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Biomedical subjects

L Benzi

Publications and source records attributed to L Benzi.

At least 19 recordsLinked to original sources
PubMed1994

A prevalence study of known diabetes mellitus in Tuscany assessed from pharmaceutical prescriptions and other independent sources.

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.

Adult↗
PubMed1994

Insulin degradation in vitro and in vivo: a comparative study in men. Evidence that immunoprecipitable, partially rebindable degradation products are released from cells and circulate in blood.

The products of insulin metabolism generated in vitro and in vivo were compared in this study. Monocytes from 10 control subjects were incubated with 125IA14-labeled insulin, acid washed, and solubilized or reincubated in insulin-free binding buffer to study both intracellular radioactivity or radioactivity released from cells to medium. To evaluate in vivo insulin metabolism, labeled insulin (100-120 microCi) was injected as a single intravenous bolus in 5 of the 10 subjects. Cellular and plasma radioactivity was characterized by high-performance liquid chromatography (HPLC). The results of the study show the following: 1) Products with superimposable HPLC elution profiles are found within cells and in medium. Two new labeled products are observed in the latter, suggesting that a membrane degradation process exists in monocytes. 2) Intermediates found within monocytes, in medium from monocytes, and in plasma have identical elution profiles, supporting the possibility that insulin is metabolized in various cells by a common pathway. 3) Insulin metabolism produces intermediates that bind well to anti-insulin antibody. The presence in plasma of these products induces a significant difference in the value of the metabolic clearance rate of insulin when HPLC or immunoprecipitation is used to detect intact insulin. 4) Immunoprecipitable products maintain, in part, the capacity to bind to insulin receptors and to be internalized into monocytes.

Chromatography, High Pressure Liquid↗
PubMed1992

Change in glucose metabolism after long-term treatment with deflazacort and betamethasone.

We have compared the long-term effects of different corticosteroids on glucose metabolism by carrying out a 75 g oral glucose tolerance test in 27 subjects before and after the administration of deflazacort or betamethasone for two months in random balanced sequence. Fasting plasma glucose and insulin concentrations were significantly higher after betamethasone, whereas deflazacort increased only fasting plasma insulin. After oral glucose there were significant increases in blood glucose and insulin after betamethasone compared with deflazacort. These results suggest that the degree of glucose intolerance and insulin resistance depends on the steroid used and on the dose given, although long-term treatment with deflazacort has a smaller effect on glucose metabolism than betamethasone.

Administration, Oral↗
PubMed1990

Insulin degradation in vivo: a high-performance liquid chromatographic analysis.

The metabolism of insulin in vivo was investigated using an isocratic reversed-phase high-performance liquid chromatographic (RP-HPLC) method. After intravenous injection of A14-[125I]insulin into normals, eight labelled insulin derivatives were found in plasma (peaks 1-8). Two of them (peaks 1 and 7) showed an elution pattern identical with those of reference [125I]monoiodotyrosine and intact A14-[125I]insulin, respectively. Of the other six peaks, five (2-6) eluted before and one (peak 8) after insulin. This pattern was highly reproducible in terms of capacity factors and peak heights. Radioactivity separated by RP-HPLC was further characterized for its trichloroacetic acid precipitability and immunoprecipitability. Fractions corresponding to peaks 4-6 and 8, which showed an immunoprecipitability higher than 50%, were pooled in order to obtain sufficient radioactivity and were found to be insulin separated by Sephadex G-50 chromatography, containing in its structure, after sulphitolysis, intact A-chain and to be partially rebindable to monocyte insulin receptors. These data demonstrate that in blood, products of insulin metabolism circulate which retain a part of the immunological and biological properties of the hormone. These products are clearly separated from one another and from intact insulin by RP-HPLC, suggesting that the appropriate use of this technique may allow a further and more accurate qualitative and quantitative characterization of in vivo insulin metabolism in physiological and pathological conditions.

Chromatography, High Pressure Liquid↗
PubMed1990

Ibopamine does not affect insulin resistance in patients with type I diabetes.

Diabetes mellitus was assessed by investigating 8 type I diabetic patients, in good metabolic control and with congestive heart failure, who were studied after 3 weeks of placebo and ibopamine (100 mg t.i.d.) treatment. Metabolic control and daily insulin dose did not change in any patient during the study. The insulin-mediated glucose uptake during the clamp studies showed no variation after placebo or ibopamine therapy. Total cholesterol, HDL-cholesterol and triglycerides concentrations remained unchanged. This study clearly suggests that ibopamine administered at a daily dose of 300 mg for 3 weeks presents a metabolic safety in type I diabetic patients.

