Microalbuminuria in insulin-dependent diabetes is associated with high levels of prothrombin fragment 1 + 2.
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Adult↗
Biomedical subjects
G Pagano
Publications and source records attributed to G Pagano.
Stage-specific effects of teratogens on sea urchin embryogenesis.
The effect of direct (chlorambucil and allopurinol) and indirect (cyclophosphamide) teratogens on the fertilization and early development of sea urchin embryos has been investigated. Fertilization was affected by none of the drugs tested. Continuous exposure of embryos to chlorambucil (10(-6) to 3 x 10(-4) M) starting after fertilization delayed the first cleavage and hatching. Developmental defects in chlorambucil-treated embryos consisted mainly of blastula and gastrula-arrested embryos and in a limited number (25%) of plutei with malformed gut or skeleton. Post-hatching exposure to chlorambucil led to malformed plutei only. Early (pre-hatching) exposure to allopurinol (10(-6) to 10(-3) M) did not affect cleavage but induced developmental defects in a ratio comparable to chlorambucil. Post-hatching exposure to allopurinol failed to affect the embryogenesis. The indirect teratogen cyclophosphamide (10(-6) to 3 x 10(-5) M) had no effect on the early embryogenesis. Results were discussed in view of using sea urchin embryos to detect and analyze the early mechanisms of teratogenic action.
Allopurinol↗
Feedback inhibition of insulin and glucagon secretion by insulin is altered in abdominal obesity with normal or impaired glucose tolerance.
We investigated the feedback inhibition of insulin and glucagon secretion during euglycemic-hyperinsulinemic clamp at about 350 pmol/l in 16 patients with abdominal obesity [8 with normal glucose tolerance (oNGT), 8 with impaired glucose tolerance (oIGT)] and 8 normal-weight subjects matched for age, sex and blood pressure. In oNGT and oIGT, fasting plasma C-peptide levels were twice those in the controls (962 +/- 51 and 915 +/- 85 vs 439 +/- 28 pmol/l, P < 0.001) and their suppression was lower than in the controls, both in absolute terms (155 +/- 19 and 185 +/- 17 vs 274 +/- 18 pmol/l, P < 0.001) and as a percentage decline from basal levels (16 +/- 2% and 21 +/- 2% vs 63 +/- 2%, P < 0.001). Fasting plasma glucagon levels were similar in the patients and in the controls, but were less suppressed during clamp in oNGT and oIGT, both in absolute terms (7.0 +/- 0.9 and 5.6 +/- 0.6 vs 13.2 +/- 1.2 pmol/l, P < 0.001) and as a percentage change from basal levels (23 +/- 3% and 19 +/- 2% vs 44 +/- 4%, P < 0.001). These results suggest that the insulin feedback on B and A cells is impaired in abdominal obesity, and that this defect is of similar degree in oNGT and oIGT. These alterations could be implicated in the pathogenesis of hyperinsulinemia in obesity.
Adult↗
Hypercholesterolemia in non-insulin-dependent diabetes mellitus: different effect of simvastatin on VLDL and LDL cholesterol levels.
