GDM, subsequent diabetes predictive of later renal damage

Women with a history of gestational diabetes mellitus who later develop diabetes had an elevated urinary albumin-to-creatinine ratio an average of 13 years later, indicating renal damage, according to a new study.

Those with a history of gestational diabetes mellitus (GDM) – but no subsequent development of diabetes – did not show an increased urinary albumin-to-creatinine ratio (UACR) but did have a higher estimated glomerular filtration rate (eGFR), hinting at early stages of glomerular hyperfiltration and renal damage.

“Our findings suggest that in women with a history of GDM, deterioration of renal function may potentially precede the development of overt diabetes, although clinically relevant outcomes such as elevated UACR may manifest only after progression to diabetes,” wrote Shristi Rawal, PhD, a postdoctoral fellow at the National Institute of Child Health and Human Development and her associates.

“These findings suggest that women with GDM-complicated pregnancies may represent a high-risk group that could benefit from regular monitoring for early-stage renal damage, timely detection of which may help clinicians initiate treatment to prevent or delay further disease progression,” they wrote.

The investigators compared outcomes among 1,226 Danish women 9-16 years after their index pregnancy during 1996-2002; a predominantly white study population, which limited the study’s generalizability to other demographic groups, the authors acknowledged. A total of 607 women had had GDM during their first pregnancy, 183 of whom developed type 1 or 2 diabetes. Of the 619 women who did not have GDM, 9 developed diabetes.

Serum creatinine and urinary albumin and creatinine measurements were taken to determine eGFR and UACR. Women with a previous GDM diagnosis had higher eGFR and UACR than women without previous GDM. The higher eGFR remained significant after adjustments for age at first pregnancy, completion of high school, smoking during pregnancy, a family history of diabetes, prepregnancy hypertension, and prepregnancy body mass index (BMI). UACR differences were not significant after adjustment.

Women with GDM and subsequent diabetes had a significantly higher UACR than women without either and had more than twice the risk of an elevated UACR of at least 20 mg/g (adjusted relative risk, 2.3), even after confounder adjustment.

The association with increased UACR was significant with the combination of a GDM history and a subsequent diabetes diagnosis, but not individually. The increased eGFR, however, remained significant after adjustment even for women with only a history of GDM, regardless of whether they later developed diabetes or even prediabetes.

“The independent association of GDM with eGFR also remained significant when we excluded women with conditions that might influence renal function markers at follow-up, including type 1 diabetes, preeclampsia/eclampsia or any hypertension complication during the index pregnancy, regular use of cholesterol-lowering drugs, or recent use of ACE inhibitors, diuretics, or H₂ blockers,” the authors reported.

“Furthermore, no effect modification was observed when we stratified the analyses by clinical and lifestyle characteristics at follow-up, including current BMI, smoking, antihypertension medication use, family history of diabetes, physical activity, and median time since index pregnancy. Associations in some strata became statistically insignificant due to reduced sample size [all P for interaction = .05],” they wrote.

The research was funded by the National Institute of Child Health and Human Development at the National Institutes of Health, the Innovation Fund Denmark, March of Dimes Birth Defects Foundation, Health Foundation, Heart Foundation and European Union.

Coauthor Allan Vaag, MD, PhD is a vice president at AstraZeneca. No other authors had disclosures.

SOURCE: Rawal S et al. Diabetes Care. 2018 May 4. doi: 10.2337/dc17-2629.

Women with a history of gestational diabetes mellitus who later develop diabetes had an elevated urinary albumin-to-creatinine ratio an average of 13 years later, indicating renal damage, according to a new study.

Those with a history of gestational diabetes mellitus (GDM) – but no subsequent development of diabetes – did not show an increased urinary albumin-to-creatinine ratio (UACR) but did have a higher estimated glomerular filtration rate (eGFR), hinting at early stages of glomerular hyperfiltration and renal damage.

“Our findings suggest that in women with a history of GDM, deterioration of renal function may potentially precede the development of overt diabetes, although clinically relevant outcomes such as elevated UACR may manifest only after progression to diabetes,” wrote Shristi Rawal, PhD, a postdoctoral fellow at the National Institute of Child Health and Human Development and her associates.

“These findings suggest that women with GDM-complicated pregnancies may represent a high-risk group that could benefit from regular monitoring for early-stage renal damage, timely detection of which may help clinicians initiate treatment to prevent or delay further disease progression,” they wrote.

The investigators compared outcomes among 1,226 Danish women 9-16 years after their index pregnancy during 1996-2002; a predominantly white study population, which limited the study’s generalizability to other demographic groups, the authors acknowledged. A total of 607 women had had GDM during their first pregnancy, 183 of whom developed type 1 or 2 diabetes. Of the 619 women who did not have GDM, 9 developed diabetes.

Serum creatinine and urinary albumin and creatinine measurements were taken to determine eGFR and UACR. Women with a previous GDM diagnosis had higher eGFR and UACR than women without previous GDM. The higher eGFR remained significant after adjustments for age at first pregnancy, completion of high school, smoking during pregnancy, a family history of diabetes, prepregnancy hypertension, and prepregnancy body mass index (BMI). UACR differences were not significant after adjustment.

