Biomedical subjects

M Muggeo

Publications and source records attributed to M Muggeo.

At least 73 records · Page 4Linked to original sources

PubMed1996

Insulin sensitivity and regular alcohol consumption: large, prospective, cross sectional population study (Bruneck study)

OBJECTIVES: To assess the relation between regular alcohol consumption and insulin sensitivity, and to estimate the importance of insulin in the association of alcohol with multiple vascular risk factors and cardiovascular disease. DESIGN: Prospective and cross sectional study of a large randomly selected population sample. SETTING: Part of the Bruneck study 1990-5 (Bolzano province, Italy). SUBJECTS: 820 health, non-diabetic women and men aged 40-79 years. MAIN OUTCOME MEASURE: Concentrations of fasting and post-glucose insulin, cholesterol, apolipoproteins, triglycerides, Lp(a) lipoprotein glucose, fibrinogen, and antithrombin III; blood pressure; insulin resistance estimated by the homeostasis model assessment. RESULTS: Fasting insulin concentrations in those who did not drink alcohol and subjects reporting low (1-50 g/day), moderate (51-99 g/day), and heavy (> or = 100 g/day) alcohol intake were 12.4, 10.0, 8.7, and 7.1 mU/l (P < 0.001). Likewise, post-glucose insulin concentrations and estimates for insulin resistance assessed by the homeostasis model assessment decreased significantly with increasing amounts of regular alcohol consumption. These trends were independent of sex, body mass index, physical activity, cigarette smoking, medication, and diet (P < 0.001). Regular alcohol intake predicted multiple changes in vascular risk factors over a five year period including increased concentrations of high density lipoprotein cholesterol and apolipoprotein A I; higher blood pressure; and decreased concentration of antithrombin III. These associations were in part attributable to the decrease in insulin concentrations observed among alcohol consumers. CONCLUSIONS: Low to moderate amounts of alcohol, when taken on a regular basis, improve insulin sensitivity. Insulin is a potential intermediate component in the association between alcohol consumption and vascular risk factors (metabolic syndrome).

Adult↗

PubMed1996

Acute effect of insulin on autonomic regulation of the cardiovascular system: a study by heart rate spectral analysis.

Insulin is suggested to have direct effects on the cardiovascular system but these are not well described. We assessed the possible influence of insulin on autonomic control of heart function. A 2-h hyperinsulinaemic euglycaemic clamp was performed in 10 healthy women (mean age 21.7 +/- 1.3 years), at two different insulin infusion rates: 80 mU m-2 and 400 mU m-2 min-1, in 7 and 3 subjects, respectively. Saline alone was infused in 4 controls. Power spectral analysis (PSA) of heart rate was recorded before and after 90-120 min of insulin infusion, as were blood pressure and heart rate. Although there were no significant changes in heart rate or blood pressure, PSA showed marked reductions of high frequency (HF) bands after insulin (2.60 +/- 0.12 vs 2.09 +/- 0.16 log ms2, p < 0.005), as at both low and high infusion rates (2.46 +/- 0.13 to 2.14 +/- 0.23 log ms2, p < 0.05, and 2.92 +/- 0.18 to 1.98 +/- 0.06 log ms2, p < 0.01, respectively). There were no significant changes of low frequency (LF) bands. Densities at LF and HF did not change significantly in control studies. As HF and LF are considered to reflect parasympathetic and mainly sympathetic control respectively, our observation of an increased LF/HF ratio (0.13 +/- 0.10 vs 0.63 +/- 0.13, p < 0.005) may be considered an index of relative sympathetic predominance induced by insulin infusion. We conclude that insulin affects the cardiovascular system, reducing vagal influence on the heart and inducing a relative hypersympathetic tone.

Adult↗

PubMed1996

Troglitazone, an insulin action enhancer, improves metabolic control in NIDDM patients. Troglitazone Study Group.

