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In order to test whether or not an in-service requalification course on diabetes care for health professionals (HP) of nondiabetological departments can enhance their level of knowledge about diabetes and the quality of care for diabetic inpatients admitted for reasons other than diabetes, we carried out a requalification course involving 171 HP (161 nurses and 10 midwives) from nondiabetological departments of our hospital. Areas of intervention were: general knowledge of diabetes (GKD), bedside monitoring of blood glucose (BMG), insulin preparation and administration (IPA), diagnosis and treatment of hypoglycemic crises (DTH), and hospitalization-related problems (HRP). HP, divided into groups of about 20 each, completed a basal evaluation by means of a 25-item multiplechoice questionnaire, and then attended six separate educative sessions, each focusing on one topic, consisting of a theory lesson and an interactive exercise of equivalent length. At the end of the course, HP were re-evaluated with the same questionnaire, and their skills in BMG, IPA and DTH were tested by means of specific operational checklists, which divided each complex operation into a sequence of single operations, and then compared them with those of a control group of untrained colleagues (CG). The global knowledge of diabetes after the course significantly improved, as gathered from the percentages of correct answers in each questionnaire (61.82%±23.64% vs 31.18%±20.00%;P<0.001); separate analysis of different areas evidenced improvements in GKD (72.28%±12.47% vs 31.46%±20.56%;P<0.01), BMG (68.77%±15.75% vs 37.50%±27.75%;P<0.01), IPA (72.02%±11.72% vs 33.45%±21.22%;P<0.05), and DTH (90.76%±6.86% vs 49.82%±26.68%;P<0.05), but not in HRP. Professional skills profiles of HP, evaluated by measuring the number of errors done performing each task, were significantly (P<0.001) better than those of CG, for BMG (1.09±0.73 vs 4.91±2.01), IPA (2.36±1.64 vs 5.64±2.25), and DHT (1.27±0.94 vs 3.82±1.12). Linear regression showed a significant (P<0.001) correlation of skills and knowledge after the course for BMG (r2=.49), IPA (r2=.53), and DTH (r2=.61). Positive although nonspecific indicators of outcomes of the course were the increase (of about 100%) of requests to our metabolic unit for diabetologic consultations from other departments as well as the mentioning of diabetes in the diagnosis of discharge, and the 200% increase in the consumption of sticks for BMG. The course produced a significant improvement of knowledge and skills on specific diabetologic items among participants.

In this study we evaluated whether isolated human (HI), porcine (PI) and bovine (BI) islets, either fresh (Fr) or cultured for 4 weeks (4w) affect cytokine release from human lymphomononuclear cells (LMC) differently. We prepared LMC from peripheral blood by density gradient purification and co-cultured 1×106 LMC for 24 h with 100 hand-picked islets, either within 48 h of isolation or after culture for 4 weeks. Soluble interleukin-2 receptor (IL-2R), interferon-gamma (IFN), interleukin-4 (IL-4) and interleukin-10 (IL-10) were measured by sandwich enzyme-linked immunoadsorbent assay. Compared with controls (Ctrl, LMC without islets), Fr-HI, Fr-PI and Fr-BI caused a similar increase of IL-2R and IFN release, whereas 4w-HI and 4w-BI did not lead to any significant production of these two cytokines. IL-10 concentrations increased with Fr-PI and Fr-BI, but not with Fr-HI, and no major effect of the 4-week culture was seen. IL-4 levels were below the detection limit of the method used in these experiments. Thus, fresh allo- and xeno-islets caused a similar increase of the release of cytokines known to be markers of Th1 activation, whereas the release of IL-10, a marker of Th2 activation, increased with xeno-, but not with allo-islets; culturing the islets for 4 weeks decreased Th1, but not Th2 activation.

