Long‐Term Effects of <scp>Sglt2</scp> Deletion on Bone and Mineral Metabolism in Mice

Gerber, Claire; Wang, Xueyan; David, Véronique; Quaggin, Susan E.; Isakova, Tamara; Martin, Aline

doi:10.1002/jbm4.10526

Cited by 7 publications

(6 citation statements)

References 41 publications

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“…In an animal model, a long-term (25 weeks) inhibition of sodium-glucose cotransporter-2 did not modulate VD concentrations but it contributed to increased bone fragility [44]. In human studies, dapagliflozin did not affect VD concentrations [45], while canagliflozin decreased them (via a rapid increase in the serum phosphorus, fibroblast growth factor 23 and parathormone levels, with a potentially negative impact on bone health) [41] and empagliflozin slightly increased VD concentrations [46].…”

Section: Discussionmentioning

confidence: 90%

Relationship of vitamin D deficiency to cardiovascular disease and glycemic control in patients with type 2 diabetes mellitus: The Silesia Diabetes-Heart Project

Kwiendacz¹,

Nabrdalik²,

Wijata³

et al. 2023

Polish Archives of Internal Medicine

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There is no consistency in the literature between observational and interventional studies regarding vitamin D deficiency (VDD) and both cardiovascular disease (CVD) and glycemic control of diabetes. The outcomes of this observational study among Polish patients with type 2 diabetes revealed that 36% of participants have VDD. We did not find an association between VDD and CVD and the difference between groups in glycemic control of diabetes was insignificant.However we found that patients with VDD had higher prevalence of treatment with sodiumglucose co-transporter-2 inhibitors (SGLT-2i) compared to patients with vitamin D (VD) concentrations within the reference range, which is, to the best of our knowledge, a novel finding. This is of high importance given the concerns that SGLT-2i may possibly affect the bone turnover through a negative influence on VD concentration.

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Section: Discussionmentioning

confidence: 90%

Relationship of vitamin D deficiency to cardiovascular disease and glycemic control in patients with type 2 diabetes mellitus: The Silesia Diabetes-Heart Project

Kwiendacz¹,

Nabrdalik²,

Wijata³

et al. 2023

Polish Archives of Internal Medicine

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“…Clinical studies have found that SGLT2 inhibitors improve heart failure and cardiovascular outcomes in patients with T2DM ( 36 ). Evidence also showed that SGLT2 inhibitors may slightly increase calcium levels by reducing urinary calcium excretion ( 37 , 38 ). This evidence suggests that SGLT2 inhibitors may be beneficiary for T2DM patients with CAN, but further studies are needed.…”

Section: Discussionmentioning

confidence: 99%

The Predictive Value of Serum Calcium on Heart Rate Variability and Cardiac Function in Type 2 Diabetes Patients

Wang

et al. 2022

Front. Endocrinol.

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BackgroundCardiovascular autonomic neuropathy (CAN) is common in patients with type 2 diabetes mellitus (T2DM), mainly presented as decreased heart rate variability (HRV) which often leads to cardiac death. However, HRV measurement is not convenient in most clinics. Therefore, identifying high-risk patients for CAN in diabetes with easier measurements is crucial for the early intervention and prevention of catastrophic consequences.MethodsIn this cross-sectional study, 675 T2DM patients with normocalcemia were selected. Of these, they were divided into two groups: normal HRV group (n = 425, 100 ms≤ SDNN ≤180 ms) vs. declined HRV group (n = 250, SDNN <100 ms). All patients’ clinical data were collected and the correlation of clinical variables with HRV were analyzed by correlation and logistic regression analysis. The area below the ROC curve was used to evaluate the predictive performance of serum calcium on HRV.ResultsIn this study, declines in HRV were present in 37.0% of T2DM patients. Significant differences in albumin-adjusted serum calcium levels (CaA) (8.86 ± 0.27 vs. 9.13 ± 0.39 mg/dl, p <0.001) and E/A (0.78 ± 0.22 vs. 0.83 ± 0.26, p = 0.029) were observed between declined HRV and normal HRV groups. Bivariate linear correlation analysis showed that CaA and E/A were positively correlated with HRV parameters including SDNN (p < 0.001), SDNN index (p < 0.001), and Triangle index (p < 0.05). The AUC in the ROC curve for the prediction of CaA on HRV was 0.730 (95% CI (0.750–0.815), p < 0.001). The cutoff value of CaA was 8.87 mg/dl (sensitivity 0.644, specificity 0.814). The T2DM patients with CaA <8.87 mg/dl had significantly lower HRV parameters (SDNN, SDNN index, rMSSD, and triangle index) than those with CaA ≥8.87 mg/dl (p < 0.01, respectively). Multivariate logistic regression analysis showed a significantly increased risk of declined HRV in subjects with CaA level <8.87 mg/dl [OR (95% CI), 0.049 (0.024–0.099), p < 0.001].ConclusionsDeclined HRV is associated with a lower CaA level and worse cardiac function. The serum calcium level can be used for risk evaluation of declined HRV in T2DM patients even within the normocalcemic range.

