Baseline and changes in serum uric acid independently predict 11-year incidence of metabolic syndrome among community-dwelling women.

INTRODUCTION: Metabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. In women, increased serum uric acid (SUA) levels are associated with MetS and its components. However, whether baseline and changes in SUA predict incidence of MetS and its components remains unclear. METHODS: The subjects comprised 407 women aged 71 ± 8 years from a rural village. We have identified participants who underwent a similar examination 11 years ago, and examined the relationship between baseline and changes in SUA, and MetS based on the modified criteria of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP) III report. RESULTS: Of these subjects, 83 (20.4%) women at baseline and 190 (46.7%) women at follow-up had MetS. Multiple linear regression analysis was performed to evaluate the contribution of each confounding factor for MetS; both baseline and changes in SUA as well as history of cardiovascular disease, low-density lipoprotein cholesterol, and estimated glomerular filtration ratio (eGFR) were independently and significantly associated with the number of MetS components during an 11-year follow-up. The adjusted odds ratios (ORs) (95% confidence interval) for incident MetS across tertiles of baseline SUA and changes in SUA were 1.00, 1.47 (0.82-2.65), and 3.11 (1.66-5.83), and 1.00, 1.88 (1.03-3.40), and 2.49 (1.38-4.47), respectively. In addition, the combined effect between increased baseline and changes in SUA was also a significant and independent determinant for the accumulation of MetS components (F = 20.29, p < 0.001). The ORs for incident MetS were significant only in subjects with age ≥ 55 years, decline in eGFR, and no baseline MetS. CONCLUSIONS: These results suggested that combined assessment of baseline and changes in SUA levels provides increased information for incident MetS, independent of other confounding factors in community-dwelling women.

Interaction between gender and uric acid on hemoglobin A1c in community-dwelling persons.

INTRODUCTION: Higher glycated hemoglobin (Hb) (HbA1c) is significantly associated with an increased risk of cardiovascular disease (CVD). Serum uric acid (SUA) levels are associated with glucose intolerance and type 2 diabetes. Whether gender-specific differences regarding the relationship between SUA levels and HbA1c exist is unknown. AIM: We recruited 1636 (men, 696 aged of 70 ± 10 years; women, 940 aged of 70 ± 9 years) participants and enrolled in the study during their annual health examination from a single community. We investigated the association between SUA levels and HbA1c within each gender. RESULTS: Multiple linear regression analysis showed that in men, SUA (ß = -0.091, p = 0.014) with prevalence of antidiabetic medication (ß = 0.428, p < 0.001) and eGFR (ß = 0.112, p = 0.016) were significantly and negatively associated with HbA1c, and in women, SUA (ß = 0.101, p = 0.002) with prevalence of antidiabetic medication (ß = 0.458, p < 0.001) were significantly and positively associated with HbA1c. Moreover, the interaction between gender and SUA (ß = 0.445, p < 0.001) as well as gender (ß = -0.465, p < 0.001), prevalence of antidiabetic medication (ß = 0.444, p < 0.001), eGFRCKDEPI (ß = 0.074, p = 0.014), and SUA (ß = -0.356, p < 0.001) was a significant and independent determinant of HbA1c. A significant interactive effect of gender and SUA on determinants of HbA1c was noted in patients not on antidiabetic medications, regardless of age, HbA1c, and renal function. CONCLUSIONS: The interaction between gender and SUA was associated with HbA1c independent of other metabolic factors in community-dwelling persons.

An unusual case of subclinical diffuse glucagonoma coexisting with two nodules in the pancreas: characteristic features on computed tomography.

