Ronald P. Stolk

Validity and reproducibility of ultrasonography for the measurement of intra-abdominal adipose tissue

OBJECTIVE: We studied the validity and reproducibility of a new abdominal ultrasound protocol for the assessment of intra-abdominal adipose tissue.MEASUREMENTS: Intra-abdominal adipose tissue was assessed by CT, MRI, anthropometry and ultrasonography on a single day. By ultrasonography the distance between peritoneum and lumbar spine was measured using a strict protocol, including the location of the measurements, pressure on the transducer and respiration. All measurements were repeated after 3 months.RESULTS: The study population consisted of 19 overweight patients with a body mass index (BMI) of 32.9 kg/m2 (s.d. 3.7), intra-abdominal adipose tissue on CT 140.1 cm2 (s.d. 55.9), and a mean ultrasound distance of 9.8 cm (s.d. 2.5). There was a strong association between the CT and ultrasonographic measures: Pearson correlation coefficient was 0.81 (P<0.001). The correlation between ultrasound and waist circumference was 0.74 (P<0.001), the correlation between CT and waist circumference was 0.57 (P=0.01). Ultrasound appeared a good method to diagnose intra-abdominal obesity: the area under the ROC curve was 0.98. During the follow-up period of 3 months, the patients lost on average almost 3 kg of body weight. The correlation coefficient between changes in intra-abdominal adipose tissue assessed by CT and ultrasound was 0.74 (P<0.001). The correlation coefficient of the mean ultrasound distance assessed by two different sonographers at baseline was 0.94 (P<0.001), the mean difference 0.4 cm (s.d. 0.9), and the coefficient of variation 5.4%, indicating good reproducibility of the ultrasound measurements.CONCLUSIONS: The results of this validation study show that abdominal ultrasound, using a strict protocol, is a reliable and reproducible method to assess the amount of intra-abdominal adipose tissue and to diagnose intra-abdominal obesity.

Discontinuation of prophylaxis for Pneumocystis carinii pneumonia in HIV-1-infected patients treated with highly active antiretroviral therapy

BACKGROUND Prophylactic drugs for Pneumocystis carinii pneumonia (PCP) are strongly recommended for HIV-1-infected patients with CD4 cell counts of less than 200 cells/microL. Because of the highly active antiretroviral therapy (HAART) currently available, we speculated that prophylaxis can be discontinued in patients with CD4 cell counts of more than 200 cells/microL. METHODS In this prospective observational study, PCP prophylaxis (primary or secondary) was discontinued in HIV-1-infected patients whose CD4 cell count had increased above 200 cells/microL (documented twice with an interval of at least 1 month) as a result of HAART. Patients and their CD4 cell counts were monitored every 3 months. The primary endpoint of the study was the occurrence or reoccurrence of PCP. FINDINGS 78 patients were enrolled: 62 patients were receiving prophylaxis for primary prevention of PCP and 16 patients for secondary prevention of PCP. At the time of discontinuation of prophylaxis, the mean CD4 cell count was 347 cells/microL, and HIV-1-RNA was not detectable in 61 patients. The lowest mean CD4 cell count during prophylaxis was 79 cells/microL. Patients stopped prophylaxis 9.8 (SD 6.4) months after they started HAART. The mean follow-up after discontinuation of prophylaxis was 12.7 (SD 7.6) months, and none of the patients developed PCP (97.5% one-sided CI 0-4.4%). INTERPRETATION The preliminary results of this study indicate that PCP prophylaxis can be stopped safely in HIV-1-infected patients whose CD4 cell counts have increased above 200 cells/microL after treatment with HAART.

Variants in the sulphonylurea receptor gene: association of the exon 16-3t variant with type II diabetes mellitus in Dutch caucasians

