Misunderstanding or error? The UGDP report after four years.
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Arteriosclerosis↗
Biomedical subjects
G Pozza
Publications and source records attributed to G Pozza.
Effect of ageing on insulin and growth hormone response to glucose and arginine in normal subjects.
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Adult↗
Association between chlorpropamide-alcohol flushing and fast acetylator phenotype in type I and type II diabetes.
Different prevalences of chlorpropamide alcohol flushing (CPAF) have been reported by different authors in either type I or type II diabetics or in normal subjects and this could be due to different methodological approaches or to different criteria of evaluation of CPAF. Previous studies in small series of patients have also suggested the existence of an association between type I diabetes and the fast acetylator phenotype (AP). The first aim of this study was to find reliable criteria for the assessment of CPAF. The second was to evaluate the prevalence of CPAF and of AP in a large series of type I and type II diabetics; and the third was to evaluate possible associations of CPAF and AP. AP and CPAF were evaluated separately in 256 diabetics (110 with type I and 146 with type II diabetes) and in 183 diabetics (74 with type I and 109 with type II diabetes), respectively. In 156 of these subjects, the two markers were evaluated together. The occurrence of CPAF was studied by subjective and objective assessment and by thermographic recording; CPAF was quantified by the differential value of skin temperature increase [delta T(C-P)] and by the value of differential speed of ascent, expressed in angle-degrees [delta a(C-P)], after treatment with placebo and with chlorpropamide. The fast AP was more frequent in type I than in type II diabetics, was not related to family history of diabetes, sex of the patients, age at onset and duration of diabetes or metabolic control. The most reliable assessment of CPAF was represented by thermographic recording of speed of ascent of skin temperature. CPAF was more frequent in females than in males, more frequent in diabetics than in healthy controls, similarly frequent in type I and in type II diabetes and showed no relationship with family history of diabetes, age at onset, duration of diabetes or metabolic control. An association between fast AP and CPAF was found in type II, but not in type I diabetics: fast acetylators were more frequently CPAF-positive, while slow acetylators were more frequently CPAF-negative. In addition, a linear relationship was found between rate of acetylation and speed of ascent of facial skin temperature after chlorpropamide and alcohol in type II diabetics, not in type I diabetics. The meaning of this association is not clear and deserves further investigations.
Acetylation↗
Characterization of the chlorpropamide-alcohol-flush in patients with type 1 and type 2 diabetes.
The aim of the present paper was to evaluate the prevalence of the chlorpropamide-alcohol-flush (CPAF) in patients with type 2 and with type 1 diabetes. Ninety-seven patients with type 2 diabetes and 33 with type 1 diabetes drank 40 ml vermouth 12 h after placebo and again 12 h after 1 tablet of chlorpropamide (250 mg) or 12 h after the last of repeated administrations of chlorpropamide (250 mg b.i.d. for 2 days). Skin temperature was recorded in all patients by a thermocouple probe connected to the left cheek. In 47 patients serum concentrations of chlorpropamide and of its metabolite CBSU were also determined. The prevalence of CPAF was similar in type 1 and type 2 diabetes, was greater in women than in men, and was significantly greater after repeated administrations than after one single administration of chlorpropamide. The increase of skin temperature during a 30-min period was significantly higher in patients with CPAF than in patients without CPAF. Serum concentrations of chlorpropamide and of its metabolite CBSU were more elevated after 4 than after 1 tablet of chlorpropamide, but were not significantly different in patients with and without CPAF. These data indicate that both genetic factors and the amount of chlorpropamide used affect the appearance of CPAF. To assess the possible role of serotonin and of dopamine in the CPAF, some patients with CPAF were tested again after treatment with metergoline, an antiserotonin agent, or with bromocriptine, a dopamine-agonist. Neither drug influenced the CPAF, indicating that the two neurotransmitters are not involved in the CPAF.
Bromocriptine↗
Plasma beta-thromboglobulin in uncomplicated insulin-dependent diabetes at rest and during physical exercise.
