European Association for the Study of Diabetes 2020 Annual Meeting

EASD 2020

While studies have exhaustively examined links between physical activity levels and risk of death or cardiovascular disease, a new study from Lund University in Sweden is providing insight into the beneficial effects of physical activity on fracture risk in aging adults.

The study, which examined the impact of multiple variables on fracture risk in more than 30,000 middle-aged patients, returned results suggesting even moderate levels of leisure-time physical activity reduced fracture risk compared to those with low levels of activity.

“Our results support the theory that even moderate physical activity in adulthood is beneficial for preventing future fractures. Furthermore, these results indicate the importance of social and psychological factors for the risk of future fractures, with subjects living alone having a 10% increased risk after adjustment for potential confounders,” wrote investigators.

As it stands, further clarification and identification of risk factors for conditions like osteoporosis could result in tangible benefits for patients in the way of reduced fracture risk. With this in mind, a trio of investigators sought to determine what aspects of physical activity and psychosocial situation were associated with incident fracture.

For the purpose of their analysis, investigators chose to pull patient data from the Malmö Diet and Cancer (MDC) study, which was a prospective population-based cohort study that enrolled 30,477 patients from 1991-1996 and followed them through 2016. Of these, 18,325 patients were female. The overall study cohort had a mean age of 58.0±7.6, the median follow-up time was 20.7 (IQR, 9.5) years, and an incident fracture occurred in 8240 (27%) of participants.

Investigators chose first incident fracture of the spine, thoracic cage, arms, shoulders, hands, pelvis, hips, or legs as the primary outcome of their study. These incident fracture events were identified through the National Patient Register. Associations between baseline variables and incident fracture were assessed in Cox regression models. Of note, baseline variables included in the investigators’ analysis included age, sex, BMI, systolic blood pressure, diastolic blood pressure, current smoking status, and daily alcohol intake.

In their analyses, results indicated age, female sex, body mass index, previous fracture, reported family history of fracture (

for all <.001), low leisure-time physical activity (

 <.001), and no or high alcohol consumption (

=.005) were factors independently associated with incident fracture. Additionally, results also indicated fracture risk score was strongly associated with incident fracture (

When assessing fracture risk in men, the incidence rate was 23.2 per 1000 person-years among men with 6 or more risk factors compared to 5.3 per 1000 person-years in those with no risk factors (HR, 5.5; 95% CI, 3.7-8.2). Among women, the incidence rate was 10.7 per 1000 person-years in those with no risk factors and 28.4 per 1000 person-years in women with 6 or more risk factors (HR, 3.1; 95% CI, 2.4-4.0).

For physical activity, results suggested even moderate levels of lesser-time physical activity were associated with a lower risk of incident fracture. Investigators pointed out results also suggested heavy work, living alone, smoking, and no or high alcohol consumption was associated with increased risk of incident fracture.

“In particular, a combination of several risk factors distinctly increases the fracture risk in later life. Our results emphasize the importance of these factors in public health initiatives for prevention of fractures,” wrote investigators.

Physical Activity and Psychosocial Factors Associated With Risk of Future Fractures in Middle-Aged Men and Women,

Articles

An analysis of more than 30k middle-aged adults from a prospective cohort study in Sweden is providing insight into the effects of exercise and other variables on fracture risk in these patients. 

Moderate Physical Activity Could Lower Fracture Risk in Middle-Aged Adults

New research from an international team based in London indicates measurements of sodium levels in the blood of patients hospitalized with COVID-19 could help clinicians identify patients at a greater risk of death or respiratory failure.

The analysis, which included data from nearly 500 patients hospitalized with COVID-19 at a pair of London-based hospitals, indicates patients who developed high sodium levels during their hospital stay were 3 times more likely to die than those who maintained normal sodium levels.

"This study shows for the first time that patients presenting at the hospital with COVID-19 and low sodium are twice as likely to need intubation or other means of advanced breathing support as those with normal sodium," said lead investigator Ploutarchos Tzoulis, MD, PhD, MSc, Honorary Associate Professor in Endocrinology at University College London (UCL) Medical School in London, 

In the past, research has established a link between dysnatremia and risk of mortality among patients with bacterial pneumonia. With this in mind, investigators sought to determine whether measurements of sodium concentration in patients with COVID-19 provided any prognostic value. To do so, they designed their analysis as a retrospective longitudinal cohort study of patients presenting with COVID-19 to a pair of hospitals in London from February-May 2020.

All patients identified for inclusion in the analysis were aged 16 years or older and had a positive RT-PCRT test for SARS-CoV-2 on nasopharyngeal swab or other specimen. During their hospitalization, participants underwent measurements of serum sodium, urea, creatinine, and CRP on the day of presentation, day 3, day 6, day 11, day 18, the day of admission to the ICU, and within the 48 hours prior to discharge or death.

Primary outcome measurements for the study included inpatient mortality, need for advanced respiratory support, and acute kidney injury. For the purpose of analysis, hyponatremia was defined as a serum sodium level less than 135 mmol/L and hypernatremia as a serum sodium level greater than 145 mmol/L.

In total, 488 patients were identified for inclusion in the study. This cohort had a median age of 68 years. At presentation, 24.6% of patients were hyponatremic and 5.3% had hypernatremia. Investigators noted most cases of hyponatremia were due to hypovolemia.

In their analyses, hypernatremia two days after admission and exposure to hypernatremia at any point during hospitalization was associated with a 2.34-fold (95% CI, 1.08-5.05; 

=.0014) and a 3.05-fold (95% CI, 1.69-5.49; 

<.0001), respectively, increased risk of death compared to their normonatremic counterparts. Further analysis suggested hyponatremia at admission was associated with a 2.18-fold (95% CI, 1.34-3.45; 

=.0011) increase in risk of needing ventilatory support.

