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Biomedical subjects

G Crepaldi

Publications and source records attributed to G Crepaldi.

At least 253 records · Page 14Linked to original sources

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↗

Effects of fat mass reduction by dieting and by lipectomy on carbohydrate metabolism in obese patients.

The interrelation of enlarged body fat mass (BFM) with reduced carbohydrate tolerance and hyperinsulinemia was studied in obese subjects with chemical diabetes. These patients were subjected to lipectomy following weight loss induced by a low-calorie, low-carbohydrate diet. An improvement in glucose tolerance and in insulin sensitivity and a reduction in insulin release during OGTT was observed after a diet-induced BFM loss of 9.9 +/-1.2 kg. Subsequent surgical reduction of BFM by 6.0 +/- 0.5 kg had no further effect upon carbohydrate tolerance, insulin release or insulin sensitivity though a marked decrease in basal plasma FFA values was observed. These findings suggest that fat mass enlargement per se has no effect on blood glucose homeostasis after oral or i.v. loading. The improvement in carbohydrate tolerance and in insulin resistance usually observed following diet-induced loss of BFM seems to be due to the reduction in calorie and carbohydrate intake rather than to decrease of BFM.

Adipose Tissue↗

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↗

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↗

Ganglioside treatment in diabetic peripheral neuropathy: a multicenter trial.

Ganglioside treatment was evaluated with a multicenter, randomized, double-blind, controlled, cross-over vs placebo trial in 140 insulin-treated diabetic subjects with peripheral neuropathy. The patients entered the study when they showed an impairment in at least two of the electroneurographic parameters, and were assigned to two protocols according to the presence and severity of their neurological symptoms. Ninety-seven diabetic subjects with no or mild symptoms were assigned to protocol I, whereas 43 symptomatic patients were assigned to protocol II. the treatment periods lasted 6 weeks with an intermediate washout period of 4 weeks. The treatment consisted in the daily i.m. administration of 20 mg gangliosides or of placebo. Electroneurographic parameters were recorded at the beginning and at the end of each treatment period, whereas clinical and metabolic data (mean daily plasma glucose, glycosuria and glycosylated hemoglobin) were evaluated every three weeks in protocol I and every two weeks in protocol II. No change in the metabolic parameters was observed throughout the trial period. However, the treatment induced a statistically significant improvement of paresthesias (protocol II) and of some electrophysiological parameters; in particular, ganglioside treatment improved MCV of peroneal nerve (p less than 0.03) in patients of protocol I, MCV o ulnar nerve (p less than 0.002) and SCV of median nerve (p less than 0.06) in patients of protocol II. Furthermore, 22 subjects of protocol II showed a 'drug preference' while 10 preferred placebo and 9 had no preference. In conclusion, ganglioside treatment seems to have a positive effect on diabetic peripheral neuropathy, improving both some symptoms and some electrophysiological parameters.

Adolescent↗

Effect of aging on growth hormone, ACTH and cortisol response to insulin-induced hypoglycemia in type I diabetes.

The influence of age on plasma growth hormone (GH) response to i.v. insulin (0.2 U/kg body weight) was evaluated in clinically stable type I (insulin-dependent) diabetics divided into four age groups (range 18.80 years). ACTH and cortisol were also assayed in two groups of diabetics under and over 50 years of age. A significant reduction with aging in GH response to insulin was observed. On the contrary, the glucose fall was similar in all the groups. ACTH and cortisol responses to insulin were slightly decreased in the older diabetics. Since insulin-induced hypoglycemia was similar in all the age groups, the progressive decline with aging in the GH response to insulin may be attributed to age-related changes of the pituitary gland. The data on ACTH and cortisol are less striking. Our data, as a whole, confirm that growth hormone response to insulin-induced glucose fall is not critical in acute glucose counterregulation in insulin-dependent diabetics. In fact, in spite of a 4-fold difference in GH levels, there was no difference in the 2-h glycemic course after 0.2 U/kg of i.v. insulin between young and aged patients. When a group of 26 type I diabetics with proliferative retinopathy was compared with a group of age-matched type I diabetics without retinopathy and with 30 age-matched normal subjects (injected i.v. with 0.1 U/kg body weight of insulin), no difference was found in GH response to insulin, indicating that GH hypersecretion is not a characteristic finding of diabetic retinopathy.

Adolescent↗

Improvement of electroimmunoassay for apolipoproteins B and A-I. (Preliminary observations in postprandial phase).

