Patricia Metcalf

Fructosamine: A new approach to the estimation of serum glycosylprotein. An index of diabetic control

The development of a novel manual method designed to measure serum glycosylprotein as an index of diabetic control is described. The method relies on the ability of ketoamines (fructosamines) to act as reducing agents in alkaline solution. Conditions are described for a simple colorimetric procedure which permits assay of both a synthetic fructosamine and purified albumin while severely limiting the contribution of interfering substances. Applied to whole sera, the measurement is linear with volume of serum assayed. It allows clear discrimination of normal and diabetic populations (p less than 0.001), and is significantly correlated with fasting blood glucose concentration (r = 0.72) and with a thiobarbituric acid procedure for measuring glycosylprotein-derived hydroxymethylfurfural (r = 0.58). The method is rapid (at least 12 samples per hour) and demands only simple equipment.

Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: The aric study

The objective of this study was to examine the relationships of serum and dietary magnesium (Mg) with prevalent cardiovascular disease (CVD), hypertension, diabetes mellitus, fasting insulin, and average carotid intimal-medial wall thickness measured by B-mode ultrasound. A cross-sectional design was used. The setting was the Atherosclerosis Risk in Communities (ARIC) Study in four US communities. A total of 15,248 participants took part, male and female, black and white, aged 45-64 years. Fasting serum Mg, lipids, fasting glucose and insulin were measured; as was usual dietary intake by food frequency questionnaire and carotid intima-media thickness by standardized B-mode ultrasound methods. The results showed that serum Mg levels and dietary Mg intake were both lower in blacks than whites. Mean serum Mg levels were significantly lower in participants with prevalent CVD, hypertension, and diabetes than in those free of these diseases. In participants without CVD, serum Mg levels were also inversely associated with fasting serum insulin, glucose, systolic blood pressure and smoking. Dietary Mg intake was inversely associated with fasting serum insulin, plasma high density lipoprotein-cholesterol, systolic and diastolic blood pressure. Adjusted for age, race, body mass index, smoking, hypertension, Low density lipoprotein-cholesterol, and field center, mean carotid wall thickness increased in women by 0.0118 mm (p = 0.006) in diuretic users and 0.0048 mm (p = 0.017) in nonusers for each 0.1 mmol/l decrease in serum Mg level; the multivariate association in men was not significant. In conclusion, low serum and dietary Mg may be related to the etiologies of CVD, hypertension, diabetes, and atherosclerosis.

Serum 25-hydroxyvitamin D3 levels decreased in impaired glucose tolerance and diabetes mellitus

A cross-sectional survey was carried out in a New Zealand Polynesian and Caucasian workforce of 5677 staff aged 40-64 years to determine whether serum concentrations of 25-hydroxyvitamin D3 are altered in people with newly diagnosed diabetes mellitus and impaired glucose tolerance (IGT). Serum 25-hydroxyvitamin D3 concentration was significantly lower in newly detected cases with diabetes and IGT (n = 238) compared with controls individually matched by sex, age (+/- 2 years), ethnicity, and date of interview (mean (S.D.): 69 (31) vs. 76 (34) nmol/l; P = 0.0016). Among controls, serum concentrations were significantly lower in Maori (mean (S.E.) = 65 (5) nmol/l; P = 0.0013) and Pacific Islanders (59 (4) nmol/l; P = 0.0001) compared with Europeans (82 (3) nmol/l), after adjusting for age, sex, and time of year. We conclude that diabetes and IGT are associated with low serum concentrations of 25-hydroxyvitamin D3 and that low concentrations of this hormone in New Zealand Polynesians may partly explain their increased prevalence of diabetes/IGT compared with Europeans.

Clustering of dyslipidemia, hyperuricemia, diabetes, and hypertension and its association with fasting insulin and central and overall obesity in a general population

