Effect of glipizide on insulin secretion and insulin metabolism in obese type II diabetic patients.

This study was designed to explore the short-term effect of glipizide on insulin secretion and metabolism. Plasma insulin and C-peptide levels in the fasting state and after a 100-g oral glucose load were measured in 17 obese newly diagnosed type II (non-insulin-dependent) diabetic subjects before and after 1 mo of treatment with glipizide (15 mg/day). Plasma glucose levels decreased significantly after treatment with glipizide. Plasma insulin and C-peptide concentrations in the fasting state did not change after glipizide treatment. Also, postglucose plasma insulin levels did not change after glipizide, whereas postglucose plasma C-peptide concentrations significantly increased. A significant relationship was found between the increase in C-peptide plasma levels and the decrease in glycemic profile after glucose load following glipizide treatment. The relation between plasma C-peptide and insulin incremental areas after the oral glucose load significantly increased after treatment. These results suggest that in obese type II diabetic patients, 1 mo of treatment with glipizide potentiates the beta-cell response to oral glucose load and increases insulin metabolism, probably within the liver.

Plasma concentrations of growth hormone during hyperglycemic clamp with or without somatostatin infusion in obese subjects.

It is known that obese subjects have a blunted GH secretory response to stimulation, but little is known about the inhibition of GH secretion in obesity. The present study was designed to evaluate the effects of obesity on the suppression of GH by hyperglycemia and/or somatostatin. Plasma GH concentrations were measured in eight nondiabetic obese subjects and eight nonobese healthy controls during a 4-h hyperglycemic clamp. During the third hour synthetic cyclic somatostatin-14 was infused at the rate of 2.5 nmol/min. Baseline plasma GH levels were similar in obese and nonobese subjects (0.9 +/- 0.1 vs. 0.8 +/- 0.2 micrograms/L; mean +/- SEM). In the last 20 min of the glucose infusion period preceding somatostatin administration (100-120 min of the study) plasma GH averaged 0.8 +/- 0.1 micrograms/L in obese patients and 0.4 +/- 0.1 micrograms/L in control subjects (P less than 0.01), with a reduction of 6 +/- 5% in the former and 35 +/- 10% in the latter (P less than 0.01). In both groups somatostatin infusion did not result in a further decrease in plasma GH. Discontinuation of the somatostatin infusion resulted in a rise in both groups; the increase was higher in nonobese subjects (8.1 +/- 3.8 vs. 2.3 +/- 0.9 micrograms/L in the period 220-240 min; P = NS). These results suggest that in human obesity, hyperglycemia has a diminished inhibitory effect on GH secretion, and somatostatin administration has no additional effect in either obese or nonobese nondiabetic subjects.

Estimates of in vivo insulin action in man: comparison of insulin tolerance tests with euglycemic and hyperglycemic glucose clamp studies.

We compared estimates of in vivo insulin action derived from insulin tolerance tests (ITT) and euglycemic and hyperglycemic glucose clamp studies in 17 normal subjects and 19 patients with various diseases characterized by insulin resistance. Fifteen subjects underwent an ITT and a euglycemic clamp study, 17 subjects underwent an ITT and a hyperglycemic clamp study, and 4 subjects underwent all 3 tests. The ITT consisted of a bolus iv injection of regular insulin (0.1 U/kg BW). The plasma glucose disappearance rate during the 3- to 15-min period following the insulin injection was taken as a measure of insulin action. In both euglycemic and hyperglycemic clamp studies, which were carried out with standard techniques, the ratio between the amount of glucose infused to maintain glycemia at the desired level and the mean plasma insulin concentration from 60-120 min (M) (euglycemic clamp studies) or 20-120 min (I) (hyperglycemic clamp studies) was used as a measure of insulin action. A close correlation was found between plasma glucose disappearance rate and the M/I ratio during either the euglycemic (r = 0.811; P less than 0.001) or the hyperglycemic (r = 0.826; P less than 0.001) clamp studies. These results suggest that the 15-min ITT is suitable as a simple and rapid estimation of in vivo insulin action when glucose clamp studies are not feasible, as in large series of subjects or serial studies.

