Leveraging technology for the treatment of type 1 diabetes in pregnancy: A review of past, current, and future therapeutic tools.

The significant risks associated with pregnancies complicated by type 1 diabetes (T1D) were first recognized in the medical literature in the mid-twentieth century. Stringent glycemic control with hemoglobin A1c (HbA1c) values ideally less than 6% has been shown to improve maternal and fetal outcomes. The management options for pregnant women with T1D in the modern era include a variety of technologies to support self-care. Although self-monitoring of blood glucose (SMBG) and multiple daily injections (MDI) are often the recommended management options during pregnancy, many people with T1D utilize a variety of different technologies, including continuous glucose monitoring (CGM), continuous subcutaneous insulin infusion (CSII), and CSII including automated delivery or suspension algorithms. These systems have yielded invaluable diagnostic and therapeutic capabilities and have the potential to benefit this understudied higher-risk group. A recent prospective, multicenter study evaluating pregnant patients with T1D revealed that CGM significantly improves maternal glycemic parameters, is associated with fewer adverse neonatal outcomes, and minimizes burden. Outcome data for CSII, which is approved for use in pregnancy and has been utilized for several decades, remain mixed. Current evidence, although limited, for commercially available and emerging technologies for the management of T1D in pregnancy holds promise for improving patient and fetal outcomes.

Urinary and Serum Angiogenic Markers in Women With Preexisting Diabetes During Pregnancy and Their Role in Preeclampsia Prediction.

OBJECTIVE: To determine the correlation between urinary and serum placental growth factor (PlGF) and investigate the predictive value as pregnancy progresses of urinary PlGF compared with serum PlGF, soluble fms-like tyrosine kinase 1 (sFLT-1), and the sFLT-1-to-PlGF ratio for the outcome of preeclampsia in women with preexisting diabetes. RESEARCH DESIGN AND METHODS: A multicenter prospective cohort study was conducted of 158 women with preexisting insulin-requiring diabetes (41 with type 1 and 117 with type 2). Urinary PlGF and serum PlGF, sFLT-1, and the sFLT-1-to-PlGF ratio were assessed four times (14, 24, 30, and 36 weeks' gestation), and the association with the outcome of preeclampsia was investigated. RESULTS: A correlation between urinary and serum PlGF was demonstrated from 24 weeks' gestation onward (P < 0.001). At all time points, those who developed preeclampsia had lower serum PlGF levels (P < 0.05), and receiver operating characteristic curves demonstrated that serum PlGF in this cohort performed better than the serum sFLT-1-to-PlGF ratio as a predictive test for preeclampsia. Preconception HbA1c ≥6.5% (48 mmol/mol) was an important discriminative predictor for preeclampsia (P = 0.01). CONCLUSIONS: This study prospectively describes the longitudinal changes in urinary PlGF alongside serum angiogenic markers throughout pregnancy in women with preexisting diabetes. We demonstrate correlation between urinary and serum PlGF and that in women with preexisting diabetes in pregnancy, serum PlGF is a better predictor of preeclampsia than the sFLT-1-to-PlGF ratio.

Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes.

OBJECTIVE: This study was conducted to determine the utility of tubular (urinary/plasma neutrophil gelatinase-associated lipocalin [NGAL] and urinary kidney injury molecule 1 [KIM-1]) and glomerular (estimated glomerular filtration rate [eGFR]) biomarkers in predicting preeclampsia (PE) in pregnant women with type 1 diabetes mellitus (T1DM) who were free of microalbuminuria and hypertension at the first trimester. RESEARCH DESIGN AND METHODS: This was a prospective study of T1DM pregnancy. Maternal urinary and plasma NGAL, urinary KIM-1 (ELISA of frozen samples), and eGFR (Chronic Kidney Disease Epidemiology Collaboration equation) were determined at three study visits (V1: 12.4 ± 1.8; V2: 21.7 ± 1.4; V3: 31.4 ± 1.5 weeks' gestation [mean ± SD]) in 23 women with T1DM with subsequent PE (DM+PE+), 24 who remained normotensive (DM+PE-), and, for reference, in 19 normotensive pregnant women without diabetes (DM-). The groups with diabetes were matched for age, diabetes duration, and parity. All subjects were normotensive and free of microalbuminuria or albuminuria at V1. All study visits preceded the onset of PE. RESULTS: Urinary creatinine-corrected NGAL (uNGALcc, ng/mg) was significantly elevated at V1 in DM+PE+ vs. DM+PE- women (P = 0.01); this remained significant after exclusion of leukocyte-positive samples (5 DM+PE+ and 2 DM+PE-) (P = 0.02). Accounting for BMI, HbA1c, and total daily insulin dose, a doubling of uNGALcc at V1 conferred a sevenfold increase in risk for PE (P = 0.026). In contrast, neither plasma NGAL nor urinary KIM-1 predicted PE. Also at V1, eGFR was elevated in DM+PE+ vs. DM+PE- (P = 0.04). CONCLUSIONS: Early tubular and glomerular dysfunction may predict PE in first trimester women with T1DM, even if free of microalbuminuria. These data suggest that subclinical renal tubular and glomerular injury, if present early in pregnancy, may predispose women with T1DM to PE.