Clustering of elevated triglycerides, decreased high-density lipoprotein cholesterol (HDL-C), hyperuricemia, diabetes, and hypertension has been related to insulin resistance/high insulin levels and central and/or overall obesity. The extent to which these abnormalities cluster and whether hyperinsulinemia, central adiposity, and overall obesity each independently associate with this clustering were evaluated in 14,481 US whites and African-Americans 45 to 64 years of age. With the exception of hypertension, abnormalities rarely existed in isolated form. Clustering greatly exceeded chance association (P < .001). Although this clustering was greater in relative terms (ratio of observed to expected cluster frequency) in the lean and less centrally obese, it was greater in absolute terms (observed minus expected cluster frequency as a percent of total population) in the more centrally and more generally obese. The greatest excesses were found for clusters that included both hypertriglyceridemia and low HDL-C. Multiple logistic regression models showed strong and independent graded relationships of clusters with quintiles of fasting insulin (fifth quintile odds ratio, 10 to 54, P < .001) and to a lesser degree with quintiles of the waist to hip ratio (2.2 to 5.4, P < .001 for most) and of body mass index (1.6 to 4.5, P < .05 for most). In conclusion, all abnormalities cluster in excess of that predicted by chance, with clusters showing remarkable and graded independent associations with fasting hyperinsulinemia and to a lesser extent with central and overall obesity. Thus, a metabolic syndrome occurs in both lean and obese middle-aged US adults.

Clinical usefulness of estimation of serum fructosamine concentration as a screening test for diabetes mellitus.

Fructosamine, a putative measure of serum glycosylated proteins, was measured in 74 subjects referred for oral glucose tolerance tests. A normal range (mean (2 SD] of 1.6 (0.4) mmol/l (40(10) mg/100 ml) derive from results obtained in 83 healthy non-diabetic volunteers permitted the detection of 15 out of 17 (88%) subjects with proved diabetes and yielded only five (9%) false positive diagnoses. Fructosamine concentrations correlated significantly (p less than 0.001) with fasting plasma glucose concentrations (r = 0.76) and glycosylated haemoglobin concentrations (r = 0.70). A longitudinal study suggested that fructosamine concentration was an index of intermediate term (one to three weeks) blood glucose control. Fructosamine concentration was not related to uraemia and did not depend on albumin or total protein concentrations, provided that serum albumin concentrations remained above 30 g/l. Estimation of fructosamine concentrations is a fully automated procedure and may provide a simple means of screening for diabetes mellitus.

B-mode-detected carotid artery plaque in a general population. Atherosclerosis Risk in Communities (ARIC) Study Investigators.

There is little information on the distribution of atherosclerotic lesions of the extracranial carotid artery wall in free-living populations. The purpose of the present study was to describe the prevalence from 1987 through 1989 of extracranial carotid artery plaque and plaque with acoustic attenuation (shadowing) lesions in a general population of white and black adults from four US communities. Methods B-mode ultrasound was used to characterize wall lesions in the common and internal carotid arteries and at the carotid artery bifurcation in 14 046 men and women 45 to 64 years old who participated in the Atherosclerosis Risk in Communities Study baseline survey. Results Thirty-four percent of participants had plaque and 6.4% had plaque with acoustic shadowing. The prevalence of plaque with acoustic shadowing increased steadily with age from 2.5% at ages 45 to 49 to 12.4% at ages 60 to 64. Overall, whites had more plaque with acoustic shadowing lesions than blacks (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.02 to 1.46), and men had more than women (OR, 1.42; 95% CI, 1.22 to 1.63). However, plaque lesions in the common carotid artery were less common among whites than among blacks, and no racial difference was observed in the prevalence of plaque with acoustic shadowing at this segment. Conclusions Although these prevalence rates are likely to be underestimated because of the emphasis on arterial boundary visualization of the scanning protocol, they show a large, mostly asymptomatic burden of atherosclerosis in these populations, especially among older individuals. Site-specific frequency rates of plaque varied between blacks and whites. Among those with plaque, however, whites had more lesions with acoustic shadowing attenuation.

Serum fructosamine concentration as measure of blood glucose control in type I (insulin dependent) diabetes mellitus.

Serum fructosamine activity was studied in 42 patients with type I (insulin dependent) diabetes mellitus and 30 non-diabetic volunteers as an index of blood glucose control. There was a significant correlation both between fructosamine and glycosylated haemoglobin values (r = 0.82) and between fructosamine and the fasting C peptide concentration (r = -0.81). Test results in 14 of the diabetics reflected the mean plasma glucose concentration calculated from 25 serial estimations in a single 24 hour period (r = 0.75; p less than 0.01) but not the mean amplitude of glycaemic excursion (r = 0.23; p greater than 0.05). Fructosamine concentrations measured in these multiple blood specimens did not change significantly throughout the day (mean coefficient of variation 4.1%) despite wide variability of the respective plasma glucose concentrations (mean coefficient of variation 36.2%). It is concluded that a single random serum sample analysed for fructosamine concentration provides a simple and reliable assessment of glucose homoeostasis in patients with type I diabetes mellitus.

