



































Total and high-molecular-weight adiponectin levels in relation to insulin resistance among overweight/obese adults


 

 

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Total and high-molecular-weight 

adiponectin levels in relation to 

insulin resistance among 

overweight/obese adults 

 

Sushama D. Acharya1,2, Rhobert 

W. Evans2, Maria M. Brooks2, 

Faina Linkov2,3, Lora E. Burke1,2 
 

1School of Nursing, University of 
Pittsburgh, 2Graduate School of Public 
Health, University of Pittsburgh, 3School 
of Medicine, University of Pittsburgh 

 

Vol. 2, No. 2 (2013)   |   ISSN 2166-7403 (online)    

DOI 10.5195/cajgh.2013.55   |   http://cajgh.pitt.edu 

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ACHARYA 

 

 

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Central Asian Journal of Global Health 

Volume 2, No. 2 (2013) | ISSN 2166-7403 (online) | DOI 10.5195/cajgh.2013.55 | http://cajgh.pitt.edu 

  

 

Abstract 

Objective: To determine whether baseline levels or intervention-associated changes in total and high molecular weight (HMW) 

adiponectin levels were associated with insulin resistance after six months of behavioral treatment for weight loss.  

Design: An ancillary study to a behavioral weight loss trial; the intervention was delivered in group sessions.  

Methods: Participants included 143 overweight/obese adults with a mean BMI of 33.7 kg/m2. The sample was 88% female, 67% 

white, and 44.2 ± 8.5 years old. Circulating adiponectin levels (total and HMW) and the homeostasis model assessment (HOMA) 

of insulin resistance were measured and evaluated.  

Results: At baseline, there was significant inverse associations between total adiponectin and HOMA (p < 0.001) and between 

HMW adiponectin and HOMA (p < 0.001) independent of weight. At 6-mo, there was a 17% improvement in HOMA, 8% 

increase in total adiponectin, 17% increase in HMW adiponectin levels, and 8.72% weight loss (p's for all< 0.001). There was 

also a significant inverse association between changes in total adiponectin and HOMA (p = 0.04) that was independent of 

baseline weight and weight loss. In contrast, the association between changes in HMW adiponectin and HOMA was attenuated 

after adjustment for weight loss.  

Conclusions: An increased level of total adiponectin was associated with improved insulin sensitivity, regardless of baseline 

weight and weight loss. However, baseline total and HMW adiponectin levels were more strongly associated with HOMA than 

changes in these measures at six months. HMW adiponectin level was not related more closely to insulin resistance than total 

adiponectin level.  

Keywords: Adiponectin, high molecular weight adiponectin, insulin resistance, homeostasis model assessment of insulin 

resistance (HOMA), weight loss and adiponectin levels 

 

Total and high-molecular-weight 

adiponectin levels in relation to 

insulin resistance among 

overweight/obese adults 

 

 

Sushama D. Acharya1,2, Rhobert W. 

Evans2, Maria M. Brooks2, Faina 

Linkov2,3, Lora E. Burke1,2 
 

1School of Nursing, University of Pittsburgh, 
2Graduate School of Public Health, 
University of Pittsburgh, 3School of Medicine, 
University of Pittsburgh 

Research 

Obesity is a significant public health problem 

with recent data indicating more than 1.4 billion 

overweight adults worldwide and nearly two-thirds of 

the global population living in countries where 

overweight and obesity affect mortality more than 

underweight.
1
 As obesity is a major risk factor for the 

development of insulin resistance (IR) and associated 

metabolic diseases including hypertension, 

hyperlipidemia, atherosclerosis, and certain types of 

cancer, significant research has been conducted to 

understand obesity mechanisms related to pathogens of 

these diseases. It is now evident that adipose tissue is no 

longer considered an inert tissue mainly devoted to 

energy storage but is now recognized as an active 

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CENTRAL ASIAN JOURNAL OF GLOBAL HEALTH 

 

 

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-No Derivative Works 3.0 United States License. 

 

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of its D-Scribe Digital Publishing Program, and is cosponsored by the University of Pittsburgh Press. 

 

Central Asian Journal of Global Health 

Volume 2, No. 2 (2013) | ISSN 2166-7403 (online) | DOI 10.5195/cajgh.2013.55 | http://cajgh.pitt.edu 

  

 

endocrine organ secreting several hormones and a 

diverse range of other protein factors.
2
 Adiponectin is 

one of the many hormones secreted by adipose tissue as 

the adipokine in the human body. IR and obesity are 

both associated with lower plasma adiponectin 

concentrations suggesting its important physiological 

role.
3
 Improvements in IR, glucose uptake in skeletal 

muscles and hepatic fatty acid oxidation upon 

administration of adiponectin in animal studies suggest 

that adiponectin may provide a link between adiposity, 

IR and diabetes.
4
 Figure 1 depicts a proposed 

mechanism linking adiposity and adiponectin with IR 

and diabetes. 

 

Figure 1. Proposed link among adiposity, adiponectin, 

insulin resistance and diabetes. 

