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Biomedical subjects

E Ferrannini

Publications and source records attributed to E Ferrannini.

At least 55 records · Page 3Linked to original sources
PubMed2001

Anti-CD38 autoimmunity in patients with chronic autoimmune thyroiditis or Graves' disease.

Autoantibodies directed against human CD38 (an enzyme catalysing the interconversion of NAD(+) and cyclic ADP-ribose) have been demonstrated recently in patients with type 2 diabetes. We tested 220 consecutive Caucasian patients with autoimmune chronic thyroiditis, 104 patients with Graves' disease, 220 subjects from the general population (control I) and 78 healthy control subjects not affected by thyroid autoimmune disorders (control II) for the presence of anti-CD38 autoimmunity. Using Western blot analysis and optical densitometry, a specific band corresponding to human recombinant CD38 was identified in the serum of several subjects. By defining anti-CD38 positivity as a standardized optical reading > 3 s.d. higher than the mean value of control I, 10.4% of patients with thyroiditis and 7.7% of Graves' patients were anti-CD38 positive (P = 0.0009 versus 1.8% of control I). Similarly, 13.1% of patients with thyroiditis and 10.5% of Graves' patients had a standardized optical reading > 3 s.d. higher than the mean value of the subjects not affected by thyroid autoimmune disorders (P = 0.002 versus 1.2% of control II). Anti-CD38 autoimmunity did not differ between euthyroid, hyperthyroid or hypothyroid patients or between patients with or without thyroid hypoechogenicity. Anti-CD38 autoantibodies were associated with higher levels of circulating antithyroid-peroxidase antibodies (P = 0.03) and they were more frequent in Graves' patients with ophthalmopathy (P < 0.05). Anti-CD38 autoantibodies are a new autoimmune marker in chronic autoimmune thyroiditis and Graves' disease. The specific role of CD38 and its autoantibodies in the modulation of thyroid cell function or growth remains to be investigated.

ADP-ribosyl Cyclase↗
PubMed2001

Effective blood pressure treatment improves LDL-cholesterol susceptibility to oxidation in patients with essential hypertension.

OBJECTIVES: LDL-cholesterol particles from hypertensive patients exhibit enhanced susceptibility to in vitro oxidation, an abnormality thought to increase cardiovascular risk. We tested whether blood pressure (BP) normalization can reverse this abnormality. DESIGN: Double-blind, randomized pharmacological intervention trial. SETTING: Clinical research centre. Subjects. A total of 29 nondiabetic, normolipidaemic patients with essential hypertension (BP= 151 +/- 3/99 +/- 1 mmHg) and 11 normotensive controls (BP=125 +/- 3/85 +/- 1 mmHg) matched for gender, age, obesity, glucose tolerance and lipid profile. Intervention. Anti-hypertensive treatment for 3 months with a calcium-antagonist in randomized combination with either an ACE inhibitor or a beta-blocker. MAIN OUTCOME MEASURES: Lag phase of copper-induced LDL oxidation, cell-mediated (human umbilical vein endothelium) generation of malondialdehyde (MDA) by LDL and vitamin E content in LDL. RESULTS: At baseline in hypertensives versus controls, lag phase was shorter (89 +/- 3 vs. 107 +/- 6 min, P < 0.04), MDA generation was higher (5.8 +/- 0.1 vs. 5.1 +/- 0.2 nmol L(-1), P=0.002), and vitamin E was reduced (6.40 +/- 0.05 vs. 6.67 +/- 0.11 microg mg(-1), P=0.03). At 3 months, BP was normalized (124 +/- 3/81 +/- 1, P < 0.0001 vs. baseline, P=ns versus controls), lag phase was prolonged (to 98 +/- 3 min, P=0.0005), MDA generation was reduced (5.6 +/- 0.1 nmol L-1, P = 0.001), and vitamin E was increased (6.53 +/- 0.05 microg mg(-1), P=0.003), with no significant differences between the randomized groups. CONCLUSIONS: In nondiabetic, nonobese, normolipidaemic patients with essential hypertension, LDL susceptibility to copper- and cell-mediated oxidation is increased. BP normalization is associated with a significant improvement, but not a full reversal, of this abnormality.

