Patrick Campbell is the assistant managing editor of Endocrinology Network, as well as its sister publication Practical Cardiology. Prior to joining these brands, he led coverage of cardiology and diabetes with HCPLive. Before joining parent company MJH Life Sciences in 2019, he spent time as a beat reporter with the Pocono Record in Stroudsburg, PA, and Star News Group in Manasquan, NJ. He also touts experience in multimedia, having spent time as a freelance multimedia specialist with NJ Advance Media and multimedia coordinator at the Pocono Record.  Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

Patrick Campbell

Reducing sedentary time by just an hour per day among patients with metabolic syndrome could reduce improve glycemic control and other markers of cardiometabolic health, according to results from a recent trial.

A trial assessing the effects of a low-intensity intervention aimed at reducing sedentary by 1 hour per day, results of the study demonstrate reducing sedentary time and increasing light-intensity physical activity was associated with improvements in several cardiometabolic biomarkers in adults with metabolic syndrome, including fasting insulin levels, HbA1c, and liver alanine aminotransferase.

“It is an encouraging thought that health benefits can be achieved by reducing the time spent sitting and increasing the amount of even light-intensity physical activity. For many, this may be an easier starting point than increasing actual exercise,” said lead investigator Taru Garthwaite, MSc

 a doctoral candidate at the University of Turku in Finland, 

Although it is common knowledge among providers and laypersons that decreasing sedentary is associated with improved health outcomes, the magnitude of benefit is the subject of debate depending on the patient population in question. With this in mind, the current study was conducted by Garthwaite and colleagues from the Turku PET Centre and the UKK Institute in Finland to assess the impact of a low-intensity intervention aimed at limiting sedentary by an hour per day and replacing it with standing time or light-intensity physical among patients with metabolic syndrome.

A parallel-group randomized controlled trial, the study was conducted between April 2017 and November 2019, with eligible patients recruited through newspaper advertisements and leaflets distributed in the local community. investigators sought to enroll a population of sedentary and inactive working-aged adults with metabolic syndrome. Specific inclusion criteria required patients to be 40-65 years of age, have less than 120 minutes per week of self-reported moderate to vigorous physical activity, accelerometer-measured sitting time of 10 hours or more per day, a baseline BMI of 25-40 kg/m2, a blood pressure greater than 160/100 mmHg, and fulfillment of at least 3 prespecified metabolic syndrome criteria.

The aim of the intervention was to reduce sedentary behavior by 1 hour per day compared to the reported sedentary time during the baseline screening. those randomized to the intervention received guidance in the form of 1-hour tailored personal counseling sessions to sit less by increasing standing and light-intensity physical activity, without intentionally adding exercise or moderate-to-vigorous physical activity.

A total of 263 patients volunteered to participate in the trial. Of these 155 were screened and 64 were ultimately selected for inclusion. Of the 64 chosen to participate, 63 completed the trial, with 1 participant dropping out due to personal reasons. The mean age of the final study cohort was 58 (SD, 7) years, 58% were women, 41% of participants were overweight and 59% were considered obese. Baseline data suggested participants spent a mean of 10.04 (SD, 1.01) hours per day engaging in sedentary behavior, a mean of 1.79 (SD, 0.59) hours per day standing, a mean of 1.74 (SD, 0.44) h/ day in light-intensity physical activity, and 0.97 (SD, 0.32) hours per day in moderate-to-vigorous physical activity, took a mean of 5149 (SD, 1825) steps per day, and experienced a mean of 29 (SD, 8) breaks in sedentary behavior daily. Of the 64 patients selected for inclusion, 33 were randomized to the intervention and 31 were randomized to the control arm of the study, with these patients receiving instruction to maintain usual lifestyle habits.

At the end of the trial, results suggested those in the intervention arm experienced a reduction in sedentary behavior of 50 (95% CI, 24 to 73) minutes per day, with this being driven by an increase in light-intensity and moderate-to-vigorous physical activity of 19 (95% CI, 8 to 30) and 24 (95% CI, 14 to 34) minutes per day, respectively. Investigators pointed out standing times increased among those in the intervention arm by 6 (95% CI, -11 to 23) minutes per day, but this difference failed to reach statistical significance. Investigators also noted baseline activity levels were maintained among those in the control arm throughout the duration of the trial.