Investigators also pointed out hyponatremia was not a risk factor for in-hospital mortality, except among a subgroup of patients with hypovolemic hyponatremia. Additionally, sodium levels were not associated with risk for acute kidney injury or length of hospitalization.

"Sodium measurements can inform doctors about which COVID-19 patients are at high risk of deterioration and death," Tzoulis added. "Sodium levels can guide decision making about whether a COVID-19 patient needs hospital admission or monitoring in the intensive care unit."

Dysnatremia is a predictor for morbidity and mortality in hospitalized patients with COVID-19,

Journal of Clinical Endocrinology & Metabolism.

An analysis of nearly 500 patients hospitalized with COVID-19 from London suggests dysnatremia could help signal which patients were at an increased risk of complications, including death and need for respiratory support. 

High Sodium Levels Predict Risk of Mortality, Need for Ventilatory Support in COVID-19 Patients

New research from a team led by investigators at the National Institutes of Health (NIH) suggests obesity could impact 

An analysis of 90 girls aged 8-15 years, results of the analysis suggest girls with greater amounts of total body fat saw the timing of puberty, presence of reproductive hormone levels, and development of reproductive organs develop at a different rate than their counterparts

"We found that in mid- to late puberty, girls with greater total body fat demonstrated higher levels of some reproductive hormones including follicle-stimulating hormone (FSH), inhibin B and male-like hormones such as testosterone. In some girls with higher total body fat, higher testosterone levels were associated with irregular menstrual cycles, acne and excess body hair," said lead investigator Natalie D. Shaw, MD, of the National Institute of Environmental Health Sciences (NIEHS) part of the NIH, 

While previous epidemiologic studies demonstrating obese girls experience thelarche and menarche earlier than girls of normal weight, investigators noted no studies have investigated how bodyweight impacts clinical and biochemical pubertal biomarkers in this patient population. With this in mind, Shaw and a team of colleagues from the NIH and the Centers for Disease Control and Prevention (CDC) designed the current study to further investigate this transition in girls from the Triangle region of North Carolina.

For inclusion in the study, investigators recruited pre-menarchal subjects with no chronic medical conditions, free from any medications or supplements that might impact puberty, and had no history of precocious puberty or premature pubarche. Additionally, subjects were required to be free from signs of hyperandrogenism. With enrollment taking place between January 2016-September 2020, investigators identified 80 girls for inclusion in their study.

As part of the study protocol, all patients were required to complete at least 1 study visit spaced approximately 8 months apart—the mean number of study visits per person was 2.8±1.7These visits included a complete physical exam with Tanner staging of the breast and pubic hair, breasts ultrasound for breast morphological statin (B-MORPH), and blood and urine collection. Additionally, monarchal status was determined at each study visit and every 3 months by phone until September 2020.

For the purpose of analysis, associations between the aforementioned factors and total body fat were tested using mixed, multi-state, or Cox proportional hazards models adjusted for baseline BMOPRH.

At baseline, normal weight girls were older than overweight or obese girls (11.3 vs 10.2; 

 <.01) at baseline and had more advanced BMOPRH (

 <.01). Results of the investigators’ initial analyses suggest luteinizing hormone, estradiol, and ovarian and uterine volumes increased with time and total body fat appeared to have no effect on this.

Investigators noted an interaction time-total body fat interaction for follicle-stimulating hormone, inhibin B, estrone, total and free testosterone, and androstenedione. In this interaction, levels were initially similar but increased in girls with higher total body fat, plateaued in girls with mod-range total body fat, and decreased in girls with lower total body fat at 1 year. Additionally, results indicated girls with higher total body fat appeared to progress through BMOPRH stage D more lowly but did achieve menarche earlier than girls with lower levels of total body fat.

"In late puberty, girls with greater body fat also showed delayed breast maturation, as determined by breast ultrasound, and earlier menarche. There were no differences in maturation of the ovaries or uterus as a function of body fat,” added Shaw.

Longitudinal investigation of pubertal milestones and hormones as a function of body fat in girls

A study of 80 young women is providing clinicians with insight into how total body fat can impact the timing of puberty and levels of pubertal hormones in women. 

Excess Body Fat Impacts Puberty Timing In Young Women

This article was originally published on 

Data from a 12-week trial of aging men on testosterone therapy suggests testosterone therapy had no beneficial effect on vascular health or function.

While some have theorized testosterone therapy could counteract the effects of aging on arteries, results of the trial indicate improvements in artery health and function were linked to increased physical activity and not testosterone therapy.

"The global increase in testosterone use has been very large, particularly among middle-aged and older men who might see it as a restorative hormone to increase energy and vitality," said lead investigator Daniel J. Green, PhD, Winthrop Professor and cardiovascular exercise physiology researcher in the School of Human Sciences at The University of Western Australia in Perth, 

. "However, previous studies are mixed as to whether replacement testosterone is beneficial or not, or whether it provides additional benefit over and above the effects of an exercise program."

With an interest in further understanding the effects of testosterone therapy in aging men, Green and a team of colleagues designed the current study to assess the impact of testosterone versus exercise training on endothelium-dependent flow-mediated dilation percentage and endothelium-independent glyceryl trinitrate percent responses. Designed as a 2x2 factorial randomized controlled trial, the 12-week study enrolled 80 men between 50-70 years of age with a waist girth of 95 centimeters or more and low to normal serum testosterone levels.

