Insulin Resistant States Contributed Differentially to the Earlier Renal tubular Injury in Chinese Young Overweight Individuals with Hyperglucagonemia

Background Hyperglucagonemia is associated to the metabolic dysregulation, but its early role in microvascular injury, especially with young and overweight state, remains unclear. Thus, this study investigates the association between hyperglucagonemia and renal tubular injury in Chinese young overweight with dysglycemic state, and compared the profile with Chinese aged type 2 diabetes (T2DM Aged). Methods The assessment was conducted on metabolic markers and renal tubular injury indicators. At 0, 30, and 120 minutes, the parameters of the oral glucose tolerance test (OGTT) were assessed. Analysis of relationships and predictors of renal impairment was conducted. Results Among young overweight patients, glucagon (GCG) levels were elevated in diabetic patients at both fasting and 30 minutes, with higher HOMA-IR and comparable HOMA-β. Elevated blood α1- and β2-MG were observed in newly diagnosed type 2 diabetic patients with hyperglucagonemia. However, when analyzed with T2DM aged (64.54 ± 10.91yrs), they exhibited elevated 30- and 120-minute GCG and reduced HOMA indices. In comparison to younger groups, aged patients exhibited profound elevated levels of α1MG. Correlational relationship analysis showed tubular markers in young patients significantly positively related to male gender, elevated FPG, HbA1c, insulin and GCG levels, as well as HOMA (P < 0.05), while ageing, elevated postprandial glucose, reduced insulin levels, postpone attenuating GCG in 30min and 120min, and decreased HOMA were significantly in T2DM Aged. The binary logistic regression analysis showed the risk of appearance of renal microvascular injury marker, UACR, in young patients was determined by 30-minute GCG (B = 0.105, OR = 1.111, P = 0.004) and increased eGFR (B = 0.050, OR = 1.052, P = 0.029), while it was associated with elevated HbA1c (B = 0.578, OR = 1.782, P = 0.002) and reduced eGFR (B=-0.039, OR = 0.962, P = 0.028) in the T2DM aged. Multilinear regression showed different tubular markers in young groups were differentially positively determined by FPG, insulin and C-peptide levels, 30minGCG and negatively with eGFR; for T2DM aged group, ageing, reduced eGFR and insulin levels, elevated postprandial GCG at 30min and 120min, reduced HOMA indices differentially contributed to the various elevated tubular markers. Conclusions Hyperglucagonemia and insulin resistance may serve as an early renal injury sign in the pathophysiology of overweight. While causes for microvascular and tubular injury were different between young overweight and aged T2DM patients which alert early effective bodyweight and metabolic management.