The Effect of Thiazolidinediones on Plasma Adiponectin Levels in Normal, Obese, and Type 2 Diabetic Subjects

Yu, Jia; Javorschi, Sandrine; Hevener, Andrea L.; Kruszynska, Yolanta T.; Norman, Rodney A.; Sinha, Madhur K.; Olefsky, Jerrold M.

doi:10.2337/diabetes.51.10.2968

Cited by 672 publications

(503 citation statements)

References 49 publications

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“…[23][24][25] It is therefore conceivable that the higher levels of insulin in insulin-resistant subjects may downregulate levels of adiponectin as suggested previously. 26,27 Although we have shown an inverse association between adiponectin and insulin resistance, it is obvious from Figure 2a that there was overlap of adiponectin levels between insulin-sensitive and insulinresistant patients and some of the insulin-sensitive individuals had low adiponectin. Some other studies have reported similar disassociation between adiponectin levels and insulin resistance 28,29 and the relationship between adiponectin and IR is probably not one of the direct cause and effect in all patients.…”

Section: Discussionmentioning

confidence: 68%

“…Some other studies have reported similar disassociation between adiponectin levels and insulin resistance 28,29 and the relationship between adiponectin and IR is probably not one of the direct cause and effect in all patients. It is possible that their inverse relationship may be mediated not only by insulin levels but also by other hormones such as catecholamines or androgens, [30][31][32] as well as by pro-inflammatory cytokines, 33,34 and some medications. 31,35 Our results also depict the prominent role that adipose tissue plays in both insulin resistance and the clinical expression of the metabolic syndrome (Figures 1 and 2).…”

Section: Discussionmentioning

confidence: 99%

“…It is possible that their inverse relationship may be mediated not only by insulin levels but also by other hormones such as catecholamines or androgens, [30][31][32] as well as by pro-inflammatory cytokines, 33,34 and some medications. 31,35 Our results also depict the prominent role that adipose tissue plays in both insulin resistance and the clinical expression of the metabolic syndrome (Figures 1 and 2). Adiponectin and the metabolic syndrome OA Mojiminiyi et al However, as the adipokines and number of the standard criteria for the metabolic syndrome change in proportion with the degree of obesity, it is not clear why some obese individuals do not present with the clinical and metabolic features of the syndrome.…”

Section: Discussionmentioning

confidence: 99%

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Adiponectin, insulin resistance and clinical expression of the metabolic syndrome in patients with Type 2 diabetes

et al. 2006

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Background: Obesity and the metabolic syndrome have emerged as clinical and public health crises in many populations, but not all obese patients have the syndrome. As adipocytes produce several adipokines that modulate insulin action as well as glucose and lipid metabolism, we postulate that estimation of adipokines may be useful addition to the criteria used to identify obese individuals with the metabolic syndrome. Objective: To evaluate the determinants and associations of plasma adiponectin in relation to the metabolic syndrome in patients with Type 2 diabetes. Design: Cross-sectional study. Setting: General Teaching Hospital. Patients: One hundred and thirty five (57 M, 78 F) patients with Type 2 diabetes mellitus. Measurements: Adiponectin, leptin, high-sensitivity C-reactive protein (hs-CRP), fasting plasma insulin, glucose, glycated hemoglobin and full lipid profile. Patients were classified on the basis of the degree of adiposity, insulin resistance (IR) (homeostasis model assessment of insulin resistance (HOMA-IR)) and the number of the American Heart Association and the National Heart, Lung and Blood Institute criteria of the metabolic syndrome. Results: Adiponectin levels were inversely correlated with age, indices of obesity, IR and hs-CRP. Overweight/obese and nonobese insulin-sensitive patients had significantly higher (Po0.05) adiponectin levels than those with IR despite similar body mass index and waist circumference. Therefore, within each category of obesity stratification, lower adiponectin levels were associated with IR. Adiponectin showed stepwise decrease with increasing number of the criteria for diagnosis of the metabolic syndrome. Using multiple logistic regression, the odds ratio of the metabolic syndrome as predicted by adiponectin was 0.73 (95% confidence interval 0.53-0.96; P ¼ 0.04). At cutoff point of 18 ng/ml, the diagnostic sensitivity and specificity of adiponectin for the metabolic syndrome were 83 and 65%, respectively, in male patients and 92 and 41%, respectively, in female patients. Receiver operating characteristic analysis showed that adiponectin had significantly higher area under the curve compared with leptin, leptin:adiponectin ratio and triglycerides for the detection of the metabolic syndrome. Conclusions: In patients with Type 2 diabetes, adiponectin concentrations are closely related to IR and the components of the metabolic syndrome. Adiponectin concentration may be a useful addition to the criteria used for identifying obese subjects with the metabolic syndrome.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Adiponectin, insulin resistance and clinical expression of the metabolic syndrome in patients with Type 2 diabetes

et al. 2006

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“…Second, the current data also suggest that chronic hypoadiponectinaemia could provide a therapeutic target for risk modification in this patient population. In this respect, it is of interest to note that thiazolidinedione therapy, which has been shown to preserve beta cell function and significantly reduce the risk of developing type 2 diabetes in women with a history of GDM [37], is also known to increase adiponectin levels [38]. It thus emerges that a pathophysiological relationship between hypoadiponectinaemia and diabetic risk following GDM could hold important clinical implications.…”

