Combined therapy with glibenclamide and ultralente insulin in lean patients with NIDDM with secondary failure of sulfonylureas. Follow up at two years.

Nine lean diabetic patients with secondary failure of oral hypoglycemic agents and with a poor residual insulin release under treatment with glibenclamide (15 mg/day) entered a cross-over study, in which ultralente insulin was administered alone or in combination with glibenclamide (15 mg/day). Combined therapy was accompanied by increased serum free-insulin levels and was more effective than glibenclamide alone on daily blood glucose profile, on glycosylated haemoglobin (HbA1C) and on Beta-OH butyrate; in 6 patients a near normalization of blood glucose control (daily blood glucose levels less than 180 mg/dl) occurred. C peptide release, evaluated as daily profile and as response to i.

Effect of acipimox, a lipid lowering drug, on growth hormone (GH) response to GH-releasing hormone in normal subjects.

Growth hormone (GH) induces lipolysis and an increase of free fatty acids (FFA), and FFA inhibit the GH response to arginine and to GH-releasing hormone (GHRH). The aim of this study was to evaluate the effect of the pharmacologic blockade of lipolysis on the GH response to GHRH. Eleven normal men underwent a saline infusion starting at 09:00 h, after administration of placebo or 500 mg acipimox, an antilipolytic agent; at 13:00 h (0 min) they received GHRH, 50 micrograms iv The GH response to GHRH (0 to 120 min) was significantly higher in subjects pretreated with acipimox than in subjects pretreated with placebo.

The glucose clamp technique for the study of patients with hypoglycemia: insulin resistance as a feature of insulinoma.

Occurrence of hypoglycemia during a prolonged fasting, accompanied by inappropriately high serum insulin levels, is considered a reliable index of the presence of insulinoma. Previous in vitro studies on insulin receptors, and in vivo hyperinsulinemic clamps have shown that patients with insulinoma are insulin resistant. In the present study 10 patients with insulinoma, 6 patients with nontumoral (also called functional or reactive hypoglycemia) hypoglycemia and 6 normal subjects were fasted for 24 h and their blood glucose levels were maintained constant by means of a programmed glucose infusion (isoglycemic glucose clamp) delivered by an artificial pancreas (Biostator).

Intranasal glucagon as remedy for hypoglycemia. Studies in healthy subjects and type I diabetic patients.

Intranasal glucagon can raise blood glucose levels in healthy subjects. The aims of this study were to 1) compare the hyperglycemic effect of intranasal and intramuscular glucagon in healthy subjects and type I (insulin-dependent) diabetes patients during euglycemic conditions and 2) test the efficacy of intranasal and intramuscular glucagon in counteracting hypoglycemic episodes in insulin-treated diabetic patients. Intranasal glucagon raised blood glucose levels in both healthy subjects and type I diabetic patients, the effect of intramuscular glucagon being similar for the first 30 min and higher thereafter.

Impairment of lymphocyte suppressive system in recent onset insulin-dependent diabetes mellitus. Correlation with blood glucose and serum insulin levels.

In a previous study, we observed an impairment of the theophylline-induced suppressive system in recent onset IDDM patients, and demonstrated also a correlation with metabolic derangement. The aim of this study was to better investigate the relationship between theophylline sensitivity (ThS) and blood glucose/plasma insulin levels in recent onset IDDM patients subjected to preprogrammed variations by an insulin/glucose clamp with artificial pancreas. Eight patients were studied within 8 weeks from the onset of IDDM.

Inhibition of the growth hormone (GH) response to GH-releasing hormone by constant Met-GH infusions.

GH release is controlled by hypothalamic hormones and insulin-like growth factor I, synthesized under the influence of GH, and perhaps also by GH itself. The availability of recombinant Met-GH was the basis for studies aimed at 1) obtaining constant serum GH levels by means of constant Met-GH infusions (40 and 80 ng/kg.min for 6 h), and 2) evaluating the metabolic effects of constant GH levels and, in particular, their effects on the serum GH response to GHRH.

Effect of intranasal growth hormone-releasing hormone and corticotropin-releasing hormone administration on growth hormone and cortisol release: improved bioavailability by means of sodium-glycocholate.