Additionally, results of the investigators’ analyses indicated randomization to the intervention arm was associated with significant improvements in fating insulin (83.4 [68.7, 101.2] vs 102.0 [95% CI, 83.3 to 125.0] pmol/l), HOMA-IR (3.2 [95% CI, 2.6 to 3.9] vs 4.0 [95% CI, 3.2 to 4.9]), HbA1c (37 [95% CI, 36 to 38] vs. 38 [95% CI, 37 to 39] mmol/mol), and liver enzyme alanine aminotransferase (28 [95% CI, 24 to 33] vs. 33 [95% CI, 28 to 38] U/l) when compared to randomization to the trial’s control arm.

“To our knowledge, this is the first study to measure sedentary behavior and physical activity with accelerometers continuously throughout the 3-month intervention, and to investigate the health effects of SB reduction in sedentary and inactive, middle-aged adults with metabolic syndrome,” wrote investigators.

Effects of reduced sedentary time on cardiometabolic health in adults with metabolic syndrome: A three-month randomized controlled trial

Journal of Science and Medicine in Sport.

Articles

A 3-month trial found reducing sedentary time by just an hour per day was enough to produce statistically significant changes in biomarkers for cardiovascular risk among patients with metabolic syndrome. 

Reducing Sedentary Time By An Hour Per Day Can Provide Health Benefits in Metabolic Syndrome

The rapid integration of continuous glucose monitoring technologies has brought forth a wave of innovation within these technologies. Among the most recent additions to the equation has been smartphone applications to optimize the use of CGM technologies in patients with diabetes.

As the market for CGM devices becomes more and more competitive, manufacturers have sought to one-up each other by providing users with cutting-edge technologies and features, such as smartphonehave applications, with their CGM. Now, a study presented at the 15th International Conference on Advanced Technologies and Treatments for Diabetes (ATTD) is offering insight into what features within a diabetes smartphone application were associated with improvements in glycemic control and what ones do not provide benefit.

“The aim of the project presented in the poster was to explore the effects of specific features in apps for people with type 2 diabetes on glycemic control, though diabetes application have the potential to support glycemic control in type 2 diabetes, there's a lack of evidence regarding to the effect of the individual features of the apps in regards to glycemic control,” said study presenter Julie Egmose, MSc, of Aalborg University, during her presentation at ATTD 2022.

Although companies have focused on making their CGM devices and product offerings the most appealing in the marketplace, Egmose and colleagues from Aalborg University designed the present study to fill current gaps in knowledge related to what features might provide the most benefit in terms of improving glycemic control. With this in mind, investigators designed their study as a review data from the PubMed, EMBASE, and CINAHL databases.

From a systematic search of literature in these databases, investigators identified 437 total records for potential inclusion in their study. After exclusion of duplicates and application of inclusion criteria, a total of 13 full-text articles were assessed for eligibility and 7 were ultimately included in the investigators’ analysis. Inclusion criteria for the study required studies to enroll patients with type 2 diabetes, assess features in diabetes mellitus management apps, and assess blood sugar as an outcome of interest. Additionally, these studies were required to have been published in English, Danish, Swedish, or Norwegian. Articles were excluded if results were not divided according to type of diabetes and if the features in the apps were not divided into the results.

From the 7 studies identified for inclusion, a total of 5 app features were identified. These included feedback mechanisms, a glucose-monitoring and feedback system, gamification, biofeedback-assisted relaxation, and diabetes education. Of note, multiple feedback mechanisms were assessed, including an insulin titration algorithm with immediate feedback mechanism and feedback from health professionals.

Upon analysis, results of the investigators’ analyses suggested only 3 of the features assessed were associated with significant improvements in glycemic c control. These features were the monitoring and feedback-system, gamification, and diabetes education.

“Overall, it seems that diabetes app should contain an educational feature gamification, and a feature for sharing data with healthcare professionals to improve glycemic control. However, more evidence is needed to determine the effect of individual features in diabetes apps,” Egmose added, during the latter portions of her presentation at ATTD 2022.

This study, “Which Diabetes App Features Improve Glycemic Control in Type 2 Diabetes? A Scoping Revie,” was presented at ATTD 2022.

A review of data presented at ATTD 2022 dissects what features within smartphone applications created to improve diabetes management actually contribute to improved glycemic control. 

Study Details Diabetes App Features Associated with Improving Glycemic Control

An analysis of data from the Cleveland Clinic Echocardiography database is sounding the alarm on the potential impact of calcium supplementation in older adults with aortic stenosis.

A retrospective longitudinal study with data from more than 2500 patients followed for nearly 70 months, results of the study indicate calcium supplementation was associated with a 31% greater risk of mortality and a 48% greater risk of aortic valve replacement among older adults with aortic stenosis.

