravenous glucose tolerance, 7–16 years of age. The majority of these children had at least one first degree relative with diabetes mellitus. Low and delayed insulin response similar to the one found in 15–20% of healthy adult subjects also occurred in 15–20 per cent of the children in this material. These findings support our previous suggestion that the low and delayed insulin response to glucose is probably genetically determined.

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Das Vorkommen von verringerter Insulinausschüttung nach Glukoseinfusion bei Kindern

Zusammenfassung Die Insulinausschüttung nach Glucoseinfusion wurde bei 42 Kindern, 7–16 Jahre alt, mit normaler intravenösen Glucosetoleranz untersucht. Die Mehrzahl dieser Kinder hatte einen diabeteskranken Eltern-oder Geschwisterteil. Eine verzögerte und verringerte Insulinfreisetzung, ähnlich denen, die bei 15–20% von gesunden Erwachsenen gefunden worden waren, war bei 7 von 42 Kindern zu sehen. Dieser Befund stützt unsere frühere Ansicht, daß die verzögerte und verringerte Insulinausschüttung bei Hyperglykämie wahrscheinlich genetisch bedingt ist.

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L'existence de réponse insulinique réduite à la perfusion de glucose chez l'enfant

Résumé La réponse insulinique à la perfusion de glucose a été étudiée chez 42 enfants âgés de 7 à 16 ans et ayant un test de tolérance au glucose normal. Chez la plupart des enfants au moins un des parents ou frères et surs avait le diabète. Une réponse insulinique réduite et retardée, similaire à celle observée chez 15 à 20% des adultes en bonne santé, a été démontrée chez 7 enfants sur les 42. Ces résultats confirment notre suggestion que ce type de réponse insulinique réduite et retardée est probablement déterminée par des facteurs héréditaires.

     

静脉输注维生素C影响血糖测定一例报告

1例患者因输注大剂量维生素C引起实验室假性低血糖症。     

The insulin response to glucose infusion in normal human pregnancy

Summary To study insulin response and insulin sensitivity a glucose infusion test was devised. Twenty normal non-pregnant and twenty normal pregnant women had an intravenous glucose tolerance test followed by a glucose infusion test. In a normal pregnant group at 38–40 weeks gestation (n=20) the plasma insulin response was found to be 3.7 times greater than that observed in a normal non-pregnant group (n=20), while in the normal pregnant group the insulin sensitivity index was only 18 per cent of that observed in the non-pregnant group. Intravenous glucose tolerance in the non-pregnant women was observed to correlate with the insulin sensitivity index (r=0.61, p<0.05) but in the pregnant women it correlated with the insulin response (r=0.66, p<0.01). These findings support the hypothesis that in the non-pregnant state intravenous glucose tolerance may be primarily related to insulin sensitivity while during pregnancy it may be related to the degree of compensatory hyperinsulinism.     

Computer analysis of intravenous glucose tolerance tests

Summary A computer program which simultaneously calculates glucose disappearance rates after intravenous injection using three different mathematical equations is described. This program has been applied to the results obtained from several groups of pregnant women. The reasons for suggesting that the absolute K value may be preferable on practical grounds are discussed. This program, written in Fortran, is available on application to D.W. Neill.

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Analyse intravenöser Glucosetoleranzteste mit Hilfe einer elektronischen Rechenmaschine

Zusammenfassung Es wird ein Programm für die elektronische Rechenmaschine angegeben, welches die Glueoseabbaurate nach intravenöser Verabfolgung gleichzeitig nach drei verschiedenen mathematischen Gleichungen errechnet. Dieses Programm wurde bei den Befunden von verschiedenen Gruppen schwangerer Frauen angewandt. Die Gründe dafür, daß im praktischen Gebrauch wahrscheinlich die absoluten K-Werte vorzuziehen sind, werden diskutiert. Das von Fortran geschriebene Programm steht allgemein zur Verfügung und kann bei D.W. Neill angefordert werden.

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Analyse sur ordinateur des tests de tolérance au glucose intraveineux

Résumé Les auteurs décrivent un programme sur ordinateur qui calcule simultanément les vitesses de disparition du glucose après injection intraveineuse, à l'aide de trois équations mathématiques différentes. Ce programme a été appliqué aux résultats obtenus dans plusieurs groupes de femmes enceintes. Les raisons suggérant que la valeur K absolue peut être préférable pour des raisons pratiques, sont discutées. Ce programme, écrit en Fortran, est disponible sur demande à D.W. Neill.

