Increased levels of tPA antigen and tPA/PAI-1 complex in myotonic dystrophy

Abstract. Johansson Å, Boman K, Cederquist K, Forsberg H, Olsson T (Umeå University Hospital, Umeå, Skellefteå County Hospital, Skellefteå, and Boden Hospital, Boden, Sweden). Increased levels of tPA antigen and tPA/PAI‐1 complex in myotonic dystrophy. J Intern Med 2001; 249 : 503–510. Objective. To assess the fibrinolytic system in myotonic dystrophy (DM1), a disease connected to features of the metabolic syndrome, including a prominent insulin resistance, increased body fat mass, and hypertriglyceridaemia. We hypothesized that abnormalities in the fibrinolytic system are linked to metabolic dysfunction in DM1. Design. Circulating morning levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI‐1) antigens, tPA/PAI‐1 complex, lipids and insulin were determined. Genetic analyses, including calculation of allele size, were performed in all patients. Body fat mass was estimated with bioelectrical impedance analysis. Setting. Out‐patient clinic in collaboration with Umeå University Hospital. Subjects. A total of 42 otherwise healthy patients with DM1 (22 men, 20 women; median age 41.5 years) and 50 controls (27 men, 23 women; median age 42.0 years). Main outcome measures. The tPA and PAI‐1 antigens, tPA/PAI‐1 complex, blood lipids and body fat mass. Results. The tPA antigen and tPA/PAI‐1 complex levels were significantly increased in DM1 patients (P < 0.001 and P < 0.05, respectively) whilst levels of PAI‐1 did not differ from controls. Triglyceride levels were increased (P < 0.001) whereas HDL cholesterol levels were lower in DM1 patients (P < 0.05). Body fat mass was increased in DM1 patients (P < 0.001). Conclusions. The fibrinolytic system is disturbed in DM1 patients, with increased levels of tPA and tPA/PAI‐1 complex but paradoxically unaltered levels of PAI‐1, in spite of a severely increased body fat mass. This may imply an abnormal function of adipose tissue in DM1, and calls for further studies of the fibrinolytic system in this disease.     

Sustained benefits of metformin therapy on markers of cardiovascular risk in human immunodeficiency virus-infected patients with fat redistribution and insulin resistance

The purpose of this study was to evaluate the metabolic and cardiovascular benefits of continued metformin therapy for HIV-infected patients with lipodystrophy. Eligible subjects who participated in the 3-month randomized study received an additional 6-month open label metformin treatment extension. Nineteen of the 25 potential subjects were eligible to receive open label metformin based on preestablished safety and efficacy criteria. Insulin and glucose response to oral glucose challenge, cardiovascular disease risk markers (e.g. tissue plasminogen activator), weight, and anthropometric measurements were the primary outcome measures. Continued treatment with metformin resulted in further significant reductions in tissue plasminogen activator antigen levels (P = 0.02) and body mass index (P = 0.03). Reductions in insulin levels were sustained during the 6-month treatment extension. In addition, waist circumference decreased significantly in subjects continuing metformin treatment (P = 0.01). Metformin was well tolerated and no one discontinued treatment due to side effects. These data demonstrate a sustained benefit of metformin treatment to reduce hyperinsulinemia and certain markers of cardiovascular disease risk in patients with HIV infection and lipodystrophy.     

Circulating resistin levels are not associated with fat redistribution, insulin resistance, or metabolic profile in patients with the highly active antiretroviral therapy-induced metabolic syndrome

