Associations of Plasma Glucagon Levels with Estimated Glomerular Filtration Rate, Albuminuria and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus

BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients. METHODS: Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUC(gla)]) levels were determined during oral glucose tolerance tests. Patients with an eGFR <60 mL/min/1.73 m(2) and/or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g who presented with diabetic retinopathy were identified as having DKD. RESULTS: Of the 2,436 recruited patients, fasting glucagon was correlated with eGFR and UACR (r=–0.112 and r=0.157, respectively; P<0.001), and AUC(gla) was also correlated with eGFR and UACR (r=–0.267 and r=0.234, respectively; P<0.001). Moreover, 31.7% (n=771) presented with DKD; the prevalence of DKD was 27.3%, 27.6%, 32.5%, and 39.2% in the first (Q1), second (Q2), third (Q3), and fourth quartile (Q4) of fasting glucagon, respectively; and the corresponding prevalence for AUC(gla) was 25.9%, 22.7%, 33.7%, and 44.4%, respectively. Furthermore, after adjusting for other clinical covariates, the adjusted odds ratios (ORs; 95% confidence intervals) for DKD in Q2, Q3, and Q4 versus Q1 of fasting glucagon were 0.946 (0.697 to 1.284), 1.209 (0.895 to 1.634), and 1.521 (1.129 to 2.049), respectively; the corresponding ORs of AUC(gla) were 0.825 (0.611 to 1.114), 1.323 (0.989 to 1.769), and 2.066 (1.546 to 2.760), respectively. Additionally, when we restricted our analysis in patients with glycosylated hemoglobin <7.0% (n=471), we found fasting glucagon and AUC(gla) were still independently associated with DKD. CONCLUSION: Both increased fasting and postchallenge glucagon levels were independently associated with DKD in T2DM patients.