     

Use of continuous intravenous insulin infusion in type 1 diabetic pregnancy complicated by nephrotic syndrome

We report a case of nephrotic syndrome complicating pregnancy in a woman with CSII-treated type 1 diabetes. This was associated with deteriorating glycaemic control which was successfully managed with continuous intravenous insulin for the two weeks before delivery.     

The effects of a low-dose intravenous insulin infusion upon plasma glucose and non-esterified fatty acid levels in very obese and non-obese human subjects

Summary After an overnight fast, the effects of a 30-min low-dose intravenous insulin infusion (2.6 units/h) upon plasma glucose and non-esterified fatty acids were compared in 29 very obese patients and 17 nonobese controls. The dose of insulin was chosen so as to have its sole or predominant hypoglycaemic effect upon hepatic glucose release. The proportional fall from basal values at 30 min of both plasma glucose and non-esterified fatty acids was significantly greater in the controls and there was no difference between males and females. In the controls the fall in plasma glucose and non-esterified fatty acids was significantly and inversely correlated with the basal plasma insulin level. Neither index of insulin sensitivity was significantly related with the basal plasma insulin in the obese subjects. Weight loss in the obese subjects led to increased insulin sensitivity; in particular, the degree of change in insulin-induced nonesterified fatty acids was significantly related to the percentage change in weight. Despite their extreme degree of obesity, the distributions of basal plasma insulin levels and the indices of insulin sensitivity in the obese subjects overlapped with those of the nonobese controls.     

Investigations on glucose uptake in isolated human leucocytes from normal and diabetic subjects

Summary 1. Leucocyte preparations have been obtained from the blood of 135 healthy control persons and 10 poorly-controlled insulin-dependent diabetics according to a procedure described earlier. Cells were suspended in a Krebs-Ringer-Bicarbonate-Buffer. Glucose uptake, lactate production and cell glucose space were determined after incubating the cells for 1 h at 37° C in an atmosphere of O₂/CO₂ (95/5). Extracellular water-space of the cell sediment was corrected by measuring U-¹⁴C-sucrose levels in the medium before and after addition to the cell sediment. — 2. The cells showed intact structures and amoeboid motility under the light-microscope as well as under the phase-contrast-microscope. During an incubation lasting 1 h, the ATP/ADP quotient diminished by about 20%; the following metabolites: glucose-6-phosphate, fructose-1,6-diphosphate, 1,3-phosphoglycerate, pyruvate and lactate increased slightly up to markedly, especially glucose-6-phosphate and lactate. — 3. Sources of methodological errors were investigated in preliminary experiments. Disregarding corrections for the extracellular space of the cell sediments led to a dilution effect which imitates an apparent glucose uptake. For measurements of intracellular glucose and cell glucose space the procedure of Crofford and Renold provided the best results. Falsely high values for cell glucose have been found using the glucose oxidase reaction. — 4. Glucose uptake of healthy leucocytes increases at first steeply, later on less with rising medium glucose concentrations. Addition of insulin (50–500 mU/ml) gave no consistent effects. At medium glucose concentrations of 400 and 600 mg/100 ml intracellular glucose could be demonstrated with statistical significance. Intracellular glucose and cell glucose space were not affected by insulin to any marked degree. Determinations of lactate production indicated that human leucocytes utilize the largest portion of glucose via glycolysis. — 5. At medium glucose concentrations of 600 mg/100 ml leucocytes from diabetics who had received no insulin for 14 h prior to incubation showed a significant diminution of glucose uptake. — 6. Theoretical curves for inward transport and phosphorylation have been calculated from the data for glucose uptake and intracellular glucose concentration.The authors are greatly indepted to Prof. Wilbrandt, Department of Pharmacology, University Bern, for advice and discussion.     

