Correlations of serum leptin and leptin resistance with depression and anxiety in patients with type 2 diabetes.

AIM: The associations of serum leptin/soluble leptin receptor (sObR) and leptin resistance with symptoms of depression and anxiety were investigated in patients with type 2 diabetes (T2D). METHODS: We report the results of two cross-sectional studies, performed 2 years apart, that included 216 and 237 T2D patients, respectively. Symptoms of depression and anxiety were assessed with specific questionnaires (Patient Health Questionnaire-9, Center for Epidemiologic Studies Depression Scale, and Generalized Anxiety Disorder-7, respectively). Laboratory data (including leptin and sObR) were collected, and free leptin index (FLI), as an estimate of leptin resistance, was calculated. One hundred forty patients had laboratory data available on both occasions, and were evaluated longitudinally. Simple and multiple correlations between depression/anxiety and parameters of interest were performed. RESULTS: In both studies, serum leptin levels were higher, whereas resting energy expenditure/leptin ratios were lower in T2D patients with depressive and moderate-severe anxiety symptoms. In the second study, patients with depressive symptoms had higher FLI and lower sObR levels, while those with moderate-severe anxiety only had higher FLI. Depression scores correlated with serum leptin (r = 0.29, [95%CI: 0.14-0.42]; r = 0.32, [95%CI: 0.18-0.45]) and FLI (r = 0.30, [95%CI: 0.15-0.43]; r = 0.32, [95%CI: 0.17-0.45]; P < 0.0001 for all). Multiple regression analyses identified leptin (ß = 0.167; t ratio = 1.98) and FLI (ß = 2.935, t ratio = 2.44) (P < 0.05 for both) as variables that significantly contributed to depressive symptoms. Depressive symptoms were present in significantly more patients with leptin levels in the highest versus the lowest quartiles on both evaluations (odds ratio: 5.98, 95%CI [1.76-20.32], P < 0.01). CONCLUSION: Depressive and moderate-severe anxiety symptoms were associated with high leptin concentrations and leptin resistance in T2D patients.

Serum leptin and leptin resistance correlations with NAFLD in patients with type 2 diabetes.

AIMS: Leptin/leptin resistance has been suggested to play a role in nonalcoholic fatty liver disease (NAFLD), and therefore we investigated the correlation of leptin/leptin-receptor system with markers of hepatic steatosis (HS) and fibrosis (HF) in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: In 159 T2D subjects with disease duration of 6.0 (0.0-27.0) years, HS was evaluated by semi-quantitative ultrasonographic scores and by clinical/biochemical variables: Fatty liver index and Hepatic steatosis index. HF was evaluated by NAFLD fibrosis score (NAFLD-FS). Serum leptin and leptin receptor (sObR) concentrations were measured and leptin resistance estimated by Free Leptin Index (FLpI). Both simple and multiple correlations between the HS and HF with the three parameters of interest were examined. RESULTS: Leptin levels and FLpI correlated with diabetes duration (0.25 [95%CI: 0.09-0.39] and 0.24 [95%CI: 0.08-0.39]; P < 0.01 for both). 76.1% of T2D patients had HS and 29% had HF. The univariate analysis indicated positive correlations of HS indexes with serum leptin, FLpI, and negative correlations with serum sObR (P < 0.0001 for all). In the multiple regression analysis leptin, sObR, FLpI, waist-to-hip ratio, HbA1c, lipids, and HOMA-IR correlated independently with HS (P < 0.0001 for all). Although the univariate analyses indicated weak correlations of NAFLD-FS with leptin, sObR, and FLpI, in the multiple regression analyses, only age and waist independently predicted HF. CONCLUSION: In patients with T2D, HS correlated positively with serum leptin and leptin resistance, and negatively with sObR, along with variables of adiposity and metabolic control, but neither of them made a significant contribution to HF.