Role of platinum-based radio-chemotherapy for locally advanced non-small-cell lung cancer: possible influence of type of platinum on survival data.
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Antineoplastic Agents↗
Biomedical subjects
K Hotta
Publications and source records attributed to K Hotta.
Continued gefitinib treatment after disease stabilisation prolongs survival of Japanese patients with non-small-cell lung cancer: Okayama Lung Cancer Study Group experience.
BACKGROUND: This study aimed to investigate the survival outcome of patients with non-small-cell lung cancer (NSCLC) who had obtained disease stabilisation with gefitinib treatment and to clarify the effect of continued treatment with gefitinib on prognosis. PATIENTS AND METHODS: We reviewed the clinical records of 365 Japanese patients with NSCLC who received gefitinib (250 mg/day). RESULTS: Of 324 (89%) patients assessable for response, 147 (45%) obtained disease stabilisation and 71 (22%) patients achieved an objective response. Overall survival in patients obtaining disease stabilisation was significantly longer than in patients with progressive disease (median survival time 12.1 versus 4.4 months; P <0.0001). In patients obtaining disease stabilisation, those who continued gefitinib treatment until disease progression tended to have longer overall and progression-free survival compared with those discontinuing gefitinib treatment (1-year survival rate 52.1% versus 36.6%, P = 0.08; 1-year progression-free survival rate 31.8% versus 5.2%, P = 0.001). Multivariate analysis showed discontinuing gefitinib was an independent risk factor for progression-free survival (hazard ratio 1.66; 95% confidence interval 1.07-2.56; P = 0.022) but not for overall survival. CONCLUSIONS: Our findings indicate the importance of achieving disease stabilisation with gefitinib treatment and continued gefitinib treatment in Japanese patients with disease stabilisation, although further studies are required to confirm these findings.
Adult↗
Nocardial infections in Japan from 1992 to 2001, including the first report of infection by Nocardia transvalensis.
In the period from 1992 to 2001, 303 cases of nocardioses were diagnosed in Japan, with the corresponding etiological agents isolated and characterized. Taxonomic analyses of these 303 strains showed that most nocardial infections were caused by members of the Nocardia asteroides group (72.3%). Speciation showed that 72 strains were N. asteroides, 31 strains were N. cyriacigeorgica, 2 strains were N. beijingensis, 81 strains were N. farcinica, and 33 strains were N. nova. Sixty-six strains of N. brasiliensis were the next most prevalent species of the total Nocardia isolates, followed by 14 strains of N. otitidiscaviarum. Infections by N. transvalensis (3 strains) and N. pseudobrasiliensis (1 strain) were also confirmed. The infections due to N. transvalensis, N. cyriacigeorgica, and N. beijingensis were the first reported in Japan. The most common factor that predisposed individuals to nocardial infection in Japan was therapy by immunosuppressive agents (22.4%), including SLE therapy (3.6%), followed by cancer (6.6%), diabetes (3.6%) and AIDS (2.0%). Nocardial infections occurred more commonly in the elderly, with most of the patients between the ages of 61 and 80 years of age. No significant difference regarding infectivity levels between the sexes was observed.
Adolescent↗
Addition of platinum compounds to a new agent in patients with advanced non-small-cell lung cancer: a literature based meta-analysis of randomised trials.
BACKGROUND: Single new agents reportedly produce promising response and survival effects, but platinum-based doublets remain the standard chemotherapy for advanced non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the effectiveness of platinum for advanced NSCLC by carrying out a meta-analysis of trials that compared platinum-based doublets with single new agent therapy alone. METHODS: We carried out a literature search to identify trials, conducted between 1994 and 2003, comparing a doublet of platinum plus a new agent with a new agent alone in previously untreated patients with advanced NSCLC. Outcomes analysed were response, survival and toxicity. RESULTS: Eight trials encompassing 2374 patients were identified. Platinum-based doublets produced an approximately two-fold higher overall (complete and partial) response rate than the new agent alone [odds ratio = 2.32; 95% confidence interval (CI)=1.68-3.20]. Platinum-based doublet therapy was also associated with a 13% prolongation of survival (hazard ratio = 0.87; 95% CI = 0.80-0.94, P <0.001). Despite significant increases in the frequencies of various toxic effects in patients receiving platinum-based doublets, no significant difference in treatment-related mortality was observed. CONCLUSION: This is the first published meta-analysis demonstrating the importance of combining platinum with single new agents in the treatment of advanced NSCLC.
