Energy balance and type 2 diabetes: a report from the Shanghai Women's Health Study

BACKGROUND AND AIMS: The combined effect of the components of energy balance (energy intake and physical activity) and the development of type 2 diabetes (T2D) has not been adequately investigated. The aim of this study was to examine the components of energy balance and the incidence of T2D in a cohort of middle-aged women. METHODS AND RESULTS: A population-based prospective study of 64,227 middle-aged Chinese women who had no prior history of diabetes or chronic disease at study recruitment. Participants completed in-person interviews at baseline and follow-up surveys that collected information on diabetes risk factors including dietary and physical activity habits and disease occurrence. Anthropometric measurements were taken by trained interviewers at recruitment. Average follow-up time was 4.6 years. During 297,755 person-years of follow-up, 1608 new cases of T2D were documented. Body mass index (BMI) and weight gain (since age 20) were strongly associated with T2D incidence. Energy intake (EI) was associated with modestly increased risk, while physical activity (PA) was associated with decreased risk of T2D. Less active women with higher EI had higher risk of T2D (RR=1.96; 95% CI: 1.44, 2.67) than active women with lower EI (P(interaction)=0.02). The EI to PA (EI:PA) ratio was positively associated with T2D risk; the association was more evident among overweight and obese women (BMI > or = 23 kg/m(2)). CONCLUSION: These data suggest that energy balance plays an important role in the development of T2D, and this effect may be modified by BMI.     

Origin of urinary nonconjugated 19-nor-deoxycorticosterone and metabolism of infused radiolabeled 19-nor-deoxycorticosterone in men and women.

It is known that 19-nor-deoxycorticosterone (19-nor-DOC) is a potent mineralocorticosteroid that is present in urine of rats and humans in a free, i.e., nonconjugated, form. In some forms of hypertension in rats, the levels of free 19-nor-DOC in urine are increased compared with those in urine of normotensive animals. Yet, despite the potential importance of this mineralocorticosteroid in the pathogenesis of certain forms of hypertension, little is known of its site of origin or metabolism. In the present investigation, we evaluated the metabolism of intravenously infused [3H]19-nor-DOC and the possibility that 19-nor-DOC was formed from plasma DOC. We found that the metabolism of [3H]19-nor-DOC infused intravenously in men and women was similar to that of DOC with important exceptions. The majority of the radiolabeled urinary metabolites of intravenously infused [3H]19-nor-DOC were excreted in urine as glucuronosides. Little radioactivity, infused as [3H]19-nor-DOC, was recovered in urine as nonconjugated or sulfoconjugated steroids. There was no free radiolabeled 19-nor-DOC in urine after the simultaneous infusion of [3H]19-nor-DOC and [14C]DOC. A major metabolite of [3H]19-nor-DOC in urine was 19-nor-DOC-21-glucuronoside, whereas little or no intravenously infused radiolabeled DOC was excreted as radiolabeled DOC-glucuronoside. We also found that intravenously infused [14C]DOC was not converted to urinary [14C]19-nor-DOC (glucuronoside) and that other tritium-labeled metabolites of infused [3H]19-nor-DOC contained no carbon-14. The production rate of 19-nor-DOC, computed from the specific activity of urinary 19-nor-DOC (glucuronoside), in one normal man was 16 micrograms/d and in the two women of this study, it was 10 micrograms/d. These findings are supportive of the proposition that free urinary 19-nor-DOC is not formed from plasma DOC; it may be formed in kidney from a precursor other than DOC or it may be formed nonenzymatically in kidney or urine from a precursor such as 19-oic-DOC.     

Intravascular tumors: transvenous biopsy

A technique is described for transfemoral biopsy of intravenous tumors. Positive results were obtained at biopsy in three patients who had an intraluminal mass in the inferior vena cava and in one patient with a mass in the iliac vein. Transvenous biopsy is helpful in obtaining a histologic diagnosis and provides an alternative method to surgery or percutaneous transabdominal needle biopsy.     

SNAP-25 deficit and hippocampal connectivity in schizophrenia

Regional abnormalities of brain connectivity may be an important substrate for the expression of schizophrenia, a severe form of mental illness. Brain imaging and postmortem morphometric studies indicate hippocampal structure is abnormal in schizophrenia. To study molecular components of hippocampal connectivity the presynaptic proteins SNAP-25 and synaptophysin were assayed in postmortem samples. Immunocytochemical studies indicated reduced SNAP-25 immunoreactivity in schizophrenia compared to controls, particularly in the terminal fields of entorhinal cortex projections. Although there were no overall changes in synaptophysin immunoreactivity, in the granule cell layer of the dentate gyrus synaptophysin immunoreactivity was increased in schizophrenia. These results indicate that disconnection of a subset of hippocampal circuitry from the entorhinal cortex, as well as intrinsic changes in hippocampal connectivity, may contribute to the mechanism of illness in schizophrenia.      

Epidemiologic background and long-term course of disease in human immunodeficiency virus type 1-infected blood donors identified before routine laboratory screening. Transfusion Safety Study Group

BACKGROUND: The long-term course of human immunodeficiency virus type 1 (HIV-1)-related disease among seropositive blood donors has not been described. The enrollment and epidemiologic background of HIV-1- infected donors in the Transfusion Safety Study and their immunologic and clinical progression are described. STUDY DESIGN AND METHODS: Through the testing of approximately 200,000 sera from donations made in late 1984 and early 1985, 146 anti-HIV-1-positive donors and 151 uninfected matched donors were enrolled. These two cohorts were followed with 6-month interval histories and laboratory testing. RESULTS: Seropositive donors detected before the institution of routine anti-HIV-1 screening disproportionately were first-time donors and men with exclusively male sexual contacts. The actuarial probability of a person's developing AIDS within 7 years after donation was 40 percent; the probability of a person's dying of AIDS was 28 percent. AIDS developed more often when the donor was p24 antigen-positive at donation. Over a 3-year period, significant decreases occurred in CD4+, CD2+CD26+, CD4+CD29+, and CD20+CD21+ counts, but not in CD8+ subsets, CD20+, or CD14+. CONCLUSION: The high proportions of first-time donations and exclusively homosexual men among seropositive donors suggest that test-seeking may have contributed to the high HIV-1 prevalence in the repository. Implementation of alternative test sites when routine donor screening began in 1985 may have averted many high- risk donations. The disease course in HIV-1-infected donors had the same wide spectrum of immunologic and clinical manifestations as were reported for other cohorts.     

Do human vascular endothelial cells produce aldosterone?

Extraadrenal production of aldosterone has been reported in several tissues, including vascular endothelial cells. The implications of local production of aldosterone in certain nonepithelial target tissues in normal and pathological physiology could be very important and merits further investigation. Human vascular endothelial cells have been reported to synthesize aldosterone under the regulation of angiotensin II. However, discrepancies are noted upon close scrutiny, the most important of which are the relative large efficiency of deoxycorticosterone conversion to aldosterone and the rate of aldosterone production in comparison to the adrenal zona glomerulosa cells. We investigated the production of aldosterone in three different human vascular endothelial cell lines, two from human umbilical veins, one from human pulmonary artery endothelial cells using a very sensitive ELISA method. Cells were incubated with the secretagogues angiotensin II, ACTH, and K(+), at various physiological concentrations with and without 1 microm deoxycorticosterone as additional substrate. In addition, RT-PCR was used to detect expression of the mRNA for the aldosterone synthase gene using a protocol developed by us that detects very low expression in subregions of the human brain. Our results failed to demonstrate mRNA for the aldosterone synthase gene or aldosterone biosynthesis in human endothelial cells.