Plasma beta-thromboglobulin (beta TG) was assayed in 10 insulin-dependent uncomplicated diabetic subjects and in 10 age- and sex-matched metabolically healthy controls, both at rest and after maximal physical exercise. Diabetic patients showed significantly higher (p less than 0.005) resting beta TG values as compared to the control group. After physical exercise, beta TG rose significantly (p less than 0.05) only in the control group, thus abolishing the difference (evaluated through beta TG values) between the two groups observed at rest. Platelet hyperactivity seems thus to be present even in uncomplicated diabetes, at rest, while exercise does not lead to a further increase in beta TG values contrary to what is observed in controls.
Adolescent↗
Role of red cell sorbitol as determinant of reduced erythrocyte filtrability in insulin-dependent diabetics.
Erythrocyte deformability measured as filtration index is clearly diminished in diabetics, thus possibly contributing to diabetes-associated microvascular complications. Moreover, the erythrocyte sorbitol level in IDD is clearly higher than that of non-diabetics, suggesting an alteration in the polyol pathway as possible determinant of diabetes-associated complications. Following this line of research, intracellular sorbitol as well as glucose, inositol, galactitol, mannitol and 2,3-diphosphoglycerate have been studied in 21 diabetics and in 14 controls matched for age and sex. In addition to confirming the high levels of intraerythrocytic glucose and sorbitol in diabetic subjects, statistically significant correlations have been demonstrated between sorbitol and filtration index, between plasma glucose, intracellular glucose level and glycosylated hemoglobin, suggesting a relationship between metabolic control and hemorheologic alterations in diabetes.
2,3-Diphosphoglycerate↗
Clinical and instrumental diagnosis of autonomic neuropathy in insulin-dependent diabetes.
The author report a study of the relationship between symptomatic autonomic neuropathy and the response to simple cardiovascular autonomic tests (Valsalva maneuver, handgrip-test, detection of postural hypotension), in a large series of insulin-dependent diabetics (IDD). Symptoms of autonomic neuropathy were referred by 28 out of 130 IDD, prevalence and severity showed a clear relationship with the duration of diabetes. Only 4 out of 36 patients examined showed a pathologic response to the handgrip-test, while an abnormal Valsalva maneuver was evident in 24 out of 113 IDD. The data show that while the recognition of symptoms indicating a widespread autonomic derangement is rather easy, the diagnosis of autonomic neuropathy may be more difficult in the presence of mild or unspecific symptoms. The Valsalva maneuver exhibited the higher frequency of abnormal responses suggesting that the parasympathetic cardiovascular regulation may be impaired earlier than the sympathetic one. This early subclinical autonomic neuropathy may be due to metabolic or functional factors. Even if clinical consequences of an autonomic derangement of cardiovascular regulation may be serious, in our opinion subclinical impairment, being detectable in a large proportion of patients within the first year of disease, is unlikely to have a short-term severe prognostic value.
Adolescent↗
Iloprost and peripheral arterial disease in diabetic patients.
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Arteriosclerosis Obliterans↗
Inappropriate thyroid-stimulating hormone release in the elderly?
In three hyperthyroid women aged more than 60 years serum TSH levels, inhibited as usual before treatment, rose and remained elevated for more than one year while on treatment with methimazole and l-thyroxine, in spite of serum T3 and T4 levels within the normal range. In two hypothyroid women aged more than 60 years, serum TSH levels, raised under basal conditions, failed to be suppressed by a one-year treatment with l-thyroxine. Repeated attempts to increase serum T3 and T4 concentrations by giving additional doses of l-thyroxine or by tapering methimazole dosage, led to clinical signs of hyperthyroidism, not accompanied by a significant reduction of serum TSH levels. These data indicate the possibility of an inappropriate TSH release in some elderly people.
Aged↗
Value of abdominal sonography and MR imaging at 0.5 T in preoperative detection of pancreatic insulinoma: a comparison with dynamic CT and angiography.