Antineoplastic Agents↗
Distant failure after treatment of postoperative locoregional recurrence of non-small cell lung cancer.
BACKGROUND: The standard treatment for patients with locoregional recurrence of non-small cell lung cancer (NSCLC) after complete resection has not been established. The aim of this study was to evaluate clinicopathologic characteristics, type of locoregional recurrence, pattern of subsequent failure, and survival after the recurrence. METHODS: Of 743 patients undergoing pulmonary resection for NSCLC in the National Cancer Center Hospital between 1990 and 1995, we retrospectively reviewed the medical charts of the 43 patients (5.8 %) found to have locoregional recurrence without distant metastasis or pleural or pericardial involvement. RESULTS: The median time to locoregional recurrence was 13.6 months (range: 1.6 - 85.8 months). The most frequent site of recurrence was the mediastinal nodes in 21 of 43 patients (49 %). 33 patients (77 %) received further treatment for the recurrence: thoracic irradiation in 26, surgery in two, systemic chemotherapy in two, and a combination of the above in 3 patients. Subsequent distant failure was detected in 26 (68 %) of the 38 patients assessable for the analysis of failure pattern: lung in 11, brain in 6, bone in 5, and others in 13. The median interval from the recurrence to distant failure was 8.4 months (range: 1.7-56.4 months). The median survival time after diagnosis of the locoregional recurrence was 10.5 months (range: 0-74.0 months). A multivariate analysis showed that local therapy for the locoregional recurrence had no significant impact on postrecurrent survival or distant failure-free survival. CONCLUSIONS: Many patients with postoperative locoregional recurrence developed distant metastases early after the first recurrence. Systemic chemotherapy in addition to local therapy may be of benefit in this population.
Adult↗
The loss of susceptibility to apoptosis in exudated tissue neutrophils is associated with their nuclear factor-kappa B activation.
Tissue neutrophils, human salivary neutrophils donated from healthy subjects and synovial fluid neutrophils collected from patients with rheumatoid arthritis were compared with circulating blood neutrophils. Concomitant treatment of circulating blood neutrophils with tumor necrosis factor-alpha (TNF-alpha) and cycloheximide induced neutrophil apoptosis, whereas the same treatment failed to induce significant apoptosis in salivary and synovial fluid neutrophils. Caspase-3 activation by TNF-alpha was observed in these tissue neutrophils, although its activity was significantly weaker than that in circulating blood neutrophils. In circulating blood neutrophils, TNF-alpha induced activation of nuclear factor-kappa B (NF-kappa B), whereas, in tissue neutrophils, NF-kappa B had been already activated without any stimulation, and no further activation was induced by the treatment with TNF-alpha. Furthermore, while pretreatment of neutrophils with an NF-kappa B inhibitor produced typical apoptotic changes in circulating blood neutrophils, this inhibitor did not produce any morphological apoptotic changes induced by TNF-alpha in tissue neutrophils. These results indicate that neutrophils undergo marked functional changes such as altered sensitivity to apoptosis-inducing stimuli in association with their exudation from blood into tissue, and that NF-kappa B activation is involved in the acquisition of resistance to TNF-alpha-induced apoptosis.
Apoptosis↗
Enhancement of the aquaporin adipose gene expression by a peroxisome proliferator-activated receptor gamma.
The current study demonstrates that aquaporin adipose (AQPap), an adipose-specific glycerol channel (Kishida, K., Kuriyama, H., Funahashi, T., Shimomura, I., Kihara, S., Ouchi, N., Nishida, M., Nishizawa, H., Matsuda, M., Takahashi, M., Hotta, K., Nakamura, T., Yamashita, S., Tochino, Y., and Matsuzawa, Y. (2000) J. Biol. Chem. 275, 20896-20902), is a target gene of peroxisome proliferator-activated receptor (PPAR) gamma. The AQPap mRNA amounts increased following the induction of PPARgamma in the differentiation of 3T3-L1 adipocytes. The AQPap mRNA in the adipose tissue increased when mice were treated with pioglitazone (PGZ), a synthetic PPARgamma ligand, and decreased in PPARgamma(+/-) heterozygous knockout mice. In 3T3-L1 adipocytes, PGZ augmented the AQPap mRNA expression and its promoter activity. Serial deletion of the promoter revealed the putative peroxisome proliferator-activated receptor response element (PPRE) at -93/-77. In 3T3-L1 preadipocytes, the expression of PPARgamma by transfection and PGZ activated the luciferase activity of the promoter containing the PPRE, whereas the PPRE-deleted mutant was not affected. The gel mobility shift assay showed the direct binding of PPARgamma-retinoid X receptor alpha complex to the PPRE. DeltaPPARgamma, which we generated as the dominant negative PPARgamma lacking the activation function-2 domain, suppressed the promoter activity in 3T3-L1 cells, dose-dependently. We conclude that AQPap is a novel adipose-specific target gene of PPARgamma through the binding of PPARgamma-retinoid X receptor complex to the PPRE region in its promoter.
