Patrick Campbell

A new study suggests use of therapies in a class known for treating hepatitis B and human immunodeficiency virus (HIV) could be useful in the management of a different disease.

Results of the study, which pooled data from 5 major databases, suggest use of nucleoside reverse-transcriptase inhibitors (NRTIs) was associated with a 33% decrease in risk of developing 

“The large scale of these clinical data and the size of the protective effect provide evidence that inflammasome inhibition in humans is beneficial,” said study investigator Jayakrishna Ambati, MD, professor at the University of Virginia School of Medicine, 

. “We are hopeful that prospective clinical trials will establish that inflammasome inhibitors known as Kamuvudines, which are less-toxic derivatives of NRTIs, will be effective not only in diabetes but also in macular degeneration and Alzheimer’s disease.”

While previously published data have suggested potential mechanistic benefits of NRTIs on the development of type 2 diabetes, Ambati and a team of UVA clinicians sought to determine whether this would translate into a clinical benefit in a real-world setting. With this in mind, they designed the current study as an analysis of real-world data related to use of NRTIs from multiple databases.

Specific databases included in the investigators’ analyses included Veterans Health Administration database, the Truven database, the PearlDiver database, the Medicare database, and the Clinformatics database. Of note, the study was originally designed to examine associations between exposure to NRTIs and development of type 2 diabetes in the Veterans Health Administration database and then assess the validity of these findings through analysis of the other 4 databases. In total, a cohort of 128,861 patients was obtained from the 5 databases.

In the main analysis, investigators identified a total of 79,744 patients with confirmed diagnoses of HIV or hepatitis B without a prior diagnosis of type 2 diabetes. During the follow-up period, 12,311 patients developed type 2 diabetes and results of the analysis suggested users of NRTIs were at a 34% lower risk of developing type 2 diabetes than their counterparts not receiving NRTIs (HR, 0.665; 95% CI, 0.625-0.708; 

From the Truven database, investigators identified a cohort of 23,634 patients. Of these, 1630 went on to develop type 2 diabetes. In adjusted models, users of NRTIs were at a 39% lower risk of developing type 2 diabetes (HR, 0.614; 95% CI, 0.524-0.718; 

 <.0001). From the PearlDiver database, investigators identified a cohort of 16,045 patients. Of these, 1068 went to on to develop type 2 diabetes during the follow-up period. In adjusted models, users of NRTIs were at a 26% lower risk of developing type 2 diabetes.

In the Medicare database, investigators identified a cohort of 3097 patients. Of these, 707 went on to develop type 2 diabetes during the follow-up period. In adjusted models, users of NRTIs were at a 17% lower risk of develop type 2 diabetes (HR, 0.828; 95% CI, 0.646-1.062; 

=.137). In the Clinformatics datable, investigators identified a cohort of 6341 patients. Of these, 1067 went on to develop type 2 diabetes during the follow-up period. In adjusted models, users of NRTIs were at a 27% lower risk of developing type 2 diabetes (HR, 0.727; 95% CI, 0.572-0.924; 

In a pooled analysis including all 128,861 patients from the 5 databases, investigators found the adjusted risk of diabetes was 33% lower among patients with NRTI exposure (HR, 0.673; 95% CI, 0.638-0.710; 

 <.0001; 95% Prediction Interval, 0.618-0.734).

Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development

Articles

An analysis of data from 5 major databases suggests NRTIs could reduce incidence of type 2 diabetes.

UVA Study Suggests NRTIs Could Reduce Risk of Developing Type 2 Diabetes

New research from Penn State Hershey Medical Center details a potential link between the number of menopause symptoms experienced and the risk of 

Results of the study, which were presented during the 2020 Virtual Annual Meeting of The North American Menopause Society (NAMS), suggest having 2 or more moderate to severe menopause symptoms was linked to an increased risk of cardiovascular disease (CVD). The study also found supplementation with calcium and vitamin D did not diminish the apparent risk observed in the 20,000-woman cohort.

