Hyperhomocysteinemia: A Predictor of Microvascular Complications in Type 2 Diabetes Mellitus

Background Diabetes mellitus (DM) is a very crippling illness that affects a large number of people around the world. Raised homocysteine levels are linked to a number of harmful health issues. It is possible that homocysteine contributes to the development of diabetic microangiopathy because it is involved in a complex and dynamic system of vascular damage and repair. Given that hyperhomocysteinemia can be treated nutritionally, this highly debated topic has significant scientific and therapeutic ramifications. Hence, the purpose of this study is to ascertain the correlation between hyperhomocysteinemia and microvascular complications in type 2 diabetes mellitus (T2DM). Thus, the expected outcomes of this study will be the discovery of a novel predictor of diabetic microangiopathy: elevated homocysteine. Aim This study aims to evaluate the levels of homocysteine in diabetes mellitus patients with and without microvascular complications and to find the association between hyperhomocysteinemia and microvascular complications of type 2 diabetes mellitus. Method This is a prospective observational study involving all type 2 diabetes mellitus patients from outpatient and inpatient settings from general medicine, endocrinology, nephrology, ophthalmology, and podiatry departments of Amrita Institute of Medical Sciences (AIMS), Kochi, conducted between February 2022 and June 2024. The study population is categorized as patients with complications and controls without complications. Fasting plasma homocysteine levels are compared. Based on the results of the mean and standard deviation (SD) of fasting plasma homocysteine among diabetic patients with complications (9.4±3.1) and without complications (7.4±2.8), as mentioned in an earlier publication, with 90% power and 95% confidence, the minimum sample size is approximately 46 participants in each group, totaling 92. Results Among the 92 study participants who are patients with diabetes mellitus, 46 were without any of the major or minor complications of diabetes mellitus, grouped as Group 1, and the remaining 46 had at least one of the minor complications of diabetes mellitus, grouped as Group 2. In the diabetic retinopathy population, the mean serum homocysteine was 17.1±5.4 µmol/L, while in those who do not have diabetic retinopathy, it was 9.8±4.3 µmol/L, with a significantly higher p-value of <0.001. In those with diabetic neuropathy, the mean serum homocysteine was 17.0±5.5 µmol/L, while in those without diabetic neuropathy, it was 9.9±4.3 µmol/L, which is significantly higher, with a p-value of <0.001. In the diabetic nephropathy population, the mean serum homocysteine was 17.7±4.9 µmol/L, while in those without diabetic nephropathy, it was 9.7±4.2 µmol/L, which is significantly higher, with a p-value of <0.001. Using the receiver operating characteristic (ROC) curve, the area under the curve (AUC) was 0.9, with a 95% confidence interval (CI) of 0.83-0.97. Serum homocysteine is showing higher AUC; hence, it can be used as a predictor of complications (p<0.001), and the cutoff is taken as 11.8 µmol/L, with a sensitivity of 83% and a specificity of 87%. Conclusion This study was able to draw a significant association between high levels of plasma homocysteine and microvascular complications such as diabetic neuropathy, nephropathy, and retinopathy.