Blood glucose level neural model for type 1 diabetes mellitus patients

This paper deals with the blood glucose level modeling for Type 1 Diabetes Mellitus (T1DM) patients. The model is developed using a recurrent neural network trained with an extended Kalman filter based algorithm in order to develop an affine model, which captures the nonlinear behavior of the blood glucose metabolism. The goal is to derive a dynamical mathematical model for the T1DM as the response of a patient to meal and subcutaneous insulin infusion. Experimental data given by continuous glucose monitoring system is utilized for identification and for testing the applicability of the proposed scheme to T1DM subjects.     

A fast generalizable solution method for glucose control algorithms

In critical care tight control of blood glucose levels has been shown to lead to better clinical outcomes. The need to develop new protocols for tight glucose control, as well as the opportunity to optimize a variety of other drug therapies, has led to resurgence in model-based medical decision support in this area. One still valid hindrance to developing new model-based protocols using so-called virtual patients, retrospective clinical data, and Monte Carlo methods is the large amount of computational time and resources needed.This paper develops fast analytical-based methods for insulin-glucose system model that are generalizable to other similar systems. Exploiting the structure and partial solutions in a subset of the model is the key in finding accurate fast solutions to the full model. This approach successfully reduced computing time by factors of 5600-144 000 depending on the numerical error management method, for large (50-164 patients) virtual trials and Monte Carlo analysis. It thus allows new model-based or model-derived protocols to be rapidly developed via extensive simulation. The new method is rigorously compared to existing standard numerical solutions and is found to be highly accurate to within 0.2%.     

Model predictive control of glucose concentration in type I diabetic patients: An in silico trial

In this paper, the feedback control of glucose concentration in type I diabetic patients using subcutaneous insulin delivery and subcutaneous continuous glucose monitoring is considered. A recently developed in silico model of glucose metabolism is employed to generate virtual patients on which control algorithms can be validated against interindividual variability. An in silico trial consisting of 100 patients is used to assess the performances of a linear output feedback and a nonlinear state-feedback model predictive controller, designed on the basis of the in silico model. More than satisfactory results are obtained in the great majority of virtual patients. The experiments highlight the crucial role of the anticipative feedforward action driven by the meal announcement information. Preliminary results indicate that further improvements may be achieved by means of a nonlinear model predictive control scheme.     

Blood glucose discrimination training in patients with type II diabetes

This study was designed to determine whether patients with Type II diabetes could be taught to discriminate blood glucose after experiencing a variety of blood glucose levels and receiving feedback on the accuracy of their estimates. Thirty-six subjects (18 on oral agents and 18 on insulin) were randomly assigned to one of two feedback conditions: (1) current feedback, which received accurate information regarding their blood glucose levels, (2) noncurrent feedback, which received blood glucose levels from the preceding session. Subjects were exposed to a wide range of blood glucose values in six training sessions by ingesting drinks with three different caloric loads. In pre/post comparisons using several indices of accuracy, both groups showed significant improvement in estimating blood glucose levels. However, feedback on current blood glucose levels did not produce greater improvement than noncurrent. Accuracy was unrelated to the degree to which subjects reported associating internal sensations to their estimates. Failure to find differences between the two feedback conditions may have been due to the noncurrent feedback group's receiving fairly accurate information, to the difficulty of the discrimination task, and to the limited number of training trials.     

A microdialysis technique for continuous subcutaneous glucose monitoring in diabetic patients (part 1)

The performances and the stability of a novel subcutaneous glucose monitoring system have been evaluated. GlucoDay (A. Menarini I.F.R. S.r.l, Florence Italy) is a portable instrument provided with a micro-pump and a biosensor coupled to a microdialysis system capable of recording the subcutaneous glucose level every 3 min. Long and short term stability of the biosensor are discussed and the results of some critical in vitro and in vivo (on rabbits) experiments are reported. A linear response up to 30 mM has been found for in vivo glucose concentration. The sensitivity referred to blood glucose is better than 0.1 mM and the zero current is typically below the equivalent of 0.1 mM. In the accuracy study a mean bias of 2.7 mg/dl and a correlation coefficient equal to 0.9697 have been found. At room temperature, an excellent membrane stability assures good performances up to 6 months from the first use.     

甘精胰岛素在2型糖尿病围手术期对血糖控制的有效性、安全性和效益成本分析

目的:比较2型糖尿病围手术期患者使用甘精胰岛素和速效胰岛素控制血糖的有效性、安全性和效益成本分析.方法:对外科系统需要择期或限期手术的2型糖尿病患者随机给予甘精胰岛素组加速效胰岛素类似物或预混胰岛素类似物控制血糖.结果:两组患者达到了类似的空腹血糖控制,但甘精胰岛素组达标率更高、血糖达标时间短以及低血糖反应更少.尽管甘精胰岛素组患者胰岛素成本较高,但其糖尿病相关检查治疗成本、病房成本以及迭标总成本更低.结论:甘精胰岛素加速效胰岛素类似物可有效控制T2DM患者的围手术期血糖,缩短血糖达标时间,减少低血糖发生率低以及降低住院费用.     

