Cardiometabolic Conversations

Gestational diabetes has long-term CV implications

Women with a history of gestational diabetes — hyperglycemia that appears in the second and third trimester of pregnancy and resolves after delivery — have increased risks for developing type 2 diabetes and cardiovascular disease and for developing the conditions at earlier ages compared with women without such a history. Endocrine Today spoke with cardiologist M. Carolina Gongora, MD, and endocrinologist Elise Brett, MD, about caring for these women.

How do you address CV risks in women with gestational diabetes, both during pregnancy and later in life?

A cardiologist weighs in.

M. Carolina Gongora

CVD is the leading cause of death among women. Complications related to a woman’s reproductive history have gained increased recognition as important risk factors for development of CVD in the near term.

The odds of subsequent CVD in women with history of gestational diabetes is about 65% higher compared with women without the condition. CVD related to gestational diabetes includes angina pectoris, myocardial infarction and hypertension and is associated with the development of type 2 diabetes, hyperlipidemia, subclinical atherosclerosis, metabolic syndrome and endothelial dysfunction.

The underlying biological mechanism has been proposed to be endothelial dysfunction in the fetoplacental vasculature as a result of abnormal production of cytokines, oxidative stress and mitochondrial dysfunction that leads to a state of chronic inflammation. Even nondiabetic women with history of gestational diabetes show increased insulin resistance and decreased endothelial-dependent relaxation. Inflammatory mediators have been found to be persistently elevated at 12 weeks postpartum.

Because of the CV and metabolic stress it causes, pregnancy provides a unique opportunity to estimate a woman’s lifetime risk. The recognition of the significant association between gestational diabetes and CVD-related mortality and morbidity resulted in the updated recommendations by the American College of Obstetricians and Gynecologists and American Heart Association for enhanced screening for CVD and integrated care for these women. In the guideline, history of gestational diabetes is at the same level as other risk factors, such as poor exercise capacity, metabolic syndrome, hypertension or dyslipidemia. Obtaining a detailed obstetric history plays a central role in the evaluation of the CV risk assessment, and adverse pregnancy outcomes should appear in the medical record of each woman.

Currently, there are no official guidelines for formal assessment of CVD in these women. However, lifestyle modifications, including smoking cessation, Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH)-style diets, regular physical activity and weight management, should be strictly implemented soon after delivery. Lipid profile, blood pressure and BMI should be assessed at baseline and then annually. Treatment of hypertension and high LDL levels should be applied according to risk profile. Women who develop coronary artery disease, cerebrovascular disease, peripheral artery disease, aortic aneurysm, diabetes or chronic kidney disease or who have a 10-year predicted CVD risk of at least 10% are at highest risk for CV mortality and have the tightest BP, glycemia, weight and lipids targets.

Gestational diabetes affects approximately 16% of pregnancies worldwide, and its prevalence is rising due to the obesity epidemic and delayed motherhood. Therefore, we need to insist on greater recognition of this pregnancy complication as origin for later CVD. Surprisingly, there is still unawareness among the medical and nonmedical community about the relationship between pregnancy-related complications, including preeclampsia and gestational diabetes, and the risk for future CVD. Interdisciplinary health care professionals should work together to provide an accurate assessment of the future CV risk and formulate specific preventive and therapeutic strategies. Appropriate referral by the obstetrician to a primary care physician or cardiologist should occur shortly after delivery for CV risk factor assessment and timely intervention in the following years.

M. Carolina Gongora, MD, assistant professor of medicine and consultant at the Women’s Heart Center at Emory University School of Medicine in Atlanta. Disclosure: Gongora reports no relevant financial disclosures.

An endocrinologist weighs in.

Elise Brett

Although the risk to the mother is minimal, untreated or inadequately treated maternal hyperglycemia has long been known to increase the risk for neonatal large for gestational age births, preeclampsia and neonatal hypoglycemia. It has also recently been confirmed that there is an increased risk for impaired glucose tolerance in childhood to the offspring of mothers with untreated maternal hyperglycemia in pregnancy. Identification and treatment of affected mothers with lifestyle intervention or insulin is recommended primarily to decrease these risks.

A diagnosis of gestational diabetes predicts future risk for type 2 diabetes and is associated with a risk for progression to type 2 diabetes of 50% at 5 years and an estimated 50% to 70% lifetime maternal risk for type 2 diabetes. The American Diabetes Association recommends that women with a prior history of gestational diabetes be screened for type 2 diabetes every 1 to 3 years depending on other risk factors, yet screening rates tend to be low. Elevated BMI is associated with greatest risk for development of type 2 diabetes postpartum. Weight loss with intensive lifestyle intervention, as well as breastfeeding, can decrease that risk.

