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Biomedical subjects

G Pozza

Publications and source records attributed to G Pozza.

At least 145 records · Page 8Linked to original sources

Magnetic resonance imaging of the kidney in type 1 (insulin-dependent) diabetes mellitus.

Reductions in the physiological cortical to medullary signal intensity ratio are found in magnetic resonance scans of the kidney in non-diabetic glomerular disease. Whether this abnormality can also characterise patients with Type 1 (insulin-dependent) diabetes mellitus and nephropathy is not known. We measured the cortical to medullary signal intensity ratio in magnetic resonance images of the kidney in 34 patients with Type 1 diabetes (ten with either clinical proteinuria or raised serum creatinine or both, nine with microalbuminuria, seven with normal urinary albumin excretion and long duration of diabetes and eight with Type 1 diabetes of short duration). The cortical to medullary signal intensity ratio showed a trend to cluster at lower values in the normoalbuminuric patients with normal serum creatinine rather than in the nine healthy individuals, independent of Type 1 diabetes duration (1.47 +/- 0.06 and 1.41 +/- 0.13 vs 1.63 +/- 0.16; five groups Scheffé F-test p = 0.05-0.1). Among the Type 1 diabetic patients, significant reductions in the cortical to medullary signal intensity ratio characterised overt nephropathy (1.19 +/- 0.15, p less than 0.05 vs all groups), but not microalbuminuria (1.47 +/- 0.13, p = NS), concomitantly with low glomerular filtration rate and elevated fractional excretion of uric acid, but independent of glycaemic control. The determinants of the renal cortical to medullary signal intensity ratio in Type 1 diabetes are uncertain. Reductions in the cortical to medullary signal intensity ratio may be a late finding in diabetic nephropathy, and parallel the accompanying impairment in kidney haemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Acipimox-induced facial skin flush: frequency, thermographic evaluation and relationship to plasma acipimox level.

Facial skin flush is the most frequent adverse effect induced by acipimox (ACX), a nicotinic acid analogue used in the management of hyperlipidaemia. The aims of the study were to evaluate the frequency, magnitude and reproducibility of the ACX flush in previously unexposed healthy subjects and to assess any possible relationship with the dose and plasma level of ACX. Seventy four healthy subjects received, on two different mornings, ACX 250 mg and placebo (P), according to a single blind, randomized, cross-over design; 33 had a clear flush after ACX and not after P.25 of those subjects were retested on five different mornings, with P, and with ACX 31.2, 62.5, 125.0, 250.0 mg, according to a double blind, randomized, cross-over design. Any increase in the local skin temperature was recorded by a thermocouple fixed to the left check. Subjective and objective assessment of the flush were strongly correlated with thermographic recordings. They indicated that a 120 min flush occurred after doses of ACX greater than 62.5 mg. In 12 of the 25 subjects, 6 with the highest and 6 with the lowest thermographic recordings, plasma ACX levels were determined. Subjects with different thermographic records had superimposable plasma ACX levels after all doses of ACX. Only the 6 subjects with the highest skin temperatures showed a significant relationship between the thermographic record and the plasma ACX. The data indicate that flush is a frequent, reproducible and dose-related adverse effect of ACX.

Adult↗

Pituitary reserve after repeated administrations of releasing hormones in young and in elderly men: reproducibility on different days.