CONTEXT: The mechanisms underlying the development of the highly active antiretroviral therapy (HAART)-induced metabolic syndrome remain to be fully elucidated. OBJECTIVE: The objective of this study was to investigate whether the adipocyte-secreted hormone, resistin, is associated with anthropometric and metabolic abnormalities of the HAART-induced metabolic syndrome. DESIGN, SETTING, AND PATIENTS: We conducted a cross-sectional study of 227 HIV-positive patients (37 women and 190 men) recruited from the infectious diseases clinics. On the basis of history, physical examination, dual-energy x-ray absorptiometry, and single-slice computed tomography, patients were classified into four groups: non-fat redistribution (n = 85), fat accumulation (n = 42), fat wasting (n = 35), and mixed fat redistribution (n = 56). MAIN OUTCOME MEASURES: The main outcome measures were serum resistin levels and anthropometric and metabolic variables. RESULTS: Mean serum resistin levels were not significantly different among subjects with fat accumulation, fat wasting, or mixed fat redistribution or between these groups and the non-fat redistribution group. We found a weak, but significant, positive correlation between resistin and percent total body fat (r = 0.20; P < 0.01), total extremity fat (r = 0.18; P < 0.01), and abdominal sc fat (r = 0.19; P < 0.01), but not abdominal visceral fat (r = -0.10; P = 0.16) or waist to hip ratio (r = -0.05; P = 0.43). When adjustments were made for gender (women, 3.92 +/- 2.71 ng/ml; men, 2.96 +/- 2.61 ng/ml; P = 0.05), correlations between resistin and the above parameters were no longer significant. Importantly, resistin levels were not correlated with fasting glucose, insulin, homeostasis model assessment of insulin resistance index, triglycerides, or cholesterol levels in the whole group. CONCLUSIONS: Resistin is related to gender, but is unlikely to play a major role in the insulin resistance and metabolic abnormalities of the HAART-induced metabolic syndrome.     

Increased serum resistin levels in patients with type 2 diabetes are not linked with markers of insulin resistance and adiposity

Abstract The role of resistin in human biology remains uncertain. We measured serum resistin levels in Japanese patients with (n=111) and without (n=98) type 2 diabetes mellitus and investigated the significance of this hormone in the pathophysiology of diabetes. The levels of serum adiponectin and leptin were also measured. Resistin levels were increased significantly in patients with type 2 diabetes compared with non-diabetic subjects (24.7±2.6 vs. 15.0±1.2 ng/ml, p=0.0013). However, there was no correlation in either patient group between serum resistin levels and markers of insulin resistance, obesity or hyperlipidaemia. These results were in direct contrast to the data of leptin or adiponectin, both of which were closely related to these clinical markers of diabetes. Multivariate regression analysis on the combined data of the two groups demonstrated that the presence of diabetes and HDL cholesterol levels were significant predictors of serum resistin levels (diabetes: =0.159, p=0.035; HDL: =-0.172, p=0.039). No correlation was observed between C-reactive protein and resistin adjusted for BMI. Taken together, these findings demonstrate that serum resistin levels are increased in patients with type 2 diabetes, but this increase is not linked to markers of insulin resistance or adiposity. Further studies are necessary to elucidate the significance of serum resistin concentration in human pathophysiology.     

Increased abdominal visceral fat is associated with reduced bone density in HIV-infected men with lipodystrophy

OBJECTIVE: To examine the relationship between bone density and changes in regional and whole body composition in HIV-infected men with and without lipodystrophy. DESIGN: Cross-sectional, observational study of HIV-infected men with and without lipodystrophy and matched HIV-negative controls. SETTING: Tertiary care academic medical institution. PATIENTS: A total of 59 men, belonging to three different groups: HIV-positive men with lipodystrophy (n = 21), HIV-positive men without lipodystrophy (n = 20), and age-matched and body mass index-matched HIV-negative controls (n = 18). METHODS: Bone density, markers of bone turnover and indices of calcium metabolism were measured in all subjects. Quantitative computed tomography was used both to determine volumetric bone density of the spine and to quantify abdominal visceral fat. Dual energy X-ray absorptiometry was used to determine whole body composition and bone density. Statistical comparisons were performed according to lipodystrophy categorization and protease inhibitor exposure. RESULTS: Men with HIV-associated lipodystrophy had reduced lumbar spine bone density compared with both HIV-infected non-lipodystrophic men [mean +/- SD, 132 +/- 29 versus 154 +/- 30 mg/cm(3); P = 0.02] and HIV-negative controls [mean +/- SD 132 +/- 29 versus 148 +/- 18) mg/cm(3); P = 0.04]. Lumbar spine bone density was reduced significantly in HIV lipodystrophy patients independently of protease inhibitor use. In an analysis among all HIV-infected subjects, increased visceral abdominal fat area was associated with decreased lumbar spine bone density (r, -0.47; P = 0.002). The association between visceral fat and bone density remained significant (P = 0.007) after controlling for age, body mass index, lowest body weight, protease inhibitor use, and extremity fat in a multivariate regression model. Markers of bone turnover were not related to bone density or lipodystrophy status. CONCLUSIONS: Lumbar spine bone density is reduced in association with increased visceral fat in HIV-infected men with lipodystrophy. Further studies are needed to determine the mechanisms of osteopenia in HIV lipodystrophy and whether increased marrow fat occurs in such patients and affects bone density.     