In total, 78 patients were included in the final analysis and underwent randomization. Of these 78, 21 were randomized to topical testosterone and a strutted exercise program, 18 were randomized to testosterone with no exercise, 20 were randomized to placebo therapy and no exercise, and 19 were randomized to placebo therapy with exercise. Of note, those randomized to testosterone therapy received 5% testosterone cream.

Investigators pointed out prescreening questionnaires allowed for the exclusion of patients based on smoking status, history of cardiovascular disease, and other factors. Additional inclusion criteria included having a fasting serum total testosterone of 6-14 nmol/L, a total cholesterol of 7 mmol/L or more, and a minimum eGFR of 45 ml/min.

Upon analysis, results indicated serum testosterone levels increased beyond 14 nmol/L among 62% of those randomized to testosterone therapy. Results also indicated exercise training was associated with increased flow-mediated dilation percent (

=.033; testosterone and exercise: +0.5, placebo and exercise: +1.0 versus testosterone and no additional exercise: −0.7, placebo and no additional exercise: +0.2%), while this effect was not apparent among those receiving testosterone therapy and it was not additive to exercise (

Additionally, there were no significant exercise or drug main effects on glyceryl trinitrate responses (

 >.05). Further analysis suggested exercise training was associated with improved endothelium-dependent vasodilator function, but testosterone therapy did not appear to influence flow-mediated dilation percent or add to the benefit of exercise. Investigators highlighted vascular smooth muscle sensitivity to nitric oxide was not modified by exercise, testosterone, or their combination.

“The results of our study suggest that if you are a healthy but relatively inactive middle-aged or older man with increased abdominal girth, and you are worried about your risk of heart attack, stroke or diabetes, then an exercise program with some support and supervision can help to improve the function and health of your arteries,” Green said. “Testosterone therapy may have some benefits, for example in increasing muscle mass in the legs, however, we didn’t find any benefits in terms of artery function, which is a determinant of future cardiovascular risk.”

Testosterone and Exercise in Middle-to-Older Aged Men

An analysis of data from a 12-week trial in overweight men on testosterone therapy is providing insight into the potential effect of testosterone therapy on vascular health and function. 

Analysis Finds Testosterone Therapy Provides No Benefit on Vascular Function

An analysis of more than 3 dozen studies examining behavioral 

 interventions has returned positive evidence in support of using digital tools for self-monitoring.

Results of the systematic review outline the potential usefulness of these new technologies by providing evidence suggesting more than 70% of patients using digital self-monitoring technologies experienced weight loss and also finding rates of engagement were greater with digital rather than manual self-monitoring in 21 of 34 comparisons.

"Digital health tools have flourished in the past decade," said Michele L. Patel, PhD, post-doctoral research fellow, Stanford Prevention Research Center, Stanford University School of Medicine, 

."What this paper sought out to explore was whether tracking via these digital tools is effective at producing greater weight loss."

With the obesity epidemic expected to expand its foothold in the US and other countries, Patel, Lindsay Wakayama, PhD, and Gary Bennet, MD, sought to evaluate how digital monitoring is being used and whether use was associated with weight loss. To do so, investigators designed the current study as a systematic review of studies examining digital self-monitoring in behavioral weight loss interventions from randomized clinical trials within the PubMed, Embase, Scopus, PsycInfo, CINAHL, and ProQuest Dissertations & Theses databases.

For inclusion in the review, studies needed to be designed as randomized controlled trials, examine interventions lasting at least 12 weeks, report weight outcomes 6 months after baseline, and include outcomes on self-monitoring engagement and their relationship to weight loss. Eligible trials were required to enroll adult patients aged 18 years or older and be published between 2009-2019. The initial search yielded 4248 records. After application of the inclusion criteria, a total of 53 papers describing 39 unique randomized trials were identified for inclusion.

These 39 trials included 8232 patients with a mean age ranging from 29-56 years. The mean baseline BMI among these studies ranged from 28.3-37.0 kg/m2. Most of the trials were conducted in the US and the duration of interventions ranged from 3-24 months, with a median of 6 months.

In total, 67 interventions using digital self-monitoring were identified within the 39 trials—weight was tracked 72% percent of interventions with digital self-monitoring, diet was tracked in 81%, and physical activity was tracked in 82%. The most common medium of self-monitoring was websites and other common mediums included apps, wearables, electronic scales, and text messaging.

"This may be because many digital tools are highly portable, and therefore allow the user to track any time of the day; digital tools also may make tracking quicker, and may be less burdensome to use," added Patel.

Results of the investigators’ analysis indicated few interventions had engagement rates of 75% or more of the study days. Additionally, results suggested rates of engagement were greater with digital- rather than paper-based arms in 21 out of 34 comparisons and lower in only 2 comparisons. When assessing impact of self-monitoring adherence, investigators found greater digital self-monitoring was associated with weight loss in 74% of occurrences.

Self-Monitoring via Digital Health in Weight Loss Interventions: A Systematic Review Among Adults with Overweight or Obesity

A review of 39 randomized clinical trials examining weight loss interventions is providing clinicians with an overview of engagement rates, mediums used, and effects of digital self-monitoring for weight loss among obese or overweight patients.

Digital Self-Monitoring Linked to Improvements in Weight Loss Trials

New research from investigators at Brigham and Women’s Hospital suggests there could between timing of physical activity and cardiovascular risk of men with 

While results indicate physical activity at any time was beneficial for reducing cardiovascular risk, investigators purport results provide evidence that exercising at a certain point during the day could provide additional benefit for a patient’s cardiovascular health, but note these effects were not seen in women.

