Jee-Young Oh

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D I A B E T E S  &  M E T A B O L I S M  J O U R N A L
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Copyright © 2012 Korean Diabetes Association http://e-dmj.org
Diabetes Metab J 2012;36:412-414
Regional Adiposity, Adipokines, and Insulin Resistance 
in Type 2 Diabetes
Jee-Young Oh
Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
Corresponding author: Jee-Young Oh
Department of Internal Medicine, Ewha Womans University Mokdong 
Hospital, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 158-710, Korea
E-mail: jyoh@ewha.ac.kr
The prevalence of obesity is rapidly increasing worldwide, and 
obesity is a well-known risk factor for type 2 diabetes involv-
ing insulin resistance. In recent decades, marked environmen-
tal and lifestyle changes have occurred and led to increased 
obesity and obesity-related cardiovascular diseases in Korea. 
Obesity is a heterogeneous condition, and body fat location 
may have a more important impact on the development of 
cardiovascular risk factors and related diseases than total ex-
cess adiposity [1]. Excessive accumulation of visceral adipose 
tissue causes low-grade chronic inflammation, dyslipidemia, 
insulin resistance, type 2 diabetes, and cardiovascular diseases. 
Recently, regional distribution of fat mass seems to correlate 
with risk level; fat mass in the lower extremities has a protec-
tive effect against insulin resistance and dyslipidemia [2,3]. 
Gluteofemoral fat, as measured by thigh circumference, hip 
circumference or leg adipose tissue mass, is independently as-
sociated with low total- and low-density lipoprotein triglycer-
ide levels and high high-density lipoprotein cholesterol levels. 
A small amount of adiposity in the lower extremities is associ-
ated with higher insulin resistance and unfavorable glucose 
level [4]. 
 Increased leg adipose tissue mass is associated with lower 
aortic calcification and arterial stiffness as well as with a de-
creased progression of aortic calcification [5,6]. Hip circum-
ference was positively associated with plasma ascorbic acid 
level, an anti-oxidant marker, and might contribute to endo-
thelial protection [7]. 
 There are a few possible mechanisms to explain the protec-
tive role of lower extremity fat deposition. First, subcutaneous 
adipose tissue acts as a buffer for the daily influx of dietary lip-
ids, protecting other tissues from a lipid overflow associated 
with lipotoxicity [8]. Second, there is differential secretion of 
adipose tissue-related proteins, called adipokines. Gluteofem-
oral adipose tissue could contribute to a protective adipokine 
profile by secreting more beneficial adipokines and fewer in-
flammatory molecules compared with abdominal fat. 
 However, even though the negative association between low-
er extremity fat mass and insulin resistance is established, it is 
still unclear whether the lower extremity fat mass per se exerts 
beneficial effects on glucose metabolism independent of the 
mere absence of trunk fat. Several metabolic characteristics of 
adipocyte size and location might influence their metabolic 
consequences. Adipocytes in the lower extremities are larger, 
less sensitive to lipolytic stimuli, and more sensitive to insulin 
compared with those in the abdomen [9,10]. Although increas-
es in adipocyte number and size can occur with increasing 
obesity level, larger adipocytes are also associated with higher 
secretion of adipokines which favorably influence insulin re-
sistance [11]. The large adipocytes in the femoral region can 
result in higher insulin sensitivity and increased secretion of 
metabolically beneficial adipokines. This combination of fac-
tors may partially “offset” the detrimental influence of abdom-
inal adiposity and offer metabolic “defense” against additional 
glucose dysregulation [12]. 
Editorial
Obesity and Metabolic Syndrome
http://dx.doi.org/10.4093/dmj.2012.36.6.412
pISSN 2233-6079 · eISSN 2233-6087
413
Regional adiposity, adipokines, and insulin resistance in type 2 diabetes
Diabetes Metab J 2012;36:412-414http://e-dmj.org
 Trunk to leg fat ratio may have a different impact according 
to age and gender. With aging, this ratio increased more mark-
edly in women than men, because the women’s lower extremi-
ty fat mass remained much the same at all ages. According to 
the literature, the relationship between leg and trunk fat mass 
is associated with the risk of insulin resistance and dyslipid-
emia in obese women, both before and after menopause [2]. 
 Adipokines are biomarkers for fat mass, fat distribution, ad-
ipose tissue function, liver fat content, insulin sensitivity, and 
subclinical chronic inflammation associated with metabolic 
diseases. Circulating biomarkers for abdominal fat accumula-
tion include adiponectin, retinol binding protein-4 (RBP4), 
vaspin, chemerin, progranulin, and fetuin-A and others [13]. 
RBP4 is predominantly secreted from the liver, but is also ex-
pressed in adipocytes. Increased RBP4 expression in visceral 
adipose induces the increased serum RBP4 levels in tissues of 
patients with insulin resistance [14]. Adiponectin and letptin 
are more likely to be associated with impaired insulin sensitiv-
ity or insulin secretion, while RBP4 is associated with adverse 
fat distribution and insulin resistance. 
 In a recent issue of Diabetes & Metabolism Journal, Kim et 
al. [15] presented an article regarding the relationship of abso-
lute or relative adiposity to insulin resistance in obese women 
with type 2 diabetes. They measured the trunk fat mass and 
lower extremities fat mass and found that relative adiposity 
(defined by peripheral fat mass/trunk fat mass) was correlated 
with insulin resistance. They also observed the positive associ-
ation of total, central, and peripheral fat mass with adiponec-
tin and leptin levels, but not with RBP4 level. The regional adi-
posity was positively associated with serum adiponectin level 
and negatively associated with RBP4 level, suggesting the fa-
vorable effect of regional adiposity. However, regional adiposi-
ty was also positively associated with insulin resistance. Al-
though the authors did not discuss these conflicting results, 
they may be due to the age distribution of the study subject’s 
considering that peripheral fat mass does not change with age, 
while visceral adiposity is markedly increased after menopause. 
Additional studies in various conditions such as age, gender, 
obesity degree, and underlying disease condition will be helpful 
for understanding the metabolic effects of regional adiposity. 
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was re-
ported.
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Regional Adiposity, Adipokines, and Insulin Resistance in Type 2 Diabetes

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Regional Adiposity, Adipokines, and Insulin Resistance in Type 2 Diabetes

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