[Relations between hypotensive effect and modifications of volemia and plasma renin activity in patients with essential hypertension treated using spironolactone]. / Correlazione tra effetto ipotensivo e modificazioni della volemia e della PRA in ipertesi essenziali trattati con spironolattone

The hypotensive effect of spironolactone and its relation to the changer in volaemia and renin activity induced by the drug were studied in 12 hospitalised patients with essential hypertension. After 4 weeks, arterial pressure was significantly decreased in direct relation to reductions in plasma volume in 9 subjects in both the erect and the recumbent position. These reductions were probably responsible for an increase in renin activity noted (sometimes at significant levels) in all subjects. It would appear that such increase does not impede the hypotensive effect of the drug. The hypotensive response was, in fact, less marked in only 3 patients, whose basal renin levels were themselves high.

[Long-term treatment of arterial hypertension with propranolol. Combination with diuretics and dihydrazinophthalazine]. / Trattamento cronico dell'ipertensione arteriosa con propranololo. Associazione con diuretici e diidrazinoftalazina.

The effect of long-term treatment of hypertension with propranolol, alone or in combination with hydrochlorothiazide and/or dihydralazine, was investigated in 93 patients with various types of hypertension. Normalisation of the B. P. was obtained within two-four weeks of treatment with propranolol alone in all cases with mild hypertension, and in 77% and 44% of moderate and severe forms respectively. These percentages were even higher when propranolol was employed with hydrochlorothiazide and/or dihydralazine. The rationale of this combination and the mechanism of the hypotensive effect of propranolol are discussed. The drug was well tolerated; major side effects did not occur.

[Physiopathological correlations between carbohydrate and lipid metabolicm and obesity]. / Contributo allo studio delle correlazioni fisiopatologiche tra metabolismo glucidico e lipidico nell'obesità.

Sugar and fat metabolism were studied in a group of obese women without diabetes. Blood triglicerides and cholesterol were, on average, within normal limits, though endogenous hypertriglyceridaemia was noted in a few cases. Triglycerides were significantly related to blood sugar (baseline and after glucose loading), whereas there was no significant connection with blood insulin. The meaning of these results is discussed.

[Controlled study on the prevention of respiratory distress syndrome with betamethasone in pregnancy and ACTH and cortisol levels in the premature newborn infant]. / Studio controllato sulla prevenzione della RDS con betametasone in gravidanza e livelli di ACTH e cortisolo nel neonato pretermine.

The influence of maternal corticosteroid administration was studied on the ACTH and cortisol concentrations in neonatal blood of 24 premature infants whose mothers received betamethasone for prevention of RDS, compared with 11 untreated subjects. Cord blood was taken at birth and from venous sample in 5th day. All samples were analyzed for ACTH and Cortisol by radioimmunoassay. No statistically significant differences between these groups were noted. Additional analysis of ACTH and Cortisol levels in 9 RDS premature infants versus 26 control ones failed to demonstrate any deficiency of corticosteroids in newborn infants with RDS. The findings provide a justification for the prepartum treatment of respiratory distress syndrome with glucocorticoids because this dose of betamethasone does not expose the newborn to potentially harmful effects.

Total and free PSA serum concentrations are not influenced by extensive physical exercise and bicycle riding.