Evaluation of biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes mellitus: A systematic review.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. Women with type 1 diabetes are considered a high-risk group for developing pre-eclampsia. Much research has focused on biomarkers as a means of screening for pre-eclampsia in the general maternal population; however, there is a lack of evidence for women with type 1 diabetes. OBJECTIVES: To undertake a systematic review to identify potential biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes. SEARCH STRATEGY: We searched Medline, EMBASE, Maternity and Infant Care, Scopus, Web of Science and CINAHL SELECTION CRITERIA: Studies were included if they measured biomarkers in blood or urine of women who developed pre-eclampsia and had pre-gestational type 1 diabetes mellitus Data collection and analysis A narrative synthesis was adopted as a meta-analysis could not be performed, due to high study heterogeneity. MAIN RESULTS: A total of 72 records were screened, with 21 eligible studies being included in the review. A wide range of biomarkers was investigated and study size varied from 34 to 1258 participants. No single biomarker appeared to be effective in predicting pre-eclampsia; however, glycaemic control was associated with an increased risk while a combination of angiogenic and anti-angiogenic factors seemed to be potentially useful. CONCLUSIONS: Limited evidence suggests that combinations of biomarkers may be more effective in predicting pre-eclampsia than single biomarkers. Further research is needed to verify the predictive potential of biomarkers that have been measured in the general maternal population, as many studies exclude women with diabetes preceding pregnancy.

Prediction of proteinuria and microalbuminuria in diabetic pregnancies with a random single void.

OBJECTIVE: To determine whether a single urine specimen could effectively replace the 24 hour (24-h) urine collection in screening for microalbuminuria and proteinuria in pregnant women with pregestational diabetes. MATERIALS AND METHODS: A total of 42 pregnant women with pregestational diabetes mellitus were involved in the eventual analysis. Demographic and clinical variables were collected and analyzed. Urinary Protein (P) to Creatinine (Cr) ratio and microalbumin (MA) to Cr ratios were measured for the spot sample, and the total P, total MA, and serum Cr were measured for the 24-h urine sample. Analysis was done using linear regression and the Pearson correlation coefficient (r). RESULTS: Mean maternal age was 30.8 years, and the mean gestational age at collection was 19.8 weeks. A strong correlation exists between the spot MA to Cr value and 24-h MA, with an r = 0.81 (P < 0.0001). The association between the spot P to Cr ratio and 24-h urinary P was not as strong, r = 0.58 (P < 0.0001). CONCLUSIONS: A strong association between spot MA to Cr ratio and 24-h urinary microalbuminuria may suggest a predictive role for random urine assessment of MA in pregnant pregestational diabetic patients. However, based on our data, the spot P to Cr ratio may be inadequate for assessing proteinuria in pregestational diabetic pregnancies.

Increased inositol phosphoglycan P-type in the second trimester in pregnant women with type 2 and gestational diabetes mellitus.