Aims/hypothesis. We have analysed to what extent two previously reported single nucleotide polymorphisms in the sulphonylurea receptor gene (SUR1) are associated with Type II (non-insulin-dependent) diabetes mellitus in The Netherlands. Furthermore, we estimated haplotype frequencies in control and diabetic populations, including data extracted from three other studies. Methods. Subjects with Type II diabetes (n = 388) and normoglycaemic subjects (n = 336) were randomly selected from two population-based studies, the Hoorn and Rotterdam studies. DNA was typed for variants in exon 16 (-3c→t variant in the splice acceptor site) and exon 18 (Thr759Thr, ACC→ACT). Results. The genotype frequencies in both populations were similar. We observed an association of the exon 16–3t variant with Type II diabetes (allele frequencies 0.41 % vs 0.48 % in NGT and Type II diabetes, respectively, p = 0.01). There was no association between Type II diabetes and the variant in exon 18 or the combination of both variants (p > 0.5). A strong linkage disequilibrium between the exon 16 and exon 18 variants was observed in the diabetic groups but not, or less pronounced, in the control groups from the different studies. Haplotype estimation shows that several different risk haplotypes exist in different Caucasian populations. Conclusion/interpretation. The exon 16–3t allele of the SUR1 gene is associated with Type II diabetes in the Netherlands. Based on estimated haplotype frequencies in different Caucasian populations we conclude that multiple haplotypes on the SUR1 gene seem to confer a risk for developing Type II diabetes in Caucasians. [Diabetologia (1999) 42: 617–620]

Angiographic distribution of lower extremity atherosclerosis in patients with and without diabetes.

Aims To determine differences in the anatomic site of atherosclerosis in the lower extremity between patients with and patients without diabetes.

Ultrasound Measurements of Visceral and Subcutaneous Abdominal Thickness to Predict Abdominal Adiposity Among Older Men and Women

Accurate measures of visceral and abdominal subcutaneous fat are essential for investigating the pathophysiology of obesity. Classical anthropometric measures such as waist and hip circumference cannot distinguish between these two fat depots. Direct imaging methods such as computed tomography and magnetic resonance imaging (MRI) are restricted in large‐scale studies due to practical and ethical issues. We aimed to establish whether ultrasound is a valid alternative method to MRI for the quantitative assessment of abdominal fat depots in older individuals. The study population comprised 74 white individuals (41 men and 33 women, aged 67–76 years) participating in the Hertfordshire Birth Cohort Physical Activity trial. Anthropometry included height, weight, waist and hip circumferences. Abdominal fat was measured by ultrasound in two compartments: visceral fat defined as the depth from the peritoneum to the lumbar spine; and subcutaneous fat defined as the depth from the skin to the abdominal muscles and compared to reference measures by MRI (10‐mm single‐slice image). Ultrasound measures were positively correlated with MRI measures of visceral and subcutaneous fat (visceral: r = 0.82 and r = 0.80 in men and women, respectively; subcutaneous: r = 0.63 and 0.68 in men and women, respectively). In multiple regression models, the addition of ultrasound measures significantly improved the prediction of visceral fat and subcutaneous fat in both men and women over and above the contribution of standard anthropometric variables. In conclusion, ultrasound is a valid method to estimate visceral fat in epidemiological studies of older men and women when MRI and computed tomography are not feasible.

Resource consumption and costs in Dutch patients with Type 2 diabetes mellitus. Results from 29 general practices

Aims The aims of this study were to estimate the costs incurred by Dutch patients with Type 2 diabetes, examine which patient and/or treatment characteristics are associated with costs, and estimate the medical and non‐medical costs of patients with Type 2 diabetes in The Netherlands.

Retinal Vascular Lesions in Patients of Caucasian and Asian Origin With Type 2 Diabetes Baseline results from the ADVANCE Retinal Measurements (AdRem) study

OBJECTIVE—The objective of this study was to describe prevalent vascular retinal lesions among patients with type 2 diabetes enrolled in the ADVANCE Retinal Measurements (AdRem) study, a substudy of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial. RESEARCH DESIGN AND METHODS—Seven-field stereoscopic photographs of both eyes were obtained at the baseline assessment of the ADVANCE trial. All photographs were graded in a central reading center. Gradable retinal images were received from 1,605 patients. RESULTS—The number of patients with any retinopathy (Early Treatment of Diabetic Retinopathy Study [ETDRS] score ≥20) was 645 (40.2% [95% CI 37.8–42.6]); of these, 35 (2.2% [1.6–3.0]) had severe diabetic retinopathy (ETDRS score ≥50). Focal arterial narrowing, venous beading, and arteriovenous nicking were present in 3.8, 5.1, and 9.8% of participants, respectively. Among participants included in this study, Chinese and South-Asian patients had more retinopathy than Caucasians, as defined both by ETDRS score (49.4, 46.0, and 31.3%, respectively; P < 0.001, adjusted for age, sex, A1C, systolic blood pressure, and duration of diabetes) and specific vascular lesions (e.g., arteriovenous nicking 12.3, 8.5, and 7.5%, respectively; adjusted P < 0.005). A1C, duration of diabetes, and systolic blood pressure were similarly associated with increased retinal lesions in Chinese, South-Asian, and Caucasian patients. CONCLUSIONS—Using a sensitive diagnostic procedure, more than one-third of patients with type 2 diabetes enrolled in the AdRem study had retinal lesions at baseline. Despite differences in prevalence and severity of retinopathy among Chinese, South-Asian, and Caucasian patients included in this study, the cross-sectional associations among established risk factors for retinopathy and retinal lesions were similar across ethnic groups.