"The general message for our patient population remains that you should exercise whenever you can as regular exercise provides significant benefits for health," said study investigator Jingyi Qian, PhD, of the Division of Sleep and Circadian Disorders at the Brigham, 

. "But researchers studying the effects of physical activity should take into account timing as an additional consideration so that we can give better recommendations to the general public about how time of day may affect the relationship between exercise and cardiovascular health."

With more evidence surrounding the effects of physical activity on cardiovascular health in various patient groups, Qian and a team of colleagues from Brigham and Women’s Hospital sought to evaluate associations of moderate-to-vigorous physical activity with cardiorespiratory fitness and cardiovascular disease risk among patients with type 2 diabetes. To do so, investigators designed their study as an observational analysis of data from the Look Action for Health in Diabetes (AHEAD) study—a major trial that began in 2001 and monitored the health of more than 5,000 patients with type 2 diabetes considered overweight or obese. Of the more than 5000 included in the original study, 2153 provided data related to physical activity from 7-day hip-worn accelerometer.

For the purpose of analysis, patients were categorized into 6 groups based on the time of day with the majority of bout-related moderate-to-vigorous physical activity. These groups were defined as 50% or more of bout-related activity occurring during the same time window, less than 50% of bout-related activity in any single time category, and 1 or more days without bout-related activity per week. Of note, those with 50% or more of their bout-related activity were grouped according to when that activity occurred: morning, midday, afternoon, or evening.

In their analyses, cardiorespiratory fitness was highly associated with timing of bout-related moderate-to-vigorous physical activity (

=.0005), regardless of weekly volume and intensity, but this effect was only present among men (

=.02). When assessing the effect of timing choice, men in the midday group appeared have the lowest level of fitness while the mixed time group was the least fit among women.

Further analysis indicated Framingham risk score was associated with timing of bout-related moderate-to-vigorous physical activity, but this also differed by sex (

=.0007). When assessing for 4-year Framingham risk score, men in the morning group appeared to have the highest score (2.18% [0.70, 3.65]) and investigators noted this association was not seen in women within the study.

"Interest in the interaction between physical activity and the circadian system is still just emerging," Qian said. "We formed a methodology for quantifying and characterizing participants based on the clock-time of their physical activity, which allows researchers to carry out other studies on other cohorts."

Association of Objectively Measured Timing of Physical Activity Bouts With Cardiovascular Health in Type 2 Diabetes

An analysis of more than 2k patients from within the Look AHEAD study suggests the timing of physical activity could play a role in mitigating cardiovascular risk among men with type 2 diabetes considered overweight or obese. 

When Men Exercise Could Influence Risk of Cardiovascular Disease, Study Finds

A new study suggests women with hypertensive disorders of pregnancy should undergo regular cardiovascular screenings, even if they are not showing symptoms of cardiovascular disease.

An analysis of data from 132 women suggests women with a history of hypertensive disorders of pregnancy had notable differences in left ventricular structure and function a decade after pregnancy.

"Hypertension is a silent killer," said lead investigator Malamo Countouris, MD, a clinical instructor in cardiology at Pitt's Department of Medicine and a co-director of the UPMC Magee-Womens Hospital Postpartum Hypertension Clinic, 

 "None of the women in our study had clinical symptoms of heart disease—they are young and probably feel well and healthy, and may not be seeing a health care provider regularly—but it's important to start screening them for high blood pressure early."

Led by Countouris, a team from the University of Pittsburgh sought to examine the long-term effects of hypertensive disorders of pregnancy on cardiac remodeling. To do so, investigators designed their study as an analysis of data from women identified within the Magee Obstetric Maternal and Infant database from the University of Pittsburgh. From the database, investigators obtained information related to medical history of women with pregnancies delivered from 2008-2009. These women were then asked to take part in an additional; visit between 2017-2019 where they underwent transthoracic echocardiograms and assessments ofheight, weight, and blood pressure by standardized methods.

In total, investigators identified 132 women for inclusion in their study. Of these, 102 had normotensive pregnancies and 30 had hypertensive digs-orders of pregnancy, including 21 with pre-eclampsia and 9 with gestational hypertension. The overall cohort was 10±1 years removed from delivery and had a mean age of 39±6 years. Of the women with pre-eclampisa, 6 had severe pre-eclampsia and 7 experienced a pre-term delivery.

Upon analysis, those with hypertensive disorders of pregnancy during their index pregnancy were more likely to have current hypertension at 8-10 years after delivery compared to their counterparts without hypertensive disorders of pregnancy when measured according to visit blood pressure or antihypertensive medication use (63.3% vs 25.5%; 

<.0001). Additionally, women with hypertensive disorders of pregnancy were more likely to have diabetes (20.7% vs 7.0%; 

=.03), higher systolic blood pressure (125±12 mmHg vs 114±13 mmHg; 

 <.0001), higher diastolic blood pressure (82 ±10 mmHg vs 74±9 mmHg; 

 <.0001), and there appeared to be a trend toward a higher proportion of placental maternal vascular malperfusion (MVM) lesions (63.3% vs 45.1%; 

After adjustment for race, age, MVM lesions, BMI, current hypertension, and HbA1c, women with a history of hypertensive disorders of pregnancy had greater inter ventricular septal thickness and relative wall thickness then those with normotensive pregnancies. Further analysis indicated both a history of hypertensive disorders of pregnancy and current hypertension had greater portions of left ventricular remodeling compared to all other groups. Additionally, investigators noted these patients also had lower mitral inflow E/A ratio and annular e’.

"Identifying women at high risk can provide a window of opportunity for targeted interventions to prevent heart disease," said Countouris. "Suggesting simple changes in lifestyle or diet, including regular exercise and better management of other cardiovascular risk factors, can prevent adverse changes in the heart and lower the risk of heart disease later in life."