Adult↗
PubMed2001

Metabolic effects of glucose-insulin infusions: myocardium and whole body.

In target organs, insulin switches substrate utilization from free fatty acids to glucose, a change that: (i) is oxygen-efficient; (ii) repletes glycogen stores; (iii) removes potentially toxic fatty acids; and (iv) restores intracellular potassium. During or after an ischaemic challenge, the insulin metabolic mode should protect cellular functions provided that insulin can reach the ischaemic tissue. Insulin, however, also exerts non-metabolic effects, such as membrane hyperpolarization, the stimulation of adrenergic activity, and inhibition of parasympathetic tone, which may counter its beneficial metabolic actions. The net balance between the favourable and unfavourable effects of insulin on ischaemic tissues depends on: (i) the dose-response of the various effects; (ii) the presence of insulin resistance; (iii) the coexistence of hyperglycaemia; and (iv) the stage of ischaemic tissue damage. At present, a role for glucose-insulin-potassium infusions in clinical practice seems to be clearly established in the case of diabetic patients with acute coronary syndromes, and in patients undergoing urgent or elective cardiac surgery. Its role as an adjunctive therapy in the management of myocardial infarction in non-diabetic individuals has been tested in several clinical trials; however, the evidence emerging from them is inconclusive.

Diabetes Complications↗
PubMed2001

Influence of long-term diabetes on renal glycogen metabolism in the rat.

BACKGROUND/AIMS: The effects of acute insulin deficiency on the kidney have been investigated in animal models of experimental diabetes; however, the impact of long-term diabetes has not been determined. METHODS: We measured renal glycogen contents in streptozotocin (STZ)-diabetic rats 3 weeks (n = 12) or 9 months (n = 12) after the induction of diabetes, and in 2 groups of control rats of similar age (n = 16 and n = 12, respectively), in the fed state and after a 24-hour fast. RESULTS: Diabetic rats had high glucose levels, low insulin but normal glucagon concentrations in portal blood. In the fasting state, kidney glycogen content was very low in both young control and young diabetic rats (54 +/- 15 and 189 +/- 26 microg/g, respectively, mean +/- SD); in contrast, glycogen levels were markedly elevated in rats with long-standing diabetes as compared to old nondiabetic animals (2,628 +/- 1,023 +/- and 1,968 +/- 989 microg/g of diabetic rat, fasting and fed, respectively, p < 0.001 vs. 0 +/- 0 and 4 +/- 6 microg/g of control rats). On electron microscopy, large glycogen clusters were localized to the renal tubules. Kidney phosphorylase activity was higher, and synthase activity lower in diabetic than control rats (p < 0.05 for both), whereas kidney glycogen was strongly related to plasma glucose levels, suggesting that the enzyme changes were secondary to glycogen accumulation itself. Renal hexosephosphates and fructose-2,6-bisphosphate contents were both increased in long-term diabetic rats (p < 0.05), implying enhanced fluxes through both glycolysis and gluconeogenesis. CONCLUSION: In chronic, untreated diabetes glycogen accumulates in the renal tubules; prolonged hyperglycemia is the sole driving force for this phenomenon.

Aging↗
PubMed2001

Polymorphisms in the hANP (human atrial natriuretic peptide) gene, albuminuria, and hypertension.

