Association of Serum Leptin Levels With Progression of Diabetic Kidney Disease in Patients With Type 2 Diabetes

Abstract

OBJECTIVETo clarify the association of serum leptin levels with progression of diabetic kidney disease in patients with type 2 diabetes (T2D).RESEARCH DESIGN AND METHODSThis was an observational cohort study of 668 patients with T2D. Patients were classified into three groups by sex-specific tertile of leptin levels. Outcome measurements were the rate of change in estimated glomerular filtration rate (eGFR) and progression to a more advanced stage of albuminuria.RESULTSPatients with low or high leptin levels had a steeper eGFR decline (−2.07 and −2.14 mL/min/1.73 m2/year) than those with midrange leptin levels (−0.82 mL/min/1.73 m2/year; P < 0.01), whereas patients with low leptin levels had an elevated risk of progression of albuminuria as compared with those with high leptin levels (hazard ratio 3.125 [95% CI 1.302–7.499]).CONCLUSIONSBoth low and high serum leptin levels were risk factors for kidney function decline. Meanwhile, lower serum leptin levels were associated with progression of albuminuria.

Diabetic kidney disease: New clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology on “The natural history of diabetic kidney disease and treatment of hyperglycemia in patients with type 2 diabetes and impaired renal function”

“…Other biomarkers that have been associated with eGFR loss include: urinary high molecular weight adiponectin [118], adiponectin [119], type IV collagen [120,121], and haptoglobin [122,123]; circulating arginine vasopressin, as measured as copeptin [124], adipocyte FABP [125], fibroblast growth factor 21 [126], kininogen and kininogen fragments [127], the angiogenic factor leucine-rich a-2 glycoprotein 1 [128], the anti-ageing hormone soluble Klotho (low levels) [129], and leptin (both high and low levels) [130]; and erythrocyte total polyunsaturated fatty acids (PUFAs), n-3 PUFAs, and n-3/n-6 PUFA ratio, but not n-6 PUFAs (low levels) [106], all in T2D patients (except urinary collagen IV, in both T1D and T2D individuals). In addition, CKD273, a multidimensional urinary proteome classifier consisting of 273 protein fragments, predicted deterioration of renal function in patients with [131] and without [132] albuminuria and also development of microalbuminuria in normoalbuminuric individuals [133].…”

Coumarins as potential antidiabetic agents

“… Anti‐inflammation, anti‐oxidation and anti‐apoptosis: (a) islet inflammation and oxidative stress; (b) chronic adipose inflammation; (c) inflammatory cytokines (TNF‐α, IL‐6, IL‐1β) and chemokines (d) histone deacetylases; (e) 12/15‐lipoxygenase enzymes; (f) CXCR1/2 pathway intervention (CXCR1/2 neutralizing antibodies, CXCR1/2 antagonist, pepducin as a peptide inhibitor, Fractalkine (CX3CL1) ) (g) free fatty acid receptor 2 (FFAR2) agonists Stimulating insulin secretion: (a) enhancing incretin system (selective GLP‐1R agonists and DPP4 inhibitors) (b) sulfonylurea receptor 1(SUR1) agonists Insulin signal pathway: (a) insulin receptors (InsR) and its substrates (IRS1/2) expression; (b) Akt and AS160 (TBC1D4)/TBC1D1 phosphorylation (c) MAPKs; (d) glucose transporter 4 (GLUT4) expression or translocation; (e) PTP1B inhibition PPARγ agonists AMPK activation Suppression of α‐glucosidases SGLT2 inhibitors Key metabolic enzymes of neoglucogenesis, glycolysis, glycogenesis: (a) hexokinase (b) phosphofructokinase (c) glucose‐6‐phosphatase (d) fructose‐1,6‐bisphosphatase (e) liver glucokinase (f) glucose‐6‐phosphate dehydrogenase (g) pyruvate kinase (h) acetyl‐CoA carboxylases (ACCs) Rebalancing relevant hormones: (a) leptin; (b) adiponectin; (c) glucocorticoids …”

Obesity as an effect modifier of the association between leptin and diabetic kidney disease

“…The UK Prospective Diabetes Study reported the differences in the risk factors for the two renal outcomes 35 . We have shown that leptin levels had different effects on kidney function decline and the progression of albuminuria in patients with type 2 diabetes 15 . Second, the number of patients reaching the end-point was small, yielding less statistical power to observe the interaction between leptin levels and obesity.…”