Relationship of fat distribution with adipokines in human immunodeficiency virus infection

BACKGROUND AND METHODS: HIV-infected patients receiving antiretroviral therapy often develop changes in body fat distribution; the dominant change is reduction in sc adipose tissue (SAT). Because adipose tissue makes important hormones involved in whole-body energy metabolism, including leptin and adiponectin, we examined plasma concentrations and their relationship to regional adiposity measured by magnetic resonance imaging in 1143 HIV-infected persons (803 men and 340 women) and 286 controls (151 men and 135 women) in a cross-sectional analysis of the FRAM study. RESULTS: Total and regional adiposity correlated positively with leptin levels in HIV-infected subjects and controls (P < 0.0001). In controls, total and regional adiposity correlated negatively with adiponectin. In HIV-infected subjects, adiponectin was not significantly correlated with total adiposity, but the normal negative correlation with visceral adipose tissue and upper trunk SAT was maintained. However, leg SAT was positively associated with adiponectin in HIV-infected subjects. Within the lower decile of leg SAT for controls, HIV-infected subjects had paradoxically lower adiponectin concentrations compared with controls (men: HIV 4.1 microg/ml vs. control 7.5 microg/ml, P = 0.009; women: HIV 7.8 microg/ml vs. control 11.6 microg/ml, P = 0.037). Even after controlling for leg SAT, exposure to stavudine was associated with lower adiponectin, predominantly in those with lipoatrophy. CONCLUSION: The normal relationships between adiponectin levels and total and leg adiposity are lost in HIV-infected subjects, possibly due to changes in adipocyte function associated with HIV lipodystrophy, whereas the inverse association of adiponectin and visceral adipose tissue is maintained. In contrast, the relationship between adiposity and leptin levels appears similar to controls and unaffected by HIV lipodystrophy.     

The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes

OBJECTIVE: Serum testosterone levels are known to inversely correlate with insulin sensitivity and obesity in men. Furthermore, there is evidence to suggest that testosterone replacement therapy reduces insulin resistance and visceral adiposity in type 2 diabetic men. Adipocytokines are hormones secreted by adipose tissue and contribute to insulin resistance. We examined the effects of testosterone replacement treatment on various adipocytokines and C-reactive protein (CRP) in type 2 diabetic men. DESIGN: Double-blinded placebo-controlled crossover study in 20 hypogonadal type 2 diabetic men. Patients were treated with testosterone (sustanon 200 mg) or placebo intramuscularly every 2 weeks for 3 months in random order followed by a washout period of 1 month before the alternate treatment phase. METHODS: Leptin, adiponectin, resistin, tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and CRP levels were measured before and after each treatment phase. Body mass index (BMI) and waist circumference were also recorded. RESULTS: At baseline, leptin levels significantly correlated with BMI and waist circumference. There was a significant inverse correlation between baseline IL-6 and total testosterone (r=-0.68; P=0.002) and bioavailable testosterone levels (r=-0.73; P=0.007). CRP levels also correlated significantly with total testosterone levels (r=-0.59; P=0.01). Testosterone treatment reduced leptin (-7141.9 +/- 1461.8 pg/ml; P=0.0001) and adiponectin levels (-2075.8 +/- 852.3 ng/ml; P=0.02). There was a significant reduction in waist circumference. No significant effects of testosterone therapy on resistin, TNF-alpha, IL-6 or CRP levels were observed. CONCLUSION: Testosterone replacement treatment decreases leptin and adiponectin levels in type 2 diabetic men. Moreover, low levels of testosterone in men are associated with pro-inflammatory profile, though testosterone treatment over 3 months had no effect on inflammatory markers.     