Atrial natriuretic peptide (ANP) jointly affects kidney function and blood pressure homeostasis and is a candidate susceptibility gene for both essential hypertension and kidney disease. We evaluated the relation between the ScaI and BstXI polymorphisms of the human ANP (hANP) gene, hypertension, and albuminuria in a clinical cohort of 1033 subjects, including type 1 and type 2 diabetic patients, nondiabetic subjects with essential hypertension, and nondiabetic normotensive control subjects. Microalbuminuria was present in 15%, 29%, and 2%, respectively, of type 1 diabetic, type 2 diabetic, and nondiabetic patients. Macroalbuminuria was present in 9% of type 1 diabetics, 21% of type 2 diabetics, and 31% of nondiabetics. Prevalence of hypertension was 31%, 58%, and 61% in normoalbuminuric, microalbuminuric, and macroalbuminuric subjects, respectively (P<0.0001). Genotype distributions were in Hardy-Weinberg equilibrium in all 4 patient subgroups. The frequency of the ScaI mutated allele (A(1)) was significantly lower in hypertensive than in control subjects (11% versus 19%, P=0.018) and in patients with macroalbuminuria (5%) as compared with normoalbuminuric subjects (16%; P<0.0001). In a nominal logistic model adjusting for gender, age, obesity, diabetes, micro/macroalbuminuria, and hypertension, the A(1) allele was independently associated with macroalbuminuria (odds ratio, 0.57; confidence interval, 1.39 to 3.59; P=0.003) but not with hypertension. In the same model, the frequency of the BstXI mutated allele (T(708)) was increased in the presence of microalbuminuria (odds ratio, 2.25; confidence interval, 1.39 to 3.59; P<0.001). We conclude that the mutated genotypes of the ScaI polymorphism are negatively associated with overt nephropathy, whereas the mutated genotypes of BstXI polymorphism are positively associated with microalbuminuria. hANP gene variants may exert a protective effect against the development and progression of kidney damage in diabetes.

Adult↗
PubMed2001

Effect of levothyroxine on cardiac function and structure in subclinical hypothyroidism: a double blind, placebo-controlled study.

Subclinical hypothyroidism (sHT) affects 5-15% of the general population; however, the need of lifelong L-T(4) therapy is still controversial. As myocardium is a main target of thyroid hormone action, we investigated whether sHT induces cardiovascular alterations. Twenty sHT patients were randomly assigned to receive placebo or L-T(4) therapy and were followed for 1 yr. Twenty sex- and age-matched normal subjects served as controls. Doppler echocardiography and videodensitometric analysis were performed in all subjects. Myocardium textural parameters were obtained as mean gray levels, which were then used to calculate the cyclic variation index (CVI; percent systolic/diastolic change in mean gray levels). Patients had a significantly higher isovolumic relaxation time (3.1 +/- 0.5 vs. 2.6 +/- 0.6; P < 0.03), peak A (0.77 +/- 0.16 vs. 0.56 +/- 0.13 m/s; P < 0.01), and preejection/ejection time (PEP/ET) ratio (0.72 +/- 0.05 vs. 0.57 +/- 0.06; P < 0.03) and a lower CVI (P < 0.0001) than controls. CVI was inversely related to TSH level (P < 0.0001) and PEP/ET ratio (P < 0.01). L-T(4)-treated patients showed a significant reduction of the PEP/ET ratio (P < 0.05), peak A (P < 0.05), and isovolumic relaxation time (P < 0.05) along with a normalization of CVI. Conversely, no changes were observed in the placebo-treated group. In conclusion, sHT affects both myocardial structure and contractility. These alterations may be reversed by L-T(4) therapy.

Adult↗
PubMed2001

A model for glucose control of insulin secretion during 24 h of free living.

The aim of this work was to develop a mathematical model describing the functional dependence of insulin secretion on plasma glucose concentrations during 24 h of free living. We obtained hourly central venous blood samples from a group of healthy volunteers who spent 24 h in a calorimetric chamber, where they consumed standardized meals. Insulin secretory rates were reconstructed from plasma C-peptide concentrations by deconvolution. The relationship between insulin release and plasma glucose concentrations was modeled as the sum of three components: a static component (describing the dependence on plasma glucose concentration itself, with an embedded circadian oscillation), a dynamic component (modeling the dependence on glucose rate of change), and a residual component (including the fraction of insulin secretion not explained by glucose levels). The model fit of the individual 24-h secretion profiles was satisfactory (within the assigned experimental error of glucose and C-peptide concentrations). The static component yielded a dose-response function in which insulin release increased quasi-linearly (from 40 to 400 pmol/min on average) over the range of 4-9 mmol/l glucose. The dynamic component was significantly different from zero in coincidence with meal-related glucose excursions. The circadian oscillation and the residual component accounted for the day/night difference in the ability of glucose to stimulate insulin release. Over 24 h, total insulin release averaged 257+/-58 nmol (or 43+/-10 U). The static and dynamic component together accounted for approximately 80% of total insulin release. The model proposed here provides a detailed robust description of glucose-related insulin release during free-living conditions. In nondiabetic subjects, non-glucose-dependent insulin release is a small fraction of total insulin secretion.

