Massimo Massi Benedetti

A Meta-analysis of Trials on Aldose Reductase Inhibitors in Diabetic Peripheral Neuropathy

Peripheral neuropathy is one of the most common and disabling long‐term seque lae 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.

Risk Factors for Lower Limb Complications in Diabetic Patients

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 practitioners 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.

Patterns of Care of an Italian Diabetic Population

We set out to describe patterns of care of an Italian diabetic population, with reference to the recommendations of the St Vincent Declaration. We investigated different aspects of care received by 2707 patients, of whom 2196 in the charge of 35 Diabetes Outpatient Clinics (DOCs) and 511 cared for by 49 General Practitioners (GPs). Data were collected by interviewing the patients, their physicians and by reviewing medical records. Our data show that diabetes care in Italy differs in many aspects from the recommendations of the St Vincent Declaration. Glycated haemoglobin measurement was lacking in 50 % of the patients in the charge of GPs and in 15 % of those attending DOCs. While the control of cardiovascular risk factors was satisfactory, information on albumin excretion was not available in one third of the patients. Overall, 79 % of the patients had had an eye examination in the previous 12 months. More than one‐third of the patients had not received adequate information on different aspects of care, with wide variations according to the setting of care. Forty‐two per cent of the patients attending DOCs and 14 % of those cared for by GPs practised blood glucose self‐monitoring; similarly, insulin therapy self‐management was performed by 50 % and 19 % of the patients attending DOCs and GPs, respectively. Our data call for vigorous efforts aimed at improving the awareness of the potential for reducing major diabetic complications. Therefore, it is essential to promote the incorporation of clearly defined clinical practice guidelines at each level of care.

Privacy impact assessment in the design of transnational public health information systems: the BIRO project

Objectives: To foster the development of a privacy-protective, sustainable cross-border information system in the framework of a European public health project. Materials and methods: A targeted privacy impact assessment was implemented to identify the best architecture for a European information system for diabetes directly tapping into clinical registries. Four steps were used to provide input to software designers and developers: a structured literature search, analysis of data flow scenarios or options, creation of an ad hoc questionnaire and conduction of a Delphi procedure. Results: The literature search identified a core set of relevant papers on privacy (n = 11). Technicians envisaged three candidate system architectures, with associated data flows, to source an information flow questionnaire that was submitted to the Delphi panel for the selection of the best architecture. A detailed scheme envisaging an “aggregation by group of patients” was finally chosen, based upon the exchange of finely tuned summary tables. Conclusions: Public health information systems should be carefully engineered only after a clear strategy for privacy protection has been planned, to avoid breaching current regulations and future concerns and to optimise the development of statistical routines. The BIRO (Best Information Through Regional Outcomes) project delivers a specific method of privacy impact assessment that can be conveniently used in similar situations across Europe.

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.

Kinetics and Metabolic Activity of Biosynthetic NPH Insulin Evaluated by the Glucose Clamp Technique

The glucose clamp technique has been used to evaluate the metabolic activity of NPH biosynthetic insulin in diabetic subjects free from anti-insulin antibodies. After overnight blood glucose normalization with a glucose-controlled insulin infusion system (Biostator), an s.c. injection of NPH insulin was given in the abdominal region. The insulin dose (0.236 ± 0.05 U/kg body wt) was related to the usual intermediate-acting insulin requirement in the morning. Glucose was clamped at 100 mg/dl by a feedback i.v. glucose infusion. The end of the action of s.c. injected insulin considered conventionally to be the time of the spontaneous rise of blood glucose to 110 mg/dl. Free insulin levels were higher and the length of action was longer after NPH porcine than after NPH biosynthetic human insulin (BHI) (area under the free insulin curve: porcine 1423 ± 556 mU/L/h; BHI 1045 ± 338 mU/L/h, P < 0.05; length of action: porcine 16.0 ± 3.2 h; BHI 13.7 ± 0.9 h, P < 0.05); the glucose requirement was higher after porcine (76.8 ± 13.5 g) than after BHI (58.5 ± 14.6 g) without reaching statistical significance. However, the metabolic activity of the bioavailable insulin (index of plasma free insulin activity) was similar for the two insulins (porcine 381 ± 77.4, BHI 342.8 ± 54.2 mU/L/g of glucose/h). We conclude that a difference in pharmacokinetics exists between NPH BHI and porcine NPH insulin, which makes the latter metabolically more active. The different behavior does not seem to be related to the insulin molecule itself but could be a consequence of the unequal content of protamine in the two pharmacologic preparations.