Patrick Campbell

New research from the University of Glasgow suggests the concept of 

 could be misleading, as data indicates these patients were still at increased risk of obesity-related adverse health outcomes.

An analysis of more than 380,000 individuals with a median follow-up of 11.2 years, results indicate patients considered to have metabolically healthy obesity were 4.3 times more likely to develop 

, 76% more likely to develop heart failure, and 18% more likely to suffer a heart attack or stroke during the follow-up period compared to their metabolically healthy counterparts without obesity.

"People with metabolically healthy obesity are not 'healthy' as they are at higher risk of heart attack and stroke, heart failure, and respiratory diseases compared with people without obesity who have a normal metabolic profile,” wrote investigators.

With the obesity epidemic continuing to swell, greater emphasis on research into different phenotypes of obesity could improve the existing knowledge base and care of patients. With this in mind, Frederick Ho, PhD, and colleagues from the Institute of Health and Wellbeing at the University of Glasgow designed the current study to assess associations of metabolically healthy obesity and obesity-related outcomes using data from the UK Biobank cohort.

A population-based prospective cohort study of more than 500,000 participants, the UK Biobank cohort contained data related to 381,363 participants who were not underweight and had complete data related to metabolic profile for inclusion in their analysis. Investigators planned to use Cox proportional hazards models to assess associations between metabolically healthy outcomes and health outcomes.

For the purpose of analysis, metabolically healthy obesity was defined as having a BMI of 30 kg/m

 or more and at least 4 of the 6 metabolically healthy criteria. These 6 markers used to define metabolic health were blood pressure, CRP, triglycerides, LDL-C, HDL-C, and HbA1c. Health outcomes of interest included incident diabetes and incident and fatal atherosclerotic cardiovascular disease (ASCVD), heart failure, and respiratory diseases.

Of the 381,363 participants included in the study, 54.7% (n=208,625) were considered metabolically healthy and of normal weight, 9.2% (n=35,103) had metabolically healthy obesity, 20.5% (78,259) were metabolically unhealthy without obesity, and 15.6% (n=59,376) were metabolically unhealthy with obesity.

In fully adjusted models, those with metabolically healthy obesity had a higher rates of incident heart failure (1.60; 95% CI, 1.45-1.75) and respiratory disease (HR, 1.20; 95% CI, 1.16-1.25) compared to those who were not obese at baseline. However, investigators noted this increased rate was not observed for ASCVD. Further analysis indicated these associations were generally weaker for fatal outcomes and only reached significance for all-cause (HR, 1.12; 95% CI, 1.04-1.21) and heart failure (HR, 1.44; 95% CI, 1.09-1.89) mortality rates.

Compared to those who were metabolically healthy without obesity, those with metabolically healthy obesity had greater rates of incident diabetes (HR, 4.32; 95% CI, 3.83-4.89), ASCVD (HR, 1.18; 95% CI, 1.10-1.27), heart failure (HR, 1.76; 95% CI, 1.61-1.92), respiratory diseases (HR, 1.28; 95% CI, 1.24-1.33) and all-cause mortality (HR, 1.22; 95% CI 1.14-1.31). Investigators also pointed out a subgroup analysis comparing those who transitioned from metabolically healthy obesity to metabolically unhealthy obesity during the follow-up to those considered metabolically healthy and of normal weight indicated these patients experienced greater rates of incident ASCVD (HR, 2.46; 95% CI, 1.12-5.41) and all-cause mortality (HR, 3.07; 95% CI, 1.44-6.56).

"Weight management could be beneficial to all people with obesity irrespective of their metabolic profile. The term 'metabolically healthy obesity' should be avoided in clinical medicine as it is misleading, and different strategies for defining risk should be explored,” wrote investigators.

Are people with metabolically healthy obesity really healthy? A prospective cohort study of 381,363 UK Biobank participants,

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Data from the UK Biobank cohort details the increased risk of adverse health outcomes, including the development of diabetes and heart failure, among patients considered to have metabolically healthy obesity. 