The effects of troglitazone, a novel thiazolidinedione, in non-insulin-dependent diabetic (NIDDM) patients were studied in a double-blind, parallel-group, placebo-controlled, dose-ranging trial. A total of 330 patients (63% male), mean age 57 years (range 39-72), with two fasting capillary blood glucose values > or = 7 and < or = 15 mmol/l (within 2.5 mmol/l of each other) were randomised to treatment with placebo or troglitazone at doses of 200, 400, 600 or 800 mg once daily, or 200 or 400 mg twice daily, for 12 weeks. Prior to the study, treatment had been with diet alone (38% patients) or with oral hypoglycaemic agents which were stopped 3-4 weeks before study treatment started. During treatment, HbA1c tended to rise in patients taking placebo (7.2-8.0%), but remained unchanged with all doses of troglitazone. After 12 weeks of treatment, HbA1c was significantly lower in the troglitazone-treated (mean 7.0-7.4%) compared to the placebo-treated (8.0%) patients (p = 0.055 to < 0.001), as was fasting serum glucose concentration (troglitazone, 9.3-11.0 mmol/l vs placebo, 12.9 mmol/l, p < 0.001). All doses of troglitazone were equally effective. Troglitazone also lowered fasting plasma insulin concentration, by 12-26% compared to placebo (p = 0.074 to < 0.001). Insulin sensitivity assessed by homeostasis model assessment (HOMA) was greater after 12 weeks of treatment in troglitazone-treated patients (troglitazone, 34.3-42.8% vs placebo, 29.9%, p < 0.05). In addition, serum triglyceride and non-esterified fatty acid concentrations were significantly lower and HDL cholesterol higher at troglitazone doses of 600 and 800 mg/day. LDL cholesterol increased at 400 and 600 mg doses only (from 4.3 and 3.9 mmol/l at baseline to 4.8 and 4.5 mmol/l, respectively at 12 weeks, p < 0.05), but not at doses of 800 mg once daily or 400 mg twice daily. LDL/HDL ratio did not change during treatment. All doses were well tolerated; incidence of adverse events in troglitazone-treated patients was no higher than in those treated with placebo. However, a tendency to reduced neutrophil counts was observed in patients taking the highest doses of troglitazone. We conclude that troglitazone is effective and well-tolerated and shows potential as a new therapeutic agent for the treatment of NIDDM.

Adult↗

PubMed1996

Outcome of long-term treatment with the 5 alpha-reductase inhibitor finasteride in idiopathic hirsutism: clinical and hormonal effects during a 1-year course of therapy and 1-year follow-up.

OBJECTIVE: To evaluate the long-term efficacy of the 5 alpha-reductase inhibitor finasteride in idiopathic hirsutism. DESIGN: Prospective clinical study. SETTING: Outpatients in a university hospital. PATIENT(S): Fourteen young women with idiopathic hirsutism. INTERVENTION(S): Finasteride, 5 mg once daily, was given for 12 months. MAIN OUTCOME MEASURE(S): Degree of hirsutism, graded by a modified Ferriman and Gallwey score, serum sex hormones, and serum and urinary markers of 5 alpha-reductase activity. Clinical outcome was evaluated up to and including the 1-year post-treatment period. RESULT(S): The Ferriman and Gallwey score showed a remarkable reduction after 12 months of finasteride treatment (4.4 +/- 0.7 versus 11.8 +/- 1.0; mean +/- SEM). Serum levels of the two 5 alpha-reductase activity markers, dihydrotestosterone and 3 alpha-androstanediol glucuronide, decreased, and urinary C19 and C21 5 beta:5 alpha steroid metabolite ratios consistently increased during finasteride administration. These changes were reversed readily after cessation of treatment. No significant adverse effect was reported. Nine of 14 women completed the 1-year post-treatment follow-up. Their hirsutism scores were increased substantially as compared with values recorded at the end of therapy, but still were lower than baseline values. CONCLUSION(S): The 5 alpha-reductase inhibitor finasteride is effective and well tolerated in longterm treatment of women with idiopathic hirsutism. Post-treatment follow-up suggests that drug effects on hair growth are sustained in the majority of subjects with this disorder.

5-alpha Reductase Inhibitors↗

PubMed1996

Serum uric acid and related factors in 500 hospitalized subjects.

The study purpose was to determine the following in a large sample of hospitalized patients: (1) the prevalence of hyperuricemia, (2) the association of hyperuricemia with other metabolic disorders, and (3) the factors independently predicting hyperuricemia. Five hundred adult patients (250 men and 250 women) were randomly selected from those admitted as inpatients over a period of 5 months. In all patients, body mass index (BMI), blood pressure, and serum glucose, lipid, creatinine, urea nitrogen, and urate concentrations were measured. The presence of diseases or use of medications known to affect serum urate levels were recorded. The mean level of serum urate was 5.6 mg/dL in the whole sample, 6.0 mg/dL in men and 5.3 mg/dL in women (P = .003, men v women). The prevalence of hyperuricemia was 27.6% (28.8% and 26.4% in men v women, P = nonsignificant). A definite or probable secondary hyperuricemia was found in 87.7% of the subjects. Hyperuricemia was rarely isolated (21%), whereas it was frequently associated with hypertension (60.1%), hyperlipidemia (31.2%), diabetes (28.3%), and obesity (21.7%). In 26.8% of the subjects, hyperuricemia was associated with two metabolic disorders, in 13.8% with three, and in 2.9% with four. Multiple metabolic disorders (three to four) were found in 16.7% of subjects with hyperuricemia. Serum urate levels progressively increased across a range of subjects from those without diabetes, hyperlipidemia, hypertension, or obesity to those with one, two, or a greater number of associated metabolic abnormalities. Multiple stepwise regression analysis showed that 43% of serum urate variability was explained by urea nitrogen levels, triglyceride levels, diuretic therapy, the inverse of creatinine (as an index linearly related to creatinine clearance), and BMI. These results indicate that in hospitalized subjects, hyperuricemia is (1) frequent, (2) a secondary phenomenon in most cases, and (3) frequently associated with other metabolic disorders. The major predictors of high serum urate levels are BMI, triglycerides, parameters of renal function, and use of diuretics. These variables explain a large proportion of serum urate variability.

