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Diabetic Nephropathy and Microalbuminuria in Pregnant Women with Type 1 and Type 2 Diabetes Prevalence, Antihypertensive Strategy, and Pregnancy Outcome

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Diabetic Nephropathy and Microalbuminuria in Pregnant Women with Type 1 and Type 2 Diabetes Prevalence, Antihypertensive Strategy, and Pregnancy Outcome Clinical Care/Education/Nutrition/Psychosocial Research ORIGINAL ARTICLE Diabetic Nephropathy and Microalbuminuria in Pregnant Women With Type 1 and Type 2 Diabetes Prevalence, antihypertensive strategy, and pregnancy outcome 1,2 1,2 JULIE AGNER DAMM, MD LENE RINGHOLM, MD, PHD In pregnant women with type 1 di- 1,2 1,4 BJÖRG ASBJÖRNSDÓTTIR, MD BERIT WOETMANN PEDERSEN, MD 1,2 1,2,3 abetes, nephropathy is associated with NICOLINE FOGED CALLESEN ELISABETH R. MATHIESEN, MD, DMSC 1,2 poor pregnancy outcome in terms of JONATHAN M. MATHIESEN increased rates of preeclampsia and pre- term delivery (11–13). In these women, d intrauterine growth restriction (11) oc- OBJECTIVE To evaluate the prevalence of diabetic nephropathy and microalbuminuria in curs almost twice as often as in the general pregnant women with type 2 diabetes in comparison with type 1 diabetes and to describe population (13), and in the late 1990s, pregnancy outcomes in these women following the same antihypertensive protocol. preterm delivery before 34 weeks oc- RESEARCH DESIGN AND METHODSdAmong 220 women with type 2 diabetes and curred in ;30% (13). In women with 445 women with type 1 diabetes giving birth from 2007–2012, 41 women had diabetic ne- type 1 diabetes and microalbuminuria, phropathy (albumin-creatinine ratio $300 mg/g) or microalbuminuria (albumin-creatinine ratio preterm delivery and preeclampsia are 30–299 mg/g) in early pregnancy. Antihypertensive therapy was initiated if blood pressure also frequent and serious complications $ $ 135/85 mmHg or albumin-creatinine ratio 300 mg/g. (11,13,14). RESULTSdThe prevalence of diabetic nephropathy was 2.3% (5 of 220) in women with type 2 In nonpregnant subjects with diabe- diabetes and 2.5% (11 of 445) in women with type 1 diabetes (P =1.00).Thefigures for micro- tes, inhibition of the renin angiotensin albuminuria were 4.5 (10 of 220) vs. 3.4% (15 of 445) (P = 0.39). Baseline glycemic control was system is a cornerstone in the treatment of comparable between women with type 2 diabetes (n = 15) and type 1 diabetes (n =26).Blood microalbuminuria and diabetic nephrop- pressure at baseline was median 128 (range 100–164)/81 (68–91) vs. 132 (100–176)/80 (63– athy (15–19). However, during preg- 100) mmHg (not significant) and antihypertensive therapy in type 2 versus type 1 diabetes was nancy, antihypertensive therapy is often used in 0 and 62%, respectively, at baseline, increasing to 33 and 96%, respectively, in late not indicated until sustained blood pres- pregnancy. Pregnancy outcome was comparable regardless type of diabetes; gestational age at sure elevations .150 mmHg systolic or delivery: 259 days (221–276) vs. 257 (184–271) (P = 0.19); birth weight 3,304 g (1,278–3,914) – 100 mmHg diastolic are documented vs. 2,850 (370 4,180) (P =0.67). (20), owing to concerns for reduced pla- CONCLUSIONSdThe prevalence of diabetic nephropathy and microalbuminuria in early cental circulation, which may cause fetal pregnancy was similar in type 2 and type 1 diabetes. Antihypertensive therapy was used more hypoxia and intrauterine growth restric- frequently in type 1 diabetes. Pregnancy outcome was comparable regardless type of diabetes. tion (21). In Copenhagen, we recommend blood pressure levels ,135/85 mmHg and urinary albumin-creatinine ratio outh onset of type 2 diabetes con- type 1 diabetes (6). Literature focusing ,300 mg/g during pregnancy in women Ytinues to increase worldwide (1), on kidney involvement in pregnant with diabetes and diabetic nephropathy and pregnancy in women with womenwithdiabetesisscarce(7–11). or microalbuminuria (14,22), regardless type 2 diabetes is a substantial clinical To our knowledge, no studies using strict of the type of diabetes. Using this strategy, problem (2). Cross-sectional studies diagnostic criteria have described the observational studies have shown that show a higher prevalence of albuminuria prevalence of diabetic nephropathy and early initiation of intensive antihyperten- in young adults with type 2 diabetes com- microalbuminuria in early pregnancy in sive therapy during pregnancy leads to a pared with type 1 diabetes (3–5). Subjects women with type 2 diabetes. Likewise, reduced prevalence of preterm delivery in with youth-onset type 2 diabetes have a recommendations for an antihypertensive women with type 1 diabetes and diabetic fourfold increased risk of end-stage kid- strategy during these pregnancies is miss- nephropathy or microalbuminuria ney disease compared with youth with ing. (14,22). Brown and Garovic (23) also recommend a lower threshold for antihy- ccccccccccccccccccccccccccccccccccccccccccccccccc pertensive treatment in pregnant women From the 1Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark; the 2De- with diabetes and kidney involvement partment of