A progressive insulin resistant state develops throughout human pregnancy. Inositol phosphoglycan P-type (P-IPG), a second messenger of insulin, was reported to negatively correlate with the degree of insulin resistance in non-pregnant diabetic subjects. Urinary levels of P-IPG were assessed in insulin resistant states during pregnancy such as gestational diabetes mellitus (GDM, n=44) and type 2 diabetes mellitus (type 2 DM, n=25) and in 69 normal pregnant women. Urinary levels of P-IPG were higher in GDM than controls with a positive trend of release throughout normal pregnancy (P<0.01). P-IPG excretion was higher in diabetic (GDM and type 2 DM) than in healthy women in the second trimester (P<0.05). A higher P-IPG urinary excretion occurs during the second trimester in pregnant women with clinically evident insulin resistance with a positive association with poor glycemic control.

Status of essential trace metals in biological samples of diabetic mother and their neonates.

OBJECTIVE: There is accumulating facts that the metabolism of essential trace elements is altered in diabetic patients. The aim of present study was to compare the status of essential trace elements, chromium (Cr), manganese (Mn), and zinc (Zn) in biological samples (whole blood, urine and scalp hair) of insulin dependent diabetic mothers (age ranged 30-40) and their newly born infants (n = 76). An age matched 68 non-diabetic mothers and their infants, residing in the same locality, were selected as referents. For a comparative study, the biological samples of non-diabetic and diabetic pregnant and non pregnant of same age group and socio-economics status were also analysed. METHODOLOGY: The biological samples (scalp hair, blood and urine) were collected from study and referent groups. The Cr, Mn and Zn concentrations in all three biological samples were determined by a flame/electrothermal atomic absorption spectrometer, prior to microwave assisted acid digestion. The validity and accuracy of the methodology was checked by certified reference materials (CRMs) and using conventional wet acid digestion method on same CRMs. RESULTS: The mean values of Cr, Mn and Zn in scalp hair and blood samples of diabetic mothers and their infants were significantly lower as compared to the referent mothers-infants pairs (p < 0.01), while urinary excretion of all these elements were high in diabetic mother-infant pair samples. CONCLUSION: The deficiencies of essential trace elements, Cr, Mn and Zn in biological samples of diabetic women, may play role in the pathogenesis of diabetes mellitus and impacts on their neonates.

[Catecholamines level variation during pregnancy in women with diabetes and preeclampsia]. / Modificación de las concentraciones de catecolaminas durante el embarazo de mujeres con diabetes y preeclampsia.

BACKGROUND: In obstetrical service it is frequent to find women with acute renal failure during second trimester of pregnancy. Main causes are related to hypertensive alterations, hemorrhage, sepsis, intrinsic renal disease and some rare disorders that produce high maternal morbidity and mortality. OBJECTIVE: [corrected] To evaluate changes of adrenal function in pregnancy as well as its associated repercussions in diabetic and preeclamsic patients. PATIENTS AND METHODS: Prospective study in 56 patients. Groups included women with normal pregnancy, patients with diabetes type 2, and women with preeclampsia. It was requested basic exams and samples from urine of 24 h for catecholamines determinations; as well as after two months of delivery. Catecholamines were measured with Bertler immune-fluorescent procedure. RESULTS: Levels of catecholamines has statistically significant difference in all groups of study during the gestation. There was high quantity in the group of patients that developed preeclampsia 4535.5 +/- 356.4 microg/24 h (p < 0.05), compared with 31.2 +/- 9.2 microg/24 h in normal pregnancy; however, those with diabetes has a trend to increas 45.6 +/- 3.7 microg/24 h, without statistical differences. Two months after pregnancy levels shown 17.1 +/- 4.9 microg/24 h in normal pregnancy group, with preeclampsia 17.2 +/- 8.7 microg/24 h, and mild permanent increase 33.8 +/- 4.7 microg/24 h in the group with diabetes (p = 0.537). CONCLUSIONS: An important catecholamines elevation is related with progress or severity of preeclampsia, and could be due to less adrenal injury associated with pregnancy, and contribute to renal failure. Longer studies are necessary to evaluate this approach in renal function.

Twenty-four-hour blood pressure monitoring in normoalbuminuric normotensive type 1 diabetic women during pregnancy.