Non-insulin-dependent diabetes mellitus (NIDDM) is often characterized by an increase in VLDL-triglyceride, VLDL-cholesterol, LDL-cholesterol and a reduction in HDL-cholesterol. HMG-CoA reductase inhibitors significantly lower cholesterol rates and have an indirect effect on the LDL receptor. We measured the effect of simvastatin in 28 hypercholesterolemic subjects, including 14 with NIDDM in good metabolic control (HbAIc 7.8% +/- 1.3%). A 24-week treatment with 10 mg/day (weeks 1-4), 20 mg/day (weeks 5-8) and 40 mg/day (weeks 9-24) simvastatin revealed different responses in diabetic and non-diabetic patients. Total cholesterol, LDL-cholesterol and apo B decreased significantly in both groups (less in the diabetics), whereas only NIDDM patients displayed a significant reduction in VLDL-cholesterol and VLDL-apo B. In the non-diabetics, the reduction in plasma cholesterol was mainly confined to the LDL fraction (276 +/- 65 vs. 132 +/- 28 mg/dl), whereas a significant fall in VLDL-cholesterol (45 +/- 19 vs. 21 +/- 10 mg/dl) was more evident in the NIDDM patients. Simvastatin also influenced plasma apo B levels (221 +/- 33 vs 134 +/- 23 mg/dl in non-diabetics and 182 +/- 44 vs. 134 +/- 30 mg/dl in diabetics). Significant reduction of apo B, LDL-apo B (205 +/- 39 vs. 128 +/- 23 mg/dl) in the non-diabetics and VLDL-apo B (16 +/- 5 vs. 9 +/- 2 mg/dl) in the diabetics, indicates that the VLDL are primarily concerned when statins are administered in NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
Anticholesteremic Agents↗
Bezafibrate affects lipid, lipo- and apolipoprotein pattern in non-insulin-dependent diabetic patients.
To assess bezafibrate efficacy in a diabetic population a single-blind randomized study was performed in 32 diet-resistant type IIb hyperlipidaemic non-insulin-dependent (NID) diabetic patients in good metabolic control (HbA1c < 8%) compared to a placebo group. In our diabetic patients one month treatment of 400 mg/day bezafibrate lowered plasma C (-14%) and TG (-37%) and globally reduced the VLDL particles and VLDL lipids (-37% for C, -56% for TG and -25% for PL), raising VLDL C/TG ratio (+46%), redistributing TG from VLDL to LDL (+10%) and mainly in HDL (+49%), lowered LDL-C and Apo B levels and increased HDL-C together with Apo A1 (+19% and +13%) and Apo A1/Apo B (+72%). PL were raised by bezafibrate treatment and were redistributed from VLDL (-25%) to LDL (+25%) and HDL (+18%), while PL/C ratio increased in VLDL and in LDL (+18% and +50% respectively). Bezafibrate use was safe and improved the lipid pattern and the apolipoprotein and lipid distribution in the lipoproteins, producing a less atherogenic pattern in our NID diabetics.
Apolipoproteins↗
Sex differences in incidence of IDDM in age-group 15-29 yr. Higher risk in males in Province of Turin, Italy.
OBJECTIVE: To report the incidence of IDDM in the age-group 0-29 yr in the Province of Turin, Italy (951, 445 inhabitants 0-29 yr of age), over a 5-yr period (1984-1988) according to age, sex, and geographical region within the area and to identify any temporal trend. RESEARCH DESIGN AND METHODS: The survey used as the primary data source the list of all patients attending diabetic clinics, and as secondary data source, used the list of hospital discharges for diabetes. RESULTS: We identified 298 incident cases of IDDM in people 0-29 yr of age. Estimated completeness of ascertainment of the registry was 97%. Age-adjusted (world-standard) incidence rates were 7.40/100,000 (95% CI 6.28-8.71), 5.83 (4.95-6.86), and 6.70 (5.97-7.51), respectively, in the age-groups 0-14, 15-29, and 0-29 yr. Incidence was significantly higher in males than in females in the age-group 15-29 yr (7.36, 6.02-8.98, vs. 4.21, 3.12-5.56). An increasing incidence from rural areas to the greater Turin area (city and its industrial belt) was evident. No significant temporal trend during the study period was found, although year-to-year variability was evident, with the highest incidence in 1984. CONCLUSIONS: This study suggests a high male-to-female ratio of incidence of IDDM after 14 yr; either sex hormones or different exposure to environmental determinants could be involved.
Adolescent↗
Thymectomy for myasthenia gravis: predictive factors and long term evolution. A retrospective study on 46 patients.
