Diabetic microangiopathy is a major cause of disability and long-term mortality in patients with type 1 diabetes mellitus (T1DM). As an essential micronutrient in the human body, magnesium participates in a variety of enzymatic reactions and plays a vital role in maintaining intracellular homeostasis, bone metabolism, neuromuscular function, as well as regulating inflammation and coagulation. However, clear evidence regarding the relationship between magnesium, coagulation abnormalities and microvascular complications in T1DM patients remains lacking.
A recent study published in Nutrition & Diabetes focused on children and adolescents with T1DM. It found that magnesium levels in this population were significantly lower than in healthy controls, and magnesium deficiency was closely associated with poor glycemic control, impaired coagulation function and diabetic microvascular complications, providing new evidence for the early prevention and intervention of complications in this group.
Hypomagnesemia and coagulopathy are common in diabetic patients, especially in those with type 2 diabetes, and magnesium deficiency can increase thrombotic risk. Nevertheless, the underlying mechanisms linking hypomagnesemia, coagulopathy and thrombotic risk in T1DM patients have not been fully elucidated.
Magnesium is an essential nutrient, acting as a cofactor for approximately 600 enzymes and an activator of 200 enzymes. It plays a key role in the homeostatic regulation of sodium, potassium and calcium, as well as in the formation, transfer and utilization of adenosine triphosphate (ATP). Meanwhile, magnesium can influence the coagulation cascade by competing with calcium ions; in vitro studies have demonstrated its anticoagulant effects, and magnesium sulfate is also used as an anticoagulant in blood collection.
Furthermore, magnesium homeostasis is closely related to insulin metabolism. Insulin can promote magnesium reabsorption by regulating the activity of the TRPM6 channel in the distal convoluted tubules, and magnesium is involved in insulin secretion and signal transduction. Previous studies have shown that plasma magnesium levels in T1DM patients are significantly lower than in healthy individuals and are negatively correlated with glycemic control.
With regard to vascular complications, hypomagnesemia may exacerbate diabetes-related vascular damage by interfering with inositol transport, elevating inflammatory factor levels and promoting the formation of advanced glycation end products. Plasminogen activator inhibitor‑1 (PAI‑1), a key antifibrinolytic factor, is closely associated with thrombotic risk, but its role in children and adolescents with T1DM has not been systematically investigated. This study aimed to clarify the relationship between serum magnesium levels, coagulation function and diabetic microvascular complications.
This was a case-control cross-sectional study that included 46 children and adolescents with T1DM and 46 age- and sex-matched healthy controls. The T1DM group was further divided into a complication subgroup (17 patients) and a non-complication subgroup (29 patients) based on the presence or absence of microvascular complications. T1DM was diagnosed according to the 2022 ISPAD criteria. Patients with hyperlipidemia, hypertension, obesity, hypocalcemia, coagulation disorders, or those taking medications affecting coagulation were excluded.
All participants underwent clinical evaluation and biochemical testing. Clinical assessment included BMI measurement, the Magnesium Deficiency Questionnaire (MDQ‑10), fundoscopy and the Toronto Clinical Scoring System (TCSS). Biochemical tests included serum magnesium, HbA1c, coagulation parameters [prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR)], PAI‑1, blood lipids and urinary microalbumin. Statistical analysis was performed using SPSS 27.0, with P<0.05 considered statistically significant.
The results showed that serum magnesium levels in children with T1DM (mean 1.3 mg/dl, range 0.6–1.5 mg/dl) were significantly lower than in healthy controls (P<0.001), and 28.3% of patients had symptoms related to magnesium deficiency (tingling, muscle cramps). The T1DM group with microvascular complications had significantly lower magnesium levels than the group without microvascular complications (P<0.001).
Compared with healthy controls, children with T1DM had significantly shorter PT and aPTT, and significantly higher PAI‑1 levels (all P<0.001). In patients with microvascular complications, PT and aPTT were further shortened and PAI‑1 further elevated, both significantly higher than in the non-complication subgroup (P<0.001).
Levels of HbA1c, triglycerides and urinary microalbumin in the T1DM group were all higher than in healthy controls (P<0.001). These indices were further increased in patients with microvascular complications, significantly exceeding those in the non-complication subgroup (P<0.001).
Correlation analysis revealed that serum magnesium levels were positively correlated with PT, aPTT and high-density lipoprotein (HDL), and negatively correlated with HbA1c, PAI‑1, triglycerides, urinary microalbumin and daily insulin dose. Multiple regression analysis further showed that in children and adolescents with T1DM, serum magnesium levels were independently associated with diabetes duration (P=0.015), HbA1c (P=0.001), PT (P=0.034), aPTT (P=0.001), PAI‑1 (P=0.001) and urinary microalbumin (P=0.005).