Olga Vaccaro

Diabetes, Other Risk Factors, and 12-Yr Cardiovascular Mortality for Men Screened in the Multiple Risk Factor Intervention Trial

OBJECTIVE To assess predictors of CVD mortality among men with and without diabetes and to assess the independent effect of diabetes on the risk of CVD death. RESEARCH DESIGN AND METHODS Participants in this cohort study were screened from 1973 to 1975; vital status has been ascertained over an average of 12 yr of follow-up (range 11–13 yr). Participants were 347,978 men aged 35–57 yr, screened in 20 centers for MRFIT. The outcome measure was CVD mortality. RESULTS Among 5163 men who reported taking medication for diabetes, 1092 deaths (603 CVD deaths) occurred in an average of 12 yr of follow-up. Among 342,815 men not taking medication for diabetes, 20,867 deaths were identified, 8965 ascribed to CVD. Absolute risk of CVD death was much higher for diabetic than nondiabetic men of every age stratum, ethnic background, and risk factor level—overall three times higher, with adjustment for age, race, income, serum cholesterol level, sBP, and reported number of cigarettes/day (P < 0.0001). For men both with and without diabetes, serum cholesterol level, sBP, and cigarette smoking were significant predictors of CVD mortality. For diabetic men with higher values for each risk factor and their combinations, absolute risk of CVD death increased more steeply than for nondiabetic men, so that absolute excess risk for diabetic men was progressively greater than for nondiabetic men with higher risk factor levels. CONCLUSIONS These findings emphasize the importance of rigorous sustained intervention in people with diabetes to control blood pressure, lower serum cholesterol, and abolish cigarette smoking, and the importance of considering nutritional-hygienic approaches on a mass scale to prevent diabetes.

International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes

Members of the International Expert Committee have recommended that diabetes should be diagnosed if A1C is ≤6.5%, without need to measure the plasma glucose concentration (1). We are concerned that practical limitations will lead to false positives and negatives with this approach. A given A1C instrument may identify some but not other abnormal hemoglobins (http://www.ngsp.org/prog/index2.html). How, therefore, can we be sure whether a hemoglobinopathy is causing (or preventing) diagnosis? Before diagnosis, should we not also exclude iron deficiency anemia, which may increase A1C by 1–1.5%, as well as hemolytic anemia and renal failure or chronic infections, which also lower …

Early abnormalities of cardiac function in non-insulin-dependent diabetes mellitus and impaired glucose tolerance

The aim of this study was to evaluate the role of diabetes and minor abnormalities of glucose homeostasis, such as impaired glucose tolerance, as determinants of cardiac function and structure in a working population. We studied a population-based sample of 64 telephone company employees (both sexes, mean age 58 years): 25 with normoglycemia, 15 with impaired glucose tolerance, and 24 with non-insulin-dependent diabetes mellitus (NIDDM) diagnosed by oral glucose tolerance test according to the recommendations of the World Health Organization. Subjects with myocardial ischemia were excluded. Left ventricular end-systolic dimension, indexed to body surface area, was greater in those with NIDDM (p < 0.05) and in those with impaired glucose tolerance (p < 0.05) with respect to normoglycemic persons. The ratio of the peak early diastolic velocity wave to the late diastolic wave was lower in those with NIDDM (p < 0.05) and in those with impaired glucose tolerance (p < 0.05) than in participants with normoglycemia. Body mass index and blood pressure were similar in the 3 groups. These results clearly indicate that early abnormalities of cardiac structure and function are observed not only in patients with NIDDM, but also in those with impaired glucose tolerance, independent of the confounding role of myocardial ischemia, body weight, and blood pressure.

Plasma Fibrinogen: A New Factor of the Metabolic Syndrome: A population-based study

