A mathematical model describing the glycemic response of diabetic patients to meal and i.v. infusion of insulin.

Nine type 1 diabetic patients were studied for 24 hours. During this period they were given three calibrated meals. The glycemia was feedback-controlled by means of an artificial pancreas. The blood concentration of glucose and the infusion speed of the insulin were measured every minute. The experimental data referring to each of the three meals were used to estimate the parameters of a mathematical model suitable for describing the glycemic response of diabetic patients at meals and at the i.v. infusion of exogenous insulin. From the estimate a marked dispersion of the parameters was found, both interindividual and intraindividual. Nevertheless the models thus obtained seem to be usable for the synthesis of a feedback controller, especially in view of creating a portable artificial pancreas that now seems possible owing to the realization (so far experimental) of sufficiently reliable glucose concentration sensors.

A detailed examination of the clinical terms and concepts required for communication by electronic messages in diabetes care.

The wider electronic exchange of clinical information between heterogeneous information systems in the delivery of diabetes care demands a common structure in the form of a message standard. A European Standard electronic diabetes message is being developed in conjunction with CEN TC251. This paper describes the methodologies that the 1998 DO IT Workshop has used to identify potential areas of difficulty in the design and implementation of the preliminary message model. To facilitate implementation and to avoid ambiguity in electronic messaging it is particularly important that there is standardisation of the definitions of the clinical terms specifically used in diabetes care across systems. Comprehensive lists of such terms to describe all areas of diabetes care do not exist and there is a lack of harmonisation of definitions in many areas. Thus, to better understand the user requirements of diabetes messaging several approaches were adopted. A review of the clinical terms and concepts contained in pre-existing datasets was undertaken with detailed study of a number of specific areas of diabetes care, analysing the conceptual structure of all the clinical terms that they comprised. Consideration of several worst case clinical scenarios for messages to communicate was also made to identify deficiencies in the message structure. This activity confirmed the importance of creating a Standard for a superset or thesaurus of diabetes specific terms, with appropriate definitions, to harmonise data communication in different IT systems to facilitate messaging. A substantial number of new terms were identified in the workshop and these will form an important first step to accomplishing a first draft superset once fully analysed. It was also apparent that certain specific areas within diabetes care, but most particularly in nursing, dietetics and podiatry, need urgent work to further develop the concepts and terms. This needs to be facilitated for an appropriate group of such professionals. To achieve such a Standard, continued co-operation with CEN/ISSS was recognised to be very important.

A model of the endogenous glucose balance incorporating the characteristics of glucose transporters.

This paper describes the development and preliminary test of a model of the endogenous glucose balance that incorporates the characteristics of the glucose transporters GLUT1, GLUT3 and GLUT4. In the modeling process the model is parameterized with nine parameters that are subsequently estimated from data in the literature on the hepatic- and endogenous- balances at various combinations of blood glucose and insulin levels. The ability of the resulting endogenous balance to fit blood glucose measured from patients was tested on 20 patients. The fit obtained with this model compared favorably with the fit obtained with the endogenous balance currently incorporated in the DIAS system.

Risk factors for lower limb complications in diabetic patients. The Italian Study Group for the Implementation of the St. Vincent Declaration.

Diabetic lower extremity complications may be influenced by a number of factors, including those related to the interaction between patients and the health-care system. Our objective is to identify risk factors for the development of lower limb complications, by looking for classical clinical variables and those related to quality of care. A case-control study was carried out between December 1993 and June 1994 by interviewing 348 patients with lower-limb diabetic complications and 1050 controls enrolled from 35 diabetes outpatient clinics and 49 general practitioner's offices in Italy. Among sociodemographic characteristics associated with increased risk of lower limb complications were male gender [odds ratio (OR) = 2.5, confidence interval (CI) 1.6-3.9], age between 50 and 70 years as opposed to younger than 50 (OR = 3.6, CI 2.1-6.3) and being single as opposed to married (OR = 1.4, CI 1.1-1.8). Among clinical variables, treatment with insulin for IDDM and NIDDM patients was an important predictor of lower extremity complications compared to NIDDM patients not being treated with insulin. Cardio-cerebrovascular disease and presence of diabetic neuropathy were associated with a higher risk of being a case (OR = 1.4, CI 1.2-1.8 and OR = 3.0, CI 2.1-4.2, respectively). Patients who needed help to reach the health facility before the onset of the complications and those who did not attend health facilities regularly were more liable to develop complications (OR = 1.5, CI 1.1-2.2 and OR = 2.0, CI 1.3-3.0, respectively). Patients who had never received educational intervention had a threefold risk of being a case as compared to those who received health information regularly. The study identifies factors most likely to be related to adverse outcome and permits to discriminate between avoidable and unavoidable factors.