Women with GDM and subsequent diabetes had a significantly higher UACR than women without either and had more than twice the risk of an elevated UACR of at least 20 mg/g (adjusted relative risk, 2.3), even after confounder adjustment.

The association with increased UACR was significant with the combination of a GDM history and a subsequent diabetes diagnosis, but not individually. The increased eGFR, however, remained significant after adjustment even for women with only a history of GDM, regardless of whether they later developed diabetes or even prediabetes.

“The independent association of GDM with eGFR also remained significant when we excluded women with conditions that might influence renal function markers at follow-up, including type 1 diabetes, preeclampsia/eclampsia or any hypertension complication during the index pregnancy, regular use of cholesterol-lowering drugs, or recent use of ACE inhibitors, diuretics, or H₂ blockers,” the authors reported.

“Furthermore, no effect modification was observed when we stratified the analyses by clinical and lifestyle characteristics at follow-up, including current BMI, smoking, antihypertension medication use, family history of diabetes, physical activity, and median time since index pregnancy. Associations in some strata became statistically insignificant due to reduced sample size [all P for interaction = .05],” they wrote.

The research was funded by the National Institute of Child Health and Human Development at the National Institutes of Health, the Innovation Fund Denmark, March of Dimes Birth Defects Foundation, Health Foundation, Heart Foundation and European Union.

Coauthor Allan Vaag, MD, PhD is a vice president at AstraZeneca. No other authors had disclosures.

SOURCE: Rawal S et al. Diabetes Care. 2018 May 4. doi: 10.2337/dc17-2629.

Women with a history of gestational diabetes mellitus who later develop diabetes had an elevated urinary albumin-to-creatinine ratio an average of 13 years later, indicating renal damage, according to a new study.

Those with a history of gestational diabetes mellitus (GDM) – but no subsequent development of diabetes – did not show an increased urinary albumin-to-creatinine ratio (UACR) but did have a higher estimated glomerular filtration rate (eGFR), hinting at early stages of glomerular hyperfiltration and renal damage.

“Our findings suggest that in women with a history of GDM, deterioration of renal function may potentially precede the development of overt diabetes, although clinically relevant outcomes such as elevated UACR may manifest only after progression to diabetes,” wrote Shristi Rawal, PhD, a postdoctoral fellow at the National Institute of Child Health and Human Development and her associates.

“These findings suggest that women with GDM-complicated pregnancies may represent a high-risk group that could benefit from regular monitoring for early-stage renal damage, timely detection of which may help clinicians initiate treatment to prevent or delay further disease progression,” they wrote.

The investigators compared outcomes among 1,226 Danish women 9-16 years after their index pregnancy during 1996-2002; a predominantly white study population, which limited the study’s generalizability to other demographic groups, the authors acknowledged. A total of 607 women had had GDM during their first pregnancy, 183 of whom developed type 1 or 2 diabetes. Of the 619 women who did not have GDM, 9 developed diabetes.

Serum creatinine and urinary albumin and creatinine measurements were taken to determine eGFR and UACR. Women with a previous GDM diagnosis had higher eGFR and UACR than women without previous GDM. The higher eGFR remained significant after adjustments for age at first pregnancy, completion of high school, smoking during pregnancy, a family history of diabetes, prepregnancy hypertension, and prepregnancy body mass index (BMI). UACR differences were not significant after adjustment.

Women with GDM and subsequent diabetes had a significantly higher UACR than women without either and had more than twice the risk of an elevated UACR of at least 20 mg/g (adjusted relative risk, 2.3), even after confounder adjustment.

The association with increased UACR was significant with the combination of a GDM history and a subsequent diabetes diagnosis, but not individually. The increased eGFR, however, remained significant after adjustment even for women with only a history of GDM, regardless of whether they later developed diabetes or even prediabetes.

“The independent association of GDM with eGFR also remained significant when we excluded women with conditions that might influence renal function markers at follow-up, including type 1 diabetes, preeclampsia/eclampsia or any hypertension complication during the index pregnancy, regular use of cholesterol-lowering drugs, or recent use of ACE inhibitors, diuretics, or H₂ blockers,” the authors reported.

“Furthermore, no effect modification was observed when we stratified the analyses by clinical and lifestyle characteristics at follow-up, including current BMI, smoking, antihypertension medication use, family history of diabetes, physical activity, and median time since index pregnancy. Associations in some strata became statistically insignificant due to reduced sample size [all P for interaction = .05],” they wrote.

The research was funded by the National Institute of Child Health and Human Development at the National Institutes of Health, the Innovation Fund Denmark, March of Dimes Birth Defects Foundation, Health Foundation, Heart Foundation and European Union.

Coauthor Allan Vaag, MD, PhD is a vice president at AstraZeneca. No other authors had disclosures.

SOURCE: Rawal S et al. Diabetes Care. 2018 May 4. doi: 10.2337/dc17-2629.