Oral Glucose Meal Research Articles

Anticipating the next meal using meal behavioral profiles: A hybrid model-based stochastic predictive control algorithm for T1DM

Automatic control of Type 1 Diabetes Mellitus (T1DM) with subcutaneous (SC) measurement of glucose concentration and subcutaneous (SC) insulin infusion is of great interest within the diabetes technology research community. The main challenge with the so-called “SC–SC” route to control is sensing and actuation delay, which tends to either destabilize the system or inhibit the aggressiveness of the controller in responding to meals and exercise. Model predictive control (MPC) is one strategy for mitigating delay, where optimal insulin infusions can be given in anticipation of future meal disturbances. Unfortunately, exact prior knowledge of meals can only be assured in a clinical environment and uncertainty about when and if meals will arrive could lead to catastrophic outcomes. As a follow-on to our recent paper in the IFAC symposium on Biological and Medical Systems (MCBMS 2009) [1], we develop a control law that can anticipate meals given a probabilistic description of the patient’s eating behavior in the form of a random meal (behavioral) profile. Preclinical in silico trials using the oral glucose meal model of Dalla Man et al. show that the control strategy provides a convenient means of accounting for uncertain prior knowledge of meals without compromising patient safety, even in the event that anticipated meals are skipped.

Anticipating Meals with Behavioral Profiles: Towards Stochastic Model Predictive Control of T1DM

The delay associated with subcutaneous glucose sensing and insulin infusion actuation significantly complicates the design of control algorithms for regulating blood glucose in patients with Type 1 Diabetes Mellitus (T1DM). Model predictive control (MPC) is one strategy for mitigating delay, where optimal insulin infusions can be given in anticipation of future meal disturbances. Unfortunately, exact prior knowledge of meals can only be assured in a clinical environment, and uncertainty about when and if meals will arrive could lead to catastrophic outcomes. In this paper we develop an MPC-like control law that can anticipate meals given a probabilistic description of the patient's eating behavior in the form of a random meal (behavioral) profile. Preclinical in silico trials using the oral glucose meal model of Dalla Man et al. show that the control strategy provides a convenient means to account for uncertain prior knowledge of meals without compromising patient safety, even in the event that anticipated meals are skipped.

IBS subjects with methane on lactulose breath test have lower postprandial serotonin levels than subjects with hydrogen.

We have previously shown that methane on lactulose breath test (LBT) is highly associated with constipation in IBS and that methane gas itself slows small bowel transit in dogs. Previous studies suggest that serotonin may have a role in the control of transit in IBS. In this study, we aim to evaluate the role of serotonin in methane producing IBS subjects. Rome I-positive IBS subjects were recruited into the study after exclusion criteria were met. A fasting LBT was performed after subjects filled out a questionnaire rating the degree of constipation and diarrhea. Within 7 days of this test, subjects returned fasting for determination of serotonin before and after a 75-g oral glucose meal. The serotonin response was compared between hydrogen and methane producing IBS subjects. After 2 subjects were excluded for inadequate blood samples, 18 subjects completed the study. Four of 18 subjects produced methane. The postprandial serotonin level in methane producing IBS subjects was lower than in hydrogen producers (P < 0.05). Methane producers had a reduction in serotonin after glucose. Methane producing IBS subjects have reduced postprandial serotonin. Whether methane is a surrogate marker of constipation or contributing to the reduced serotonin remains to be determined.

Renal extraction of insulin and C-peptide in man before and after a glucose meal.

It was recently shown that the early rise in arterial insulin concentration after an oral glucose meal is largely because of a decreased extraction of the hormone. The kidney is a major site for extraction of insulin and C-peptide. We therefore measured the renal extraction of insulin and C-peptide in eight healthy individuals before and after ingestion of 75 g of glucose. Arterial, renal venous and hepatic venous catheters were inserted. Splanchnic and renal plasma flow were measured, as well as arterial, hepatic venous and renal venous concentrations of insulin and C-peptide. Renal fractional extraction of insulin increased significantly, from 21% to a maximum of 48% after the meal while the renal fractional extraction of C-peptide did not change significantly. Renal blood flow decreased slightly but significantly after the meal. It is concluded that renal fractional extraction of insulin increases and that renal blood flow decreases after a glucose meal.

Hepatic nonoxidative disposal of an oral glucose meal in patients with liver cirrhosis.