Insulin sensitivity is correlated with subcutaneous but not visceral body fat in overweight and obese prepubertal children

AIM: Our aim was to explore the relationship between insulin sensitivity, body fat distribution, ectopic (liver and skeletal muscle) fat deposition, adipokines (leptin and adiponectin), and inflammation markers (highly sensitive C-reactive protein, IL-6, IL-10, and TNF-alpha) in prepubertal children. SUBJECTS AND METHODS: Thirty overweight and obese children (16 males and 14 females with body mass index z-score range of 1.1-3.2) were recruited. Body fat distribution and fat accumulation in liver and skeletal muscle were measured using magnetic resonance imaging. Insulin sensitivity was assessed by iv glucose tolerance test. RESULTS: Insulin sensitivity was associated with sc abdominal adipose tissue (SAT) (r = -0.52; P < 0.01) and liver fat content (r = -0.44; P < 0.02) but not with visceral abdominal adipose tissue (VAT) (r = -0.193; P value not significant) and fat accumulation in skeletal muscle (r = -0.210; P value not significant). Adipokines, but not inflammation markers, were significantly correlated to insulin sensitivity. VAT correlated with C-reactive protein (r = 0.55; P < 0.01) as well as adiponectin (r = -0.53; P <0.01). Multiple regression analysis showed that only SAT and liver fat content were independently correlated to insulin sensitivity (P < 0.01; 20 and 16% of explained variance, respectively). CONCLUSIONS: In overweight and moderately obese prepubertal children, insulin sensitivity was negatively correlated with SAT and liver fat content. Furthermore, contrary to adults, VAT and inflammation markers were not correlated with insulin sensitivity in children.     

Plasma levels of tumor necrosis factor-alpha (TNF-alpha) are essentially dependent on visceral fat amount in type 2 diabetic patients

TNF-alpha is considered as one of the potential determinants of insulin resistance. However several data suggest that TNF-alpha expression itself, could be modulated by the degree of adiposity and/or plasma insulin levels. To clarify the determinants of plasma TNF-alpha levels in type 2 diabetes mellitus, we studied the impact of intensive insulin treatment on plasma TNF-alpha levels in 16 type 2 diabetic subjects with failure to oral antidiabetic medication (HbA1c: 10.8 +/- 1.2 %). Furthermore, we analyzed the relationship between plasma TNF-alpha levels and total or regional body fat measurements using anthropometry, bienergetic absorptiometry and computed tomography in a cohort of 33 caucasian obese type 2 diabetic subjects (BMI: 32.2 +/- 4.4 kg/m(2) ). The plasma TNF-alpha level was neither affected by plasma glucose level variations nor intensive insulin treatment despite a 37 % decrease in daily insulin needs at the end of insulin therapy (total duration: 11.5 +/- 2.0 days). The plasma TNF-alpha level was similar in men and women and unrelated to age, fasting glycemia or HbA1c. A relationship was highlighted with BMI (r =0.39, p <0.02), but not with total fat mass. This relationship was only dependent on the intra-abdominal fat mass amount as assessed by the waist-to-hip circumference ratio (r =0.52, p <0.01) and the visceral adipose tissue area (r =0.56, p <0. 01). These results show that plasma TNF-alpha levels are essentially dependent on visceral fat amount, thus suggesting that TNF-alpha could be one of the factors mediating insulin resistance and cardiovascular risk in obese type 2 diabetic patients.     

Effect of pioglitazone on circulating adipocytokine levels and insulin sensitivity in type 2 diabetic patients

