Patrick Campbell is the senior 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. In his free time, he enjoys traveling, sports, and exploring the great outdoors. Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

Patrick Campbell

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A new study has returned surprising results, suggesting elevated NT-proBNP in early pregnancy was associated with a lower risk of hypertensive disorders and future hypertension.

An analysis of data from more than 4000 women, results of the study suggest higher NT-proBNP concentrations were associated with a lower risk of HDP and hypertension 2-7 years post partum, even after adjustment for variables including age, race, BMI, and lifestyle facts.

“Contrary to our hypothesis, we demonstrated that higher NT-proBNP concentrations in early pregnancy were associated with a lower risk of HDP. This association was present after controlling for early-pregnancy blood pressure and traditional risk factors,” wrote investigators.

Few conditions are associated with as substantial of an increase for risk of future cardiovascular disease as HDPs. With this in mind, investigators sought to determine whether measurements of NT-proBNP could serve as useful markers for subclinical cardiac dysfunction and a predictor of HDP as well as future hypertension risk. Performed on behalf of the NICHD nuMoM2b and NHLBI nuMoM2b Heart Health Study Networks, the study was designed to assess potential associations of NT-proBNP and HDP and future hypertension risk in a cohort of patients from The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health study.

From the prospective multicenter observational study, investigators were able to identify a cohort of 4103 nulliparous women with complete data and no pregnancy hypertension or diabetes at baseline who were treated at 8 clinical sites in the US. As part of their participation in the study, women provided a nonfasting blood sample in the first trimester, attended study visits at 3 time points prior to delivery, allowed medical records access, and agreed to postpartum follow-up. Follow-up was performed via telephone or email at 6-month intervals beginning at least 6 months after delivery and required patients to undergo an in-person cardiovascular assessment visit at least 2 years after delivery.

The study cohort had a mean age of 27 (SD, 5.6) years. Of the 4103 included in the study, 909 (22.2%) had an adverse pregnancy outcome and 817 (19.9%) had stage 1 hypertension or greater at the follow-up visit. Compared to women without hypertension at follow-up, women who had hypertension were older at baseline, more likely to self-report being non-Hispanic Black, and had higher early-pregnancy BMIs.

Results demonstrated higher NT-proBNP concentrations were associated with a lower risk of HDP (aOR per doubling, 0.81 [95% CI, 0.73-0.91]), which investigators noted persisted after adjustment for age, self-reported race and ethnicity, early-pregnancy BMI, smoking, and aspirin use. When assessing NT-proBNP and hypertension risk 2-7 years after delivery, results indicated higher NT-proBNP concentrations were associated with a Lowe risk of incident hypertension (aOR per doubling, 0.84 [95% CI, 0.770.93]), which investigators pointed out was an association that persisted after adjustment for confounders, including HDP.

“Findings from this cohort study support the importance of early-pregnancy cardiovascular adaptation not only for healthy pregnancy outcomes but also as a marker of future cardiovascular health. Taken together, these findings suggest that early-pregnancy cardiovascular physiology, as assessed with NT-proBNP concentration, may be an important determinant of both pregnancy outcome as well as future CVD,” wrote investigators.

Association of N-Terminal Pro–Brain Natriuretic Peptide Concentration in Early Pregnancy With Development of Hypertensive Disorders of Pregnancy and Future Hypertension

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New data suggests higher concentrations of NT-proBNP in early pregnancy could help predict women at a lower risk for developing hypertensive disorders of pregnancy and future hypertension.

High NT-proBNP in Early Pregnancy Could Signal Lower HDP, Future Hypertension Risk

An analysis of Medicare claims data is providing clinicians with new insight into the rate of long-term discontinuation of medications for obesity-related comorbidities following sleeve gastrectomy or gastric bypass.

A comparative effectiveness study of adult Medicare beneficiaries with up to 5 years of follow-up data, results of the study suggest both procedures were associated with medication discontinuation, but gastric bypass was associated with a greater cumulative incidence of medication discontinuation and a lower incidence of medication restart. 