Adult↗
PubMed2001

Human anti-CD38 autoantibodies raise intracellular calcium and stimulate insulin release in human pancreatic islets.

CD38 is involved in transmembrane signaling in many cell types; anti-CD38 autoantibodies have been described in diabetic patients. We tested whether human anti-CD38 antibodies possess signaling properties by measuring their ability to raise intracellular calcium ([Ca2+]i) using the fluo-3-acetoxymethyl ester method in a human-derived T-cell line (Jurkat T-cells, expressing high levels of surface CD38) and in dispersed human islet cells from normal donors. In Jurkat T-cells, 11 of 19 anti-CD38-positive sera raised [Ca2+]i (by > or =20% of baseline), whereas no [Ca2+]i-mobilizing activity was found in 27 anti-CD38-negative sera (chi2 = 20.5, P < 0.0001). In dispersed human islet cells, 5 of 11 anti-CD38-positive sera (and none of three anti-CD38-negative sera) raised [Ca2+]i significantly. When preincubated with Staphylococcus aureus protein A to remove IgG, anti-CD38-positive sera showed a 70 +/- 5% reduction in [Ca2+]i-mobilizing activity. Preincubation with CD38-transfected NIH-3T3 fibroblasts, but not with mock-transfected NIH-3T3 cells, abolished [Ca2+]i mobilization. In blocking experiments, preincubation with nonagonistic anti-CD38 monoclonal antibodies also prevented [Ca2+]i mobilization. In cultured human islets, anti-CD38-positive sera exhibiting [Ca2+]i-mobilizing activity in Jurkat T-cells (n = 6) significantly stimulated insulin release at 3.3 mmol/l glucose (median [interquartile range] 738 microU/ml [234], P = 0.0001 vs. 320 [52] microU/ml of control), whereas 6 anti-CD38-positive sera without [Ca2+]i-mobilizing activity and 10 anti-CD38-negative did not. In further incubations, the five anti-CD38-positive sera displaying [Ca2+]i-mobilizing activity in dispersed islet cells significantly stimulated insulin release at both 3.3 mmol/l glucose (2.2 +/- 0.3% of insulin islet content, P < 0.002 vs. 1.2 +/- 0.1% of control) and 16.7 mmol/l glucose (3.7 +/- 0.3 vs. 2.3 +/- 0.3%, P < 0.002). We conclude that human anti-CD38 autoantibodies with agonistic properties on the CD38 effector system occur in nature; in human islets, their [Ca2+]i-mobilizing activity is coupled with the ability to stimulate insulin release.

3T3 Cells↗
PubMed2001

Effect of physiological hyperinsulinemia on gluconeogenesis in nondiabetic subjects and in type 2 diabetic patients.

Gluconeogenesis (GNG) is enhanced in type 2 diabetes. In experimental animals, insulin at high doses decreases the incorporation of labeled GNG precursors into plasma glucose. Whether physiological hyperinsulinemia has any effect on total GNG in humans has not been determined. We combined the insulin clamp with the (2)H(2)O technique to measure total GNG in 33 subjects with type 2 diabetes (BMI 29.0 +/- 0.6 kg/m(2), fasting plasma glucose 8.1 +/- 0.3 mmol/l) and in 9 nondiabetic BMI-matched subjects after 16 h of fasting and after euglycemic hyperinsulinemia. A primed-constant infusion of 6,6-(2)H-glucose was used to monitor endogenous glucose output (EGO); insulin (40 mU. min(-1). m(-2)) was then infused while clamping plasma glucose for 2 h (at 5.8 +/- 0.1 and 4.9 +/- 0.2 mmol/l for diabetic and control subjects, respectively). In the fasting state, EGO averaged 15.2 +/- 0.4 micromol. min(-1). kg(-1)(ffm) (62% from GNG) in diabetic subjects and 12.2 +/- 0.7 micromol. min(-1). kg(-1)(ffm) (55% from GNG) in control subjects (P < 0.05 or less for both fluxes). Glycogenolysis (EGO - GNG) was similar in the two groups (P = NS). During the last 40 min of the clamp, both EGO and GNG were significantly (P < 0.01 or less, compared with fasting) inhibited (EGO 7.1 +/- 0.9 and 3.6 +/- 0.5 and GNG 7.9 +/- 0.5 and 4.5 +/- 1.0 respectively) but remained significantly (P < 0.05) higher in diabetic subjects, whereas glycogenolysis was suppressed completely and equally in both groups. During hyperinsulinemia, GNG micromol. min(-1). kg(-1)(ffm) in diabetic and control subjects, was reciprocally related to plasma glucose clearance. In conclusion, physiological hyperinsulinemia suppresses GNG by approximately 20%, while completely blocking glycogenolysis. Resistance of GNG (to insulin suppression) and resistance of glucose uptake (to insulin stimulation) are coupled phenomena. In type 2 diabetes, the excess GNG of the fasting state is carried over to the insulinized state, thereby contributing to glucose overproduction under both conditions.