We examined the effect of pioglitazone (PIO) on circulating adipocytokine levels to elucidate the mechanisms by which thiazolidinediones improve insulin resistance in type 2 diabetes mellitus (T2DM). Twenty-three subjects with T2DM (age 54 +/- 2 yr, body mass index 29 +/- 1 kg/m(2)) were randomly assigned to receive placebo (n = 11) or PIO, 45 mg/d (n = 12), for 4 months. Before and after treatment, subjects received a 75-g oral glucose tolerance test (OGTT); euglycemic insulin clamp (40 mU/m(2).min) with 3-(3)H-glucose; determination of fat mass ((3)H(2)O); and measurement of fasting glucose, free fatty acids (FFAs), leptin, adiponectin, and TNFalpha concentrations. After 4 months of PIO, fasting plasma glucose concentration (Delta = -2.7 mol/liter), mean plasma glucose during OGTT (Delta = -3.8 mol/liter), and hemoglobin A(1c) (Delta = 1.7%) decreased (P < 0.05 vs. placebo) without change in fasting or post-OGTT plasma insulin levels. Fasting FFAs (Delta = 168 micromol/liter) and TNFalpha (Delta = 0.7 pg/ml) concentrations decreased (P < 0.05 vs. placebo), whereas adiponectin (Delta = 8.7 microg/ml) increased (P < 0.01 vs. placebo). Despite the increase in body fat mass (Delta = 3.4 kg) after PIO, plasma leptin concentration did not change significantly. No changes in plasma glucose, FFAs, or adipocytokine levels were observed in placebo-treated subjects. During the insulin clamp, endogenous (hepatic) glucose production decreased (Delta = -2.67 micromol/fat-free mass.min, P < 0.05 vs. placebo), whereas metabolic clearance rate of glucose (MCR) increased (Delta = 0.58 ml/fat-free mass.min, P < 0.05 vs. placebo) after PIO. In all subjects, before and after PIO, the decrease in plasma FFA concentration was correlated with the changes in both endogenous (hepatic) glucose production (r = 0.47, P < 0.05) and MCR (r = -0.41, P < 0.05), whereas the increase in plasma adiponectin concentration was correlated with the change in endogenous (hepatic) glucose production (r = -0.70, P < 0.01) and MCR (r = 0.49, P < 0.05). These results suggest that the direct effects of PIO on adipose tissue to decrease plasma FFA levels and increase plasma adiponectin contribute to the improvements in hepatic and peripheral insulin sensitivity and glucose tolerance in patients with T2DM.     

Lower plasma adiponectin is a marker of increased intima-media thickness associated with type 2 diabetes mellitus and with male gender

OBJECTIVE: We tested the extent to which altered plasma adipokine levels may contribute to the increased carotid artery intima-media thickness (IMT) associated with type 2 diabetes mellitus and with male gender, independently of conventional cardiovascular risk factors, insulin resistance, and plasma C-reactive protein (CRP). DESIGN: IMT (mean of three segments of both carotid arteries by ultrasonography), insulin resistance (homeostasis model assessment; HOMA(ir)), plasma CRP, lipids, adiponectin, leptin, resistin, and tumor necrosis factor-alpha (TNF-alpha) were measured in 84 type 2 diabetic patients and 85 control subjects. RESULTS: In diabetic patients, IMT (P<0.001), mean arterial pressure (P<0.001), HOMA(ir) (P<0.001), plasma CRP (P=0.003), triglycerides (P=0.037), leptin (P=0.023), resistin (P=0.003), and TNF-alpha (P=0.003) levels were higher, whereas high-density lipoproteins (HDL) cholesterol (P<0.001) and adiponectin (P<0.001) levels were lower compared with control subjects. Plasma adiponectin (P<0.001) and leptin (P<0.001) were substantially lower in men than in women. IMT was positively and independently associated with age (P<0.001), diabetes (P=0.049), and male gender (P=0.002) in a multivariate regression model, not including other variables. Further analyses showed that IMT was positively related to age (P<0.001) and plasma triglycerides (P=0.038) and negatively to adiponectin (P<0.001), without independent effects of diabetes, gender, and HOMA(ir). CONCLUSIONS: Increased IMT in type 2 diabetes may in part be explained by lower plasma adiponectin and higher triglycerides, but not by leptin, resistin, and TNF-alpha. The gender effect on IMT is related to lower plasma adiponectin.     

Flow mediated dilatation and carotid intimal media thickness in South Indian type 2 diabetic subjects

OBJECTIVE: The aims of this study were to determine: (1). endothelial function in type 2 diabetic subjects with and without diabetic microvascular complications using flow mediated dilatation method (FMD); (2). influence of other variables on FMD; and (3). the correlation between FMD and carotid intimal media thickness (IMT). RESEARCH, DESIGN AND METHODS: In this cross-sectional study, flow mediated dilatation (FMD) and intimal media thickness (IMT) were determined using high resolution ultrasonography in 20 non-diabetic subjects, in 23 type 2 diabetic subjects without any complications and in 23 type 2 diabetic patients with nephropathy and retinopathy. RESULTS: Age-adjusted mean (S.D.) FMD value in diabetic subjects (8.9 +/- 5%) was lower (P < 0.0001) when compared with the group of control subjects (18.8 +/- 7.5 %. However, there was no difference in the age-adjusted FMD values between diabetic subjects with and without complications (7.3 +/- 3.3 % versus 10.5 +/- 5.9 %). FMD levels did not vary significantly between sexes in both non-diabetic and diabetic groups. FMD correlated negatively with carotid IMT (r = -0.23, P < 0.05). In multiple linear regression analysis, age adjusted FMD was associated only with type 2 diabetes with complications (P = 0.012). The variance explained was 21.9%. CONCLUSION: Abnormal FMD and increased carotid IMT were present in type 2 diabetes. Both these parameters negatively correlated with each other supporting an association between impaired FMD and atherogenesis. As these abnormalities existed even in diabetic subjects with no microvascular complications, it is likely that they preceded the development of these complications.     

Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus

The aim of the present study was to investigate the association of serum adiponectin concentration with regional adiposity and insulin resistance in subjects with type 2 diabetes mellitus. A total of 73 Japanese men with type 2 diabetes (aged 59 +/- 11 years and body mass index [BMI] 23.8 +/- 3.0 kg/m(2), mean +/- SD) were studied. Fasting serum adiponectin and leptin concentrations were determined by radioimmunoassay. Regional adiposity was measured by abdominal computed tomography (CT) at the umbilical level, and insulin resistance was estimated by homeostasis model assessment (HOMA-R). Univariate regression analysis showed that serum adiponectin levels were negatively correlated with subcutaneous and visceral fat areas. With multivariate regression analysis, visceral fat area was a predominant determinant of serum adiponectin levels. In contrast, subcutaneous fat area was strongly associated with serum leptin concentrations. Among subcutaneous and visceral fat areas, BMI, and serum leptin levels, both subcutaneous and visceral fat areas were independently associated with HOMA-R. In another model incorporating serum adiponectin levels, serum adiponectin levels were selected as an independent determinant of HOMA-R instead of visceral fat area. In conclusion, hypoadiponectinemia was associated with visceral fat accumulation rather than subcutaneous fat depot in Japanese men with type 2 diabetes mellitus. Both subcutaneous and visceral fat accumulation contribute to insulin resistance in these subjects, and the contribution of visceral fat may be mediated, in part, by hypoadiponectinemia.     

The metabolic syndrome is associated with circulating adipokines in older adults across a wide range of adiposity

BACKGROUND: Circulating levels of adipokines are elevated with adiposity and are closely linked with the clustering of traditional metabolic risk factors for cardiovascular disease. The purpose of this study was to examine the relationship of metabolic syndrome to several adipokines and the role of total and visceral adiposity in influencing this relationship in older adults. METHODS: A cross-sectional analysis was conducted including 1914 individuals aged 70-79 years without cardiovascular disease or type 2 diabetes. The metabolic syndrome was defined by the updated Adult Treatment Panel III criteria. Circulating levels of leptin, adiponectin, plasminogen activator inhibitor type 1 (PAI-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP) were measured. Body composition and abdominal visceral fat area were determined. RESULTS: Both the presence of metabolic syndrome and the number of metabolic syndrome components were associated with higher levels of leptin, PAI-1, IL-6, TNF-alpha, and CRP and with lower levels of adiponectin (all p <.0001). The odds ratios for the prevalence of metabolic syndrome associated with adipokines were attenuated after adjustment for total fat mass and/or visceral fat area, but remained significant. Levels of leptin, PAI-1, IL-6, and TNF-alpha were higher (all p <.05 to p <.0001), and adiponectin was lower (all p <.0001), in persons with, compared to those without, metabolic syndrome within each tertile of percent body fat. CONCLUSION: The metabolic syndrome is associated with adipokines in older adults across a wide range of adiposity, including in those with low or normal overall fatness.     