Association of Hypertensive Disorders of Pregnancy With Left Ventricular Remodeling Later in Life

Journal of the American College of Cardiology.

An analysis of data from more than 130 women suggests hypertensive disorders of pregnancy were associated with cardiac remodeling and risk of cardiovascular disease later in life. 

Hypertensive Disorders of Pregnancy Associated with Heart Disease Risk a Decade Later

: A woman in her 50’s with a history of asthma presents to the emergency department for cough, tactile fever and SOB. She denies syncope, palpitations, chest pain or other complaints. She thinks she’s probably having an asthma attack but hasn’t had one in over a decade so did not have medicine at home.

: Vital signs are notable for a pulse of 134, BP 113/62, temperature is 98.6, and a saturation of 95% on RA. Exam is notable for obesity, tachycardia, and mild wheezing with good air movement and no respiratory distress. There is no leg edema.

COMPUTER EKG READ: Sinus tachycardia, Left axis deviation, Low voltage QRS, Inferior infarct, age undetermined.

Our latest case report from Dr. Brady Pregerson features a woman in her 50s presenting with cough, tactile fever, and shortness of breath. Can you determine the correct diagnosis?

Case Report: Cough and Tachycardia 

New research suggests more than 50% of patients hospitalized with severe coronavirus disease 2019 (COVID-19) could suffer long-term heart damage. 

An analysis of MRI data more than 140 patients discharged from acute care hospitals, results indicate about half of the patients hospitalized with severe COVID-19 with increased troponin levels appeared to suffer from subsequent cardiovascular issues in the following months, with infarction, myocarditis, ischemia, and combinations of all 3 appearing in this patient population.

“Importantly, the pattern of damage to the heart was variable, suggesting that the heart is at risk of different types of injury,” said Marianna Fontana, MD, lead investigator and a professor of cardiology at University College London, 

. “While we detected only a small amount of ongoing injury, we saw injury to the heart that was present even when the heart's pumping function was not impaired and might not have been picked up by other techniques. In the most severe cases, there are concerns that this injury may increase the risks of heart failure in the future, but more work is needed to investigate this further.”

With previous studies suggesting severe COVID-19 could have lingering effects on cardiovascular health and those with pre-existing cardiovascular conditions at an increased risk of severe outcomes during an infection, Fontana and a team of colleagues designed the current study to assess the potential for myocardial injury in recovered patients. With this in mind, investigators designed their study as an analysis of patients treated at 6 different London-area hospitals.

For inclusion in the analysis, patients needed to be discharged before June 20, 2020, have a confirmed diagnosis of COVID-19, and have undergone multi-parametric cardiovascular magnetic resonance (CMR) at least 1 month after discharge from the hospital. Additionally, patients were required to have elevated troponin levels, which was defined as hsTnT greater than 14 ng/L for females or greater than 34 ng/L for men, depending on the hospital.

In total, investigators identified 148 patients for inclusion in their analysis. The mean age of this group was 64±12 years, 70% were men, 32% required ventilatory support, and the median time after discharge to CMR was 68 days.

Upon analysis, investigators found patients had a mean LVEF of 89% (67±11%). Results also indicated late gadolinium enhancement or ischemia was observed in 80 of the 148 patients included in the study. Specifically, a myocarditis-like scar was seen in 39 patients, infarction or ischemia was noted in 32 patients, and the presence of both was observed in a group of 9 patients.

When assessing myocarditis-like injuries, investigators pointed out injury was limited to 3 or less myocardial segments in 35 of 40 cases and there was no observed left ventricular dysfunction observed. Additionally, investigators noted 30% of these patients had active myocarditis. Investigators found myocardial infarction in 28 of the 148 patients and inducible ischemia in 20 of 76 with data related to adenosine stress perfusion.

Among portents with an observed ischemic injury pattern (n=41), none of them had a past history of coronary artery disease. Furthermore, investigators noted there was no evidence of diffuse fibrosis or edema in the remote myocardium when comparing COVID-19 patients to matched controls treated prior to January 1, 2020.

"These findings give us two opportunities: firstly, to find ways of preventing the injury in the first place, and from some of the patterns we have seen, blood clotting may be playing a role, for which we have potential treatments. Secondly, detecting the consequences of injury during convalescence may identify subjects who would benefit from specific supporting drug treatments to protect heart function over time,” added Fontana.

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance

An analysis of more than 100 patients hospitalized with severe COVID-19 indicates subsequent heart damage was discovered in more than half of these patients in imaging more than a month after discharge. 

Heart Damage Common Following Hospitalization for Severe COVID-19

A 20-year follow-up study of gender diverse people suggests transgender men receiving testosterone therapy were at an 11% greater risk of developing blood clots.

Led by investigators from the Department of Endocrinology and Center of Expertise on Gender Dysphoria at Vrije Universiteit Medical Center, results of the study indicate patients saw the greatest increase of hematocrit during the first year and provide insight into potential avenues for mitigating this risk.

"Erythrocytosis is common in transgender men treated with testosterone, especially in those who smoke, have high body mass index (BMI) and use testosterone injections," said lead investigator Milou Cecilia Madsen, MD, of the VU University Medical Center Amsterdam in the Netherlands, 

. "A reasonable first step in the care of transgender men with high red blood cells while on testosterone therapy is to advise them to quit smoking, switch injectable testosterone to gel, and if BMI is high, to lose weight."

With testosterone therapy common among transgender men undergoing gender-affirming treatment, investigators sought to develop a greater understanding of the prevalence and predictors of erythrocytosis in these patients. To do so, the current study was designed as part of the Amsterdam Cohort of Gender Dysphoria (ACOG) study, which was conducted from 1972-2015 and contained data from 6793 people who visited the Center of Expertise on Gender Dysphoria.

