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.

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2. Leth H, Andersen KK, Frystyk J, Tarnow L, Rossing P, Paeving HH, et al. Elevated levels of high-molecular- weight adiponectin in type 1 diabetes. J Clin Endocrinol Metab. 2008;93:3186-91.

3. Oh DK, Ciaraldi T, Henry RR. Adiponectin in health and disease. Diabetes Obes Metab. 2007; 9:282-9.

4. Stefan N, Bunt JC, Salbe AD, Funahashi T, Matsuzawa Y, Tataranni PA. Plasma adiponectin concentrations in children: relationships with obesity and insulinemia. J Clin Endocrinol Metab. 2002; 87: 4652-6.

5. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001; 86:1930-5.

6. Galler A, Gelbrich G, Kratzsch J, Noack N, Kapellen T, Kiess W. Elevated serum levels of adiponectin in children, adolescents and young adults with type 1 diabetes and the impact of age, gender, body mass index and metabolic control: a longitudinal study. Eur J Endocrinol. 2007;157:481-9.

7. El-Mesallamy HO, Hamdy NM, Ibrahim SM. Adiponectin and pro-inflammatory cytokines in obese diabetic boys. Indian Pediatr. 2011; 48: 815-6.