Vigorous and prolonged physical exercise and mechanical involvement of the perineal region might influence prostatic function and measurement of both total (PSA) and free prostate specific antigen (fPSA), decreasing the diagnostic efficiency of the laboratory screening for either benign or neoplastic prostate disorders in athletes. To investigate the effects of regular and strenuous physical exercise with or without bicycle riding on integrity and biochemical function of prostatic tissue, we measured serum PSA and fPSA in 69 elite and professional cyclists, 31 members of the Italian national cross-country ski team, and in 43 sedentary healthy controls. The concentration of both PSA and fPSA did not differ significantly between sedentary individuals and physically active cross-country skiers (PSA 0.43 +/- 0.30 vs. 0.36+/-0.25, ns; fPSA 0.16+/-0.12 vs. 0.12+/-0.12, ns) or cyclists (PSA 0.43 +/- 0.30 vs. 0.36 +/- 0.23, ns; fPSA 0.16 +/- 0.12 vs. 0.13 +/- 0.08, ns), and the relative distribution of values appeared almost overlapping. We hypothesize that neither a heavy and regular physical exercise nor the extensive and prolonged mechanical involvement of the prostate region by the bicycle riding have significant influence on release of both PSA and fPSA.

[Diagnostic and prognostic value of the separated renin in hypertension due to monolateral nephropathy]. / Il valore diagnostico e prognostico della renina separata nell'ipertensione da nefropatia monolaterale

Renin activity in renal vein plasma and in peripheral plasma was measured in twentytwo hypertensive patients presenting unilateral renal artery stenosis or other unilateral renal abnormalities. A discrepancy between peripheral and renal vein renin levels was noted only in one case. In seven patients the difference between the renal vein renin of the diseased kidney and that of its contralateral mate was very significant. They responded successfully to surgery for hypertension, confirming the predictive value of a renal vein renin ratio greater than 1.5. In all the other patients with less significant differences between the renin levels of the two kidneys surgery was not performed because they benefited from the hypotensive therapy.

[The hypotensive effect of propranolol: pathophysiological and clinical approach (author's transl)]. / Effetto ipotensivo del propranololo: approccio fisiopatologico e clinico

The hypotensive effect of propranolol and its correlation with the fall in heart rate, plasma volume and plasma renin activity produced by this drug, were studied in 20 hypertensive hospitalised patients. Heart rate and plasma volume fell to approximately the same level (20%) in all cases, while the hypotensive response varied according to the pretreatment levels of plasma renin activity. Patients with low renin did not respond, while those with normal renin and especially those with high renin responded with a significant fall in blood pressure which was directly correlated to the fall of plasma renin activity. It is concluded that propranolol might be the specific treatment for hypertension in those cases which are accompanied or caused by high plasma renin.

The effects of propranolol on spontaneous and experimental hypertension in the rat.

1. The hypotensive effect of propranolol and its correlation with the changes in heart rate, plasma volume and plasma renin activity produced by this drug were studied in normotensive rats and in rats with spontaneous, renovascular and deoxycorticosterone-induced hypertension. 2. No correlation was found between the fall in arterial pressure and the reduction in heart rate and plasma volume. On the contrary, a direct correlation was found between the hypotensive response and plasma renin activity: rats with high renin showed the maximum response, those with low renin no response. 3. Studies on blood volume distribution in different organs and the direct measurement of blood flow in the splanchnic bed demonstrated a significant correlation between the effect of propranolol on capillary permeability and the haemodynamic changes which it causes, namely a significant increase in portal venous pressure.

Unilateral cryptorchidism with compensatory hypertrophy of descended testicle in prepubertal boys.

5 prepubertal boys with unilateral cryptorchidism and compensatory hypertrophy of the descended testicle, 22 prepubertal boys with unilateral cryptorchidism and without CTH, and 14 prepubertal normal boys were submitted to LH-RH and to HCG tests in order to study the hormonal behaviour in CTH phenomenon before puberty. High but normal peaks of plasma LH and FSH were observed after LH-RH in CTH boys who showed a significant increase of testosterone after HCG stimulation. On the contrary the LH response to LH-RH and the testosterone response to HCG of the boys with unilateral cryptorchidism and without CTH were, as expected, significantly lower than in the control ones.

