Atypical responses to the glucose tolerance test in normal subjects

On 138 normal subjects, 20–45 years of age 198 glucose tolerance tests have been performed. In some individuals the test was repeated after a prolonged interval. Synchronous responses above the normal pattern were found in different subjects over periods of several months, alternating with episodes of below normal responses. The speed of responses to GTT and shape of response-curve were also atypical. All types of atypical responses observed were seen in the same individuals when the test was repeated on more than one occasion. The probability of these fluctuations being due to random changes was calculated for one set of results to be less than 10^–9. The simultaneous rhythmicity of these atypical responses to GTT suggested the intervention of some external factor. This has been discussed.

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Zusammenfassung Bei 138 normalen Versuchspersonen zwischen 20 und 45 Jahren wurden 189 Messungen der Glukosebelastung (GTT) vorgenommen.Bei einigen Personen wurde der Test nach einer längeren Pause wiederholt. Über Perioden von mehreren Monaten wurden bei verschiedenen Versuchspersonen Perioden mit Reaktionen oberhalb der Normalwerte abwechselnd mit Perioden unterhalb der Normalwerte gefunden. Die Geschwindigkeit der GTT-Reaktion und die Form der Reaktionskurve waren ebenfalls atypisch. Alle beobachteten Arten von atypischen Reaktionen wurden bei den gleichen Versuchspersonen gefunden, wenn der Versuch mehr als einmal wiederholt wurde.Die Wahrscheinlichkeit dieser Variationen auf grund von zufälligen Schwankungen wurde für eine Versuchsreihe auf weniger als 10^–9 geschätzt. Die gleichzeitige Rhythmik dieser atypischen GTT-Reaktion weist auf den Einfluss einiger äusserer Faktoren hin.

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Resume On a procédé à 189 mesures de la tolérance au glucose (GTT)sur 138 personnes âgées de 20 à 45 ans. Chez certaines de ces personnes, on a renouvelé l'essai après une longue période d'attente. Chez certaines, on a en outre trouvé, au cours de périodes de plusieurs mois, des valeurs supérieures à la normale alternant avec des valeurs inférieures à la normale et cela de façon synchronisée. La vitesse de réaction du GTT et la forme de la courbe de réaction sont également atypiques.Toutes les sortes de réactions atypiques se rapportent aux mêmes personnes si l'essai a été répété plus d'une fois. La probabilité de telles variations basée sur des fluctuations dues au hasard a été estimée à moins de 10^–9 pour une série d'essais.Le rythme simultané des valeurs atypiques de GTT laisse supposer l'influence de facteurs extérieurs. Cette influence est discutée.

     

Cardiorespiratory responses to hypoxia in intact and bilaterally vagotomized pigeons

Bilateral, cervical vagotomy in birds denervates, among other receptors, the carotid bodies. To test whether such neural section removes sensitivity to hypoxia, we measured respiratory, cardiovascular, and blood gas responses to hypoxia at 84-, 70-, and 49-Torr inspiratory O2 partial pressure (PIO2) in five pigeons with intact vagi and in five bilaterally, cervically vagotomized pigeons. Normoxic respiratory frequency (fresp) and expiratory flow rate (VE) were decreased after vagotomy. Intact pigeons showed large increases in VE in response to hypoxia, effected mostly by increases in fresp. VE also increased greatly in response to hypoxia in vagotomized pigeons, but increases were largely the result of tidal volume. O2 consumption, CO2 production, and respiratory exchange ratio increased slightly in all pigeons during hypoxia. Normoxic heart rate was greater after vagotomy; cardiac output increased in all pigeons in response to hypoxia, but stroke volume increased only in intact pigeons. During normoxia, arterial and mixed venous O2 partial pressure, O2 concentration, and pH were lower and arterial and mixed venous CO2 partial pressure was higher, after vagotomy. In all pigeons during hypoxia, arterial and mixed venous O2 and CO2 partial pressure and O2 concentration decreased and arterial and mixed venous pH increased; changes were roughly parallel in intact and vagotomized pigeons. The arteriovenous O2 concentration differences during normoxia and hypoxia were similar in all pigeons. We conclude that bilateral, cervical vagotomy in the pigeon causes hypoventilation and tachycardia during normoxia, but strong respiratory and cardiovascular responses to hypoxia are still present.     

Duodenal glands in normal and vagotomized rats

In Wistar rats by means of the stereo- and morphometry methods, using semithin sections, histotopography of the duodenal glands (DG) and effect of vagotomy (VT) on them have been studied. The zone of the DG arrangement in the submucosal tela of the duodenum is about 5,000 mcm long. In the proximo-distal direction of the zone mentioned three parts can be distinguished--oral, middle and caudal. In the DG light-optically four varieties of mucocytes are identified. VT results in decreasing thickness of the zone of the DG arrangement, in outgrowth of the connective tissue and in a lowered amount of secrete in mucocytes.     

