Obesity as an effect modifier of the association between leptin and diabetic kidney disease.
OBJECTIVE
Obesity has been shown to be a modifier of the association between leptin levels and cardiovascular events. We examined whether obesity modifies the association between serum leptin levels and the progression of diabetic kidney disease.


METHODS
This was an observational longitudinal study on patients with type 2 diabetes. We enrolled 410 and 348 patients in the eGFR and ACR cohorts, respectively. Patients were classified into three groups by sex-specific tertile of leptin levels. Obesity was defined as body mass index ≥25 kg/m(2). Outcomes were the rate of change in estimated glomerular filtration rate (eGFR) and progression to a more advanced stage of albuminuria.


RESULTS
In the eGFR cohort, the mean eGFR change during the median follow-up period of 4.7 years was -1.4 mL/min/1.73 m(2)/year. An interaction between leptin levels (low, medium or high) and obesity (present or absent) on the change in eGFR was detected (P interaction = 0.003). In the lean group, adjusted eGFR decline in patients with low leptin was steeper than that in patients with medium leptin (2.1 and 0.8 mL/min/1.73 m(2)/year, P = 0.023). In the obese group, patients with high leptin had a steeper adjusted eGFR decline than those with medium leptin (1.7 and 0.6 mL/min/1.73 m(2)/year, P = 0.044). In the ACR cohort, 29 patients showed progression of albuminuria during the median follow-up period of 3.9 years. There was no interaction between leptin levels and obesity on the outcome (P interaction = 0.094).


CONCLUSIONS
Obesity might modify the effects of leptin on kidney function decline in patients with type 2 diabetes.
Division of Nephrology and Hypertension Diabetes Center Tokyo Women's Medical University School of Medicine Tokyo Japan.
Ko
K
Hanai
Division of Nephrology and Hypertension Diabetes Center Tokyo Women's Medical University School of Medicine Tokyo Japan.
Tetsuya
T
Babazono
Division of Nephrology and Hypertension Diabetes Center Tokyo Women's Medical University School of Medicine Tokyo Japan.
Michino
M
Takagi
Division of Nephrology and Hypertension Diabetes Center Tokyo Women's Medical University School of Medicine Tokyo Japan.
Naoshi
N
Yoshida
Division of Nephrology and Hypertension Diabetes Center Tokyo Women's Medical University School of Medicine Tokyo Japan.
Izumi
I
Nyumura
Division of Nephrology and Hypertension Diabetes Center Tokyo Women's Medical University School of Medicine Tokyo Japan.
Kiwako
K
Toya
Division of Nephrology and Hypertension Diabetes Center Tokyo Women's Medical University School of Medicine Tokyo Japan.
Nobue
N
Tanaka
Diabetes Center Tokyo Women's Medical University School of Medicine Tokyo Japan.
Yasuko
Y
Uchigata
Diabetic kidney disease; Leptin; Obesity