Adult↗

PubMed1996

Early changes in plasma glucagon and growth hormone response to oral glucose in experimental hyperthyroidism.

The mechanisms underlying deterioration of glucose tolerance associated with hyperthyroidism are not completely understood. Increases in glucagon and growth hormone (GH) secretion have been previously found in hyperthyroid subjects, and could play a crucial role in this phenomenon. However, studies have not yet established the time sequence of changes in plasma glucose on the one hand and glucagon and GH on the other. To assess the early effects of thyroid hormone excess on glucose tolerance and plasma concentrations of the main glucoregulatory hormones, 12 nondiabetic euthyroid subjects underwent an oral glucose tolerance test (OGTT) before and after triiodothyronine ([T3] 120 micrograms/d) was administered for 10 days. Plasma levels of glucose, insulin, glucagon, and GH were determined at fasting and after the glucose load. T3 administration caused a marked increase in serum T3 (8.8 +/- 0.6 v 2.0 +/- 0.1 nmol/L), with clinical and biochemical signs of thyrotoxicosis. During the treatment, plasma glucose significantly increased both at fasting and after the glucose load (basal, 5.3 +/- 0.1 v 4.9 +/- 0.2 mmol/L, P < .05; area under the curve [AUC] for OGTT, 7.7 +/- 0.3 v 6.7 +/- 0.4 mmol/L min, P < .01) without any change in plasma insulin levels. After T3 administration, plasma glucagon levels were lower than at baseline (basal, 92 +/- 7 v 148 +/- 35 ng/L; AUC, 74 +/- 6 v 98 +/- 16 ng/L.min, P < .05), showing an appropriate reduction by the increased glucose levels. Conversely, plasma GH showed impaired suppression by hyperglycemia (AUC, 1.2 +/- 0.3 v 0.7 +/- 0.2 microgram/L.min, P < .05). In conclusion, thyroid hormone excess rapidly impairs glucose tolerance. Altered secretion of GH is an early event in thyrotoxicosis accompanying the onset of hyperglycemia, whereas plasma glucagon is appropriately suppressed by the increased plasma glucose levels. Thus, GH but not glucagon may contribute to the early hyperglycemic effect of thyrotoxicosis.

Administration, Oral↗

PubMed1996

Plasma factor VII and its relation to adipose tissue fatty acids and other atherogenic risk factors in healthy men.

In this study the authors examined the relationships of plasma factor VII (F-VII) to adipose tissue fatty acid composition, as an objective index of the habitual dietary fat intake, as well as to a number of other atherogenic risk factors in 60 healthy male volunteers (aged 38 years). Significant positive correlations were found between plasma F-VII [measured as antigen (F-VIIAg) and coagulant activity, using bovine thromboplastin (F-VIIbt)] and body mass index (BMI), waist-thigh girth ratio (WTR), cigarette smoking and plasma triglyceride concentration. After adjustment for BMI, only plasma triglycerides remained positively correlated with F-VII (r = 0 center dot 27, P = 0 center dot 03, and r = 0 center dot 29, P < 0 center dot 01, for F-VIIbt and F-VIIAg respectively). A significant positive relation was found between F-VII and the total proportion of fatty acid as monounsaturated fatty acid (r = 0 center dot 26, P < 0 center dot 05, for F-VIIAg), whereas inverse relations were found between F-VII, the total proportion of fatty acid as polyunsaturated fatty acid (r = -0 center dot 26 and r = -0 center dot 25, P < 0 center dot 05, for F-VIIbt and F-VIIAg respectively), polyunsaturated-saturated fat ratio (r = -0 center dot 25, P < 0 center dot 05, for F-VIIbt) and, more significantly, between F-VII and adipose-tissue alpha-linolenic acid (r = -0 center dot 29, P < 0 center dot 01, for F-VIIbt and r = -0 center dot 49, P < 0 center dot 001, for F-VIIAg). All these correlations remained significant after matching for BMI. In a multiple linear regression analysis, only adipose tissue alpha-linolenic acid was a negative and independent predictor of F-VIIAg (P = 0 center dot 004) and, at borderline significance, of F-VIIbt (P = 0 center dot 061) when allowance was made for BMI, WTR, smoking and plasma triglycerides. In conclusion, this study shows significant relations between F-VII and adipose tissue fatty acid composition in healthy male individuals; it supports the possibility that adipose tissue poly-unsaturated fatty acids, derived from dietary intake, play a role in the relation between F-VII and coronary heart disease (CHD), thus suggesting that high dietary polyunsaturated fatty acid intake (especially alpha-linolenic acid) may reduce the risk for CHD by an improvement of a number of risk factors, including a lowering of plasma F-VII (both activity and antigen).