“We believe these results demonstrate that both procedures are associated with long-term discontinuation of obesity-related medication and suggest that patients who underwent gastric bypass may be slightly more likely to remain free from their diabetes, antihypertensive, and lipid-lowering medications,” wrote investigators.

 has grown, so has the role of bariatric surgery in obesity management. To better inform clinical decision-making in patients with obesity, a team led by Ryan Howard, MD, of the Department of Surgery at the University of Michigan, designed their study to compare rates of medication discontinuation and restart of diabetes, hypertension, and lipid-lowering medications up to 5 years after gastric bypass or sleeve gastrectomy.

Using fee-for-service Medicare claims for patients who underwent laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass from 2012-2018. For the purpose of analysis, investigators created 3 study cohorts to assess effects on medication discontinuation in cohorts defined by use of diabetes, hypertension, and lipid-lowering medications, respectively.

The primary outcome of interest for the study was the discontinuation of diabetes, hypertension, or hyperlipidemia medications, with discontinuation defined as a lapse in claims for a medication refill of 6 months or longer. The secondary outcome of interest was the restart of medication after discontinuation.

Investigators identified a cohort of 95,405 patients for inclusion in their analyses. This cohort had a mean age of 56.6 (SD, 11.8) years and 74.8% (n=71,348) were female. Of the 95,405 patients in the overall study cohort, 30,588 were included in the diabetes cohort, 52,081 were included in the hypertension cohort, and 35,055 were included in the hyperlipidemia cohort.

In the diabetes cohort, the median follow-up time was 307 (IQR, 160-795) days for 16,809 patients who underwent sleeve gastrectomy and 260 (IQR, 158-702) days for 13,779 patients who underwent gastric bypass. In the hypertension cohort, the median follow-up time was 545 (IQR, 250-1091) days for 31,126 patients who underwent sleeve gastrectomy and 613 (IQR, 265-1349) days for 20,955 patients who underwent gastric bypass. In the hyperlipidemia cohort, the median follow-up time was 487 (IQR, 218-963) days for 20,654 patients who underwent sleeve gastrectomy and 419 (IQR, 172-1006) days for 14,401 patients who underwent gastric bypass.

Results of the analysis suggested gastric bypass, when compared with sleeve gastrectomy, was associated with a greater 5-year cumulative incidence of medication discontinuation in the diabetes cohort (74.7% [95% CI, 74.6-74.9] vs 72.0% [95% CI, 71.8-72.2]), the hypertension cohort (53.3% [95% CI, 53.2-53.4] vs 49.4% [95% CI, 49.3-49.5]), and the hyperlipidemia cohort (64.6% [95% CI, 64.5-64.8] vs 61.2% [95% CI, 61.1-61.3]). Similarly, further analysis indicated gastric bypass, when compared with sleeve gastrectomy, was associated with a lower incidence of medication restart in the diabetes cohort (30.4% [95% CI, 30.2-30.5] vs 35.6% [95% CI, 35.4-35.9]), the hypertension cohort (67.2% [95% CI, 66.9-67.4] vs 70.6% [95% CI, 70.3-70.9]), and the hyperlipidemia cohort (46.2% [95% CI, 46.2-46.3] vs 52.5% [95% CI, 52.2-52.7]).

“Long-term prospective trials are needed to explain the mechanisms and factors associated with the differences in medication discontinuation and comorbidity resolution after bariatric surgery,” noted investigators in their conclusion.

Medication Use for Obesity-Related Comorbidities After Sleeve Gastrectomy or Gastric Bypass

A comparative effectiveness study of Medicare claims data suggests gastric bypass surgery was associated with a greater rate of discontinuation of medications for obesity-related comorbidities than sleeve gastrectomy. 

Gastric Bypass Associated with Greater Medication Discontinuation than Sleeve Gastrectomy

Data from an analysis of the Avon Longitudinal Study of Parents and Children (ALSPAC) suggests arterial stiffness in adolescence could cause insulin resistance and dyslipidemia in young adulthood.

The study, which investigators suggest is the largest of its kind to date, provide an overview of the associations between arterial stiffness, as measured by carotid-femoral pulse wave velocity (cfPWV), and carotid item-media thickness (cIMT) progression on the risk of dysglycemia, insulin resistance, and dyslipidemia.