The glucoregulatory response to intravenous glucose infusion in normal man: Roles of insulin and glucose

In order to differentiate the roles of hyperinsulinemia and hyperglycemia per se in the homeostatic response to i.v. glucose administration, two groups of normal subjects were given either glucose alone (3.5 mg kg^?1 min^?1) or glucose (3 mg kg^?1 min^?1) in conjunction with somatostatin (500 μg hr^?1), insulin (0.15 mU kg^?1 min^?1) and glucagon (1 ng kg^?1 min^?1). Glucose kinetics were measured by the primed-constant infusion of 3-³H-glucose. During the infusion of glucose alone, plasma glucose stabilized at levels 45–50 mg/dl above the fasting values. Endogenous glucose output was markedly suppressed by 85%–90% while glucose uptake rose to values very close to the infusion rate of exogenous glucose. Glucose clearance remained unchanged. Plasma insulin rose three-fourfold while plasma glucagon fell by 25%–30%. When glucose was infused with somatostatin, insulin, and glucagon, plasma insulin was maintained at levels 50% above baseline while glucagon remained at preinfusion levels. Under these conditions, the infusion of exogenous glucose resulted in a progressive increase of plasma glucose which did not stabilize until the end of the study period (190 mg/dl at 120 min). Endogenous glucose production was consistently suppressed (52%) but significantly less than observed with the infusion of glucose alone (p < 0.01). Glucose uptake increased to the same extent as with glucose alone, despite the more pronounced hyperglycemia. Thus, glucose clearance fell significantly below baseline (25%–30%; p < 0.01). These data demonstrate that hyperglycemia per se (fixed, near basal levels of insulin and glucagon) certainly contributes to the glucoregulatory response to i.v. glucose administration by both inhibiting endogenous glucose output and increasing tissue glucose uptake. However, the extra-insulin evoked by hyperglycemia is necessary for the glucoregulatory system to respond to the glucose load with maximal effectiveness.     

The insulin response to glucose infusion in gestational diabetes

Summary Using a glucose infusion test insulin responses and insulin sensitivities were studied in 15 gestational diabetic women at 36–40 weeks gestation. In all women intravenous glucose tolerance had returned to normal at six weeks postpartum. Twelve women had a repeat glucose infusion test done 7–24 weeks (mean 17 weeks) postpartum. The results were compared with previously evaluated normal non-pregnant and normal pregnant standards and insulin responses below the normal 15^th percentile were defined as low. Twelve women had low insulin responses in late pregnancy, and six had low insulin responses postpartum. The mean insulin sensitivity index of 1.34±1.21 (mean ±SD) was significantly higher in the gestational diabetic group during pregnancy compared with a control pregnant group at 0.53±0.21 (p<0.01). The findings in this study support the hypothesis that gestational diabetes may arise in women who are unable to achieve adequate insulinogenic compensation to pregnancy. Increased insulin sensitivity in gestational diabetes may be a compensatory mechanism.     

Renal response to intravenous somatostatin in insulin-dependent diabetic patients and normal subjects

The acute effects of iv somatostatin (SRIH; 100 micrograms/h) on the urinary flow (Uvol), effective renal plasma flow (RPF), and glomerular filtration rate (GFR) were compared with those of a control infusion of 0.15 M NaCl in nine insulin-dependent diabetic (IDD) patients of less than 10 yr disease duration and six normal subjects (NS). RPF and GFR were measured using a standard primed constant isotope infusion of [125I]iodohippurate and [51Cr]chromium EDTA. Uvol, RPF, and GFR were measured during 20-min clearance periods. During the NaCl infusion mean Uvol, RPF, and GFR were 14.1 +/- 0.2 (+/- SEM), 708 +/- 4, and 150 +/- 1 mL/min in the IDD group and 12.7 +/- 0.4, 568 +/- 5, and 110 +/- 2 mL/min in the NS group, respectively. In the IDD patients Uvol, RPF, and GFR decreased from 16.6 +/- 1.8, 670 +/- 30, 146 +/- 4 mL/min pre-SRIH to 9.2 +/- 1 (P less than 0.001), 553 +/- 25 (P less than 0.001), and 130 +/- 5 (P less than 0.001) mL/min, respectively, at 120 min during the SRIH infusion. Similarly, in the NS group mean Uvol, RPF, and GFR were 14.2 +/- 0.6, 552 +/- 15, and 112 +/- 5 mL/min pre-SRIH and decreased to 7.4 +/- 0.6 (P less than 0.001), 422 +/- 7 (P less than 0.001), and 93 +/- 3 (P less than 0.001) mL/min, respectively, after 120 min of the SRIH infusion. SRIH, therefore, had a profound effect on renal function in both IDD patients and NS, resulting in a reduction in RPF, GFR, and, as a consequence, Uvol.     

