Oral diabetes medication monotherapy and short-term mortality in individuals with type 2 diabetes and coronary artery disease

Objective To determine whether sulfonylurea use, compared with non-sulfonylurea oral diabetes medication use, was associated with 2-year mortality in individuals with well-controlled diabetes and coronary artery disease (CAD). Research design and methods We studied 5352 US veterans with type 2 diabetes, obstructive CAD on coronary angiography, hemoglobin A1c ≤7.5% at the time of catheterization, and taking zero or one oral diabetes medication (categorized as no medications, non-sulfonylurea medication, or sulfonylurea). We estimated the association between medication category and 2-year mortality using inverse probability of treatment-weighted (IPW) standardized mortality differences and IPW multivariable Cox proportional hazards regression. Results 49%, 35%, and 16% of the participants were on no diabetes medications, non-sulfonylurea medications, and sulfonylureas, respectively. In individuals on no medications, non-sulfonylurea medications, and sulfonylureas, the unadjusted mortality rates were 6.6%, 5.2%, and 11.9%, respectively, and the IPW-standardized mortality rates were 5.9%, 6.5%, and 9.7%, respectively. The standardized absolute 2-year mortality difference between non-sulfonylurea and sulfonylurea groups was 3.2% (95% CI 0.7 to 5.7) (p=0.01). In Cox proportional hazards models, the point estimate suggested that sulfonylurea use might be associated with greater hazard of mortality than non-sulfonylurea medication use, but this finding was not statistically significant (HR 1.38 (95% CI 1.00 to 1.93), p=0.05). We did not observe significant mortality differences between individuals on no diabetes medications and non-sulfonylurea users. Conclusions Sulfonylurea use was common (nearly one-third of those taking medications) and was associated with increased 2-year mortality in individuals with obstructive CAD. The significance of the association between sulfonylurea use and mortality was attenuated in fully adjusted survival models. Caution with sulfonylurea use may be warranted for patients with well-controlled diabetes and CAD, and metformin or newer diabetes medications with cardiovascular safety data could be considered as alternatives when individualizing therapy

Diabetes, microvascular complications, and cardiovascular complications: what is it about glucose?

Glycemic control is the primary mediator of diabetic microvascular complications and also contributes to macrovascular complications. A new study (see related article beginning on page 1049) reveals a previously unrecognized association between oxidant activation of poly(ADP ribose) polymerase (PARP) and upregulation of known mediators of glycemic injury. Inhibitors of PARP may have potential therapeutic roles in the prevention of diabetic complications

Raw and processed microscope images of fixed cells at baseline and following various experimental perturbations

The data included in this article comprise raw and processed images of fixed cells at baseline and subjected to various experimental perturbations. This dataset includes images of HUVEC cells fixed and subsequently incubated at either 37 °C or room temperature, primary rat vascular smooth muscle cells exposed to 25 mM glucose, and SH-SY5Y neurons exposed to hydrogen peroxide. Raw images appear exactly as they were captured on the microscope, while processed images show the binarization provided by software used for measurements of mitochondrial morphology. For in-depth discussion of the experiments and computational methods pertaining to this data, please refer to the corresponding research article titled “Fully automated software for quantitative measurements of mitochondrial morphology” (McClatchey et al., in press) [1]

Three-year data from 5 HARMONY phase 3 clinical trials of albiglutide in type 2 diabetes mellitus : Long-term efficacy with or without rescue therapy

Aims Diabetes therapies that provide durable glycaemic control for people with type 2 diabetes mellitus (T2DM) are needed. We present efficacy results of albiglutide, a glucagon-like peptide-1 receptor agonist, in people with T2DM over a 3-year period. Methods Five of the 8 HARMONY phase 3 trials, comparing albiglutide with other therapies or placebo across a spectrum of clinical care, lasted for a preplanned 3 years. Participants with uncontrolled hyperglycaemia who met predetermined criteria could receive rescue medication. The ability to remain on study medication without needing additional rescue was an efficacy measure. Glycaemic measures and body weight were analysed in 2 populations: those who remained rescue-free and all participants. Results Participants (n = 3132) were randomised to albiglutide or comparator. A greater proportion of participants who received albiglutide remained rescue-free (55–71%) compared with placebo (35–51%; p < 0.001 to p = 0.002). The proportion of rescue-free participants with albiglutide did not differ from glimepiride or insulin glargine, was higher than with sitagliptin (p = 0.013), and lower than with pioglitazone (p = 0.045). At 3 years, albiglutide was associated with clinically significant reductions in hyperglycaemia (eg, rescue-free participants: HbA1c −0.52% [SE0.11] to −0.98% [0.12]; −5.7 mmol/mol [1.2] to −10.7 mmol/mol [1.3] and all participants: HbA1c −0.29% [0.11] to − 0.92% [0.13]; −3.2 mmol/mol [1.2] to −10.1 mmol/mol [1.4]). Albiglutide was also associated with modest reductions in body weight vs pioglitazone, glimepiride, and insulin glargine, which were associated with weight gain. Conclusion These 3-year efficacy data support long-term use of albiglutide in the management of people with T2DM. ClinicalTrials.gov NCT00849056, NCT00849017, NCT00838903, NCT00838916, NCT00839527

Sex Differences in Physical Activity Among Individuals with Type 2 Diabetes Across the Lifespan: A Systematic Review and Meta-Analysis

   Background: Physical activity (PA) is a cornerstone of type 2 diabetes mellitus (T2DM) treatment. Sex differences in PA behavior or barriers/facilitators to PA among individuals with T2DM are unclear. Purpose: To summarize the evidence related to sex differences in participation in PA and barriers/facilitators to PA among individuals with T2DM across the lifespan. Data Source: Systematic searches (CRD42021254246) were conducted using Ovid Medline, EMBASE, Web of Science, CINAHL, AMED, PsychINFO, and SPORTDiscus. Study Selection: Studies assessing PA, sedentary behaviors (SB) or barriers/facilitators to PA among individuals with T2DM by sex or gender. Data Extraction: Participant characteristics, meeting PA guidelines, participation in PA and SB, and barriers/facilitators to PA were extracted by two independent reviewers.  Data Synthesis: Fifty-three articles (65,344 participants) were included in the systematic review; 21 articles in the meta-analysis. Sex differences were not observed in meeting PA guidelines among adolescents (OR [95% CI], 0.70 [0.31, 1.59]), but males were more likely than females to meet PA guidelines among adults (1.65 [1.36, 2.01]) and older adults (1.63 [1.27, 2.09]). Males performed more moderate to vigorous PA (MVPA) than females across all age groups. Common barriers were lack of time (men) and lack of social support and motivation (women).  Limitations: Limitations include heterogeneity of measures used to assess PA and lack of stratification of data by sex. Conclusions: Sex differences in meeting PA guidelines were not observed among adolescents, but were apparent among adults and older adults with T2DM. Females consistently engaged in less MVPA than males across the lifespan.</p