Women with a prior history of gestational diabetes are more likely to have additional CV risk factors, such as larger waist circumference, higher body weight, dyslipidemia, hypertension, higher fasting glucose and higher fasting insulin compared with those without the condition. Gestational diabetes can be characterized as an early expression of metabolic syndrome, and women with the condition have also been shown to have greater left ventricular (LV) mass, impaired LV relaxation and reduced LV systolic function.

These risk factors translate to an actual increase in CVD in subsequent decades. In a recent retrospective cohort from Canada of more than 1 million white women followed for 25 years after delivery, gestational diabetes was associated with 1.7 times the risk for hospitalization for CVD after 25 years and with an increased risk for CV hospitalization starting 8 to 15 years after delivery. These women had a higher risk for ischemic heart disease, MI, angioplasty and coronary artery bypass grafting.

Similarly, in the Nurses’ Health Study II, a prospective cohort of 89,479 parous nurses followed for 26 years, those with a prior history of gestational diabetes had a 60% greater risk for CVD compared with those without that history. Elevated risk was seen in women with prior gestational diabetes and subsequent type 2 diabetes. Those without progression to type 2 diabetes did not experience elevated CV risk after adjusting for weight change and other lifestyle factors. Women who followed a healthy diet, were very physically active, did not smoke and had normal BMI were ultimately not at increased CV risk. The authors concluded that sustained unhealthy lifestyle after pregnancy contributes to CVD risk.

The identification of CV risk factors early on can be an opportunity to intervene with intensive lifestyle modification and, possibly, pharmacotherapy to reduce the metabolic risk. The most important goal, perhaps, is achievement and maintenance of normal BMI after pregnancy. Interventions may include dietary modification, increased physical activity, smoking cessation, use of statins when appropriate, metformin to treat prediabetes and anti-obesity agents to help reduce body weight.

Elise Brett, MD, associate clinical professor of medicine in the division of endocrinology, diabetes and bone disease at the Icahn School of Medicine at Mount Sinai. Disclosure: Brett reports that her husband is employed by Novo Nordisk Inc.

Editor’s note: Cardiometabolic Conversations is a new feature in Endocrine Today that will be published throughout the year. Email the editors at endocrinology@healio.com for more information or to suggest a topic.

Women with a history of gestational diabetes — hyperglycemia that appears in the second and third trimester of pregnancy and resolves after delivery — have increased risks for developing type 2 diabetes and cardiovascular disease and for developing the conditions at earlier ages compared with women without such a history. Endocrine Today spoke with cardiologist M. Carolina Gongora, MD, and endocrinologist Elise Brett, MD, about caring for these women.

How do you address CV risks in women with gestational diabetes, both during pregnancy and later in life?

A cardiologist weighs in.

M. Carolina Gongora

CVD is the leading cause of death among women. Complications related to a woman’s reproductive history have gained increased recognition as important risk factors for development of CVD in the near term.

The odds of subsequent CVD in women with history of gestational diabetes is about 65% higher compared with women without the condition. CVD related to gestational diabetes includes angina pectoris, myocardial infarction and hypertension and is associated with the development of type 2 diabetes, hyperlipidemia, subclinical atherosclerosis, metabolic syndrome and endothelial dysfunction.

The underlying biological mechanism has been proposed to be endothelial dysfunction in the fetoplacental vasculature as a result of abnormal production of cytokines, oxidative stress and mitochondrial dysfunction that leads to a state of chronic inflammation. Even nondiabetic women with history of gestational diabetes show increased insulin resistance and decreased endothelial-dependent relaxation. Inflammatory mediators have been found to be persistently elevated at 12 weeks postpartum.

Because of the CV and metabolic stress it causes, pregnancy provides a unique opportunity to estimate a woman’s lifetime risk. The recognition of the significant association between gestational diabetes and CVD-related mortality and morbidity resulted in the updated recommendations by the American College of Obstetricians and Gynecologists and American Heart Association for enhanced screening for CVD and integrated care for these women. In the guideline, history of gestational diabetes is at the same level as other risk factors, such as poor exercise capacity, metabolic syndrome, hypertension or dyslipidemia. Obtaining a detailed obstetric history plays a central role in the evaluation of the CV risk assessment, and adverse pregnancy outcomes should appear in the medical record of each woman.