The response of serum glucose,free fatty acid and immunoreactive insulin to oral glucose and intravenous tolbutamide in normal,potentially diabetic and diabetic subjects

Summary Glucose, free fatty acids and immunoreactive insulin levels were measured in 323 normal, potentially diabetic and diabetic subjects after an oral glucose load and an intravenous injection of tolbutamide. The results indicate that, in potentially diabetic and diabetic subjects, the insulinogenic response to glucose lasted longer than in normal subjects. It is suggested that this phenomenon be due to the loss of cell sensitivity to the recently demonstrated inhibitory feedback induced by insulin itself. The insulinogenic response to tolbutamide and the FFA response to tolbutamide and insulin did not help in differentiating prediabetic from normal subjects. No consistent relationship was found between body weight and serum insulin response to glucose.This work was aided by Grant No. AM 06034 from the National Institutes of Health and by a Grant from the Upjohn Company.     

Studies in prediabetes. Insulin response to oral glucose,intravenous tolbutamide and rapid intravenous glucose infusion in genetic prediabetics

Summary Twenty-two non-obese genetic prediabetics (offspring with both parents diabetic) were compared with 34 normal volunteers, closely matched by age and weight, in their response to three standardized stimuli: oral glucose tolerance test (with 100 g of glucose), intravenous tolbutamide tolerance test (1 g) and rapid intravenous glucose infusion (0.33 g/kg body weight). Blood sugar, immunoreactive insulin and non-esterified fatty acids (N.E.F.A.) were estimated in both groups in the fasting state and at different time intervals during each of the three tests. — Results showed no significant differences (either in carbohydrate tolerance or in the behaviour of the N.E.F.A. levels) between normals and prediabetics at any time in the course of the selected tests. Plasma immunoreactive insulin fasting levels were also closely comparable in both groups, no significantly different insulin release in normals and prediabetics being elicited either by the oral glucose load or by the intravenous tolbutamide injection. However, the rapid intravenous glucose infusion brings about a markedly diminished insulin secretion in the prediabetic group limited to the very early response phase. — Our results strongly support the idea that an impaired ability to secrete insulin under the specific stimulus of the intravenous glucose is a distinguishing feature of the pancreatic beta cell in those humans pre-disposed to diabetes mellitus.

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Untersuchungen zum Prädiabetes. Insulinausschüttung nach oraler Glucosezufuhr und intravenösen Gaben von Tolbutamid und schnell injizierter Glucose bei genetischen Prädiabetikern

Zusammenfassung Die Reaktion von 22 normalgewichtigen genetischen Prädiabetikern, deren beide Elternteile Diabetiker waren, wurde mit der von 34 stoffwechselgesunden Freiwilligen entsprechenden Alters und Gewichtes verglichen. Als standardisierte Stimulationsmethoden dienten: der orale Glucosetoleranztest (100 g Glucose), der i.v. Tolbutamid-Toleranztest (1 g) und die schnelle i.v. Injektion von 0.33 g Glucose/kg Körpergewicht. Die Spiegel des Blutzuckers, des immunreaktiven Insulins und der unveresterten Fettsäuren (NEFA) wurden bei beiden Gruppen im Nüchternzustand und zu verschiedenen Zeiten während der 3 Tests bestimmt.-Die Resultate zeigten keine signifikanten Unterschiede in bezug auf die Kohlenhydrat-Toleranz und das Verhalten der NEFA zu irgend einem Zeitpunkt der benutzten Tests bei Normalpersonen und Prädiabetikern. Bei enger Übereinstimmung der Nüchternspiegel des plasma-immunreaktiven Insulins fanden sich auch keine signifikanten Unterschiede in der Ausschüttung nach oraler Glucosegabe oder i.v. Tolbutamidinjektion. Dagegen ergab sich nach schneller i.v. Glucoseinjektion eine deutlich verringerte Insulinfreisetzung bei der Gruppe der Prädiabetiker, die sich jedoch auf die Frühphase beschränkte. — Unsere Resultate sprechen durchaus dafür, daß eine verringerte Kapazität zur Ihsulinausschüttung nach dem spezifischen Reiz der i.v. Glucosebelastung ein Charakteristikum der Pankreas--Zelle der Menschen darstellt, die zum Diabetes mellitus prädisponiert sind.