血浆纤溶酶原激活物抑制物1与胰岛素抵抗的相关性研究

目的：探讨血浆纤溶酶原激活物抑制物1（plasminogen activitor inhibitor one,PAI-1)活性及其基因启动子区4G／5G多态性与胰岛素抵抗综合征的关系。方法：应用等位基因特异性PCR扩增技术，对胰岛素抵抗综合征患者（160例）和对照组（90例）PAI－1 4G／5G多态位点的基因型进行检测，用发色底物法测血浆PAI－1活性。结果：（1）胰岛不抵抗综合综合患者PAI－1活性明显升高，空腹胰岛素，空腹血糖，甘油三酯与PAI－1活性升高密切相关（P＜0．01）。（2）对照组和胰岛素抵抗综合征患者，4G／5G基因型频率分别为0．52和0．48，两组比较无明显差异（P＞0．05），但胰岛素抵抗综合征不同基因型者PAI－1活性差异显著（P＜0．01），4G／4G基因型者PAI－1活性高于4G／5G和5G／5G基因型者（P＜0．01）。（3）血糖、甘油三酯对PAI－1活性的调节受基因型的影响。4G／4G基因型者血糖，甘油三酯与PAI－1活性密切相关（P＜0．01），而4G／5G和5G／5G基因型者血糖。甘油三酯与PAI－1活性无明显相关（P＞0．05）。（4）胰岛素对PAI－1活必的影响无基因型依赖性。结论：PAI－1活性升高是胰岛素抵抗综合征患进的特征之一，免疫反应性胰岛素，血糖，甘油三酯与PAI－1活性升高有关，血糖，甘油三酯对PAI－1活性的调节存在明显的基因型依赖性。     

Increased serum soluble tumor necrosis factor receptor levels are associated with insulin resistance in liver cirrhosis

Insulin resistance is present in nearly all patients with liver cirrhosis, but its etiology remains unclear. Recent studies have shown that tumor necrosis factor-alpha (TNF-alpha) system is involved in the insulin resistance of human obesity. Serum concentrations of TNF-alpha, and 2 soluble TNF receptors (sTNF-RI and sTNF-RII) are increased in cirrhotic patients. This study explored whether TNF-alpha system activity was associated with insulin resistance in liver cirrhosis. A total of 26 male nondiabetic patients with liver cirrhosis (mean age, 59 +/- 3 years; body mass index, 23.7 +/- 0.4 kg/m2) and 25 male control subjects (age, 65 +/- 2 years; body mass index, 24.4 +/- 0.5 kg/m2) were studied. Serum insulin, c-peptide, TNF-alpha, sTNF-RI, and sTNF-RII concentrations were determined by immunoassay. The insulin resistance was estimated by homeostasis assessment model (HOMA IR). In cirrhotic patients, serum levels of TNF-alpha, sTNF-RI, and sTNF-RII were all higher than those in the controls, and correlated with disease severity. Also, the serum c-peptide, insulin concentrations, and the HOMA IR were higher in liver cirrhosis with comparable blood glucose to control subjects, indicating a degree of insulin insensitivity. In the whole population, there was a moderate, but statistically significant, correlation between serum sTNF-RI or sTNF-RII, and HOMA IR. Also, body mass index was associated with HOMA IR, but not related to serum TNF-alpha, and sTNF-Rs levels. In multiple regression analysis, both sTNF-RII and body mass index jointly contributed to 30% variance of HOMA IR. Our study demonstrated that elevated sTNF-RII levels were associated with insulin resistance in liver cirrhosis. The data indicated that TNF-alpha system might play a role in modulating insulin action in patients with liver cirrhosis.     