Several peptide hormones are effective when administered intranasally (in); these include oxytocin, vasopressin, insulin, glucagon, and calcitonin. With regard to GHRH and CRH, previous studies demonstrated that their bioavailability following in administration was very low. In this study we evaluated the serum GH response to 50 micrograms GHRH iv and to 700 micrograms GHRH in, the latter given alone and with 5 and 15 mg sodium-glycocholate (SGC), a surfactant, in six normal men.

Secondary failure to oral hypoglycaemic agents in non-obese patients with non-insulin-dependent diabetes is related to reduced insulin release.

The frequency of secondary failure to oral hypoglycaemic agents (OHA) in patients with non-insulin dependent diabetes (NIDDM) is still unknown, despite more than 30 years of use of OHA. The term secondary failure should be limited to patients who, despite maximal dosages of OHA and despite full compliance with diet and therapy, are no longer controlled and require insulin to obtain an acceptable glucose metabolism. We evaluated 248 out-patients, either on OHA, or on insulin because of poor metabolic control with OHA, in order to assess duration of treatment with OHA since diagnosis, by means of actuarial curves (Mantel-Cox test).

Nasal administration of glucagon and human calcitonin to healthy subjects: a comparison of powders and spray solutions and of different enhancing agents.

The systemic availability of glucagon and human calcitonin given intranasally to healthy volunteers as spray solutions or powders has been examined. Glucagon was absorbed only when surfactants were used, and 9-lauryl ether (as a spray) and sodium glycocholate (as spray or powder) were equally active. Calcitonin was poorly absorbed when given alone but the surfactants dihydrofusinate (as spray or powder) and glycocholate (as a spray) were equally active in promoting absorption.

Pancreatoduodenectomy with occlusion of the residual stump by Neoprene injection.

Pancreatojejunal anastomosis disruption still represents the main postoperative complication after pancreatoduodenectomy. In this study, a technique of occlusion of the residual pancreatic stump instead of pancreatojejunal anastomosis is proposed. Between March, 1981 and August, 1987, we performed 51 pancreatoduodenectomies, using Neoprene injection in the Wirsung duct, for carcinoma of the pancreatic head (28 cases), ampullary carcinoma (12 cases), islet cell carcinoma (5 cases), and chronic pancreatitis (6 cases).

Insulin requirement in elderly patients with non-insulin dependent diabetes mellitus (NIDDM).

Diabetes mellitus in the elderly is mainly of the non-insulin dependent type (NIDDM). A large proportion of such patients are treated with insulin, after many years of therapy with oral hypoglycemic agents (OHA), on the assumption that these lose their efficacy with time. Moreover, many such patients are obese and show preserved insulin release.

Blood glucose control and insulin secretion improved with combined therapy in type 2 diabetic patients with secondary failure to oral hypoglycaemic agents.

The influence of combined therapy using insulin and oral hypoglycaemic agents on blood glucose control and on insulin secretion in Type 2 diabetic patients with secondary failure to oral hypoglycaemic agents was evaluated. Type 2 diabetic patients (n = 180) (98 normal-weight, 82 over-weight), at least 3 years from diagnosis, and having poor blood glucose control on oral hypoglycaemic agents for at least 3 months (fasting plasma glucose greater than 10.0 mmol l-1) despite intensive efforts at improvement, were included in the study.

Retinal laser photocoagulation in diabetic patients causes prolactin, growth hormone and cortisol release.

Stress of many kinds (psychological, physical, metabolic) is able to induce endocrine modifications in humans, such as growth hormone (GH), prolactin (PRL), luteinizing hormone (LH), glucagon and cortisol release. Argon laser photocoagulation of the retina (RP), the treatment of choice for diabetic retinopathy, is a painful and stressful maneuvre and represents a direct injury onto a nervous tissue. Therefore it was decided to evaluate the possible endocrine modifications induced by RP in diabetic patients affected by retinopathy.

Inhibition of basal and metoclopramide-induced prolactin release by cabergoline, an extremely long-acting dopaminergic drug.

The aim of this study was to evaluate the effectiveness of the ergoline derivative cabergoline in inhibiting the serum PRL response to metoclopramide (MCP; 5 mg, iv) and the duration of this effect. Seven normal men received cabergoline (600 micrograms, orally) on day 0 and underwent a MCP test on days -1, 1, 4, 8, 15, and 28. Fasting serum PRL levels were significantly depressed from days 1-14; the nadir value occurred on day 4.