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Etude du prédiabète. Réponse de Vinsuline au glucose oral, au tolbutamide intraveineux et à la rapide infusion intraveineuse de glucose chez des sujets génétiquement prédiabétiques

Résumé Vingt-deux sujets non-obèses, génétiquement prédiabétiques (issus de deux parents diabétiques) ont été comparés à 34 sujets normaux de même âge et de même poids, en ce qui concerne leur réponse à trois stimuli standardisés: test de tolérance au glucose oral (avec 100 g de glucose), test de tolérance au tolbutamide intraveineux (1 g) et rapide infusion intraveineuse de glucose (0.33 g/kg de poids corporel). La glycémie, l'insuline immunoréactive et les acides gras non-estérifLés (NEFA) ont été mesurés dans les deux groupes à l'état de jeûne et à différents intervalles de temps au cours de chacun des trois tests.-Les résultats n'ont montré de différence significative ni dans la tolérance aux hydrates de carbone, ni dans le comportement des taux de NEFA entre les sujets normaux et les prédiabétiques, à aucun moment au cours des tests choisis. Les taux à jeun d'insuline plasmatique immunoréactive étaient également étroitement comparables dans les deux groupes; ni la charge orale de glucose, ni l'injection intraveineuse de tolbutamide ne provoquait une libération d'insuline significativement différente chez les sujets normaux et les prédiabétiques. Cependant, la rapide infusion intraveineuse de glucose provoquait une sécrétion d'insuline nettement diminuée dans le groupe prédiabétique qui était plutôt limitée à la phase de réponse très précoce.-Nos résultats confirment fortement l'idée qu'une capacité diminuée à sécréter de l'insuline sous l'influence du stimulus spécifique constitué par la charge brutale de glucose intraveineux est un trait plutôt caractéristique de la cellule bêta pancréatique chez ces sujets qui sont fortement prédisposés au diabète sucré.

     

Lack of thermogenic response to glucose/insulin infusion in diabetic obese subjects

The change in energy expenditure consecutive to the infusion of glucose/insulin was examined in 17 non-obese (ten young, seven middle-aged) and 27 diabetic and non-diabetic obese subjects by employing the euglycemic insulin clamp technique in conjunction with continuous indirect calorimetry. The obese subjects were divided into four groups according to their response to a 100-g oral glucose test: group A, normal glucose tolerance; group B, impaired glucose tolerance; group C, diabetes with increased insulin response; group D, diabetes with reduced insulin response. The glucose/insulin infusion provoked an increase in energy expenditure in both young and middle-aged controls (+8.2 +/- 1.3 percent and +5.9 +/- 0.5 percent over the preinfusion baseline respectively), but a lower increase in the non-diabetic obese groups A and B (+4.0 +/- 0.7 percent and +2.0 +/- 1.0 percent over the preinfusion baseline respectively, P less than 0.05 and P less than 0.01 vs young controls). However, in the diabetic obese groups C and D, energy expenditure failed to increase in response to the glucose/insulin infusion (mean change: +0.1 +/- 1.0 percent and -2.0 +/- 1.9 percent (P less than 0.01, vs middle-aged) over the preinfusion baseline respectively). When the glucose-induced thermogenesis (GIT) was related to the glucose uptake--taking into account the hepatic glucose production--the GIT was found to be similarly reduced in the diabetics groups (C and D). The net change in the rate of energy expenditure was found to be significantly correlated with the rate of glucose uptake (r = +0.647, n = 44, P less than 0.001) when all the individuals were pooled. In conclusion, this study shows that the low glucose-induced thermogenesis in obese diabetics during glucose insulin infusion is mainly related to a reduced rate of glucose uptake; in addition, inhibition of gluconeogenesis by the glucose/insulin infusion may also contribute to decrease the thermogenic response.     