 

 A strong inverse relationship between 

adiponectin and IR has been reported in population 

cross-sectional studies.
5-7

 Moreover, longitudinal data 

also suggest a relationship between lower adiponectin 

levels and the development of IR and diabetes.  In a 

study of Pima Indians, those with high adiponectin 

concentration were found to be at a lower risk of 

developing diabetes than those with a low 

concentration, suggesting a potential role of adiponectin 

in the pathogenesis of diabetes.
8
 Similarly, an inverse 

association between adiponectin and diabetes risk was 

reported among a large population of healthy women,
9
 a 

middle-aged population cohort,
10

 and adults with 

insulin-resistance.
11

 Mather et al. reported baseline 

adiponectin as a better marker of diabetes prevention 

than changes in adiponectin levels over one year in the 

Diabetes Prevention Program (DPP).
12

 However, no 

association was found between adiponectin and IR 

despite improved insulin sensitivity in response to 

weight loss among obese women,
13

 obese adults,
14

 and 

insulin resistant adults who were not diabetic.
15

 

Additionally, part of the difficulty also is that despite 

short term weight loss, successful long-term weight loss 

maintenance is extremely difficult as most individuals 

regain most of their weight with a few years.
16

 Because 

of these variations due to population, sample size, 

differences in baseline degree of insulin resistance, and 

adiponectin, the evidence provided by these studies on 

the relationship between IR and adiponectin in the 

presence of weight loss remains equivocal. 

Adiponectin exists in circulation in three 

distinct forms: low molecular weight (LMW), medium 

molecular weight (MMW), and high molecular weight 

(HMW) forms.
3,17

 HMW adiponectin has been 

suggested to be the most active form of adiponectin and 

more closely associated with IR with an ability to 

enhance insulin action.
18,19

 However, a major limitation 

of many epidemiological and intervention studies is the 

measurement of only total adiponectin level. Thus, little 

is known about how the relationship between HMW 

adiponectin and IR might differ from the relationship 

between total adiponectin and IR. Hence, the aims of 

this study were to determine whether baseline levels or 

intervention-associated changes in total and HMW 

adiponectin levels were associated with IR after 6 

months of behavioral treatment for weight loss.  

 

Materials and Methods 

Study design  

This was an ancillary study to the PREFER 

trial, an 18-month behavioral weight loss study designed 

to evaluate the effects of treatment preference 

(Preference-Yes vs. Preference-No) and two dietary 

treatment options, standard calorie restricted low fat diet 

(STD-D)  vs. lacto-ovo-vegetarian diet (LOV-D). 

Participants were randomly assigned first to one of the 

two preference conditions (yes or no). If assigned to the 

Preference-No condition, they were further randomly 

assigned to one of the two diet conditions, STD-D or 

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-No Derivative Works 3.0 United States License. 

 

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of its D-Scribe Digital Publishing Program, and is cosponsored by the University of Pittsburgh Press. 

 

Central Asian Journal of Global Health 

Volume 2, No. 2 (2013) | ISSN 2166-7403 (online) | DOI 10.5195/cajgh.2013.55 | http://cajgh.pitt.edu 

 

 

LOV-D. If assigned to Preference-Yes condition, they 

were assigned to the diet they indicated as preferred at 

screening. The design, recruitment, and randomization 

procedures for the PREFER trial have been described in 

detail elsewhere.
20

 Refer to Figure 2 for the number of 

participants at each stage. The study protocol was 

approved by the University of Pittsburgh Institutional 

Review Board; all participants provided written 

informed consent. The PREFER trial was conducted 

between 2000 and 2005, and unthawed aliquots of 

serum samples were stored at -80
0
C. The current 

analysis was limited to the 143 participants whose sera 

samples were available from baseline and 6-month 

assessments.  

 

Figure 2. PREFER trial flowchart (included only 6-mo 

assessment). 

 

Participants  

The study population included adults between 

18 and 55 years of age, a body mass index (BMI) 

between 27 and 43 kg/m
2
 inclusively, and adequately 

completed a 5-day food diary at screening. Individuals 

were excluded if they had diabetes or a medical 

condition requiring physician supervision of diet or 

physical activity, were pregnant, participated in a 

behavioral or pharmacological weight-loss program in 

the last 6 months, reported alcohol intake of  ≥ 4 drinks 

per day, and reported abstention from eating meat, 

poultry, or fish in the past month.  

 

Intervention  

All four treatment groups received the same 

standard behavioral intervention. The only difference 

between the diet groups was that the LOV-D 

participants were instructed to eliminate meat, poultry, 

and fish form their diet by the 6th week of the program. 

Details of the intervention have been reported 

elsewhere.
20

 In brief, all participants received a daily 

energy and fat gram goal based on gender and baseline 

body weight as described in Table 1. Participants were 

instructed to increase their physical activity gradually, 

primarily via walking, until they reached a goal of 150 

minutes by week 6. As an alternative to walking, 

aerobic activities such as bicycling, swimming, and 

jogging were encouraged. Use of frequent, short bouts 

to meet one’s exercise goal, for example exercising for 

10–15 minutes three times per day, was also promoted. 

The intervention group sessions were held weekly 

during the first six months. The cognitive-behavioral 

intervention used several strategies from models of 

motivation and behavior change. All participants 

received nutritional and behavioral counseling and were 

provided with practical hands-on experience to develop 

skills to implement a healthy lifestyle. All participants 

self-monitored their daily energy and fat intake, as well 

as physical activity (duration and type) they performed 

during the study period.  

 

Table 1. Daily dietary goals. 