Adipose Tissue↗

PubMed1996

The white blood cell count: its relationship to plasma insulin and other cardiovascular risk factors in healthy male individuals.

OBJECTIVES: To evaluate the relationships of total and differential white blood cell (WBC) count to the components of the so-called insulin resistance syndrome. SUBJECTS AND DESIGN: The study population consisted of a random sample of 90 38-year-old healthy men with normal glucose tolerance. INTERVENTIONS: A 75 g oral glucose tolerance test was performed in all participants. MAIN OUTCOME MEASURES: Total and differential WBC count, lipids, blood pressure, plasma glucose, C-peptide and insulin (at fasting and 2 h after glucose load). RESULTS: Total WBC count correlated consistently with plasma 2-h glucose (r = 0.38; P < 0.001), fasting and 2-h postload insulin (r = 0.26 and r = 0.33; P < 0.01-0.001, respectively) and C-peptide (r = 0.28 and r = 0.32; P < 0.01-0.001) concentrations. Smokers had significantly higher total leukocytes (P < 0.01), neutrophils and lymphocytes than nonsmokers. Furthermore, total WBC count correlated positively with body mass index, blood pressure, plasma triglycerides, fibrinogen, and negatively with HDL cholesterol concentration. As differential WBC count, most variables correlated essentially to neutrophils and/or lymphocytes, whereas plasma insulin and C-peptide concentrations correlated essentially to lymphocytes and monocytes, but not to neutrophils. In a multiple linear regression analysis, only 2-h plasma glucose (P < 0.01) and fibrinogen (P < 0.05) were positive predictors of total WBC count after adjusting for all potentially confounding variables. CONCLUSIONS: The results indicate that increased, albeit normal, WBC count associates with the cluster of metabolic and haemodynamic disorders typical of the insulin resistance syndrome, and suggest that increased WBC count may be yet another component of this syndrome.

Adult↗

PubMed1996

Insulin infusion amplifies 17 alpha-hydroxycorticosteroid intermediates response to adrenocorticotropin in hyperandrogenic women: apparent relative impairment of 17,20-lyase activity.

Recent data suggest that insulin is a modulator of ovarian and adrenal steroidogenesis and that, in the ovary of hyperandrogenic women, hyperinsulinemia might cause dysregulation of cytochrome P450c17 alpha activity. To further assess in vivo the effects of insulin on adrenal steroidogenesis, ACTH stimulation was carried out in 21 hyperandrogenic women during a 3-h hyperinsulinemic (80 mU/m2-min) euglycemic clamp. In all of these women the procedure was repeated during saline infusion as n control. In nonamenorrheic patients, the tests were performed in the early follicular phase of two different menstrual cycles. Serum cortisol, progesterone, 17-hydroxypregnenolone (17-OHJPREG). 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), and androstenedione (A) were measured after 2 h of insulin or saline infusion (zero time) and, subsequently, 30 and 60 min after an iv bolus of 0.25 mg ACTH-(1-24). At zero time, no difference was found in the serum steroid concentrations between the two protocols. ACTH-stimulated serum 17-OHPREG and, to a lesser extent, 17-OHP were significantly higher during insulin than during saline infusion (peaks, 60.6 +/- 9.0 vs. 40.7 +/- 7.9 and 7.7 +/- 7.7 vs. 6.6 +/- 0.6 nmol/L; P < 0.005 and P < 0.01, respectively). Serum DHEA was also slightly higher during hyperinsulinemia, although only after 30 min (54.5 +/- 3.0 vs. 48.2 +/- 4.2 nmol/L; P < 0.05). No statistically significant difference in the cortisol, progesterone, or androstenedione response to ACTH was found between the two protocols. ACTH-stimulated 17-OHPREG/DHEA and 17-OHP/A molar ratios, indexes of apparent 17,20-lyase activity, were significantly higher during the clamp studies than during saline infusion (by ANOVA, F = 12.8; P < 0.001 and F = 6.7; P < 0.005, respectively), suggesting an impaired enzyme activity. These in vivo data support the hypothesis that insulin potentiates ACTH-stimulated steroidogenesis. This effect of insulin seems to be associated with a relative impairment of 17,20-lyase activity.

