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Biomedical subjects

D Fedele

Publications and source records attributed to D Fedele.

At least 109 records · Page 6Linked to original sources
PubMed1975

Glucagon secretion in primary endogenous hypertriglyceridemia before and after clofibrate treatment.

Arginine-induced insulin and glucagon secretion preceding and following clofibrate treatment was studied in 13 patients with endogenous hypertriglyceridemia. A positive correlation was demonstrated between fasting insulin and triglyceride levels and between the fasting insulin/glucagon molar ratio and triglyceride levels. In patients with endogenous hypertriglyceridemia, anginine infusion induced a significantly increased glucagon response with respect to that found in controls. No correlation was found to exist between glucagon and free fatty acids (FFA) or between glucagon and triglyceride levels. The same lack of correlation was found in normal subjects rendered hypertriglyceridemic by means of Intralipid infusion, which did not modify the fasting glucagon-like immunoreactivity (GLI) or the GLI response to arginine. Clofibrate treatment induces a triglyceride reduction (incrementTG) which is correlated with the reduction in the insulin/glucagon molar ration (incrementI/G). After clofibrate treatment there is also a significant reduction in fasting GLI levels and in the insulin response to arginine, and an increase in the glucagon response. Clofibrate could exercise its hypolipidemic effect by modifying the relationship between insulin and glucagon levels.

Adult↗
PubMed1975

The influence of plasma triglycerides on human growth hormone response to arginine and insulin: a study in hyperlipemics and normal subjects.

Human growth hormone (HGH) response to arginine (25 gm IV in 30 min) and to insulin (0.1 U/kg B.W.) was studied in 12 male patients (mean age 36 +/- 2 years), with normal glucose tolerance and normal body weight, affected with Fredrickson's Type IV primary hyperlipemia. The patients were examined both when plasma triglycerides (TG) were elevated and following clofibrate (2 gm/die for 30-60 days) induced TG reduction. No variations in glucose or FFA behaviour or in body weight were observed after clofibrate. HGH response to arginine was absent, while that to insulin was only inhibited, when plasma TG were elevated. A significant increase in HGH peaks after arginine (from 1.99 +/- 0.59 to 9.34 +/- 1.58 ng/ml) and a slight increment in HGH peaks after insulin (from 23.09 +/- 7.19 to 31.46 +/- 7.95 ng/ml) were observed following reduction in plasma TG. Arginine test was carried out in 7 normal subjects during saline infusion and at the 3rd hour of lipid infusion (Intralipid 20%). HGH response to arginine was absent in all of the subjects during lipid infusion. The HGH response to insulin test, carried out in 9 other normal subjects during saline infusion and at the 3rd hour of lipid infusion (Lipiphysan 15%) was significantly inhibited during lipid infusion. Since lipid infusion provoked an increment, not only in plasma TG but also in FFA, the inhibition of HGH release could be correlated with the elevated plasma levels of both TG and FFA. The results obtained in both spontaneous and experimental hyperlipemia not only confirm the role played by FFA in the regulation of HGH secretion, but also support the hypothesis that elevated TG levels could inhibit HGH response to some stimuli.

Adult↗
PubMed1975

Human growth hormone and cortisol response to insulin stimulation in aging.

The influence of age on plasma growth hormone (HGH) and cortisol response to i.v. insulin (0.1 U/kg of body weight) was evaluated in 32 healthy subjects whose ages ranged between 20 and 84 years. A significant reduction in HGH response to insulin was observed with aging. In the young (20-34 years), middel-aged (35-49 years), and elderly (53-84 years) groups, average HGH peaks were 46.51 +/- 7.37, 29.95 +/- 5.35, and 14.31 +/- 2.39 ng/ml while average HGH areas were 2.911 +/- 0.484, 1.654 +/- 0.316, and 0.699 +/- 0.149 mug-min, respectively. Since insulin's hypoglycemic effect became less rapid with aging, this could, in part, explain the progressive decline in the HGH response to insulin. This phenomen may also be attributed to histological changes occurring in the pituitary with aging. Moreover, cortisol response was similar to all three age groups. These findings suggest that, while HGH response to insulin is correlated with age, adrenal response does not show any important modifications with aging.

Adult↗
PubMedDate not supplied

The role of mass spectrometry in the study of non-enzymatic protein glycation in diabetes.