BACKGROUND: Abdominal sonography, computed tomography (CT), angiography, and magnetic resonance (MR) imaging are the most widely used modalities for preoperative localization of insulinomas. CT and angiography are generally considered the techniques of reference, and the role of sonography and MR imaging in these patients is controversial. The purpose of this study was to compare these four modalities in a group of patients with pancreatic insulinoma and determine an effective radiological approach to this disease. METHODS: Twenty-eight patients with clinical and biochemical signs of pancreatic insulinoma underwent abdominal sonography, MR imaging at 0.5 T (spin echo technique), bolus dynamic CT, and digital subtraction angiography. Examinations were evaluated independently for the presence, size, and location of the lesions; preoperative diagnoses were compared with surgical findings based on palpation and intraoperative sonography. Tumoral vascularity was histologically graded. Sensitivities of the four imaging techniques were calculated and compared with the size, location, and vascularity of the tumors. Detection rates of combined techniques were finally determined. RESULTS: At surgery, 29 lesions in the 28 patients were found (range = 0.8-4.3 cm, average = 1.65 cm). Sensitivities of abdominal sonography. MR imaging, CT, and angiography were 79.3%, 65.5%, 44.8%, and 69% respectively. Correct localization of tumor was achieved in 96.6% of cases by a combination of sonography and MR imaging and in 72.4% of cases by using CT with angiography. CONCLUSION: In our experience, sonography and MR imaging performed well in the preoperative detection of pancreatic insulinoma. Therefore, we believe that the combination of abdominal sonography and MR imaging may represent the first radiological approach in clinically suspected insulinomas and that CT and angiography should be reserved for negative and/or doubtful cases.
Angiography, Digital Subtraction↗
Microalbuminuria and its associated risk factors in a representative sample of Italian type II diabetics.
A multicenter population-based study was undertaken from 1983 to 1985 in 12 diabetes centers in Lombardy, in order to assess the prevalence of microalbuminuria and clinical proteinuria. Out of a total population of 17,704 diabetics, 1,155 were randomly selected within four strata of duration of disease and albumin excretion rate (AER) assessment was carried out in 541 unselected subjects. Albuminuria was evaluated from an overnight urine collection using a radioimmunoassay. The overall prevalence rates were 25.8% for microalbuminuria (30 less than or equal to AER less than 350 micrograms/min) and 3.0% for macroalbuminuria (AER less than or equal to 350 micrograms/min). In Type II diabetes the rate of microalbuminuria increases with duration of disease up to 10 years and then tends to level off. This could be due to the existence of two subgroups of diabetics with different life expectancy and different degree of risk of nephropathy. The Italian prevalence of microalbuminuria appears to be rather similar to that of other studies, while the prevalence of macroalbuminuria is quite low with respect to middle and northern Europe, indicating a rather slow rate of progression to clinical proteinuria. This could be explained on the basis of differing protein intakes. The cases with AER greater than or equal to 30 micrograms/min, greater than or equal to 70 micrograms/min, and greater than or equal to 350 micrograms/min have been compared with matched diabetic controls with AER less than or equal to 15 micrograms/min.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Insulin-secreting pituitary GH3 cells: a potential beta-cell surrogate for diabetes cell therapy.
In a companion article, we describe the engineering and characterization of pituitary GH3 cell clones stably transfected with a furin-cleavable human insulin cDNA (InsGH3 cells). This article describes the performance of InsGH3 (clones 1 and 7) cell grafts into streptozotocin (STZ)-induced diabetic nude mice. Subcutaneous implantation of 2 x 10(6) InsGH3 cells resulted in the progressive reversal of hyperglycemia and diabetic symptoms, even though the progressive growth of the transplanted cells (clone 7) eventually led to glycemic levels below the normal mouse range. Proinsulin transgene expression was maintained in harvested InsGH3 grafts that, conversely, lose the expression of the prolactin (PRL) gene. Elevated concentrations of circulating mature human insulin were detected in graft recipients, demonstrating that proinsulin processing by InsGH3 cells did occur in vivo. Histologic analysis showed that transplanted InsGH3 grew in forms of encapsulated tumors composed of cells with small cytoplasms weakly stained for the presence of insulin. Conversely, intense insulin immunoreactivity was detected in graft-draining venules. Compared to pancreatic betaTC3 cells, InsGH3 cells showed in vitro a higher rate of replication, an elevate resistance to apoptosis induced by serum deprivation and proinflammatory cytokines, and significantly higher antiapoptotic Bcl-2 protein levels. Moreover, InsGH3 cells were resistant to the streptozotocin toxicity that, in contrast, reduced betaTC3 cell viability to 50-60% of controls. In conclusion, proinsulin gene expression and mature insulin secretion persisted in transplanted InsGH3 cells that reversed hyperglycemia in vivo. InsGH3 cells might represent a potential beta-cell surrogate because they are more resistant than pancreatic beta cells to different apoptotic insults and might therefore be particularly suitable for encapsulation.
