Ectopic cardiovascular fat in middle-aged men: effects of race/ethnicity, overall and central adiposity. The ERA JUMP study.

BACKGROUND/OBJECTIVES: Higher volumes of ectopic cardiovascular fat (ECF) are associated with greater risk of coronary heart disease (CHD). Identifying factors that are associated with ECF volumes may lead to new preventive efforts to reduce risk of CHD. Significant racial/ethnic differences exist for overall and central adiposity measures, which are known to be associated with ECF volumes. Whether racial/ethnic differences also exist for ECF volumes and their associations with these adiposity measures remain unclear. SUBJECTS/METHODS: Body mass index (BMI), computerized tomography-measured ECF volumes (epicardial, pericardial and their summation) and visceral adipose tissue (VAT) were examined in a community-based sample of 1199 middle-aged men (24.2% Caucasians, 7.0% African-Americans, 23.6% Japanese-Americans, 22.0% Japanese, 23.2% Koreans). RESULTS: Significant racial/ethnic differences existed in ECF volumes and their relationships with BMI and VAT. ECF volumes were the highest among Japanese-Americans and the lowest among African-Americans. The associations of BMI and VAT with ECF differed by racial/ethnic groups. Compared with Caucasians, for each 1-unit increase in BMI, African-Americans had lower, whereas Koreans had higher increases in ECF volumes (P-values<0.05 for both). Meanwhile, compared with Caucasians, for each 1-unit increase in log-transformed VAT, African-Americans, Japanese-Americans and Japanese had similar increases, whereas Koreans had a lower increase in ECF volumes (P-value<0.05). CONCLUSIONS: Racial/ethnic groups differed in their propensity to accumulate ECF at increasing level of overall and central adiposity. Future studies should evaluate whether reducing central adiposity or overall weight will decrease ECF volumes more in certain racial/ethnic groups. Evaluating these questions might help in designing race-specific prevention strategy of CHD risk associated with higher ECF.

Particle numbers of lipoprotein subclasses and arterial stiffness among middle-aged men from the ERA JUMP study.

We examined the association between serum lipoprotein subclasses and the three measures of arterial stiffness, that is, (i) carotid-femoral pulse wave velocity (cfPWV), which is a gold standard measure of central arterial stiffness, (ii) brachial-ankle PWV (baPWV), which is emerging as a combined measure of central and peripheral arterial stiffness and (iii) femoral-ankle PWV (faPWV), which is a measure of peripheral arterial stiffness. Among a population-based sample of 701 apparently healthy Caucasian, Japanese American and Korean men aged 40-49 years, concentrations of lipoprotein particles were assessed by nuclear magnetic resonance (NMR) spectroscopy, and the PWV was assessed with an automated waveform analyzer (VP2000, Omron, Japan). Multiple linear regressions were performed to analyse the association between each NMR lipoprotein subclasses and PWV measures, after adjusting for cardiovascular risk factors and other confounders. A cutoff of P<0.01 was used for determining significance. All PWV measures had significant correlations with total and small low-density lipoprotein particle number (LDL-P) (all P<0.0001) but not LDL cholesterol (LDL-C) (all P>0.1), independent of race and age. In multivariate regression analysis, no NMR lipoprotein subclass was significantly associated with cfPWV (all P>0.01). However, most NMR lipoprotein subclasses had significant associations with both baPWV and faPWV (P<0.01). In this study of healthy middle-aged men, as compared with cfPWV, both baPWV and faPWV had stronger associations with particle numbers of lipoprotein subclasses. Our results may suggest that both baPWV and faPWV are related to arterial stiffness and atherosclerosis, whereas cfPWV may represent arterial stiffness alone.

ß-cell autoimmunity in overweight non-diabetic youth: any implications?