UNLABELLED: We monitored blood pressure (BP) for a 24-h period in type 1 diabetic women at each trimester of pregnancy (10-13, 20-22, and 30-33 weeks of gestation) to identify early alterations of BP profile in pregnancies complicated by hypertension. PATIENTS AND METHODS: We prospectively studied 71 type 1 diabetic pregnant women and 48 nondiabetic pregnant women (homogeneous by age and pre-pregnancy BMI) consecutively recruited at 10+/-2 weeks of pregnancy in the space of 2 years (1999-2000). They were all normotensive (<130/80 mm Hg) and normoalbuminuric (AER<20 microg/min) at entry to the study. STATISTICS: Analysis of variance (ANOVA) and simple regression and chi(2) were applied as appropriate by an Apple software program (Stat View). RESULTS: In diabetic women, we recorded higher levels of diastolic BP (even if within a normal range) at each time point; diabetic vs. nondiabetic women: first trim daytime diastolic BP: 71.35+/-8.75 vs. 67.7+/-9.7, P=.01; second trim nighttime diastolic BP: 62.15+/-6.45 vs. 58.05+/-6.7, P=.05; third trim nighttime diastolic BP: 66.03+/-8.72 vs. 60.7+/-6.5, P=.01. Among diabetics, those who later developed pregnancy-induced hypertension (36.6%) showed significantly higher values of BP at the first and third trimester compared to those who remained normotensive. In the two groups, there were no differences in age and pre-pregnancy BMI by contrast of diabetes duration (hypertensive vs. normotensive, 19.18+/-7.3 vs. 14.35+/-9.1 years, P=.03) and age of diagnosis (hypertensive vs. normotensive, 9.6+/-5.5 vs. 14.7+/-8.6 years, P=.01). Positive correlation was found between fasting blood glucose and diastolic BP at each trimester of pregnancy.

Increased rate of lipid peroxidation and protein carbonylation in experimental diabetic pregnancy.

AIMS/HYPOTHESIS: Maternal Type I (insulin-dependent) diabetes mellitus is associated with an increased risk for fetal malformations and spontaneous abortions. Although the pathogenic mechanism is not fully understood, reactive oxygen species have been shown to contribute to the pathogenesis in experimental studies. By measuring 8-iso-PGF2alpha and protein carbonyls, radical oxygen damage to lipids and proteins can be estimated. The aim of this study was to investigate the status of lipid peroxidation and protein carbonylation in mothers and fetuses in experimental diabetic pregnancy. METHODS: Non-pregnant and pregnant rats with and without streptozotocin-induced diabetes were studied after 4 weeks of diabetes or at gestational day 19, respectively. Gross morphology of the offspring was studied and 24 h urine, plasma, amniotic fluid, maternal and fetal livers were collected. Concentrations of 8-iso-PGF2alpha, 15-keto-DH-PGF2alpha and other oxidative stress variables were measured. RESULTS: Malformation and resorption rates were increased in diabetic litters, whereas fetal weights were decreased in the control rats. There were no statistically significant differences in maternal plasma concentrations of 8-iso-PGF2alpha, but plasma protein carbonyl content was increased in the diabetic groups. Pregnancy increased 24 h urinary excretion of 8-iso-PGF2alpha in diabetic rats but not in the control rats. There was no difference in the amniotic fluid concentration of 8-iso-PGF2alpha between the normal and the diabetic group. However, in the diabetic group there was a correlation between the uterine horn concentration of 8-iso-PGF2alpha and the percentage of resorptions. CONCLUSIONS/INTERPRETATION: In diabetic pregnancy, both diabetes and pregnancy are promoting oxygen radical damage. Fetal oxidative stress markers do not clearly reflect fetal morphology.

Ambulatory blood pressure as predictor of preeclampsia in diabetic pregnancies with respect to urinary albumin excretion rate and glycemic regulation.