Tissue inhibitor of metalloproteinase-1 predicts adiposity in humans

OBJECTIVE: Tissue inhibitor of metalloproteinase (TIMP)-1 is upregulated in fat of obese rodents and promotes adipose tissue development in these animals. However, it is unclear whether TIMP-1 independently predicts adiposity in humans and whether serum levels are increased in s.c. and visceral obesity. DESIGN: Twenty-four lean, 16 s.c. obese, and 20 visceral obese subjects were studied. METHODS: Plasma TIMP-1 concentrations were quantified using ELISAs and correlated to clinical parameters. RESULTS: Plasma TIMP-1 levels were significantly different between lean (156 +/- 42 microg/l), s.c. obese (186 +/- 52 microg/l), and visceral obese (198 +/- 42 microg/l) subjects (P < 0.01). Furthermore, TIMP-1 correlated positively with body mass index (BMI), waist-to-hip ratio (WHR), % body fat, fasting insulin, free fatty acids, cholesterol, leptin, interleukin-6, and negatively with adiponectin (P < 0.05). Moreover, TIMP-1 serum levels predicted % body fat but not WHR independent of age, sex, and plasma insulin. CONCLUSIONS: We demonstrate that increased TIMP-1 serum levels are found with increased adiposity in humans.     

脂联素水平及脂联素基因多态性与糖尿病视网膜病变的关系

目的研究血清脂联素（APN）水平及脂联素基因单核苷酸多态性（SNP）45T→G与2型糖尿病（T2DM）视网膜病变（DR）之问的关系。方法运用聚合酶链反应-限制性片段长度多态性方法，对76例T2DM患者[无DR（NDR）组27例、非增殖型DR（NPDR）组28例、增殖型DR（PDR）组21例]，和35例正常对照（Nc）者的APN基因SNP45多态性位点进行基因分型；用放射免疫法检测空腹血清APN浓度；比较各组基因型和等位基因频率，并分析各指标间的相关性。结果（1）T2DM组血清APN水平明显低于NC组（P＜0.01）；PDR组APN浓度明显低于NDR和NPDR组，差异有统计学意义（P均＜0.01）；（2）血清APN浓度与年龄、收缩压、空腹血糖、空腹胰岛素、HbA1C、TG、LDL-C、HO—MA—IR呈显著负相关；（3）SNP45多态性位点的基因型和等位基因频率在NDR、NPDR、PDR组和NC组三间无统计学差异（P〉O．05），三种基因型的血清APN水平无统计学差异（P＞0.05）。结论T2DM患者血清APN水平降低，APN在DR的发病机制中发挥作用且与DR的严重度相关；而APN基因SNP45多态性位点与青岛地区汉族人群中DR无明显相关性。     

Increased plasma adiponectin concentrations are associated with microangiopathy in type 1 diabetic subjects

Aims/hypothesis Insulin resistance is related to an increased risk of diabetic retinopathy and nephropathy in type 1 diabetes. Patients with insulin resistance and/or macrovascular disease have abnormally low levels of adiponectin. The aim of this study was to investigate the relationships between adiponectin and renal and retinal diabetic complications in type 1 diabetic patients.Methods In this 6-year prospective follow-up observational study, we evaluated the severity of retinopathy at baseline and determined the incident risk of microalbuminuria in 126 normoalbuminuric patients with type 1 diabetes. Each patient was age- and sex-matched to two non-diabetic control subjects.Results Plasma adiponectin concentrations were significantly higher in diabetic subjects than in control subjects (p<0.0001). The adiponectin concentration was significantly higher in patients with severe diabetic retinopathy than in those without (39.1±14.0 vs 29.0±13.0 g/ml, p=0.0005). The 18 patients who developed persistent microalbuminuria had higher adiponectin concentrations than the other patients (35.8±14.5 vs 30.6±13.7 g/ml). Increased adiponectin concentrations were independently associated with the occurrence of microalbuminuria (p=0.0158) after adjustment for baseline urinary albumin concentration (p=0.004), sex (p=0.0054), blood pressure (NS) and metabolic control (NS).Conclusions/interpretation The elevated adiponectin concentrations observed in subjects with microvascular disease may indicate an altered regulation of this adipocytokine in patients with complications associated with type 1 diabetes.     