 

Measures  

Baseline demographic characteristics were 

collected via a self-administered, standardized 

questionnaire. All anthropometric, biochemical, and 

adiponectin measurements were obtained at baseline 

and 6 months. Weight was measured on a digital scale 

(Tanita Corporation of America, Inc., IL) in 

light clothing and without shoes. Height was measured 

with a wall-mounted stadiometer. The physical activity 

assessment was conducted via a self-administered 

Paffenbarger Activity Questionnaire.
21

 This 

questionnaire has been shown to have good test-retest 

reliability. A metabolic equivalent value was assigned to 

each leisure activity, from which the total energy 

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expenditure was calculated. Blood samples, obtained 

following a 12-hour fast were assayed at the Heinz 

Nutrition Laboratory, University of Pittsburgh. Plasma 

glucose was measured with the use of the hexokinase-

glucose 6-phosphate dehydrogenase enzymatic assay 

(Sigma Diagnostics, St. Louis, MO), and insulin 

concentration was measured by a radioimmunoassay kit 

(Linco Research, St. Charles, MO). Insulin resistance 

was assessed by homeostasis model assessment of 

insulin resistance (HOMA-IR) and was calculated as 

fasting insulin concentration (U/mL) x fasting glucose 

concentration (mmol/L)/22.5. HOMA is a mathematical 

assessment of the balance between hepatic glucose 

output and insulin secretion and has been widely 

validated and applied for quantifying insulin resistance 

and β-cell function. Serum levels of total and HMW 

adiponectin were determined using the ELISA 

technique (ALPCO Diagnostics, Salem, NH). The intra-

assay and inter-assay CVs were 6.4% and 12.7% for 

total adiponectin and 6.4% and 12.6% for HMW 

adiponectin, respectively. All samples were assayed in 

duplicate.   

 

Statistical analysis  

Statistical analyses were performed using SAS 

(version 9.2; SAS Institute Inc, Cary, NC). All 

continuous variables were checked for normality. Basic 

statistics were expressed as mean ± SD or as 

proportions, unless otherwise specified. For all 

continuous variables, comparisons between baseline and 

6-month measures were examined using a paired 

sample’s t-test. A chi-square test was performed for 

comparing the categorical variables at baseline. 

Associations between continuous variables were 

assessed using the Pearson or Spearman correlation 

coefficient. Separate multiple linear regression models 

were used for HOMA at baseline and change in HOMA 

score (6-month – baseline scores) as the dependent 

variables to examine associations between total and 

HMW adiponectin at baseline and 6 months. The 

models were adjusted for age, gender, race, baseline 

weight, baseline energy expenditure, changes in weight, 

and energy expenditure. All tests performed were two-

sided, and significance level was set at p < 0.05. 

 

Results 

Of the 176 participants randomized at baseline, 

151 completed the 6-month assessment, and the sera 

samples of 143 (95%) participants were available from 

both baseline and 6-month assessments. The majority of 

participants were female (88%), white (67%), currently 

married or living with a partner (65%), and employed 

(94%). The mean age was 44.2 ± 8.5 years old with a 

BMI range of 26.71 to 42.56 kg/m
2 

(Mean= 33.78 

kg/m
2
) and, on average, 15.3 years of formal education. 

No differences in baseline characteristics were found 

between participants who were excluded and those 

included in the analysis. There was no significant 

difference in HOMA between the two diet groups; STD-

D vs. LOV-D (4.28 ± 2.15 vs. 4.62 ± 2.32; p = 0.3), nor 

were there differences by the two preference groups; 

Preference-Yes vs. Preference-No (4.60 ± 2.18 vs. 4.28 

± 2.27; p = 0.4). Additionally, there were no significant 

differences in total adiponectin level by diet group (7.82 

± 3.74 vs. 7.64 ± 2.87 ug/ml; p = 0.7) or preference 

group (7.76 ± 3.57 vs. 7.62 ± 7.66 ug/ml; p = 0.7), nor 

did HMW adiponectin level differ by diet group (3.33 ± 

2.21 vs. 3.23 ± 1.68 ug/ml; p = 0.8) or preference group 

(3.30 ± 1.97 vs. 3.23 ± 20.01; p = 0.8). Since there were 

no significant differences between the two diet groups 

and the two preference groups, further analyses were 

conducted as a single sample without regard to 

randomized diet or preference condition.  

At baseline, HOMA did not differ by gender 

(female vs. male: 4.36 ± 2.23 vs. 4.97 ± 2.24; p = 0.3) or 

race (white vs. non-white: 4.47 ± 2.34 vs. 4.33 ± 20.00; 

p = 0.7). However, females had significantly higher 

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Central Asian Journal of Global Health 

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total (7.85 ± 3.32 vs. 6.31 ± 2.58 ug/ml; p = 0.04) and 

HMW adiponectin levels (3.37 ± 2.9 vs. 2.39 ± 1.43 

ug/ml; p = 0.03) than males. Figure 3 describes the 

baseline and 6-month measures of the studied variables. 

From baseline to 6 months, there was a 17% reduction 

in HOMA (p < 0.001), 8% increase in total adiponectin 

(p = 0.001), and 17% increase in HMW adiponectin 

levels (p < 0.001). Further, there was a significant 

weight loss (8.72%) at 6 months (p < 0.001). There 

were highly significant correlations between total and 

HMW adiponectin levels at baseline (r = 0.95; p < 

0.001) and also at 6 months (r = 0.95; p < 0.001). At 

baseline and 6 months, weight, BMI, glucose, and 

insulin showed significant positive associations with the 

HOMA score while total and HMW adiponectin levels 

showed significant negative association with HOMA (p 

for all < 0.001).  

 

Figure 3. Measures at baseline and 6-month 

assessments. 