Adult↗
PubMed2001

Improved glycemic control and enhanced insulin sensitivity in type 2 diabetic subjects treated with pioglitazone.

OBJECTIVE: To elucidate the effects of pioglitazone treatment on glucose and lipid metabolism in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 23 diabetic patients (age 30-70 years BMI < 36 kg/m2) who being treated with a stable dose of sulfonylurea were randomly assigned to receive either placebo (n = 11) or pioglitazone (45 mg/day) (n = 12) for 16 weeks. Before and after 16 weeks of treatment, all subjects received a 75-g oral glucose tolerance test (OGTT) and hepatic peripheral insulin sensitivity was measured with a two-step euglycemic insulin (40 and 160 mU x min(-1) x m(-2) clamp performed with 3-[3H]glucose and indirect calorimetry HbA1c measured monthly throughout the study period. RESULTS: After 16 weeks of pioglitazone treatment, the fasting plasma glucose (FPG; 184 +/- 15 to 135 +/- 11 mg/dl, P < 0.01), mean plasma glucose during OGTT(293 +/- 12 to 225 +/- 14 mg/dl, P < 0.01), and HbA1c (8.9 +/- 0.3 to 7.2 +/- 0.5%, P < 0.01 ) decreased significantly without change in fasting or glucose-stimulated insulin/C-peptide concentrations. Fasting plasma free fatty acid (FFA; 647 +/- 39 to 478 +/- 49) microEq/l, P < 0.01) and mean plasma FFA during OGTT (485 +/- 30 to 347 +/- 33 microEq/l, P < 0.01) decreased significantly after pioglitazone treatment. Before and after pioglitazone treatment, basal endogenous glucose prodution (EGP) and FPG were strongly correlated (r = 0.67, P < 0.01). EGP during the first insulin clamp step was significantly decreased after pioglitazone treatment (P < 0.05) whereas insulin-stimulated total and nonoxidative glucose disposal during the second insulin clamp was increased (P < 0.01). The change in FPG was related to the change in basal EGP, EGP during the first insulin clamp step, and total glucose disposal during the second insulin clamp step. The change in mean plasma glucose concentration during the OGGTT was strongly related to the change in total body glucose disposl during the second insulin clamp step. CONCLUSIONS: These results suggest that pioglitazone therapy in type 2 diabetic patients decreases lasting and postprandial plasma glucose levels by improving hepatic and peripheral (muscle) tissue sensitivity to insulin.

Adipose Tissue↗
PubMed2000

Insulin resistance and hyperinsulinemia: No independent relation to left ventricular mass in humans.