'Metabolically Healthy' Obesity Still Puts Patients at Increased Risk of Adverse Health Outcomes

An analysis of nearly 175k patients with 

 associated with the common hormonal endocrine disorder.

Results of the analysis suggest young women with PCOS were at an increased risk of adverse cardiovascular events and also indicate weight and diabetes status stood out as potentially modifiable risk factors for this association.

“This is the largest study to confirm an increased incidence of major cardiovascular morbidity in patients with PCOS and emphasizes the importance of recognizing the disorder as a higher-risk vascular condition,” wrote investigators.

With PCOS the most common endocrine condition impacting young women and the relationship between PCOS and cardiovascular risk unclear, a UK-based team of investigators sought to explore these potential associations using data from the Clinical Practice Research Datalink Aurum database. With more than 200,000 women with PCOS included in the database from 1998-2017, investigators identified a cohort of 181,916 meeting eligibility criteria for inclusion in their matched analyses.

All patients included in the study were at least 18 years of age or older and were matched in a 1:1 ratio to a set of non-PCOS controls based on age, BMI category, and primary care practice. Investigators pointed out patients with a history of myocardial infarction, stroke, angina, or revascularization were excluded from survival analyses.

The primary outcome of interest for the study was time to major adverse cardiovascular event (MACE), which was defined as myocardial infarction, stroke, angina, revascularization, and cardiovascular mortality. The secondary outcomes of interest were individual components of the composite MACE endpoint.

Of the 181,916 deemed eligible for inclusion, 174,660 were matched to non-PCOS controls. The median follow-up time for patients with PCOS was 3.83 (IQR, 1.89-7.78) years and 3.00 (IQR, 1.37-6.36) for controls. Investigators noted significant differences in presence of extreme obesity (4.65% vs 3.12%) were evident at baseline between the cohorts and women with PCOS were also more to have a higher Charlson Index score and higher blood pressure.

Analysis indicated crude rates of the composite endpoint, MI, stroke, angina, revascularization, and cardiovascular mortality were 82.7, 22.7, 27.4, 32.8, 10.5, and 6.97 per 100,000 patient-years, respectively, for women with PCOS and 64.3, 15.9, 25.7, 19.8, 7.13, and 7.75 per 100,000 patient-years, respectively, for matched controls. In adjusted models, women with PCOS were at 26% greater risk of the composite outcome (HR, 1.26; 95% CI, 1.13-1.41) and 38%, 60%, and 50% greater risk for myocardial infarction (HR, 1.38; 95 CI, 1.11-1.72), angina (HR, 1.50; 95% CI, 1.32-1.94), and revascularization (HR, 1.50; 95% CI, 1.08-2.07), respectively, when compared to non-PCOS controls.

In time-dependent models, results suggested weight gain (HR, 1.01; 95% CI, 1.00-1.01), prior type 2 diabetes (HR, 2.40; 95% CI, 1.76-3.30), and social deprivation (HR, 1.53; 95% CI, 1.11-2.11) were factors associated with increased risk of progression to the composite endpoint.

“Our study demonstrates that young women with a diagnosis of PCOS have an increased incidence of major cardiovascular events, whether captured as a composite outcome or as myocardial infarction, angina and revascularization individually,” wrote investigators. “High-quality longitudinal studies are now needed to understand any effect of disease phenotype and ethnicity on risk, and whether screening strategies with targeted intervention can lead to improved cardiovascular outcomes.”

Women with Polycystic Ovary Syndrome have an increased risk of major cardiovascular events: a population study

Journal of Clinical Endocrinology and Metabolism.

A comparison of women with PCOS to matched controls indicates women with PCOS were at a 26% greater risk of experiencing major adverse cardiovascular events than their counterparts without polycystic ovary syndrome. 

Women with Polycystic Ovary Syndrome at Increased Risk of Cardiovascular Disease Events

Despite practice-changing advances in technology and pharmacy, new research from the Johns Hopkins Bloomberg School of Public Health suggests rates of glycemic control among 

 have declined significantly in the past decade.

