Discrimination Between Obesity and Insulin Resistance in the Relationship With Adiponectin

Fahim Abbasi; James W. Chu; Cindy Lamendola; Tracey McLaughlin; John Hayden; Gerald M. Reaven; Peter D. Reaven


Diabetes. 2004;53(3) 

In This Article


Demographic and clinical characteristics for all four groups are presented in Table 1 . SSPG concentration was significantly higher (and similar), by selection, in the insulin-resistant groups (242 ± 32 and 241 ± 27 mg/dl) than in the insulin-sensitive groups (71 ± 14 and 74 ± 14 mg/dl, P < 0.001 for ANOVA and post hoc comparisons). In contrast, no significant differences in age, blood pressure, total cholesterol, LDL cholesterol, FFA, and fasting glucose concentrations were present across all four groups. Neither BMI nor weight significantly differed between insulin-sensitive and insulin-resistant individuals within each category of obesity. On the other hand, obese subjects were heavier and had higher BMI than nonobese subjects, regardless of their category of insulin action (P < 0.01 for all comparisons). Insulin-resistant subjects (both nonobese and obese) had higher insulin and triglyceride levels and significantly lower HDL cholesterol levels than their insulin-sensitive counterparts.

Adiponectin concentrations were not similar across all four groups, as shown in Fig. 1 (ANOVA, P < 0.001). Although adiponectin concentrations were essentially equal in both nonobese and obese insulin-resistant subjects (16.3 ± 7.5 and 17.1 ± 5.9 µg/ml, respectively), they were significantly lower than in either of the insulin-sensitive groups (29.8 ± 15.3 and 34.3 ± 13.1 µg/ml, P ≤ 0.01 compared with each insulin-resistant group). There were no differences in adiponectin levels between nonobese and obese individuals within the insulin-sensitive or insulin-resistant groups. In the subset of 33 individuals with waist circumference measurements, plasma adiponectin levels were also similar in the obese and nonobese individuals within each insulin-sensitive or insulin-resistant group when the subjects were classified using the Adult Treatment Panel III criteria for visceral obesity.

Comparison of plasma adiponectin concentrations in the four experimental groups. Vertical bars represent the mean adiponectin concentrations, and error bars represent the SD. IS, insulin sensitive; IR, insulin resistant. *Mean adiponectin levels were not similar across the four groups as compared by one-way ANOVA (P < 0.001); †post hoc pairwise comparisons showed that adiponectin levels were significantly different (P ≤ 0.01) between insulin-sensitive and insulin-resistant groups within each obesity category, whereas there were no significant differences (P = 1.0) between the nonobese and obese groups within each insulin action category.

Figure 2 graphically depicts the relationship of fasting adiponectin levels with BMI (A) and SSPG concentrations (B) in the entire study sample. It can be seen that there was no correlation between adiponectin levels and BMI (Spearman correlation coefficient, r s = 0.01, P = 0.96), whereas plasma adiponectin levels were inversely correlated (r s = -0.44, P < 0.001) with SSPG concentrations. Correlation between SSPG and adiponectin concentrations was essentially identical in the 33 individuals with measurements of waist circumference (r s = -0.438, P = 0.01). Moreover, the SSPG-adiponectin relationship only changed modestly when it was adjusted for differences in waist circumference among subjects (Spearman partial correlation coefficient, r s = -0.38, P < 0.01). Interestingly, adiponectin levels in insulin-sensitive subjects (SSPG <100 mg/dl) ranged from very low to very high values (Fig. 2B) and showed significantly greater variation (variance = 201 [95% CI 127-364]) than levels in insulin-resistant (SSPG >190 mg/dl) subjects (variance = 44 [28-80]). In fact, 19 of 30 insulin-sensitive subjects had adiponectin levels that overlapped with those of insulin-resistant subjects, and several insulin-sensitive subjects had levels of adiponectin that were as low as the lowest values in the insulin-resistant group, demonstrating that there were many instances where reduced adiponectin levels were not associated with insulin resistance.

Relationship between plasma adiponectin concentrations, BMI, and SSPG concentrations in 60 nondiabetic volunteers. A: The relationship between plasma adiponectin levels and BMI is shown, where subjects are identified by their insulin resistance status, insulin sensitive (IS, ) and insulin resistant (IR, •). B: The relationship between plasma adiponectin levels and SSPG concentrations is shown, where subjects are identified by their obesity status, either nonobese () or obese (•). The Spearman correlation coefficient (rs) describes the strength of association between the graphed variables.

Relationships in the entire study group between adiponectin and various demographic and metabolic parameters were also evaluated. Although weight, blood pressure, total cholesterol, LDL cholesterol, glucose, and FFAs were not significantly correlated with adiponectin concentrations, insulin (r = -0.49, P < 0.001) and triglyceride (r = -0.27, P = 0.04) levels were both negatively correlated with adiponectin concentrations. As has been reported previously, HDL cholesterol levels (r = 0.50, P < 0.001) and age (r = 0.30, P = 0.02) were also significantly correlated with adiponectin levels. Interestingly, within each category of insulin action, where SSPG values were continuously distributed, adiponectin was poorly correlated with SSPG (insulin sensitive, r = 0.02, P = 0.58, and insulin resistant, r = 0.13, P = 0.51).

In multivariate regression analysis, insulin (β = -0.38) and HDL cholesterol concentrations (β = 0.38) were both strongly related to adiponectin levels. Age (β = 0.21) and BMI (β = 0.15) were also related to adiponectin levels, although with much reduced standardized regression coefficients. If SSPG concentration was entered in the model instead of insulin levels, as high collinearity prevents their simultaneous entry, it was also strongly (β = -0.42) related to adiponectin concentrations.

It should be noted that plasma insulin levels were strongly associated with SSPG concentrations (r s = 0.67, P < 0.001) as well, indicating that in these insulin-sensitive or insulin-resistant subjects, insulin concentration is the one factor that appears to be linked to both adiponectin levels and degree of insulin resistance. To look more carefully at the potential role of insulin in modulating adiponectin levels, we compared levels of adiponectin across quintiles of fasting insulin levels for the entire study group. These results, depicted in Fig. 3, show that the mean levels of adiponectin trended lower as insulin levels increased (P = 0.001, by one-way ANOVA). Consistent with this notion, 11 of the 12 subjects with insulin levels in the highest quintile had adiponectin levels below the median value (19.9 µg/ml), whereas only 3 of the 12 subjects in the lowest quintile of insulin had adiponectin levels below this value.

Relationship between fasting plasma adiponectin and quintiles of fasting insulin concentrations. Vertical bars represent the mean adiponectin concentration for each fasting insulin quintile. *Mean adiponectin levels were not similar across quintiles as compared by one-way ANOVA (P = 0.001). Individual data points are also shown. †Insulin concentrations are given in microunits per milliliter.


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