Serum concentrations of advanced glycation endproducts are associated with the development of atherosclerosis as well as diabetic microangiopathy in patients with type 2 diabetes

We measured serum concentrations of advanced glycation endproducts (AGEs) in patients with type 2 diabetes, to elucidate the mechanisms underlying the elevated serum concentrations of AGEs and to clarify the relationship between serum AGE concentrations and the development of microangiography and macroangiopathy. Serum AGEs were significantly higher in diabetic patients than in age-matched control subjects (p < 0.0001). In diabetic patients, serum AGEs were positively correlated with HbA1c (r = 0.47, p < 0.0001), urinary albumin excretion (UAE) (r = 0.42, p < 0.0001), diabetes duration (r = 0.31, p = 0.0030), and fasting plasma glucose (r = 0.34, p = 0.0010). Multiple regression analysis disclosed that only the HbA1c and UAE levels independently correlated with serum AGE levels. Serum AGEs in diabetic patients with progressive retinopathy and overt nephropathy were significantly higher than in those with less severe retinopathy and nephropathy. Serum AGEs were significantly higher in the diabetic patients with coronary heart disease (CHD) than in those without CHD. These results suggest that the HbA1c and UAE levels are independent risk factors for increased serum AGE concentrations in type 2 diabetic patients, and that higher serum AGE concentrations are associated with increased severity of diabetic retinopathy and nephropathy. Serum AGE concentrations may be a useful marker not only for the severity of diabetic microangiopathy but also for the development of CHD in patients with type 2 diabetes mellitus. Received: 8 May 2000 / Accepted in revised form: 5 September 2000     

Circulating adiponectin levels, body composition and obesity-related variables in Prader-Willi syndrome: comparison with obese subjects

BACKGROUND: People with obesity and/or the metabolic syndrome have an increased risk for developing diabetes and cardiovascular disease and may have low adiponectin levels. The obesity associated with Prader-Willi syndrome (PWS) would be expected to have similar complications. However, it was recently reported that, despite their adiposity, people with PWS have reduced visceral fat and are less likely to develop diabetes mellitus or the metabolic syndrome compared with people with simple obesity. OBJECTIVE: To determine if plasma adiponectin levels and other variables relevant to diabetes and cardiovascular risk are different in a cohort of PWS subjects with known genetic subtypes compared with age-, sex- and weight-matched control subjects. RESULTS: Fasting plasma glucose, C-peptide, triglycerides, leptin and cholesterol levels were similar in PWS and obese subjects. Our 20 PWS subjects (mean age = 27.7 years) had higher percent body fat (54.1 vs 48.5%) determined by DEXA measurements and lower percent lean mass (45.9 vs 51.5%) compared with 14 obese controls (mean age = 26.9 year). Plasma adiponectin levels were significantly higher in PWS (15.5 +/- 8.2 microg/ml) than in obese controls (7.5 +/- 2.7 microg/ml). A significant positive correlation was found with insulin sensitivity in PWS subjects (r = 0.75, P = 0.0003) but not in obese controls (r = 0.36, P = 0.20). DISCUSSION: Our study confirmed an earlier observation of higher adiponectin levels in PWS subjects and less insulin resistance proportionate to their obesity status than found in subjects with simple obesity. Furthermore, no differences were seen in PWS subjects with the chromosome 15 deletion or maternal disomy 15. The reported excessive visceral adiposity in subjects with simple obesity compared with PWS may be associated with decreased production and lower circulating levels of adiponectin.     

Serum adiponectin is related to plasma high-density lipoprotein cholesterol but not to plasma insulin-concentration in healthy children: the FLVS II study

Although low levels of plasma adiponectin were associated with an increase in cardiovascular risk in adults, few data investigated that relationship in children. The aim of this study was to investigate the relationship between plasma adiponectin and cardiovascular risk factors in healthy children. This cross-sectional population-based study was conducted in Fleurbaix and Laventie, 2 cities in the north of France. The main outcome measure was the correlations between plasma adiponectin and adiposity variables (the body mass index, the sum of 4 skinfolds, waist circumference [WC], and percent body fat [bioimpedance]), blood pressure, plasma glucose, triglycerides, high-density lipoprotein (HDL) cholesterol and insulin. In 398 children of both sexes, adiponectin was not significantly related to age and pubertal stage. In boys only, adiponectin correlated with WC (r = -0.19; P = .008) and body mass index (r = -0.15; P = .04) but not with other adiposity variables. After taking into account WC, adiponectin was positively correlated with HDL-cholesterol in boys (r = 0.14; P = .05) and girls (r = 0.25; P = .0004), but was not correlated with insulin and homeostasis model assessment index for insulin resistance in both sexes. These results suggest that, in apparently healthy children, adiponectin is related to the level of HDL-cholesterol independently of fat mass. The relationship between adiponectin and insulin resistance previously reported in obese or diabetic children was not apparent in these subjects and may therefore occur only at later age with fat accumulation.     