BACKGROUND: Twenty-four-hour ambulatory blood pressure was evaluated as a predictor of preeclampsia in women with insulin-dependent diabetes mellitus with respect to urinary albumin excretion rate and glycemic regulation. METHODS: One hundred and fifty-one women with insulin-dependent diabetes mellitus were consecutively recruited from the outpatient maternity ward for 24 hour ambulatory blood pressure measurement with a portable monitor (SpaceLab 90207). Blood pressure was measured three times during pregnancy and once after delivery. Evaluation was performed with receiver-operator-characteristics curves in primiparous women. Stratified analysis and multiple regression was applied with respect to urinary albumin excretion rate, HbA1c, age, duration of diabetes mellitus, uric acid, and BMI. RESULTS: The incidence of preeclampsia was significantly associated with increasing urinary albumin excretion rate, primiparity, and ambulatory blood pressure. Ambulatory blood pressure was associated with HbA1c throughout pregnancy adjusted for urinary albumin excretion rate. The ambulatory blood pressure was higher from first trimester throughout pregnancy in women developing preeclampsia compared to women who did not have preeclampsia. The best sensitivity and specificity for predicting preeclampsia in primiparous women were at cut-off values of systolic and diastolic day ambulatory blood pressure above 122 and 74 mmHg, respectively. The relative risk of preeclampsia was significantly higher when ambulatory blood pressure was above the cut-off values and increased further with higher urinary albumin excretion rate. CONCLUSIONS: The relationship between ambulatory blood pressure and preeclampsia is not confined to women with macroalbuminuria but is also present in women with normo- and microalbuminuria. Poor glycemic control and increased urinary albumin excretion rate is associated with preeclampsia when ambulatory blood pressure is above cut-off values of 122/74 mmHg (systole/diastole). Ambulatory blood pressure is a reliable measurement for prediction of preeclampsia in primiparous women with insulin-dependent diabetes mellitus.

Increased serum angiotensin-converting enzyme activity and plasma angiotensin II levels during pregnancy and postpartum in the diabetic rat.

OBJECTIVE: The renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure, electrolyte balance and renal function in normal human pregnancy. The present study was designed to assess various components of the RAS and renal function during pregnancy and immediately after pregnancy in the streptozotocin (STZ)-diabetic rat. METHODS: Pregnant Wistar rats were allocated to three groups: I-control, non-diabetic rats (n=24), II-STZ-diabetic rats (STZ 55 mg/kg body weight, i.v. on day 10 of pregnancy, n=24), III-diabetic rats, as above, treated with insulin (4 units/day, s.c. n=21). On days 17-18 of pregnancy, or within 24 hours after delivery, the rats were sacrificed and the various components of the RAS were determined. RESULTS: Urinary protein excretion (UP) and creatinine clearance(CCr) were greater in group II, four days after STZ, than in group I (UP: I-7.6+/-2.8, II-18.6+/-6.3 mg/24-hour, p<0.001, CCr: I-1.04+/-0.33, II-2.38+/-0.7 ml/minute, p<0.001). Mean (+/-SD) serum angiotensin-converting enzyme (ACE) activity and plasma angiotensin II(Ang II) levels at days 17-18 of pregnancy were greater in the untreated diabetic rats than in control pregnant rats (ACE: 163+/-18 vs. 111+/-21 nmol/ml/minute, p<0.001, Ang II: 115+/-45 vs. 43+/-10 pg/ml, p<0.005). Postpartum serum ACE activity and plasma Ang II levels were greater in group II (ACE: I-123+/-14, II-142+/-24, III-108+/-21 nmol/ml/minute, p<0.01, Ang II: I-56+/-38, II-148+/-62, III-38+/-17 pg/mI, p<0.001). ACE activity in the lung was greater, whereas the activity in the renal cortex was less, in group II than in group I. Kidney weight in untreated diabetic rats was greater than in the other two groups. CONCLUSION: Increased serum ACE activity during pregnancy and postpartum in the untreated diabetic rat is associated with enhanced serum Ang II levels, which may contribute to increased protein excretion and renal hypertrophy.

Urinary albumin excretion and 24-hour blood pressure as predictors of pre-eclampsia in Type I diabetes.