Using data from the National Health and Nutrition Examination Survey (NHANES), investigators paint a picture portraying more than a decade of progress lasting from 1999 to the early 2010s that has been derailed and is currently backsliding.

"These trends are a wake-up call, since they mean that millions of Americans with diabetes are at higher risk for major complications," said lead investigator Michael Fang, PhD, a postdoctoral fellow at the Bloomberg School, 

 "Our study suggests that worsening control of diabetes may already be having a detrimental effect at the national level."

The current landscape of diabetes management is one of the most complex in all of medicine. A paradigm where historic progress has been disrupted by rising rates of obesity and inactivity, Fang and a team of colleagues sought to identify and provide an overview of trends in diabetes treatment and risk-factor control from 1999-2018.

To do so, the current study was designed as a cross-sectional analysis of all patients enrolled in NHANES from 199-2018 who were 20 years of age or older with a diagnosis of diabetes and who were not pregnant. For the purpose analysis, surrey years were pooled into 4-year intervals—defined as 1999-2002, 2003-2006, 2007-2010, 2011-2014, and 2015-2018.

Specific risk factors of interest for the analysis included HbA1c, blood pressure, and lipids. Glycemic control was defined as an HbA1c less than 7.0%, blood pressure control was defined as less than 140/90 mmHg but investigators also considered a more stringent target of 130/80 mmHg, and lipid control was defined as non-HDL-C target was less than 130 mg/dL.

Initial analyses indicated trends for glycemic, blood pressure, and lipid control were nonlinear with an apparent inflection point around 2010. Between 1999-2002 and 2007-2010, the proportion of patients achieving glycemic control increased from 44.0% (95% CI, 38.9-49.3) to 57.4% (95% CI, 52.9-61.8). However, investigators noted this number began to decline and fell to 50.5% in 2015-2018 (95% CI, 45.8-55.3).

For blood pressure control, rates rose of patients with diabetes reaching a goal of less than 140/90 mmHg rose from 64.0% in 1999-2002 (95% CI, 59.2-68.5) to 74.2% in 2011-2014 (95% CI, 70.7-77.4). Similar to trends in glycemic control, this number decline to 70.4% in 2015-2018 (95% CI, 66.7-73.8). Investigators noted similar trends were observed when using a blood pressure target of less than 130/80 mmHg. For lipid control, the proportion of patients with a non-HDL-C level of less than 130 mg/dL increased from 25.3% in 1999-2002 (95% CI, 20.8-30.4) to 52.3% in 2007-2010 (95% CI, 49.2-55.3). However, this improvement appeared to plateau with a rate of 55.7% in 2015-2018 (95% CI, 50.8-60.5).

In analyses assessing percentage of patients achieving glycemic, blood pressure, and lipid control goals, results indicated rates more than doubled from 9.0% in 1999-2002 to 24.9% in 2007-2010 then became stagnant with a rate of 22.2% from 2015-2018 (95% CI, 17.9-27.3). Investigators highlighted the annual rate of change in diabetes control decreased for all outcomes when all years were modeled.

"These are concerning findings. There has been a real decline in glycemic control from a decade ago, and overall, only a small proportion of people with diabetes are simultaneously meeting the key goals of glycemic control, blood pressure control, and control of high cholesterol," said senior investigator Elizabeth Selvin, PhD, MPH, a professor in the Bloomberg School's Department of Epidemiology.

When assessing trends in medication use, investigators found the percentage of patients who used any glucose-lowering medication or blood pressure-lowering medications improved until 2010 and were unchanged after that point. Additionally, use of statin therapy increased but plateaued following 2014. Investigators pointed out use of combination glucose-lowering therapy began to decline among the general population, and more severely in those with poor glycemic control, beginning after 2010.

Selvin went on to note investigators hypothesized the shift in approach may have been spurred by results of the ACCORD and ADVANCE trials, which found intensive glucose control did not result in the levels of cardiovascular benefit many had expected.