OBJECTIVE To evaluate whether hyperfibrinogenemia represents a component of the metabolic syndrome. RESEARCH DESIGN AND METHODS A cross-sectional study was conducted on the relation between fibrinogen and the metabolic syndrome in a working population of 1,252 nondiabetic men, aged 35–64 years, randomly selected among all men participating in a health screening. We measured anthropometric characteristics, blood pressure, fasting plasma fibrinogen, cholesterol (total, LDL, and HDL), triglycerides, glucose, and insulin. Individuals with two or more metabolic abnormalities (defined as being in the highest quartile of the distribution of diastolic blood pressure, plasma glucose, or triglycerides or being in the lowest quartile of HDL cholesterol) were considered to have the metabolic syndrome. RESULTS Age-adjusted fibrinogen levels correlated significantly with BMI, waist-to-hip ratio, systolic and diastolic blood pressure, plasma total cholesterol, LDL cholesterol, triglycerides, insulin, and HDL cholesterol (inversely). Subjects with the metabolic syndrome had significantly higher plasma fibrinogen levels than those without (285.1 ± 1.9 vs. 300.2 ± 3.0 mg/dl, mean ± SE, P = 0.0001). Plasma fibrinogen concentrations and the prevalence of hyperfibrinogenemia (defined as ≥350 mg/dl) increased progressively from 279 to 307 mg/dl (P = 0.0001) and from 9 to 22% (P = 0.0024), respectively, across categories with an increasing number of metabolic disorders characterizing the syndrome (only one, any two, three or more). In multivariate analyses, both plasma insulin and the metabolic syndrome were significantly and independently associated with plasma fibrinogen. CONCLUSIONS The finding suggests that hyperfibrinogenemia may be considered a component of the metabolic syndrome. This may also explain the increased cardiovascular risk associated with hyperinsulinemia/insulin resistance.

Heterogeneous Effect of Peroxisome Proliferator-activated Receptor γ2 Ala12 Variant on Type 2 Diabetes Risk

Conflicting results have been reported regarding whether the PPARγ2 Pro12Ala polymorphism plays a role in the risk of type 2 diabetes (T2D), suggesting genetic heterogeneity. To investigate this issue, a meta‐analysis of 41 published and 2 unpublished studies (a total of 42,910 subjects) was conducted. Ala12 carriers had a 19% T2D risk reduction, but this association was highly heterogeneous (p = 0.005). A great proportion (48%) of heterogeneity was explained by the controls’ BMI, with risk reduction being greater when BMI was lower. Risk reduction of Ala12 carriers in Asia (35%) was higher than in Europe (15%, p = 0.02) and tended to be higher than in North America (18%, p = 0.10). Difference between Asians and Europeans was no longer significant (p = 0.15) after adjusting for the controls’ BMI. Studies from Europe were still heterogeneous (p = 0.02) with risk reduction in Ala12 carriers being progressively smaller (test for trend in the odds ratios, p = 0.02) from Northern (26% reduction, p < 0.0001) to Central (10%, p = 0.04) and Southern (0%, p = 0.94) Europe. In conclusion, in our meta‐analysis, the reduced risk of T2D in Ala12 carriers is not homogeneous. It is greater in Asia than in Europe and, among Europeans, it is higher in Northern Europe, barely significant in Central Europe, and nonexistent in Southern Europe.

Abdominal Adiposity Is Associated With Elevated C-Reactive Protein Independent of BMI in Healthy Nonobese People

OBJECTIVE There is debate over the most appropriate adiposity markers of obesity-associated health risks. We evaluated the relationship between fat distribution and high-sensitivity C-reactive protein (hs-CRP), independent of total adiposity. RESEARCH DESIGN AND METHODS We studied 350 people with abdominal adiposity (waist-to-hip ratio [WHR] ≥0.9 in male and ≥0.85 in female subjects) and 199 control subjects (WHR <0.9 in male and <0.85 in female subjects) matched for BMI and age. We measured hs-CRP and major cardiovascular risk factors. RESULTS Participants with abdominal adiposity had BMI similar to that in control subjects (24.8 ± 2.5 vs. 24.7 ± 2.2 kg/m2, respectively), but significantly higher waist circumference (96.4 ± 6.0 vs. 83.3 ± 6.7 cm; P < 0.01) and WHR (1.07 ± 0.08 vs. 0.85 ± 0.05; P < 0.001). Compared with the control subjects, participants with abdominal adiposity had an adverse cardiovascular risk factor profile, significantly higher hs-CRP (1.96 ± 2.60 vs. 1.53 ± 1.74 mg/dl; P < 0.01), and a twofold prevalence of elevated CRP values (>3 mg/dl). CONCLUSIONS In nonobese people, moderate abdominal adiposity is associated with markers of subclinical inflammation independent of BMI.

Cardiovascular risk in women with diabetes

Women with diabetes have a high risk of cardiovascular disease that, almost completely eliminates the gender difference in cardiovascular morbidity and mortality between non-diabetic men and women. In this chapter we have reviewed data showing that cardiovascular risk factors are more common, more likely to cluster, or more severe in diabetic women than men; this may be due to biological or behavioural factors. Disparities in accessibility, quality and, possibly, effectiveness of care further disadvantage diabetic women. Based on available data it can be concluded that a large number of CVD deaths are preventable in diabetic women; therefore special attention should be paid to risk factors detection and correction, as well as timely CHD diagnosis and treatment in diabetic women. To meet these needs gender specific guidelines and implementation measures may be in order.