3T3 Cells↗
Differential uptake of grepafloxacin by human circulating blood neutrophils and those exudated into tissues.
The uptake of the antimicrobial quinolone agent, grepafloxacin, both by human circulating blood neutrophils and by those exudated into tissues, was evaluated in vitro by comparing the intracellular drug concentrations. In circulating blood neutrophils, the uptake of grepafloxacin was rapid and saturable at 37 degrees C. The uptake of grepafloxacin into circulating blood neutrophils was reduced by lowering the environmental temperature or by the presence of metabolic inhibitors, suggesting the involvement of an active transport mechanism. Furthermore, the uptake of grepafloxacin by tissue (salivary) neutrophils was also partially temperature-dependent and was significantly greater than that by circulating blood neutrophils, i.e. exudation of neutrophils into tissue results in a markedly enhanced transport mechanism for grepafloxacin. This phenomenon may be related to the higher defense activity against infection seen in exudated tissue neutrophils.
Anti-Infective Agents↗
Galectin-12, an Adipose-expressed Galectin-like Molecule Possessing Apoptosis-inducing Activity.
Galectins constitute a family of proteins that bind to beta-galactoside residues and have diverse physiological functions. Here we report on the identification of a galectin-like molecule, galectin-12, in a human adipose tissue cDNA library. The protein contained two potential carbohydrate-recognition domains with the second carbohydrate-recognition domain being less conserved compared with other galectins. In vitro translated galectin-12 bound to a lactosyl-agarose column far less efficiently than galectin-8. Galectin-12 mRNA was predominantly expressed in adipose tissue of human and mouse and in differentiated 3T3-L1 adipocytes. Caloric restriction and treatment of obese animals with troglitazone increased galectin-12 mRNA levels and decreased the average size of the cells in adipose tissue. The induction of galectin-12 expression by the thiazolidinedione, troglitazone, was paralleled by an increase in the number of apoptotic cells in adipose tissue. Immunocytochemical analysis revealed that galectin-12 was localized in the nucleus of adipocytes, and transfection with galectin-12 cDNA induced apoptosis of COS-1 cells. These results suggest that galectin-12, an adipose-expressed galectin-like molecule, may participate in the apoptosis of adipocytes.
3T3 Cells↗
Caspase activation as an apoptotic evidence in the gerbil hippocampal CA1 pyramidal cells following transient forebrain ischemia.
To determine whether apoptotic process is involved in the delayed neuronal death in hippocampal CA1 region following forebrain ischemia in gerbils, time dependent activation of caspase and DNA fragmentation were evaluated by immuno-staining and terminal dUTP nick-end-labeling staining, respectively. After transient forebrain ischemia in gerbils, activation of apoptosis related caspase, including caspase-3, was apparent, and it preceded DNA fragmentation in CA1 region. These observations suggest that apoptotic process is involved in hippocampal delayed neuronal death.
Animals↗
Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages.
BACKGROUND: Excessive lipid accumulation in macrophages plays an important role in the development of atherosclerosis. Recently, we discovered an adipocyte-specific plasma protein, adiponectin, that is decreased in patients with coronary artery disease. We previously demonstrated that adiponectin acts as a modulator for proinflammatory stimuli and inhibits monocyte adhesion to endothelial cells. The present study investigated the effects of adiponectin on lipid accumulation in human monocyte-derived macrophages. METHODS AND RESULTS: Human monocytes were differentiated into macrophages by incubation in human type AB serum for 7 days, and the effects of adiponectin were investigated at different time intervals. Treatment with physiological concentrations of adiponectin reduced intracellular cholesteryl ester content, as determined using the enzymatic, fluorometric method. The adiponectin-treated macrophages contained fewer lipid droplets stained by oil red O. Adiponectin suppressed the expression of the class A macrophage scavenger receptor (MSR) at both mRNA and protein levels by Northern and immunoblot analyses, respectively, without affecting the expression of CD36, which was quantified by flow cytometry. Adiponectin reduced the class A MSR promoter activity, as measured by luciferase reporter assay. Adiponectin treatment dose-dependently decreased class A MSR ligand binding and uptake activities. The mRNA level of lipoprotein lipase as a marker of macrophage differentiation was decreased by adiponectin treatment, but that of apolipoprotein E was not altered. Adiponectin was detected around macrophages in the human injured aorta by immunohistochemistry. CONCLUSIONS: The adipocyte-derived plasma protein adiponectin suppressed macrophage-to-foam cell transformation, suggesting that adiponectin may act as a modulator for macrophage-to-foam cell transformation.