The effects of the angiotensin-converting enzyme lisinopril were compared with those of the calcium antagonist nifedipine in 162 non-insulin-dependent diabetic hypertensive patients for a 24-week period. In 83 and 79 patients, respectively, lisinopril and slow-release nifedipine produced similar reductions in blood pressure (systolic/diastolic: -16/-13 mmHg supine and -14/-11 mmHg standing after lisinopril; -15/-12 mmHg supine and -14/-11 mmHg standing after nifedipine). Fasting and post-prandial plasma glucose, glycosylated haemoglobin and plasma lipids appeared to be unaffected by either agent. Also, 28% of the patients on lisinopril and 30% of those on nifedipine presented microalbuminuria. Both drugs induced a reduction in the albumin excretion rate (AER). The geometric meanxx: tolerance factor of the reduction in AER among the 23 microalbuminuric patients on lisinopril (-10.0xx:1.3 µg/min) was greater, though not significantly so, than that observed in the 26 on nifedipine (-0.9x:1.2 µg/min). Moreover, lisinopril appeared to be better tolerated than nifedipine in our study population. Microalbuminuria is an important risk factor for cardiovascular mortality in non-insulin-dependent diabetic patients as well as in the general population. To what extent a reduction in the AER could ameliorate the cardiovascular prognosis in non-insulin-dependent diabetic patients is, at present, unknown. Finally, both lisinopril and nifedipine showed a similar antihypertensive effect in these patients which was not associated with significant differences in plasma glucose, insulin or lipid concentrations. The clinical consequences of the insignificant differences in AER remain unclear.

This study evaluates the prevalence of diabetes mellitus (DM) in Pisa (Tuscany, Italy) using four independent data sources. The main source, represented by computerized prescriptions for anti-diabetic agents collected over a 4-month period, was validated using three secondary sources: (a) the list of diabetic patients who receive material of self-care from the National Health Service; (b) the clinical records of diabetic patients obtained from a random sample of family doctors; (c) the clinical records of diabetic patients attending our outpatient clinic. The main source provided 3806 patients, and 697 patients were added from the secondary sources, thus identifying a total number of 4503. The prevalence of known DM in the “Pisa area” exclusively reckoned by the main source, was 2.01%, and the prevalence corrected by the addition of the various sources resulted in 2.4%. The capture-recapture method showed a completeness of ascertainment of the survey of 90.1%, and thus an estimated prevalence of known diabetes of 2.64%. Of these, 141 patients had insulin-dependent diabetes mellitus (IDDM) corresponding to 3.2% of identified diabetic subjects (prevalence 0.07% inhabitants); 4362 patients had non-insulin-dependent diabetes mellitus (NIDDM), 96.8% of identified diabetic subjects (prevalence 2.36%). Of patients with NIDDM 10.5% was treated by diet, 65% with oral hypoglycaemic agents (OHA), 23% with insulin and 1.5% with insulin plus OHA. This study shows that the method used in this survey is suitable for epidemiological studies because it does not demand the cooperation of the diabetic patients, is addressed to the entire diabetic population without age discrimination and singles out the diabetic population in a very reliable way.

We tested the level of knowledge on diabetes and professional skills in a group of 60 non-diabetological health care professionals at the Policlinic of Pisa regarding the recognition and treatment of hypoglycaemia, the storage, mixing and administration of insulin, blood glucose stick monitoring, and the prevention and treatment of diabetic foot. The evaluation was carried out using a multiple-choice questionnaire and observation of the jubjects, performance by means of pre-defined observation of a blend of rapid-intermediate insulin, the use of blood glucose sticks and the management of a simulated hypoglycaemic crisis. As regards hypoglycaemia, 90% of subjects did not give a correct definition, 88.3% were unaware of the existence of asymptomatic hypoglycaemia, and 96.6% did not give a complete answer as to the treatment of hypoglycaemia. For insulin, 51.7% did not know the standards for correct storage of insulin, 88.3% did not know the difference between “clear” and “opaque” insulins, and 91.7% ignored the required interval between administration of regular insulin and meals. For foot care, 45% admitted that the problems with diabetics' feet were frequently not controlled, and between 21.7% and 63.3% did not known the hygiene rules for feet. Assessment of the performance of the subjects using schedules revealed incorrect use of sticks and administration of insulin (80.2% mixed and 92.4% injected the insulin incorrectly). There is clearly a need for education of non-diabetological health professionals regarding the disease. This is supported by the health professionals themselves, 94.5% of whom wished to participate in a course on diabetes.

