Sodium-glucose cotransporter 2 inhibitors and renin-angiotensin-aldosterone system, possible cellular interactions and benefits.

Sodium glucose cotransporter 2 inhibitors (SGLT2is) are a newly developed class of anti-diabetics which exert potent hypoglycemic effects in the diabetic milieu. However, the evidence suggests that they also have extra-glycemic effects. The renin-angiotensin-aldosterone system (RAAS) is a hormonal system widely distributed in the body that is important for water and electrolyte homeostasis as well as renal and cardiovascular function. Therefore, modulating RAAS activity is a main goal in patients, notably diabetic patients, which are at higher risk of complications involving these organ systems. Some studies have suggested that SGLT2is have modulatory effects on RAAS activity in addition to their hypoglycemic effects and, thus, these drugs can be considered as promising therapeutic agents for renal and cardiovascular disorders. However, the exact molecular interactions between SGLT2 inhibition and RAAS activity are not clearly understood. Therefore, in the current study we surveyed the literature for possible molecular mechanisms by which SGLT2is modulate RAAS activity.

Obesity and Diabetic Complications: A Study from the Nationwide Diabetes Report of the National Program for Prevention and Control of Diabetes (NPPCD-2021) Implications for Action on Multiple Scales.

BACKGROUND: Obesity plays a major role in the pathogenesis and development of macro- and microvascular complications of type 2 diabetes (T2D) and type 1 diabetes (T1D). We aimed to assess the association between obesity and macrovascular and microvascular complications of diabetes. METHODS: This study consisted of 111,830 patients (age range: 1-106) with diabetes including 10,641 T1D (3187 obese [38.2% men] and 7454 non-obese [45.5% men]) and 101,189 T2D (51,873 obese [27.5% men] and 49,316 non-obese [33.4% men]) from the National Program for Prevention and Control of Diabetes (NPPCD-2021) in Iran, who attended academic tertiary care outpatient clinics from February 2016 to April 2021. A pooled logistic regression model was used to examine the association between obesity and diabetic complications. RESULTS: Among patients with T1D, a significant association was found between obesity and cardiovascular disease (CVD), neuropathy, nephropathy and retinopathy (OR= 1.75, 1.56, 1.80 and 1.92, P-value= 0.001, 0.004, 0.001 and <0.001, respectively). In T2D, a statistically significant association was found between obesity and CVD, neuropathy and nephropathy (OR= 1.63, 1.98, 1.21, respectively, P-values <0.001). CONCLUSION: Obesity was independently associated with CVD, neuropathy and nephropathy in patients with T1D and T2D and with retinopathy only in T1D, to different degrees. The association between obesity and retinopathy and neuropathy was the strongest among T1D and T2D, respectively. Findings from this study suggest that obesity affects diabetic complications differently among the two types of diabetes, in terms of epidemiology and pathophysiology. This signifies the importance of different preventive and therapeutic approaches to obesity in T1D compared to T2D, on a national and global scale.