 

Separate multiple regression analyses were 

performed for both baseline and 6-month measures with 

baseline HOMA and the change in HOMA scores as the 

dependent variables, respectively. The final model, with 

baseline measures adjusted for weight, indicated 

significant inverse associations between total 

adiponectin and the HOMA score (p < 0.001) and 

between HMW adiponectin and HOMA (p < 0.001). 

The estimates for total and HMW adiponectin still 

remained highly significant after adjustment for baseline 

weight (Table 2). At 6 months, the final regression 

model revealed a significant inverse association 

between changes in total adiponectin and HOMA (p = 

0.04) that was independent of baseline weight and 

weight loss. In contrast, higher HMW adiponectin was 

associated with improvements in the HOMA score 

without weight loss in the model (p = 0.02), but the 

association was no longer significant after adjustment 

for weight loss (Table 3). Additional adjustment for 

energy expenditure at baseline and 6 months did not 

alter the results.  

 

Table 2:  Multiple regression models of total and HMW 

adiponectin levels on baseline HOMA measure (N = 

143). 

 

Table 3: Multiple regression models of total and HMW 

adiponectin levels on change in HOMA measure at 6 

months (N = 143). 

 

Discussion 

A better understanding of the extent of the 

association of adiponectin with IR in obesity might help 

clarify mechanisms of insulin sensitivity, which in turn, 

might be beneficial in identifying preventive approaches 

to enhance insulin sensitivity and thereby reduce the 

risk for developing diabetes. The study's findings 

revealed that the higher baseline levels of total and 

HMW adiponectin levels were significantly associated 

with lower HOMA score, independent of body weight. 

At 6 months there were significant reductions in the 

HOMA score and weight, which paralleled the 

improvements in total and HMW adiponectin levels. 

The increase in total adiponectin was inversely 

associated with a decrease in the HOMA score 

independent of baseline weight and weight change. 

However, the significant association between changes in 

HMW adiponectin level and the HOMA score was 

attenuated after adjustment for weight change.   

There were significant inverse associations of 

total and HMW adiponectin levels with the HOMA 

score at baseline, even after adjusting for baseline 

weight, indicating an independent association of total 

and HMW adiponectin levels with the HOMA score 

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regardless of the degree of obesity. The association 

between total adiponectin and HOMA is consistent with 

findings from previous studies among individuals with 

type 2 diabetes,
22

  a representative community adult 

population,
6
 and a community-based cohort with and 

without the metabolic syndrome.
5
 The DPP study also 

reported an inverse association between baseline total 

adiponectin levels and future diabetes independent of 

baseline adiposity among individuals at increased risk 

for diabetes.
12

 The findings suggest the persistence of an 

independent role of not only total adiponectin but also 

HMW adiponectin levels in relation to IR among a 

generally healthy overweight/obese population with no 

diabetes or clinical vascular disease.  

The association between changes in total and 

HMW adiponectin levels and HOMA scores were 

examined separately after 6 months of intervention. The 

degree of univariate association between HOMA and 

total and HMW adiponectin levels at both baseline and 

6 months remained unchanged. There were 

intervention-associated significant reductions in weight, 

the HOMA score and improvements in total, and HMW 

adiponectin levels. The increase in total and HMW 

adiponectin was associated with the change in weight 

suggesting that change in total and HMW adiponectin 

levels might reflect body weight change. The multiple 

regression analysis showed that an increased level of 

total adiponectin contributed to improved insulin 

sensitivity independent of baseline weight and change in 

weight. Although the estimate for change in total 

adiponectin decreased by 34% when change in weight 

was added to the model, these results indicate that 

improvements in total adiponectin level contributed to 

improved insulin sensitivity above the usual clinical 

markers of diabetes. The present study highlights the 

importance of adiponectin in the development of IR and 

subsequent development of Type 2 diabetes. Thus, 

interventions, such as the one used in this study, that 

target weight loss and increase total adiponectin levels 

may improve insulin sensitivity and reduce the risk of 

diabetes for overweight individuals.  

A few studies have reported HMW adiponectin 

to have a stronger association than total adiponectin 

level in the incidence of type 2 diabetes
23,24

 and insulin 

sensitivity.
17-19,25

 Most of these studies either had only a 

single measurement of HMW adiponectin level,
19,23-25

 

were limited by the small sample size,
15,17,18

 or had a 

pharmacological intervention.
26

 There was a highly 

significant association between total and HMW at 

baseline. Bluher et al. reported no superiority of HMW 

adiponectin over total adiponectin values in predicting 

insulin sensitivity.
27

 Likewise, the study results also 

showed a similar magnitude of correlations between 

both total and HMW adiponectin levels with the HOMA 

score at baseline suggesting no clinical differences 

between total and HMW adiponectin levels in relation 

to insulin resistance.  

At 6 months, the significant association 

between changes in HMW adiponectin level and 

HOMA was attenuated after adjustment for change in 

weight and was no longer significant, despite an 

increase in HMW adiponectin that was more than 

double the increase in total adiponectin. This finding 

indicates a possible threshold level of HMW 

adiponectin that might be needed to have an 

independent effect on change in the HOMA score. 