Evaluating the glucose tolerance test in mice

The objective of this study was to determine the optimal conditions under which to assess glucose tolerance in chow- and high-fat-fed C57BL/6J mice. Mice were fed either chow or high-fat diet for 8 wk. Variables tested were fasting duration (0-, 3-, 6-, and 24-h and overnight fasting), route of administration (intraperitoneal vs. oral) load of glucose given (2, 1, or 0.5 g/kg and fixed 50-mg dose), and state of consciousness. Basal glucose concentrations were increased in high-fat- compared with chow-fed mice following 6 h of fasting (9.1 +/- 0.3 vs. 7.9 +/- 0.4 mmol/l P = 0.01). Glucose tolerance was most different and therefore significant (P = 0.001) in high-fat-fed mice after 6 h of fasting (1,973 +/- 96 vs. 1,248 +/- 83 mmol.l(-1).120 min(-1)). The difference in glucose tolerance was greater following an OGTT (142%), in contrast to an IPGTT, with a 127% difference between high fat and chow. We also found that administering 2 g/kg of glucose resulted in a greater level of significance (P = 0.0008) in glucose intolerance in high-fat- compared with chow-fed mice. A fixed dose of 50 mg glucose regardless of body weight was enough to show glucose intolerance in high-fat- vs. chow-fed mice. Finally, high-fat-fed mice showed glucose intolerance compared with their chow-fed counterparts whether they were tested under conscious or anesthetized conditions. We conclude that 2 g/kg glucose administered orally following 6 h of fasting is best to assess glucose tolerance in mice under these conditions.     

Adipokine pattern in subjects with impaired fasting glucose and impaired glucose tolerance in comparison to normal glucose tolerance and diabetes

Aim

Altered adipokine serum concentrations early reflect impaired adipose tissue function in obese patients with type 2 diabetes (T2D). It is not entirely clear whether these adipokine alterations are already present in prediabetic states and so far there is no comprehensive adipokine panel available. Therefore, the aim of this study was to assess distinct adipokine profiles in patients with normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or T2D.

Methods

Based on 75 g oral glucose tolerance tests, 124 individuals were divided into groups of IFG (n = 35), IGT (n = 45), or NGT (n = 43). Furthermore, 56 subjects with T2D were included. Serum concentrations of adiponectin, chemerin, fetuin-A, leptin, interleukin (IL)-6, retinol-binding protein 4 (RBP4), monocyte chemoattractant protein (MCP)-1, vaspin, progranulin, and soluble leptin receptor (sOBR) were measured by ELISAs.

Results

Chemerin, progranulin, fetuin-A, and RBP4, IL-6, adiponectin and leptin serum concentrations were differentially regulated among the four investigated groups but only circulating chemerin was significantly different in patients with IGT compared to those with IFG. Compared to T2D the IFG subjects had higher serum chemerin, progranulin, fetuin-A and RBP4 levels which was not detectable in the comparison of the T2D and IGT group.

Conclusion

Alterations in adipokine serum concentrations are already detectable in prediabetic states, mainly for chemerin, and may reflect adipose tissue dysfunction as an early pathogenetic event in T2D development. In addition, distinct adipokine serum patterns in individuals with IFG and IGT suggest a specific role of adipose tissue in the pathogenesis of these prediabetic states.     

Oral glucose tolerance test in polycystic ovary syndrome

OGTT was used to clarify the problem of hyperinsulinism and insulin resistance previously investigated by us in PCOS, using the tolbutamide test. The results of this latter investigation were in agreement with the previous found by us and with the similar already reported by other Authors. 26 women (7 obese), aged 14-34 years, affected by PCOS, were studied. The diagnosis of PCOS was made using clinical, hormonal, radiologic and echographic criteria. 16 age matched healthy women were used as controls. Glucose and insulin curves, glucose (GA) and insulin (IA) response areas and IA/GA ratio (insulin resistance in dex-IRI-) were studied by OGTT. Blood insulin values of patients resulted significantly more elevated than that of controls at any point of the curve and more significantly elevated were decreasing values. Mean values of insulin peaks, of insulin areas and of IRI resulted more elevated than that of controls. The presence of both an hyperinsulinism and an insulin resistance in PCOS seems therefore evident. A correlation was found between IRI values and plasma testosterone levels in non obese patients with increased urinary 17-ketosteroid output. A relationship between hyperandrogenism on one hand and hyperinsulinism and insulin resistance on the other is suggested.     

Modeling glucose and free fatty acid kinetics in glucose and meal tolerance test

Background

Quantitative evaluation of insulin regulation on plasma glucose and free fatty acid (FFA) in response to external glucose challenge is clinically important to assess the development of insulin resistance (World J Diabetes 1:36–47, 2010). Mathematical minimal models (MMs) based on insulin modified frequently-sampled intravenous glucose tolerance tests (IM-FSIGT) are widely applied to ascertain an insulin sensitivity index (IEEE Rev Biomed Eng 2:54–96, 2009). Furthermore, it is important to investigate insulin regulation on glucose and FFA in postprandial state as a normal physiological condition. A simple way to calculate the appearance rate (Ra) of glucose and FFA would be especially helpful to evaluate glucose and FFA kinetics for clinical applications.

Methods

A new MM is developed to simulate the insulin modulation of plasma glucose and FFA, combining IM-FSIGT with a mixed meal tolerance test (MT). A novel simple functional form for the appearance rate (Ra) of glucose or FFA in the MT is developed. Model results are compared with two other models for data obtained from 28 non-diabetic women (13 African American, 15 white).

Results

The new functional form for Ra of glucose is an acceptable empirical approximation to the experimental Ra for a subset of individuals. When both glucose and FFA are included in FSIGT and MT, the new model is preferred using the Bayes Information Criterion (BIC).

Conclusions

Model simulations show that the new MM allows consistent application to both IM-FSIGT and MT data, balancing model complexity and data fitting. While the appearance of glucose in the circulation has an important effect on FFA kinetics in MT, the rate of appearance of FFA can be neglected for the time-period modeled.