Human insulin plus sodium glycocholate in a nasal spray formulation: improved bioavailability and effectiveness in normal subjects.

Intranasal insulin is effective in raising serum insulin (IRI) levels and lowering blood glucose levels in normal subjects and in diabetics, but its bioavailability is low. Our aim was to improve the bioavailability of intranasally administered insulin in normal subjects as a prerequisite to extended clinical trials. Solutions of regular porcine and human insulin, 40 U/ml, with sodium glycocholate 1 % w/v as a surfactant, administered in drops (0.

Risk factors for micro- and macroangiopathic complications in type 2 diabetes: lack of association with acetylator phenotype, chlorpropamide alcohol flush and ABO and Rh blood groups.

Genetic markers would be useful to study the transmission of type 2 diabetes and to identify patients with enhanced risk of development of late diabetic complications. The aim of this study was to evaluate the influence of selected possible genetic markers on the development of diabetic complications. One hundred and eighty patients with type 2 diabetes (79 males, 101 females) were therefore studied with respect to ABO and Rh blood grouping and chlorpropamide alcohol flush (CPAF) and acetylator phenotype status, in addition to life style (smoking, dietary, alcohol and drug taking habits) and metabolic indexes (HbA1, M-value, serum cholesterol, serum triglycerides), with regard to late complications coronary heart disease (CHD), arterial hypertension (AH), peripheral vascular disorders (PVD), retinopathy and nephropathy.

Effects of arginine and arginine plus somatostatin infusion on insulin release in diabetic patients submitted to pancreas allotransplantation.

The present study was aimed at evaluating the role of the Autonomic Nervous System (ANS) in the insulin (IRI) response to arginine in humans. Nine patients who were recipients of simultaneous segmental pancreatic and renal grafts (6 receiving steroids and azathioprine as immuno suppression therapy, 3 treated with Cyclosporine A), 3 non-diabetic patients with kidney grafts (receiving steroid and azathioprine) and 10 normal subjects were studied. Arginine induced a clear IRI release in all subjects with no significant difference among the groups.

Ineffectiveness of ceruletide to reduce food intake and body weight in obese women hospitalized for weight reduction and treated with a restricted diet. A double-blind study.

Ceruletide is a synthetic decapeptide closely resembling the 8-carboxy-terminal peptide of cholecystokinin (CCK-8) with which it shares several biological properties. In a double-blind study versus placebo, we evaluated the effects of ceruletide on self-rated hunger and food intake at lunch time, as well as on body weight in 14 obese women hospitalized for weight reduction and on a restricted diet. During two 6-day courses of treatment with ceruletide or placebo, ceruletide 0.

Selective and extremely long inhibition of prolactin release in man by 1-ethyl-3-(3'-dimethylaminopropyl)-3-(6'-allylergoline-8'-beta- carbonyl)-urea-diphosphate (FCE 21336).

The effects on anterior pituitary function of FCE 21336 (1-ethyl-3-(3'-dimethylaminopropyl)-3-(6'-allylergoline-8'-beta-ca rbonyl)-urea- diphosphate), a synthetic ergoline derivative with selective dopamine agonistic properties, were studied. Circulating PRL, GH, TSH, cortisol and LH levels were determined up to 96 h after single oral doses of 50, 100, 200 and 300 micrograms of the compound to eight healthy males, and up to 168 h after single oral doses of 400 and 600 micrograms to six healthy males, according to double-blind, within subjects, experimental designs vs placebo. Vital signs, ECG, laboratory tests and the appearance of newly observed signs and symptoms were monitored.

Puerperal lactation, gonadotropin release and estradiol release: effects of metergoline and bromocriptine.

The exact cause of amenorrhea during the puerperium is still a matter of debate. PRL might inhibit primarily the release of FSH and LH or their stimulating effects on the ovary. In the study presented here, 28 healthy women were investigated, 13 of them lactating puerperae.

Clinical, endocrine, roentgenographic, and immune characterization of hyperprolactinemic women.

Seventy-one hyperprolactinemic women were analyzed for medical history, gonadotropin and ovarian hormonal levels, and prolactin (PRL) responsiveness to benserazide. Sellar tomography was then performed on a yearly basis for 3 years in all women, computerized coronal and sagittal tomography in 54 of them. Under basal conditions, 30 women had roentgenographic evidence of pituitary adenoma; at the end of the follow-up period, such evidence was seen in 44.