17-Hydroxycorticosteroids↗

PubMed1996

The insulin resistance in women with hyperandrogenism is partially reversed by antiandrogen treatment: evidence that androgens impair insulin action in women.

To assess whether androgen excess per se might impair insulin action, insulin sensitivity was measured by a two-step (20 and 80 mU/m2.min) hyperinsulinemic euglycemic clamp combined with indirect calorimetry and tracer glucose infusion in 43 women (13 obese and 30 nonobese) with normal glucose tolerance and clinical evidence of increased androgen action (hirsutism and/or polycystic ovary syndrome) as well as 12 age- and body mass index-matched healthy controls. Hyperandrogenic women were studied basally and after 3-4 months of antiandrogen treatment with 3 different drugs: spironolactone (n = 23), flutamide (n = 10), or the GnRH agonist buserelin (n = 10). Six women given spironolactone were also reexamined after 1 yr of therapy. At baseline, insulin-mediated glucose uptake was lower in hyperandrogenic women than in controls (by ANOVA, F = 14.3; P < 0.001). Insulin resistance was observed in both ovarian and nonovarian hyperandrogenism, as distinguished by acute GnRH agonist testing. After antiandrogen therapy, insulin action on glucose metabolism significantly increased for both the patients as a whole (F = 7.4; P < 0.01) and each treatment group separately. However, insulin action remained lower than in controls and showed no further improvement in patients reevaluated after I yr of treatment. Increases in both oxidative and nonoxidative glucose metabolism accounted for the improvement in substrate disposal induced by antiandrogen drugs. The increase in the effectiveness of insulin was greater in the lean subjects, whereas the change was small and not statistically significant in the obese women. Response to treatment was more pronounced in women with nonovarian hyperandrogenism, particularly at the low insulin infusion rate. Endogenous glucose production in hyperandrogenic patients was similar to that in healthy women and was unaffected by therapy. In conclusion, antiandrogen treatment partially reversed the peripheral insulin resistance associated with hyperandrogenism regardless of which antiandrogen was used. These data strongly suggest that in women, androgen excess per se contributes to impairment of insulin action.

Adult↗

PubMed1996

Power spectral analysis of heart rate in hyperthyroidism.

The aim of the present study was to evaluate the impact of hyperthyroidism on the cardiovascular system by separately analyzing the sympathetic and parasympathetic influences on heart rate. Heart rate variability was evaluated by autoregressive power spectral analysis. This method allows a reliable quantification of the low frequency (LF) and high frequency (HF) components of the heart rate power spectral density; these are considered to be under mainly sympathetic and pure parasympathetic control, respectively. In 10 newly diagnosed untreated hyperthyroid patients with Graves' disease, we analyzed power spectral density of heart rate cyclic variations at rest, while lying, and while standing. In addition, heart rate variations during deep breathing, lying and standing, and Valsalva's maneuver were analyzed. The results were compared to those obtained from 10 age-, sex-, and body mass index-matched control subjects. In 8 hyperthyroid patients, the same evaluation was repeated after the induction of stable euthyroidism by methimazole. Heart rate power spectral analysis showed a sharp reduction of HF components in hyperthyroid subjects compared to controls [lying, 13.3 +/- 4.1 vs. 32.0 +/- 5.6 normalized units (NU; P < 0.01); standing, 6.0 +/- 2.7 vs. 15.0 +/- 4.0 NU (P < 0.01); mean +/- SEM]. On the other hand components were comparable in the 2 groups (lying, 64.0 +/- 6.9 vs. 62.0 +/- 6.5 NU; standing, 77.0 +/- 6.5 vs. 78.0 +/- 5.4 NU). Hence, the LF/HF ratio, which is considered an index of sympathovagal balance, was increased in hyperthyroid subjects while both lying (11.3 +/- 4.5 vs. 3.5 +/- 1.1; P < 0.05) and standing (54.0 +/- 12.6 vs. 9.8 +/- 2.6; P < 0.02). This parameter was positively correlated with both T3 (r = 0.61; P < 0.05) and free T4 (r = 0.63; P < 0.05) serum levels. Among traditional cardiovascular autonomic tests, the reflex response of heart rate during lying to standing was significantly lower in hyperthyroid patients than in controls (1.12 +/- 0.03 vs. 1.31 +/- 0.04; P < 0.002). No statistically significant difference in reflex responses between the two groups was found in deep breathing or Valsalva's maneuver. In the 8 patients reexamined after methimazole treatment, we observed complete normalization of altered cardiovascular parameters, with slight predominance of the vagal component compared with controls. These results suggest that thyroid hormone excess may determine reduced parasympathetic activity and, thus, a relative hypersympathetic tone.