“Our novel findings are clinically significant for pediatric and adolescent health, in that preventing and treating insulin resistance, young-onset type 2 diabetes mellitus, and dyslipidemia may necessitate strategies to concurrently reduce arterial stiffness, particularly from adolescence,” said Andrew Agbaje, MD, MPH, a physician and clinical epidemiologist at the University of Eastern Finland, 

As the diabetes epidemic continues to balloon in the US and abroad, understanding factors associated with increased risk of incident type 2 diabetes could prove beneficial in alleviating the burden of diabetes on individuals and health systems. Citing recent evidence suggesting arterial stiffness could be a novel risk factor in the causal pathway of type 2 diabetes, Agbaje and a team of investigators sought to further investigate potential associations using data from the ALSPAC birth cohort.

A cohort of more than 14,901 children surviving beyond 1 year, the ALSPAC cohort contained data from 3862 participants with data from cfPWV and cIMT assessments performed at 17.7 years. Using this cohort, investigators designed their study to assess temporal causal longitudinal associations of cfPWV and cIMT with fasting LDL-C, HDL-C, triglyceride, glucose, insulin, insulin resistance, and pancreatic beta-cell function at the 24.5-year follow-up.

Compared to their male counterparts, women included in the study had higher fasting total cholesterol, HDL-C, and insulin but lower glucose at both the 17.7-year and 24.5-year follow-up. Investigators noted 9.2%, 41.6%, 24.5%, 7.5%, and 10.3% of 3862 participants were at risk of high glucose, insulin, LDL, triglyceride, and low HDL, respectively, at 24.5 years.

Upon analysis, results suggested a higher cfPWV at 17.7 years was associated with increased insulin at 24.5 years, which investigators pointed out was slightly attenuated after adjustment for covariates. Higher cIMT at 17.7 years was associated with lower insulin at 24.5 years after adjustment for covariates.

In mixed-effect models, results indicated the 7-year progression of cfPWV was directly associated with an increase in triglycerides. Further analysis demonstrated cIMT progression was associated with increases in LDL-C, triglycerides, and glucose. In cross-lagged models suggested higher cfPWV at 17.7 years was associated with higher insulin (β=.06, SE, 0.12, 

=.014), HOMA of insulin resistance, and HOMA-percent pancreatic beta-cell function at 24.5 years. However, in the same models, insulin, HOMA of insulin resistance, and HOMA-percent pancreatic beta-cell function at 17.7 years were not associated with cfPWV at 24.5 years.

Investigators pointed out higher cIMT at 17.7 years was associated with reduced insulin HOMA of insulin resistance, and HOMA-percent pancreatic beta-cell function at 24.5 years, but not vice versa. Additionally, higher glucose at 17.7 years was associated with higher cfPWV and cIMT at 24.5 years.

Effect of Arterial Stiffness and Carotid Intima-Media Thickness Progression on the Risk of Dysglycemia, Insulin Resistance, and Dyslipidemia: a Temporal Causal Longitudinal Study,

The largest study of its kind to date provides evidence suggesting a causal relationship between cfPWV and cIMT in adolescence with increased insulin resistance and dyslipidemia in young adulthood. 

Arterial Stiffness Could Cause Insulin Resistance, Dyslipidemia

Data from a recent study is providing clinicians with insight into the fracture risk during 

 drug holidays after long-term therapy with a pair of popular agents.

A propensity score-matched cohort study comparing the fracture risk during drug holidays after treatment with risedronate and alendronate, results of the study demonstrate drug holidays after long-term therapy with risedronate were associated with a small increase in risk of hip fracture compared with alendronate, but investigators note further research is needed to better understand risk mitigation.

“We found little difference in the association between risedronate versus alendronate drug holidays and hip fractures until approximately 2 years of not receiving therapy. Over 3 years, drug holidays after risedronate therapy were associated with an 18% relative and 0.6–percentage point absolute increased risk for hip fracture compared with alendronate drug holidays,” wrote investigators.

Funded by the Canadian Institutes of Health Research and citing a lack of direct comparisons between the agents, the current study was designed and led by a team of investigators representing multiple institutions in North America. To do so, investigators designed their study as a retrospective population-based, matched, cohort study using province-wide health care administrative databases detailing comprehensive coverage of Ontario residents aged 65 years or older from November 2000-March 2020.