BACKGROUND AND OBJECTIVE: The presence of ß-cell antibodies is associated with a high risk of type 1 diabetes. With increasing rates of obesity, the distinction between obese T1DM and T2DM has become difficult. Moreover, increasing body mass index (BMI) in at-risk children has been proposed not only as a possible contributor to T1DM by increasing insulin resistance, but also as exerting an effect via the immunomodulatory properties of certain adipokines. This study aimed to determine prevalence of ß-cell autoantibodies (AA) in overweight non-diabetic children and assess insulin sensitivity and secretion derived from an oral glucose tolerance test (OGTT) in those with vs. without ß-cell AA. RESEARCH DESIGN AND METHODS: A total of 357 overweight (BMI > 85%) youths underwent OGTTs, dual energy X-ray absorptiometry (DEXA) and measurement of GAD65 and IA-2 AA according to the NIDDK harmonization assay. Using the same methodology, AA were measured in 90 normal weight, non-diabetic individuals. RESULTS: About 1.9% of overweight and 4.4% of control normal weight children had evidence of ß-cell autoimmunity, with GAD65 AA detected in all subjects but none with IA-2. Youth with positive vs. those with negative AA had higher leptin/adiponectin ratio, glucose at 60 min and C-peptide at 90 min. CONCLUSIONS: These findings suggest that the prevalence of ß-cell AA in overweight youth may be similar to that in non-overweight children. Further studies using standardized methods are required.

Reproducibility of the oral glucose tolerance test in overweight children.

OBJECTIVE: We examined the reproducibility of the oral glucose tolerance test (OGTT) in overweight children and evaluated distinguishing characteristics between those with concordant vs. discordant results. DESIGN: Sixty overweight youth (8-17 yr old) completed two OGTTs (interval between tests 1-25 d). Insulin sensitivity was assessed by the surrogate measures of fasting glucose to insulin ratio, whole-body insulin sensitivity index, and homeostasis model assessment of insulin resistance, and insulin secretion by the insulinogenic index with calculation of the glucose disposition index (GDI). RESULTS: Of the 10 subjects with impaired glucose tolerance (IGT) during the first OGTT only three (30%) had IGT during the second OGTT. The percent positive agreement between the first and second OGTT was low for both impaired fasting glucose and IGT (22.2 and 27.3%, respectively). Fasting blood glucose had higher reproducibility, compared with the 2-h glucose. Youth with discordant OGTTs, compared with those with concordant results, were more insulin resistant (glucose/insulin 2.7+/-1.4 vs. 4.1+/-1.8, P=0.006, whole-body insulin sensitivity index of 1.3+/-0.6 vs. 2.2+/-1.1, P=0.003, and homeostasis model assessment of insulin resistance 10.6+/-8.1 vs. 5.7+/-2.8, P=0.001), had a lower GDI (0.45+/-0.58 vs. 1.02+/-1.0, P=0.03), and had higher low-density lipoprotein cholesterol (117.7+/-36.6 vs. 89.9+/-20.1, P=0.0005) without differences in physical characteristics. CONCLUSIONS: Our results show poor reproducibility of the OGTT in obese youth, in particular for the 2-h plasma glucose. Obese youth who have discordant OGTT results are more insulin resistant with higher risk of developing type 2 diabetes mellitus, as evidenced by a lower GDI. The implications of this remain to be determined in clinical and research settings.

Is type 2 diabetes a chronic inflammatory/autoimmune disease?

The classification of diabetes mellitus into 2 main types, defined as Type 1 and 2 diabetes (T1DM, T2DM) relies mostly on the requirement of insulin therapy and on the presence of detectable immunologic abnormalities. However, this distinction is far from straightforward and there is considerable overlap between these 2 types of diabetes. Islet cell autoimmunity, which is characteristic of T1DM, appears in fact to be present in up to 10-15% of subjects diagnosed clinically with T2DM. In the UK Prospective Diabetes Study (UKPDS), it was reported that in patients diagnosed with in T2DM, the presence of autoantibodies to the enzyme glutamic acid decarboxylase (GAD) and cytoplasmic islet cell antibodies (ICA) were a predictor of insulin requirement as compared with patients not carrying these autoantibodies. These results are strikingly similar to a number of prospective studies carried out in childhood diabetes. If islet cell autoimmunity is truly present in 10-15% of subjects clinically diagnosed with T2DM, up to two million Americans might have an unidentified autoimmune form of T2DM, a prevalence similar to that of recent onset childhood diabetes. In addition, we found that in a subset of T2DM patients, a pronounced activation of the acute phase response that seems to be associated with islet cell autoimmunity. These results may in part explain the defect in insulin secretion as well as insulin resistance seen in T2DM. The identification of a subgroup of individuals at risk of developing T2DM using autoantibody as well as inflammatory markers is of public health interest, not only for the correct classification of diabetes, but also because immunomodulatory therapeutic strategies could potentially be instituted sufficiently early in a large number of patients diagnosed as having T2DM and most likely delay the onset of insulin requirement and the complications related with hyperglycemia.