Patterns of aspirin use in middle-aged adults : The atherosclerosis risk in communities (ARIC) study

To determine correlates of and recent trends in aspirin use in middle-age men and women, we analyzed data from population-based samples selected in four U.S. communities. Aspirin use (during a 2-week period preceding the study examination) was more prevalent in whites than in blacks (30% vs 11%; p < 0.001) and in men than in women among whites (31% vs 28%; p < 0.002) but not blacks (10% in both sexes). In all four race and sex groups, there was a graded positive relation between estimated coronary heart disease (CHD) risk and age-adjusted prevalence of aspirin use. For example, 33% of CHD-free white men who reported diagnoses of hypercholesterolemia and hypertension and had ever smoked reported aspirin use as compared with 25% of their risk factor-free counterparts (p < 0.001). Among men with symptomatic CHD or at high risk for CHD, aspirin use increased by four percentage points between 1987 and 1989 in conjunction with the publication of results from the aspirin primary prevention trials. However, nearly 50% of participants reporting a history of myocardial infarction apparently did not take aspirin regularly.

Microalbuminuria in a Middle-Aged Workforce: Effect of hyperglycemia and ethnicity

OBJECTIVE To determine the prevalence of microalbuminuria in a mixed, thnic population and to find the extent that ethnic variation in microalbuminuria can be explained by abnormal glucose metabolism, obesity, hypertension, hypertriglyceridemia, and life-style factors. RESEARCH DESIGN AND METHODS Urinary albumin concentrations were measured in 5467 middle-aged Maori, Pacific Islander, and European workers who participated in a health-screening survey of 46 New Zealand companies. Participants provided a first-voided, morning urine sample; had a 75-g oral glucose tolerance test; had weight, height, and blood pressure measured; and completed a self-administered questionnaire about past medical history and sociodemographic status. RESULTS A significantly higher prevalence of microalbuminuria was found in individuals with new cases of diabetes mellitus (24.1%), in cases of diabetes mellitus previously diagnosed (20.6%), and in those with impaired glucose tolerance (16.1%) compared with nondiabetic individuals (4.0%). Moreover, in the general population, a piecewise linear relationship was detected between albuminuria and plasma glucose with significant changes of slope corresponding with 2 h plasma glucose concentrations (95% confidence interval) of 6.7 (6.4–7.0) and 9.2 (8.6–9.8) mM, respectively. After adjusting for sex, obesity, hypertension, hypertriglyceridemia, cigarette smoking, and heavy alcohol consumption in a multivariate model, glycemia was the most significant determinant of urinary albumin concentrations in all three ethnic groups. However, blood glucose concentrations did not completely explain the higher relative risk (95% confidence interval) of microalbuminuria in Maori (5.97; 4.48–7.78) and Pacific Islander (5.33; 4.13–6.87) workers compared with European workers. CONCLUSIONS Of the variables investigated, hyperglycemia was the most important factor explaining the high prevalence of microalbuminuria in Maori and Pacific Islander workers compared with the European workers. However, only 14.9% of the variation in urinary albumin concentrations was found in our multivariate model, and we have speculated on the contribution of other factors such as diet and coexisting renal diseases.

Reproducibility of extracranial carotid atherosclerotic lesions assessed by B-mode ultrasound: The atherosclerosis risk in communities study

The reproducibility in the identification of carotid artery lesions using B-mode ultrasound was studied in a large random sample selected from the Atherosclerosis Risk in Communities (ARIC) Study. Carotid lesions were defined as plaque with or without acoustic shadowing (indicative of mineralization). A weighted kappa (kappa w) statistic was used as a chance-adjusted measure of repeatability. In the ARIC baseline survey, the kappa w values for the assessment of lesions on repeat reading were 0.47, 0.60 and 0.69 in the left common carotid artery, the carotid bifurcation and the internal carotid artery, respectively. In a repeat scanning, the kappa w values ranged from 0.59 to 0.79 in the left carotid segments. The results were similar in the left and right carotid arteries. Covariates (age, race, gender, body mass index, study center) did not influence the reproducibility. Similar results were also found in both the baseline survey and the first follow-up examination. In conclusion, reproducibility in the assessment of carotid lesions by B-mode ultrasound can be achieved in multicenter studies at fair to good levels of agreement.