Seven patients with liver cirrhosis and five healthy subjects were studied over 4 hours after ingestion of a glucose meal to determine whether alterations of hepatic nonoxidative glucose disposal participate in the pathogenesis of impaired glucose tolerance. Hepatic uridyl-diphosphoglucose (UDPG) turnover was calculated from the isotopic enrichment of urinary acetaminophen glucuronide during continuous infusion of 13C-galactose and used as an index of hepatic glycogen synthesis. Patients with cirrhosis had postprandial hyperglycemia and decreased glucose clearance, but hepatic UDPG turnover was not altered (1.84 +/- 0.29 mg/kg fat-free mass min v 1.76 +/- 0.15 in controls, nonsignificant). It is concluded that hepatic postprandial glycogen synthesis is unaltered in patients with advanced cirrhosis, demonstrating important hepatic functional reserve.

Obese mice have higher insulin receptor levels in the hepatocyte cell nucleus following insulin stimulation in vivo with an oral glucose meal

Internalization of the insulin receptor occurs following insulin binding at the cell surface, which serves to attenuate the insulin signal as well as modulate the number of surface insulin receptors. Obese animals exhibit decreased cell surface insulin receptor number as well as defects in insulin receptor internalization and processing. The insulin receptor may also translocates to the nucleus of hepatocytes and adipocytes following stimulation of cells with insulin. The objective of this study was to determine if insulin receptor trafficking to the hepatocyte cell nucleus could be observed in vivo and whether this process was altered in obese compared to lean mice. Mice were fasted for 12 h to reduce serum insulin to basal levels. Animals were then given an oral meal of glucose to stimulate the binding of insulin to receptor in vivo. Hepatocyte plasma membrane and nuclei were fractionated to purity following the glucose meal. Levels of insulin receptor were determined using insulin binding assays and a Western blotting assay using anti-insulin receptor antibody. As the amount of serum insulin increased following the glucose meal, a corresponding increase in nuclear insulin binding occurred in lean animals but not obese animals ( P<0.05). Following the glucose meal, insulin receptor detected in the cell nucleus was increased in obese compared to lean mice ( P<0.05). Thus insulin receptor translocation to the nucleus was demonstrated in vivo following a glucose meal in hepatocytes of both lean and obese animals. It is suggested that serum hyperglycemia and hyperinsulinemia in obese mice increased translocation of the insulin receptor to the nucleus.

Glycemic Index and Insulin Response to a Liquid Nutritional Formula Compared with a Standard Meal

Objective: To determine the glycemic index and metabolic responses to a nutritional formula, and to compare these responses to those following an oral glucose meal and a standard test meal.Methods: Six male and six female healthy non-diabetic volunteers aged 18 to 48 years met screening examination and laboratory assessment criteria. Three test meals were administered, each containing 50 g of carbohydrate: nutritional formula (NF), standard test meal (ST) and a glucose test meal (GT). Each subject underwent the three test meals on separate days in randomized sequence. Blood samples were taken at intervals over 5 hours for determination of glucose, insulin and triglycerides.Results: The glycemic index was similar for the NF (60.8±13.1) and for the ST (57.8±12.9) meals. The incremental area under the curve for glucose was similar for NF and ST, but each was significantly lower than for the GT meal. The total area under the curve for insulin was significantly greater for the NF meal than for the ST meal. The serum triglyceride responses were similar for NF and ST meals.Conclusion: In healthy non-diabetic subjects, the blood glucose and triglyceride responses are similar for a nutritional formula compared to an isoenergetic standard test meal. However, the insulin response differs. This information is important in managing tube-fed patients.

Portal Vein Insulin Flux and Arterial Glucose Fluctuations in Response to an Oral Meal Test in Islet Cell-Transplanted Dogs