Adult↗
PubMed1990

Improvement with metformin in insulin internalization and processing in monocytes from NIDDM patients.

This study investigated the relative effect of obesity alone and in combination with non-insulin-dependent diabetes mellitus (NIDDM) on the intracellular processing of insulin and evaluated the effect of metformin therapy on this process. Monocytes from 11 obese hyperinsulinemic subjects, 13 obese hyperinsulinemic NIDDM patients, and 7 nondiabetic control subjects were incubated with A14-125I-labeled insulin for 60 min at 37 degrees C, and intracellular insulin degradation was characterized by high-performance liquid chromatography. Total cell-associated insulin (insulin binding) and internalized and degraded insulin were decreased in obese subjects and significantly decreased in obese NIDDM patients compared with nondiabetic control subjects. In NIDDM patients, intracellular insulin degradation was inversely correlated with fasting plasma glucose (P less than 0.01). Eight obese subjects and 9 obese NIDDM patients were restudied after 4 wk of therapy with metformin (850 mg twice a day). Plasma levels of the drug were superimposable in the two groups. Metformin therapy did not change glucose and insulin levels in obese subjects but caused a decrease in blood glucose in obese NIDDM patients. Total cell-associated radioactivity (insulin binding) significantly increased in both groups (P less than 0.01). On the contrary, internalized radioactivity increased (0.83 +/- 0.3 vs. 1.31 +/- 0.35%, P less than 0.01), and similarly, insulin degradation was enhanced (54.6 +/- 8.9 vs. 74.22 +/- 9.15%, P less than 0.01) only in monocytes from obese NIDDM patients. However, the levels of these parameters were still lower than in control subjects (internalization, 2.94 +/- 0.68%; degradation, 93.03 +/- 3.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗
PubMed1990

Diurnal pattern of plasma metformin concentrations and its relation to metabolic effects in type 2 (non-insulin-dependent) diabetic patients.

The authors describe the diurnal profile of plasma metformin concentrations in a group of 6 Type 2 (noninsulin-dependent) diabetic patients studied at two different daily metformin doses (500 mg and 850 mg b.d.) and report data on the relationships between plasma metformin and metabolic effects over a 14 h period. In addition, the effect of circulating metformin on insulin binding to isolated monocytes has been evaluated. At the two different daily doses fasting plasma metformin concentrations were similar (3.23 +/- 0.35 mumol/l and 3.86 +/- 0.72 mumol/l, mean values +/- SEM, at low and high dose respectively). Drug peak values and averaged concentrations (4.66 +/- 0.39 mumol/l vs 6.35 +/- 0.69 mumol/l) were significantly higher when more drug was administered. Mean plasma glucose was lower when 1,700 mg/day instead of 1,000 mg/day of metformin was given (7.3 +/- 0.4 mmol/l vs 9.1 +/- 0.9 mmol/l, p less than 0.05). After dosing, at higher plasma metformin concentrations corresponded lower plasma glucose values. The averaged blood lactate levels resulted 1.46 +/- 0.4 mmol/l (p less than 0.05 vs matched diet treated diabetic patients) at the higher drug dose. A significant positive correlation emerged between mean plasma metformin concentrations and mean blood lactate levels (r: 0.76, p less than 0.02). Alanine, glycerol and B-OH-butyrate levels were similar at the two metformin daily doses, and were not correlated to plasma metformin. The binding of insulin to isolated human monocytes was similar in metformin-treated diabetic patients (4.48 +/- 0.45) as in healthy volunteers (4.62 +/- 0.34); insulin binding was correlated (p less than 0.05) with plasma metformin levels.

Alanine↗
PubMed1989

Decreased salivary glucose secretory rate: usefulness for detection of diabetic patients with autonomic neuropathy.

