Cardiac tissue damage due to myocardial infarction (MI) is one of the leading causes of mortality worldwide. The available treatments of MI include pharmaceutical therapy, medical device implants, and organ transplants, all of which have severe limitations including high invasiveness, scarcity of donor organs, thrombosis or stenosis of devices, immune rejection, and prolonged hospitalization time. Injectable hydrogels have emerged as a promising solution for in situ cardiac tissue repair in infarcted hearts after MI. In this review, an overview of various natural and synthetic hydrogels for potential application as injectable hydrogels in cardiac tissue repair and regeneration is presented. The review starts with brief discussions about the pathology of MI, its current clinical treatments and their limitations, and the emergence of injectable hydrogels as a potential solution for post MI cardiac regeneration. It then summarizes various hydrogels, their compositions, structures and properties for potential application in post MI cardiac repair, and recent advancements in the application of injectable hydrogels in treatment of MI. Finally, the current challenges associated with the clinical application of injectable hydrogels to MI and their potential solutions are discussed to help guide the future research on injectable hydrogels for translational therapeutic applications in regeneration of cardiac tissue after MI.

OBJECTIVE To compare the long-term efficacy of initiating therapy with metformin/pioglitazone/exenatide in patients with new-onset type 2 diabetes mellitus (T2DM) versus sequential addition of metformin followed by glipizide and insulin. RESEARCH DESIGN AND METHODS Drug-naive patients (N = 318) with new-onset T2DM were randomly assigned to receive for 3 years either 1) combination therapy with metformin, pioglitazone, and exenatide (triple therapy) or 2) sequential addition of metformin followed by glipizide and insulin (conventional therapy) to maintain HbA1c at <6.5% (48 mmol/mol). Insulin sensitivity and β-cell function were measured at baseline and 3 years. The primary outcome was the difference in HbA1c between the groups at 3 years. RESULTS Baseline HbA1c ± SEM values were 9.0% ± 0.2% and 8.9% ± 0.2% in the triple therapy and conventional therapy groups, respectively. The decrease in HbA1c resulting from triple therapy was greater at 6 months than that produced by conventional therapy (0.30% [95% CI 0.21–0.39]; P = 0.001), and the HbA1c reduction was maintained at 3 years in patients receiving triple therapy compared with conventional therapy (6.4% ± 0.1% and 6.9% ± 0.1%, respectively), despite intensification of antihyperglycemic therapy in the latter. Thus, the difference in HbA1c between the two treatment groups at 3 years was 0.50% (95% CI 0.39–0.61; P < 0.0001). Triple therapy produced a threefold increase in insulin sensitivity and 30-fold increase in β-cell function. In conventional therapy, insulin sensitivity did not change and β-cell function increased by only 34% (both P < 0.0001 vs. triple therapy). CONCLUSIONS Triple therapy with agents that improve insulin sensitivity and β-cell function in patients with new-onset T2DM produces greater, more durable HbA1c reduction than agents that lower glucose levels without correcting the underlying metabolic defects.

Background Diabetic kidney disease (DKD) affects about 40% of patients with diabetes. It is incurable and usually leads to end-stage renal disease (ESRD). The pathogenesis of DKD is still not fully understood, and the genetics of DKD have not yet been extensively studied. In this study, we investigate the genetic basis of DKD in type 2 diabetes (T2D) to provide more insights into the pathogenesis of the disease. Results Using the data provided by the UK Biobank (UKBB), we performed a DKD genome-wide association study (GWAS) in 13,123 individuals with T2D as well as two creatinine estimated glomerular filtration rate (eGFR) GWA studies: one in 26,786 individuals with T2D and the other in 339,080 non-diabetic individuals. We also conducted a DKD GWAS meta-analysis combining our results with those published by the surrogate markers for micro- and macro-vascular hard endpoints for Innovative diabetes Tools (SUMMIT) consortium. We confirm two loci previously reported to be associated with chronic kidney disease (CKD) and eGFR in T2D. The UMOD-PDILT locus is associated with DKD (P = 1.17E−09) as well as creatinine eGFR in both people with T2D (P = 1.31E−15) and people without diabetes (P = 3.95E−73). The PRKAG2 locus is associated with creatinine eGFR in people with (P = 2.78E−10) and without (P = 5.65E−72) T2D. Our meta-analysis reveals a novel association between DKD and variant rs72763500 (chr1:236116561) which is a splicing quantitative trait locus (sQTL) for nidogen-1 (NID1) gene. Conclusion Our data confirm two loci previously reported in association with CKD and creatinine eGFR in T2D. It also suggests that NID1, a major component of the renal tubular basement membrane, could play a role in DKD development in T2D. While our NID1 finding remains to be replicated, it is a step toward a more comprehensive understanding of DKD pathogenesis.

<b>Objective:</b> To compare the long term efficacy of initiating therapy with metformin/pioglitazone/exenatide in new onset T2DM patients versus sequential addition of metformin followed by glipizide and insulin. <p><b>Research Design and</b> <b>Methods</b>: 318 drug naïve, new onset T2DM were randomized to receive for 3 years: (1) combination therapy with metformin/pioglitazone/ exenatide (Triple Therapy) or (2) sequential addition of metformin followed by glipizide and insulin (Conventional Therapy) to maintain HbA1c <6.5% (48 mmol/mol). Insulin sensitivity and beta cell function were measured at baseline and at 3 years. The primary outcome was the difference in HbA1c between the groups at 3 years. </p> <p><b>Results:</b> Baseline HbA1c was 9.0±0.2% and 8.9±0.2% in the Triple Therapy and Conventional Therapy groups. The decrease in HbA1c produced by Triple Therapy was greater at 6 months than Conventional Therapy (0.30%, 95% CI=0.21-0.39) (p=0.001), and the HbA1c reduction was maintained at 3 years in subjects receiving Triple Therapy compared to Conventional Therapy (6.4±0.1% and 6.9±0.1%, respectively) despite intensification of antihyperglycemic therapy in the latter. Thus, the difference in HbA1c between the two treatment groups at 3 years was 0.50% (95% CI=0.39-0.61, P<0.0001). </p> <p>Triple Therapy produced 3-fold increase in insulin sensitivity and 30-fold increase in beta cell function. In Conventional Therapy insulin sensitivity did not change and beta cell function increased by only 34% (both p<0.0001 versus Triple Therapy). </p> <p><b>Conclusion: </b> Triple Therapy with agents that improve insulin sensitivity and beta cell function in new onset T2DM patients produce greater, more durable HbA1c reduction, than agents that lower glucose without correcting the underlying metabolic defects. </p>