BACKGROUND: Hyperinsulinemia and insulin resistance may contribute to the development of cardiac hypertrophy. In humans, however, the evidence is inconclusive. METHODS AND RESULTS: We studied 50 nondiabetic subjects covering a wide range of age (20 to 65 years), body mass index (BMI, 19 to 40 kg x m(-2)), and mean blood pressure (72 to 132 mm Hg). Plasma insulin concentrations and secretory rates were measured at baseline and during an oral glucose tolerance test; insulin sensitivity was measured by the insulin clamp technique. Left ventricular mass (LVM) (by 2D M-mode echocardiography) was distributed normally and was higher in obese (BMI >/=27 kg x m(-2), n=16) or hypertensive patients (blood pressure >140/90 mm Hg, n=21) (50+/-8 and 55+/-10 g x m(-2.7), respectively) than in 13 nonobese, normotensive subjects (40+/-8 g x m(-2.7), P:=0.0004). In a multivariate model adjusting for sex, age, BMI, and blood pressure, neither insulin concentrations (fasting or postglucose) nor insulin sensitivity or secretory rates were significant correlates of LVM. Systolic blood pressure (P:=0.003) and BMI (P:=0.01) were the only independent correlates of LVM. From the regression, the impact of hypertension (as a systolic pressure of 180 versus 140 mm Hg=+20%) was twice as large as that of obesity (as a BMI of 35 versus 25 kg x m(-2)=+11%), the two factors being additive. CONCLUSIONS: When adequate account is taken of body mass and blood pressure, insulin, as concentration, secretion, or action, is not an independent determinant of LVM in nondiabetic subjects.

Adult↗
PubMed2000

Long-term interferon beta-1b therapy for MS: is routine thyroid assessment always useful?

BACKGROUND: The authors previously reported on the development of thyroid dysfunction and autoimmunity during 1-year treatment of patients with MS with interferon-beta 1b (IFN beta-1b). OBJECTIVE: To evaluate the evolution of incident thyroid disease and the possible development of more thyroid disease during longer term therapy. PATIENTS: The authors studied 31 patients (aged 34 +/- 7 years; 21 women) with relapsing-remitting MS during 3 years of IFN beta-1b treatment. Systematic thyroid assessment was performed every 3 or 6 months, depending on the development of thyroid disease. RESULTS: After the first year of IFN beta-1b treatment, no further cases of thyroid disease were observed. Among the six patients with early incident subclinical hypothyroidism, thyroid dysfunction persisted only in those with baseline autoimmune thyroiditis (n = 2). The three patients who developed transient hyperthyroidism remained euthyroid throughout the treatment course. A positive autoantibody titer was continually detected in only two out of five patients without baseline autoimmunity. CONCLUSIONS: The risk of thyroid disease seems related to IFN beta-1b treatment during the first year only, particularly in patients with preexisting thyroiditis. Furthermore, incident thyroid dysfunction is generally transient and mild in degree. Indeed, we recommend a routine systematic thyroid assessment only in patients with baseline thyroiditis. During the first year of therapy, serum thyroid-stimulating hormone measurement should suffice as first line test; a systematic thyroid assessment is only useful for those patients with incidental and persistent dysfunction. Further studies with many patients will be necessary to confirm our suggestions as broad clinical guidelines.

Adult↗
PubMed2000

Coronary atherosclerosis in Type II diabetes: angiographic findings and clinical outcome.

AIMS/HYPOTHESIS: Prevalence and incidence of coronary heart disease (CHD) are increased in patients with Type II (non-insulin-dependent) diabetes mellitus; whether this is entirely due to more extensive coronary atherosclerosis is, however, controversial. METHODS: We analysed the clinical, angiographic and follow-up data of 2253 consecutive patients undergoing coronary angiography over the decade 1983-1992. RESULTS: Abnormal coronary arteries (> or =50% stenosis) were found more frequently in diabetic than in non-diabetic subjects (85 vs 67%, p < 0.0001), the excess being explained by a higher prevalence of three-vessel disease (36 vs 17%, p < 0.0001). The sum of all angiographically detectable lumen stenoses (atherosclerosis score, ATS) was higher in diabetic than in non-diabetic subjects (352 +/- 232 vs 211 +/- 201 units, p < 0.0001). After adjusting for measured cardiovascular risk factors, diabetes was still associated with an excess ATS (114 units in men and 187 units in women, p < 0.0001 for both, p < 0.03 for the interaction ATS x sex). Within the diabetic group, the only variable that was independently (of sex and age) associated with ATS was serum cholesterol, whereas plasma glucose concentration, disease duration and type of treatment were not correlated with the severity of coronary atherosclerosis. In contrast, clinical grade proteinuria was not associated with a more diffuse coronary atherosclerosis either in diabetic (366 +/- 243 vs 354 +/- 233 units) or non-diabetic subjects (231 +/- 201 vs 207 +/- 197 units). Over a mean follow-up period of 88 months, 19% of diabetic patients compared with 10% of non-diabetic patients died of a cardiac cause (age and sex-adjusted odds ratio OR = 1.34 [1.14-1.57]). In a Cox model adjusting for age, sex and all major risk factors, diabetes was still associated with a significant excess risk of dying of a cardiac cause (OR = 1.37 [1.14-1.60]); this excess was similar to, and independent of, that carried by the presence of prior myocardial infarction in the whole population (OR = 1.42 [1.25-1.62]). Proteinuria was associated with a higher risk of cardiac death, particularly in diabetic patients, independently of coronary atherosclerosis (adjusted OR = 1.46 [1.03-1.99]). CONCLUSION/INTERPRETATION: In patients undergoing angiography, diabetes, especially in women, is associated with more severe and diffuse coronary atherosclerosis which is not explained by either the traditional risk factors or the presence of proteinuria. On follow-up, these patients experience an excess of cardiac deaths, to which coronary atherosclerosis and proteinuria make independent, quantitative contributions.