Section: Discussionmentioning

confidence: 99%

Low adiponectin concentration during pregnancy predicts postpartum insulin resistance, beta cell dysfunction and fasting glycaemia

Retnakaran

Qi²,

Connelly

et al. 2009

Diabetologia

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Aims/hypothesis The postpartum phase following gestational diabetes (GDM) is characterised by subtle metabolic defects, including the beta cell dysfunction that is believed to mediate the increased future risk of type 2 diabetes in this patient population. Low circulating levels of adiponectin and increased leptin and C-reactive protein (CRP) have recently emerged as novel diabetic risk factors, although their relevance to GDM and subsequent diabetes has not been characterised. Thus, we sought to determine whether adiponectin, leptin and CRP levels during pregnancy relate to the postpartum metabolic defects linking GDM with type 2 diabetes.Methods Metabolic characterisation, including oral glucose tolerance testing, was undertaken in 487 women during pregnancy and at 3 months postpartum. Based on the antepartum OGTT, there were 137 women with GDM, 91 with gestational impaired glucose tolerance and 259 with normal glucose tolerance. Results Adiponectin levels were lowest (p<0.0001) and CRP levels highest (p=0.0008) in women with GDM. Leptin did not differ between the glucose tolerance groups (p = 0.4483). Adiponectin (r = 0.41, p < 0.0001), leptin (r= −0.36, p <0.0001) and CRP (r = −0.30, p < 0.0001) during pregnancy were all associated with postpartum insulin sensitivity (determined using the insulin sensitivity index of Matsuda and DeFronzo [IS OGTT ]). Intriguingly, adiponectin levels were also related to postpartum beta cell function (insulinogenic index/HOMA of insulin resistance; r=0.16, p=0.0009). Indeed, on multiple linear regression analyses, adiponectin levels during pregnancy independently predicted both postpartum insulin sensitivity (t=3.97, p<0.0001) and beta cell function (t=2.37, p=0.0181), even after adjustment for GDM. Furthermore, adiponectin emerged as a significant negative independent determinant of postpartum fasting glucose (t=−3.01, p=0.0027). Conclusions/interpretation Hypoadiponectinaemia during pregnancy predicts postpartum insulin resistance, beta cell dysfunction and fasting glycaemia, and hence may be relevant to the pathophysiology relating GDM with type 2 diabetes.

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“…This finding is in line with previous publications that thiazolidinedione increases plasma adiponectin levels in obese and in type 2 diabetic patients, as well as in normal subjects to a similar extent. This is accompanied by improvements in different metabolic variables in obese and diabetic, but not in lean insulin-sensitive subjects [40]. This discrepancy has been recently elucidated by the finding that it is not the absolute amount, but rather the distribution of low-and highmolecular weight adiponectin that is important for improved insulin sensitivity in the liver [11].…”

Section: Discussionmentioning

confidence: 99%

Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects

et al. 2004

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Aims/hypothesis: We examined whether shortterm treatment with a thiazolidinedione improves insulin sensitivity in non-obese but insulin-resistant subjects and whether this is associated with an improvement in dysregulated adipose tissue (reduced expression of IRS-1, GLUT4, PPARγ co-activator 1 and markers of terminal differentiation) that we have previously documented to be associated with insulin resistance. Methods: Ten nondiabetic subjects, identified as having low IRS-1 and GLUT-4 protein in adipose cells as markers of insulin resistance, underwent 3 weeks of treatment with pioglitazone. The euglycaemic-hyperinsulinaemic clamp technique was used to measure insulin sensitivity before and after treatment. Serum samples were analysed for glucose, insulin, lipids, total and high-molecular-weight (HMW) adiponectin levels. Biopsies from abdominal subcutaneous adipose tissue were taken, cell size measured, mRNA and protein extracted and quantified using real-time RT-PCR and Western blot. Results: Insulin sensitivity was improved after 3 weeks treatment and circulating total as well as HMW adiponectin increased in all subjects, while no effect was seen on serum lipids. In the adipose cells, gene and protein expression of IRS-1 and PPARγ co-activator 1 remained unchanged, while adiponectin, adipocyte P 2, uncoupling protein 2, GLUT4 and liver X receptor-α increased. Insulin-stimulated tyrosine phosphorylation and p-ser-PKB/Akt increased, while no significant effect of thiazolidinedione treatment was seen on the inflammatory status of the adipose tissue in these non-obese subjects. Conclusions/interpretation: Short-term treatment with pioglitazone improved insulin sensitivity in the absence of any changes in circulating NEFA or lipid levels. Several markers of adipose cell differentiation, previously shown to be reduced in insulin resistance, were augmented, supporting the concept that insulin resistance in these individuals is associated with impaired terminal differentiation of the adipose cells.

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The Effect of Thiazolidinediones on Plasma Adiponectin Levels in Normal, Obese, and Type 2 Diabetic Subjects

Cited by 672 publications

References 49 publications

Adiponectin, insulin resistance and clinical expression of the metabolic syndrome in patients with Type 2 diabetes

Adiponectin, insulin resistance and clinical expression of the metabolic syndrome in patients with Type 2 diabetes

Low adiponectin concentration during pregnancy predicts postpartum insulin resistance, beta cell dysfunction and fasting glycaemia

Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects

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