Publications by authors named "Simeon Taylor"
Evolving Approaches for Pharmacological Therapy of Obesity.
Annu Rev Pharmacol Toxicol
September 2024
Obesity is a global health concern. Progress in understanding the physiology of obesity and weight reduction has provided new drug targets. Development and testing of new antiobesity medications (AOMs) has the potential to quickly expand options for treatment.
View Article and Find Full Text PDFGLP1R agonists and precision medicine: In search of predictive biomarkers.
J Clin Endocrinol Metab
August 2024
Although clinical guidelines recommend measuring total plasma 25-hydroxyvitamin D (25[OH]D) to assess vitamin D (VitD) status, this index does not account for 3-fold inter-individual variation in VitD binding protein (VDBP) level. We present 3 individuals with total plasma 25(OH)D levels of 10.8 to 12.
View Article and Find Full Text PDFArticle Synopsis
- DPP4 inhibitors like sitagliptin are commonly used to treat type 2 diabetes, and this study aimed to explore genetic factors that influence individual responses to the drug.
- In a pilot study with 47 healthy volunteers, sitagliptin was shown to significantly lower glucose levels during an oral glucose tolerance test (OGTT) and increase early insulin secretion.
- The study noted sex differences in glucose and insulin levels over time, with females showing higher levels, but no significant sex-related differences in the drug's effect on insulin secretion were found, highlighting the T30:T60 ratio as a key metric for evaluating DPP4 inhibitor responses.
Article Synopsis
- The body has mechanisms to maintain calcium and vitamin D levels, with PTH playing a crucial role.
- A study was conducted with 11 individuals who had vitamin D deficiency to investigate how these mechanisms work and to evaluate vitamin D status after supplementation.
- Results showed significant increases in vitamin D levels after supplementation, and a specific ratio (1,25(OH)2D/24,25(OH)2D) was found to effectively predict vitamin D metabolism, highlighting the suppression of 24-hydroxylase enzyme activity as a key protective mechanism against vitamin D deficiency.
Uncoupler therapy for NAFLD: is flushing a possible harbinger of a safety concern?
Lancet Gastroenterol Hepatol
February 2024
Article Synopsis
- This study investigates how genetic factors influence the responses to DPP4 inhibitors, like sitagliptin, used to treat type 2 diabetes.
- A pilot study with 47 healthy volunteers showed that sitagliptin significantly reduced glucose levels and increased insulin secretion during an oral glucose tolerance test (OGTT).
- The findings also highlighted sex differences in glucose and insulin levels but indicated that these differences did not affect the overall response to sitagliptin.
Article Synopsis
- Canagliflozin, a diabetes medication, may increase bone fracture risk by lowering vitamin D levels and raising parathyroid hormone (PTH), prompting concerns about its safety.
- The study explored whether vitamin D deficiency increased vulnerability to these effects and if vitamin D3 supplementation could provide protection, involving 11 individuals from the Amish community.
- Results showed that vitamin D3 supplementation significantly raised vitamin D levels and mitigated the adverse changes in bone-related biomarkers caused by canagliflozin, suggesting that vitamin D3 could be protective in deficient individuals.
Aim: To validate pharmacodynamic responses to sodium-glucose co-transporter-2 (SGLT2) inhibitors and test for association with genetic variants in SLC5A4, SLC5A9, and SLC2A9.
Methods: Canagliflozin (300 mg), a SGLT2 inhibitor, was administered to 30 healthy volunteers. Several endpoints were measured to assess clinically relevant responses, including drug-induced increases in urinary excretion of glucose, sodium and uric acid.
Context: The body has evolved homeostatic mechanisms to maintain free levels of Ca and 1,25-dihydroxyvitamin D [1,25(OH)D] within narrow physiological ranges. Clinical guidelines emphasize important contributions of PTH in maintaining this homeostasis.
Objective: To investigate mechanisms of homeostatic regulation of vitamin D (VitD) metabolism and to apply mechanistic insights to improve clinical assessment of VitD status.
Article Synopsis
- Glucagon-like peptide-1 receptor agonists, like exenatide, offer benefits for type 2 diabetes patients including better blood sugar control, weight loss, and lower cardiovascular risks, leading to a study aimed at finding genetic factors influencing drug effectiveness.
- A pilot study involving 62 healthy volunteers tested exenatide versus saline, revealing that exenatide significantly boosted insulin secretion and glucose clearance but had a minimal effect on insulin sensitivity.