Combined testing of the pituitary gland by administration of GHRH, CRH, GnRH and TRH has been proposed for clinical studies, although some reports indicate that individual endocrine responses can be different when releasing hormones are used alone or in combination. Aims of this study were to evaluate: 1) the reproducibility of the combined test on different days; 2) the endocrine responses to the combined test applied twice at 3h and at 5h interval; 3) differences of endocrine responses in young and in elderly men. Six healthy young men (aged 25 to 35 yr) and 6 healthy elderly men (aged 65 to 75 yr) were evaluated: elderly men had lower testosterone, free T3, and somatomedin-c levels than young men, while 17 beta-estradiol and inhibin were not significantly different, all values being within normal laboratory limits. The 12 men were tested on day 1 with iv GHRH (50 micrograms) CRH (50 micrograms), GnRH (100 micrograms) and TRH (200 micrograms) at 08:00h and again at 11:00h; on day 8, the same men were tested at 08:00h and again at 13:00h. At 08:00h, the endocrine responses were similar on day 1 and on day 8. The second GH (young and elderly men) and PRL (only young men) response was blunted on day 1, when the interval between two consecutive stimuli was 3h, but not on day 8, when the interval was 5h. Elderly men differed from young men only for GH and for PRL release on day 1 at 08:00h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Plasma free fatty acids and serum insulin in subjects feeding at 12-hour intervals; effects of methionyl growth hormone and of acipimox, an inhibitor of lipolysis.

In normal men, plasma free fatty acids (FFA) are influenced by feeding and by fasting; in addition, iv infusions of methionyl growth hormone (met-GH), so far performed during morning hours, induce an FFA rise that can be blocked by acipimox (ACX), a nicotinic acid analogue. The aims of the present study were to evaluate, in the absence of food interferences, the following aspects: i) Fasting FFA, glycerol, and insulin (IRI) in the morning and in the evening, and their response to met-GH ii) The effect of ACX and of a sustained release ACX formulation (ACX-SR) on fasting and met-GH induced lipolysis and on IRI levels. In a double blind study, 6 normal men received 50% cal at 09:30 h and 50% at 21:30 h; during placebo administrations FFA, glycerol, and IRI levels were lower at 06:30 h than at 18:30 h, and an iv met-GH infusion (160 ng/kg/min lasting 180 min) had a similar effect on FFA and on glycerol at 06:30 h and at 18:30 h. ACX-SR, administered at 21:30 h and 09:30 h, lowered FFA and glycerol in the morning as well as in the evening, and prevented met-GH induced lipolysis in the morning, but not in the evening.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian Rhythm↗

Intravenous infusion of diarginylinsulin, an insulin analogue: effects on glucose turnover and lipid levels in insulin-treated type II diabetic patients.

Diarginylinsulin is an intermediate in the conversion of proinsulin to insulin and is usually present in small amounts in vivo in humans. This study was designed to evaluate the following in insulin-treated type II diabetic patients: (1) the feasibility of an overnight intravenous infusion of diarginylinsulin, as compared with an overnight intravenous infusion of short-acting insulin, and the degree of early morning glycemic control; and (2) the effects of diarginylinsulin and human insulin on hepatic glucose production (HGO) in the postabsorptive state and on the glucose turnover rate and peripheral insulin sensitivity during an euglycemic hyperinsulinemic clamp. Diarginylinsulin and regular human insulin maintained a comparable degree of normoglycemia during the night, without significant glucose increases in the morning. Free-diarginylinsulin and free-insulin concentrations were not significantly different, and (HGO) was 2.1 +/- 0.5 versus 2.1 +/- 0.4 mg/kg/min with diarginylinsulin and regular human insulin, respectively (NS). During the euglycemic clamp, glucose infusion rate per unit of diarginylinsulin or human insulin infused (M/I ratio) was similar, and HGO was equally suppressed with diarginylinsulin and regular human insulin. No significant differences were seen in NEFA and triglyceride levels. In conclusion, these results indicate that diarginylinsulin is as potent as regular human insulin; it is normalizes HGO in the postabsorptive state; and its hepatic and peripheral actions on glucose and lipids are comparable to those of human insulin during an euglycemic hyperinsulinemic clamp.

Circadian Rhythm↗

Human islets chronically exposed in vitro to different stimuli become unresponsive to the same stimuli given acutely: evidence supporting specific desensitization rather than beta-cell exhaustion.