“Strengthened by its large sample size and extended follow-up period, our study suggests that calcium supplementation does not confer any cardiovascular benefit, and instead may reflect an elevated overall risk of aortic valve replacement and mortality, especially in those not undergoing aortic valve replacement,” wrote investigators.

With calcium and vitamin D among the most commonly supplemented vitamins and minerals among aging populations, particularly those at 

, the current study was designed by investigators at the Cleveland Clinic Foundation to assess the impact of supplemental calcium and vitamin D on mortality and progression of aortic stenosis. With this in mind, investigators designed their study as a retrospective longitudinal study of patients aged 60 years and older with mild-moderate native aortic stenosis from the Cleveland Clinic Echocardiography database from 2008-2016.

From this search, investigators identified 2657 patients for inclusion in their analyses. These patients had a mean age of 74 years, 42% were women, and the median follow-up duration was 69 months. Patients included in the analyses were stratified into groups defined by the absence of supplementation, supplementation with vitamin D alone, and supplementation with calcium plus vitamin D. Of the 2657 patients included, 49% did not supplement, 12% supplemented with vitamin D alone, and 39% supplemented with calcium and vitamin D.

The primary outcomes of interest for the investigators’ analyses were mortality and aortic valve replacement. Of note, mortality was assessed as all-cause mortality, cardiovascular mortality, and non-cardiovascular mortality. Secondary outcomes of interest included aortic stenosis progression by aortic valve area and peak/mean gradients. investigators pointed out primary outcomes were assessed through survival analyses with Kaplan-Meier nonparametric method.

Overall, there were 540 deaths that occurred among the study cohort, with 150 being classified as cardiovascular death, 155 classified as noncardiovascular death, 235 were deaths of unknown etiology. A total of 774 cases of aortic valve replacement were identified during the follow-up period.

Results of the investigators’ analyses indicated supplementation with calcium and vitamin D was associated with a significantly higher risk of all-cause mortality (absolute rate [AR]=43.0/1000 person-years; HR=1.31, [95% CI, 1.07-1.62]; 

=.009), cardiovascular mortality (AR, 13.7/1000 person-years; HR, 2.0 [95% CI, 1.31-3.07]; 

=.001), and aortic valve replacement (AR, 88.2/1000 person-years; HR, 1.48 [95% CI, 1.24-1.78]; 

<.001) compared to the nonsupplementation arm. investigators noted the increased risk of all-cause mortality was greater among those supplementing with calcium and vitamin D when compared against those supplementing vitamin D alone as well (

Investigators pointed out analysis of those who supplemented with calcium alone, which was a cohort of 115 patients, indicated these individuals experienced a similar rate of all-cause mortality (HR, 1.24 [95% CI, 0.77-1.99]; 

=.38) but a higher risk of aortic valve replacement (HR, 2.7 [95% CI, 1.76-4.08]; 

, Jutta Bergler-Klein, a professor of the Medical University of Vienna, detailed the contemporary trends in supplement use among older patients, but added clinicians may need to rethink the potential risk posed by calcium supplements in those with osteoporosis at high risk for cardiovascular disease.

“In patients with calcific aortic stenosis and high-risk cardiovascular disease, the present study strongly adds to the evidence that long-term continuous calcium supplementation should be avoided if not mandatory,” wrote Bergler-Klein.

Supplemental calcium and vitamin D and long-term mortality in aortic stenosis,

An analysis of data from a Cleveland Clinic database indicates calcium supplementation in older adults with aortic stenosis was linked to an increased risk of mortality and worsening aortic stenosis. 

Calcium Supplementation Could Increase Risk of Death in Older Adults with Cardiovascular Disease

The UK National Osteoporosis Guideline Group (NOGG) has released updated guidance for 

Published on April 20, the guideline, which has been endorsed by the International Osteoporosis Foundation (IOF) and by the European Society for the Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), represents the first update to guidance for prevention and treatment of osteoporosis since the NOGG’s guidelines update in 2017.

“The NOGG, established in 2007, is a multidisciplinary group of 20 individuals that includes patient representation and professionals involved in the care of people with osteoporosis,” said lead author Celia Gregson, PhD, professor of clinical epidemiology in the Musculoskeletal Research Unit at the University of Bristol, 

. “It has taken this team more than 18 months to review, appraise and collate the necessary evidence to write this important new guideline for primary and secondary care use. The guideline has been reviewed and supported by 18 professional and/or patient organizations in the field, including the Royal Osteoporosis Society.”