AIMS/HYPOTHESIS: To evaluate the value of 24-h blood pressure monitoring compared to office blood pressure and urinary albumin excretion in predicting pre-eclampsia in Type I (insulin-dependent) diabetes mellitus. METHODS: The study included 136 consecutive pregnancies in Caucasian women with Type I diabetes before gestation without diabetic nephropathy, anamnestic hypertension or early abortion. Values of urinary albumin excretion and office blood pressure before pregnancy and the HbA1C value at the time of conception were obtained. Microalbuminuria was defined as urinary albumin excretion of 30-300 mg/24 h in two out of three consecutive urine samples. Single measurements of 24-h urinary albumin excretion, office blood pressure and HbA1C were done five 5 times during pregnancy. In a subgroup of 74 women 24-h blood pressure measurements were done at 10 and 28 weeks of gestation. Pre-eclampsia was defined as office blood pressure higher than 140/90 mmHg accompanied by proteinuria above 0.3 g/24 h later than 20 weeks of gestation. RESULTS: Urinary albumin excretion and systolic blood pressure were higher before and throughout pregnancy in 14 women developing pre-eclampsia compared with women remaining normotensive (p <0.001; p < 0.05, respectively). By logistic regression analysis the best predictor for pre-eclampsia was microalbuminuria before pregnancy (p < 0.05) with no additive predictive effect of 24-h blood pressure or office blood pressure measurement. The night:day ratio of blood pressure was similar in the two groups. CONCLUSION/INTERPRETATION: Microalbuminuria before pregnancy is the strongest predictor of pre-eclampsia in Type I diabetes. Measuring 24-h blood pressure early in pregnancy did not improve the ability to identify women at risk.

Inositol phosphoglycans and signal transduction systems in pregnancy in preeclampsia and diabetes: evidence for a significant regulatory role in preeclampsia at placental and systemic levels.

Measurements have been made of the urinary content of inositol phosphoglycans IPG P-type and IPG A-type, putative insulin second messengers, in preeclampsia, in type I insulin-treated diabetic pregnant women and their matched control subjects, and nonpregnant women of child-bearing age. The content of IPG P-type and IPG A-type was also measured in the placenta from preeclamptic patients and from normal pregnancies. Pregnancy was associated with an increase, approximately twofold, in urinary output of IPG-P-type relative to nonpregnant controls (P<0.01). The 24-h output of IPG P-type in urine in preeclamptic women was significantly higher (2- to 3-fold) than in pregnant control subjects matched for age, parity, and stage of gestation (P<0.02). In contrast, insulin-dependent diabetic pregnant women did not show any significant change in urinary output of IPG P-type or IPG A-type relative to pregnant control subjects. Evidence for a possible relationship and correlation between the urinary excretion of IPG P-type and markers of preeclampsia, including proteinuria (r = 0.720, P<0.01), plasma aspartate transaminase (r = 0.658, P<0.05), and platelet counts (r = 0.613, P<0.05) is presented. A high yield of IPG P-type was extracted from human placenta, in preeclampsia some 3-fold higher (P = 0.03) than the normal value, whereas no IPG A-type (with lipogenic-stimulating activity) was found. Low concentrations of placental IPG A-type were detected relative to IPG P-type using assay systems dependent upon the effect of this mediator on cAMP-dependent protein kinase or on a proliferation assay using thymidine incorporation into DNA of EGFR T17 fibroblasts. It is postulated that the high urinary excretion IPG P-type in preeclampsia reflects high placental levels and relates to the accumulation of glycogen in the placenta. The paracrine effects of placental IPG P-type (stimulation off other endocrine glands and/or endothelial cells) could contribute to the pathogenesis of the maternal syndrome. A possible theoretical link between elevated placental IPG P-type and apoptosis is proposed.

Plasma 1,5-anhydroglucitol concentrations are influenced by variations in the renal threshold for glucose.

