Clinical Effects of Sodium-Glucose Transporter Type 2 Inhibitors in Patients With Partial Lipodystrophy.

OBJECTIVE: Severe insulin resistance syndromes, such as lipodystrophy, lead to diabetes, which is challenging to control. This study explored the safety and efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in a series of 12 patients with severe insulin resistance due to partial lipodystrophy. METHODS: A retrospective chart review of the safety (N = 22) and efficacy (N = 12) of SGLT2is in patients with partial lipodystrophy was conducted at our institution. The efficacy outcomes included hemoglobin A1C level, insulin dose, fasting plasma glucose level, C-peptide level, lipid profile, 24-hour urinary glucose excretion, estimated glomerular filtration rate, and blood pressure before and after 12 months of SGLT2i treatment. RESULTS: The hemoglobin A1C level decreased after SGLT2i treatment (at baseline: 9.2% ± 2.0% [77.0 ± 21.9 mmol/mol]; after 12 months: 8.4% ± 1.8% [68.0 ± 19.7 mmol/mol]; P = .028). Significant reductions were also noted in systolic (P = .011) and diastolic blood pressure (P = .013). There was a trend toward a decreased C-peptide level (P = .071). The fasting plasma glucose level, lipid level, and estimated glomerular filtration rate remained unchanged. The adverse effects included extremity pain, hypoglycemia, diabetic ketoacidosis (in a patient who was nonadherent to insulin), pancreatitis (in a patient with prior pancreatitis), and fungal infections. CONCLUSION: SGLT2is reduced the hemoglobin A1C level in patients with partial lipodystrophy, with a similar safety profile compared with that in patients with type 2 diabetes. After individual consideration of the risks and benefits of SGLT2is, these may be considered a part of the treatment armamentarium for these rare forms of diabetes, but larger trials are needed to confirm these findings.

Clinical Study on the Relationship between the SNP rs8192675 (C/C) Site of SLC2A2 Gene and the Hypoglycemic Effect of Metformin in Type 2 Diabetes.

This study investigates the correlation between the gene polymorphism of rs8192675 (C/C) locus of SLC2A2 in patients with type 2 diabetes (T2DM) and the efficacy of metformin. For this purpose, we have selected 110 T2DM patients (T2DM group) and 110 healthy people (control group) who were treated in our hospital from January 2019 to January 2020 as the research subjects. PCR-restriction fragment length polymorphism (PCR-RFLP) method detects the distribution frequency of gene polymorphism. The patients in the T2DM group were treated with metformin and followed up for 90 days to analyze the relationship between the efficacy of metformin and the SLC2A2 gene polymorphism. The genotypes of SLC2A2 rs8192675 in the control group and in the T2DM group conformed to the Hardy-Weinberg equilibrium law. Compared with the control group, the CT type and the CC type at rs8192675 in the T2DM group were significantly higher (P < 0.05). For rs8192675, there was no significant difference in TT, CT, CC FPG, 2hPBG, and HbA1c levels before treatment (P > 0.05); after metformin treatment, the reduction in FPG, 2hPBG, and HbA1c in CC patients was lower than that of TT and CT patients (P < 0.05). SLC2A2 gene polymorphism site rs8192675 CC type T2DM patients are sensitive to metformin and have a better hypoglycemic effect.

Emerging Concepts in Brain Glucose Metabolic Functions: From Glucose Sensing to How the Sweet Taste of Glucose Regulates Its Own Metabolism in Astrocytes and Neurons.

The astrocyte-neuron lactate shunt (ANLS) hypothesis is the most widely accepted model of brain glucose metabolism. However, over the past decades, research has shown that neuronal and astrocyte plasma membrane receptors, in particular, GLUT2, Kir6.2 subunit of the potassium ATP-channel, SGLT-3 acting as glucosensors, play a pivotal role in brain glucose metabolism. Although both ANLS hypothesis and glucosensor model substantially improved our understanding of brain glucose metabolism, the latter appears to be gaining more attention in the scientific community as the former could not account for new research data indicating that hypothalamic and brainstem neurons may not require astrocyte-derived lactate for energy. More recently, emerging evidences suggest a crucial role of sweet taste receptors in brain glucose metabolism. Furthermore, a couple of intracellular molecules acting as glucosensors have been identified in central astrocytes and neurons. This review integrates new data on the mechanisms of brain glucose sensing and metabolism. The role of the glucosensors including the sweet taste T1R2 + T1R3-mediated brain glucose-sensing and metabolism in brain glucose metabolic disorders is discussed. Possible role of glucose sensors (GLUT2, K-ATPKir6.2, SGLT3, T1R2 + T1R3) in brain diseases involving metabolic dysfunctions and the therapeutic significance in targeting central glucosensors for the treatment of these brain diseases are also discussed.