Animals↗
Patient survival and cardiovascular events after kidney-pancreas transplantation: comparison with kidney transplantation alone in uremic IDDM patients.
In diabetic patients cardiovascular morbidity and mortality is still a major problem. Our aim was to study the effect of kidney-pancreas transplantation on survival, cardiovascular events, and causes of death in diabetic type 1 uremic patients. Three hundred and thirty-three uremic IDDM patients were enrolled in our waiting list for kidney-pancreas transplantation: 107 underwent kidney-pancreas transplantation (KP), 34 underwent kidney transplantation alone (KA), whereas 192 patients remained on dialysis (WL). Actuarial survival and causes of death were recorded over a period of 7 years. Seven-year survival rate was 75% for the KP group, 63% for the KA group, and 37% for the WL group (p = 0.001). Cardiovascular death rate was 9.8% in the KP group, 17.6% in the KA group, and 18.1% in the WL group (KP vs. WL, p = 0.05). Rate of acute myocardial infarction in the KP group was lower than in the KA group (2.4% vs. 17.6%, p = 0.005) as well as rate of acute pulmonary edema (0.8% vs. 23.5%, p = 0.0001) and rate of hypertensive patients at 1 (40.9% vs. 85.0%, p = 0.0001) and at 2 years (57.6% vs. 80%, p = 0.03). Kidney-pancreas transplant helped to obtain euglycemia with positive effects on survival and cardiovascular events.
Adult↗
Immunocytochemical detection and characterization of intrahepatic human pancreatic islets after combined liver-islet allotransplantation.
The unique availability of an explanted liver-islet allograft, removed for primary nonfunction of the liver, led us to evaluate distribution and phenotype of exocrine and endocrine components of the pancreatic graft. Immunocytochemistry was used to map patterns of gene products for islet hormones, proprotein processing enzymes, panneuroendocrine markers, and pancreatic exocrine markers. When compared with age-matched control pancreases, insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-producing cells were similarly represented and distributed within the grafted islet. We also demonstrate that the intrahepatic transplanted islets retained the enzyme machinery able to process the hormone precursors into bioactive fragments. In the clinical setting, this resulted in an immediate functioning of the graft and insulin-independence of the patient one month after transplantation. The purity in islets, as assessed by immunocytochemistry with antibodies to tissue constituents of endocrine and exocrine lineages, was around 40%. Despite the massive intraportal presence of pancreatic acinar tissue, no signs or symptoms attributable to ectopic hypersecretion of exocrine enzymes occurred. In fact, when tested with antibodies to such enzymes, low levels of immunoreactivity were observed in the grafted acinar cells.
Biomarkers↗
Secondary failure of oral hypoglycaemic agents in lean patients with type 2 diabetes mellitus: insulin sensitivity, insulin response to different stimuli, and the role of cyclic-AMP.