With accreditation from the National Institute of Health and Care Excellence, the guideline reviews the assessment and diagnosis of osteoporosis, the therapeutic interventions available, and the approaches for the prevention of fragility fractures, in postmenopausal women, and in men aged 50 years or older. Published on the 

, the guideline is accompanied by a 2-page summary of the main recommendations, a set of 52 frequently asked questions, and a multitude of other useful resources.

Composed by Gregson and 19 colleagues from institutions across Europe, recommendations in the document are based on data obtained within systematic reviews, meta-analyses and randomized controlled trials related to osteoporosis management. In their statement announcing the release, the IOF highlighted multiple updates within the guideline, including recommendations regarding fracture liaison services, training of clinicians and allied health professionals, service commissioning, and criteria for audit and quality improvement in service provision. Other major updates within the new guidelines highlighted by the IOF in their statement included:

Greater emphasis on vertebral fracture detection

New concept of ‘very high fracture risk’ which should prompt consideration of the use of parenteral anti-osteoporosis therapy

New guidance regarding anabolic treatment options

Urgent need to get patients with a fragility fracture onto treatment to reduce refracture risk with follow-up to check tolerance and ensure adherence

Use of intravenous zoledronate as a first-line anti-osteoporosis therapy

Intervention thresholds for patients too frail to undergo bone density scanning

“Given the underdiagnosis and undertreatment of osteoporosis, it is critically important that physicians are aware of best-practice standards and the many recent advances in the field. We hope that the updated NOGG guidelines, which include recommendations for improved service provision in both primary and secondary care settings, will be widely disseminated to clinicians across the UK,” added John Kanis, honorary president of the IOF and a professor and director in the Centre for Metabolic Bone Diseases at the University of Sheffield, in the aforementioned statement.

Clinical Guideline for the Prevention and Treatment of Osteoporosis

” was published on the NOGG website and simultaneously published as an open-access position paper in 

On April 20, the UK National Osteoporosis Guideline Group released updated guidance for the diagnosis, prevention, and treatment of osteoporosis, which has received endorsements from the IOF and ESCEO.

New UK Guidelines Released for Diagnosis, Management of Osteoporosis 

Achieving treatment goals could extend life expectancy by more than a decade among adults with type 2 diabetes.

Using data from more than 400 patients and a diabetes-specific microsimulation model, investigators from the University of Florida determined those in the lowest population quartile for BMI, HbA1c, systolic blood pressure, and LDL-C experience life expectancy gains of 3.9, 3.8, 1.9, and 0.9 years, respectively, when compared to their counterparts in the highest quartile for each category.

“This study quantified the potential gains in LE associated with different levels of biomarkers in patients with diabetes. Differences in HbA1c and BMI were found to have the strongest association with LE gain from a population perspective,” wrote investigators.

As diagnoses of type 2 diabetes become more commonplace despite increasing prevention efforts, the research focus for many has shifted to potential avenues for improving quality of life and life expectancy among these patients. With this in mind, a team from the University of Florida led by Hui Shao, MD, PhD, used the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes model to quantify to potential gains in life expectancy from achieving different target levels for HbA1c, systolic blood pressure, LDL-C, and BMI in patients with type 2 diabetes.

Designed using data from the ACCORD trial, the BRAVO diabetes model is a discrete-time patient-level microsimulation model that leverages a patient’s risk profile to project long-term health outcomes. For the current study, investigators calibrated the model using data from NHANES linked with short-term mortality data from the National Death Index.

From the 2015-2016 NHANES survey cycle, investigators identified 421 patients representative of the US adult type 2 diabetes population for inclusion in their analysis. This sample had a mean age of 65 (SD, 8.9) years and 46% were women. Patients within the cohort were grouped into quartiles based on HbA1c, systolic blood pressure, LDL-C, and BMI.

HbA1c quartiles were defined as less than 6.4%, 6.4-7.2%, 7.3-8.2%, and greater than 8.2%. Systolic blood pressure quartiles were defined as less than 122 mmHg, 122-132 mmHg, 133-144 mmHg, greater than 144 mmHg. LDL-C quartiles were defined as less than 73 mg/dL, 73-96 mg/dL, 97-122 mg/dL, greater than 122 mg/dL. BMI quartiles were defined as less than 27, 27-31, 32-36, and greater than 36 kg/m2.

Compared to those in the highest quartile of BMI, those in the first, second, and third quartiles of BMI had 3.9, 2.9, and 2.0 years of additional life expectancy, respectively. Compared to those in the highest quartile of systolic blood pressure, those in the first, second, and third quartiles of systolic blood pressure had 1.9, 1.5, and 1.1 years of additional life expectancy, respectively. Compared to those in the highest quartile of LDL-C, those in the first, second, and third-lowest quartiles of LDL-C gained 0.9, 0.7, and 0.5 years of additional life expectancy, respectively.