Aged↗
PubMed2000

Determinants of postabsorptive endogenous glucose output in non-diabetic subjects. European Group for the Study of Insulin Resistance (EGIR).

AIM/HYPOTHESIS: To gain insight into the physiologic determinants of postabsorptive endogenous glucose output (EGO) in humans. METHODS: We analysed the data of 344 non-diabetic subjects (212 men and 132 women) with a wide range of age (18-85 years) and body mass index (15-55 kg/m2) who participated in the European Group for the Study of Insulin Resistance (EGIR) project. Whole-body endogenous glucose output was measured by tracer ([3H]glucose) dilution at steady-state, peripheral insulin sensitivity (alpha glucose clearance/alpha insulin) was measured by the euglycaemic insulin (7 pmol x min(-1) x kg(-1)) clamp technique. RESULTS: Whole-body endogenous glucose output showed a large variability (mean = 768 +/- 202 micromol x min(-1), range 209-1512) and was strongly related to lean body mass (r = 0.63,p < 0.0001). This association entirely explained the endogenous glucose output being higher in men than in women (827 +/- 189 vs 674 x 187 micromol x min(-1), p < 0.0001), its relation to body mass (+ 10 +/- 2 per unit of body mass index, p < 0.0001) and its trend to decline with age (-1.1 +/- 0.7 micromol x min(-1) per year, p = 0.10). Although inversely related to one another (r = -0.41, p < 0.0001), peripheral insulin sensitivity and fasting plasma insulin were both independently associated with endogenous glucose output in an inverse fashion (with partial r's of 0.19 and 0.21, respectively, after adjusting for lean body mass and centre, p < 0.0001 for both). CONCLUSION/INTERPRETATION: Among non-diabetic subjects in the postabsorptive condition, total body endogenous glucose output variability is wide and is largely explained by the amount of lean mass; this, in turn, explains differences in total endogenous glucose output due to sex, obesity and age. Independently of the amount of lean mass, peripheral insulin resistance is associated with a higher endogenous glucose output independently of fasting plasma insulin concentration, suggesting coupled regulation of insulin action in peripheral tissues and the liver.

Adolescent↗
PubMed2000

Familial paroxysmal exercise-induced dyskinesia and benign epilepsy: a clinical and neurophysiological study of an uncommon disorder.

We report a family with 6 members affected by a long-lasting paroxysmal exertion-induced dyskinesia. Fasting and stress were precipitating factors. All the patients of this family had also epileptic seizures mainly of generalised type with a favourable outcome. All patients were submitted to a neurophysiological study which included somatosensory evoked potentials by median nerve stimulation (MN-SEPs), somatosensory evoked potentials by posterior tibial nerve stimulation (PTN-SEPs), brainstem auditory evoked potentials (BAEPs), visual evoked potentials (VEPs), motor evoked potentials (MEPs) by magnetic transcranial cortical stimulation (TCS) and electromyography (EMG). The neurophysiological findings suggest a hyperexcitability at the muscular and brain membrane levels, probably due to an ion channel disorder.

Adult↗