Alternatively, a different pathway of an intervention-

associated change in HMW adiponectin level from the 

baseline HMW adiponectin level could not be ruled out 

as a possibility. Regardless of the mechanism, the study 

refutes the hypothesis of a predominant role of HMW 

adiponectin level over total adiponectin level in relation 

to IR. The study also provided a unique opportunity to 

examine if baseline or intervention associated changes 

in total and HMW adiponectin levels were more 

strongly associated with IR. The degree of association 

between total and HMW adiponectin level were 

stronger at baseline than the relationship between 

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Central Asian Journal of Global Health 

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changes in total adiponectin and the HOMA score at 6 

months. Moreover, the significant association between 

change in HMW adiponectin level and HOMA score 

was taken over by weight loss. Consistent with the 

findings of Mather et al.,
12

 baseline total and HMW 

adiponectin levels were more closely related to IR than 

the changes in these measures at 6 months. 

The potential mechanism of how plasma 

adiponectin levels influence IR is still not known. A 

higher level of adiponectin level has been reported to 

increase fatty acid oxidation with subsequent reduction 

of triglycerides thereby directly sensitizing the body to 

insulin and reserving IR in animal models of obesity 

and diabetes
28

 and in humans.
25

 Through in vitro 

studies, adiponectin has been shown to trigger the 

protein kinase, an insulin independent enzyme known to 

stimulate glucose use and increase fatty acid oxidation 

in skeletal muscle.
4
 It has been reported that some 

inflammatory markers, such as tumor necrosis factor-α, 

interleukin-6 or C-reactive protein have an adiponectin 

inhibitory effect, which in turn may lead to IR.
7,29

 It is 

possible that the levels of these markers decrease with 

the corresponding increase in adiponectin levels with 

weight loss and may improve insulin sensitivity.  

A main limitation of the study included a 

measure of IR with a surrogate marker. However, 

HOMA derived from the mathematical model has been 

shown to be an adequate indicator of IR and has been 

used in many epidemiological and clinical studies. Also, 

the generalizability of these findings may be limited due 

to the relatively homogenous study population; 

however, the minority representation exceeded that of 

the local community. The strengths of the study 

included the measurements of both total and HMW 

adiponectin. An additional strength was its longitudinal 

design and examination of the relationship between total 

and HMW adiponectin levels with IR cross-sectionally 

and over time. Moreover, the clinical measures were 

obtained via a standardized protocol and assays were 

performed with good precision and the study included a 

larger sample than what has been reported in the 

literature. 

 

Conclusions 

An increased level of total adiponectin 

contributed to improved insulin sensitivity regardless of 

baseline weight and weight loss. However, the 

association of change in total adiponectin and HOMA 

score was modest compared to baseline measures 

suggesting that the cross-sectional measure of total 

adiponectin might be a comparable indicator of IR and 

subsequent risk of developing diabetes among 

overweight or obese adults.  These findings provide 

support for the importance of adiponectin levels and a 

need for their improvements to prevent diabetes.  Thus, 

interventions that enhance adiponectin secretion or 

action may have potential for diabetes risk reduction. 

Improvements in the HMW adiponectin level were 

largely explained by the weight loss suggesting the role 

of HMW adiponectin level is no more important than 

that of total adiponectin in relation to improved insulin 

sensitivity. These findings provide evidence for the 

importance of weight loss as a significant public health 

preventive measure to enhance adiponectin levels 

among the studied population, which could impact the 

progression of atherosclerosis and associated metabolic 

diseases. 

 

Acknowledgements  

Thank you to the participants of the SMART 

trial for their time; the Project Director, Mindi Styn, 

PhD and the Data Manager, Edvin Music, MSIS. The 

ancillary study was supported by the 5
th

 Annual 

Epidemiology Small Grant Program, University of 

Pittsburgh Graduate School of Public Health, 

Department of Epidemiology. The parent study was 

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CENTRAL ASIAN JOURNAL OF GLOBAL HEALTH 

 

 

This work is licensed under a Creative Commons Attribution-Noncommercial 

-No Derivative Works 3.0 United States License. 

 

This journal is published by the University Library System of the University of Pittsburgh as part  

of its D-Scribe Digital Publishing Program, and is cosponsored by the University of Pittsburgh Press. 

 

Central Asian Journal of Global Health 

Volume 2, No. 2 (2013) | ISSN 2166-7403 (online) | DOI 10.5195/cajgh.2013.55 | http://cajgh.pitt.edu 

  

 

supported by the following grants: NIDDK, #RO1-

DK58631 and partial support by NIH K24 Award, 

NR010742. The conduct of the study was also 

supported by the Data Management Core of the Center 

for Research in Chronic Disorders NIH-NINR #P30-

NR03924, the Obesity and Nutrition Research Center 

NIH-NIDDK #DK-046204, and the General Clinical 

Research Center, NIH-NCRR-GCRC #5MO1-RR00056 

at the University of Pittsburgh. 

A poster based on these data was presented at 

the 50
th 

Annual American Heart Association 

Epidemiology and Prevention Council/Nutrition 

Physical Activity and Metabolism Conference in San 

Francisco, CA on 5
th

 March 2010.  

 

References 

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sheet.  http://www.who.int/mediacentre/factsheets/fs311/en/. 

Accessed 2013 Aug 10. 

2. Trayhurn P, Wood IS. Adipokines: inflammation and the 

pleiotropic role of white adipose tissue. Br J Nutr. 2004 

Sep;92(3):347-355. 

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an adipose-specific protein, adiponectin, in obesity. Biochem 

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stimulates glucose utilization and fatty-acid oxidation by 

activating AMP-activated protein kinase. Nat Med. 2002 

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5. Hivert MF, Sullivan LM, Fox CS, et al. Associations of 

adiponectin, resistin, and tumor necrosis factor-alpha with 

insulin resistance. J Clin Endocrinol Metab. 2008 

Aug;93(8):3165-3172. 

