SGLT2 Inhibitors – The New Standard of Care for Cardiovascular, Renal and Metabolic Protection in Type 2 Diabetes: A Narrative Review

Seidu, Samuel; Alabraba, Vicki; Davies, Sarah; Newland-Jones, Philip; Fernando, Kevin; Bain, Stephen C.; Diggle, Jane; Evans, Marc; James, June; Kanumilli, Naresh; Milne, Nicola; Viljoen, Adie; Wheeler, David C.; Wilding, John P. H.

doi:10.1007/s13300-024-01550-5

Cited by 2 publications

(1 citation statement)

References 111 publications

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“…Moreover, other studies revealed, that GPR146 may be important in vascular remodelling, along with adipose tissue development and metabolism [ 4 , 5 ]. SGLT2 inhibitors (SGLT2i) are routinely prescribed drugs to T2DM patients with cardiovascular disease, though theirs cardioprotective effects are not fully elucidated [ 6 ]. Hypotheses include the beneficial impact of decreased volemic load due to iSGLT2, anti-inflammatory properties or a direct influence of SGLT2i on cardiomyocytes.…”

Section: Introductionmentioning

confidence: 99%

Cholesin receptor signalling is active in cardiovascular system-associated adipose tissue and correlates with SGLT2i treatment in patients with diabetes

Ryk,

Marcinkiewicz,

Chrzanowski

et al. 2024

Cardiovasc Diabetol

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Background Recently deorphanized G protein-coupled receptor 146 (GPR146) was shown to respond to signal from a newly identified hormone—cholesin—and to play a role in hepatic lipid metabolism. However, the importance of its biological activity in human organism remains elusive, mainly due to the lack of studies on human tissues up to this point. This study aimed to identify the cholesin receptor-associated genes and clinical factors linked with their expression in cardiovascular system and associated adipose tissues. Methods Right cardiac auricle, aortic wall, saphenous vein, and adipose tissue (periaortic-PAT, epicardial-EAT, thymic-TAT) samples were collected during coronary artery bypass grafting. Clinical records of the study participants were assessed for the presence of diabetes, medications taken and serum cholesterol levels. GPR146 mRNA expression in all gathered tissues was assessed with qPCR, and RNA seqencing was performed in selected tissues of 20 individuals to identify pathways associated with GPR146 expression. Results We included 46 participants [37 male, 23 with type 2 diabetes, median age 68.50 (Q1–Q3: 63.00–72.00) years, BMI 28.39 (26.06–31.49) kg/m2]. GPR146 expression in adipose tissues significantly correlated with BMI, c-peptide, total cholesterol, and LDL concentrations. Selected metabolic pathways were significantly and positively enriched in GPR146-dependent manner. GPR146-coexpressed genes contained key regulators of lipid metabolism involved in such pathways as fatty acid metabolism, tricarboxilic acid cycle and peroxisomal metabolism. Those genes correlated positively with serum concentrations of LDL, HDL, and total cholesterol. SGLT2i treatment was associated with inversion of GPR146-related signature in EAT, suggesting potential impact on cholesin-GPR146 network. Conclusions GPR146 expression is associated with serum lipids and metabolically-relevant transcriptomic changes in EAT similar to SGLT2i-associated ones. Graphical abstract

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Section: Introductionmentioning

confidence: 99%

Cholesin receptor signalling is active in cardiovascular system-associated adipose tissue and correlates with SGLT2i treatment in patients with diabetes

Ryk,

Marcinkiewicz,

Chrzanowski

et al. 2024

Cardiovasc Diabetol

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Low muscle mass index is associated with type 2 diabetes risk in a Latin-American population: a cross-sectional study

Suárez,

Andrade,

Bautista-Valarezo

et al. 2024

Front. Nutr.

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ObjectiveDiabetes mellitus is a growing disease with severe complications. Various scores predict the risk of developing this pathology. The amount of muscle mass is associated with insulin resistance, yet there is no established evidence linking muscle mass with diabetes risk. This work aims to study that relationship.Research methods and proceduresThis cross-sectional study included 1,388 employees. The FINDRISC score was used to assess type 2 diabetes risk, and bioimpedance was used for body composition analysis. Appendicular skeletal muscle mass adjusted by body mass index (ASM/BMI) was analyzed. Sociodemographic, clinical and anthropometric measures were evaluated, logistic regression models with sex stratification were conducted and ROC curves were calculated to determine the ability of ASM/BMI index to predict T2D risk.ResultsIt was observed that patients with higher ASM/BMI had a lower FINDRISC score in both men and women (p < 0.001). A logistic regression model showed and association between ASM/BMI and diabetes risk in women [OR: 0.000 (0.000–0.900), p = 0.048], but not in men [OR: 0.267 (0.038–1.878), p = 0.185]. However, when the body mass index variable was excluded from the model, an association was found between muscle mass adjusted to BMI and diabetes risk in both men [OR: 0.000 (0.000–0.016), p < 0.001], and women [OR:0.001 (0.000–0.034), p < 0.001]. Other risk factors were having a low level of physical activity, waist circumference, age and sedentary lifestyle. A ROC curve was built and the optimal ASM/BMI cut-of value for predicting T2D risk was 0.82 with a sensitivity of 53.71% and specificity of 69.3% [AUC of 0.665 (0.64–0.69; p < 0.0001)].ConclusionWhen quantifying the risk of type 2 diabetes in both women and men, assessing muscle mass can help detect adult individuals with a high risk of developing type 2 diabetes.

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SGLT2 Inhibitors – The New Standard of Care for Cardiovascular, Renal and Metabolic Protection in Type 2 Diabetes: A Narrative Review

Cited by 2 publications

References 111 publications

Cholesin receptor signalling is active in cardiovascular system-associated adipose tissue and correlates with SGLT2i treatment in patients with diabetes

Cholesin receptor signalling is active in cardiovascular system-associated adipose tissue and correlates with SGLT2i treatment in patients with diabetes

Low muscle mass index is associated with type 2 diabetes risk in a Latin-American population: a cross-sectional study

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