"As a result of these trials, what we may be seeing is that doctors of people with diabetes may have backed off a bit on glycemic control, with potentially damaging results," Selvin said.

Trends in Diabetes Treatment and Control in U.S. Adults, 1999–2018

A cross-sectional analysis of NHANES data paints a grim picture related to rates of patients with diabetes achieving goals for glycemic, blood pressure, and lipid control. 

Despite Advances, Rates of Glycemic Control Backsliding in Past Decade

Using data from the Women’s Health Initiative Study, new research indicates any fracture among aging women was associated with greater risk of subsequent fracture—suggesting 

 should include both traumatic and nontraumatic fractures.

Analysis of more than 65,000 women followed for an average of 8 years, results demonstrated that while women with nontraumatic fracture were still at a greater risk of subsequent fracture compared to their counterparts with traumatic fractures, those with traumatic fracture were still at a 25% increased risk of subsequent fractures.

“This study’s findings suggest that all fractures, whether traumatic or nontraumatic, should warrant evaluation for osteoporosis (including BMD testing) and counseling regarding subsequent increased fracture risk. These results advance our understanding of the burden of potentially preventable fractures, which is higher in women with initial traumatic fractures as well as those with initial nontraumatic fractures,” wrote investigators.

With fractures posing a significant burden to the health and well-being of patients, particularly aging women, a team of clinicians from multiple institutions across the US designed the current study as a prospective observational study of data from women enrolled in the WHI study between September 1994 and December 1998. Containing data related to more than 160,000 women aged 50-79 years from across the US, WHI provided investigators with a cohort sample of 75,335 patients with an incident fracture for inclusion their analyses.

After exclusion of those with no follow-up for incident fracture and those missing covariates data, 66,874 patients with a mean follow-up of 8.1 (SD, 1.6) years were identified for inclusion in the final analytical sample. Of these, 7142 experienced an incident fracture event during the study period. When assessing fractures, 1624 were considered traumatic, 3891 were considered nontraumatic, and 1627 were considered of unknown trauma.

In adjusted analyses, risk of subsequent fracture was 49% greater after initial fracture (aHR, 1.49; 95% CI, 1.38-1.61). Among women with a traumatic fracture, the risk of experiencing a subsequent fracture was 25% greater (aHR, 1.25; 95% CI, 1.06-1.48; 

=.01) and this risk was 52% greater among women with a nontraumatic fracture (HR, 1.52; 95% CI, 1.37-1.68; 

 <.001) when compared to those with no fracture history. Further analysis indicated experiencing a traumatic fracture was not associated with a significantly increased risk of experiencing a subsequent fracture when compared to those who experienced a nontraumatic fracture (aHR, 0.82; 95% CI,0.68-1.00; 

, Anne Schafer, MD, and Dolores Shoback, MD, both of UCSF, wrote the findings from this study help underline the importance of treating bone health in fracture patients.

“The idea that nontraumatic vs traumatic is a distinction without a difference will likely be welcomed by busy clinicians. What clinician would not appreciate being relieved of the tedium of trying to accurately interrogate a patient about the energy and impact of the fall, the step from which they fell, the softness or hardness of the surface for landing, the rung of the ladder on which they had been standing, or the speed the car had been moving?,” wrote the pair.

Risk of Subsequent Fractures in Postmenopausal Women After Nontraumatic vs Traumatic Fractures

An analysis of data from the Women's Health Initiative provides an overview of the risk of subsequent fracture seen among women with a history of traumatic versus nontraumatic fracture in postmenopausal women. 

Patrick Campbell

Articles

'Metabolically Healthy' Obesity Still Puts Patients at Increased Risk of Adverse Health Outcomes

Women with Polycystic Ovary Syndrome at Increased Risk of Cardiovascular Disease Events

Despite Advances, Rates of Glycemic Control Backsliding in Past Decade

Evaluating Subsequent Fracture Risk in Aging Women with Traumatic Fractures