In this study we investigated whether the presence of diabetic autonomic neuropathy (DAN) leads to an altered composition of saliva. DAN was evaluated in 33 normal subjects and 31 diabetic patients by means of the Valsalva manoeuvre, R-R variation during deep breathing, heart rate response to standing and lying down and blood pressure response to standing. Salivary flow (ml/h), salivary glucose levels (mumol/l) and salivary glucose secretory rate (mumol/h) were measured in each subject. Twelve diabetic patients were positive for DAN. Salivary flow (13 +/- 2 ml/h) and glucose concentration (330 +/- 50 mumol/l) were not significantly lower in patients with DAN than in normal subjects (18 +/- 2 ml/h, 500 +/- 50 mumol/l) and diabetic patients without DAN (16 +/- 1.9 ml/h, 500 +/- 40 mumol/l). The salivary glucose secretion rate was significantly lower (P less than 0.02) in diabetic patients with DAN (4.2 +/- 1.0 mumol/h) than in normal subjects and diabetic patients without DAN (9.0 +/- 1.0 mumol/h and 8.0 +/- 0.9 mumol/h respectively). The test had a good sensitivity and specificity, and appeared to be particularly indicated in discriminating patients without DAN. It is suggested that the measurement of salivary glucose may represent a simple, quick and inexpensive method for the screening of diabetic autonomic neuropathy.

Adult↗
PubMed1989

Defects in insulin-receptor internalization and processing in monocytes of obese subjects and obese NIDDM patients.

We investigated intracellular processing of the insulin-receptor complex in monocytes from 12 healthy control subjects, 11 obese nondiabetic subjects, and 13 obese patients with non-insulin-dependent diabetes mellitus (NIDDM) by measuring receptor internalization, recovery of cell-surface insulin binding after receptor internalization, and the release of intracellular intact insulin (insulin retroendocytosis). When monocytes from the three groups of subjects were exposed to 100 nM unlabeled insulin for 30 min at 37 degrees C, the subsequent cell-surface 125I-labeled insulin binding was reduced, but the total number of insulin receptors, measured by radioimmunoassay, was not changed. These findings indicate a redistribution of insulin receptors from the surface to the cell interior. Insulin-receptor internalization was significantly lower in monocytes of obese NIDDM patients (mean +/- SE 17.8 +/- 4.7%) than in obese subjects and healthy control subjects (33.5 +/- 4.5%, P less than .05, and 34.4 +/- 3.7%, P less than .02, respectively). Moreover, in downregulated cells, a complete recovery of the initial insulin binding was observed in control subjects but not in obese NIDDM patients or obese nondiabetic subjects. The release of internalized insulin was also reduced in obese NIDDM patients and obese subjects (t 1/2 = 49.0 +/- 2.4 min, P less than .02; 47.4 +/- 5.7 min, P less than .05; and 32.9 +/- 3.8 in NIDDM patients, obese subjects, and control subjects, respectively). In the radioactivity released from monocytes of obese subjects and obese NIDDM patients, the percentage of intact insulin was higher (P less than .05) than in control subjects, suggesting reduced intracellular insulin degradation in obese subjects and obese NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus↗
PubMed1989

Effects of metformin therapy on plasma amino acid pattern in patients with maturity-onset diabetes.

Plasma amino acid concentrations and metformin levels were measured by high-performance liquid chromatography in a group of diabetic patients on therapy with the biguanide drug. Diabetic patients treated with metformin showed higher concentrations of plasma glutamate, asparagine, alanine, methionine and tryptophan, and lower levels of ornithine in comparison with normal subjects, and higher levels of alanine when compared to diet-treated diabetic patients. No correlation emerged between amino acid concentrations and metformin dose or plasma concentration. It is concluded that besides the various metabolic abnormalities that are known to occur during metformin treatment, patients on therapy with metformin also show multiple changes of plasma amino acid pattern.

Aged↗
PubMed1988

Insulin degradation into monocytes from normal subjects: a high performance liquid chromatographic analysis.

In this work the fate of A14-125 I-insulin inside human cells has been investigated by the complementary use of gel permeation and reversed-phase high performance liquid chromatography to obtain a better resolution of the cell processed radioactive material resulting from the internalization of labeled insulin. Mononuclear leukocytes from 12 normals were incubated with pure A14-125 I insulin at 37 C and internalized radioactivity was characterized after 2, 15 and 60 min. Nearly 14% of intracellular radioactivity was associated to materials with a molecular weight of approximately 300,000. The remaining 86% had a molecular weight lower than 20,000. High molecular weight material showed an elution profile very similar to that obtained from purified human placental insulin receptor and was partially precipitable with antireceptor antibody. The reversed phase high performance liquid chromatography analysis of the low molecular weight material showed two main peaks corresponding to 125 I and A14-125 I-insulin and three intermediate peaks, a, b, c, accounting for about 8% of the recovered radioactivity. By increasing the incubation time of A14-125 I-insulin with monocytes a decrease of insulin peak (2 min: 38 +/- 18%; 15 min: 25 +/- 11%; 60 min: 6 +/- 4%) and a corresponding increase of iodide peak was observed. Immunoprecipitability with anti-insulin antibody was 0% for iodide and a peaks, 60% for peak b, 78% for peak c and 90% for A14-insulin peak. Our results show that intracellular insulin degradation procedes rapidly and in a time-dependent manner and that this process produces insulin derivatives which partially retain the immunological properties of intact A14-125 I insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Plasma biguanide levels are correlated with metabolic effects in diabetic patients.