Increased endothelin-1 levels in women with polycystic ovary syndrome and the beneficial effect of metformin therapy

Women with polycystic ovary syndrome who present with hyperandrogenemia, hyperinsulinemia, and insulin resistance appear to be at high risk of cardiovascular disease. Elevated levels of endothelin-1, a marker of vasculopathy, have been reported in insulin-resistant subjects with endothelial dysfunction. Male gender also seems to be an aggravating factor for cardiovascular disease. In this study we investigated endothelin-1 levels in women with polycystic ovary syndrome, and we evaluated the effect of an insulin sensitizer, metformin, on endothelin-1 levels. Plasma endothelin-1 levels were measured in 23 obese (mean age, 24.3 +/- 4.6 yr; body mass index, 35 +/- 5.6 kg/m(2)) and 20 nonobese women with polycystic ovary syndrome (24.1 +/- 3.6 yr; body mass index, 21.8 +/- 2.5 kg/m(2)) as well as in 7 obese and 10 nonobese healthy, normal cycling, age-matched women. Additionally, endothelin-1 levels were evaluated in a subgroup of women with polycystic ovary syndrome (10 obese and 10 nonobese) 6 months postmetformin administration (1700 mg daily). Our results showed that obese and nonobese women with polycystic ovary syndrome had higher levels of endothelin-1 compared with the controls [obese, 2.52 +/- 1.87 vs. 0.44 +/- 0.23 pmol/liter (by analysis of covariance, P < 0.02); nonobese, 1.95 +/- 1.6 vs. 0.43 +/- 0.65 pmol/liter (P < 0.009)]. All of the participating women with polycystic ovary syndrome (n = 43) when compared with the total group of controls (n = 17) demonstrated hyperinsulinemia (polycystic ovary syndrome, 24.5 +/- 19.6; controls, 11.2 +/- 3.4 U/liter; P < 0.03), lower glucose utilization (M40) during the hyperinsulinemic euglycemic clamps (3.4 +/- 2.4 vs. 5.6 +/- 1.75 mg/kg.min; P < 0.045, by one-tailed test), and higher levels of endothelin-1 (polycystic ovary syndrome, 2.52 +/- 1.87; controls, 0.44 +/- 0.23 pmol/liter; P < 0.02, analysis of covariance covariate for body mass index). A positive correlation of endothelin-1 with free T levels was also shown (r = 0.4, P = 0.002) as well as a negative correlation of endothelin-1 with glucose utilization (r = -0.3; P = 0.033) in the total studied population. Finally, after metformin therapy, endothelin-1 levels were significantly reduced in obese (endothelin-1 before, 3.25 +/- 2.2; endothelin-1 after, 1.1 +/- 0.9 pmol/liter; P < 0.003) and nonobese (endothelin-1 before, 2.7 +/- 2; endothelin-1 after, 0.7 +/- 0.4 pmol/liter; P < 0.01) women with polycystic ovary syndrome, with no change in body mass index. Moreover, after metformin therapy, hyperandrogenemia and hyperinsulinemia were normalized, and glucose utilization improved [obese before: total T, 0.9 +/- 0.15 ng/ml; fasting insulin, 22.2 +/- 12.1 U/liter; glucose utilization, 2.15 +/- 0.5 mg/kg.min; obese after: total T, 0.5 +/- 0.2 ng/ml; fasting insulin, 11.6 +/- 6 U/liter; glucose utilization, 4.7 +/- 1.4 mg/kg.min 9P < 0.003, P < 0.006, and P < 0.002, respectively); nonobese before: total T, 1 +/- 0.5 ng/ml; fasting insulin, 15.5 +/- 7.6 U/liter; glucose utilization, 3.4 +/- 0.7 mg/kg.min; nonobese after: total T, 0.8 +/- 0.5 ng/ml; fasting insulin, 9 +/- 3.8 U/liter; glucose utilization, 6 +/- 1.7 mg/kg.min (P < 0.04, P < 0.02, and P < 0.0008, respectively)]. In conclusion, our data clearly demonstrate that women with polycystic ovary syndrome, obese and nonobese, have elevated endothelin-1 levels compared with the age-matched control group. In addition, 6 months of metformin therapy reduces endothelin-1 levels and improves their hormonal and metabolic profile.     