- The findings highlight the importance of specific glucose metabolism measurements and support further research to explore genetic influences on the effectiveness of diabetes medications like semaglutide.
Article Synopsis
- Canagliflozin may increase the risk of bone fractures by lowering levels of 1,25-dihydroxyvitamin D and raising parathyroid hormone (PTH), particularly in individuals with vitamin D deficiency.
- A study tested the effects of vitamin D3 supplementation on bone health in 11 vitamin D deficient participants from the Amish community by administering canagliflozin before and after supplementation.
- Results showed that vitamin D3 significantly raised 25(OH)D and 24,25(OH)D levels, while reducing the adverse effects of canagliflozin on 1,25(OH)D and PTH, indicating that vitamin D3 can protect against these effects.
Article Synopsis
- GLP1R agonists, like exenatide, help manage type 2 diabetes by improving blood sugar control, promoting weight loss, and reducing cardiovascular risks, but individual responses to these drugs differ widely.
- Exenatide significantly enhanced insulin secretion and glucose disappearance in a study involving 62 healthy volunteers, indicating its potential impact on glucose metabolism.
- The findings validate the use of the FSIGT method for ongoing research into how genetic factors may influence responses to GLP1R agonists, highlighting key measures like insulin secretion and glucose effectiveness.
Aim: SGLT2 inhibitors provide multiple benefits to patients with type 2 diabetes - including improved glycemic control and decreased risks of cardiorenal disease. Because drug responses vary among individuals, we initiated investigations to identify genetic variants associated with the magnitude of drug responses.
Methods: Canagliflozin (300 mg) was administered to 30 healthy volunteers.
Insulin-resistant diabetes in Rabson-Mendenhall syndrome (RMS) is relatively unresponsive to first-line antidiabetic treatments, including metformin and insulin. We report 2 patients with RMS treated with 2 different sodium-glucose cotransporter inhibitors 2: empagliflozin in an 11-year-old boy and dapagliflozin in a 12-year-old girl. In the first patient, we began empagliflozin at 2.
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- Increased levels of low-density lipoprotein cholesterol (LDL-C) and fibrinogen are major risks for cardiovascular disease, and a specific genetic variant (p.Asn352Ser) in an Amish population is linked to lower levels of both.
- This genetic variant leads to a significant reduction in LDL-C (by 13.9 mg/dL) and fibrinogen (by 29 mg/dL), correlating with a lower risk of coronary artery disease as shown in a large analysis involving nearly 545,000 subjects.
- The study indicates that modifying protein galactosylation might be a promising strategy for preventing cardiovascular issues, as evidenced by reduced LDL-C and fibrinogen levels noted in experiments with genetically altered mice.
Diabetes mellitus is a major public health problem, affecting about 10% of the population. Pharmacotherapy aims to protect against microvascular complications, including blindness, end-stage kidney disease, and amputations. Landmark clinical trials have demonstrated that intensive glycemic control slows progression of microvascular complications (retinopathy, nephropathy, and neuropathy).
View Article and Find Full Text PDFIdentifying genes that result in monogenic diabetes can provide insights that can build a scientific foundation for precision medicine. At present, nearly 20% of neonatal diabetes cases have unknown causes. In this issue of the JCI, De Franco and Lytrivi et al.
View Article and Find Full Text PDFSummary: A patient with atypical partial lipodystrophy who had a transient initial response to metreleptin experienced acute worsening of her metabolic state when neutralizing antibodies against metreleptin appeared. Because her metabolic status continued to deteriorate, a therapeutic trial with melanocortin-4 receptor agonist setmelanotide, that is believed to function downstream from leptin receptor in the leptin signaling system, was undertaken in an effort to improve her metabolic status for the first time in a patient with lipodystrophy. To achieve this, a compassionate use (investigational new drug application; IND) was initiated (NCT03262610).
View Article and Find Full Text PDFSGLT2 inhibitors as adjunctive therapy for type 1 diabetes: balancing benefits and risks.
Lancet Diabetes Endocrinol
December 2019
Article Synopsis
- * Eight clinical trials examining SGLT2 inhibitors like canagliflozin and dapagliflozin in type 1 diabetes show that while they effectively lower HbA1c levels, this effect diminishes over time beyond 8-12 weeks.
- * However, there are significant risks associated with SGLT2 inhibitors, notably a six-fold increase in diabetic ketoacidosis risk, raising concerns about the overall safety and risk-to-benefit ratio for their use in type 1 diabetes patients.