Metabolic abnormalities occur in biguanide-treated diabetic patients. We investigated the relationship between plasma metformin and phenformin concentrations and metabolic effects. Drug levels were measured in 37 type II diabetic patients by HPLC. The method was sensitive, specific, and linear over a wide range of drug concentrations. Metformin and phenformin values ranged from 236 to 718 ng/ml and from 28 to 114 ng/ml, respectively. The plasma metformin level was correlated with triglycerides (r = -0.55; P less than 0.05) but not with drug dosage, plasma glucose, HbA1, creatinine, creatinine clearance, lactate, pyruvate, lipid, and clinical parameters. Plasma phenformin concentrations correlated with lactate (r = 0.49; P less than 0.05) and HbA1 (r = 0.50; P less than 0.05) but not with drug dosage, parameters of diabetes control, creatinine, creatinine clearance, pyruvate, and clinical parameters. The clinical usefulness of this HPLC method, the evidence that the increase of lactate is related to the circulating phenformin levels, and the demonstration that the metformin effect on triglyceride metabolism is correlated to plasma drug levels are the positive findings of this work.

Aged↗
PubMed1987

Intracellular insulin processing is altered in monocytes from patients with type II diabetes mellitus.

We studied total cell-associated A14-[125I]insulin radioactivity (including surface-bound and internalized radioactivity), insulin internalization, and its intracellular degradation at 37 C in monocytes from nonobese type II untreated diabetic patients (n = 9) and normal subjects (n = 7). Total cell-associated radioactivity was decreased in diabetic patients [2.65 +/- 1.21% (+/- SD) vs. 4.47 +/- 1.04% of total radioactivity; P less than 0.01]. Insulin internalization was also reduced in diabetic patients (34.0 +/- 6.8% vs. 59.0 +/- 11.3% of cell-associated radioactivity; P less than 0.01). Using high performance liquid chromatography six intracellular forms of radioactivity derived from A14-[125I] insulin were identified; 10-20% of intracellular radioactivity had approximately 300,000 mol wt and was identified as radioactivity bound to the insulin receptor, and the remaining intracellular radioactivity included intact A14-[125I]insulin, [125I]iodide, or [125I]tyrosine, and three intermediate compounds. A progressive reduction of intact insulin and a corresponding increase in iodine were found when the incubation time was prolonged. Intracellular insulin degradation was reduced in monocytes from diabetic patients; intracellular intact insulin was 65.6 +/- 18.1% vs. 37.4 +/- 18.0% of intracellular radioactivity (P less than 0.01) after 2 min and 23.6 +/- 22.3% vs. 3.9 +/- 2.3% (P less than 0.01) after 60 min in diabetic patients vs. normal subjects, respectively. In conclusion, 1) human monocytes internalize and degrade insulin in the intracellular compartment in a stepwise time-dependent manner; and 2) in monocytes from type II diabetic patients total cell-associated radioactivity, insulin internalization, and insulin degradation are significantly reduced. These defects may be related to the cellular insulin resistance present in these patients.

Aged↗
PubMed1987

Long-term therapy with biosynthetic human insulin: importance of short-acting/intermediate-acting insulin ratio on determining efficacy of treatment.

This report describes the efficacy of biosynthetic human insulin (BHI) in long-term (one year) therapy of type I diabetic patients previously treated with conventional insulins. The results were compared with those obtained in a group of diabetic patients kept on their usual treatment. In the latter, fasting plasma glucose, HbA1, insulin dose and relative proportions of insulin formulations remained constant throughout the study. In patients switched to BHI, hypoglycaemic episodes occurred during the first week of treatment and fasting plasma glucose was higher than basally at the first two visits (7th and 30th days). Both hypoglycaemia and high fasting plasma glucose were avoided by reducing the amount of short-acting insulin and increasing that of intermediate-acting insulin, so that the short-acting/intermediate-acting insulin ratio was significantly lower during BHI therapy, although the total daily insulin dose remained unchanged. HbA1 levels remained fairly constant throughout the study. It was concluded that in order to achieve full clinical efficacy of BHI, it is important to modify the proportions of short- and intermediate-acting insulin preparations accurately when switching patients from conventional insulin to biosynthetic human insulin.