Raised plasma adiponectin levels in type 1 diabetic pregnancies

OBJECTIVES: Adiponectin has antidiabetic properties. Our aim was to determine plasma adiponectin levels during pregnancy and postpartum (PP), in women with type 1 diabetic mellitus (T1DM) and nondiabetic (ND) women. PATIENTS AND METHODS: Fasting plasma adiponectin and leptin levels were measured in 20 ND and 19 T1DM women, at 20 and 30 weeks' gestation, and 9 months' PP. Insulin measurements were made in ND women. RESULTS: In both groups, after accounting for body mass index (BMI), leptin levels increased during pregnancy (P < 0.01) and were significantly higher than PP (P < 0.001). However, no significant differences in leptin levels were noted between both groups at any stage (P = 0.46). Conversely, adiponectin levels were higher in T1DM at all stages of the study (P < 0.001). A significant fall in adiponectin levels was seen between 20 and 30 weeks' gestation in both groups (ND: P < 0.001; T1DM: P < 0.05); however, this decrease was attenuated in the T1DM group. Adiponectin levels PP were significantly higher than at 30 weeks (ND: P < 0.001; T1DM: P < 0.001). Furthermore, in T1DM, adiponectin appeared to correlate negatively with leptin, but only reached significance PP (r = -0.46, P < 0.001). In the ND group, adiponectin correlated negatively with both leptin (PP: r = -0.56, P < 0.0001) and insulin (P < 0.005). CONCLUSIONS: Higher adiponectin levels were noted in T1DM throughout gestation compared to ND pregnancies, with no difference in leptin levels. The significance of these findings needs to be determined.     

Possible relationship between adiponectin and renal tubular injury in diabetic nephropathy

Adiponectin is an adipose-derived protein which has anti-inflammatory and anti-atherogenic properties in addition to insulin-sensitizing effects. To date, the role of adiponectin in the pathogenesis of diabetic nephropathy remains unclear. The aim of the present study was to explore the relationship between adiponectin and renal tubular injury in diabetic nephropathy. We determined serum and urinary adiponectin levels in type 2 diabetic patients with normoalbuminuria (n = 19), microalbuminuria (n = 18), and overt diabetic nephropathy (n = 16), and then analyzed the correlations between serum and urinary adiponectin, urinary N-acetylglucosaminidase (NAG) as a clinical marker of renal tubular injury, urinary monocyte chemoattractant protein-1 (MCP-1) as an inflammatory marker in renal tubulointerstitium, and clinical markers of renal disease. Notably, serum and urinary adiponectin levels were significantly increased in patients with overt diabetic nephropathy compared to those with normoalbuminuria and microalbuminuria. In univariate linear regression analysis, serum adiponectin levels were positively correlated with serum creatinine (r = 0.648, P<0.0001), urinary albumin (r = 0.583, P<0.0001), urinary NAG (r = 0.406, P<0.01), urinary MCP-1 (r = 0.514, P<0.0001), and urinary adiponectin (r = 0.691, P<0.0001) levels in all diabetic patients. Urinary adiponectin levels were also positively correlated with serum creatinine (r = 0.729, P<0.0001), urinary albumin (r = 0.799, P<0.0001), urinary NAG (r = 0.701, P<0.0001), and urinary MCP-1 (r = 0.801, P<0.0001) levels in all diabetic patients. Multiple linear regression analysis showed that serum creatinine and urinary adiponectin levels were independently associated with serum adiponectin levels (r(2) = 0.522), and that serum creatinine, urinary NAG, urinary MCP-1, and serum adiponectin levels were independent determinants of urinary adiponectin levels (r(2) = 0.851). These results collectively indicate that renal insufficiency and tubular injury possibly play a contributory role in increases in serum and urinary adiponectin levels in overt diabetic nephropathy. We presume that an increase in circulating adiponectin in overt diabetic nephropathy might be a physiological response to mitigate renal tubular injury and to prevent the further progression of diabetic nephropathy through its anti-inflammatory and anti-atherogenic effects.     