Blood glucose control in healthy subject and patients receiving intravenous glucose infusion or total parenteral nutrition using glucagon-like peptide 1

AIMS: It was the aim of the study to examine whether the insulinotropic gut hormone GLP-1 is able to control or even normalise glycaemia in healthy subjects receiving intravenous glucose infusions and in severely ill patients hyperglycaemic during total parenteral nutrition. PATIENTS AND METHODS: Eight healthy subjects and nine patients were examined. The volunteers received, in six separate experiments in randomised order, intravenous glucose at doses of 0, 2 and 5mg kg(-1) min(-1), each with intravenous GLP-1 or placebo for 6 h. Patients were selected on the basis of hyperglycaemia (>150 mg/dl) during complete parenteral nutrition with glucose (3.2+/-1.4 mg kg(-1) min(-1)), amino acids (n=8; 0.9+/-0.2 mg kg(-1) min(-1)), with or without lipid emulsions. Four hours (8 a.m. to 12 a.m. on parenteral nutrition plus NaCl as placebo) were compared to 4 h (12 a.m. to 4 p.m.) with additional GLP-1 administered intravenously. The dose of GLP-1 was 1.2 pmol kg(-1) min(-1). Blood was drawn for the determination of glucose, insulin, C-peptide, GLP-1, glucagon, and free fatty acids. RESULTS: Glycaemia was raised dose-dependently by glucose infusions in healthy volunteers (p<0.0001). GLP-1 ( approximately 100-150 pmol/l) stimulated insulin and reduced glucagon secretion and reduced glucose concentrations into the normoglycaemic fasting range (all p<0.05). In hyperglycaemic patients, glucose concentrations during the placebo period averaged 211+/-24 mg/dl. This level was reduced to 159+/-25 mg/dl with GLP-1 (p<0.0001), accompanied by a rise in insulin (p=0.0002) and C-peptide (p<0.0001), and by trend towards a reduction in glucagon (p=0.08) and free fatty acids (p=0.02). GLP-1 was well tolerated. CONCLUSIONS: Hyperglycaemia during parenteral nutrition can be controlled by exogenous GLP-1, e.g. the natural peptide (available today), whereas the chronic therapy of Type 2 diabetes requires GLP-1 derivatives with longer duration of action.     

Internal model sliding mode control approach for glucose regulation in type 1 diabetes

Patients with type 1 diabetes require insulin therapy to maintain blood glucose levels within safe ranges since their pancreas is unable to complete its function. The development of a closed-loop artificial pancreas capable of maintaining normoglycemia during daily life will dramatically improve the quality of life for insulin-dependent diabetic patients. In this work, a closed-loop control strategy for blood glucose level regulation in type 1 diabetic patients is presented. A robust controller is designed using a combination of internal model and sliding mode control techniques. Also, the controller is provided with a feedforward loop to improve meal compensation. A simulation environment designed for testing the artificial pancreas control algorithms has been used to evaluate the controller. The simulation results show a good controller performance in fasting conditions and meal disturbance rejection, and robustness against model–patient mismatch and meal estimation errors.     

Increased fructose-lysine of nail protein and blood glucose control in diabetic patients

Furosine, which was formed by acid hydrolysis of fructose-lysine, was determined and used as an indicator of glycosylated protein. The diabetic patients had significantly higher fructose-lysine levels in finger nails than healthy subjects [10.8 +/- 4.6% (mean +/- S.D.) vs 4.2 +/- 1.1%]. The best correlation was found between the fructose-lysine value and the fasting blood glucose level determined 3 to 5 months before sampling nails in diabetics. These results suggest that the furosine derived from fructose-lysine in finger nails may become an indicator of blood glucose control during the past 3 to 5 months in diabetics.     

Blood sugar control in diabetic patients bearing microinfusors: the importance of the dawn phenomenon

Significant early morning hyperglycemia (the so-called "dawn phenomenon") has been observed in insulin-dependent diabetics who were otherwise well controlled. This phenomenon, if present, could lead to errors in adapting the basal insulin infusion in CSII treated diabetic patients, because a normal glucose level in the morning could be associated with asymptomatic hypoglycemic values in the night. In order to observe the occurrence and to quantify the magnitude of this phenomenon 14 well controlled CSII-treated type I diabetics were hospitalized for 1 night and samples for the determination of blood glucose (14 patients) and serum cortisol, free insulin and NEFA (8 patients) were drawn at 24.00, 02.00, 04.00, 06.00, 08.00 h. Blood glucose values were slightly but significantly higher at 06.00 than at 02.00 (106 +/- 7.92 v.s. 88.57 +/- 7.02 mg/dl, p less than 0.025, paired Student t test) while serum free insulin values decreased from midnight to 02.00 and then they remained stable. It is concluded that the small increase of blood glucose values in the morning is not a major clinical problem in CSII treated diabetic patients.     

