There is an explosion of information related to
adiponectin in the last decade. We know that adipose tissue secretes
many adipocytokines of which adiponectin modulates a number of vital
metabolic processes related to glucose homeostasis and fatty acid
catabolism [1]. It is exclusively secreted from adipose tissue into the
blood and is abundant in plasma at levels of 5-10 µg/mL. Girls have
higher levels than boys. Levels of the hormone are inversely correlated
with BMI and body fat percentage in adults. The association in infants
and young children is less clear.
Genomic studies have helped us to understand the
action of adiponectin better. Adiponectin self-associates into larger
structures. Three adiponectin oligomers bind together to form a trimer;
trimers self-associate to form hexamers, dodecamers or high molecular
mass (HMW) isoforms consisting of at least 12 to 18 protomers. Thus
adiponectin circulates in at least three different sub-forms. Each
isoform of adiponectin exerts distinct biological properties in target
tissues [2]. Recent studies indicate that HMW oligomer may be the most
biologically active form concerning glucose homeostasis, whereas the
central actions are attributed to the low molecular weight oligomers
[3].
Adiponectin modulates a number of metabolic processes
including those resulting in type 2 diabetes (T2DM), obesity, coronary
artery disease and metabolic syndrome. Contrary to expectations,
adiponectin is decreased in obesity. The association of low adiponectin
levels with obesity and hyperinsulinemia has been confirmed in cross
sectional studies in 5 and 10 year old children; however, the
association with hyperin-sulinemia is not completely independent of
obesity [4]. Probably adiponectin plays a less important role in whole
body insulin sensitivity in children.
In adults with T2DM, circulating levels of HMW
adiponectin are selectively decreased due to an impaired secretion of
this oligomer from adipocytes [5]. Their levels increase after weight
reduction and following bariatric surgery. Single-nucleotide
polymorphisms in the adiponectin gene associated with low plasma
adiponectin levels and T2DM have been identified.
The story is different in type 1 diabetes (T1DM).
Adult T1DM patients, especially with diabetic nephropathy have elevated
total levels of the adiponectin unlike T2DM. Adiponectin probably
increases as a compensatory response in these patients with
microvascular complications [4]. Renal failure may lead to the
stimulation of adiponectin production as a physiological response to
restrict endothelial damage. It may also decrease adiponectin clearance,
and the kidney may develop secondary resistance to adiponectin. Still
high total adiponectin levels were predictive of development of
microalbuminuria in T1DM in some studies suggesting a causal association
[1]. Studies on large cohorts of healthy subjects also have shown that
adiponectin levels increase before the onset of nephropathy.
Recent studies have shown that the levels of
adiponectin remain higher in persons with type 1 diabetes than in
non-diabetics, even after controlling for renal function, obesity and
HDL cholesterol. The absolute concentrations of total adiponectin and
all subforms were higher in T1DM patients than healthy controls. This
increase in concentration of total adiponectin was primarily caused by a
major increase of the HMW sub-form. This association was not associated
with gender or diabetic nephropathy status [2].
Compared to adults, studies in children are limited.
A longitudinal study from Germany showed that children and adolescents
with T1DM have BMI-dependent elevated serum adiponectin compared with
healthy children [6]. There were similar observations in obese diabetic
boys in an earlier study published in Indian Pediatrics [7]. In
this issue of the journal, Habeeb, et al. provide another
observation of adiponectin as a marker for complications in children
with T1DM [8].
How these deleterious effects of adiponectin are
induced is not well understood. In vitro experiments have
suggested that adiponectin may increase NFkB production. HMW oligomer
may be protective with inhibition of NFkB, whereas the low and medium
subforms are associated with nephropathy. Altered glycosylation of
lysine leading to changed adiponectin function has been postulated as
another mechanism.
Has adiponectin come of age as a routine test or as a
predictor of obesity, T2DM, T1DM or even development of microangiopathy
or comorbidities? Not yet. There are simpler and better clinical methods
now. To some extent it may have role in adult T2DM. Its utility in T1DM,
especially children, is far from clear.
Funding: None; Competing interests: None
stated.
References
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2003;148:293-300.
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