A meta-analysis of trials on aldose reductase inhibitors in diabetic peripheral neuropathy. The Italian Study Group. The St. Vincent Declaration.

Peripheral neuropathy is one of the most common and disabling long-term sequelae of diabetes mellitus. Aldose reductase inhibitors (ARIs) have been proposed and are increasingly used in many countries for the prevention and treatment of diabetic neuropathy. The aim of this study was to review existing evidence on the effectiveness of ARIs in the treatment of peripheral diabetic neuropathy, with particular reference to the type and clinical relevance of the end point used and to the consistency of results across studies. Thirteen randomized clinical trials (RTCs) comparing ARIs with placebo, published between 1981 and 1993 were included in the meta-analysis. Nerve conduction velocity (NCV) was the only end point reported in all trials. Treatment effect was thus evaluated in terms of NCV mean difference in four different nerves: median motor, median sensory, peroneal motor, and sural sensory. A statistically significant reduction in decline of median motor NCV was present in the treated group as compared to the control group (mean 0.91 ms-1; 95% CI 0.41-1.42 ms-1). For peroneal motor, median sensory, and sural sensory nerves results did not show any clear benefit for patients treated with ARIs. When the analysis was limited to trials with at least 1-year treatment duration, a significant effect was present for peroneal motor NCV (mean 1.24 ms-1; 95% CI 0.32-2.15 ms-1) and a benefit of borderline statistical significance was also present for median motor NCV (mean 0.69 ms-1; 95% CI-0.07-1.45 ms-1). A heterogeneous picture emerged when looking at the results of different studies and serious inconsistencies were also present in the direction of treatment effects among nerves in the same studies. Although the results of 1-year treatment on motor NCV seem encouraging, the uncertainty about the reliability of the end-point employed and the short treatment duration do not allow any clear conclusion about the efficacy of ARIs in the treatment of peripheral diabetic neuropathy.

Validation of a computerised measurement system for guided routine evaluation of cardiovascular autonomic neuropathy.

A study for evaluating the use of the Cardionomic system was conducted in six Italian Centres for Diabetes. Cardionomic is a portable computerised system that is used for a guided step-by-step performance of several cardiovascular tests for autonomic neuropathy (heart rate and blood pressure). It has been compared to the traditional method using an electrocardiograph. In this study, which involved 74 diabetic patients, 392 cardiovascular tests were conducted with the electrocardiograph and 392 were done using the portable system. The results were compared to the results obtained with the ECG assuming the latter as the standard ones. All the indices of validity that were investigated (sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio) indicate that the proposed system is reliable. Because it saves a considerable amount of time and is also easy to use, it represents a valid alternative for the routine screening of autonomic neuropathy.

A comprehensive assessment of the avoidability of long-term complications of diabetes. A case-control study. SID-AMD Italian Study Group for the Implementation of the St. Vincent Declaration.