“We found that even severe hot flashes were not associated with any adverse clinical health outcomes when occurring on their own, but if they or any other moderate to severe menopause symptoms were present in combination, there was an association with an increased risk of cardiovascular disease,” said lead investigator Matthew Nudy, MD, an internal medicine specialist, in 

With an interest in the overall impact of vasomotor menopausal symptoms on clinical health outcomes, Nudy and a team of colleagues designed their study with the intent of detailing potential associations between severity and/or number of symptoms in women from the Women’s Health Initiative (WHI)-Calcium and Vitamin D (CaD) trial. Of note, the WHI-CaD trial was a randomized, double-blind, placebo-controlled study assessing the effects of vitamin D and calcium supplementation on incident hip fracture and other clinal outcomes in 36,282 women aged 50-79 years old from the original WHI.

From WHI-CaD, Nudy and team identified a cohort of 20,050 women for inclusion in the current study. Investigators also obtained information related to outcomes of interest including hip fracture, colorectal cancer, invasive breast cancer, all-cause mortality, CaD global index, coronary heart disease, stroke, cardiovascular death, and total CVD—all of which were used as outcomes the current analysis. Of note, CaD global index was defined as a composite end point of hip fracture, colorectal cancer, invasive breast cancer, and all-cause mortality.

Menopausal symptoms of interest for the NAMS 2020 study included hot flashes night sweats, dizziness, heart racing or skipping beats, tremors, feeling restless or fidgety, feeling tired, difficulty concentrating, forgetfulness, mood swings, vaginal dryness, breast tenderness, headache or migraine, and waking up multiple times at night. Severity and incidence of symptoms was recorded in a questionnaire at baseline of the trial.

For the purpose of the analysis, severity of symptoms was defined as none, mild, moderate, or severe. Additionally, patients were classified into groups defined as having no symptoms, 1 symptom, and 2 or more symptoms.

Investigators planned multiple analyses as part of their study. These included use of multivariable Cox proportional hazards regression models to test associations between symptom severity and number of symptoms with health outcomes, an analysis to assess whether calcium and vitamin D supplementation modified any associations, and an exploratory analysis to examine associations between severity of each menopausal symptom and total CVD events.

Results of the investigators’ analyses revealed no associations between severity of hot flashes or night sweats and any of the health outcomes of interest. Results indicated number of menopausal symptoms was significantly associated with risk for stroke (HR, 1.41; 95% CI, 1.04-1.91 for 2 or more symptoms vs. none; HR, 1.19; 95% CI, 0.88-1.61 for 1 symptoms vs. none, 

 for trend=.02)and total cardiovascular disease (HR, 1.37; 95% CI, 1.20-1.56, for 2 or more symptoms vs none; HR, 1.00; 95% CI, 0.87-1.15 for 1 symptom vs. none; 

After stratification by randomization status, investigators found no impact from supplementation on any of the aforementioned associations. Results also indicated severities of individual menopausal symptoms, such as night sweats, restless and fidgety, difficulty concentrating, dizziness, heart racing or skipping beats, feeling tired, and forgetfulness were associated with higher total CVD.

The Severity of Vasomotor Symptoms and Number of Menopausal Symptoms in Postmenopausal Women and Select Clinical Health Outcomes in the Women’s Health Initiative Calcium and Vitamin D Randomized Clinical Trial

An analysis of data from the Women's Health Initiative is offering clinicians a look into the impact of menopause symptoms on cardiovascular health in older women.

Increased Number of Menopause Symptoms Tied to Increased Cardiovascular Disease Risk

The evolution of SGLT2 inhibitors from an agent known for mild reductions in HbA1c and body weight to a therapy with proven cardiovascular and renal benefits has captured the attention of endocrinologists, cardiologists, nephrologists, and even primary care providers. What were once trends and observational results have now been confirmed by landmark clinical trials. It seems every major cardiology or diabetes conference in the past few years have been headlined by such a trial and it is hard to see that trend ending any time soon—especially with so many unanswered questions remaining related to the mechanism of actions behind these therapies.