Adipocytes↗
Analysis of the microheterogeneity of the IgA1 hinge glycopeptide having multiple O-linked oligosaccharides by capillary electrophoresis.
It was found that the self-aggregation of IgA1 was closely connected with the glycoform of a mucin-type sugar chain on its hinge portion. In this report, normal human serum IgA1 was separated into two subfractions by a jacalin column. The elution condition, 25 mM galactose, used here was similar to that reported for the glycoprotein with a single mucin-type sugar chain per molecule. The IgA1 eluted under this condition was substantially the monomeric form. In contrast, the remaining IgA1 eluted from the column with 0. 8 M galactose was substantially the aggregated form. An analytical method for the microheterogeneity of the IgA1 hinge glycopeptide (HGP33) was developed to determine the difference between these IgA1 fractions by capillary electrophoresis (CE). Native HGP33 from both IgA1 fractions was separated into peaks 1-11, depending on their glycoforms. Because the sialic acid-rich component migrated slowly on CE, the 25 mM fraction was abundant in the sialic acid-rich components (peaks 7-11), but the 0.8 M fraction was abundant in the sialic acid-poor components (peaks 1-4). Comparison of the number of sugar chains per hinge peptide indicated that the 25 mM fraction was relatively well glycosylated. Thus, application of CE analysis to the HGP33 indicated that the monomeric IgA1 was composed of a relatively complete molecule with respect to the glycoform rather than the aggregated IgA1.
Chromatography, Affinity↗
Thiazolidinedione derivative improves fat distribution and multiple risk factors in subjects with visceral fat accumulation--double-blind placebo-controlled trial.
BACKGROUND: It has been clarified that visceral fat accumulation leads to atherosclerosis through multiple risk factors such as insulin resistance, glucose intolerance, hyperlipidemia and hypertension. So far, it has been reported that a thaizolidinedione derivative, troglitazone, improves the insulin resistance in subjects with diabetes, glucose intolerance and obesity. However, it has not been reported yet that troglitazone affects fat distribution in subjects concomitant with visceral fat accumulation and multiple risk factors. METHODS: Twenty-nine subjects with visceral fat accumulation who had at least two risk factors including glucose intolerance, hyperlipidemia and hypertension were investigated. They were randomly assigned to receive either 200 or 400 mg per day of troglitazone or placebo for 12 weeks. A 75 g oral glucose tolerance test (OGTT) was performed before and after the treatment for 12 weeks. Fasting plasma glucose, insulin, HbA(1c), total serum cholesterol (T-chol), triglyceride (TG), HDL-cholesterol (HDL-C), and blood pressure, as well as the number of risk factors were measured periodically during the treatment. The change of the abdominal fat distribution was evaluated using computed tomographic scanning (CT scan) at the umbilicus level. RESULTS: After the treatment for 12 weeks, the area under the curve (AUC) of plasma glucose from a 75 g OGTT decreased dose-dependently. HbA(1c) and TG decreased significantly in the high-dose troglitazone group (400 mg per day) compared with the placebo group (P<0.05). Systolic blood pressure was significantly lower in subjects with hypertension in the pooled troglitazone group than in the placebo group (P<0.05). Therefore, the number of risk factors decreased with the troglitazone treatment. The ratio of visceral fat area (VFA) to subcutaneous fat area (SFA) (V/S ratio) decreased in the troglitazone groups due to decreased VFA and increased SFA. CONCLUSION: These results suggest that thiazolidinedione derivative may be a useful drug to improve multiple risk factors by changing the fat distribution in subjects with visceral fat accumulation.