Forty-six patients with myasthenia gravis (MG) underwent transternal thymectomy between 1975 and 1991 and were observed over a long term follow up period (mean 6 years). Surgery was well tolerated and was followed in 32.6% of patients by remission of symptomatology. The severity of symptoms according to the Osserman scale was significantly reduced: slight forms of myasthenia increased soon after thymectomy more frequently than moderate and severe forms. Response to thymectomy at 3 months, according to the Hankins scale, was found to be positive (remission or amelioration of symptoms) in 31/41 patients, and worse in patients with thymoma. Probability of clinical remission and death were both significantly correlated with clinical response at three months after thymectomy. No other preoperatory clinical factor (onset age, sex, initial severity of MG, interval from symptom onset to thymectomy) was found to predict the response to treatment. Preoperatory mediastinic CT had a good reliability (> 85%) in diagnosing thymona, but was rarely able to distinguish between thymic hyperplasia and atrophy.
Adolescent↗
The artificial endocrine pancreas in clinical practice and research. The present position and future perspectives.
The artificial endocrine pancreas (AEP) is a controlled glucose and/or insulin infusion system in which continuously monitored blood sugar values are fed to a computerised analyser that uses predetermined algorithms to establish the doses to be administered. Since its first appearance in clinical practice and diabetological research during the Sixties, the AEP has been modified in various ways to overcome technical problems associated with the gluco-sensor and algorithms so as to make better use of the glucose-insulin feedback mechanism, and hence obtain a closer correspondence to physiological islet cell activity. As a result of these changes, the AEP can be employed in accordance with the physiopathological principles of insulin secretion in a variety of clinical conditions to secure the short-term control of metabolic alterations in the diabetic. Surgery is one field in which the AEP is used to great advantage, since this and its accompanying anaesthetics are the source of stress, which in turn may result in a rapid and sometimes serious postoperative metabolic derangement, including an increased secretion of anti-insulin hormones. The AEP has also been proposed for diabetic pregnancy and for the treatment of subjects in diabetic coma. It has proved useful in the diagnosis and management of hypoglycaemia due to organic hyperinsulinism, in diabetics with renal failure, in the honeymoon period, and in cases of unstable diabetes. The versatility of its application and its underlying physiopathological principles have enabled the AEP to be predominantly employed in research.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Glucose↗
A population-based prevalence survey of known diabetes mellitus in northern Italy based upon multiple independent sources of ascertainment.
The aims of this survey were (1) to estimate the prevalence of known diabetes mellitus in 1988 in Casale Monferrato (Northern Italy); (2) to validate different data sources available in Italy; (3) to identify a population-based cohort of diabetic patients. Multiple independent data sources were used and the capture-recapture method was applied to estimate the completeness of ascertainment of the survey. The primary data source was the list of all patients attending the diabetic clinic or those referred by family physicians and paediatricians of the area. The secondary data sources were the list of hospital discharges, the prescriptions data source and the list of all people using reagent strips and insulin syringes. On 1 October 1988 (the cut-off date) 2,069 cases of known diabetes were identified. The estimated completeness of ascertainment of the survey was 91%. Prevalence of known diabetes, Type 1 (insulin-dependent), Type 2 (non-insulin-dependent) and insulin-treated diabetes were, respectively, 2.21% (95% CI 2.13-2.29), 0.80/1,000 (0.62-0.98) and 2.10% (2.01-2.19), 2.92/1,000 (2.57-3.27). A higher prevalence of Type 2 diabetes was observed in women (2.30%, 2.18-2.42) than in men (1.88%, 1.76-2.00). Age-specific prevalence of Type 2 diabetes increased with age. Computerized data sources routinely available in the Piedmont Region (hospital discharges and prescriptions data sources) showed a low completeness of ascertainment when considered together (65%, 1,338 of 2,069), indicating the need to involve the diabetic clinic and family physicians in the ascertainment of known diabetes. In conclusion, the prevalence of known diabetes in Italy was lower than in Northern Europe and the United States.