A reliable method for determining serum apoprotein levels is an essential condition for investigating the role of apoproteins in atherogenesis. Electroimmunoassay according to Laurell has been studied and applied with some modifications for the determination of the two main apoproteins: Apo A-I and Apo B. Apo B immunoplates containing 0.4% v/v of rabbit anti-Apo B antiserum were processed for 4 h at 10 V/cm. Samples were incubated at 52 degrees C for 3 h, diluted and then 10 microliter were seeded in each well. Apo A-I immunoplates (8% v/v of sheep antiserum) were processed for 24 h at 2 V/cm. Agarose gel concentration, exsiccation procedure and staining were the same for both apoproteins. The method was standardized employing a secondary standard consisting of a serum pool obtained from normal subjects. Apo A-I and Apo B levels of the pool have been previously determined employing as primary standards the HDL3 (1.120-1.230 g/ml) and the LP-B (1.035-1.050 g/ml) fractions, respectively, which were isolated by preparative ultracentrifugation. Preliminary observations from a study on 20 healthy volunteers with normal lipid levels revealed different apoprotein levels in young men and women and significant differences between postmenopausal women and women in the fertile age.

Apolipoprotein A-I↗

Long-term effects of colestipol (U-26,597 A) on plasma lipids in familial type II hyperbetalipoproteinaemia.

Results related to long term treatment with Colestipol (a new resin sequestering bile acids) in 23 subjects with familial hypercholesterolaemia, 12 with Type IIA, 8 with Type IIB and 3 homozygotes are reported. Patients were given 15 g/day active drug for a period of 12 months and a double dose (30 g/day) for a successive period of 4 months along with a low cholesterol, low saturated fat, polyunsaturated fat-rich diet. Mean cholesterol decrease was --42 +/- 18 mg/dl (P less than 0.05) after 12 months of 15 g/day Colestipol and --69 +/- 17 mg/dl (P less than 0.01) after the following 4 months of 30 g/day Colestipol. The difference between the two periods of treatment (15 g and 30 g/day was not statistically significant. A slight but not significant increase in triglyceride levels was observed. Serum uric acid showed a significant increase throughout the entire period of treatment. No malabsorption syndrome or signs of toxicity were seen. Most frequent side effects were constipation, nausea, and metheorism which, with the exception of 4 cases which were withdrawn from the study, were reported as being transitory and mild.

Adult↗

Growth hormone response to insulin and to arginine in patients with familial hypercholesterolaemia.

Human growth hormone (HGH) response to i.v. insulin (0.1 U/kg body weight) and arginine infusion (25 g of L-arginine for 30 min) was studied in 9 patients (5 males and 4 females) with primary familial hypercholesterolaemia and belonging to 4 families. Mean age was 28 +/- 2 years (range 18-36) and body weight was less than 105% of ideal body weight. Glucose tolerance and insulin response to oral glucose were normal in all patients. HGH release after insulin and after arginine was slightly increased as compared to 21 normal controls, but the differences were not significant. Insulin and glucagon response to arginine in these patients was within the normal range. Plasma glucose and free fatty acids were normal after both insulin and arginine. Moreover, no significant correlation was found between fasting cholesterol and HGH peaks after insulin and after arginine, nor between cholesterol and insulin and glucagon responses. Despite marked hyperlipidaemia, HGH-deficient patients examined by other authors never present signs of atherosclerotic disease. Our data suggest that HGH, in the presence of elevated cholesterol levels, might play an important role in the development of atherosclerotic lesions.

Adolescent↗

Effects of clofibrate treatment on arginine-induced insulin secretion in endogenous hypertriglyceridemia.

Arginine-induced insulin secretion was evaluated in 13 patients with endogenous hypertriglyceridemia (Fredrickson's Type IV) before and after a two-month period of Clofibrate therapy. Clofibrate reduced triglyceride, cholesterol and FFA levels by 68, 28 and 15% respectively and provoked a significant reduction in arginine-induced insulin secretion without modifying glucose response. Arginine-induced insulin secretion was also studied in 11 normal subjects during saline and intralipid infusions. Glucose and insulin basal values, and glucose and insulin response to arginine infusion were not influenced by Intralipid infusion in these controls. These results confirm that clofibrate reduces insulin secretion thereby contributing to decreased serum triglyceride levels.

Adult↗

Collisional spectroscopy as a screening procedure for the determination of FFI in complex natural matrices.