For the purpose of the current study, investigators only included transgender men who started testosterone therapy and had at least one follow-up visit after starting testosterone therapy. Of note, the investigators excluded patients if they discontinued testosterone therapy during follow-up or if they were missing information related to the starting date of testosterone therapy or laboratory results.

Additionally, the study also allowed investigators access to information related to medication use, medical history, duration of hormonal treatment, testosterone administration route, BMI, tobacco use, alcohol use, and laboratory results of testosterone levels and hematocrit.

In total, 1073 patients were identified for inclusion in the study. The ACOG study included 2398 transgender men, but 431 were excluded due to a missing start date of hormone therapy and an additional 894 were excluded due to no available laboratory results. Of the 1073 included, the median age at the start of hormone therapy was 22.5 (IQR, 18.4-31.8) years and the mean BMI at the start of hormone therapy was 24.5 (SD, 5.5) years. Inv4estigaots noted 38% reported tobacco use and 8.6% reported having conditions associated with erythrocytosis—these included pulmonary conditions associated with erythrocytosis (7.6%), obstructive sleep apnea (0.7%), and polycythemia vera (0.4%).

For the purpose of analysis, investigators categorize patients based on hematocrit levels. These groups were defined as greater than 0.50 l/l, greater than 0.52 l/l, and greater than 0.54 l/l. 

Upon analysis, results indicated erythrocytosis occurred in 11% of transgender men with hematocrit levels of 0.50 l/l, 3.7% of transgender men with hematocrit levels greater than 0.52 l/l, and 0.5% of transgender men with a hematocrit level greater than 0.54 l/l. Results of the analysis suggest tobacco use (OR, 2.2; 95% CI, 1.6-3.3), long-acting undecanoate injections (OR, 2.9; 95% CI, 1.7-5.0), age at initiation of hormone therapy (OR, 5.9; 95% CI, 2.8- 12.3), BMI (OR, 3.7; 95% CI, 2.2-6.2), and a medical history of pulmonary conditions (OR, 2.5; 95% CI, 1.4-4.4) were associated with increased risk of erythrocytosis in patients with hematocrit greater than 0.50 l/l.

Additionally, results indicated hematocrit levels increased most during the first year of testosterone therapy, with levels increasing from 0.39 l/l at baseline to 0.45 l/l after the first year. Investigators pointed out that there was only a slight continuation of this increase in the remainder of the follow-up period, but the risk for develop erythrocytosis continued to increase from 10% after 1 year to 38% after 10 years.

Erythrocytosis in a large cohort of trans men using testosterone: a long-term follow-up study on prevalence, determinants and exposure years

Journal of Clinical Endocrinology and Metabolism.

Data from a 20-year follow-up of gender diverse individuals indicate transgender men receiving testosterone therapy were at an 11% increased risk of developing erythrocytosis. 

Transgender Men Receiving Testosterone at Greater Risk of Blood Clots

In what investigators are calling the first study of its kind, new research from Northwestern Medicine suggests the cardiovascular health of a mother during her first pregnancy could offer insight into the long-term health of her children.

An analysis of more than 2000 mother-child pairs indicates 

 at 28 weeks’ gestation, which was assessed based on BMI, blood pressure, and other factors, can help predict offspring 

"Our new findings suggest that the children of this large group of mothers with suboptimal cardiovascular health may be at higher risk for early declines in their own cardiovascular health during childhood," said lead investigator Amanda Perak, MD, assistant professor of pediatrics and preventive medicine at Lurie Children's Hospital and Northwestern University Feinberg School of Medicine, 

. "If we can address these underlying causes of children's poor heart health, we can hopefully help them avoid future heart attacks, strokes and premature deaths as they grow up."

Using data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study and HAPO Follow-up study, Perak and a team of colleagues from Northwestern and Lurie Children’s Hospital designed their study with the hope of assessing how maternal cardiovascular health during pregnancy might be associated with offspring cardiovascular health in adolescence. From the studies, investigators identified a cohort of 2302 mother-child dyads from 9 centers in multiple countries for inclusion. Of note, this represents 48% of the HAPO Follow-up study population.

For the purpose of analysis, cardiovascular health was assessed according to 5 metrics: BMI, blood pressure, total cholesterol levels, glucose level, and smoking status. Mothers underwent assessments of each of these metrics at 28 weeks’ gestation. For their offspring, investigators assessed cardiovascular health using 4 metrics: BMI, blood pressure, total cholesterol levels, and glucose level, which were assessed between the ages of 10-14 years. Scores for mothers ranged from 0-10 and scores for offspring ranged from 0-8.

From the HAPO studies, investigators obtained disinformation related to maternal demographics, parity, and alcohol use through patient questionnaires. Additionally, maternal gestational age was determined by last menstrual period or an ultrasound. All of these factors were used as covariates in fully-adjusted analysis.

Among the dyads included in the study, mothers had a mean age of 29.6 (SD, 2.7) years and children had a mean age of 11.3 (SD, 1.1) years. During pregnancy, mothers had a mean maternal cardiovascular health score of 8.6 out of 10.

Upon analysis, 32.8% of pregnant mothers had metrics considered ideal, but 6.0% had 2 or more poor metrics and the distribution of cardiovascular health categories among offspring varied according to maternal cardiovascular health category. In adjusted models, results indicated women with worse maternal cardiovascular health, which was defined as having 2 or more poor metrics, had a greater relative risk of having offspring with 1 (RR, 2.02; 95% CI, 1.55-2.64) and 2 or more (RR, 7.82; 95% CI, 4.12-14.85) poor metrics when compared to mothers with ideal metrics.