Adolescent↗
Comparison of the metabolic effects of mixed meal and standard oral glucose tolerance test on glucose, insulin and C-peptide response in healthy, impaired glucose tolerance, mild and severe non-insulin-dependent diabetic subjects.
Dietary constituents other than glucose can influence insulin secretion in non-insulin-dependent diabetes mellitus and administration of a standard mixed meal has been proposed as a more physiological test in regard to human diet for evaluating the patient both at the time of diagnosis and during follow-up. This study was carried out to compare the effects of a standard meal and the oral glucose tolerance test on glucose, insulin and C-peptide plasma levels in four groups of subjects: healthy controls, subjects with impaired glucose tolerance, patients with mild non-insulin-dependent diabetes, and non-insulin-dependent diabetic patients with secondary failure to oral agents. Plasma glucose values were significantly higher after the oral glucose tolerance test than after the mixed meal in all four groups of subjects. Plasma insulin and C-peptide values were similar during the two tests in all groups of subjects except in non-insulin-dependent diabetics with secondary failure (flattened curves). Insulin and C-peptide responses per unit rise in blood glucose were significantly higher after the oral glucose tolerance test than after the mixed meal both in mild non-insulin-dependent diabetics (P less than 0.05 and P less than 0.05) and in non-insulin-dependent diabetics in secondary failure (P less than 0.01 and P less than 0.05). There was significant correlation between oral glucose tolerance test and mixed meal glucose incremental areas (r = 0.511, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Glucose↗
Change in glucose metabolism after long-term treatment with deflazacort and betamethasone.
We have compared the long-term effects of different corticosteroids on glucose metabolism by carrying out a 75 g oral glucose tolerance test in 27 subjects before and after the administration of deflazacort or betamethasone for two months in random balanced sequence. Fasting plasma glucose and insulin concentrations were significantly higher after betamethasone, whereas deflazacort increased only fasting plasma insulin. After oral glucose there were significant increases in blood glucose and insulin after betamethasone compared with deflazacort. These results suggest that the degree of glucose intolerance and insulin resistance depends on the steroid used and on the dose given, although long-term treatment with deflazacort has a smaller effect on glucose metabolism than betamethasone.
Administration, Oral↗
The glucoregulatory and antilipolytic actions of insulin in abdominal obesity with normal or impaired glucose tolerance: an in vivo and in vitro study.
To evaluate the effects of obesity and impaired glucose tolerance on insulin sensitivity, we performed a euglycaemic-hyperinsulinemic clamp at about 350 pmol l-1, combined with 3H-glucose infusion, in 14 obese patients, BMI 36.5 +/- 1.2 and in 12 matched controls, BMI 23.9 +/- 0.4. Six obese patients had normal glucose tolerance (oNGT), and eight had impaired glucose tolerance (oIGT). The ability of insulin to inhibit lipolysis in isolated adipocytes was also studied. Insulin-mediated glucose utilization was more severely impaired in oIGT than in oNGT with respect to the controls (621 +/- 51 vs. 897 +/- 83 vs. 1298 +/- 55 mumol m-2 min-1, P < 0.001). Plasma glycerol was higher in oIGT than in oNGT and in the controls, both fasting (238 +/- 12 vs. 179 +/- 14 vs. 112 +/- 8 mumol l-1, P < 0.001) and during the clamp (175 +/- 21 vs. 120 +/- 12 vs. 36 +/- 6 mumol l-1, P < 0.001). The correlation between glucose utilization and the percent reduction of plasma glycerol during the clamp was significant in the study group as a whole (r = 0.809, P = 0.0001), and in each of the groups separately (oIGT: r = 0.929, P = 0.002; oNGT: r = 0.943, P = 0.036; controls: r = 0.902, P = 0.0001). Inhibition by insulin of noradrenaline-stimulated lipolysis in isolated adipocytes was more severely impaired in oIGT than in oNGT compared with the controls (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Abdomen↗
Cutaneous cryptococcosis resembling molluscum contagiosum in a homosexual man with AIDS. Report of a case and review of the literature.
