Novel control system for blood glucose using a model predictive method

We developed a novel blood glucose control system, using a model predictive method, to achieve optimal control of the blood glucose level in severely diabetic or pancreatectomized patients. This system is designed to predict glucose level changes in advance, considering delayed response time and the administered doses of insulin. This method is also designed to calculate the most appropriate insulin infusion rate by considering differences in individual response to insulin. In this study, we compared our system with a conventional proportional and differential controller (PD controller) to determine whether the new system could regulate the glucose level efficiently in pancreatectomized dogs. The model predictive control method resulted in a significant reduction of mean insulin infusion rate compared with the conventional PD controller (0.71 mU/kg per min vs. 1.81 mU/kg per min, p = 0.0005), when the glucose level in both methods reached the planned target level (100 mg/dl). The new system also tended to have a reduced mean glucose infusion rate for compensating for overshooting of the glucose level compared with the PD controller (0.7 mg/kg per min vs. 1.1 mg/kg per min, p = 0.16). These results indicate that the new system should be a useful tool for regulating the glucose level in severely diabetic patients.     

Non-invasive monitoring of gingival crevicular fluid for estimation of blood glucose level

Development of a non-invasive method for measuring the blood glucose level is an urgent necessity, and putting such a method into practical use will enable some of the physical and mental stress that patients with diabetes have to endure to be removed. To realise a non-invasive blood glucose monitor, the gingival crevicular fluid (GCF) was measured. A GCF-collecting device was developed that was designed to be disposable, biocompatible and small enough to be inserted in the gingival crevice for collection of a sub-microlitre sample of GCF. Also, a high-sensitivity glucose testing tape incorporated in the device was developed. Red laser light in a portable optical device measured the colour density of the testing tape. Standard glucose solutions were used to investigate the measurement accuracy of the GCF glucose monitor and showed a correlation coefficient of R=0.99 (n=20) between the optical density and the glucose levels. The GCF glucose monitor was evaluated on healthy Swedish and Japanese adults (n=10) and both GCF glucose levels (GCFLs) and blood glucose levels (BGLs) were measured in conjunction with meal loads. The GCFLs were about 1/10-1/560 lower than the BGLs. No difference in the range of GCFLs between the Swedish and the Japanese subjects was observed. Therefore it was concluded that physique, body mass index and life-style, such as dietary habit, did not significantly influence the GCFLs. Further, the correlation coefficients of all the subjects were 0.70 and 0.88 with each group. it was suggested that GCF could be used as a method of non-invasive blood glucose measurement.     

Determination of blood glucose using an oxidase-peroxidase system with a non-carcinogenic chromogen

Manual and automated methods for the determination of blood glucose have been devised using an oxidase/peroxidase system, with dl adrenaline, a non-carcinogen, as oxygen acceptor. The manual technique employs a stable single solution protein precipitant and the other reagents used are also stable. The automated methods are operated at 40/hr sample speed and washover between samples, over a very wide concentration range, is negligible.     

The hepatocellular uptake of glucose, galactose and fructose in conscious sheep.

1. Surgical techniques for chronic catheterization of hepatic and portal veins in the sheep are described. These catheters remained usable for 2-6 months and did not alter hepatic morphology. 2. Hepatocellular uptake of monosaccharides was estimated from their ability to pass the boundaries of the sucrose space in a double indicator dilution procedure in conscious fed sheep. 3. A large proportion (81%) of D-glucose carried in the portal blood was found to enter an hepatic cellular compartment. 4. The radioactive label of D-glucose infused in the portal vein remained associated with D-glucose in hepatic venous blood samples during the experimental period. 5. A large proportion (74%) of an infused trace of D-galactose, a smaller proportion (33%) of D-fructose, and negligible amounts of L-glucose were taken up in a single passage through the liver. 6. Raised blood concentrations of sucrose or of methyl-alpha-D-glucoside (Me-alpha-DG) significantly diminished the proportional uptake of D-glucose. Raised blood concentrations of glucose, galactose or Me-alpha-DG diminished the proportional uptake of D-galactose. Raised blood concentrations of fructose diminished the proportional uptake of fructose. 7. Neither total hepatic blood flow changes nor competitive effects within the cell could account for these findings. 8. It is concluded that these monosaccharides enter the liver cell by facilitated diffusion, and share at least some of the membrane elements that mediate this process. It seems likely that only a proportion of the glucose-transporting apparatus is accessible to galactose.     

Impairment of glycine absorption by glucose and galactose in man

1. In order to investigate a possible competition for intestinal transport between amino acids and monosaccharides in man, iso-osmotic solutions containing (A) 100 m-mole glycine 1.(-1), (B) 100 m-mole glycine and 200 m-mole monosaccharide (glucose or galactose) 1.(-1), and (C) 200 m-mole monosaccharide 1.(-1), were successively perfused into the upper jejunum of twelve African Zambian patients. None had clinical evidence of malnutrition or small-intestinal disease. By using a double-lumen tube and by reference to a non-absorbable marker (polyethylene glycol, 4000), the rates of absorption of these substances have been calculated for a 30 cm jejunal segment.2. The presence of glucose and galactose produced a significant impairment (up to 50%) in the rate of absorption of glycine. There was also a significant decrease in the uptake of both monosaccharides from the solutions in which glycine was also present.3. If this observation also applies to other amino acids it could have a practical value in population groups living on high carbohydrate diets with a marginal concentration of some essential amino acids. It could have special importance when the jejunal mucosa is damaged in severe malnutrition or gastrointestinal infection. This impairment of amino acid uptake may explain the very high incidence of genetically determined lactase-deficiency in Africa.     

The estimation of precipitating antibody using a turbidimetric technique

The development of turbidity resulting from the precipitation between bovine serum albumin (BSA) and anti-BSA serum was studied in the spectrophotometer. Data obtained with the turbidimetric method correlated well with those obtained using the classical tube precipitin determination. The equivalence ratio and the concentration of precipitating antibody were determined turbidimetrically by a comparison of the data from both methods. Antibody concentration can be determined with this method in about 1 hour as compared with the 3 or more days required by the tube test. In addition, this technique requires substantially less reagent than other methods.