In fully-adjusted models, which accounted for birth factors including preeclampsia, did not fully explain significant associations observed in the other analyses. Specifically, results indicated children born to mothers with 2 or more poor metrics during pregnancy were at a 6.23-fold increase in risk of having 2 or more poor metrics at follow-up (RR, 6.23; 95% CI, 3.03-12.82).

"Our study combined multiple factors across a range of levels, and found that the associations of maternal cardiovascular health with offspring cardiovascular health were not driven by any one metric (such as obesity)," Perak added. "Instead, all metrics were related to the offspring's later health."

Associations of Maternal Cardiovascular Health in Pregnancy With Offspring Cardiovascular Health in Early Adolescence

An analysis of more than 2k mother-child pairs indicates assessments of maternal cardiovascular health could shed light on the potential for poor cardiovascular health among their children at ages 10-14 years. 

Cardiovascular Health During Pregnancy Helps Predict Heart Health in Children, Study Finds

: A 62-year-old male with a history of obesity, coronary disease, anxiety, and COPD presents to the emergency department for 2 days of intermittent shortness of breath after starting Keflex for cellulitis. He denies any chest pain, fever, rash, throat or lip swelling, or cough. He states the SOB seems to get worse about an hour after taking Keflex but then gradually gets better, which is why he thinks it may be an allergic reaction. His inhalers don’t seem to help.

: Vital signs are normal including pulse ox and respiratory rate. Exam is otherwise normal except for the cellulitis which is both in his groin below his pannus and in his right lower leg. Specifically, there is no rash, oral swelling, rales, or wheezing.

COMPUTER EKG READ: Sinus rhythm with occasional PVC. Possible inferior infarct, age undetermined

Our latest case report from Brady Pregerson, MD, features a 62 y/o male with a history of obesity, CAD, anxiety, and COPD presenting with SOB after stating cefalexin. Can you determine the correct diagnosis?

Case Report: Shortness of Breath After Cefalexin

This episode of the Endocrine Outlook podcast features an interview from MJH Life Sciences’ Medical World News from February, 14. In the interview, Ariana Chao, PhD, CRNP, an associate professor of nursing from University of Pennsylvania’s School of Nursing and author of a recent study published in the 

 titled “Dietary interventions for obesity: clinical and mechanistic findings”, discusses her study, its findings, and then takes a deeper dive into a general discussion related to dietary science and the role of nutrition in obesity management.

Podcasts

This episode of the Endocrine Outlook podcast features an interview on dietary interventions and the role of nutrition in obesity management with Ariana Chao, PhD, CRNP, of the University of Pennsylvania. 

Dietary Interventions and the Role of Nutrition in Obesity with Ariana Chao, PhD, CRNP

Results of a recent survey report indicate the COVID-19 pandemic has slowed the diagnosis and treatment of osteoporosis. 

the study focused on the changes that have occurred during the pandemic for patients with osteoporosis concluded there has been delays in dual-energy X-ray absorptiometry (DXA) scanning, problems with medication supply, a decrease in face-to-face consultations, and reductions in parenteral medication delivery.

Investigators first created surveys focused on the management and treatment of osteoporosis in the early stages of the pandemic and dispersed them to members of the International Osteoporosis Foundation (IOF) and the National Osteoporosis Foundation (NOF). Details such as the location and specialty of the physicians were included, as well as questions about face-to-face consultations, alterations in risk assessment and medication ascertainment, telemedicine experience, and electronic health record (EHR) utilization.

The NOF surveys were conducted between April 15 and 24, 2020, and IOF surveys between May 18 and June 8, 2020. The questionnaires were sent to 400 and 526 healthcare providers, respectively, via a SurveyMonkey platform. Survey responses were received from 209 members across 53 countries, including Europe (28%), North America (24%), the Asia Pacific region (19%), the Middle East (17%), and Latin America (12%). Participants were largely made up of physicians (85%), with the 3 main specialty groups being rheumatology (40%), endocrinology (22%), and orthopedics (15%).

Results indicated that 33% of physicians conducted telephone consultations and 21% utilized video consultations. Only 29% obtained DXA scans in a timely manner and 33% decided to delay DXA scans for when risk of COVID-19 infections had lessened. As the assessment and management of osteoporosis is mainly performed in-office, including the prescription and delivery of medication, physicians have faced logistical challenges during the pandemic. Access to the FRAX® fracture risk assessment tool was down 60% in April compared with February 2020, indicating that assessments have suffered during that time. Additionally, 43% of physicians had difficulty obtaining and dispensing osteoporosis medications to their patients; however, 60% had plans in place to identify patients receiving parenteral medication in order to proactively discuss care.

Of the 43% reporting issues with medications, the main reasons included limited supply, delays in administering parenteral medication, and patient reluctance to face-to-face visits. For the “healthcare professional-administered treatment,” 46% of physicians felt their safeguards were sufficient enough to minimize risk of COVID-19 exposure, 21% delayed treatment, 13% wanted to switch patients to an oral medication, 8% considered in-home administration, and 3% moved to another clinical location.

During the pandemic, 28% of providers conducted virtual appointments for established patients needing diagnostic services, 40% were available for established patients needing treatment decisions, yet only 19% were willing to see new patients via telemedicine. Additionally, although 63% prescribed both refills and new prescriptions for their patients, 28% were comfortable prescribing refills only, and 3% made new prescriptions only.

More than half (57%) of physicians surveyed were open to patients for telemedicine or face-to-face appointments for both emergencies and routine appointments, 21% were open for emergencies only, 23% for routine visits only, and 7% were closed entirely.