Supranormal urinary albumin excretion (microalbuminuria) is an early indicator of microangiopathy, i.e. diabetic nephropathy, and is associated with higher cardiovascular mortality in both type 1 and type 2 diabetes. The relationship between the presence of microalbuminuria and some atherosclerotic risk factors has been evaluated in 318 (170 male, 148 female) type 2 (non-insulin-dependent) diabetic subjects [age 63±10 years; known duration of diabetes 10.9±8.8 years; age at diabetes diagnosis 52±11 years; systolic blood pressure (BP) 150±23 mmHg; diastolic BP 86±11 mmHg (mean±SD)]. In “early morning” urine samples, albumin (immunonephelometry) and creatinine were assayed. On the basis of the albumin/creatinine ratio (A/C, mg/mmol), patients were categorized as normoalbuminuric (Na; A/C<2.0;n=159, 50%), microalbuminuric (ma; A/C 2–20;n=135, 42.5%) or macroalbuminuric (Ma; A/C >20;n=24, 7.5%). The three groups were closely matched for age, age at diagnosis, duration of diabetes, and fasting plasma and urinary glucose levels. Systolic and diastolic BP rose progressively with increasing urinary A/C ratio levels. While high-density lipoprotein (HDL) cholesterol was unaffected by albuminuria, total cholesterol (218±45 vs 198±43 mg/dl,P<0.001) and low-density lipoprotein (LDL) cholesterol (145±42 vs 131±38 mg/dl,P<0.05) levels were higher in microalbuminuric than in normoalbuminuric patients. Further, a significant correlation (r=0.16,P<0.01) existed between albuminuria and triglyceride concentrations. Prevalence of arterial hypertension, defined as BP=160/95 mmHg and/or drug treatment (Na, 51%; ma, 65%; Ma, 78%;P<0.001) and obesity, defined as body mass index (BMI)>30 (Na, 15%; ma, 26%; Ma, 32%;P<0.05) rose with increasing A/C ratios. Both coronary heart disease (30% vs 15%) and intermittent claudication (18% vs 7%) were more frequent in microalbuminuric than in normoalbuminuric subjects. Finally, multiple stepwise regression analysis showed that urinary albumin excretion is significantly and independently associated with coronary heart disease and intermittent claudication, also taking into account hypertension and other established cardiovascular risk factors. In type 2 diabetes microalbuminuria tends to aggregate with risk factors for atherosclerotic vascular disease, e.g. increased prevalence of hypertension and obesity, elevated total and LDL cholesterol, and raised triglycerides levels. These abnormalities may only explain the excess of cardiovascular morbidity and mortality in part. Microalbuminuria per se may be an important and independent cardiovascular risk factor.

The prevalence of microalbuminuria and arterial hypertension among type 1 (insulin-dependent) diabetic patients is poorly known in Italy. In the preliminary phase of a large outpatient screening programme, we addressed the possibility of using non-time urine samples to predit the chance of detecting albumin excretion rate (AER) in the range of microalbuminuria. We therefore measured urinary albumin and creatinine concentration in timed overnight collections from 641 type 1 diabetic patients with serum creatinine levels lower than 133 µmol/l. AER was strongly and comparably predicted both by urinary albumin concentration (UAlb;r2=0.754) and by the urinary albumin to creatinine concentration ratio (A/C;r2=0.773). After exploring several independent cut-off levels for UAlb and A/C, AER in the range 20–200 µg/min (n=91) was found to be predicted with 90% sensitivity and specificity either by UAlb?20 mg/l or by A/C?2.0 mg/mmol. UAlb was negatively associated with diuresis, and false negative outcomes were explained by polyuria when screening by this variable. A/C was positively associated with female gender among normoalbuminuric patients, in line with the lower urinary excretion of creatinine in women (7.2±0.25 vs 10.2±0.35 µmol/min,P<0.00001). A significant excess of false positive outcomes in women compared with men was found when screening by any A/C cut-off level equal to or less than 2.5 mg/mmol. Simplified screening techniques seem to remain, however, a practicable option for the detection of microalbuminuria both in epidemiology and in clinical practice.