Adipose Tissue↗
Purification and characterization of alpha-L-fucosidases from Streptomyces sp. OH11242.
alpha-L-Fucosidases were found in the culture fluid of Streptomyces sp. OH11242 grown with porcine gastric mucin (PGM) as the sole carbon source. The alpha-L-fucosidases were purified by ammonium sulfate precipitation followed by chromatography on Sepharose CL-4B, hydroxyapatite, Resource Q and Mono Q. Two enzyme fractions, termed Fase-I and Fase-II, were obtained, each bearing different substrate specificity. Fase-I hydrolyzed fucose residues from fucose-containing oligosaccharide chains on PGM, but not p-nitrophenyl alpha-L-fucoside (Fucalpha-O-PNP). In contrast, Fase-II cleaved fucose from Fucalpha-O-PNP, but not fucose-containing oligosaccharides on PGM. Fase-I also hydrolyzed the alpha1-2 fucosidic linkage in various oligosaccharides, but not alpha1-3 and alpha1-4 fucosidic linkages. Fase-II was separated into two fractions, Fase-IIa and -IIb by Mono Q chromatography, Fase-IIb hydrolyzed alpha1-3 and alpha1-4 fucosidic linkages, but not alpha1-2 fucosidic linkages, while Fase-IIa hydrolyzed none of them. Fase-I was purified to homogeneity by SDS-polyacrylamide gel electrophoresis, the molecular mass was estimated to be approximately 59000 and 76000 Da by SDS-PAGE and gel-permeation chromatography, respectively. The optimum pH for Fase-I activity was 5.5-6.0. These fucosidases with different substrate specificities might be useful to reveal the physiological role of fucose-containing oligosaccharides in the gastric mucins.
Animals↗
The expression of SPARC in adipose tissue and its increased plasma concentration in patients with coronary artery disease.
OBJECTIVE: Adipocytes secrete various cytokines and matrix proteins. Several of them precipitate in obesity-associated diseases, including atherosclerosis. In the current study, we have examined the expression of secreted protein, acidic and rich in cysteine (SPARC) in adipose tissue and its significance in obesity and coronary artery disease (CAD). RESEARCH METHODS AND PROCEDURES: The SPARC mRNA expressions both in vivo and in vitro were detected by Northern blot analysis. Plasma SPARC concentrations were measured by enzyme immunosorbent assay. First, we investigated the plasma SPARC levels of 88 unrelated adult Japanese subjects (62 men and 26 women; average age: [+/- SD] 50 +/- 12 years; body mass index [BMI]: 16 to 46 kg/m(2)). Additionally 31 subjects with CAD diagnosed by coronary angiography (20 men and 11 women) were also investigated. RESULTS: Human adipose tissues expressed abundant SPARC mRNA. SPARC expression in adipose tissues was upregulated in obese db/db mice. Markedly enhanced expression of SPARC mRNA was observed in 3T3-L1 fibroblasts during adipocyte differentiation. Consistent with these results, plasma SPARC levels proved a positive correlation with BMI in humans (r = 0.27; p < 0.01). Interestingly, plasma SPARC concentrations were significantly elevated in age- and BMI-matched subjects with CAD (p < 0.05). DISCUSSION: SPARC was expressed in adipose tissues and its expression was enhanced in obese mice. In human, plasma SPARC levels were elevated in obesity and CAD patients. This elevated SPARC may be involved in the progression of CAD.
Adipose Tissue↗
Expression of a specific mucin type recognized by monoclonal antibodies in the rat gastric mucosa regenerating from acetic acid-induced ulcer.
BACKGROUND: Detailed research on the healing process of gastric mucosa from injury due to various necrotizing agents is important for regenerating medicine as well as for estimating the quality of ulcer healing. To elucidate this issue, we prepared monoclonal antibodies reacting with mucin molecules present in the specific region and layer of the gastrointestinal mucosa. METHODS: Acetic acid-induced gastric ulcers were prepared in 8-week-old male Wistar rats. Following 24-h fasting, the animals were killed at 20, 30 and 50 days after acid insult and their stomachs were removed immediately. Serial paraffin sections of the ulcer area were made and immunostained with three distinct monoclonal antibodies. RGM21 and HIK1083 react with mucins derived from the surface mucous cells of the corpus and the gland mucous cells of corpus and antrum, respectively. HCM31 stains sialomucin present in the small intestine and colonic mucosa of rat, but does not react with the intact gastric mucosa, except in the very narrow cardiac gland area. RESULTS: On the 20th day after ulcer preparation, the cells stained with RGM21 and HIK1083 were restricted only to the surface layer and the bottom layer of regenerating epithelia, respectively. HCN31 staining covered most of the regenerating epithelia. On the 30th day, the staining of HCM31 was enhanced in the regenerating area. Staining of RGM21 did not change, but the HIK1083 stained area increased in the lower part of the regenerating epithelia. On the 50th day, the staining with HCM31 weakened markedly in the lower part, and this area was occupied with HIK1083 positive cells. CONCLUSION: A notable but temporary expression of a kind of sialomucin specifically stained with HCM31 was observed in the regenerating epithelia during the healing stage of acetic acid-induced gastric damage.