The aim of this study was to evaluate the effects of long term in vitro exposure of human pancreatic islets to different secretagogues on their subsequent secretory activity. Therefore, groups of 100 islets were cultured for 48 h in standard tissue culture medium (CMRL 1066) in the presence of 1 of the following: 5.5 mmol/L glucose, 16.7 mmol/L glucose, 5.5 mmol/L glucose plus 10 mmol/L L-arginine, or 5.5 mmol/L glucose plus 100 mumol/L tolbutamide. Insulin levels in the culture medium declined with time under all culture conditions. Islets were then perifused and acutely stimulated with glucose (16.7 mmol/L), L-arginine (10 mmol/L), and tolbutamide (100 mumol/L). Islets cultured in 16.7 mmol/L glucose showed no response to 16.7 mmol/L glucose [net area under the curve (delta AUC), 11% of control], and a reduced response to acute tolbutamide (delta AUC, 35% of control), but responded to L-arginine (delta AUC, 75% of control). Islets cultured in the presence of 10 mmol/L L-arginine had reduced responses to glucose (delta AUC, 11% of control) and tolbutamide (delta AUC, 27% of control), but responded to L-arginine (delta AUC, 75% of control). Islets cultured in tolbutamide did not respond to tolbutamide (delta AUC, 14% of control) and showed a reduced responses to acute glucose (delta AUC, 36% of control) and L-arginine (delta AUC, 24% of control). In a second set of experiments, islets cultured in 5.5 or 16.7 mmol/L glucose showed an insulin response to a supramaximal glucose stimulation (30 mmol/L glucose plus 0.5 mmol/L isobutylmethylxanthine) that was not statistically different. Similarly, islets that were cultured in the presence of 100 mumol/L tolbutamide still responded to 1 mmol/L tolbutamide. In conclusion, all stimuli evaluated in this study, chronically applied, reduced the insulin response to further acute stimulations. The different patterns of unresponsiveness observed together with the finding of a preserved insulin content in the islets after perifusions and a maintained capability to release insulin in response to supramaximal stimulations suggest that after chronic exposure to different stimuli, human islets become selectively desensitized to the same stimuli given acutely and do not become exhausted.

Arginine↗

Effect of soya and cellulose fibers on postprandial glycemic response in type II diabetic patients.

OBJECTIVE: We studied the effect on serum glucose and insulin of a preprandial ingestion of 7 g of soya fibers or of an equal amount of purified cellulose on eight non-insulin-dependent (type II) diabetic patients. RESEARCH DESIGN AND METHODS: Four tests were conducted in each patient in random order. In the first study, soya or cellulose was ingested before a standard breakfast, and postprandial glucose and insulin curves were determined. In the second study, intestinal absorption was investigated by means of a standard D-xylose absorption excretion test after the ingestion of soya or cellulose. RESULTS: Insulin profiles did not differ between the two treatments. The glycemic profiles after soya ingestion were lower than those after cellulose ingestion. The area under the glucose curve and glucose peaks were significantly higher after cellulose ingestion (area under the curve 20.2 +/- 3.88 vs. 15.57 +/- 4.42 mM x min, P = .05; glucose peaks 4.97 +/- 0.76 vs. 3.77 +/- 0.77 mM, P less than 0.02). The xylose tests were in the normal range, indicating that there was no interference with exose absorption, and no statistical difference was found between cellulose and soya treatment. CONCLUSIONS: It is concluded that soya fiber compared with purified cellulose has a favorable effect on the rise of postprandial glycemia in type II diabetic patients; moreover, the use of soya fibers did not carry any untoward side effect.

Blood Glucose↗

In vivo demonstration of insulin-receptor defect with 123I-labeled insulin and scintigraphic scanning in severe insulin resistance.