The aim of this study was to evaluate the insulin (IRI) response to different stimuli and insulin sensitivity in Type 2 diabetic patients responsive to oral hypoglycaemic agents (OHA) and in Type 2 diabetic patients with secondary failure of OHA (SF), all patients being of normal body weight (relative body weight less than 120%), and the possible role of cyclic AMP in the reduced IRI release. SF patients, without islet cell antibodies (ICA), with hyperglycaemia lasting more than 3 months, underwent tests with i.v. tolbutamide (n = 21), i.v. glucose (n = 14), i.v. glucagon (n = 19), i.v. arginine infusion (n = 18); the arginine infusion was repeated in 12 patients during administration of aminophylline, an inhibitor of phosphodiesterase. The same tests were performed in groups of 8 to 15 OHA patients and in groups of 6 to 17 healthy subjects. During all the tests, blood glucose levels were higher in SF patients, than in OHA patients and in healthy subjects. Both SF patients and OHA patients had no IRI response to glucose; SF patients, in contrast to OHA patients, had a reduced IRI response to tolbutamide and to glucagon. The IRI response to arginine was not different in OHA, in SF patients and in healthy controls, but was significantly enhanced by aminophylline only in healthy controls. Insulin infusions (1.66 mU/Kg/min for 90 min) were performed in OHA patients and in SF patients at blood glucose levels of 150 and of 250 mg/dl: during the last 60 min, the amount of glucose metabolized (M), and the insulin sensitivity (M/I) index were greater in OHA than in SF patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Aminophylline↗
Catabolic response and parenteral nutrition after simultaneous kidney-pancreas transplantation.
The aim of the study was to quantify the catabolism rate induced by simultaneous kidney-pancreas transplantation and to evaluate the impact of parenteral nutrition (PN) on recovery of graft function. Twenty-six diabetic uremic patients were studied. The average urea nitrogen production (UNP) was 5.2 +/- 1.7 g during the first 24 h after transplantation, while patients did not receive energy and nitrogen support. Energy (30 kcal.kg-1.day-1) and nitrogen (0.15 g.kg-1.day-1) intake started 24 h after surgery. In 14 patients, a mixed regimen was adopted (70% carbohydrates, 30% lipids), and 12 patients received only hypertonic glycidic solutions. The recovery of kidney function was immediate in all cases, with a prompt decrease in blood urea nitrogen and serum creatinine levels. C-peptide levels rose immediately after the revascularization of the pancreas graft and remained within the normal range during the PN period. No significant difference was observed in UNP or glucose tolerance between the mixed-regimen and glycidic groups. However, on average 6.6, and 1.5 hyperglycemic episodes occurred during the 1st wk of PN in the glycidic and mixed-regimen groups, respectively. The posttransplantation catabolism rate was similar to that induced by an elective major surgical procedure. Eucaloric PN did not affect the recovery of kidney and pancreas graft function. A mixed energy regimen seems to be most suitable for kidney-pancreas transplant patients because it prevents hyperglycemia which might be misdiagnosed as rejection.
Adult↗
Ultrasonographic evaluation of gallbladder volume and contractility in diabetic patients of different ages.
Gallbladder volume and contractility were measured, by means of real-time ultrasonography, in 48 insulin treated diabetic patients free from autonomic neuropathy, and in 91 healthy control subjects. All controls and diabetic patients were on a isocaloric and balanced diet. Gallbladder measurements were taken after an overnight fast and again 60-75 minutes after each meal. Gallbladder volume was at all times significantly greater in diabetic patients than in controls, while gallbladder contractility was similar. In diabetic patients, but not in controls, gallbladder volume was greater in the elderly than in adults, with no relationship between gallbladder volume and duration of diabetes. It is concluded that enlargement of the gallbladder might be a risk factor for gallstones in diabetic patients.
Adult↗
[Evaluation of an impedance measurement method for determining body composition in diabetic subjects and normal controls].
The reproducibility of impedance measurements made using the Human-IM system (Dietosystem, Milan-Italy) was assessed in a group of normal and diabetic subjects on the basis of three tests made under the same experimental conditions on three consecutive days. A total of 22 normal subjects, 29 insulin-dependent (IDD) and 6 noninsulin dependent (NIDD) diabetic patients were included in the study. The coefficient of variation between the three successive tests ranged between 0 and 2.7% (normals 1.1 +/- 0.7%, IDD 1.6 +/- 0.7%, NIDD 1.1 +/- 0.4%), thus confirming the good reproducibility of the method in all groups. There was no significant difference between impedance measurement tests in the two group of diabetic patients with regard to TBW, FAT and FFM. NIDD patients differed from normal subjects due to higher FAT levels, whereas there was no significant difference between IDD patients and normal subjects.
Adipose Tissue↗