AIM:To analyze the ocular findings of patients who received lifelong leptin therapy due to congenital leptin deficiency(CLD),an extremely rare condition.METHODS:A prospective,cross-sectional comparative study was perf...AIM:To analyze the ocular findings of patients who received lifelong leptin therapy due to congenital leptin deficiency(CLD),an extremely rare condition.METHODS:A prospective,cross-sectional comparative study was performed on six patients with CLD and 13 healthy age-and sex-matched controls.The central corneal thickness(CCT),anterior chamber depth(ACD),axial length(AL),keratometry(K1,K2),optical coherence tomography(OCT),and OCT angiography parameters were compared between the leptin and control groups at the baseline visit.The change in these measurements in leptin patients over a two-year period was analyzed.RESULTS:CLD patients had lower mean AL,ACD,and CCT(P≤0.012 for all).Mean K1,K2(P≤0.047 for both),choroidal thickness(P≤0.001),and central ganglion cell layer(GCL)thickness(P=0.029)were higher in the leptin group.Perifoveal superficial capillary plexus(SCP)density was decreased in all quadrants except the temporal region(P<0.05),and parafoveal deep capillary plexus(DCP)density was decreased in the superior hemisphere,temporal quadrant(P≤0.036 for both)and nasal quadrant(P=0.048)in the leptin group.During the two-year follow-up,no changes in anterior and posterior segment measurements were observed in the leptin patients,except for subfoveal choroidal thickness(P<0.001).CONCLUSION:CLD patients exhibit structural alterations in both the anterior and posterior segments of the eye,including notable changes in retinal and choroidal vasculature.However,there is limited evidence concerning the influence of leptin therapy on the eye.展开更多
BACKGROUND Epigenetic regulation of leptin(LEP)plays a critical role in metabolic disorders,yet its promoter methylation patterns in lean diabetic populations remain poorly characterized.Emerging evidence suggests DNA...BACKGROUND Epigenetic regulation of leptin(LEP)plays a critical role in metabolic disorders,yet its promoter methylation patterns in lean diabetic populations remain poorly characterized.Emerging evidence suggests DNA methylation may precede clinical hyperglycemia,offering potential for early risk stratification.While obesity-associated LEP methylation is well-studied,lean Asian populations who exhibit high diabetes prevalence despite lower adiposity,represent an underexplored cohort.This study hypothesizes that LEP promoter methylation in peripheral leukocytes decreases progressively from normoglycemia to prediabetes and type 2 diabetes mellitus(T2DM),correlating inversely with serum LEP levels in lean Chinese adults[body mass index(BMI)<24 kg/m^(2)].AIM To investigate LEP promoter methylation status and its association with serum LEP levels across glycemic states in lean Chinese adults.METHODS We enrolled 392 participants including 120 normoglycemic controls,94 prediabetes[44 impaired fasting glucose(IFG)/50 impaired glucose tolerance(IGT)],178 T2DM aged 40-60 years with BMI<24 kg/m^(2).Genomic DNA from peripheral leukocytes underwent bisulfite conversion followed by methylation-specific PCR to assess CpG methylation in the LEP promoter.Serum LEP was quantified via enzyme-linked immunosorbent assay,with other parameters measured through standard assays.Statistical analyses included analysis of variance,χ²tests,and Pearson correlation(Bonferroni-corrected P value).RESULTS Methylation frequencies declined progressively:59.2%(controls)reduced to 43.6%(prediabetes;IFG:38.6%,IGT:48%)reduced to 31.5%(T2DM)(all P<0.05 vs controls;T2DM vs IGT:P=0.030).Serum LEP levels increased significantly in T2DM(16.94±4.19μg/L)vs controls(11.33±3.10μg/L;P=0.002),with intermediate values in prediabetes(IFG:13.79±3.32μg/L;IGT:12.62±4.81μg/L).A near-perfect inverse correlation between methylation and LEP levels was observed(r=-0.95,95%CI:-0.97 to-0.92,P<0.001),persisting after adjusting for age and BMI(β=-0.91,P<0.001).CONCLUSION LEP promoter hypomethylation parallels worsening glycemic status in lean Chinese adults,suggesting its potential as a blood-based epigenetic biomarker for diabetes progression,pending validation in longitudinal cohorts.展开更多