When assessing the life expectancy based on HbA1c levels, results indicated those in the third quartile had an additional 3.4 years in life expectancy compared to those in the highest quartile of HbA1c, but further reduction to the second quartile was only associated with a mean of 0.5 years of life expectancy gained. Further analysis demonstrated reduction to the lowest quartile was not associated with any additional gains of life expectancy, with those in the lowest quartile gaining 3.8 additional years of life expectancy compared to those in the highest quartile of HbA1c.

“Our findings can be used by clinicians and patients in selecting optimal treatment goals, to motivate patients in achieving them, and to measure potential health benefits for interventions and programs to improve diabetes care in the US,” wrote investigators.

Potential Gains in Life Expectancy Associated With Achieving Treatment Goals in US Adults With Type 2 Diabetes

A microsimulation model provides insight into potential years of life expectancy gained by meeting recommended treatment goals for HbA1c, LDL-C, BMI, and blood pressure among adult patients with type 2 diabetes.

Study Quantifies Life-Years Added from Meeting Treatment Goals in Type 2 Diabetes

An observational study of children in Portugal provides data suggesting use of gonadotropin-releasing hormone agonist (GnRHa) was associated with increased body weight gain among children with central precocious puberty.

Assessing the anthropometric differences among children of both sexes before and after GnRHa treatment, results of the study, which included data from 241 patients treated over a 17-year period, suggests use of GnRHa treatment for central precocious puberty was associated with increases in BMI-SD score (BMI-SDS) that demised 1 year after discontinuation of treatment among girls, but this effect was not observed among boys and investigators purport differences in increases in height during the study could have contributed to the apparent lack of effect in boys versus girls.

“The treatment of CPP with GnRHa causes a transient increase in BMI-SDS with a return to the basal BMI-SDS a year after stopping GnRHa. The increase in BMI-SDS is more evident in children with normal weight before treatment, but this effect is reversible and does not induce obesity,” investigators wrote.

Led by Ana Luisa Leite, of the Centro Hospitalar de Vila Nova de Gaia, investigators designed their study as an observational cohort study of patients who received care at 1 of 11 pediatric endocrinology clinics throughout Portugal from January 2000 through December 2017. A total of 241 children with a diagnosis of central precocious puberty were identified for inclusion. Of these, 92 were included in the final study cohort. Of the 92 patients included in the study, 84 were girls and 8 were boys.

For the purpose of analysis, investigators defined a diagnosis of CPP as Tanner stage 2 breast development in girls younger than 8 years or testicular enlargement of 4 ml or greater in boys younger than 9 years with a baseline luteinizing hormone (LH) level of 0.3 IU/L or greater or a GnRHa-stimulated LH peak greater than 5 IU/L. Investigators noted idiopathic and other cases of CPP were included in their study. Exclusion criteria for the study included not receiving treatment with GnRH agonists or not having completed treatment, use of known weight-modifying medications, having a weight-modifying illness, or having missing or incomplete data.

The study cohort had a mean age at onset of symptoms of 6.5±1.6 years, 90% had idiopathic central precocious puberty as the main diagnosis, and 39% were overweight at baseline. Investigators pointed out boys made up 33% of the secondary central precocious puberty diagnoses.

Upon analysis, results suggested BMI-SDS tended to increase with treatment but decreased a year after stopping treatment. Investigators noted initial results suggested BMI-SDS variation at the end of treatment was negatively correlated with BMI-SDS at baseline (

 <.001). When assessing this association based on sex, results indicated BMI-SDS increased with GnRHa therapy in girls but diminished 1 year after stopping therapy. Investigators also pointed out boys grew taller and faster than girls in the study (

 <.001) and this could have influenced their BMI-SDS trajectory.

“In our study, we noted a similar increase in BMI, but we also observed its resolution and reversal after only 1 year of termination of the GnRHa therapy. As reported previously, our data demonstrated that the pattern of change in BMI-SDS varies according to the individual's BMI,” wrote investigators. “One explanation might be that fatty mass redistribution/deposition due to gonadal axis suppression is more significant in lean children than in overweight or obese children.”

Do GnRH Agonists Really Increase Body Weight Gain? Evaluation of a Multicentric Portuguese Cohort of Patients With Central Precocious Puberty,

An observational study from Portugal indicates GnRHa therapy as a treatment for central precocious puberty was associated with an increase in body weight that subsided 1 year after treatment cessation.