A 43-year-old homosexual man with the Acquired Immunodeficiency Syndrome (AIDS) developed cutaneous molluscum contagiosum-like lesions on face, ears, neck, hands and feet. He was admitted to our unit with fever, malaise and headache. Cytologic examination of skin brushing revealed numerous encapsulated budding yeasts, identified as Cryptococcus neoformans. Such a finding calls for a cytologic examination of skin lesions in patient with AIDS who present with fever and headache, in order to rule out a potentially life-threatening fungal infection.
Acquired Immunodeficiency Syndrome↗
Zidovudine prophylaxis after accidental exposure to HIV: the Italian experience. The Italian Study Group on Occupational Risk of HIV Infection.
OBJECTIVES: To evaluate the use of zidovudine prophylaxis in HIV-exposed health-care workers (HCW) in Italy and to determine its short-term toxicity. DESIGN: Longitudinal, open study with retrospective and prospective collection of data. SETTING: All Italian clinical centres that care for HIV-infected patients and are licensed by the Ministry of Health to dispense zidovudine and 30 hospitals participating in the Italian Multicentre Study on Occupational Risk of HIV Infection. STUDY POPULATION: HCW and other individuals who accepted zidovudine prophylaxis after accidental exposure to HIV. RESULTS: Data were collected for 224 HIV-exposed individuals until 30 June 1991. An increase in zidovudine prophylaxis was observed. All but 10 subjects received 1000-1250 mg zidovudine per day. Anaemia (five cases), neutropenia (one case) and an increase in serum alanine aminotransferase levels (two cases) were the only haematochemical side-effects observed; none of the subjects ceased prophylaxis because of side-effects. More than 50% of subjects had constitutional reactions; as a result, prophylaxis was stopped by 29 patients. These adverse effects began within 10 days of prophylaxis; all resolved after prophylaxis was stopped. No HIV-antibody seroconversions were observed after a mean follow-up of 8 months. CONCLUSIONS: Zidovudine prophylaxis has become a feature of the management of occupational exposures to HIV in health-care settings; short-term toxicity is mild, dose-related and reversible. Further studies are needed to assess the risk of long-term sequelae.
Administration, Oral↗
Urinary protein excretion induced by exercise: effect of a mountain agonistic footrace in healthy subjects. Renal function and mountain footrace.
The increase in albuminuria induced by exercise in healthy subjects is variably dependent on an increased glomerular filtration and/or to a decreased tubular reabsorption of albumin, in relation to the intensity of muscular work. Membrane anionic charges and haemodynamic changes have been implicated in exercise-induced albuminuria. We evaluated in 12 healthy subjects albumin and beta-2-microglobulin excretion rate and the presence in urine of cationic compounds before and after an agonistic mountain footrace. Albumin excretion rate increased significantly (3.7 +/- 1.3 vs 43.7 +/- 10.0 micrograms/min) (p less than 0.001) and beta-2-microglobulin excretion rate (16.5 +/- 4.4 vs 37.9 +/- 7.4 micrograms/min) (p less than 0.025), too. In 3/4 subjects, urines revealed a peak of highly cationic proteins, sharing antigenic and biological characteristics with platelet-derived cationic proteins. The increase in albuminuria induced by strenuous exercise of an agonistic mountain footrace is of mixed type (both glomerular and tubular) and is associated to the urinary excretion of cationic proteins.
Adult↗
Urinary excretion of glycated albumin in insulin-dependent diabetic patients with micro- and macroalbuminuria.