AIMS: Measurement of serum 1,5-anhydroglucitol (1,5AG) concentrations has been proposed as an alternative to HbA1c as both a marker of diabetic glycaemic control and as a screening test for diabetes. The sugar competes with glucose for renal tubular reabsorption, so hyperglycaemia leads to reduced serum 1,5AG concentrations through increased urinary loss. This study has sought to establish whether plasma 1,5AG can be influenced by not only hyperglycaemia, but by variations in renal threshold for glucose. METHODS: Thirty-eight pregnant women (median age 30 years, range 20-43) found to be normoglycaemic after a 75-g carbohydrate load had plasma 1,5AG and urine glucose measured. RESULTS: Using multivariate analysis, the presence and degree of detectable glycosuria at 2 h post glucose load was strongly predictive of a low plasma 1,5AG concentration (P=0.0012) independently of fasting plasma glucose (P=0.96), 2 h glucose (P=0.029), subject age (P=0.97) and gestation (P=0.36). Thus, when matched for plasma glucose areas under the glucose load curve, 16 glycosuric subjects had significantly lower 1,5AG concentrations compared to 16 nonglycosuric ones (median 1,5AG 46 micromol/l (IQR 30-56) vs. 72 micromol/l (IQR 55-79, P=0.017). CONCLUSIONS: People with the same glucose tolerance may demonstrate variable plasma 1,5AG concentrations depending on their renal threshold for glucose. This inherent characteristic is likely to limit the usefulness of the test when monitoring or screening for diabetes.

Pregnancy outcome in women with insulin-dependent diabetes mellitus complicated by nephropathy.

We retrospectively analysed pregnancy complicated by diabetic nephropathy in patients attending a University teaching hospital (1990-97), to examine fetal/maternal outcomes. Fetal outcomes included early intrauterine deaths, stillbirths, neonatal/perinatal mortality, size for gestational age, malformations, and need for neonatal unit care. Maternal outcomes included change in frequency of hypertension or severe proteinuria, serum creatinine data, and caesarean section rate. There were 21 pregnancies in 18 women, resulting in 21 live infants. Neonatal mortality (RR 10, 95% CI 0-3.9), perinatal mortality (RR 5, 95% CI 0-3.3) and congenital malformations (RR 5.0, 95% CI 0.3-26.3) were greater than in the background population. At delivery, 76% of babies were appropriate in size for gestational age; 57% were preterm, all of whom required neonatal unit care. The caesarean section rate was 90.5% vs. 20% in the background population (RR 4.5, 95% CI 3.4-5.0) (p < 0.05). Hypertension frequency (p < 0.001) and high-grade proteinuria (p < 0.05) increased from booking to delivery. Although the take-home baby rate was 90%, perinatal/neonatal mortality, congenital malformations and caesarean sections, in addition to maternal morbidity, were significantly higher in women with diabetic nephropathy than in the background population.

Renal function in the diabetic pregnant rats.

Diabetic nephropathy is associated with increased urinary albumin and reduce kallikrein excretion. Increased activity of the renal kallikrein-kinin system has been suggested as one of the possible mechanisms underlying diabetic hyperfiltration. The present study shown that the Kallikrein-kinin system is progressively increased in the diabetic-pregnant rats at 7, 14, 21 days; 48 and 7 days after pregnancy (P < 0.05 vs Control). However, this increase during diabetic pregnancy did not reached the levels of control pregnancy. On the other hand albumin excretion shown a significant and progressive renal damage in the diabetic state. These findings suggest that the diabetic pregnancy could impair the renal hemodynamic, but, on the other side could modulate the vasodilator system at pregnancy in the attempt to protect the fetus.

Pregnant woman with transient diabetes insipidus resistant to 1-desamino-8-D-arginine vasopressin.

We encountered a pregnant woman with transient diabetes insipidus which developed during the third trimester. A hypertonic saline infusion study did not concentrate the osmolality of urine. Her laboratory data showed hypokalemia, hyperreninemia, an increased concentration of plasma aldosterone and an increased urinary excretion rate of prostaglandin E2, which resembled hyperprostaglandin E-syndrome. T1-weighted magnetic resonance imaging of the posterior pituitary gland revealed decreased intensity. Polyuria reached 4-6 L daily, and urine osmolality remained dilute despite a lapse of four days since treatment with intranasal 1-desamino-8-D-arginine vasopressin (dDAVP: 10-25 microg every 12 h). The patient was conservatively managed without medical treatment, then delivered in the 38th week of pregnancy without complication. The osmolality of the patient's urine was higher than that of the plasma when tested 3 days postpartum. The abnormality of magnetic resonance imaging of the posterior pituitary gland disappeared at 6 months after delivery. We consider that subclinical nephrogenic diabetes insipidus in our patient was exacerbated during pregnancy.