Insulin flux was determined in the portal vein and simultaneously arterial blood glucose was measured before and during an oral glucose meal in conscious normal and pancreatic islet cell-autotransplanted dogs to test their insulinogenic reserve. These dogs had previously been chronically instrumented with blood flow probes on the portal vein and carotid artery, and blood sampling catheters in the portal vein, hepatic vein, carotid artery, and right external jugular vein. Such a model permits quantitative portal-peripheral comparisons and assessment of hepatic extraction. Sixteen dogs, 10 normal (N) and six long-term (2 months to 2 yrs) islet cell-transplanted dogs (IT) were fed an oral glucose meal as a test (OMT). Baseline portal vein insulin fluxes (PVF) were similar in both groups (25.6 +/- 0.04 pmol/min in N and 24.7 +/- 19.4 pmol/min in IT). Immediately after OMT, PVF rose to 248.2 +/- 40.9 pmol/min in N, but only to 55.9 +/- 17.9 pmol/min in IT. After 30 min PVF peaked for the second time in N at 156 +/- 35.9 pmol/min, declining slowly to baseline after 3 h. In IT, a similar peak at 30 min was seen (143.7 +/- 22.1 pmol/min), declining to a value not different from baseline after 3 h. However, cumulative insulin PV fluxes in the two groups over 3 h were not different. Differences were also seen in postprandial glucose fluctuations, which reached a maximum excursion of 11.8 +/- 0.45 mM in IT, while never rising above 7.8 +/- 0.33 mM in N. After 3 h both groups had similar glucose values.(ABSTRACT TRUNCATED AT 250 WORDS)

A chronic conscious dog model for direct transhepatic studies in normal and pancreatic islet cell transplanted dogs

A chronic conscious, large mammal model for repeated transhepatic studies over a period of 6–8 weeks has been developed for application to the study of the hepatic effects of pancreatic hormone secretion and glucose metabolism, studies of the hepatic mechanisms associated with high first-pass drug metabolism and food interactions, and studies of insulin balance in dogs that have undergone previous pancreatectomy and islet cell auto-transplantation. The preparation of specialized blood sampling catheters and blood flow probes, surgical preparations, pre- and postoperative care, catheter maintenance, and possible complications are described. Data from an oral glucose meal (OMT) are presented. Frequent blood samples from portal, hepatic and jugular veins, and carotid artery were collected and analyzed for plasma insulin concentrations (IRI) and glucose. IRI fluxes were determined for each time period by interpolation of flux X time curves. Total IRI flux was determined as the sum of the areas under the curves for each sampling period. Hepatic insulin extraction was calculated for each sampling interval. By this method of analysis, it was possible to determine hepatic IRI extraction during non-steady-state conditions. The techniques described in the development of this complex animal model, which allows for repeated transhepatic studies in the same conscious subject, may also have application in other chronic studies involving organs other than the liver.

Evaluation of Postprandial Symptoms-Reply

In Reply.— Patients with postprandial complaints resembling the clinical manifestations of hypoglycemia pose a perplexing diagnostic problem for their physicians. Since symptoms are frequently vague and nonspecific, they may represent manifestations of psychosomatic, psychiatric, or metabolic disorder. It is important to differentiate among the various diagnostic possibilities since the patient will benefit from appropriate therapy. The goal of our study was to develop unbiased and objective diagnostic criteria for the postprandial syndrome. Therefore, we included in the study only patients whose symptom manifestations could be confirmed by an outside observer. The eight patients 1 excluded from our study reported only subjective complaints, and there was no assurance that they had the postprandial syndrome. Some of them could have been suffering from the unrelated conditions that create diagnostic confusion. The oral glucose meal has evolved as a standardized, objective procedure to evaluate conditions of patients with postprandial symptoms, since the test

Originalarbeiten: Thyroid Functions in Young Diabetics

Assessment of the thyroid-pituitary axis was performed in uncontrolled (20 cases) and controlled (22 cases) insulin-dependent young diabetics who were university students attending the university hospital. A third age-matching group (21 normal subjects) was also investigated. Fasting plasma glucose level as well as 2 hours after an oral glucose meal (50 g) were determined. Thyroxine (T4), triiodothyronine (T3) and thyroid stimulaling hormone (TSH) were assayed by RIA. The data obtained showed a lowered level of T3 and T4and a raised level in TSH level in uncontrolled young diabetics than the corresponding values for age matching normals. The group of controlled diabetics showed near normal T3 level and increased T4 but still lower than normal. TSH levels dropped significantly to the normal level.

Effect of epinephrine on insulin release in man induced by secretin.

SEVERAL observations taken together support the suggestion that the pancreatic β-cell responds in different ways to an oral glucose meal and to an intravenous infusion of glucose. (1) Oral glucose produces a greater rise in concentrations of plasma insulin than does an identical intravenous load1,2; (2) oral glucose provokes a response in plasma insulin four or five times greater than that achieved by infusing glucose intravenously to comparable concentrations of blood glucose3; (3) epinephrine blunts the release of insulin usually encountered after intravenous infusion of glucose4, but fails to suppress the rise in concentrations of plasma insulin which follows an oral glucose meal5.