Associations Among Glycemic Variability, Hypomagnesemia, Thyroid Function, and Albuminuria in Patients With Type 2 Diabetes Mellitus: A Cross-Sectional Study.

Background Albuminuria is an important marker of diabetic kidney disease (DKD) and is associated with adverse renal and cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM). Although sustained hyperglycemia is a recognized contributor to DKD, glycated hemoglobin (HbA1c) does not fully capture short-term glycemic variability. Emerging evidence suggests that hypomagnesemia and altered thyroid function may be associated with albuminuria, but their combined relationships with albuminuria and the possible statistical mediating role of thyroid hormones remain unclear. This study was conducted to identify the associations of albuminuria with glycemic variability, serum magnesium, and thyroid function in T2DM patients. Materials and methods A cross-sectional study included 330 adults aged 30-84 years with T2DM of more than five years' duration. Continuous glucose monitoring (CGM)-derived measures, including mean glucose, glucose standard deviation (SD), coefficient of variation (CV), time in range (TIR), and mean amplitude of glycemic excursions (MAGE), were assessed alongside HbA1c, serum magnesium, free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and urinary albumin-to-creatinine ratio (UACR). Associations with albuminuria were examined using univariable and multivariable logistic regression, with additional correlation and exploratory regression-based mediation analysis. Ethical approval and written informed consent were obtained. Results Among 330 participants, 208 (63%) had normal UACR, 98 (29.7%) had microalbuminuria, and 24 (7.3%) had macroalbuminuria. Hypomagnesemia was associated with more than twofold higher odds of albuminuria in univariable analysis (odds ratio (OR)=2.26; 95% confidence interval (CI): 1.38-3.70; p=0.001). In Model IV, which was adjusted for demographic variables, higher HbA1c (OR=1.66; 95% CI: 1.34-2.05; p<0.001), SD (OR=1.63; 95% CI: 1.18-2.26; p=0.003), CV (OR=1.06; 95% CI: 1.01-1.10; p=0.016), and MAGE (OR=1.25; 95% CI: 1.07-1.45; p=0.005) were independently associated with higher odds of albuminuria. In contrast, higher FT3 was inversely associated with albuminuria (OR=0.46; 95% CI: 0.28-0.74; p=0.001). TIR, FT4, and TSH were not significantly associated with albuminuria in univariable analysis. HbA1c was negatively correlated with FT3 (ρ=-0.133; p=0.016). Similarly, SD was negatively correlated with FT3 (ρ=-0.227; p<0.001). Exploratory mediation analysis indicated that FT3 statistically accounted for 6.9% of the association between HbA1c and albuminuria and 21.4% of the association between glucose SD and albuminuria. Conclusion Greater glycemic variability and lower FT3 levels were independently associated with albuminuria in patients with T2DM, while hypomagnesemia was associated with albuminuria in univariable analysis. Exploratory mediation analysis suggested that FT3 statistically accounted for a modest proportion of the associations of HbA1c and glucose SD with albuminuria. These findings indicate that CGM-derived variability measures, alongside magnesium status and thyroid function, may provide complementary information in the assessment of DKD. Prospective multicenter studies are required to clarify the temporal relationships and clinical significance of these findings.