Serum levels of C-reactive protein are associated with obesity, weight gain, and hormone replacement therapy in healthy postmenopausal women.

The authors evaluated the cross-sectional and prospective associations between the serum concentration of C-reactive protein and measures of obesity and fat distribution, hormone replacement therapy (HRT) use, and serum sex hormones in postmenopausal women from the Healthy Women Study (Allegheny County, Pennsylvania, 1998). The authors tested the hypothesis that C-reactive protein levels would be higher among HRT users and among women with greater body mass index, waist circumference, or visceral fat. There were 207 women in the study who were > or =8 years postmenopausal (101 HRT users and 106 HRT nonusers). The median levels of C-reactive protein were 3.01 mg/liter in HRT users compared with 1.74 mg/liter in nonusers (p = 0.002). C-reactive protein levels were strongly positively correlated with measures of body size, fatness, fat distribution, and weight gain among HRT users and nonusers. C-reactive protein was also positively correlated with serum estrone levels (r(s) = 0.38) among HRT nonusers. The highest level of C-reactive protein was found among HRT users in the highest quartile of visceral fat (4.29 mg/liter) compared with women not on HRT and in the lowest quartile of visceral fat (0.96 mg/liter). The use of HRT and measures of overall body fatness are important correlates of C-reactive protein among postmenopausal women.

Evidence of islet cell autoimmunity in elderly patients with type 2 diabetes.

In light of an occurring growth of elderly people affected by type 2 diabetes and recent observations indicating that type 2 diabetes may be a disease of the innate immune system, we evaluated whether signs of islet cell autoimmunity are associated with an abnormal glucose control, the presence of insulin requirement, or an activation of the acute-phase response in older individuals with type 2 diabetes. GAD65 and IA-2 autoantibodies along with the acute-phase response markers fibrinogen and C-reactive protein were tested in 196 serum samples from patients with type 2 diabetes and in 94 nondiabetic control subjects over the age of 65 years from the Pittsburgh cohort of the Cardiovascular Health Study. Of the diabetic patients, 12% (24 of 196) had autoantibodies against GAD65 and/or IA-2, a prevalence significantly higher than that found in nondiabetic individuals (1 of 94, 1.1%; P = 0.001). Type 2 diabetic patients who were positive for GAD65 and/or IA-2 autoantibodies (Ab+), as compared with those negative for these autoantibodies (Ab-), had an abnormal oral glucose tolerance test (OGTT) (P = 0.03) before and a higher frequency of oral hypoglycemic treatment (P = 0.003) at the time of autoantibody testing. No differences were seen in the percentage of insulin requirement in the two groups. Moreover, a statistically significant increase in fibrinogen (P = 0.005) and C-reactive protein levels (P = 0.025) was found in type 2 diabetic patients with high levels of GAD65 and/or IA-2 autoantibodies as compared with Ab-patients and control subjects. In conclusion, in type 2 diabetic subjects > or =65 years old, the presence of islet cell autoimmunity is associated with an impairment of the acute-phase insulin secretion, as revealed by an OGTT. A pronounced activation of the acute-phase response, found to be associated with islet cell autoimmunity, may in part explain this defect in insulin secretion. These findings not only have direct implications for adequate classification and treatment of diabetes in the elderly, but also for understanding the autoimmune/inflammatory mechanisms involved in the pathogenesis of hyperglycemia.

Telepreventive medicine.

There have been dramatic improvements in health during the past 50 years, and public health measures have made a major contribution. Much of public health consists of information transfer. The application of telecommunications technology to public health and preventive medicine would enhance our ability to transmit information and improve global health. The idea of telemedicine has received considerable attention but has not thus far included preventive medicine. We have outlined a global electronic health network with seven main components: connectivity, telemonitoring of disease, "distance education" for public health workers, electronic connection of nongovernment organizations, a combined degree in public health and communications, an electronic scientific research server, and a home page on the World Wide Web. A commitment to the integration of telecommunications and public health holds great promise for improving the health status of the world's population.