justification for a trial of plasma glucose modulation in acute stroke patients with mild to moderate hyperglycaemia. 1
Weir CJ, Murray GD, Dyker AG, Lees KR. Is hyperglycaemia an independent risk factor after acute stroke? Results of a long term follow up study. BMJ 1997; 314: 1303–06. Scott JF, Gray CS, O’Connell JE, Alberti KGMM. Glucose in insulin therapy in acute stroke; why delay further? Q J Med 1998; 91: 511–15. Woo E, Ma JTC, Robinson JD, Yu YL. Hyperglycaemia is a stress response in acute stroke. Stroke 1988; 19: 1359–64. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. Classification and natural history of clinically identifiable subtypes of cerebral infarctions. Lancet 1991; 337: 1521–26. American Diabetes Association: clinical practice recommendations 1997. Diabetes Care 1997; 20: S1–S70.
Department of Clinical Geriatrics, University of Newcastle-upon-Tyne and Sunderland City Hospitals NHS Trust, Sunderland SR4 7TP, UK (J F Scott); and Department of Statistics, University of Newcastle-uponTyne
Pre-pregnancy microalbuminuria predicts pre-eclampsia in insulindependent diabetes mellitus Pia Ekbom and the Copenhagen Pre-eclampsia in Diabetic Pregnancy Study Group
The incidence of pre-eclampsia is substantially increased in diabetic pregnancies, which leads to higher maternal and perinatal morbidity and mortality.1,2 Microalbuminuria (urinary albumin excretion 30–300 mg/24 h) is an early manifestation of microvascular disease and predicts diabetic nephropathy, a major risk factor for pre-eclampsia.3–5 We investigated whether microalbuminuria before pregnancy in women with insulin-dependent diabetes mellitus (IDDM) could be a marker for predicting pre-eclampsia. We prospectively included all white women with IDDM without diabetic nephropathy or hypertension (n=74) admitted consecutively from the eastern part of Denmark to our obstetric clinic before 17 weeks’ gestation with a living fetus. Six women with abortions were excluded. Besides insulin, four women were treated with levotroxine, hydrocortisone, and/or antiepileptics. The women visited our obstetric clinic, local diabetes centres, or both every 1 or 2 weeks. They were asked to do home blood glucose measurements four times daily and to adjust insulin doses, aiming at a preprandial blood glucose level of 3–6 mmol/L. We obtained mean urinary albumin excretion and blood pressure values for 2 years before pregnancy, and the haemoglobin A1C (HbA1C) value at the Pre-eclampsia (n=8) Age (years) Duration of diabetes (years) Body-mass index (kg/m2) Nulliparous Microalbuminuria before pregnancy (n)‡ Early pregnancy urinary albumin excretion >30 mg/24 h (n)§ Haemoglobin A1c (%) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Retinopathy (n)¶ White class B+C/D (n) Smokers
No pre-eclampsia (n=60)
33 (5)* 23 (7)† 27 (5)* 5 (63%) 6 (75%)† 5 (63%)‡
30 (5) 12 (8) 24 (3) 26 (43%) 4 (7%) 7 (12%)
8·3 (0·8) 128 (11)|| 79 (3)* 7 (88%)|| 0+1/7|| 4 (50%)
7·8 (1·3) 117 (10) 74 (7) 21 (36%) 23+14/23 17 (28%)
Values mean (SD) unless otherwise indicated. *p<0·05. †p<0·001. ||p<0·01. ‡Totals eight and 56, respectively (pre-pregnancy data on albumin excretion available in 64 [94%] women). §Totals eight and 57, respectively. ¶Totals eight and 58, respectively.
Baseline data for women with IDDM stratified according to development of pre-eclampsia
THE LANCET • Vol 353 • January 30, 1999
time of conception from local records. Microalbuminuria was defined as urinary albumin excretion of 30–300 mg/24 h in two of three consecutive urine samples. On admission, at 14 weeks’, 20 weeks’, 28 weeks’, 32 weeks’, and 36 weeks’ gestation we took single measurements of 24 h urinary albumin excretion, blood pressure, and HbA1C. Urine samples were analysed by ELISA. Haemoglobin A1C was analysed by antibody immunoassay or by high-performance liquid chromatography (comparable). Pre-eclampsia was defined as blood pressure of more than 140/90 mm Hg accompanied by proteinuria of more than 0·3 g/24 h after 20 weeks’ gestation. We used unpaired Student’s t test and Fisher’s exact test to compare the groups. We took p<0·05 (two-tailed) to be significant. Eight of 68 (12%) women developed pre-eclampsia (24–36 weeks’ gestation; table). In six of the eight women antihypertensive treatment was started shortly after the diagnosis. Three women developed thrombocytopenia and two had increased serum uric acid concentrations. Pregnancy had to be terminated preterm (29–37 weeks’ gestation) in six (75%) women. Mean birthweight of the six babies (singletons) of mothers with pre-eclampsia was 2918 (SD 594) g, compared with 3548 (747) g for the 56 infants of mothers without pre-eclampsia (p=0·05). Preconception urinary albumin excretion concentrations (n=7) were regained at 5·6 (1–10) months after delivery. By logistic regression analysis, in which microalbuminuria before pregnancy, raised urinary albumin excretion in early pregnancy, systolic blood pressure, diabetes duration, and retinopathy were controlled for the confounding effect of the other variables, only microalbuminuria before pregnancy (p<0·01) and diabetes duration (p<0·05) were independently associated with pre-eclampsia. Six (60%) of ten women with microalbuminuria before pregnancy developed pre-eclampsia compared with two (4%) of 54 with normal urinary albumin excretion (p<0·0001). The relative risk for pre-eclampsia in women with microalbuminuria before pregnancy was 16 (95% CI 4–69); 75% of pre-eclamptic women had microalbuminuria before pregnancy (sensitivity) and 93% of the women without pre-eclampsia had normal albumin excretion (specificity). Pre-existing microalbuminuria therefore predicts development of pre-eclampsia in women with IDDM. The Copenhagen Pre-eclampsia in Diabetic Pregnancy Study Group— Peter Damm, Edna Stage, Bo Feldt-Rasmussen, Ulla Feldt-Rasmussen, Lars Mølsted-Pedersen, Kirsten Nørgaard, Annette Svenningsen, Peter Clausen, Laust H Nielsen, Elizabeth R Mathiesen. We thank statistician Åge Vølund, Novo Nordisk, Bagsvaerd, Denmark. 1
Garner PR, D’Alton ME, Dudley DK, Huard P, Hardie M. Preeclampsia in diabetic pregnancies. Am J Obstet Gynecol 1990; 163: 505–08. Biesenbach G, Zazgornik J, Stöger H, et al. Abnormal increases in urinary albumin excretion during pregnancy in IDDM women with pre-existing microalbuminuria. Diabetologia 1994; 37: 905–10. Combs CA, Rosenn B, Kitzmiller JL, Khoury JC, Wheeler BC, Miodovnik M. Early-pregnancy proteinuria in diabetes related to preeclampsia. Obstet Gynecol 1993; 82: 802–07. Feldt-Rasmussen B. Increased transcapillary escape of albumin in type 1 (insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 1986; 29: 282–86. Mogensen CE, Chachati A, Christensen CK, et al. Microalbuminuria: an early marker of renal involvement in diabetes. Uremia Invest 1986; 9: 85–95.
Copenhagen Preeclampsia in Diabetic Pregnancy Study Group; Obstetric Clinic and Department of Nephrology and Endocrinology, National University Hospital, Copenhagen and Steno Diabetes Center, Gentofte, Denmark (E Mathiesen e-mail: [email protected]