Mass spectrometry has been applied successfully to the study of non-enzymatic protein glycation, which is a topic of wide interest in the diabetes field. Low- and high-resolution mass spectra, GC/MS, and collisional activation spectroscopy allow the structural identification and quantitative evaluation of advanced glycation end-products, which represent important molecules for monitoring diabetes. More recently available techniques, such as ESI and MALDI/MS, have had a significant impact on analytical problems in diabetes. In particular, MALDI has been applied to the study of protein glycation in in vitro and in vivo conditions, because the number of glucose molecules that condense onto the protein can be easily determined by this approach. In the former case, glycation kinetics have been studied in various sugars and sugar concentrations, proteins, and buffer concentrations; in the latter, comparisons of MALDI spectra of circulating proteins from healthy and diabetic subjects determine the exposure of patients to high glucose levels. The method has been applied to an evaluation of the glycation level of immunoglobulins, and indicates that glycation takes place preferentially on the Fab fragment of the protein; data are relevant in relating immunological impairment with glycation-induced changes in the functionality of immunoglobulins.

Animals↗
PubMedDate not supplied

Diabetes and mass spectrometry.

Mass spectrometry (MS) has been successfully employed to investigate non-enzymatic protein glycation, a process relevant in diabetic disease. The high sensitivity and specificity of this technique allowed the development of methods that can individuate and evaluate some glycation markers to be validly employed in monitoring diabetes. More recent mass spectrometric techniques, such as the matrix-assisted laser desorption/ionization (MALDI), are able to determine the molecular weight of intact proteins. They were first employed in studying the in vitro reaction between hexoses and different proteins. Once the validity of the results obtained by this analytical approach was confirmed, a series of investigations on plasma proteins were undertaken in healthy and diabetic subjects. The method led to the evaluation of the number of glucose molecules condensed on the protein being studied, and consequently can be validly used for an accurate follow-up of metabolic control in diabetic patients. When applied to studies on haemoglobin glycation, the method showed that both alpha- and beta-globins are glycated to a similar extent and that the simply glycated molecules are accompanied by glyco-oxidized species therefore giving information on the oxidative stress experimented on in the subject. Furthermore, in the case of immunoglobulins, MALDI/MS was able to determine not only the total glycation level of IgG, but also to establish that the fragment antigen binding (Fab) moiety is the most glycated one, thus suggesting that the possible immunological impairment sometimes invoked in diabetes is related to the inhibition of the process of molecular recognition between antibody and antigen.

Globins↗
PubMedDate not supplied

Insulin therapy in pregnancy complicated by diabetes: are insulin analogs a new tool?

It has been demonstrated that good metabolic control maintained throughout pregnancy can reduce maternal and fetal complications in diabetes. To achieve good metabolic control, before conception and throughout pregnancy, insulin therapy needs to be optimized, and, in this context, the new insulins currently on the market may help. We therefore review here what is known about the potential benefits and risks related to the use of these new insulins in pregnancy. Clinical and experimental data on insulin lispro strongly suggest that lispro does not have adverse maternal or fetal effects during pregnancy in women with preexisting diabetes, and also that its use in these women results in improved glycemic control, fewer hypoglycemic episodes, and improved patient satisfaction. In women with gestational diabetes mellitus (GDM), the use of insulin lispro is efficient in reducing postprandial hyperglycemia and some neonatal features related to hyperglycemia, thus stressing its usefulness in this condition. As for insulin aspart, clinical data on GDM patients shows the same efficacy as insulin lispro in lowering postprandial hyperglycemia, indicating that insulin aspart may be used in GDM when this condition is characterized by postprandial hyperglycemia. The results of a multicentric study now in progress on the efficacy and safety of insulin aspart in type 1 pregnant diabetic patients will definitely be useful in establishing whether this insulin is safe in pregnancy. For the moment, the use of insulin glargine during pregnancy is not recommended owing to the lack of data on maternal and fetal effects.

Diabetes Mellitus, Type 1↗
PubMedDate not supplied

Glucagon levels and ketogenesis in human diabetes following total or partial pancreatectomy and severe chronic pancreatitis.

In three groups of patients with insulin-dependent diabetes following total (n = 5) or partial (n = 5) pancreatectomy or chronic pancreatitis (n = 7) and in a group of idiopathic diabetics, ketogenic capacity following insulin withdrawal and during a 24-h fast was studied. Basal glucagon values were significantly increased in all diabetic groups with no significant intergroup differences. Basal ketone body values and their increase during starvation and insulin withdrawal were high and not different in totally pancreatectomized and primary diabetics, both showing unmeasurable C-peptide levels. On the contrary, ketogenesis was reduced in partially pancreatectomized and in pancreatitis diabetics with persistent levels of C-peptide. Our data confirmed the persistence of immunoreactive glucagon after pancreatectomy and demonstrated that ketogenesis is not suppressed in pancreatectomized diabetics and depends above all on residual B-cell function. A possible ketogenic effect of extra-pancreatic glucagon-like substances cannot be excluded.