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“…Inhibition of SGLT2 has been reported to potentially improve glucose control but may increase the risk of infection, malnutrition, and mortality [ 17 ]. The mutant mice showed normal serum calcium and phosphate, parathyroid hormone, vitamins D, and fibroblast growth factor levels [ 55 ]. Although no changes in trabecular or cortical bone micro-structure were observed in Sweet Pee mice, a decrease in cortical bone mineral density was reported compared to wild-type mice at 25 weeks [ 55 ].…”

Section: Renal Glucosuria Models In Experimental Animalsmentioning

confidence: 99%

“…The mutant mice showed normal serum calcium and phosphate, parathyroid hormone, vitamins D, and fibroblast growth factor levels [ 55 ]. Although no changes in trabecular or cortical bone micro-structure were observed in Sweet Pee mice, a decrease in cortical bone mineral density was reported compared to wild-type mice at 25 weeks [ 55 ]. Loss of SGLT2 function in mice may contribute to long-term bone fragility.…”

Section: Renal Glucosuria Models In Experimental Animalsmentioning

confidence: 99%

Mouse Models with SGLT2 Mutations: Toward Understanding the Role of SGLT2 beyond Glucose Reabsorption

Unno

Taguchi

Takagi³

et al. 2023

IJMS

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The sodium–glucose cotransporter 2 (SGLT2) mainly carries out glucose reabsorption in the kidney. Familial renal glycosuria, which is a mutation of SGLT2, is known to excrete glucose in the urine, but blood glucose levels are almost normal. Therefore, SGLT2 inhibitors are attracting attention as a new therapeutic drug for diabetes, which is increasing worldwide. In fact, SGLT2 inhibitors not only suppress hyperglycemia but also reduce renal, heart, and cardiovascular diseases. However, whether long-term SGLT2 inhibition is completely harmless requires further investigation. In this context, mice with mutations in SGLT2 have been generated and detailed studies are being conducted, e.g., the SGLT2−/− mouse, Sweet Pee mouse, Jimbee mouse, and SAMP10-ΔSglt2 mouse. Biological changes associated with SGLT2 mutations have been reported in these model mice, suggesting that SGLT2 is not only responsible for sugar reabsorption but is also related to other functions, such as bone metabolism, longevity, and cognitive functions. In this review, we present the characteristics of these mutant mice. Moreover, because the relationship between diabetes and Alzheimer’s disease has been discussed, we examined the relationship between changes in glucose homeostasis and the amyloid precursor protein in SGLT2 mutant mice.

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Long‐Term Effects of Sglt2 Deletion on Bone and Mineral Metabolism in Mice

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 7 publications

References 41 publications

Relationship of vitamin D deficiency to cardiovascular disease and glycemic control in patients with type 2 diabetes mellitus: The Silesia Diabetes-Heart Project

Relationship of vitamin D deficiency to cardiovascular disease and glycemic control in patients with type 2 diabetes mellitus: The Silesia Diabetes-Heart Project

The Predictive Value of Serum Calcium on Heart Rate Variability and Cardiac Function in Type 2 Diabetes Patients

Mouse Models with SGLT2 Mutations: Toward Understanding the Role of SGLT2 beyond Glucose Reabsorption

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