scholarly journals Effect of luseogliflozin on bone microarchitecture in elderly patients with type 2 diabetes: Study protocol for a randomized controlled pilot trial using second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT)

2020 ◽  
Author(s):  
Ai Haraguchi ◽  
Riyoko Shigeno ◽  
Ichiro Horie ◽  
Shimpei Morimoto ◽  
Ayako Ito ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Fracture Risk ◽  
Bone Metabolism ◽  
Bone Microarchitecture ◽  
Pilot Trial ◽  
Quantitative Computed Tomography ◽  
Sglt2 Inhibitor ◽  
Peripheral Quantitative Computed Tomography ◽  
Sglt2 Inhibitors

Abstract Background Elderly patients with type 2 diabetes mellitus (T2DM) have an increased risk of bone fracture independent of their bone mineral density (BMD), which is explained mainly by the deteriorated bone quality in T2DM compared to non-diabetic adults. Sodium-glucose co-transporter (SGLT) 2 inhibitors have been studied in several trials in T2DM, and the Canagliflozin Cardiovascular Assessment Study showed an increased fracture risk related to treatment with the SGLT2 inhibitor canagliflozin, although no evidence of increased fracture risk with treatment with other SGLT2 inhibitors has been reported. The mechanism of the difference in the fracture risk between the SGLT2 inhibitors is unknown, but the differences among the SGLT2 inhibitors in the selectivity of SGLT2 against SGLT1 may affect bone metabolism, since among the SGLT2 inhibitors the selectivity of canagliflozin is lowest. We will investigate whether the SGLT2 inhibitor luseogliflozin, which has higher SGLT2 selectivity, affects bone metabolism by using high-resolution peripheral quantitative computed tomography (HR-pQCT) which provides direct in vivo morphometric information about the bone microarchitecture. Methods This is a single-center, randomized, open-label, active-controlled, parallel pilot trial. Eligible participants are elderly (age ≥60 years) individuals with T2DM with HbA1c levels at 7.0%–8.9%. A total of 24 participants will be allocated to either the luseogliflozin group (taking luseogliflozin) or control group (taking metformin) in a 1:1 ratio to compare the groups' changes in bone microarchitecture of radius and tibia which are analyzed by HR-pQCT before and 48 weeks after the administration of each medication. The laboratory data associated with glycemic control and bone metabolism will be collected every 12 weeks during the study. Recruitment began in June 2019. Discussion The reason we use metformin as an active control is to avoid yielding differences in glycemic control between the luseogliflozin and control groups. Besides, metformin is considered to have neutral effect on bone. This trial will reveal the effect of luseogliflozin on bone metabolism in elderly patients with T2DM.

scholarly journals Effect of luseogliflozin on bone microarchitecture in elderly patients with type 2 diabetes: Study protocol for a randomized controlled trial using second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT)

2019 ◽  
Author(s):  
Ai Haraguchi ◽  
Riyoko Shigeno ◽  
Ichiro Horie ◽  
Shimpei Morimoto ◽  
Ayako Ito ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Elderly Patients ◽  
Fracture Risk ◽  
Bone Metabolism ◽  
Bone Microarchitecture ◽  
Quantitative Computed Tomography ◽  
Sglt2 Inhibitor ◽  
Peripheral Quantitative Computed Tomography ◽  
Sglt2 Inhibitors

Abstract Background Elderly patients with type 2 diabetes mellitus (T2DM) have an increased risk of bone fracture independent of their bone mineral density (BMD), which is explained mainly by the deteriorated bone quality in T2DM compared to non-diabetic adults. Sodium-glucose co-transporter (SGLT) 2 inhibitors have been studied in several trials in T2DM, and the Canagliflozin Cardiovascular Assessment Study showed an increased fracture risk related to treatment with the SGLT2 inhibitor canagliflozin, although no evidence of increased fracture risk with treatment with other SGLT2 inhibitors has been reported. The mechanism of the difference in the fracture risk between the SGLT2 inhibitors is unknown, but the differences among the SGLT2 inhibitors in the selectivity of SGLT2 against SGLT1 may affect bone metabolism, since among the SGLT2 inhibitors the selectivity of canagliflozin is lowest. We will investigate whether the SGLT2 inhibitor luseogliflozin, which has higher SGLT2 selectivity, affects bone metabolism by using high-resolution peripheral quantitative computed tomography (HR-pQCT) which provides direct in vivo morphometric information about the bone microarchitecture.Methods This is a single-center, randomized, open-label, active-controlled, parallel pilot trial. Eligible participants are elderly (age ≥60 years) individuals with T2DM with HbA1c levels at 7.0%–8.9%. A total of 24 participants will be allocated to either the luseogliflozin group (taking luseogliflozin) or control group (taking metformin) in a 1:1 ratio to compare the groups' changes in bone microarchitecture of radius and tibia which are analyzed by HR-pQCT before and 48 weeks after the administration of each medication. The laboratory data associated with glycemic control and bone metabolism will be collected every 12 weeks during the study. Recruitment began in June 2019.Discussion The reason we use metformin as an active control is to avoid yielding differences in glycemic control between the luseogliflozin and control groups. Besides, metformin is considered to have neutral effect on bone. This trial will reveal the effect of luseogliflozin on bone metabolism in elderly patients with T2DM.

