Peroxisome proliferator-activated receptors as stimulants of angiogenesis in cardiovascular disease and diabetes

The incidence of diabetes is directly related to the incidence of obesity, which is at epidemic proportions in the US. Cardiovascular disease is a common complication of diabetes, which results in high morbidity and mortality. Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear hormone receptors that regulate lipid and glucose metabolism. PPAR-α agonists such as fenofibrate and PPAR-γ agonists such as the thiozolidinediones have been used to treat dyslipidemia and insulin resistance in diabetes. Over the past few years research has discovered the role of PPARs in the regulation of inflammation, proliferation, and angiogenesis. Clinical trials looking at the effect of PPAR agonists on cardiovascular outcomes have produced controversial results. Studies looking at angiogenesis and proliferation in various animal models and cell lines have shown a wide variation in results. This may be due to the differential effects of PPARs on proliferation and angiogenesis in various tissues and pathologic states. This review discusses the role of PPARs in stimulating angiogenesis. It also reviews the settings in which stimulation of angiogenesis may be either beneficial or harmful

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Pioglitazone in the Treatment of Type 2 Diabetes: Safety and Efficacy Review

The increase in obesity and the aging of the population has lead to an increase in the incidence of type 2 diabetes. This has led to the development of new drugs such as thiazolidinediones (TZDs) which are Peroxisome Proliferator-Activated Receptor (PPAR-gamma) agonists, to treat type 2 diabetes. TZDs have recently been at the center of a controversy with regards to their cardiovascular safety. Pioglitazone is a TZD which has been shown to be effective in glycemic control by lowering insulin resistance. Pioglitazone also has beneficial effects on lipid metabolism and cardiovascular risk. The safety and efficacy of pioglitazone including its pleotropic effects are discussed at length in this article

The impact of apathy on glycemic control in diabetes: A cross-sectional study

Objective: Diabetes mellitus is a major public health problem with a prevalence of 6–7%. Self-care behaviors play a major role in the control of diabetes. Apathy is characterized by loss of initiative and motivation. Apathy may interfere with self-care behavior and glycemic control. The primary objective was to determine the prevalence of apathy in patients with diabetes. The secondary objective was to determine if there was an association between clinically significant apathy and factors that affect glycemic control. Research design and methods: We conducted a cross-sectional study of 100 patients with diabetes who were assessed with the Apathy Evaluation Scale-Clinician version (AES-C), the Hamilton Depression Scale (HAM-D), and the Self-Care Inventory (SCI). For this study we defined clinically significant apathy as AES-C score of \u3e30. We excluded patients with a HAM-D score of \u3e14 (n = 19) to avoid confounding from depression. T-tests were used to compare clinical characteristics between subjects with and without apathy. Multiple linear regression modeling was used to investigate the association between clinically significant apathy and factors that affect glycemic control. Results: Fifty (61.7% of 81) patients had clinically significant apathy. Compared to the nonapathetic patients, those with apathy had a higher mean BMI (30.5 kg/m2 versus 34.1 kg/m2 (p = 0.03)) and were less likely to adhere to an exercise plan (p = 0.01) or insulin regimen (p = 0.003). After adjustment for age, BMI, cholesterol, mild depression and the average Self- Care Index score, the mean HbA1C level was 0.66% greater for apathetic compared to nonapathetic subjects (P = 0.08). Conclusion: Apathy is highly prevalent in patients with diabetes without depression. Apathy may have a negative impact on self-care behaviors and diabetes control

Investigating Speed Deviation Patterns During Glucose Episodes: A Quantile Regression Approach

Given the growing prevalence of diabetes, there has been significant interest in determining how diabetes affects instrumental daily functions like driving. Complication of glucose control in diabetes includes hypoglycemic and hyperglycemic episodes, which may impair cognitive and psychomotor functions needed for safe driving. The goal of this paper was to determine patterns of diabetes speed behavior during acute glucose to drivers with diabetes who were euglycemic or control drivers without diabetes in a naturalistic driving environment. By employing distribution-based analytic methods that capture distribution patterns, our study advances prior literature that has focused on conventional approach of average speed to explore speed deviation patterns.This is a preprint of an article published as Joshi, Aparna, Jennifer Merickel, Cyrus V. Desouza, Matthew Rizzo, Pujitha Gunaratne, and Anuj Sharma. "Investigating Speed Deviation Patterns During Glucose Episodes: A Quantile Regression Approach." arXiv preprint arXiv:2310.02351 (2023). doi:https://doi.org/10.48550/arXiv.2310.02351

The Impact of Type 1 Diabetes on Neural Dynamics

Type 1 diabetes (T1D) has been shown to affect the structure and function of the brain. The current study sought to uncover the neural dynamics underlying cognitive processing in adults with T1D using non-invasive neuroimaging. Adults with T1D and without major complications and a demographically-matched control group underwent magnetoencephalography (MEG) while performing tasks tapping attention, working memory and motor functioning. MEG data from each task was examined using a beamformer source imaging approach and probed statistically for group differences. Our results for the flanker attention task indicated that neural activity in the anterior cingulate, paracentral lobule, and parietal function was altered, such that participants with T1D had stronger flanker interference responses in parietal and weaker responses in anterior cingulate regions (p \u3c .001). Further, the overall strength of the anterior cingulate and paracentral lobule responses significantly correlated with disease duration, r = -.46, p = .006, and r = -.42, p = .013, respectively. Group differences in parietal-occipital responses were found throughout encoding and maintenance phases of the working memory task, where participants with T1D had stronger parietal activity in encoding and weakened parietal-occipital activity in maintenance (ps \u3c .01). Activity in several regions correlated with duration and A1C in participants with T1D (ps \u3c .01). Motor responses were also altered in participants with T1D, where specific frequency responses differentially predicted behavioral outcomes. These findings demonstrate significant alterations in neurophysiology underlying major cognitive processes, likely affecting outcomes in later life