The specific intent of the investigators’ efforts was to compare risks of drug holidays after long-term therapy with either agent, with long-term therapy defined as 3 years or more. The primary outcome of interest for the propensity score-matched analyses was hip fracture within 3 years after a 120-day ascertainment period. Investigators pointed out secondary analyses were planned to assess shorter follow-ups and sex-specific estimates.

The investigators' initial search identified 91,928 patients who received at least 3 years of continuous alendronate or risedronate therapy and had a subsequent drug holiday. After application of inclusion criteria, investigators identified 60,636 patients with at least 120 days of follow-up and without a history of hip or vertebral fracture for inclusion. The median age of this cohort at the start of the drug holiday was 80.2 (IQR, 10.3) years and 81% were women.

Of the 60,636 patients included in the study, 55% had long-term risedronate therapy and 45% had long-term alendronate therapy. Using propensity score-matching, 25,077 patients receiving alendronate were matched to 25,077 receiving risedronate, which yielded a cohort of 50,154 for inclusion in the final analyses.

Upon analysis, results suggested hip fractures rates were greater among risedronate than alendronate drug holidays, with event rates of 12.4 and 10.6 events per 1000 patient-years, respectively (HR, 1.18 [95% CI, 1.04-1.34]. Further analysis indicated this relationship became attenuated when any fracture was included as the outcome (HR, 1.07 [CI, 1.00-1.16]) and with shorter drug holidays (1 year: HR, 1.03 [CI, 0.85-1.24]; 2 years: HR, 1.14 [CI, 0.96-1.32]).

“We emphasize that our results do not indicate that alendronate therapy should be preferred over risedronate therapy. Indeed, several real-world studies identify little difference in fractures while treatment is received, with the exception of 2 of 5 secondary analyses that identified higher hip fracture risk after 3 years of therapy,” wrote investigators.

Comparative Fracture Risk During Osteoporosis Drug Holidays After Long-Term Risedronate Versus Alendronate Therapy

An analysis of data from more than 50k patients using risedronate or alendronate from Ontario compares the risk of hip fracture and other outcomes during drug holidays.

Comparing Fracture Risk with Risedronate vs Alendronate During Drug Holidays

A new study from the University of Virginia Health System is providing insight into predictors of arterial stiffness in adolescents and young adults with type 1 diabetes. 

Leveraging carotid-femoral pulse wave velocity (cfPWV) from a cohort of young adults and adolescents with type 1 diabetes, investigators determined age, sex, and flow-mediated dilation (FMD) were uniquely associated with arterial stiffness in type 1 diabetes, which was not observed with other factors such as duration of diabetes, HbA1c, or heart rate.

“Age, sex, and FMD were the only factors uniquely associated with cfPWV in our cohort of adolescents and adults with uncomplicated type 1 DM. Male participants had higher cfPWV, indicating greater central arterial stiffness, but similar FMD and AIx to female participants,” wrote investigators.

Although it is well-established patients with type 1 diabetes face an increased risk of increased arterial stiffness, relatively few studies provide insight into predictors of arterial stiffness among younger patients with type 1 diabetes. With this in mind, a team of investigators from the University of Virginia Health System sought to assess the relationship between cfPWV and age, duration of diabetes, sex, HbA1c, augmentation index, mean arterial pressure, FMD, and heart rate.

Led by Kaitlin Love, MD, and Eugene Barrett, MD, the study included a cohort of 41 participants, including 16 adolescents and 25 adults. The cohort had a mean age of 24 years, a mean duration of diabetes of 14 years, a mean HbA1c of 7.9%, and 34% were female. Investigators pointed out male and female participants were similar in age, diabetes duration, HbA1c, blood pressure, BMI, and lipid profile.

Inclusion criteria included having a BMI below 30 kg/m2, an HbA1c below 9%, and blood pressure below 160/90 mmHg at the time of screening. Additionally, patients were excluded if they were current smokers or had quit smoking in the prior 6 months, were taking vasoactive medications outside of antihypertensive medication, or had any history of cardiovascular, peripheral vascular, or liver disease.

Upon analysis, only age, sex, and FMD were associated with arterial stiffness in adolescents and adults with uncomplicated toys 1 diabetes. Although men and women included in the study had similar cardiovascular risk factors, male patients with diabetes had higher cfPWV than women with diabetes, but no differences were observed for any other macrovascular outcomes, including FMD and AIx.