scholarly journals Ethnic Differences in Bone Microarchitecture

2020 ◽  
Vol 18 (6) ◽  
pp. 803-810
Author(s):  
Ruth Durdin ◽  
Camille M Parsons ◽  
Elaine Dennison ◽  
Nicholas C Harvey ◽  
Cyrus Cooper ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Bone Density ◽  
Fracture Risk ◽  
Ethnic Differences ◽  
Bone Microarchitecture ◽  
Imaging Techniques ◽  
Quantitative Computed Tomography ◽  
Peripheral Quantitative Computed Tomography ◽  
Fracture Incidence ◽  
Advanced Imaging

Abstract Purpose of the Review The aim of this review is to briefly introduce updates in global fracture epidemiology and then to highlight recent contributions to understanding ethnic differences in bone density, geometry and microarchitecture and consider how these might contribute to differences in fracture risk. The review focuses on studies using peripheral quantitative computed tomography techniques. Recent Findings Recent studies have contributed to our understanding of the differences in fracture incidence both between countries, as well as between ethnic groups living within the same country. In terms of understanding the reasons for ethnic differences in fracture incidence, advanced imaging techniques continue to increase our understanding, though there remain relatively few studies. Summary It is a priority to continue to understand the epidemiology, and changes in the patterns of, fracture, as well as the underlying phenotypic and biological reasons for the ethnic differences which are observed.

scholarly journals Longitudinal Evolution of Bone Microarchitecture and Bone Strength in Type 2 Diabetic Postmenopausal Women With and Without History of Fragility Fractures—A 5-Year Follow-Up Study Using High Resolution Peripheral Quantitative Computed Tomography

2021 ◽  
Vol 12 ◽  
Author(s):  
Ursula Heilmeier ◽  
Gabby B. Joseph ◽  
Courtney Pasco ◽  
Nhan Dinh ◽  
Soheyla Torabi ◽  
...  
Keyword(s):  
Bone Strength ◽  
Bone Disease ◽  
Bone Microarchitecture ◽  
Quantitative Computed Tomography ◽  
Fragility Fractures ◽  
Peripheral Quantitative Computed Tomography ◽  
Cortical Porosity ◽  
History Of ◽  
Type 2 Diabetic

IntroductionDiabetic bone disease is characterized by an increased fracture risk which may be partly attributed to deficits in cortical bone quality such as higher cortical porosity. However, the temporal evolution of bone microarchitecture, strength, and particularly of cortical porosity in diabetic bone disease is still unknown. Here, we aimed to prospectively characterize the 5-year changes in bone microarchitecture, strength, and cortical porosity in type 2 diabetic (T2D) postmenopausal women with (DMFx) and without history of fragility fractures (DM) and to compare those to nondiabetic fracture free controls (Co) using high resolution peripheral quantitative computed tomography (HR-pQCT).MethodsThirty-two women underwent baseline HR-pQCT scanning of the ultradistal tibia and radius and a FU-scan 5 years later. Bone microarchitectural parameters, including cortical porosity, and bone strength estimates via µFEA were calculated for each timepoint and annualized. Linear regression models (adjusted for race and change in BMI) were used to compare the annualized percent changes in microarchitectural parameters between groups.ResultsAt baseline at the tibia, DMFx subjects exhibited the highest porosity of the three groups (66.3% greater Ct.Po, 71.9% higher Ct.Po.Volume than DM subjects, p < 0.022). Longitudinally, porosity increased significantly over time in all three groups and at similar annual rates, while DMFx exhibited the greatest annual decreases in bone strength indices (compared to DM 4.7× and 6.7× greater decreases in failure load [F] and stiffness [K], p < 0.025; compared to Co 14.1× and 22.2× greater decreases in F and K, p < 0.020).ConclusionOur data suggest that despite different baseline levels in cortical porosity, T2D women with and without fractures experienced long-term porosity increases at a rate similar to non-diabetics. However, the annual loss in bone strength was greatest in T2D women with a history of a fragility fractures. This suggests a potentially non-linear course of cortical porosity development in T2D bone disease: major porosity may develop early in the course of disease, followed by a smaller steady annual increase in porosity which in turn can still have a detrimental effect on bone strength—depending on the amount of early cortical pre-damage.