文摘AIM:To analyze the ocular findings of patients who received lifelong leptin therapy due to congenital leptin deficiency(CLD),an extremely rare condition.METHODS:A prospective,cross-sectional comparative study was performed on six patients with CLD and 13 healthy age-and sex-matched controls.The central corneal thickness(CCT),anterior chamber depth(ACD),axial length(AL),keratometry(K1,K2),optical coherence tomography(OCT),and OCT angiography parameters were compared between the leptin and control groups at the baseline visit.The change in these measurements in leptin patients over a two-year period was analyzed.RESULTS:CLD patients had lower mean AL,ACD,and CCT(P≤0.012 for all).Mean K1,K2(P≤0.047 for both),choroidal thickness(P≤0.001),and central ganglion cell layer(GCL)thickness(P=0.029)were higher in the leptin group.Perifoveal superficial capillary plexus(SCP)density was decreased in all quadrants except the temporal region(P<0.05),and parafoveal deep capillary plexus(DCP)density was decreased in the superior hemisphere,temporal quadrant(P≤0.036 for both)and nasal quadrant(P=0.048)in the leptin group.During the two-year follow-up,no changes in anterior and posterior segment measurements were observed in the leptin patients,except for subfoveal choroidal thickness(P<0.001).CONCLUSION:CLD patients exhibit structural alterations in both the anterior and posterior segments of the eye,including notable changes in retinal and choroidal vasculature.However,there is limited evidence concerning the influence of leptin therapy on the eye.
文摘BACKGROUND Epigenetic regulation of leptin(LEP)plays a critical role in metabolic disorders,yet its promoter methylation patterns in lean diabetic populations remain poorly characterized.Emerging evidence suggests DNA methylation may precede clinical hyperglycemia,offering potential for early risk stratification.While obesity-associated LEP methylation is well-studied,lean Asian populations who exhibit high diabetes prevalence despite lower adiposity,represent an underexplored cohort.This study hypothesizes that LEP promoter methylation in peripheral leukocytes decreases progressively from normoglycemia to prediabetes and type 2 diabetes mellitus(T2DM),correlating inversely with serum LEP levels in lean Chinese adults[body mass index(BMI)<24 kg/m^(2)].AIM To investigate LEP promoter methylation status and its association with serum LEP levels across glycemic states in lean Chinese adults.METHODS We enrolled 392 participants including 120 normoglycemic controls,94 prediabetes[44 impaired fasting glucose(IFG)/50 impaired glucose tolerance(IGT)],178 T2DM aged 40-60 years with BMI<24 kg/m^(2).Genomic DNA from peripheral leukocytes underwent bisulfite conversion followed by methylation-specific PCR to assess CpG methylation in the LEP promoter.Serum LEP was quantified via enzyme-linked immunosorbent assay,with other parameters measured through standard assays.Statistical analyses included analysis of variance,χ²tests,and Pearson correlation(Bonferroni-corrected P value).RESULTS Methylation frequencies declined progressively:59.2%(controls)reduced to 43.6%(prediabetes;IFG:38.6%,IGT:48%)reduced to 31.5%(T2DM)(all P<0.05 vs controls;T2DM vs IGT:P=0.030).Serum LEP levels increased significantly in T2DM(16.94±4.19μg/L)vs controls(11.33±3.10μg/L;P=0.002),with intermediate values in prediabetes(IFG:13.79±3.32μg/L;IGT:12.62±4.81μg/L).A near-perfect inverse correlation between methylation and LEP levels was observed(r=-0.95,95%CI:-0.97 to-0.92,P<0.001),persisting after adjusting for age and BMI(β=-0.91,P<0.001).CONCLUSION LEP promoter hypomethylation parallels worsening glycemic status in lean Chinese adults,suggesting its potential as a blood-based epigenetic biomarker for diabetes progression,pending validation in longitudinal cohorts.
