The present study compares basal plasma adipokine, inflammatory marker, and FFA concentrations between non-obese and obese type 2 diabetes patients versus non-obese normoglycemic controls. We show that basal plasma FFA, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), leptin, and triglyceride levels are elevated in obese type 2 diabetes patients, as opposed to healthy, normoglycemic controls (Fig. ; Table ). On the other hand, no such differences were found between non-obese type 2 diabetes patients and healthy normoglycemic controls. Consequently, altered plasma FFA, IL-6, hsCRP, and leptin levels seem to be more related to adipose tissue mass than to the presence or absence of the type 2 diabetic state and/or the level of glycemic control. This is further supported by the observation that parameters that assess glycemic control were no longer correlated with plasma FFA, IL-6, hsCRP and leptin levels when data were adjusted for trunk adipose tissue mass (Table ). Therefore, our findings suggest that elevated basal plasma FFA, IL-6, hsCRP, and leptin concentrations are not necessarily related to the type 2 diabetic state.
Our findings seem to be in contrast with findings from some, but not all, studies which show that in non-obese type 2 diabetes patients, plasma FFA, IL-6, and CRP concentrations are higher, and adiponectin and leptin levels are lower, when compared with matched normoglycemic controls (Abdelgadir et al. 2005
; Bahceci et al. 2007
; Chanchay et al. 2006
; Hasegawa et al. 2005
; Hotta et al. 2000
; Marita et al. 2005
; Sayeed et al. 2003
; Yang et al. 2006
). This might be attributed to differences in the ethnic background of the volunteers in the different studies (Carroll et al. 2009
; Lee and Jensen 2009
; Reimann et al. 2007
), which show large differences in adipose tissue mass distribution and/or the level of insulin resistance (Banerji et al. 1999
; Chandalia et al. 1999
). For example, Asian and Mid-Eastern populations show a relatively greater truncal adipose tissue mass when compared with BMI-matched Caucasians (Banerji et al. 1999
; Chandalia et al. 1999
). This might be accompanied by differences in adipokine and inflammatory marker secretion between populations of various ethnic backgrounds. Additionally, in none of these studies habitual physical activity was controlled for between groups. Different levels of habitual activity are likely to affect plasma adipokine and inflammatory marker levels, complicating the interpretation of such findings (You and Nicklas 2008
Recent in vitro studies examined the relation between adipocyte size and adipokine/inflammatory factor release/expression derived from Caucasian human subcutaneous adipose tissue biopsies (Jernas et al. 2006
; Skurk et al. 2007
). These studies indicate that leptin and IL-6 secretion were significantly greater in enlarged adipocytes. No such relation was observed for adipocyte size and TNFα and/or adiponectin release. Moreover, a correlation between serum amyloid A (SAA) gene expression in human adipocytes and adipocyte size has previously been reported (Jernas et al. 2006
). SAA is an acute-phase protein involved in inflammation, and contributes to adipocyte-derived CRP and IL-6 release. A correlation between adipocyte-derived FFA release and adipocyte size has been well-established. These findings seem to agree with our observation that plasma hsCRP, FFA, leptin and IL-6 are no longer significantly correlated with the level of glycemic control when adjusted for trunk adipose tissue mass. Consequently, we conclude that alterations in plasma FFA, IL-6, hsCRP, and leptin levels in obese type 2 diabetes patients are attributed to the greater adipose tissue mass, and not necessarily to the presence of the type 2 diabetic state.
Data from the present study imply that systemic low-grade inflammation, a disturbed blood lipid profile, and lowered oxygen uptake capacity are more prevalent in obese, as opposed to non-obese, type 2 diabetes patients. The development of type 2 diabetes in subjects with excess adipose tissue mass is currently believed to be related to many factors. Besides genetic predisposition and ethnicity, a low skeletal muscle oxidative capacity and/or altered protein/cytokine secretion from adipocytes is linked to impairments in whole-body carbohydrate metabolism. However, we failed to observe any significant differences in whole-body oxygen uptake capacity and/or blood plasma adipokine and inflammatory markers levels in the non-obese type 2 diabetes patients when compared to the matched normoglycemic controls. Therefore, other factors are likely to play a more prominent role in the etiology of insulin resistance and type 2 diabetes in the non-obese population.
One of the more challenging features of this work was the inclusion of non-obese type 2 diabetes patients. Recent studies report that only ~10% of all Caucasian type 2 diabetes patients have a normal lean phenotype, whereas more than 60% is obese (Kramer et al. 2009
). Nonetheless, the comparison of plasma adipokine and inflammatory marker concentrations in non-obese and obese type 2 diabetes patients generates the possibility to differentiate between the impact of type 2 diabetes and obesity.
This study has some important clinical implications. The presented data confirm that obese type 2 diabetes patients are clearly at a high risk of developing cardiovascular disease (based on body composition, blood lipid profile and inflammation parameters, oxygen uptake capacity). Based on these parameters, the non-obese type 2 diabetes patients seem to be at a lower risk of developing cardiovascular complications. Since strong correlations have been reported between low-grade inflammation, disturbed blood lipid profile, reduced whole-body oxidative capacity, and the risk of developing cardiovascular complications, obese type 2 diabetes patients should be stimulated to adhere to effective exercise, nutritional, and pharmaceutical intervention to reduce excess adipose tissue mass and improve glycemic control. Interestingly, our data show that the proposed link between plasma adipokines, inflammation parameters, FFA and type 2 diabetes are more related to the level of adiposity, as opposed to insulin sensitivity and/or glycemic control. Further study remains warranted to elucidate the proposed role of these plasma parameters in the etiology of obesity and/or type 2 diabetes.
In conclusion, elevated plasma FFA, IL-6, hsCRP, leptin, and triglyceride concentrations are observed in obese, as opposed to non-obese, type 2 diabetes patients. Elevated plasma leptin, hsCRP, IL-6, and FFA concentrations are attributed to the prevalence of obesity and not necessarily associated with the type 2 diabetic state.