Adolescent↗

PubMed1996

Increase in circulating products of lipid peroxidation in smokers with IDDM.

OBJECTIVE: To measure plasma malondialdehyde (MDA) concentration, a product of lipid peroxidation, both in IDDM patients and in healthy control subjects and to examine whether smoking has a negative impact on the plasma MDA levels in diabetic patients. RESEARCH DESIGN AND METHODS: Plasma total MDA concentration (as a thiobarbituric acid adduct by high-performance liquid chromatography) was measured in 56 young IDDM patients and in a group of 32 age-, sex-, BMI-, and smoking habit-matched healthy subjects. RESULTS: Plasma MDA concentration in IDDM patients was significantly higher than that in healthy control subjects (mean +/- SE: 0.95 +/- 0.03 vs. 0.54 +/- 0.03 mumol/l; P < 0.0001). After stratification by smoking status, it was seen that diabetic smokers had values of age, BMI, serum lipids, blood pressure, metabolic control, and diabetes duration and its chronic complications superimposable on those of their nonsmoking counterparts. Nevertheless, plasma MDA concentration was significantly higher in IDDM patients who smoked than in IDDM patients who didn't smoke (1.03 +/- 0.4 vs. 0.87 +/- 0.03 mumol/l; P = 0.002), without any sex difference with regard to MDA levels. CONCLUSIONS: These data show an increase in circulating products of lipid peroxidation in young diabetic smokers, thus further supporting the clinical importance of discouraging the initiation of smoking as well as promoting its cessation in people with IDDM.

Adult↗

PubMed1996

Attending the diabetes center is associated with increased 5-year survival probability of diabetic patients: the Verona Diabetes Study.

OBJECTIVE: The aim of the present study is to compare the survival of patients attending diabetes centers with that of patients exclusively consulting family physicians. RESEARCH DESIGN AND METHODS: The study was carried out in the frame of the Verona Diabetes Study, a population-based survey of known diabetes prevalence with a subsequent 5-year mortality follow-up. A cohort of 7,488 diabetic patients were identified on 31 December 1986 from three different sources: a drug consumption database, family physicians, and diabetes centers (one for children and one for adults). As of 31 December 1986, 3,288 patients in the entire cohort exclusively consulted their own family physicians, while 4,200 patients also had periodic examinations at the diabetes centers. The life status of the diabetic cohort was ascertained on 31 December 1991. RESULTS: Compared with the nondiabetic population, diabetic patients seen only by family physicians had a standardized mortality ratio (SMR) of 1.62 (95% CI 1.51-1.74), while patients attending both family physicians and diabetes centers showed an SMR of 1.44 (1.34-1.54), the difference being statistically significant (P = 0.017). The 5-year survival probability, estimated by the Kaplan-Meier method, was 0.76 (0.75-0.78) in patients seen only by family physicians and 0.81 (0.80-0.82) in patients attending the diabetes centers. Multivariate analysis by Cox regression model showed that attending the diabetes centers was an independent predictor of survival even after adjusting for sex, age, and therapy of diabetes. The relative risk of 5-year all-cause mortality amounted to 0.83 (0.75-0.92) in patients also attending the diabetes centers with respect to patients consulting only family physicians (P < 0.001). CONCLUSIONS: These data on patients' survival indicate that diabetes centers play a crucial role in diabetes care. As a corollary, an integration between primary-care physicians and diabetes centers is strongly recommended.

Adolescent↗

PubMed1996

Cardiovascular disease and its risk factors in IDDM in Europe. EURODIAB IDDM Complications Study Group.