6. Hung J, McQuillan BM, Thompson PL, Beilby JP. 

Circulating adiponectin levels associate with inflammatory 

markers, insulin resistance and metabolic syndrome 

independent of obesity. Int J Obes (Lond). 2008 

May;32(5):772-779. 

7. Mojiminiyi OA, Abdella NA, Al Arouj M, Ben Nakhi A. 

Adiponectin, insulin resistance and clinical expression of the 

metabolic syndrome in patients with Type 2 diabetes. 

International Journal of Obesity. 2007;31(2):213-220. 

8. Lindsay RS, Funahashi T, Hanson RL. Adiponectin and 

development of type 2 diabetes in the Pima Indian population. 

Lancet. 2002;360:57-58. 

9. Heidemann C, Hoffmann K, Spranger J, et al. A dietary 

pattern protective against type 2 diabetes in the European 

Prospective Investigation into Cancer and Nutrition (EPIC)--

Potsdam Study cohort. Diabetologia. 2005 Jun;48(6):1126-

1134. 

10. Saltevo J, Laakso M, Jokelainen J, Keinanen-

Kiukaanniemi S, Kumpusalo E, Vanhala M. Levels of 

adiponectin, C-reactive protein and interleukin-1 receptor 

antagonist are associated with insulin sensitivity: a population-

based study. Diabetes Metab Res Rev. 2008 Jul-

Aug;24(5):378-383. 

11. O'Leary VB, Jorett AE, Marchetti CM, et al. Enhanced 

adiponectin multimer ratio and skeletal muscle adiponectin 

receptor expression following exercise training and diet in older 

insulin-resistant adults. Am J Physiol Endocrinol Metab. 2007 

Jul;293(1):E421-427. 

12. Mather KJ, Funahashi T, Matsuzawa Y, et al. Adiponectin, 

change in adiponectin, and progression to diabetes in the 

Diabetes Prevention Program. Diabetes. 2008 Apr;57(4):980-

986. 

13. Polak J, Kovacova Z, Jacek M, et al. An increase in 

plasma adiponectin multimeric complexes follows hypocaloric 

diet-induced weight loss in obese and overweight pre-

menopausal women. Clin Sci (Lond). 2007 Jun;112(11):557-

565. 

14. Xydakis AM, Case CC, Jones PH, et al. Adiponectin, 

inflammation, and the expression of the metabolic syndrome in 

obese individuals: the impact of rapid weight loss through 

caloric restriction. J Clin Endocrinol Metab. 2004 

Jun;89(6):2697-2703. 

15. Abbasi F, Chang SA, Chu JW, et al. Improvements in 

insulin resistance with weight loss, in contrast to rosiglitazone, 

are not associated with changes in plasma adiponectin or 

adiponectin multimeric complexes. Am J Physiol Regul Integr 

Comp Physiol. 2006 Jan;290(1):R139-144. 

16. Wing RR, Phelan, S. Long-term weight loss maintenance. 

Am J Clin Nutr. 2005;82(Suppl.):222S-225S. 

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adiponectin oligomer composition by moderate weight 

reduction. Diabetes. 2005 Sep;54(9):2712-2719. 

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http://www.who.int/mediacentre/factsheets/fs311/en/


 

 

ACHARYA 

 

This work is licensed under a Creative Commons Attribution-Noncommercial 

-No Derivative Works 3.0 United States License. 

 

This journal is published by the University Library System of the University of Pittsburgh as part  

of its D-Scribe Digital Publishing Program, and is cosponsored by the University of Pittsburgh Press. 

 

Central Asian Journal of Global Health 

Volume 2, No. 2 (2013) | ISSN 2166-7403 (online) | DOI 10.5195/cajgh.2013.55 | http://cajgh.pitt.edu 

 

 

18. Fisher FF, Trujillo ME, Hanif W, et al. Serum high 

molecular weight complex of adiponectin correlates better with 

glucose tolerance than total serum adiponectin in Indo-Asian 

males. Diabetologia. 2005 Jun;48(6):1084-1087. 

19. Hara K, Horikoshi M, Yamauchi T, et al. Measurement of 

the high-molecular weight form of adiponectin in plasma is 

useful for the prediction of insulin resistance and metabolic 

syndrome. Diabetes Care. 2006 Jun;29(6):1357-1362. 

20. Burke LE, Choo J, Music E, Styn MA, Steenkiste AR, 

Warziski M. PREFER study: a randomized clinical trial testing 

treatment preference and two dietary options in behavioral 

weight management-rationale, design and baseline 

characteristics. Contemp Clin Trials. 2006;27:34-48. 

21. Ainsworth BE, Haskell WL, Whitt MC, et al. Compendium 

of physical activities: an update of activity codes and MET 

intensities. Med Sci Sports Exerc. 2000 Sep;32(9 Suppl):S498-

504. 

22. Weyer C, Funahashi T, Tanaka S, et al. 

Hypoadiponectinemia in obesity and type 2 diabetes: close 

association with insulin resistance and hyperinsulinemia. J Clin 

Endocrinol Metab. 2001 May;86(5):1930-1935. 

23. Heidemann C, Sun Q, van Dam RM, et al. Total and high-

molecular-weight adiponectin and resistin in relation to the risk 

for type 2 diabetes in women. Ann Intern Med. 2008 Sep 

2;149(5):307-316. 