Relation of insulin resistance to left ventricular hypertrophy and diastolic dysfunction in obesity

OBJECTIVE: To assess relations of left ventricular (LV) geometry and function to insulin resistance in obesity – a condition associated with volume overload and abnormal LV relaxation.DESIGN: Cross-sectional relational study.SUBJECTS: 27 healthy overweight–obese subjects (18 women, body mass index (BMI)=35.0±4.0 kg/m2) and 31 age-matched normal-weight controls (21 women, BMI=22.6±2.4 kg/m2).MEASUREMENTS: Subjects were studied by Doppler-echocardiography the same day and hour (08.00 h) as measurements of fasting insulin and blood glucose were made. Insulin resistance was determined by the ‘Homeostasis Assessment Model’.RESULTS: Twelve obese subjects with insulin resistance (IR) had higher body size than 15 patients without IR and higher blood pressure than normal-weight controls (all P<0.01). Relative IR was related to isovolumic relaxation time. This relation was not maintained after controlling for age, blood pressure, weight and height. Isovolumic relaxation time was, however, positively related to diastolic blood pressure, a measure of load, in normal controls (r=0.44) and obese without IR (r=0.62) but not in insulin resistant subjects (r=0.14).CONCLUSION: IR does not independently influence myocardial relaxation in uncomplicated obesity, but modulates the effect of load on active diastole.

Long term metabolic effects of two dietary methods of treating hyperlipidaemia

Abstract Objectives : To compare the long term metabolic effects of two diets for treating hyperlipidaemia. Design : Randomised controlled study: after three weeks of normal (control) diet, subjects were randomly allocated to one of two test diets and followed up for six months. Setting : Lipid clinic of tertiary referral centre in Naples. Subjects : 63 subjects with primary type IIa and IIb hyperlipoproteinaemia entered the study, and 44 completed it. Exclusion criteria were taking drugs known to influence lipid metabolism, evidence of cardiovascular disease, homozygous familial hypercholesterolaemia, and body mass index over 30. Interventions : Two test diets with reduced saturated fat (8%) and cholesterol (-200 mg/day): one was also low in total fat and rich in carbohydrate and fibre, and the other was low in carbohydrate and fibre and rich in polyunsaturated and monounsaturated fats. Main outcome measures : Fasting plasma lipid and lipoprotein concentrations; blood glucose, insulin, and triglyceride concentrations before and after a test meal. Results : In comparison with the control diet, both test diets induced significant and similar decreases in low density lipoprotein cholesterol concentrations (by a mean of 0.72 (SE 0.15) mmol/1, P<0.001, for low total fat diet; by 0.49 (0.18) mmol/l, P<0.05, for high unsaturated fat diet) and plasma triglyceride concentrations (by 0.21 (0.09) mmol/l, P<0.05, for low total fat diet; by 0.39 (0.15) mmol/l, P<0.05, for high unsaturated fat diet), while high density lipoprotein cholesterol concentrations after fasting and plasma glucose and insulin concentrations during test meals were not modified by either diet. Conclusions : Both test diets are suitable (alone or in combination) for treatment of hypercholesterolaemia.

Dietary habits in type II diabetes mellitus: how is adherence to dietary recommendations?

Objective:To clarify adherence of type II diabetic patients to dietary recommendations.Subjects and methods:The dietary habits of a group of 540 patients, with type II diabetes (male 322/female 218, mean age 61±5 years, body mass index (BMI) 29.7±5.2 kg/m2; mean±s.d.) referring to six Italian diabetes centres were evaluated by means of a 3-day diet record (2 workdays, 1 holiday). Diet records were analysed according to Italian food composition tables and compared with the dietary recommendations of the Diabetes and Nutrition Study Group of the European Association for the study of Diabetes.Results:Calorie intake was 1725±497 kcal (1800 for men, 1610 for women). Mean intake for each nutrient was close to the recommended amount, except for fibre (12/1000 vs 20 g/1000 kcal). Calculating the percentage of patients who complied with each recommendation, the intakes of saturated fat and fibre least reflected the dietary target: in 43% of patients saturated fat was >10% of total calories, in only 6% was fibre intake ⩾20 g/1000 kcal (considered ideal), and in 25% it was ⩾15 g/1000 kcal (acceptable).Conclusions:These results indicate that compliance to dietary recommendations is not completely satisfactory, even in Italy. Calorie intake is a bit elevated, given the high BMI of our diabetic population. As to dietary composition, there are two crucial issues: the high intake of saturated fat and – most importantly – the low intake of fibre. All strategies aiming to a proper implementation of guidelines should take these results into due account.