The build-up of brown products on long-lived proteins could be an important factor in determining long-term diabetic complications. A brown product 2-(2-furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI), present in the acid hydrolysate mixtures of beta-polylysine and beta-albumin has been identified by collisional spectroscopy, using a commercial double-focusing, reverse-geometry mass spectrometer. Using this approach the analyses were carried out without any sample derivatization or need for chromatographic separation procedures.

Albumins↗

Effects of one-year cyclical treatment with clodronate on postmenopausal bone loss.

We studied 60 women with postmenopausal bone loss randomly allocated to the following treatments: Group 1 (20 patients), no treatment; Group 2 (20 patients), clodronate 400 mg daily by mouth for 30 consecutive days, followed by 60 days of no treatment; Group 3 (20 patients) oral calcitriol 2 mcg by mouth for 5 days and oral clodronate 400 mg daily for additional 25 days, followed by 60 days of no treatment. The therapeutic cycles were repeated four times in the 12-month study period. In the 36 treated patients of Groups 2 and 3 who completed the study period we observed a progressive and significant increase in lumbar bone density both at 6 and 12 months of therapy, without significant differences between the two treatment protocols (+3.88 +/- 0.65%, P < 0.001 and +3.21 +/- 0.89%, P < 0.005 in Groups 2 and 3, respectively, at the end of the study). In contrast, there was a progressive and significant decline of bone mineral density in untreated patients (-2.34 +/- 0.49%, P < 0.001). After 12 months serum calcium values in treated subjects were higher than in untreated patients (P < 0.05). Serum phosphate was raised only in Group 2, mean values being higher after 12 months than before treatment (P < 0.05); parathyroid hormone (PTH) declined in all treated patients, the fall being significant in Group 2 (P < 0.02). No important side effects were observed with treatment and no patient withdrew because of these. We conclude that cyclical low dose clodronate therapy induced a gain in lumbar spine bone mass in patients with postmenopausal osteoporosis.

Administration, Oral↗

[International study of the effect of dexfenfluramine in obesity (ISIS): 6 months' results].

International study of the effect of dexfenfluramine in obesity (ISIS): 6 months results. ISIS is a multicentre therapeutic trial of the "intention to treat" type organized to test the effectiveness and side-effects of dexfenfluramine combined with diet in the treatment of obesity. This was a randomized, double-blind drug versus placebo study programmed for a one-year period. Eight hundred and twenty-two obese patients were included. Dexfenfluramine was administered in doses of 15 mg b.d. The intermediate results after 6 months of treatment are presented. Significant differences were observed between the dexfenfluramine group (n = 404) and the placebo group (n = 418). In the treated group: 1) the drug withdrawal rate was lower, mainly due to a greater number of patients in the placebo group dissatisfied with their weight loss; 2) about twice as many patients achieved an important loss of weight in terms of percentage of the initial weight or overweight; 3) the cumulative loss of weight was greater; 4) there was a higher incidence of transient side-effects, such as fatigue, diarrhoea, dry mouth, polyuria and drowsiness. These results suggest that dexfenfluramine will be suitable for a more prolonged treatment of obese patients, in addition to diet.

Adult↗

Modification of cardiovascular risk factors during antihypertensive treatment: a multicentre trial with quinapril.

A large multicentre study involving 6003 [3044 males, 2959 females; mean (+/- SD) age 59 +/- 11 years] mild-to-severe hypertensive patients was carried out to evaluate the effects of the angiotension converting enzyme inhibitor quinapril on blood pressure and on metabolic cardiovascular risk factors during 3-6 months' treatment (mean follow-up 90.4 days). The study population included 551 elderly [mean (+/- SD) age 71.9 +/- 9.3 years] patients, 1314 subjects with diabetes mellitus and 154 non-diabetic patients with hyperlipaemia; 4% of patients were lost to follow-up. Diastolic blood pressure decreased from 102 to 87 mmHg (intent-to-treat analysis) and 62% of patients were normalized (diastolic blood pressure below 90 mmHg) at the last evaluable visit. Overall, serum lipids were favourably affected during quinapril treatment; when corrected for changes in body weight, a significant improvement in total, low- and high-density lipoprotein cholesterol, and triglycerides was detected. Quinapril treatment in elderly patients was efficacious and well tolerated, and quinapril appears to be an effective antihypertensive drug devoid of untoward effects on metabolic risk factors for cardiovascular disease.

Aged↗