OBJECTIVE: To study the prevalence of cardiovascular disease (CVD), its risk factors, and their associations in IDDM patients in different European countries. RESEARCH DESIGN AND METHODS: The prevalence of CVD (a past history or electrocardiogram abnormalities) and its risk factors were examined in a cross-sectional study in 3,250 IDDM patients from 16 European countries (EURODIAB IDDM Complications Study). The patients were examined in 31 centers and were stratified between centers for age, sex, and duration of diabetes. The mean +/- SD duration of diabetes was 14.7 +/- 9.3 years. RESULTS: The prevalence of CVD was 9% in men and 10% in women. The prevalence increased with age (from 6% in patients 15-29 years old to 25% in patients 45-59 years old) and with duration of diabetes. The between-center variation for the whole population was from 3 to 19%. In both sexes, fasting triglyceride concentration was higher and HDL cholesterol lower in those patients with CVD than in those without. In men, duration of diabetes was longer, waist-to-hip ratio greater, and hypertension more common in patients with CVD. In women, a greater BMI was associated with increased prevalence of CVD. There was no association between insulin dose, HbA1c level, age-adjusted rate of albumin excretion, or smoking status and CVD. Waist-to-hip ratio, particularly in men, was positively associated with age, age-adjusted HbA1c, prevalence of smoking, daily insulin dose, albumin excretion rate, and fasting triglyceride concentrations. CONCLUSIONS: The overall prevalence of CVD in these IDDM patients was approximately 10%, increasing with age and duration of diabetes and with a sixfold variation between different European centers. CVD prevalence was most strongly associated with elevated triglyceride and decreased HDL cholesterol concentrations. CVD was also associated with albuminuria, but when adjusted by age, this association vanished. Increasing waist-to-hip ratio was associated with a number of adverse characteristics, particularly in IDDM men, reflecting the metabolic syndrome previously described in other populations.

Adolescent↗

PubMed1996

Moderate alcohol consumption and its relation to visceral fat and plasma androgens in healthy women.

OBJECTIVE: To study the inter-relationships between daily alcohol intake, fat distribution and plasma androgens in order to verify whether daily alcohol intake correlates with abdominal body fat and, if so, to what extent such a relation is mediated by plasma androgens. SUBJECTS: A random sample of 87 clinically healthy women (aged 38 y) with a light-moderate alcohol consumption and without clinical evidence suggestive of any endocrine disorder. MEASUREMENTS: Anthropometric and computed tomography (CT scans made at the level of L4-L5 in a subgroup of 18 women) measurements of body fatness and adipose tissue distribution, main behavioural factors, including daily alcohol intake and plasma androgens (i.e. total and free testosterone levels). RESULTS: After adjustment for BMI, cigarette smoking and physical activity, significant differences were found in waist circumference and waist-hip ratio as well as in plasma androgens with increasing daily alcohol intake. Waist-thigh ratio tended to parallel waist-hip ratio, but did not achieve statistical significance. In simple linear regression analysis, abdominal visceral fat area, derived from CT, correlated positively with both plasma free testosterone and alcohol intake. While the above reported difference in body fat distribution totally disappeared after controlling also for free testosterone level, the differences in plasma androgens with increasing alcohol intake remained essentially unchanged when allowance was made also for waist-hip ratio. In multiple linear regression analysis, daily alcohol intake appeared to be positively and independently correlated to both plasma total and free testosterone levels. Neither BMI nor waist-hip ratio nor fasting insulin made any significant contribution to the prediction of plasma androgens after daily alcohol intake had been taken into account. CONCLUSIONS: The results of this study show that moderate alcohol consumption correlates with abdominal distribution of body fat, likely due to enlarged visceral fat area, and increased plasma androgenicity (i.e. higher total and free testosterone levels) in adult healthy women. These data also suggest that the relation between alcohol intake and fat distribution may be, at least in part, mediated by plasma androgens.

Adipose Tissue↗

PubMed1996

Cardiovascular risk profile in 38-year and 18-year-old men. Contribution of body fat content and regional fat distribution.