Adult↗
PubMed1986

A14-[125I]monoiodoinsulin purified by different high-performance liquid chromatographic procedures and by polyacrylamide gel electrophoresis: preparation, immunochemical properties and receptor binding affinity.

Reversed-phase high-performance liquid chromatography (RP-HPLC) allows the rapid separation of A14-[125I]monoiodoinsulin directly from the iodination mixtures. It remains to be clarified, however, whether the RP-HPLC chromatographic conditions affect the properties of the purified tracer. In this study we prepared A14-[125I]insulin purified by polyacrylamide gel electrophoresis (PAGE) and by three different RP-HPLC mobile phases containing, respectively, ammonium acetate, sodium perchlorate and trifluoroacetic acid. The binding characteristics of all these tracers were examined using an insulin antiserum and insulin cell receptors. The specific radioactivity corresponded to the theoretical maximum for the RP-HPLC-purified tracers and was significantly lower for the PAGE-purified tracers. Significant differences were found in the binding of different tracers to the insulin antiserum: maximum binding ranged from 94 to 99% and was significantly lower for tracers purified by RP-HPLC eluents B and C; antiserum dilution giving 50% tracer binding was lower for tracers purified by RP-HPLC eluent B. The four insulin derivatives showed no difference in non-specific precipitation and in the affinity constant values calculated from the Scatchard analysis. No significant difference was found in the binding of the four insulin derivatives to the human-cultured IM-9 lymphocytes and to the human circulating monocytes. In conclusion, the present work demonstrates that the immunological properties of the A14-[125I]monoiodoinsulin purified by RP-HPLC may be partially affected by the composition of the mobile phase. In order to obtain a fully potent A14-[125I]insulin derivative and to have the possibility of comparing data from different laboratories, the chromatographic conditions must be taken into account.

Adult↗
PubMed1986

Salivary insulin concentrations in type 2 (non-insulin-dependent) diabetic patients and obese non-diabetic subjects: relationship to changes in plasma insulin levels after an oral glucose load.

The presence of immunoreactive insulin in saliva and its relationship to plasma immunoreactive insulin was investigated in healthy subjects, newly diagnosed non-obese Type 2 (non-insulin-dependent) diabetic patients and obese non-diabetic subjects, basally and after an oral glucose tolerance test. The mean +/- SEM fasting values of plasma and salivary immunoreactive insulin were significantly higher in diabetic patients and obese non-diabetic subjects than in normal volunteers (p less than 0.05). During the glucose challenge, the increase of salivary insulin was related with that of plasma in the three groups of subjects, with a time lag in normal and obese subjects. In normal volunteers, plasma and salivary peak values were respectively 49.5 +/- 13.4 microU/ml (p less than 0.05 vs obese subjects) at 60 min and 12.0 +/- 3.3 microU/min (p less than 0.05 vs obese subjects) at 120 min; in diabetic patients, the values were 51.7 +/- 5.6 microU/ml (p less than 0.05 vs obese subjects) and 14.6 +/- 4.1 microU/min at 120 min; in obese subjects, the peak value for plasma insulin was 111.5 +/- 40.1 microU/ml at 90 min and for salivary insulin 15.6 +/- 5.1 microU/min at 120 min. A positive linear relationship was shown between plasma and salivary insulin during the oral glucose tolerance test. The identity of salivary insulin was assessed by reversed-phase HPLC. We conclude that salivary immunoreactive insulin can be found in Type 2 diabetic patients and in obese non-diabetic subjects, as well as normal volunteers, that plasma and salivary insulin are related after a glucose load, and that differences exist in salivary insulin secretion patterns among the three groups of subjects.

Adult↗
PubMed1980

Decrease in plasma glucose concentration during storage at -20 degrees C.

We measured glucose concentrations with the Beckman Glucose Analyzer, before and after storage at -20 degrees C for various intervals, in 228 plasma samples from oral glucose tolerance tests on 17 normal subjects and 21 patients with impaired carbohydrate tolerance, and also in 82 control samples collected daily, after overnight fast, from seven insulin-dependent diabetics. We found a significantly (p < 0.001) positive relation between storage interval and percentage decrease in glucose concentration. Evidently, the longer plasma is stored, the greater the decrease in glucose.

Blood Glucose↗