Acetic Acid↗
A phase I/II study of cisplatin and vinorelbine chemotherapy in patients with advanced non-small cell lung cancer.
BACKGROUND: A combination of cisplatin and vinorelbine chemotherapy is effective in cases of advanced non-small cell lung cancer, but the optimum administration schedule for both drugs has not yet been defined. The aim of this study was to determine the maximum dose of vinorelbine that can be tolerated while receiving a fixed dose of cisplatin every 3 weeks and to observe the response in Japanese patients with advanced non-small cell lung cancer who had not previously received chemotherapy. METHODS: Cisplatin was given at a dose of 80 mg/m2 on day 1. Vinorelbine was administered on days 1 and 8 at a starting dose of 25 mg/m2 that was then increased by 5 mg/m2 increments. This treatment was repeated every 3 weeks. RESULTS: Twenty-one patients received a total of 54 chemotherapy cycles consisting of three different vinorelbine dosages. Toxicity and efficacy were evaluated in all of the patients. The main dose-limiting toxicity was neutropenia. Grades 3-4 leukopenia and neutropenia were observed in 57% and 86% of all cycles, respectively. These conditions were reversible and did not result in death from toxicity. The most severe non-hematological toxicity symptom was a grade 3 infection and reaction at the site of injection. The maximum tolerated dose of vinorelbine was 35 mg/m2. The objective response was noted in one of six patients at dose level 1, in four of 12 patients at dose level 2 and in two of three patients at dose level 3. CONCLUSION: The recommended doses were 80 mg/m2 for cisplatin and 30 mg/m2 for vinorelbine. The combination of cisplatin and vinorelbine repeated every 3 weeks is well tolerated and has shown promising anti-tumor activity against non-small cell lung cancer.
Adult↗
Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia.
Plasma concentrations of adiponectin, a novel adipose-specific protein with putative antiatherogenic and antiinflammatory effects, were found to be decreased in Japanese individuals with obesity, type 2 diabetes, and cardiovascular disease, conditions commonly associated with insulin resistance and hyperinsulinemia. To further characterize the relationship between adiponectinemia and adiposity, insulin sensitivity, insulinemia, and glucose tolerance, we measured plasma adiponectin concentrations, body composition (dual-energy x-ray absorptiometry), insulin sensitivity (M, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) in 23 Caucasians and 121 Pima Indians, a population with a high propensity for obesity and type 2 diabetes. Plasma adiponectin concentration was negatively correlated with percent body fat (r = -0.43), waist-to-thigh ratio (r = -0.46), fasting plasma insulin concentration (r = -0.63), and 2-h glucose concentration (r = -0.38), and positively correlated with M (r = 0.59) (all P < 0.001); all relations were evident in both ethnic groups. In a multivariate analysis, fasting plasma insulin concentration, M, and waist-to-thigh ratio, but not percent body fat or 2-h glucose concentration, were significant independent determinates of adiponectinemia, explaining 47% of the variance (r(2) = 0.47). Differences in adiponectinemia between Pima Indians and Caucasians (7.2 +/- 2.6 vs. 10.2 +/- 4.3 microg/ml, P < 0.0001) and between Pima Indians with normal, impaired, and diabetic glucose tolerance (7.5 +/- 2.7, 6.1 +/- 2.0, 5.5 +/- 1.6 microg/ml, P < 0.0001) remained significant after adjustment for adiposity, but not after additional adjustment for M or fasting insulin concentration. These results confirm that obesity and type 2 diabetes are associated with low plasma adiponectin concentrations in different ethnic groups and indicate that the degree of hypoadiponectinemia is more closely related to the degree of insulin resistance and hyperinsulinemia than to the degree of adiposity and glucose intolerance.
Adiponectin↗