Insulin resistance syndrome and left ventricular mass in an elderly population (The Rotterdam Study)

In a study of elderly men and women, age, body mass index, and systolic blood pressure (and in men, also glucose) were significant predictors of left ventricular mass. Postload insulin was not independently associated with left ventricular mass.

Validation of Ultrasound Estimates of Visceral Fat in Black South African Adolescents

Accurate quantification of visceral adipose tissue (VAT) is needed to understand ethnic variations and their implications for metabolic disease risk. The use of reference methods such as computed tomography (CT) and magnetic resonance imaging (MRI) is limited in large epidemiological studies. Surrogate measures such as anthropometry and dual‐energy X‐ray absorptiometry (DXA) do not differentiate between VAT and subcutaneous abdominal adipose tissue (SCAT). Ultrasound provides a validated estimate of VAT and SCAT in white populations. This study aimed to validate the use of ultrasound‐based assessment of VAT in black South African adolescents. One hundred healthy adolescents (boys = 48, girls = 52) aged 18–19 years participating in the birth to twenty cohort study had VAT and SCAT measured by single slice MRI at L4. These MRI “criterion measures” were related to ultrasound VAT and SCAT thickness, anthropometry (BMI, waist and hip circumferences), and DXA android region fat. Ultrasound VAT thickness showed the strongest correlations with MRI VAT (Spearmans correlation coefficients: r = 0.72 and r = 0.64; in boys and girls, respectively), and substantially improved the estimation of MRI VAT compared to anthropometry and DXA alone; in regression models the addition of ultrasound VAT thickness to models containing BMI, waist, and DXA android fat improved the explained variance in VAT from 39% to 60% in boys, and from 31% to 52% in girls. In conclusion, ultrasound substantially increased the precision of estimating VAT beyond anthropometry and DXA alone. Black South African adolescents have relatively little VAT compared to elderly whites, and we therefore provide new ultrasound‐based prediction equations for VAT specific to this group.

Virulence factors of Escherichia coli isolated from urine of diabetic women with asymptomatic bacteriuria: correlation with clinical characteristics

Since Escherichia coli isolated from compromised patients with symptomatic urinary tract infections (UTIs) express fewer virulence factors than those isolated from healthy controls, the question arises whether this is also the case for diabetic patients with asymptomatic bacteriuria (ASB). Polymerase chain reaction (PCR) assays were conducted on 111E. coli strains, isolated from the urine of diabetic women with ASB, using primers for the major subunit A and the G-adhesin (I, II, and III) of P fimbriae, type 1 fimbriae, S fimbriae, afimbrial adhesin, cytotoxic necrotizing factor (CNF), and aerobactin. Phenotypically, hemolysis, mannose-sensitive hemagglutination, mannose-resistant hemagglutination and O:K:H-serotypes were determined. Furthermore, we investigated the associations between virulence factors and patient characteristics (including deterioration of renal function). Type 1 fimbriae were the most prevalent virulence factor (86% by genotyping and 59% phenotypically). Except for a lower prevalence of known uropathogenic O-serotypes, we found the same number of virulence factors in our compromised patient group as listed in the literature in noncompromised patients with ASB. Certain virulence factors (type 1 and S fimbriae and CNF) of the causative E. colicorrelated with the risk of a decline in renal function. In conclusion, the number of virulence factors in E. coli isolated from the urine of diabetic women with ASB are comparable with the results found in other (noncompromised) patients with ASB. Furthermore, certain virulence factors of E. colimight contribute to a decline in renal function.