We have compared the chemical and clinical characteristics of an immunonephelometric assay (INA), two immunoturbidimetric assays (ITA) and two semiquantitative methods with those of a solid-phase radioimmunoassay (RIA) for measurement of urinary albumin (UA) concentration in 136 diabetic patients. INA and RIA had similar accuracy, and provided comparable results. However, RIA has slightly greater sensitivity than INA, which is easier and faster. Good agreement was also found between RIA and the two ITA methods, although one of these overestimated RIA values in the low-medium range (5–30 mg/l) of urinary albumin. ITA seems suitable for initial screening of albuminuria in diabetic patients but more sensitive procedures (such as RIA and INA) seem preferable for measurement of UA concentrations in the normal range. The two semi-quantitative methods showed high sensitivity but poor specificity, because of the large number of false positive results. About 50% of diabetic patients “positive” by these methods did not have microalbuminuria. The utility of these methods is questionable, because many samples from diabetic patients need to be reassayed by a more specific and sensitive assay such as the RIA, INA or ITA methods.

Bovine islets are being evaluated for their potential in transplantation studies. We studied the recovery, morphology, and function of purified bovine islets cultured up to 4 weeks under varying conditions. Approximately 60% of the initial islet mass could be recovered after 4 weeks at 37°C in CMRL 1066 or M 199 culture medium, and the cultured islets were well preserved histologically and viable both in vitro and in vivo. On the other hand, culture with RPMI 1640 caused disaggregation of the islets within a few days, with altered in vitro viability. Thus, culturing purified bovine islets with appropriate media is a suitable procedure to maintain islet mass, morphology, and function in the long term.

It is still a controversial question whether insulin suppresses its own secretion. We prepared pure human islets from three pancreases by collagenase digestion and density gradient purification. Aliquots of 200 islet equivalents (IE, 150-µm sized-islets) were sequentially perifused at 37°C with 3.3 mmol/l glucose (3.3G, 40 min), 16.7 mmol/l glucose (16.7G, 30 min) and again 3.3G (30 min) after 24 h, 37°C culture in CMRL 1066 medium with or without the addition of either 200 or 400 µU/ml human insulin in the incubation medium (6 replicates each). Insulin secretion was assessed by C-peptide (Cp) measurement in the perufusate. Without added insulin (C) and with 200 (Ins200) or 400 (Ins400) µU/ml added insulin, basal Cp release was 0.12±0.03, 0.14±0.02 and 0.14±0.04 ng/ml, respectively. At 16.7G, the first-phase secretion peak (expressed as Cp value) was significantly lower with Ins200 (0.47±0.13 ng/ml,P<0.02) and Ins400 (0.68±0.15 ng/ml,P<0.05) than C (0.83±0.15 ng/ml). The second-phase secretion peak was also significantly (P<0.05) reduced with added insulin (Ins200: 0.47±0.08 ng/ml; Ins400: 0.45±0.07 ng/ml) than in its absence (C: 0.65±0.09 ng/ml). Accordingly, total Cp secretion was lower with Ins200 (10.6±2.3 ng/ml,P=0.03) and Ins400 (11.8±2.3 ng/ml) than with C (16.0±2.2 ng/ml). Thus, the addition for 24 h of either 200 or 400 µU/ml insulin in the culture medium caused a significant decrease of insulin (as assessed by Cp measurement) secretion from perifused human islets, suggesting that feedback suppression of insulin release is at least in part due to a direct action of insulin on the islets.

Abstract: Isolated human pancreatic islets were prepared by collagenase digestion and density gradient purification, and the effects of glibenclamide (0.5 and 5.0 µmol/l) and metformin (20 and 200 µmol/l), alone or in combination, on insulin release were evaluated at varying glucose concentrations. At 3.3 mmol/l glucose level, the addition of 5.0 µmol/l glibenclamide or 5.0 µmol/l glibenclamide plus 200 µmol/l metformin caused a significant increase of insulin release, compared with glucose alone. At 16.7 mmol/l glucose concentration, a significant increase of insulin secretion, compared with glucose alone, was produced by the addition of either 5.0 µmol/l glibenclamide, 200 µmol/l metformin, or both 5.0 µmol/l glibenclamide and 200 µmol/l metformin. The effect of the combination of the two drugs was significantly higher than that with either drug used alone. Thus, glibenclamide was shown to have an insulinotropic effect on human islets at both low and high glucose concentrations, and metformin at high glucose concentrations. A possible synergistic effect of glibenclamide and metformin at high glucose concentrations is also suggested.