scholarly journals SGLT2 inhibitors and the risk of diabetic ketoacidosis among adults with Type 2 Diabetes: A systematic review and meta-analysis

2021 ◽  
Author(s):  
Michael Colacci ◽  
John Fralick ◽  
Ayodele Odutayo ◽  
Michael Fralick
Keyword(s):  
Diabetic Ketoacidosis ◽  
Observational Studies ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Controlled Trials ◽  
Absolute Rate ◽  
Randomized Controlled

Importance: The risk of diabetic ketoacidosis (DKA) with sodium-glucose cotransporter-2 (SGLT2) inhibitors is unclear. Objective: To examine the risk of DKA with SGLT2 inhibitors in both observational studies and large clinical trials. Data Sources: Searches of PubMed, EMBASE and CENTRAL (inception to 15 April 2019) without language restrictions; conference proceedings; and reference lists. Study Selection: Randomized controlled trials and observational studies that quantified the rate of diabetic ketoacidosis with an SGLT2 inhibitor in comparison to another diabetes medication or placebo. Data Extraction and Synthesis: Two independent investigators abstracted study data and assessed the quality of evidence. Data were pooled using random effects models with the Hartung-Knapp-Sidik-Jonkman method. Main Outcome and Measures: Absolute event rates and hazard ratios for diabetic ketoacidosis were extracted from each study. Results: Seven randomized trials encompassing 42,375 participants and five cohort studies encompassing 318,636 participants were selected. Among the 7 randomized controlled trials, the absolute rate of DKA among patients randomized to an SGLT2 inhibitor ranged from 0.6 to 2.2 events per 1000 person years. Four randomized trials were included in the meta-analysis, and compared to placebo or comparator medication, SGLT2 inhibitors had a 2.4-fold higher risk of DKA (Relative Risk [RR] = 2.46 [95% CI, 1.16-5.21]; I2 = 0%; P = 0.54). Among the 5 observational studies, the absolute rate of DKA associated with SGLT2 inhibitor use ranged from 0.6 to 4.9 per 1000 person years and a 1.7-fold higher rate of DKA compared to another diabetes medication (RR = 1.74 [95% CI, 1.01-2.93]; I2 = 45%; P = 0.12). Conclusions and Relevance: In adults with type 2 diabetes, SGLT2 inhibitors increase the risk of DKA in both observational studies and large randomized clinical trials. Registration: CRD42019146855 Funding Source: None

scholarly journals Impact of sodium–glucose cotransporter 2 inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease with normoalbuminuria

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Akinobu Nakamura ◽  
Hideaki Miyoshi ◽  
Hiraku Kameda ◽  
Kumiko Yamashita ◽  
Yoshio Kurihara
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Creatinine Ratio ◽  
Sodium Glucose Cotransporter ◽  
Clinical Records

Abstract Background We compared the effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease (CKD) classified by degree of albuminuria. Methods A retrospective review of the clinical records of Japanese participants with type 2 diabetes (age > 20 years; SGLT2 inhibitor treatment > 2 years; estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) was conducted. Based on the urinary albumin-to-creatinine ratio (UACR) or urinary protein-to-creatinine ratio (UPCR) at the start of SGLT2 inhibitor administration, participants were categorized into three groups: normoalbuminuria (A1; UACR < 30 mg/g Cr or UPCR < 0.15 g/g Cr), microalbuminuria (A2; UACR 30 to < 300 mg/g Cr or UPCR 0.15 to < 0.50 g/g Cr), and macroalbuminuria (A3; UACR ≥ 300 mg/g Cr or UPCR ≥ 0.50 g/g Cr). The study outcome was a comparison of the rates of change in renal function evaluated by eGFR at 2 years after starting SGLT2 inhibitor among the three groups. Results A total of 87 participants (40 females, 47 males) were categorized into three groups: A1 (n = 46), A2 (n = 25), and A3 (n = 16). eGFR was similarly decreased at 2 years before starting SGLT2 inhibitor in all three groups. However, the decline in eGFR was ameliorated at 2 years after starting SGLT2 inhibitor, and eGFR was rather increased in the A1 and A2 groups. Interestingly, the rate of change in eGFR at 2 years after starting SGLT2 inhibitor in the A1 group was significantly higher than that in the A3 group. Conclusions These results demonstrate that more favorable effects of SGLT2 inhibitors on renal function were observed in participants with type 2 diabetes and CKD with normoalbuminuria compared with those with macroalbuminuria. Trial registration UMIN-CTR: UMIN000035263. Registered 15 December 2018

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