Carbohydrate metabolism in patients with nephrotic syndrome and normal renal function.

The effects of a standard oral glucose tolerance test (OGTT) on the serum concentrations of glucose, insulin, growth hormone (GH) and cortisol were evaluated in 38 adult patients with primary nephrotic syndrome and with normal renal function, and in 10 normal subjects. 14 patients had a diabetic-like response and 24 were not different from controls. In both groups of patients an increase in insulin pool secretion, probably due to elevated serum GH levels, was observed. The increased GH values were not related to serum albumin nor to urinary protein losses. No significant difference in serum cortisol values was observed in patients with nephrotic syndrome as compared to controls. There was no strict correlation between the various histologic lesions and the metabolic abnormalities. However, patients with a diabetic-like response to OGTT had a higher frequency of membranous glomerulopathy or focal glomerular sclerosis.

Relationship between serum vitamin D metabolites and dietary intake of phosphate in patients with early renal failure.

Serum vitamin D metabolites and their relationship with dietary intake of phosphate were evaluated in 41 adult patients with early renal failure (glomerular filtration rate [GFR] 50 +/- 12 ml/min). On free diet, mean serum levels of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] were reduced and were a function of GFR and dietary intake of phosphate (beta-weight coefficients were 0.69 and -0.49, respectively). Serum levels of 24, 25(OH)2D3 were comparable to controls and were significantly correlated with serum 25(OH)D3 concentrations only. After 29 +/- 2 months of phosphate restricted (700 mg), calcium supplemented (1,300-1,800 mg) diet, serum phosphate and parathyroid hormone (PTH) levels were unchanged and serum calcium, 1,25(OH)2D3 and 24,25(OH)2D3 concentrations significantly increased in those patients whose GFR did not change. On the other hand, serum PTH increased and serum vitamin D metabolites remained persistently low in those patients whose GFR declined to 12 +/- 5 ml/min. A retrospective analysis of bone histology in 234 patients with chronic renal failure showed that in early renal failure (GFR 75-31 ml/min) the prevalence of osteomalacia and bone resorption was reduced by phosphate restriction (12 vs. 33%, p less than 0.05, and 12 vs. 28%, p = not significant, respectively). In advanced renal failure (GFR 30-10 ml/min), phosphate restriction reduced the prevalence of osteoclastic bone disease (17 vs. 61%, p less than 0.001), but did not change that of osteomalacia (35 vs. 32%, not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary kallikrein excretion and plasma renin activity in patients with essential hypertension and primary aldosteronism.

1. The 24 h urinary excretion of kallikrein has been studied in 40 normotensive control subjects and in 74 age-matched patients with essential hypertension under similar conditions. By use of the renin-sodium index, hypertensive patients were divided into two subgroup: low-renin hypertension and normal-renin hypertension patients. Urinary kallikrein determinations were also obtained from six hypertensive patients with primary aldosteronism. 2. Urinary kallikrein was significantly lower both in patients with normal-renin and low-renin essential hypertension. Urinary kallikrein excretion was very high in the patients with primary aldosteronism. 3. In nine hypertensive patients beta-adreno-receptor-blocking therapy caused a significant decrease of plasma renin activity, but had no significant effect on urinary kallikrein excretion. 4. The results support the concept that low urinary kallikrein is likely to be a marker of essential hypertension. Under certain conditions its excretion is positively related to mineralocorticoid hormone concentrations but it is not primarily related to the renin-angiotensin system.

Contribution of four markers of tubular proteinuria in detecting upper urinary tract infections. A multivariate analysis.

The presence of tubular involvement, as a marker for the detection of urinary tract infection (UTI) site, was examined in 19 patients with pyelonephritis and in 15 patients with cystitis or asymptomatic bacteriuria. The urinary excretion of four markers of tubular proteinuria, beta 2-microglobulin (beta 2M), lysozyme (LZ), lactic dehydrogenase isoenzyme V (LAD-5) and N-acetyl-beta D-glucosaminidase (NAG), was investigated. LAD-5 appeared particularly valuable for the early detection of upper UTI. However, the overall diagnostic accuracy appeared to be further strengthened using, besides LAD-5, one additional variable. A set of simple and noninvasive biochemical tests on urine samples can reliably help to identify the site of UTI.