OBJECTIVE: To identify and quantify risk factors for the development of long-term diabetic complications (i.e., critical limb ischemia, amputation, chronic renal failure [creatinine > 3 mg/dl], dialysis treatment, proliferative retinopathy, blindness), with particular emphasis on those variables that, being related to quality of care, can be considered avoidable. RESEARCH DESIGN AND METHODS: We designed a case-control study that enrolled 886 patients with long-term diabetic complications and 1,888 control subjects without complications from 35 diabetic outpatient clinics and 49 general practitioners offices during a 6-month period. Selected socioeconomic, pathophysiologic, self-care, health care, and lifestyle information were collected for all patients. RESULTS: A logistic regression analysis showed that several factors are related to the development of major diabetic complications. Among patient characteristics, male sex (odds ratio [OR] = 1.8, 95% CI 1.4-2.3) and age (OR = 1.7, 95% Cl 1.2-2.4 for patients between 50 and 69 years of age as opposed to those younger than 50 years of age) were associated with an increased risk of complication. Among clinical variables, the type and the duration of diabetes were the most important predictors of diabetic complications. The presence of hypertension was also associated with the development of diabetic complications, particularly when it was poorly controlled by treatment (OR = 3.1, 95% CI 2.3-4.3). Patients who needed help to reach a health care facility and those who did not regularly attend such a facility were at higher risk of developing complications (OR = 1.5, 95% CI 1.2-1.9; OR = 1.7, 95% CI 1.3-2.2, respectively). Educational aspects were also related to the outcome: patients who did not receive any kind of educational intervention had an increased risk of developing complications (OR = 4.1, 95% CI 1.7-9.7), while self-management of insulin therapy had a protective effect (OR = 0.6, 95% CI 0.5-0.8). The summary attributable risk related to avoidable risk factors (i.e., uncontrolled hypertension, poor compliance with visit scheduling, inadequate diabetes education, no self-management of insulin treatment) was 0.39. CONCLUSIONS: Our data suggest that, by removing avoidable risk factors, the number of diabetic complications considered could be reduced by more than one-third. The case-control methodology represents an efficient way of monitoring clinical practice and relating it to important outcomes. It can be of help for policy makers in identifying the more effective strategies and in tailoring specific interventions aimed at improving the quality of the care delivered to diabetic patients.

Advanced health care initiatives in Europe on quality development, epidemiology and medical documentation.

Since the St. Vincent Declaration was published in 1989, several different but logically linked activities have been initiated. In addition, there are projects in adjacent fields supporting each other by exchange of information and partial co-operation. This paper provides an overview of their structure and describes the different projects.

Lactate and pyruvate electrochemical biosensors for whole blood in extracorporeal experiments with an endocrine artificial pancreas.

Glucose, lactate, and pyruvate can be continuously measured in whole blood by using three extracorporeal electrochemical biosensors. We fixed two newly developed sensors, for lactate and pyruvate, in series with an endocrine artificial pancreas ("Betalike") without affecting its performance. These new sensors for use with whole blood should be able to clarify the fate of the intermediary metabolites of glucose in diabetic patients receiving infusions of drugs or insulin.

A reliable and reproducible test for adequate glucose counterregulation in type I diabetes mellitus.

The safety, reproducibility, and reliability of an insulin infusion test for assessment of adequate glucose counterregulation were evaluated in 18 patients with type I (insulin-dependent) diabetes mellitus. When the test (a 60-min, 30-mU/m2/min insulin infusion) was administered on three separate occasions at 3-4-wk intervals, coefficients of variation for plasma glucose and counterregulatory hormone (glucagon, epinephrine, cortisol, and growth hormone) responses averaged less than 8%. No patient experienced symptoms requiring discontinuation of the test and plasma glucose concentrations increased spontaneously after stopping the insulin infusion. Using objective criteria based on plasma glucose nadirs or postnadir rates of plasma glucose recovery, no patient judged to have adequate glucose counterregulation by the test (postnadir rates of plasma glucose recovery or plasma glucose nadir above 0.4 mg/dl/min and 45 mg/dl) developed severe hypoglycemia (plasma glucose less than 40 mg/dl) during up to 7 mo of intensive insulin therapy, whereas nearly all patients with inadequate counterregulation did. We conclude that this test, when performed in standardized conditions, is safe and reproducible and can reliably predict those patients with type I diabetes who are at risk of developing severe hypoglycemia during intensive insulin therapy.

Glucose intolerance in uremia (A- and B-cell function during conservative and dialytic management.

Glucose tolerance and insulin and glucagon secretion were investigated in two groups of uremic patients, respectively on conservative and hemodialytic treatment. For this purpose, a glucose infusion was performed in the fasting state. Glucose intolerance was observed in uremic patients; hemodialysis improved, but did not normalize the glucose disposal. In uremic patients both on conservative and dialytic treatment plasma insulin and glucagon levels were higher than in the control group; the pattern of glucagon suppression was well maintained. The data obtained suggest that glucose intolerance in uremia is related mainly to peripheral insulin resistance and is not due to hyperglucagonemia.