Non-enzymatic glycosylation (glycation) involves both circulating proteins, such as albumin and structural proteins, such as the components of the glomerular basement membrane. Glycated albumin is more anionic than unmodified plasma albumin at physiologic pH. Preferential urinary excretion of glycated proteins has occasionally been reported in diabetes. We therefore investigated the selectivity index (renal clearance of non-glycated/glycated albumin) in 25 insulin-dependent diabetic patients (17 with microalbuminuria and 8 with macroalbuminuria), and 19 healthy subjects. The selectivity index was significantly higher (p less than 0.01) in the microalbuminuric patients than in the macroalbuminuric patients and the control subjects: 1.11 +/- 0.03 SEM vs 0.94 +/- 0.08 vs 0.98 +/- 0.02. These results are not consistent with preferential urinary excretion of glycated albumin in insulin-dependent diabetic patients with increased urinary albumin excretion.
Adult↗
The increase in albuminuria induced by exercise is not associated with preferential excretion of glycated albumin in type 1 (insulin-dependent) diabetic patients.
The increase in urinary albumin excretion induced by acute exercise in Type 1 (insulin-dependent) diabetic patients is associated with the urinary excretion of cationic proteins. To test whether the renal excretion of glycated albumin (more anionic than non-glycated albumin) is affected by exercise, we submitted seven normoalbuminuric (albumin excretion rate less than 30 mg/24 h) Type 1 diabetic patients and six well-matched healthy subjects to an exercise test (600 kpm/min for 20 min) on a bicycle ergometer, preceded and followed by a 1-h resting period. The selectivity index (renal clearance of non-glycated/glycated albumin) was not significantly different among the pre-exercise, exercise and post-exercise periods, either in the normal subjects (1.01 +/- 0.03 vs 1.08 +/- 0.06 vs 1.08 +/- 0.05) or in the diabetic patients (1.25 +/- 0.09 vs 1.20 +/- 0.07 vs 1.20 +/- 0.06), whereas it was significantly higher (p less than 0.05) in diabetic patients compared to healthy subjects during pre-exercise. These results are not consistent with the hypothesis that acute exercise may induce a preferential excretion of glycated albumin.
Adult↗
Benfluorex and blood glucose control in non insulin-dependent diabetic patients.
Benfluorex has been reported to decrease blood glucose in different dismetabolic conditions, particularly in noninsulin-dependent diabetic (NIDD) patients, but the mechanism of this effect is poorly known. We evaluate fasting glucose production (3H-glucose infusion) and B-cell secretion (phi 1, phi 2 and glucose utilization SI) (minimal model technique) in 7 mild, diet treated, NIDDM patients after 6-week administration of benfluorex (450 mg/day) and placebo, in random sequence and double blind design. Body weight, HbA1c, plasma glucose profile, fasting plasma insulin, lactate, pyruvate, beta-OH-butyrate, total cholesterol, HDL-cholesterol and triglycerides were also measured at the end of each treatment. Mean values of body weight (71 +/- 4 vs 69 +/- 4 kg, p less than 0.01), HbA1c (8.3 +/- 0.2 vs 7.7 +/- 0.2%, p less than 0.01), fasting plasma glucose (137.0 +/- 6.5 vs 121.4 +/- 5.6 mg/dl, p less than 0.01), lactate (1.82 +/- 0.13 vs 1.22 +/- 0.11 mmol/l, p less than 0.0025) pyruvate (0.164 +/- 0.011 vs 0.095 +/- 0.010 mmol/l, p less than 0.0005), and beta-OH-butyrate (0.91 +/- 0.06 vs 0.66 +/- 0.04 mmol/l, p less than 0.005) were significantly lower after benfluorex than after placebo. phi 1, phi 2 and SI values were not significantly different in the two treatments. Fasting glucose production was significantly lower after benfluorex than after placebo: 2.46 +/- 1.57 vs 1.84 +/- 0.85 mg/kg.min, p less than 0.02. These results demonstrate that 6-week treatment with benfluorex produces a significant blood glucose lowering effect in mild NIDDM patients, mainly by decreasing glucose production.
Blood Glucose↗