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Biomedical subjects

R Navalesi

Publications and source records attributed to R Navalesi.

At least 109 records · Page 6Linked to original sources

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↗

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↗

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↗

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↗

Metabolic effects of three new low-dose pills: a six-month experience.

We evaluated the effects on glucose and lipid metabolism in 57 healthy volunteers randomly assigned to one of three low-dose oral contraceptives: two monophasic (desogestrel + ethinylestradiol, EE, and cyproterone acetate + EE) and one triphasic (gestodene + EE) contraceptives. Glucose and insulin responses during OGTT were slightly affected by the cyproterone pill. The insulin area/glucose area ratio and HbA1c level were unchanged in all women. No preparation affected total and LDL-cholesterol levels. Triglycerides rose in all groups, while HDL-CH did only in women taking the two monophasic pills. The three low-dose pills assessed in this study have negligible effects on glucose and lipid metabolism.

Adult↗

Clinical and metabolic effects of a pill containing 30 mcg ethinylestradiol plus 75 mcg gestodene.

The clinical and metabolic effects of a short-term treatment with a combination contraceptive pill containing 30 mcg ethinylestradiol and 75 mcg gestodene were evaluated in a group of 31 healthy women. The pill exerted good cycle control and the incidence of irregular bleeding was low. Side effects rarely occurred, and an improvement in premenstrual symptoms was reported during pill intake. Among the different biochemical parameters tested to monitor the coagulatory system, the only modification observed was an increase of fibrinopeptide A plasma levels, confirming that low-dose pills have less effects on the haemostatic system than oral contraceptives with a higher estrogen content. No significant modification in plasma total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-CH), HDL2-CH, nor low density lipoprotein-cholesterol were observed. HDL3-CH levels were significantly increased. Moreover, the pill did not significantly alter the fasting insulin and glucose levels nor their response to an oral glucose tolerance test. It may be suggested that this new formulation has high efficacy and clinical acceptability, primarily due to the total absence of any adverse metabolic effect.

Adult↗

Pharmacokinetic-pharmacodynamic relationships of oral hypoglycaemic agents. An update.

Oral hypoglycaemic drugs, sulphonylureas and biguanides, occupy an important place in the treatment of Type II (non-insulin-dependent) diabetic patients who fail to respond satisfactorily to diet therapy and physical exercise. Although the precise mechanisms of action of these compounds are still poorly understood, there is sufficient agreement that sulphonylureas have both pancreatic and extrapancreatic effects, whereas biguanides have predominantly extrapancreatic actions. By using labelled compounds or measuring the circulating concentrations, the main pharmacokinetic properties of oral hypoglycaemic agents have been assessed and, in some cases, their pharmacokinetic-pharmacodynamic relationships have been evaluated. A correlation between diabetes control and plasma sulphonylurea or biguanide concentrations is generally lacking at the steady-state, with the possible exception of long-acting agents; after either oral or intravenous dosing, the reduction of plasma glucose is usually related to the increased circulating drug concentrations. The toxic effects of oral hypoglycaemic drugs are more frequent in the elderly and in the presence of conditions that may lead to drug accumulation or potentiation (increased dosage, use of long-acting compounds, hepatic and renal disease, interaction with other drugs); however, a relationship between toxic effects and drug plasma levels has been reported only for biguanides.

Administration, Oral↗

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↗

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↗

Urinary albumin excretion in normal subjects and in diabetic patients measured by a radioimmunoassay: methodological and clinical aspects.

We have developed a radioimmunoassay method (RIA) to measure urinary albumin excretion. We determined the albumin excretion rate (AER) (micrograms/min) of 122 healthy subjects and 145 diabetic patients (115 type I, 30 type II). The results indicate that the RIA is sensitive (0.39 +/- 0.08 mg/L), precise (CV 5-8%), and gives reliable results on previously frozen urine samples. The distribution of the AER values in healthy subjects and diabetic patients was not normal. It was normalized by log or square-root transformation of the data. Seventy-three percent of diabetic patients lay within the normal range (0.6-10.6 micrograms/min). Twenty percent could be considered "at risk" to develop overt diabetic nephropathy because their albuminuria exceeded a threshold level of 15 micrograms/min chosen previously as the cutoff value for microalbuminuria. We found no correlation between AER and glycated hemoglobin, and only a weak correlation between AER and diabetes duration in type I diabetic patients.

Adolescent↗

[A case of factitious hypoglycemia with unusual presentation].

In this paper the Authors describe a case of factitious hypoglycemia in a 30-year-old nurse who came to the practitioner saying she was drug-addict. A careful history and the clinical examinations showed that the symptoms were due to hypoglycemic episodes. The finding of high plasma insulin levels together with low plasma C-peptide concentrations enabled us to exclude organic causes of hypoglycemia, suggesting the diagnosis of factitious hypoglycemia. After the patient was told we suspected a case of factitious hypoglycemia, the symptoms disappeared.

Adult↗