Endothelial dysfunction was highly prevalent among our participants regardless of DM duration. Further study is warranted to determine the generalizability of our results and define the sequence of and sex differences in macrovascular dysfunction present in type 1 DM,” wrote investigators.

Predictors of arterial stiffness in adolescents and adults with type 1 diabetes: a cross-sectional study,

Results of a study examining predictors of arterial stiffness in type 1 diabetes concluded age, sex, and flow-mediated dilation were uniquely associated with increased arterial stiffness. 

Study Details Predictors of Arterial Stiffness in Adolescents, Young Adults with Type 1 Diabetes

New research from investigators at Sao Paulo State University details the impact of a soy-based infant diet on the onset of puberty.

The study, which was a systematic review and meta-analysis designed to evaluate associations between soy-based infant diets and onset of puberty in girls, boys, and both, concluded there were no statistically significant associations between soy-based infant diets and onset of puberty in boys or girls.

“We did not observe any association between a soy-based infant diet and the onset of puberty in boys or girls. The meta-analyses did not show any significant differences between groups in the risk of precocious puberty and menarche age,” wrote investigators.

Citing conflicting evidence from previous studies, a team of 6 investigators from Sao Paulo State University sought to assess the associations between a soy-based infant diet and the onset of puberty. To do so, investigators designed a systematic review and meta-analysis with the intent of examining the associations in a contemporary cohort of observational and randomized clinical trials.

Performing a search of the Embase, Medline, LILACS, Cochrane, Trip database, SCOPUS, and Web of Science databases, investigators identified 962 references for possible inclusion in their systematic review and meta-analysis. The search terms used by investigators were “Soy Foods,” “Soy Milk,” “Soybeans,” “Soybeans Protein,” “Soybean oil,” “Puberty,” “Puberty, precocious,” “Sexual Maturation,” and “Menstruation Disturbances”. Of the 962 references, 16 were selected for final examination and 8 met all eligibility criteria for the systematic review and meta-analysis. Investigators noted, of the 8 studies excluded, 1 was a literature review, 1 was a case report, 2 presented only laboratory outcomes, 1 was an animal study, 1 did not describe clinical outcomes related to puberty, and in 2 studies the time of follow-up was insufficient to evaluate the health outcomes.

Of the 8 studies included, 7 were observational studies and 1 was a randomized clinical trial. Within these 8 studies, investigators identified a cohort of 598 children who consumed a soy-based diet and 2957 who did not. Primary outcomes of interest for the study were the onset of puberty in girls, boys, and both. Puberty outcomes in girls included thelarche, pubarche, and menarche age. For boys, puberty outcomes included pubarche, voice change, and testicular and penis enlargement age. When assessing both, the puberty outcome of interest was risk of delayed precocious puberty.

In their analyses, investigators hoped to calculate the odds ratio and mean difference as a measure of the association between soy consumption and outcomes. Investigators pointed out random-effects model was used to pool results across studies and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the certainty of evidence.

Upon analysis, investigators found the only primary outcomes of interest that could be plotted within the meta-analysis were the risk of precocious puberty and age at menarche. In their analyses, investigators observed no statistical difference between groups for precocious puberty based on soy consumption (OR, 0.51 [95% CI, 0.09 to 2.94]; 3 studies, 206 participants, low certainty of evidence. Further analysis revealed no between-group difference for menarche age (MD, 0.14 [95% CI, -0.16 to 0.45]; 3 studies, 605 children, low certainty of evidence).

Investigators noted a single study reported the outcome of menarche age in terms of median and interquartile range. In this study, the onset of menarche was increased in girls who received a soy-based diet, but the reported age was within the normal age range for menarche.

Investigators underlined the need for more research to further evaluate potential associations between soy-based infant diets and the onset of puberty in boys and girls.

“Cohort studies with large sample sizes and appropriate methodology are required to evaluate whether the lack of an association between a soy-based infant diet and the onset of puberty remains when the results are compared considering the length of exposure, amount of soy consumption, and assessment of pubertal development through self-report or physical examination,” wrote investigators.

Association between a soy-based infant diet and the onset of puberty: A systematic review and meta-analysis

A systematic review and meta-analysis provide insight into the risks of precocious puberty and early menarche based on consumption of a soy-based infant diet. 