Increased serum adiponectin levels in type 1 diabetic patients with microvascular complications

Abstract

Aims/hypothesis: Low serum adiponectin (ADPN) has been associated with increased risk of cardiovascular disease (CVD) and retinopathy in patients with type 2 diabetes mellitus. In type 1 diabetic patients, the relationship between ADPN and the presence of vascular complications is largely unknown. Methods: We investigated the relationship between serum ADPN and the presence of retinopathy, nephropathy and CVD in patients with type 1 diabetes, divided into matched groups with normoalbuminuria and no retinopathy (n=67), simplex retinopathy (n=106) or proliferative retinopathy (n=19), and nephropathy with simplex (n=62) or proliferative retinopathy (n=137). Healthy control subjects (n=25) were included. Results: Serum ADPN was increased in subjects with type 1 diabetes compared with control subjects (p<0.0001). Further, serum ADPN was higher in patients with than in those without nephropathy (p<0.0001). It was also higher in normoalbuminuric patients with than in those without proliferative retinopathy (p<0.0001). These differences remained significant after adjustment for known risk factors (p<0.03). CVD was also associated with elevated ADPN levels (p<0.05), but this difference became insignificant after risk factor adjustment. The most important predictor of serum ADPN was sex (r 2 =19%) in normoalbuminuric patients and GFR in patients with nephropathy (r 2 =18%). Conclusion/interpretation: Patients with type 1 diabetes and microvascular complications have higher serum levels of ADPN than patients without complications. It remains to be clarified whether elevated levels of ADPN are pathogenically related to the development of microvascular complications or represent a beneficial counter-regulatory response.

The development of microalbuminuria is associated with raised longitudinal adiponectin levels in female but not male adolescent patients with type 1 diabetes

“…Previous cross-sectional studies in adults with type 1 diabetes have shown a variable relationship between adiponectin levels and glycaemic control, with a negative [1], a positive [11] or no correlation at all [13]. In these studies, differences between the sexes were either not found or not reported.…”

“…Adiponectin Serum adiponectin was analysed with an inhouse time-resolved immunofluorometric assay based on commercial reagents (R & D Systems, Abingdon, UK) as recently described [13]. All samples were analysed in duplicates in a final dilution of 1:206.…”

“…In adults with type 1 diabetes, higher adiponectin levels have been observed compared with controls [10], which, paradoxically, may be associated with microalbuminuria [11,12], reduced glomerular filtration rate [11,12], overt nephropathy and retinopathy [13]. Such observations conflict with data showing associations between insulin resistance and risk of microvascular complications in type 1 diabetes [14].…”

Association of fasting glucagon and proinsulin concentrations with insulin resistance

“…The glucagon assay (developed in J. Holst's laboratory in Copenhagen, Denmark) is highly specific for the free C terminus of the molecule, and therefore specific for pancreatic glucagon, with the following assay characteristics: sensitivity <1 pmol/l, within-assay CV <5% at 20 pmol/l, between-assay CV <12%. Serum adiponectin was assayed by a novel, in-house timeresolved immunofluorimetric method, previously described in detail [15], which measures total circulating adiponectin (including high-and low-molecular-mass isoforms).…”

“…IFG and IGT were grouped together as IGR (n=152 or 11.7% of the total cohort). Insulin sensitivity was expressed as the ratio of the M value, averaged over the final 40 min of the 2 h clamp and normalised for fat-free mass (FFM; measured by electrical bioimpedance [15] In either sex, glucagon and proinsulin increased across sex-specific quartiles of IR, whereas adiponectin displayed the opposite trend (p≤0.02 for all; Fig. 1).…”