A lesion was discovered in the tail of the pancreas by ultrasonography performed during a health checkup for a 59-year-old Japanese man. Abdominal contrast-enhanced computed tomography (CE-CT) revealed strong enhancement in a 4-cm tumor in the pancreatic tail and in a 1-cm tumor in the pancreatic body. Serum glucagon levels were elevated to 54,405 pg/mL and a preoperative diagnosis of glucagonoma was made. The pancreatic tail and spleen were resected en bloc, along with a protruding tumor in the pancreatic body. However, histopathological evaluation revealed diffuse glucagonoma throughout the pancreas. When we retrospectively reviewed abdominal CE-CT after the operation, the entire pancreas was seen to be enlarged and diffusely enhanced by strong spots. Immunohistochemical examination using anti-CD31 demonstrated rich microvessels in two solid glucagonomas as well as microglucagonoma throughout the entire pancreas, indicating hypervascularity. Enlarged pancreas and diffuse enhancement of the pancreas by strong spots may be characteristic features of diffuse glucagonoma on abdominal CE-CT.

Macrophage migration inhibitory factor in hepatocellular carcinoma and liver cirrhosis; relevance to pathogenesis.

The levels of macrophage migration inhibitory factor (MIF), a proinflammatory and carcinogenic cytokine, were significantly higher in the sera from patients with hepatocellular carcinoma (HCC; 25.6+/-15.3 ng/ml, n=55) and liver cirrhosis (LC; 18.9+/-10.7 ng/ml, n=26) compared with sera from patients with gastrointestinal cancer (6.8+/-7.5 ng/ml, n=29) and normal controls (5.6+/-1.2 ng/ml, n=45; P<0.01). Hepatocytes from patients with LC and HCC, but not from chronic hepatitis, expressed very high levels of MIF. A possible association between overexpression of MIF and hepatocarcinogenesis is suggested.

Increased serum levels of macrophage migration inhibitory factor in alcoholic liver diseases and their expression in liver tissues.

OBJECTIVES: To study the role of macrophage migration inhibitory factor (MIF) in the pathogenesis of alcoholic liver diseases. DESIGN AND METHODS: The levels of MIF in the sera were estimated by an enzyme-linked immunosorbent assay in 13 patients with alcoholic hepatitis (ALH), 9 patients with alcoholic cirrhosis (ALC) and 26 normal controls. MIF was localized in the liver specimens by immunohistochemistry. RESULTS: The mean levels of MIF in the sera were significantly higher in ALH and ALC compared with the normal controls (p < 0.05). Serial observations revealed a relationship between serum MIF levels and the serum transaminase levels. MIF was expressed by the hepatocytes and by the infiltrating cells around the site of accumulation of neutrophils and ballooned hepatocytes in ALH. CONCLUSIONS: This is the first report on MIF in human alcoholic liver diseases, and the data suggest that MIF may be related to abnormal cytokine homeostasis in ALH.

Mechanisms of alcoholic liver disease: cytokines.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Manuela G. Neuman. The presentations were (1) New aspects of hepatic fibrosis, by D. A. Brenner; (2) Cellular immune response in hepatitis C models, by B. Rehermann; (3) The role of interleukin-10 in acute alcoholic hepatitis, by J. Taieb, S. Chollet-Martin, M. Cohard, J. J. Garaud, and T. Poynard; (4) Cytokine-mediated apoptosis in vitro, by M. G. Neuman; (5) Signaling for apoptosis and repair in vitro, by G. G. Katz, R. G. Cameron, N. H. Shear, and M. G. Neuman; (6) Interferons activate the P42/44 mitogen-activated protein kinase and Janus Kinase signal transducers and activation of transcription (JAK-STAT) signaling pathways in hepatocytes: Differential regulation by acute ethanol via a protein kinase C-dependent mechanism, by B. Gao; (7) Genetic polymorphisms of interleukin-1 in association with the development of Japanese alcoholic liver disease, by M. Takamatsu, M. Yamauchi, M. Ohata, S. Saito, S. Maeyama, T. Uchikoshi, and G. Toda; and (8) Increased levels of macrophage migration inhibitory factor in sera from patients with alcoholic liver diseases, by T. Kumagi, S. M. F. Akbar, M. Abe, K. Michitaka, N. Horiike, and M. Onji.