24. Nakashima R, Kamei N, Yamane K, Nakanishi S, 

Nakashima A, Kohno N. Decreased total and high molecular 

weight adiponectin are independent risk factors for the 

development of type 2 diabetes in Japanese-Americans. J Clin 

Endocrinol Metab. 2006 Oct;91(10):3873-3877. 

25. Lara-Castro C, Luo N, Wallace P, Klein RL, Garvey WT. 

Adiponectin multimeric complexes and the metabolic syndrome 

trait cluster. Diabetes. Jan 2006 Jan;55(1):249-259. 

26. Salani B, Briatore L, Andraghetti G, Adami GF, Maggi D, 

Cordera R. High-molecular weight adiponectin isoforms increase 

after biliopancreatic diversion in obese subjects. Obesity (Silver 

Spring). 2006 Sep;14(9):1511-1514. 

27. Bluher M, Brennan AM, Kelesidis T, et al. Total and high-

molecular weight adiponectin in relation to metabolic variables 

at baseline and in response to an exercise treatment program: 

comparative evaluation of three assays. Diabetes Care. 2007 

Feb;30(2):280-285. 

28. Haluzik M, Parizkova J, Haluzik MM. Adiponectin and its 

role in the obesity-induced insulin resistance and related 

complications. Physiol Res. 2004;53(2):123-129. 

29. Bruun JM, Lihn AS, Verdich C, et al. Regulation of 

adiponectin by adipose tissue-derived cytokines: in vivo and in 

vitro investigations in humans. Am J Physiol Endocrinol Metab. 

2003 Sep;285(3):E527-533. 

  

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ACHARYA 

 

 

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of its D-Scribe Digital Publishing Program and is cosponsored by the University of Pittsburgh Press. 

 

Central Asian Journal of Global Health 

Volume 2, No. 2 (2013) | ISSN 2166-7403 (online) | DOI 10.5195/cajgh.2013.55 | http://cajgh.pitt.edu 

  

 

Table 1. Daily dietary goals. 

Baseline  

weight (lbs) 

Prescribed daily goals 

Energy intake  

(kcal) 

Total fat intake 

(g)* 

Male Female Male Female 

< 200 1500 1200 42 33 

≥ 200 1800 1500 50 42 

     * 25% of the total energy intake for everyone.  

 

  

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ACHARYA 

 

 

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of its D-Scribe Digital Publishing Program and is cosponsored by the University of Pittsburgh Press. 

 

Central Asian Journal of Global Health 

Volume 2, No. 2 (2013) | ISSN 2166-7403 (online) | DOI 10.5195/cajgh.2013.55 | http://cajgh.pitt.edu 

  

 

Table 2:  Multiple regression models of total and HMW adiponectin levels on baseline HOMA measure (N = 143). 

Models Baseline HOMA R
2
 Models Baseline HOMA R

2
 

Estimate s.e. P Estimate s.e. P 

Model 1 

    Adiponectin (ug/ml) 

 

-0.28 

 

0.05 

 

< 0.001 

 

0.17 

Model 1 

   HMW (ug/ml) 

 

-0.42 

 

0.09 

 

< 0.001 

 

0.14 

Model 2  

   Adiponectin (ug/ml) 

   Gender 

   Race 

   Age (yr) 

 

-0.29 

-0.12 

-0.40 

-0.02 

 

0.05 

0.55 

0.37 

0.02 

 

< 0.001 

0.83 

0.28 

0.27 

 

0.18 

Model 2 

   HMW (ug/ml) 

   Gender 

   Race 

   Age (yr) 

 

-0.45 

-0.10 

-0.52 

0.01 

 

0.09 

0.56 

0.38 

0.02 

 

< 0.001 

0.85 

0.17 

0.40 

 

0.15 

Model 3 

   Adiponectin (ug/ml) 

   Gender 

   Race 

   Age (yr) 

   Weight (kg)  

 

-0.26 

0.45 

-0.46 

0.02 

0.06 

 

0.05 

0.34 

0.01 

0.02 

0.01 

 

< 0.001 

0.39 

0.18 

0.20 

< 0.001 

 

0.30 

Model 3 

   HMW (ug/ml) 

   Gender 

   Race 

   Age (yr) 

   Weight (kg) 

 

-0.38 

0.44 

0.55 

0.02 

0.06 

 

0.09 

0.54 

0.36 

0.02 

0.01 

 

< 0.001 

0.42 

0.12 

0.32 

< 0.001 

 

0.27 

HMW= high molecular weight; HOMA= homoeostasis model assessment of insulin resistance. 

Reference groups: gender-males, race- white 

  

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CENTRAL ASIAN JOURNAL OF GLOBAL HEALTH 

 

 

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of its D-Scribe Digital Publishing Program, and is cosponsored by the University of Pittsburgh Press. 

 

Central Asian Journal of Global Health 

Volume 2, No. 2 (2013) | ISSN 2166-7403 (online) | DOI 10.5195/cajgh.2013.55 | http://cajgh.pitt.edu 

  

 

Table 3: Multiple regression models of total and HMW adiponectin levels on change in HOMA measure at 6 months (N = 143). 