Normal inhibition by somatostatin of glucose-stimulated B cell secretion in the obese subjects.

Aim of the present study was to evaluate whether the inhibitory effect of somatostatin on pancreatic B-cell secretion is normal in nondiabetic obese subjects. For this purpose plasma C-peptide concentrations were measured in 10 nondiabetic obese subjects and 10 nonobese healthy controls during a 4-h hyperglycemic (11 mmol/l) glucose clamp. Somatostatin was infused (2.5 nmol/min) during the third hour of the study period in order to inhibit glucose-stimulated B-cell secretion. Fasting C-peptide averaged 0.46 +/- 0.04 nmol/l (mean +/- SEM) in nonobese subjects, and 0.85 +/- 0.08 nmol/l in obese patients (P less than 0.001). In the period 0-120 min the area under the plasma C-peptide curve was significantly higher in obese than in nonobese subjects (292 +/- 23 vs. 230 +/- 17 nmol/l x 120 min, P less than 0.05), however, in the last 20 min of the glucose infusion period without somatostatin (100-120 min) plasma C-peptide was not significantly different in the two groups (2.94 +/- 0.32 nmol/l in nonobese subjects and 3.21 +/- 0.19 nmol/l in obese patients, p = NS). During somatostatin infusion while maintaining hyperglycemia, plasma C-peptide decreased in both groups, and in the period 160-180 min it averaged 0.89 +/- 0.12 nmol/l in control subjects and 0.93 +/- 0.08 nmol/l in obese patients (P = NS), with a percent reduction similar in the two groups (70 +/- 2% in controls and 71 +/- 2% in obese patients). After discontinuing somatostatin infusion, plasma C-peptide increased to concentrations which were higher in obese than in nonobese subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone histology and calcium metabolism in patients with nephrotic syndrome and normal or reduced renal function.

Bone histology and its relationship with calcium metabolism was evaluated in adult patients with nephrotic syndrome: 29 had normal renal function (GFR 103 +/- 4 ml/min/1.73 m2) (group 1) and 20 had renal insufficiency (GFR 31 +/- 4 ml/min/1.73 m2) (group 2). In group 1, serum PTH, 1.25-HCC and 24.25-HCC levels were normal, while 25-HCC values were reduced. Bone histology was normal in 76% of the patients, while 17% had isolated osteomalacia and 7% an associated bone resorption. Group 2 showed a higher incidence of bone resorption when compared with a matched group of patients with renal failure and no proteinuria (40% vs. 13%) and a comparable frequency of isolated mineralization defect (25% vs. 34%). PTH levels were definitely increased and serum total calcium and all the vitamin D metabolites were reduced. A significant correlation between the apparent duration of the disease and the severity of osteodystrophy was found only in group 2. In conclusion, no constant derangement of calcium metabolism and bone histology is evident in patients with nephrotic syndrome and normal renal function, while patients with persistent proteinuria are at high risk of osteodystrophy even in the early phases of renal failure.

Estrogen and progesterone receptors in breast cancer: correlation with clinical and pathological features and with prognosis.

Estrogen and progesterone receptor status was reviewed in 405 patients from prior adjuvant breast cancer trials at the University of Verona. Only 233 patients were actually examined with respect to hormone status and outcome. No relationship between hormone receptor status and most of the commonly followed prognostic signs, i.e. tumor size, nodal status, and age, was found. Overall survival was correlated with hormone receptor positivity for patients with more than 4 positive axillary nodes. Disease-free survival was correlated only with PgR positivity, in premenopausal and in T1 groups.