OBJECTIVE: To evaluate whether young and middle-age men differ in blood pressure and serum lipid profiles and, if so, to what extent these differences are dependent on total body fat, regional fat distribution, plasma insulin and behavioural variables. SUBJECTS: Random samples of 94 young (18 year-old) and 94 middle-age (38 year-old) healthy men matched for body mass index (BMI). MEASUREMENTS: BMI, total body fat (by bioelectrical impedance), regional fat distribution (by anthropometry), serum lipids, blood pressure, fasting insulin and some behavioural variables. RESULTS: Total body fat was similar in the two groups (mean +/- s.e.: 16.6 +/- 0.5 vs 16.0 +/- 0.6 kg and 20.8 +/- 0.5 vs 20 +/- 0.5%), while waist/hip circumference ratio (WHR) was significantly higher in middle-age as compared to young men (0.96 +/- 0.001 vs 0.92 +/- 0.003, P < 0.0001). The former also had significantly higher serum concentrations of total cholesterol (6.21 +/- 0.13 vs 4.10 +/- 0.10 mmol/l; P < 0.0001). LDL-cholesterol (4.24 +/- 0.11 vs 2.34 +/- 0.10 mmol/l; P < 0.0001), triglycerides 1.40 +/- 0.09 vs 1.02 +/- 0.06 mmol/l; P < 0.01) as well as higher systolic (134.0 +/- 1.6 vs 126.3 +/- 1.4 mmHg; P < 0.0001) and diastolic (86.8 +/- 0.9 vs 82.0 +/- 1.1 mmHg; P < 0.001) blood pressure values. HDL-cholesterol and fasting insulin concentrations were similar in the two groups (1.33 +/- 0.03 vs 1.28 +/- 0.03 mmol/l and 13.7 +/- 0.6 vs 14.7 +/- 0.7 mU/l, respectively). Significant differences in the two groups also were found in daily alcohol consumption (49.6 +/- 5.7 vs 20.0 +/- 3.4 g/day; P < 0.0001), whereas no significant differences were found in smoking and physical activity level. The comparison of subgroups (n = 41) of young and middle-age men matched for both BMI and WHR showed virtually unchanged differences in serum lipids and blood pressure. When age, BMI, WHR, fasting insulin and behavioural variables were included as independent variables in a multiple linear regression analysis in which subjects of the two groups were pooled, age was a significant predictor of total and LDL cholesterol, triglycerides and systolic blood pressure, insulin predicted HDL cholesterol and systolic blood pressure, BMI predicted triglycerides and diastolic blood pressure and WHR was not an independent predictor of any risk factor. CONCLUSIONS: These results indicate that middle-age men have a cardiovascular risk profile less favourable than young men, which is largely independent of differences in total body fat content, regional fat distribution and behavioural variables.

Adipose Tissue↗

PubMed1996

Liver steatosis and its relation to plasma haemostatic factors in apparently healthy men--role of the metabolic syndrome.

The relationship between liver steatosis, evaluated by ultrasonography, and various plasma haemostatic factors was examined in 64 apparently healthy males, aged 38 years. Plasma levels of factor VII clotting activity (F-VIIc), plasminogen activator inhibitor-1 (PAI-1) activity and antigen, tissue-type plasminogen activator (t-PA) activity significantly differed in men with liver steatosis (n = 31) as compared with those without steatosis (n = 33). No significant differences were found in t-PA antigen and F-VII antigen. The men with liver steatosis also had significantly higher body mass index (BMI), plasma triglyceride and 2 h post-load insulin concentrations. While the differences in plasma haemostatic factors were substantially unchanged after adjustment for BMI, they totally disappeared when further allowance was made for plasma triglyceride and 2 h insulin concentrations. In conclusion, these results indicate that liver steatosis correlates specifically with increased PAI-1, F-VIIc and decreased t-PA levels, and suggest that such a relation is largely mediated by concomitant alterations in plasma triglyceride and insulin concentrations.

Adult↗

PubMed1996

Ultrasonographic intra-abdominal depth and its relation to haemostatic factors in healthy males.

OBJECTIVE: To examine the relationship of intra-abdominal fat to plasma haemostatic factors. SUBJECTS: 60 healthy, predominantly nonobese, male volunteers aged 38 years. MEASUREMENTS: Anthropometry, sonographic intra-abdominal depth (IAD), as an indicator of intra-abdominal fat, plasma lipids, plasma insulin (at fasting and after glucose load), various plasma haemostatic factors. RESULTS: Sonographic IAD correlated positively with plasma fibrinogen (r = 0.33; P < 0.01), PAI-1 activity (r = 0.52; P < 0.0001) and antigen (r = 0.32; P < 0.05), and negatively with t-PA activity, at baseline and after stasis (r = -0.28 and r = 0.31; P < 0.05). Factor VII levels did not correlate significantly with sonographic IAD. Haemostatic variables were also closely associated with BMI, plasma triglyceride and insulin concentrations. Most correlations of haemostatic factors with IAD disappeared after adjustment for either BMI or insulin or triglycerides, except PAI-1 levels which maintained a significant association even after simultaneous adjustment for all potential confounders. CONCLUSIONS: These results, obtained by sonography, confirm our previous findings of significant associations of haemostatic variables with visceral fat accumulation by using computed tomography, and highlight the role of the intra-abdominal fat as an independent predictor of PAI-1 activity.

Abdomen↗