Plasma levels of agouti-related protein are increased in obese men

To investigate the relationship between peripheral blood levels of agouti-related protein (AGRP) and various parameters of obesity, we measured the plasma level of AGRP in 15 obese and 15 nonobese men and evaluated its relationship with body mass index (BMI), body fat weight, and visceral, sc, and total fat areas measured by computed tomography, fasting insulin levels, glucose infusion rate during an euglycemic hyperinsulinemic clamp study, serum leptin, and plasma alpha-MSH. Obese men had significantly higher plasma concentrations of AGRP than nonobese men (P < 0.01). Univariate analysis showed that the plasma levels of AGRP are proportionally correlated with BMI, body fat weight, and sc fat area in obese men (BMI: r = 0.732, P < 0.01; body fat weight: r = 0.603, P < 0.02; sc fat area: r = 0.668, P < 0.01) and in all men (BMI: r = 0.839, P < 0.0001; body fat weight: r = 0.818, P < 0.0001; sc fat area: r = 0.728, P < 0.0001). In all men, the plasma levels of AGRP were significantly correlated with the visceral fat area (r = 0.478, P < 0.01), total fat area (r = 0.655, P < 0.0001), fasting insulin level (r = 0.488, P < 0.01), glucose infusion rate (r = -0.564, P < 0.01), serum level of leptin (r = 0.661, P < 0.0001), and the plasma level of alpha-MSH (r = 0.556, P < 0.01). In all subjects, multiple regression analysis showed that the plasma levels of AGRP are significantly (F = 15.522, r = 0.801, P < 0.03) correlated with the plasma levels of alpha-MSH, independently from the total fat area. However, the correlation between plasma levels of AGRP and serum levels of leptin was found to be dependent on the total fat area. In brief, these findings showed that the circulating levels of AGRP are increased in obese men and that they are correlated with various parameters of obesity. Although correlation does not prove causation, the results of this study suggest that peripheral AGRP may play a role in the pathogenesis of obesity.     

2型糖尿病患者视网膜病变与颈动脉内膜中层厚度的关系

目的 探讨2型糖尿病患者视网膜病变(DR)与颈动脉内膜中层厚度(IMT)之间的关系.方法 选取2008、2009年在哈尔滨医科大学附属第四医院内分泌科确诊的2型糖尿病患者123例作为观察对象,根据眼底检查结果 分为DR组和非DR(NDR)组.采集病史(病程、吸烟、家族史等),同时检测颈动脉IMT、收缩压、舒张压、总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、糖化血红蛋白、体质量指数等指标.两组颈动脉IMT增厚发生率的比较采用χ2检验,两组平均颈动脉IMT值的比较采用独立样本t检验:应用Logistic回归分析糖尿病DR病变的影响因素.结果 ①DR组IMT增厚的发生率为50.98%(26/51),NDR组为33.33%(24/72),两组比较差异有统计学意义(χ2=3.85,P<0.05).②DR组平均颈动脉IMT值为(1.01±0.23)mm,NDR组为(0.91±0.24)mm,两组比较差异有统计学意义(t=-2.21,P<0.05).③单因素分析糖尿病DR病变的影响因素为;吸烟(χ2=6.20,P<0.05),病程(t=-4.13,P<0.01),高密度脂蛋白胆固醇(t=4.49,P<0.01),颈动脉IMT(t=-2.21,P<0.05),收缩压(t=-2.37,P<0.05).④Logistic回归分析糖尿病DR病变的影响因素为:病程、高密度脂蛋白胆固醇、颈动脉IMT、吸烟(χ2值分别为7.77、12.77、6.05、4.15,P均<0.01或0.05).结论 2型糖尿病DR病变患者颈动脉IMT增厚的比例明显增加,且平均颈动脉IMT厚度亦明显增加.2型精尿病合并DR病变与其颈动脉IMT厚度之间关系密切.