Currently, there are no official guidelines for formal assessment of CVD in these women. However, lifestyle modifications, including smoking cessation, Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH)-style diets, regular physical activity and weight management, should be strictly implemented soon after delivery. Lipid profile, blood pressure and BMI should be assessed at baseline and then annually. Treatment of hypertension and high LDL levels should be applied according to risk profile. Women who develop coronary artery disease, cerebrovascular disease, peripheral artery disease, aortic aneurysm, diabetes or chronic kidney disease or who have a 10-year predicted CVD risk of at least 10% are at highest risk for CV mortality and have the tightest BP, glycemia, weight and lipids targets.

Gestational diabetes affects approximately 16% of pregnancies worldwide, and its prevalence is rising due to the obesity epidemic and delayed motherhood. Therefore, we need to insist on greater recognition of this pregnancy complication as origin for later CVD. Surprisingly, there is still unawareness among the medical and nonmedical community about the relationship between pregnancy-related complications, including preeclampsia and gestational diabetes, and the risk for future CVD. Interdisciplinary health care professionals should work together to provide an accurate assessment of the future CV risk and formulate specific preventive and therapeutic strategies. Appropriate referral by the obstetrician to a primary care physician or cardiologist should occur shortly after delivery for CV risk factor assessment and timely intervention in the following years.

M. Carolina Gongora, MD, assistant professor of medicine and consultant at the Women’s Heart Center at Emory University School of Medicine in Atlanta. Disclosure: Gongora reports no relevant financial disclosures.

PAGE BREAK

An endocrinologist weighs in.

Elise Brett

Although the risk to the mother is minimal, untreated or inadequately treated maternal hyperglycemia has long been known to increase the risk for neonatal large for gestational age births, preeclampsia and neonatal hypoglycemia. It has also recently been confirmed that there is an increased risk for impaired glucose tolerance in childhood to the offspring of mothers with untreated maternal hyperglycemia in pregnancy. Identification and treatment of affected mothers with lifestyle intervention or insulin is recommended primarily to decrease these risks.

A diagnosis of gestational diabetes predicts future risk for type 2 diabetes and is associated with a risk for progression to type 2 diabetes of 50% at 5 years and an estimated 50% to 70% lifetime maternal risk for type 2 diabetes. The American Diabetes Association recommends that women with a prior history of gestational diabetes be screened for type 2 diabetes every 1 to 3 years depending on other risk factors, yet screening rates tend to be low. Elevated BMI is associated with greatest risk for development of type 2 diabetes postpartum. Weight loss with intensive lifestyle intervention, as well as breastfeeding, can decrease that risk.

Women with a prior history of gestational diabetes are more likely to have additional CV risk factors, such as larger waist circumference, higher body weight, dyslipidemia, hypertension, higher fasting glucose and higher fasting insulin compared with those without the condition. Gestational diabetes can be characterized as an early expression of metabolic syndrome, and women with the condition have also been shown to have greater left ventricular (LV) mass, impaired LV relaxation and reduced LV systolic function.

These risk factors translate to an actual increase in CVD in subsequent decades. In a recent retrospective cohort from Canada of more than 1 million white women followed for 25 years after delivery, gestational diabetes was associated with 1.7 times the risk for hospitalization for CVD after 25 years and with an increased risk for CV hospitalization starting 8 to 15 years after delivery. These women had a higher risk for ischemic heart disease, MI, angioplasty and coronary artery bypass grafting.

Similarly, in the Nurses’ Health Study II, a prospective cohort of 89,479 parous nurses followed for 26 years, those with a prior history of gestational diabetes had a 60% greater risk for CVD compared with those without that history. Elevated risk was seen in women with prior gestational diabetes and subsequent type 2 diabetes. Those without progression to type 2 diabetes did not experience elevated CV risk after adjusting for weight change and other lifestyle factors. Women who followed a healthy diet, were very physically active, did not smoke and had normal BMI were ultimately not at increased CV risk. The authors concluded that sustained unhealthy lifestyle after pregnancy contributes to CVD risk.

The identification of CV risk factors early on can be an opportunity to intervene with intensive lifestyle modification and, possibly, pharmacotherapy to reduce the metabolic risk. The most important goal, perhaps, is achievement and maintenance of normal BMI after pregnancy. Interventions may include dietary modification, increased physical activity, smoking cessation, use of statins when appropriate, metformin to treat prediabetes and anti-obesity agents to help reduce body weight.

Elise Brett, MD, associate clinical professor of medicine in the division of endocrinology, diabetes and bone disease at the Icahn School of Medicine at Mount Sinai. Disclosure: Brett reports that her husband is employed by Novo Nordisk Inc.

Editor’s note: Cardiometabolic Conversations is a new feature in Endocrine Today that will be published throughout the year. Email the editors at endocrinology@healio.com for more information or to suggest a topic.