Abstract
Simple SummaryType 1 and type 2 diabetes can lead to serious health problems that affect many organs including the nerve, the eye, and the kidney. These health problems can be disabling or even life-threatening, and to date, there are no effective therapies that can slow or prevent their development. We studied the effect of empagliflozin, a medication that reduces blood sugar levels and the risk of cardiovascular disease, on the nerve, eye, and kidney in a side-by-side comparison of type 1 and type 2 mouse models. Empagliflozin had no beneficial effects on disease progression in type 2 diabetic mice, but improved nerve function in the type 1 diabetic model, an effect that was accompanied by reduced markers of oxidative injury. These findings support the concept that different mechanisms contribute to nerve damage in type 1 and type 2 diabetes. Our results further support our view that the concept of one therapy will benefit all complications should be abandoned as we pursue more personalized, tissue-specific, diabetes type-specific treatments.Microvascular complications account for the significant morbidity associated with diabetes. Despite tight glycemic control, disease risk remains especially in type 2 diabetes (T2D) patients and no therapy fully prevents nerve, retinal, or renal damage in type 1 diabetes (T1D) or T2D. Therefore, new antidiabetic drug classes are being evaluated for the treatment of microvascular complications. We investigated the effect of empagliflozin (EMPA), an inhibitor of the sodium/glucose cotransporter 2 (SGLT2), on diabetic neuropathy (DPN), retinopathy (DR), and kidney disease (DKD) in streptozotocin-induced T1D and db/db T2D mouse models. EMPA lowered blood glycemia in T1D and T2D models. However, it did not ameliorate any microvascular complications in the T2D model, which was unexpected, given the protective effect of SGLT2 inhibitors on DKD progression in T2D subjects. Although EMPA did not improve DKD in the T1D model, it had a potential modest effect on DR measures and favorably impacted DPN as well as systemic oxidative stress. These results support the concept that glucose-centric treatments are more effective for DPN in T1D versus T2D. This is the first study that provides an evaluation of EMPA treatment on all microvascular complications in a side-by-side comparison in T1D and T2D models.
Highlights
Type 1 (T1D) and type 2 diabetes (T2D) are major public health problems affecting over 463 million individuals worldwide [1]
Similar to diabetic peripheral neuropathy (DPN), our findings suggest that EMPA may be more effective at improving diabetic retinopathy (DR) in type 1 diabetes (T1D) versus T2D mice
We previously demonstrated in a meta-analysis of multiple clinical cohorts that glucose control effectively manages DPN in T1D patients, but much less so in T2D patients [45]
Summary
Type 1 (T1D) and type 2 diabetes (T2D) are major public health problems affecting over 463 million individuals worldwide [1]. Up to 50% of diabetes patients suffer from microvascular complications, including diabetic peripheral neuropathy (DPN), diabetic retinopathy (DR), and diabetic kidney disease (DKD) [2,3,4], leading to lower quality of life and higher mortality. T2D patients, and can lead to disability with nonhealing ulcers and eventual lower limb amputation [2]. DKD prevalence is ≈25 and ≈30–40% of T1D and T2D patients, respectively, and is the leading cause of end-stage renal disease [4]. Hyperglycemia is a major risk factor for developing microvascular complications, yet despite good glycemic control, diabetes patients, T2D individuals, can still develop diabetes-induced nerve, retinal, and/or renal damage
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