OBJECTIVE: Insulin-receptor function in humans is usually studied in vitro on readily available cells, e.g., erythrocytes and fibroblasts. Although these cells are not metabolically important targets for insulin action, information derived from them are often taken as representative of other tissues. The aim of this study was to investigate insulin receptors in vitro on erythrocytes and in vivo on one of the main insulin-target organs, the liver. RESEARCH DESIGN AND METHODS: A 16-yr-old girl affected by severe insulin resistance was identified. Insulin receptor binding was measured on the erythrocytes of the patient and of 6 nondiabetic volunteers. The biodistribution of 123I-labeled insulin was studied in vivo by scintigraphic scanning in the insulin-resistant patient and in 10 nondiabetic volunteers. RESULTS: Erythrocytes of this patient displayed a markedly reduced [125I]insulin binding. In vivo 123I-insulin biodistribution was characterized by lack of hormone uptake by the liver (4 vs. 21% of the injected dose in control subjects) contrasting with intense accumulation of radioactivity in the kidneys. CONCLUSIONS: Our studies show that defects of insulin binding can be directly demonstrated in vivo on liver receptors with a noninvasive technique with low radiotoxicity.

Adolescent↗

Improvement of glucose tolerance by minimal doses of glipizide in obese subjects with different degrees of glucose intolerance.

Obesity and impaired glucose tolerance (IGT) are risk factors for non insulin dependent diabetes mellitus (NIDDM) and for ischemic heart disease. Long term treatment of IGT subjects with diet and tolbutamide prevents progression of IGT to NIDDM. We have evaluated the lowest dose of glipizide, a second-generation sulfonylurea, able to improve glucose tolerance in response to oral glucose in 31 obese subjects, 12 with NIDDM, 9 with IGT and 10 with normal glucose tolerance (NGT). All subjects underwent four OGTTs, preceded by placebo and by different doses of glipizide (0.5, 1.0, 2.5 mg). Glucose tolerance was progressively improved by increasing glipizide doses in all groups, probably by peripheral mechanism and by enhanced insulin release.

Blood Glucose↗

[Vascular access for chronic hemodialysis in diabetic patients].

The aim of this study carried out on 33 uremic diabetic patients submitted to chronic hemodialytic treatment was to assess the kind of complications related to the vascular approach used as well as their short- and long-term incidences. Out of the 46 anastomoses prepared, 39 were arteriovenous fistulae according to Brescia-Cimino and 7 were PTFE grafts. The actuarial survival rate was 88%, 79%, and 63% after one, two and four years, respectively. The most frequent compliance was thrombosis. Our experience demonstrates that the distal arteriovenous fistula may be considered a valid vascular access for hemodialysis also in diabetic patients.

Adult↗

Diabetic retinopathy after successful kidney-pancreas allotransplantation: a survey of 18 patients.

To investigate the effects of normoglycaemia on diabetic retinopathy, we evaluated 18 uremic diabetic patients before and after successful pancreas kidney transplantation. In all, 12 uremic diabetic patients who submitted to kidney transplantation alone served as the control group; 4 of these subjects received a kidney transplantation alone, whereas 8 underwent a double kidney-pancreas transplantation but lost the pancreas graft within the first few weeks post-surgery. The mean age and the mean duration of both diabetes and dialysis were comparable in the two groups. All patients were studied prior to and at 6 and 9 months after surgery, then at annual intervals. Subjects were divided into three groups according to follow-up: less than 1 year, between 1 and 3 years and greater than 3 years. At each control visit, a complete clinical examination was performed by two independent examinators; retinal fluorescein angiography was carried out as well. The following parameters were evaluated: visual acuity, capillary closure, macular oedema, neovascularization at the disk and elsewhere and vitreous haemorrhage. A score ranging from -2 to +2 was assigned to each parameter for quantification of the variation between baseline values and those obtained at the end of the follow-up. This score was assigned by two different ophthalmologists. Eyes that were affected at baseline by end-stage diabetic retinopathy (secondary retinal detachment, neovascular glaucoma) were not entered in the study. A total of 18 eyes were lost to follow-up in the 2 groups because of laser treatment, cataract extraction, anterior ischaemic optic neuropathy and cytomegalovirus retinitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