Subcutaneous abdominal, but not femoral fat expression of plasminogen activator inhibitor-1 (PAI-1) is related to plasma PAI-1 levels and insulin resistance and decreases after weight loss

Aims/hypothesis: Abdominal fat produces plasminogen activator inhibitor-1 (PAI-1) and could contribute to increased plasma PAI-1 values in human obesity associated with insulin resistance. Femoral fat, which is not associated with insulin resistance, is thought to be metabolically different from the abdominal fat. This study aimed to assess PAI-1 expression in these two fat territories in obese and lean subjects and to determine if concomitant changes of plasma and adipose tissue PAI-1 values occur after weight reduction. Methods: In 24 obese and 16 lean subjects, PAI-1 expression in abdominal and femoral subcutaneous fat, plasma PAI-1, insulin, triglyceride concentrations and insulin resistance were determined at the start of the study and in obese subjects after a 3-month weight reduction programme as well. Results: PAI-1 mRNA content in the abdominal subcutaneous fat was higher in obese than in lean subjects and positively correlated with plasma PAI-1 values (p < 0.01) and markers of insulin resistance (p < 0.05). In 18 obese subjects, re-examined after successful dieting, PAI-1 mRNA content decreased in the abdominal subcutaneous fat along with plasma PAI-1. However, the absolute changes of these two variables were not associated. In contrast, PAI-1 mRNA content in the femoral subcutaneous fat did not differ between lean and obese subjects, was not associated with plasma PAI-1 values or with markers of insulin resistance, and did not change after weight loss. Conclusion/interpretation: Only the abdominal, but not the femoral subcutaneous fat PAI-1 expression is a potential contributor to increases in plasma PAI-1 in obesity. Both plasma and abdominal subcutaneous fat PAI-1 values decreased significantly after weight reduction, although their absolute changes were not associated. [Diabetologia (2001) 44: 2025–2031] Received: 19 March 2001and in revised form: 3 August 2001     

二甲双胍对胰岛素抵抗的基因1型慢性丙型肝炎患者抗病毒疗效的影响

目的 研究在聚乙二醇干扰素联合利巴韦林治疗基础上加用二甲双胍对胰岛素抵抗的基因1型慢性丙型肝炎患者抗病毒疗效的影响.方法 胰岛素抵抗的基因1型慢性丙型肝炎患者98例,随机分为治疗组和对照组.对照组给予聚乙二醇干扰素α-2a联合利巴韦林治疗,治疗组在对照组的基础上加用二甲双胍.比较两组患者病毒学应答率、胰岛素抵抗稳态评估模型指数(HOMA-IR)及不良反应发生率.应用多元逻辑回归分析影响患者获得持续性病毒学应答(SVR)的因素.结果 治疗组和对照组各49例患者中,获得SVR各有29例和19例,SVR率为59.2％和38.8％(x2 =4.083,P=0.043).治疗12、24、48周,随访24周时治疗组HOMA-IR指数分别为3.00±0.65、1.90±0.45、1.75±0.40和1.60±0.35;明显低于对照组的3.50±0.72、2.90±0.64、2.74±0.48和2.60±0.55(t分别为3.610、8.947、11.091、10.738,均P＜0.01).治疗组腹泻的发生率明显高于对照组(28.6％比10.2％;x2=5.288,P=0.021).在多因素分析中,二甲双胍治疗(P=0.009)和治疗24周时HOMA-IR指数＜2(P=0.011)是预测患者获得SVR的独立因素.结论 聚乙二醇干扰素、利巴韦林和二甲双胍联合治疗安全,能增加胰岛素的敏感性,提高胰岛素抵抗的基因1型慢性丙型肝炎患者的SVR率.     

Increased fat accumulation in the liver in HIV-infected patients with antiretroviral therapy-associated lipodystrophy

OBJECTIVE: To determine liver fat content in patients with highly active antiretroviral therapy (HAART)-associated lipodystrophy. BACKGROUND: Lipodystrophy in several animal models is associated with fat accumulation in insulin-sensitive tissues, such as the liver. This causes hyperinsulinaemia, dyslipidaemia and other features of insulin resistance. DESIGN: A cross-sectional study. SUBJECTS AND METHODS: Three age- and weight-matched groups were compared: 25 HIV-positive men with HAART-associated lipodystrophy (HAART+LD+), nine HIV-positive men receiving HAART, but without lipodystrophy (HAART+LD-), and 35 HIV-negative healthy men (HIV-). Liver fat content was measured using proton spectroscopy. Intra-abdominal and subcutaneous fat were determined using magnetic resonance imaging. RESULTS: Liver fat content was significantly higher in the HAART+LD+ (8 +/- 10%) than the HIV- (5 +/- 7%; P < 0.05) or the HAART+LD- (3 +/- 5%; P < 0.01) group. Liver fat content correlated with serum fasting insulin in the HAART+LD+ (r = 0.47; P < 0.05) and HIV- groups (r = 0.65; < 0.001), but not with the amount of intra-abdominal fat. Within the HAART+LD+ group, serum insulin did not correlate with the amount of intra-abdominal fat. The HAART+LD+ group had a lower serum leptin concentration when compared to the two other groups. Features of insulin resistance, including hepatic fat accumulation, were not found in HAART+LD-group. CONCLUSIONS: The severity of the insulin resistance syndrome in patients with HAART-associated lipodystrophy is related to the extent of fat accumulation in the liver rather than in the intra-abdominal region. Fat accumulation in the liver may therefore play a causative role in the development of insulin resistance in these patients.     