Endocrinology, Rigshospitalet, Copenhagen, Denmark; the 3Faculty of Health Sciences, compared with nondiabetic pregnant University of Copenhagen, Denmark; and the 4Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark. women. Corresponding author: Julie Agner Damm, [email protected]. However, it has not been evaluated Received 1 May 2013 and accepted 16 June 2013. whether women with type 2 diabetes DOI: 10.2337/dc13-1031 benefit from intensive antihypertensive © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly therapy to the same degree as women cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/ licenses/by-nc-nd/3.0/ for details. with type 1 diabetes during pregnancy. care.diabetesjournals.org DIABETES CARE 1 Diabetes Care Publish Ahead of Print, published online September 5, 2013 Nephropathy and pregnancy in type 2 diabetes In this study, we evaluated the prev- weight, HbA1c, insulin dose, and blood death (death occurring between 22 com- alence of diabetic nephropathy and mi- pressure were recorded, and the urine pleted weeks and 1 completed week after croalbuminuria as well as pregnancy was screened for proteinuria with a dip- delivery), low 5-min Apgar score (,7), outcome in a recent cohort of pregnant stick test (Urinstix; Bayer Diagnostics, transient tachypnea of the newborn (the women with type 2 or type 1 diabetes Bridgend, U.K.) on sterile urine. Further need of continuous positive airway pres- treated according to the same protocol for analysis of urinary albumin-creatinine ra- sure for .1 h), neonatal hypoglycemia intensive antihypertensive treatment dur- tio was performed if proteinuria (.1+ on (plasma glucose ,2.5 mmol/L) on the ing pregnancy. the dipstick) was present. The urinary al- first plasma glucose value measured 2 h bumin excretion was analyzed using an after delivery, or neonatal jaundice (need RESEARCH DESIGN AND ELISA (26), and the blood creatinine con- of photo therapy). Birth weight was eval- METHODSdA retrospective cohort centration was measured by standard lab- uated by calculating SD z score to adjust study among 665 singleton pregnancies oratory methods. for gestational age and sex and small- and in women with type 2 or type 1 diabetes Blood pressure was measured with a large-for-gestational age (weight for ges- with a living fetus at 22 weeks delivering digital blood pressure monitor (A&D In- tational age ,10th percentile and .90th at our center from January 2007 until struments, Abingdon, U.K.) in a sitting percentile, respectively) (28). October 2012 was conducted. The center position after 5–10 min of rest. The study was approved by the Dan- is a referral center for all pregnant women If urinary albumin-creatinine ratio ish Data Protection Agency. According to with type 2 or type 1 diabetes from a was $300 mg/g or blood pressure Danish law, the regional committees for geographically well-defined area of 2.5 $135/85 mmHg, antihypertensive ther- ethics and science did not have to be million inhabitants. All women were apy was initiated or intensified. If ACE contacted. askedtobringtwourinesamplesfor inhibitors were withdrawn during pre- analysis of urinary albumin excretion at pregnancy planning, another antihyper- Statistics the first pregnancy visit. Urinary albu- tensive therapy was initiated unless the Data are given as median (range) or n (%). min-creatinine ratio was used in the urinary albumin-creatinine ratio was Differences between groups were ana- majority of cases to evaluate kidney in- close to normal (22). lyzed using Fisher exact test and x2 test, volvement since we previously reported a Methyldopa (14,27) was the first- as appropriate, for categorical variables high concordance between albumin ex- choice therapy in most cases, and, when and Mann-Whitney test for continuous cretion in 24-h urine collection and uri- indicated, labetalol and/or nifedipine (14) variables as data were nonnormally dis- nary albumin-creatinine ratio (24). At were added. If given before pregnancy, tributed. least two values within the range of micro- furosemide or thiazide was continued The associations were considered to albuminuria or diabetic nephropathy during pregnancy to reduce the risk of re- be statistical significant at a two-sided P were required to classify the patients. bound fluid retention with increased value ,0.05. All statistical analyses were Forty-one women were identified with blood pressure and urinary albumin ex- performed using SPSS statistics 20.0 kidney involvement defined as presence cretion when discontinuing the drug (SPPS, Chicago, IL). of diabetic nephropathy (urinary albu- (14,22). min-creatinine ratio $300 mg/g) or mi- Nonstress testing with cardiotocogra- RESULTSdThe prevalence of diabetic croalbuminuria (urinary albumin- phy was used routinely at least once nephropathy at baseline was 2.3% (5 of creatinine ratio 30–299 mg/g). At the first weekly from 32–34 gestational weeks in 220) in women with type 2 diabetes and pregnancy visit, three women had ne- addition to daily kick-counting. Fetal 2.5% (11 of 445) in women with type 1 phrotic proteinuria (urinary albumin-cre- growth was evaluated routinely by obstet- diabetes (P = 1.0).
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