During the COVID-19 pandemic, 93% of physicians reported that it took as much or even more time to chart EHRs because of issues including communication and documentation, technical, workflow, treatment, and safety.

Reimbursement for telemedicine appointments proved to be another issue for physicians during that time, as it was unavailable for 20% of respondents, 14% were unsure about policies or status, and reimbursements were not applicable for 17%. 

“In many countries, there appears to be a substantial impact on reimbursement due to the change in number and type of patient visits, which may have implications for the ability to sustain and offer various osteoporosis clinical services and tests such as DXA,” investigators explained. “This must be carefully monitored as such changes could lead to a reduction in resources, a decrease in the assessment and treatment of patients with osteoporosis and osteoporosis-related fracture, and could ultimately translate into increased fracture rates and burden in the future.”

Investigators do believe there may be a silver lining to the shift into virtual appointments. 

The way in which osteoporosis care is offered has profoundly changed with almost 1 in 3 healthcare providers performing telephone consultations and 1 in 5 performing video consultations. Over a fifth of respondents reported over 20 telemedicine appointments per week,” they stated. “It will be interesting to see whether this modality of patient contact continues to be widely accepted and used as lockdowns lift and we return to the ‘new normal.’ The move toward telemedicine may be advantageous in the long term, with previous studies demonstrating financial savings and increased efficiencies for healthcare systems, and increased convenience and satisfaction for patients.”

The COVID-19 pandemic has impacted the way physicians treat their patients with osteoporosis, which in turn has negatively affected the assessment and management of these patients. This may result in a rise of fracture rates and morbidity. 

“The long-term impact the COVID-19 pandemic will have on chronic disease management and global health systems is difficult to predict,” investigators concluded. “In the short-term, we see immediate challenges to maintaining appropriate levels of care, particularly for patients at greater risk for the COVID-19 virus.”

How has COVID-19 affected the treatment of osteoporosis? An IOF-NOF-ESCEO global survey

A survey of providers within the IOF and NOF provides insight into the effects of the COVID-19 pandemic on the diagnosis and treatment of osteoporosis across multiple regions throughout the world. 

COVID-19 Pandemic Has Slowed Diagnoses, Treatment of Osteoporosis 

In the wake of many new studies outlining risks of worsening neurological health associated with poor glycemic control, new research suggests patients with 

 were also at a higher risk of cognitive decline and vascular dementia.

While investigators noted absolute rates of both conditions were low, higher than normal blood sugar levels were associated with a 42% increase in risk of cognitive decline over the next 4 years and a 54% higher risk of developing vascular dementia over the next 8 years.

"Previous research has found a link between poorer cognitive outcomes and diabetes but our study is the first to investigate how having blood sugar levels that are relatively high - but do not yet constitute diabetes - may affect our brain health,” said Victoria Garfield, lead investigator, and research associate at the University College London (UCL) Institute of Cardiovascular Science and the UCL MRC Unit for Lifelong Health & Ageing, 

To more fully understand the relationship between HbA1c levels and neurological health, Garfield and a team of colleagues designed their current study as an analysis of data from within the UK Biobank cohort. From the UK Biobank cohort, investigators identified data related to more 450,000 individuals, including 449,973 without dementia or cognitive impairment at baseline. From this cohort, investigators identified more than 50,000 patients with follow-up visual memory and exposure/covariate data or data related to structural MRI measures, which were used to assess cognitive decline.

Specific outcomes of interest for the analysis included incident all-cause dementia, vascular dementia, Alzheimer’s disease, hippocampal volume, white matter hyperintensity volume, and cognitive function and decline.

For the purpose of analysis, undiagnosed diabetes was defined as an HbA1c of 48 mmol/mol or greater, prediabetes was defined as 42-48 mmol/mol, and normoglycemia was defined as 35-42 mmol/mol. Of those included in the study, 210,309 had low-normal glycemic HbA1c levels, 198,969 were considered normoglycemic, 15,229 had prediabetes, 3279 had undiagnosed diabetes, and 22,187 had known diabetes.

In their analyses, investigators found a diagnosis of prediabetes (HR, 1.54; 95% CI, 1.04-2.28) or known diabetes (HR, 2.97; 95% CI, 2.26-3.90) was associated with incident vascular dementia. Additionally, known diabetes was associated with all-cause (HR, 1.91; 95% CI, 1.66-2.21) and Alzheimer’s dementia (HR, 1.84; 95% CI, 1.44-2.36) risk. When assessing cognitive decline, results suggested prediabetes (OR, 1.42; 95% CI, 1.48-2.96) and known diabetes (OR, 1.39; 95% CI, 1.04-1.75) were associated with increased risk of cognitive decline.

Further analysis indicated prediabetes, undiagnosed, and known diabetes were associated with higher white matter hyperintensity volumes (3%, 22%, and 7%, respectively) and lower hippocampal volume (36, 80, and 82 mm3, respectively). Investigators noted patients with normal HbA1c levels had 1% lower white matter hypertension volume and 12 mm3 greater hippocampal volume compared to their counterparts with increased HbA1c.

"In this relatively young age group, the risks of cognitive decline and of dementia are very low; the excess risks we observe in relation to elevated blood sugar only modestly increase the absolute rates of ill health. Seeing whether these effects persist as people get older, and where absolute rates of disease get higher, will be important,” added senior investigator Nishi Chaturvedi, PhD, professor in the UCL MRC Unit for Lifelong Health & Ageing.

HbA1c and brain health across the entire glycaemic spectrum

An analysis of data from the UK Biobank cohort is adding to the understanding of HbA1c and neurological health, suggesting patients with prediabetes were at an increased risk of cognitive decline and vascular dementia. 