Circulating endothelial progenitor cell levels are not reduced in HIV-infected men

Reduced levels of endothelial progenitor cells (EPCs) have been associated with increased cardiovascular (CV) risk, but limited data are available on EPC levels in the human immunodeficiency virus (HIV)-infected population. EPCs (CD45(dim)/CD34(+)/kinase domain receptor(+)) from 36 HIV-uninfected and 30 antiretroviral therapy-naive HIV-infected men without known CV risk factors were enumerated using flow cytometry. The mean EPC levels (± standard error of the mean) were 1.4 ± 0.5 cells/μL in the HIV-infected group and 3.7 ± 2.2 cells/μL in the control group (P = .92). EPC levels were not associated with disease parameters, such as CD4 cell count or viral load. Reductions in EPC levels do not seem to explain the increased risk of CV disease among HIV-infected men.     

Low circulating adiponectin levels are associated with insulin resistance in non-obese peritoneal dialysis patients

In patients with end-stage renal disease (ESRD), circulating adipokine levels are increased due to decreased renal clearance, irrespective of obesity. However, whether adipokines play a role in the development of insulin resistance (IR) in non-obese ESRD patients is unknown. We conducted a cross-sectional study to identify factors associated with IR in 62 non-obese patients on peritoneal dialysis (PD). Non-obesity was defined as body mass index (BMI) <25 kg/m2. IR was determined using homeostatic model assessment-IR (HOMA-IR). We also measured serum concentrations of adiponectin, leptin, resistin, high-sensitivity C-reactive protein (hsCRP), and IL-6. The average BMI of the study patients was 21.6 kg/m2. When patients were divided into two groups according to the median value of HOMA-IR, serum adiponectin levels were significantly lower in patients with HOMA-IR > 1.85 than in those with HOMA-IR ≤1.85, whereas serum concentrations of leptin and resistin did not differ between the two groups. In addition, log-transformed HOMA-IR was negatively correlated with adiponectin (γ = -0.464, P < 0.001) and log-transformed high-density lipoprotein cholesterol (γ = -0.250, P = 0.050) and positively correlated with age (γ = 0.334, P = 0.008) and triglyceride (γ = 0.392, P = 0.002). However, resistin, log-transformed leptin and log-transformed hsCRP were not associated with HOMA-IR. In a multiple linear regression model, adiponectin was independently associated with HOMA-IR (β = -0.023, P = 0.015). In conclusion, this study suggests that low circulating adiponectin levels might be involved in IR even in non-obese patients undergoing PD.     

High-density lipoprotein cholesterol is low in HIV-infected patients with lipodystrophic fat expansions: implications for pathogenesis of fat redistribution

OBJECTIVE: To demonstrate relationships between plasma high-density lipoprotein (HDL) cholesterol and fat expansions in the fat redistribution syndrome. DESIGN: Patients who had significant buffalo humps or intra-abdominal fat (IAF) expansions were identified and their HDL levels were measured. Control patients were all those undergoing a single trial of antiretroviral treatment. Some patients answered a self-administered questionnaire concerning self-perceived fat expansions, and their responses were related to their HDL levels. In other patients, relationships were studied between IAF measured by cross-section computerized tomography scans and HDL levels. Finally, patients who had IAF > 70 cm(2), were administered niacin, 3000 mg/day for > or = 6 months, in order to test whether raising HDL induced a decrease in IAF. RESULTS: Twenty-three patients with buffalo humps had mean HDL of 30.4 mg/dl; 47 HIV-positive controls had mean HDL of 41.9 mg/dl (P = 0.001). In 27 patients, IAF area and HDL were negatively correlated (r, 0.40; P = 0.04). Among these 27, the 17 patients with IAF area > 100 cm(2) had mean HDL of 35.3 mg/dl; the 10 patients with IAF area < 100 cm(2) had mean HDL of 51 mg/dl (P < 0.05). The 24 patients who indicated in a questionnaire that they had self-perceived IAF expansion had a median HDL of 36.0 mg/dl; the 20 who indicated that they did not have IAF expansion had a median HDL of 44.5mg/dl (P = 0.06). IAF decreased by 26.9% in 13 (81%) of the 16 patients who took niacin for 1 year; and the decrease in IAF was associated with a significant (P = 0.002) increase in HDL.     