静脉输液反应诱发老年患者心电图、心肌酶及cTnI改变初探

目的 观察老年患者输液反应时心电图、心肌酶及肌钙蛋白Ⅰ（cTnI）变化情况.方法 对我院2010年6月至2012年6月出现输液反应的62例老年患者（输液反应组）进行心电图、血清心肌酶和cTnI检测,并以60例无输液反应老年患者作为对照组进行比较.结果 输液反应组患者心电图异常率高于对照组（P＜0.05或P＜0.01）;血清天冬氨酸转移酶（AST）、乳酸脱氢酶（LDH）、肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）和cTnI水平及阳性例数亦明显高于对照组（P＜0.01）;输液反应组患者cTnI异常率高于其他心肌酶指标.结论 静脉输液反应可诱发老年患者潜在性心肌损伤,导致心电图、心肌酶及cTnI发生改变,应加强检测,尽早发现及时治疗.     

The metabolic and hormonal responses to glucose infusion in anaesthetized normal and diabetic dogs controlled by an artificial B-cell

Summary The metabolic response to glucose infusion in anaesthetized normal and pancreatectomized dogs has been assessed. Normoglycaemia was achieved in the diabetic dogs with an external artificial B-cell which administered insulin into the peripheral circulation. No differences were found in the levels of blood glucose, glucagon, lactate, pyruvate and plasma non-esterified fatty acids, either in the fasting state or in response to glucose infusion. However, compared to normal animals normoglycaemic diabetic dogs had significantly elevated circulating levels of insulin and alanine at all times. Fasting levels of the same hormones and metabolites were also measured in conscious dogs. Blood pyruvate levels were higher, and plasma non-esterified fatty acid levels lower, in the anaesthetized animals. There were also minor but consistent changes in blood glucose and plasma insulin while glucagon, lactate and alanine levels were unaffected by anaesthesia. In conclusion, controlled barbiturate anaesthesia has relatively minor effects on the metabolic and hormonal status of the dog. The metabolic and hormonal response to glucose infusion in pancreatectomized dogs treated with an artificial B-cell was almost entirely normalized, except for peripheral hyperinsulinaemia and hyperalaninaemia.     

Red cell sorbitol concentration in relation to short- and medium-term variation of plasma glucose

Summary To evaluate the time course of changes in red cell sorbitol (RCS) concentration in relation to variations of plasma glucose levels, RCS was determined in 7 normal subjects during i.v. glucose infusion (IVGTT); in 6 hyperglycemic insulin-dependent diabetic subjects while glycemia was normalized with Biostator GC 115 and in 4 diabetic patients in previously poor metabolic control, in whom normal glycemia was obtained in 8–10 days by intensive insulin therapy. During IVGTT, plasma glucose levels increased with significant differences from baseline at 5, 10, 16, 25, 60, 100 and 160 min and returned to basal levels after 3h; RCS concentration showed small and insignificant increases. During i.v. insulin infusion, plasma glucose fell to almost normal levels within roughly 3h; RCS levels showed a gradual reduction becoming significant at 180 min. In the third study, decrease in plasma glucose was always associated with a fall in RCS level which became significant between the 2nd and the 3rd day of the study. Thus, RCS levels were not affected by very short-term variations of glycemia but by a previous hyperglycemic crisis that lasted a few hours. There were therefore medium-term variations of RCS level. In conclusion, RCS determination is not useful as an index of metabolic control in diabetes.     

Effect of cephalic glucose infusion on insulin secretion

Sumary The continous infusion of glucose (1 mg/kg/min) via the carotid artery in anesthetized dogs produces a biphasic pattern of insulin secretion. The first peak reaches a maximum 3 min after glucose infusion and drops to basal level at 7 min. As long as the glucose infusion persists a slow and mantained increase in insulin level in the pancreaticoduodenal vein can be observed. The same amount of glucose infused in the general circulation via the jugular vein provoked a different pattern of insulin secretion. Cerebral glucose infusion to vagotomized dogs also produced a two phase response in insulin secretion, but the levels reached in the first phase were lower that those observed in the normal dogs. The infusion of glucose, via the jugular vein, in vagotomized dogs, failed to induce any change in plasma insulin levels. Our data suggest that a glucose load to the brain induces pancreatic insulin secretion mediated partially by the vagus nerves. These results are also compatible with the hypothesis that a humoral factor could be involved in the pancreatic response.Members of Carrera del Investigador Cientofico, Consejo Nacional de Investigaciones Cientoficas Técnicas, Argentina.