Models Change in  HOMA R
2
 Models Change in  HOMA R

2
 

Estimate s.e. P Estimate s.e. P 

Model 1 

   Adiponectin Δ (ug/ml) 

 

-0.25 

 

0.09 

 

0.004 

 

0.06 

Model 1 

   HMW Δ (ug/ml) 

 

-0.34 

 

0.14 

 

0.02 

 

0.04 

Model 2  

   Adiponectin Δ (ug/ml) 

   Gender 

   Race 

   Age (yr) 

 

-0.25 

0.95 

0.38 

0.01 

 

0.08 

0.43 

0.29 

0.01 

 

0.005 

0.03 

0.20 

0.9 

 

0.11 

Model 2  

   HMW Δ (ug/ml) 

   Gender 

   Race 

   Age (yr) 

 

-0.32 

  0.99 

  0.33 

  0.0003 

 

0.15 

0.43 

0.30 

0.01 

 

0.03 

0.02 

0.28 

0.98 

 

0.09 

Model 3 

   Adiponectin Δ (ug/ml) 

   Gender 

   Race 

   Age (yr) 

   Baseline weight (kg)  

 

-0.26 

0.64 

0.44 

-0.000 

-0.03 

 

0.09 

0.43 

0.29 

0.02 

0.009 

 

0.003 

0.14 

0.13 

0.97 

0.003 

 

0.16 

Model 3 

   HMW Δ (ug/ml) 

   Gender 

   Race 

   Age (yr) 

   Baseline weight (kg)  

 

-0.34 

0.68 

0.38 

-0.001 

-0.03 

 

0.15 

0.44 

0.29 

0.02 

0.009 

 

0.02 

0.12 

0.19 

0.92 

0.003 

 

0.14 

Model 4 

   Adiponectin Δ (ug/ml) 

   Gender 

   Race 

   Age (yr) 

   Baseline weight (kg) 

   Weight Δ (kg) 

 

-0.17 

0.06 

0.46 

0.0005 

-0.03 

0.10 

 

0.08 

0.42 

0.27 

0.01 

0.009 

0.02 

 

0.04 

0.88 

0.09 

0.97 

0.005 

< 0.0001 

 

0.27 

Model 4 

   HMW Δ (ug/ml) 

   Gender 

   Race 

   Age (yr) 

   Baseline weight (kg) 

   Weight Δ (kg) 

 

-0.18 

0.10 

0.40 

0.000 

-0.02 

0.10 

 

0.14 

0.48 

0.27 

0.01 

0.008 

0.02 

 

0.21 

0.82 

0.14 

0.99 

0.006 

< 0.0001 

 

0.26 

HMW=high molecular weight; HOMA= homoeostasis model assessment of insulin resistance; Δ=change. 

Changes values were defined as 6 months - baseline.  

Reference groups: gender-males, race- white  

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of its D-Scribe Digital Publishing Program and is cosponsored by the University of Pittsburgh Press. 

 

Central Asian Journal of Global Health 

Volume 2, No. 2 (2013) | ISSN 2166-7403 (online) | DOI 10.5195/cajgh.2013.55 | http://cajgh.pitt.edu 

  

 

Figure 1. Proposed link among adiposity, adiponectin, insulin resistance and diabetes. 

Obesity 

 

↑ Adiposity 

 

↓ Adiponectin 

 

 

↓ Glucose uptake ↑ Gluconeogenesis 

(muscle)  (liver) 

 

 

Insulin Resistance 

 

 

Diabetes 

  

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CENTRAL ASIAN JOURNAL OF GLOBAL HEALTH 

 

 

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Central Asian Journal of Global Health 

Volume 2, No. 2 (2013) | ISSN 2166-7403 (online) | DOI 10.5195/cajgh.2013.55 | http://cajgh.pitt.edu 

  

 

Figure 2. PREFER trial flowchart (included only 6-mo assessment). 

 

 

  

Screened for eligibility by phone (n=932) 

Sent screening packets (n=425) 

Returned 5-Day Food Diary (n=218) 

Invited to Information Session (n=298) 

Attended Baseline Assessment 

(n=204) 

Randomized (n=200) 

PREFER - NO PREFER - YES 

SBT (n=48) 

Completed 6-month 

assessment 

(n=42, 87.5%) 

SBT+LOV (n=35) 

Completed 6-

month assessment       

(n=29, 82.9%) 

 

 

(n=29, 82.9%) 

 

(n=29, 82.9%) 

SBT (n=48) 

Completed 6-month 

assessment         

(n=41, 85.4%) 

 

(n=41, 85.4%) 

SBT+LOV (n=45) 

Completed 6-month 

assessment         

(n=39, 86.7%) 

 

(n=39, 86.7%) 

Discarded (n=15) 

Ineligible (n=9) 

Included in this ancillary study (N=143)* 

STD-D = Standard Diet; LOV-D = Lacto-Ovo-Vegetarian Diet 

*Blood samples on 94.7% of participants who attended the 6-mo assessment were 

stored and analyzed 

 

 

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ACHARYA 

 

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Central Asian Journal of Global Health 

Volume 2, No. 2 (2013) | ISSN 2166-7403 (online) | DOI 10.5195/cajgh.2013.55 | http://cajgh.pitt.edu 

 

 

Figure 3. Measures at baseline and 6-month assessments. 

 

1

10

100

1000

baseline  6-mo

Weight (kg)

BMI (kg/m2)

Glucose (mg/dl)

Insulin (uU/mg)

HOMA

Adiponectin (ug/ml)

HMW (ug/ml)

* 
* 

o 

* 

* 
* * 

* 

* 

* 

+ 

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