Effect of IGF-I on FFA and glucose metabolism in control and type 2 diabetic subjects

The effects of insulin-like growth factor I (IGF-I) and insulin on free fatty acid (FFA) and glucose metabolism were compared in eight control and eight type 2 diabetic subjects, who received a two-step euglycemic hyperinsulinemic (0.25 and 0.5 mU x kg(-1) x min(-1)) clamp and a two-step euglycemic IGF-I (26 and 52 pmol x kg(-1) x min(-1)) clamp with [3-(3)H]glucose, [1-(14)C]palmitate, and indirect calorimetry. The insulin and IGF-I infusion rates were chosen to augment glucose disposal (R(d)) to a similar extent in control subjects. In type 2 diabetic subjects, stimulation of R(d) (second clamp step) in response to both insulin and IGF-I was reduced by approximately 40-50% compared with control subjects. In control subjects, insulin was more effective than IGF-I in suppressing endogenous glucose production (EGP) during both clamp steps. In type 2 diabetic subjects, insulin-mediated suppression of EGP was impaired, whereas EGP suppression by IGF-I was similar to that of controls. In both control and diabetic subjects, IGF-I-mediated suppression of plasma FFA concentration and inhibition of FFA turnover were markedly impaired compared with insulin (P < 0.01-0.001). During the second IGF-I clamp step, suppression of plasma FFA concentration and FFA turnover was impaired in diabetic vs. control subjects (P < 0.05-0.01). CONCLUSIONS: 1) IGF-I is less effective than insulin in suppressing EGP and FFA turnover; 2) insulin-resistant type 2 diabetic subjects also exhibit IGF-I resistance in skeletal muscle. However, suppression of EGP by IGF-I is not impaired in diabetic individuals, indicating normal hepatic sensitivity to IGF-I.     

Blood glucose monitoring devices: the need for education,supervision and control.

In this decade liver transplantation has been established as the preferred treatment for children and adults with irreversible end-stage liver disease. Biliary atresia in children and nonalcoholic cirrhosis in adults are the most common indications for the procedure. Transplantation currently plays only a minor role in the treatment of hepatic malignant disease. Blood group compatibility between donor and recipient is preferred, but histocompatibility matching (tissue typing) currently has no significant role in the selection of recipients. Approximately 70% of recipients survive for 1 year, and these patients have an excellent prospect of long-term survival. The emerging evidence indicates that the quality of life and rehabilitation of most liver recipients are good. The current success of liver transplantation can be attributed to critical selection of recipients, modern anesthetic and surgical techniques, improved perioperative care, accurate diagnosis of rejection and superior immunosuppression with cyclosporine.     

A polymorphism in the cyclooxygenase 2 gene in type 1 diabetic patients with nephropathy

Diabetic nephropathy (DN), the most serious complication of Type 1 diabetes (DM1), has a strong genetic component. Cyclooxygenase-2 (COX-2), an inducible enzyme by a number of stimuli, has been implicated in pathophysiology of cardiovascular and renal disease, including DN. The allele -765C, of the -765G > C polymorphism (rs20417) in the COX-2 promoter has lower promoter activity compared with the -765G allele and protective effects in cardiovascular disease. This polymorphism was not investigated in patients with DM1 and nephropathy. The study was conducted in 779 Caucasian patients with DM1 and compared to a representative sample of healthy Czech population. The patients demonstrated lower frequencies of the CC genotype (P = 0.005). From the DM1 cohort, 153 patients met the criteria for low risk of the development of DN (LRDN, duration of DM1 > 10 years, normoalbuminuria, normotension) and 139 patients had manifest DN. There were no differences in -765G > C polymorphisms between LRDN and DN patients. Moreover, the C/G allele frequencies did not also differ between the groups. In conclusion, patients with DM1 display lower freqencies of the protective CC genotype as compared to healthy subjects. However, the study did not reveal associations of -765G > C polymorphism with the risk of DN.     

Fertility effects of family planning programs: A methodological review

Abstract

Extensive effort over the last ten to fifteen years has been applied to questions of what family planning programs do to birth rates. Here we review this body of work, looking especially at the different methods used. First, attention is called to the diversity of the field, in its questions, its techniques, in the program types studied, and in assumptions as to modes of actions. Then clarifications are suggested regarding which program features can produce fertility change and which patterns in fertility trends can result from the net action of these factors. Each of the major methods used is then presented, with its advantages and disadvantages and with recent illustrations of its application. A matrix comparison of the methods is added to show their characteristics in relation to each other, and suggestions are made as to the appropriate circumstances for using each. Finally, recent work is described that promises partially to give more comparability of results across different methods and program settings.