Chronic Disease↗
PubMedDate not supplied

Glucagon and insulin secretion in potential diabetes.

Insulin and glucagon have been studied in 20 subjects (both of the subjects' parents were diabetic or in case of only one diabetic parent, the other showed a first degree familiarity of diabetes): 10 showed normal glucose tolerance ('true prediabetics') and 10 impaired glucose tolerance ('genetic chemical diabetes'). Mean insulin response to oral (100 g) and i.v. glucose load (200 mg/kg followed by 20 mg/kg/min for 60 min) and to arginine infusion (25 g in 30 min) was normal in the prediabetics and delayed and higher in the subjects with chemical diabetes as compared to the control group. Glucagon response to arginine was higher, but not significantly, in prediabetics and in subjects with chemical diabetes. In both of these groups glucagon suppression by glucose was not observed. The insulin/glucagon molar ratio was significantly reduced after glucose infusion in these two groups. No correlation was found between insulin and glucagon secretion after arginine or glucose. A possible alteration in the mechanism controlling glucagon secretion even in the earliest phases of diabetes is suggested.

Adult↗
PubMedDate not supplied

Glycated serum proteins and glucose tolerance.

Glycated serum proteins (GSP), stable glycated hemoglobin (HbA1c) together with some metabolic parameters were evaluated in 120 subjects, 30 with normal glucose tolerance (NGT), 30 with impaired glucose tolerance (IGT), 30 with non-insulin-dependent diabetes mellitus (NIDD), and 30 with insulin-dependent diabetes mellitus (IDD). GSP levels were significantly higher in IGT, NIDD and IDD than in NGT. HbA1c levels were not significantly higher in IGT in comparison with NGT, but were significantly higher in NIDD and in IDD than in NGT and IGT. GSP correlated better than HbA1c with all metabolic parameters considered. Taking into account the distribution of the values, GSP showed a smaller overlap than HbA1c in all four groups studied. Moreover, only 9 subjects (30%) with IGT showed GSP levels above the normal range. Therefore, GSP assay is able to distinguish between normal and diabetic subjects but is unable by itself to discriminate subjects with normal from those with reduced glucose tolerance.

Adult↗
PubMedDate not supplied

Serum lipid and lipoprotein levels and metabolic control in insulin-treated diabetics.

Serum lipid and lipoprotein levels were evaluated in 50 insulin-treated diabetic out-patients (25 male and 25 female) and in 46 normal volunteers (22 male and 24 female). In these groups metabolic evaluation was carried out by assaying fasting plasma glucose, glucose in urine and glycosylated hemoglobin (G-HbA1). No differences were observed in the lipid and lipoprotein patterns between diabetic patients and normals. HDL values were significantly lower in male subjects, diabetic and normal, as compared to females, but there were no differences between the diabetic and the normal group. G-HbA1 was significantly correlated to fasting plasma glucose and glucose in urine, but also to WS-TG and VLDL-TG. Fasting plasma glucose too was correlated to WS-TG and VLDL-TG. Moreover, a negative correlation was found between HDL-Ch and WS-TG and VLDL-TG. These results show that sufficiently well-controlled insulin-treated diabetics do not have altered plasma lipid and lipoprotein levels. In particular, in these patients HDL-Ch values can be normal, because insulin levels are sufficient to activate lipoprotein lipase and to guarantee an adequate plasma VLDL clearance.

Adult↗
PubMedDate not supplied

Glycosylated hemoglobin in endogenous hypertriglyceridemia.

Fifty out-patients with endogenous hypertriglyceridemia were submitted to glycosylated hemoglobin (GHb) and glucose tolerance assessment. Fifteen had normal glucose tolerance (NGT), 15 had impaired glucose tolerance (IGT) and 20 had non-insulin-dependent diabetes mellitus (NIDDM). GHb was 6.3% in NGT, 7.3% in IGT and 8.11% in NIDDM and was significantly correlated to fasting and post-prandial plasma glucose (p less than 0.001) in NIDDM group and to peak, area (p less than 0.001) and 2-h plasma glucose levels (p less than 0.05) of OGTT in the NGT and IGT groups. Out of the 15 IGT subjects only 6 had GHb levels above the control range, while 9 had normal GHb values. These data show that also in hyperlipemic subjects GHb values are related to glucose tolerance, and suggest that GHb evaluation alone is not sufficient for the diagnosis of impaired glucose tolerance. In order to evaluate whether plasma turbidity can affect GHb dosage, GHb was evaluated in 10 hyperlipemic subjects with various degrees of hypertriglyceridemia both in the presence (whole blood hemolysate) and absence (isotonic saline hemolysate) of plasma triglycerides. The results show that, with our method, plasma turbidity does not affect GHb evaluation.

Adult↗