4 research outputs found
“Impact Of Metformin Therpy on Serum Cobalamin and Homocysteine Among the Type II Diabetes Mellitus Patients”
Objective: The aim of the study is to observe the long-term treatment of metformin and its associated effect on Vitamin B12 among Type II Diabetes mellitus south Indian patients. Methods: An observational study conducted over a period of 54 months on Type II Diabetes mellitus patients who are in chronic therapy with metformin. The study described the Vitamin B12 levels among the Type II DM patients, which could alert the patients who are in the low and borderline range of serum Vitamin B12, which may prevent the risk of peripheral neuropathic complications and anaemic conditions, etc. Findings: Totally, 387 patients were enrolled as per the inclusion and exclusion criteria, including 232 males (59.94%) and 155 females (40.05%). A total of 39 patients had been observed to have low levels of Vitamin B12, among them 23 females (Mean 184.17 ± S.D. 10.69) and 16 males (Mean 185.31± S.D 7.56), followed by 16 patients found to be above the normal range of Vitamin B12, among them 02 females (Mean 991 ± S.D. 15.55) and 14 males (Mean 1578.14 ± S.D. 406.93), followed by 76 patients had been found to be borderline of Vitamin B12, among them 43 females (Mean 220.76 ± S.D 6.50). Conclusion: High doses of chronic Metformin therapy may alter Vitamin B12 levels. Some of the patients had an abnormally high level of serum Vitamin B12, whose medical condition should be ruled out, and such Patients’ diet histories were also cross-examined, which was a mixed normal diet, and they had various medical conditions. However, the high chances of metformin-associated effects on Vitamin B12 with higher doses and long-term therapy of metformin, whose duration was 10 to 20 years, Moreover, age is also an important factor, and the study reveals that, among genders, female populations had a higher rate of low-level Vitamin B12 than male populations. Patients in the age group between 50 and 65 years had a higher rate of low-level Vitamin B12 than other age groups, total 20 patients, among them 12 females (Mean 183.08 ± S.D. 13.17) and 8 males (Mean 185.5 ± S.D. 4.3). Patients with other comorbid conditions also had low levels and borderline levels of Vitamin B12 and had been on long-term metformin therapy. Further, homocysteine investigations had been done on low and borderline vitamin B12 patients. Investigation of homocysteine had been done on low range (39) and border line (76) of vitamin B12 patients. Among Low vitamin B12, 13 patients have elevated level of Homocysteine (6 males & 7 females). Among border line of vitamin B12, 4 patients (2 males and 3 females) have elevated level of Homocysteine. Therefore, our study concluded that chronic therapy and higher doses of metformin may lead to a deficit in serum Vitamin B12, which requires regular checks on Vitamin B12 among Type 2 DM patients to avoid the risk of Peripheral neuropathy and other complications
Succinate dehydrogenase/complex II is critical for metabolic and epigenetic regulation of T cell proliferation and inflammation.
Effective T cell-mediated immune responses require the proper allocation of metabolic resources to sustain growth, proliferation, and cytokine production. Epigenetic control of the genome also governs T cell transcriptome and T cell lineage commitment and maintenance. Cellular metabolic programs interact with epigenetic regulation by providing substrates for covalent modifications of chromatin. By using complementary genetic, epigenetic, and metabolic approaches, we revealed that tricarboxylic acid (TCA) cycle flux fueled biosynthetic processes while controlling the ratio of succinate/α-ketoglutarate (α-KG) to modulate the activities of dioxygenases that are critical for driving T cell inflammation. In contrast to cancer cells, where succinate dehydrogenase (SDH)/complex II inactivation drives cell transformation and growth, SDH/complex II deficiency in T cells caused proliferation and survival defects when the TCA cycle was truncated, blocking carbon flux to support nucleoside biosynthesis. Replenishing the intracellular nucleoside pool partially relieved the dependence of T cells on SDH/complex II for proliferation and survival. SDH deficiency induced a proinflammatory gene signature in T cells and promoted T helper 1 and T helper 17 lineage differentiation. An increasing succinate/α-KG ratio in SDH-deficient T cells promoted inflammation by changing the pattern of the transcriptional and chromatin accessibility signatures and consequentially increasing the expression of the transcription factor, PR domain zinc finger protein 1. Collectively, our studies revealed a role of SDH/complex II in allocating carbon resources for anabolic processes and epigenetic regulation in T cell proliferation and inflammation