Low plasma insulin-like growth factor-1 levels are associated with reduced insulin sensitivity and increased insulin secretion in nondiabetic subjects

Background and aimWeight gain is associated with a decline in insulin sensitivity and a compensatory increase in insulin secretion. IGF-1 is a plausible candidate to explain these divergent phenomena. In this cross-sectional study, we analyzed the relationship between IGF-1 levels, insulin sensitivity and secretion in 110 nondiabetic subjects with a wide range of BMI to verify this hypothesis.Methods and resultsSubjects underwent OGTT, IVGTT and euglycemic-hyperinsulinemic clamp. HOMA-beta, IVGTT-derived and OGTT-derived indexes for first-phase and second-phase insulin secretion were higher in obese as compared with overweight and normal-weight groups, while glucose disposal was lower. IGF-1 levels were negatively correlated with IVGTT-derived and OGTT-derived indexes first-phase and second-phase insulin secretion, and positively correlated with glucose disposal. These correlations were no longer significant after adjustment for BMI.In a multivariate analysis, the variables associated with glucose disposal were IGF-1, age, triglycerides, and 2-h post-load glucose accounting for 23.4% of its variation. When BMI was entered into the model, the variables associated with glucose disposal were triglycerides, 2-h post-load glucose and BMI accounting for 27.2% of variation. In a multivariate analysis, the only variable associated with IVGTT-derived first-phase and second-phase insulin secretion was IGF-1 accounting for 10.4% and 15.1% of variation, respectively. When BMI was entered into the model, it became the only variable associated with both first-phase and second-phase insulin secretion accounting for 25.7% and 37.6% of variation, respectively.ConclusionThese data suggest that progressive reduction in IGF-1 levels may be involved in obesity-related changes in both insulin sensitivity and secretion.     

Fasting serum insulin levels and insulin resistance are associated with colorectal adenoma in Koreans

Aims/Introduction

Insulin has been associated with the risk of colorectal cancer (CRC). However, few studies have evaluated the association between insulin and colorectal adenoma. We investigated the relationship between fasting serum insulin levels or homeostasis model assessment of insulin resistance (HOMA‐IR) and colorectal adenoma.

Materials and Methods

We retrospectively enrolled 15,427 participants who underwent both fasting serum insulin measurement and colonoscopy for a routine health examination at Asan Medical Center from January 2007 to December 2008. Participants with a history of any cancer, previous colectomy or polypectomy, those taking antidiabetic medications, and inflammatory bowel disease, non‐specific colitis, non‐adenomatous polyps only or CRC on colonoscopic findings were excluded. Finally, 3,606 participants with histologically confirmed colorectal adenoma and 6,019 controls with no abnormal findings on colonoscopy were included. Participants were categorized into quartiles (Q) based on fasting serum insulin levels and HOMA‐IR.

Results

Fasting serum insulin and HOMA‐IR were significantly higher in participants with colorectal adenomas compared with controls. Multivariate regression analysis adjusting for age, sex, smoking habits, drinking habits and family history of CRC showed that participants with higher quartiles of fasting serum insulin levels (odd ratio [OR] 1.17 for 2nd Q, 1.19 for 3rd Q, and 1.42 for 4th Q, P < 0.05) or HOMA‐IR (OR 1.18 for 2nd Q and 1.45 for 4th Q, P < 0.05) showed significantly increased ORs of colorectal adenoma compared with the lowest quartiles.

Conclusions

These findings showed that increased serum insulin levels and insulin resistance were significantly associated with the presence of colorectal adenoma.