The most recent of these presentations was given by David Cherney, MD, PhD, associate professor in the departments of Medicine and Pharmacology and Toxicology at the University of Toronto, when he presented an analysis of VERTIS-CV examining the renal outcomes with use of ertugliflozin (Steglatro) in the cardiovascular outcomes trial. While the trial demonstrated the benefits of ertugliflozin on renal function in the study population, 

reached out to Cherney to learn more about the implications of this trial.

In the following interview, Cherney offers his perspective on what specialists bare the responsibility of prescribing these agents to patients for whom they are appropriate and to learn more about why multiple fields being knowledgable of SGLT2 inhibitors will improve the care of patients.

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An associate professor from University of Toronto discusses whose responsibility it is to prescribe SGLT2 inhibitors to patients.

David Cherney, MD: SGLT2 Inhibitors and Prescribing Responsibility

New data from a team of investigators in Taiwan is underlining the importance of physical activity and exercise for long-term survival in patients with type 2 diabetes.

Presented at the European Association for the Study of Diabetes (EASD) 2020 Annual Meeting, the analysis of more than 4500 patients over a 15-year period suggests greater levels of exercise was linked to a 25-32% reduction in risk of all-cause mortality among patients with type 2 diabetes.

"Among people with type 2 diabetes, those with increased exercise capacity had a significantly decreased risk of all-cause mortality. Further studies should investigate the type and dose of exercise that is most helpful to promote health and prolong life expectancy,” wrote study investigators.

While many studies have examined the effects of exercise in diabetics, investigators noted few had examined associations between exercise capacity and all-cause mortality. To provide further information on this subject, investigators from the Taichung Veterans General Hospital in Taiwan designed their study as an analysis of data from the National Health Interview Survey (NHIS) and the National Health Insurance research databases.

As part of NHIS, patients underwent standardized face-to-face interviews in 2001, 2005, 2009, and 2013. Through a search of the National Health Insurance research database from 2000-2016, investigators were able to confirm comorbidities for each patient and, from the National Registration of Death, investigators were able to ascertain instances of mortality.

Investigators identified a total of 4859 adult participants with type 2 diabetes for their study. Of these, 49.15% (n=2389) were men and the cohort had a mean age of 59.5 (12.63) years. Using Kaplan-Meier curves, of all-cause mortality stratified by exercise capacity, investigators unveiled significant findings. In univariate Cox regression analysis, investigators found those with higher exercise capacity had a significantly decreased risk of all-cause mortality compared to those with no exercise habits (moderate exercise with 0-800 kcal/week HR, 0.83; 95% CI, 0.71-0.97, high exercise with more than 800 kcal/week HR, 0.77; 95% CI, 0.67-0.89).

After adjustment for potential confounders, a multivariate Cox regression analysis indicated those with a higher exercise capacity was associated with a significantly decreased risk of all-cause mortality compared to those with no exercise habits (moderate exercise with 0-800 kcal/week: HR, 0.75, 95% CI: 0.62-0.91, high exercise with more than 800 kcal/week: HR, 0.68, 95% CI, 0.57-0.81). Additionally, investigators noted a significant trend (

In a sensitivity analysis excluding mortality in the first and second year in the study period, results suggest those with increased exercise capacity had a significantly decreased risk of all-cause mortality.

Association between exercise capacity and all-cause mortality in people with type 2 diabetes

A study presented at EASD 2020 examines the impact of increased exercise capacity on risk of all-cause mortality among more than 4k patients with type 2 diabetes.

Author | Patrick Campbell

Articles

UVA Study Suggests NRTIs Could Reduce Risk of Developing Type 2 Diabetes

Increased Number of Menopause Symptoms Tied to Increased Cardiovascular Disease Risk

David Cherney, MD: SGLT2 Inhibitors and Prescribing Responsibility

Study Finds Increased Exercise Lowers Mortality Risk 25-32% Among Diabetics