The unexplored role of sedentary time and physical activity in glucose and lipid metabolism-related placental mRNAs in pregnant women who are obese: the DALI lifestyle randomised controlled trial.

OBJECTIVE: We aimed to explore: (i) the association of sedentary time (ST) and physical activity (PA) during pregnancy with the placental expression of genes related to glucose and lipid metabolism in pregnant women who are obese; (ii) maternal metabolic factors mediating changes in these placental transcripts; and (iii) cord blood markers related to the mRNAs mediating neonatal adiposity. DESIGN: Multicentre randomised controlled trial. SETTING: Hospitals in nine European countries. POPULATION: A cohort of 112 pregnant women with placental tissue. METHODS: Both ST and moderate-to-vigorous PA (MVPA) levels were measured objectively using accelerometry at three time periods during pregnancy. MAIN OUTCOME MEASURES: Placental mRNAs (FATP2, FATP3, FABP4, GLUT1 and PPAR-γ) were measured with NanoString technology. Maternal and fetal metabolic markers and neonatal adiposity were assessed. RESULTS: Longer periods of ST, especially in early to middle pregnancy, was associated with lower placental FATP2 and FATP3 expression (P < 0.05), whereas MVPA at baseline was inversely associated with GLUT1 mRNA (P = 0.02). Although placental FATP2 and FATP3 expression were regulated by the insulin-glucose axis (P < 0.05), no maternal metabolic marker mediated the association of ST/MVPA with placental mRNAs (P > 0.05). Additionally, placental FATP2 expression was inversely associated with cord blood triglycerides and free fatty acids (FFAs; P < 0.01). No cord blood marker mediated neonatal adiposity except for cord blood leptin, which mediated the effects of PPAR-γ on neonatal sum of skinfolds (P < 0.05). CONCLUSIONS: In early to middle pregnancy, ST is associated with the expression of placental genes linked to lipid transport. PA is hardly related to transporter mRNAs. Strategies aimed at reducing sedentary behaviour during pregnancy could modulate placental gene expression, which may help to prevent unfavourable fetal and maternal pregnancy outcomes. TWEETABLE ABSTRACT: Reducing sedentary behaviour in pregnancy might modulate placental expression of genes related to lipid metabolism in women who are obese.

Effect of metformin and insulin vs. placebo and insulin on whole body composition in overweight patients with type 2 diabetes: a randomized placebo-controlled trial.

Some studies indicate potential beneficial effects of metformin on body composition and bone. This trial compared metformin + insulin vs placebo + insulin. Metformin treatment had a small but positive effect on bone quality in the peripheral skeleton, reduced weight gain, and resulted in a more beneficial body composition compared with placebo in insulin-treated patients with type 2 diabetes. INTRODUCTION: Glucose-lowering medications affect body composition. We assessed the long-term effects of metformin compared with placebo on whole body bone and body composition measures in patients with type 2 diabetes mellitus. METHODS: This was a sub-study of the Copenhagen Insulin and Metformin Therapy trial, which was a double-blinded randomized placebo-controlled trial assessing 18-month treatment with metformin compared with placebo, in combination with different insulin regimens in patients with type 2 diabetes mellitus (T2DM). The sub-study evaluates the effects on bone mineral content (BMC), density (BMD), and body composition from whole body dual-energy X-ray absorptiometry (DXA) scans which were assessed at baseline and after 18 months. RESULTS: Metformin had a small, but positive, (p < 0.05) effect on subtotal, appendicular, and legs BMC and BMD compared with placebo. After adjustment for sex, age, vitamin D, smoking, BMI, T2DM duration, HbA1c, and insulin dose, the effects on appendicular BMC and BMD persisted (p < 0.05 for both). The changes in appendicular BMC and BMD corresponded approximately to a 0.7% and 0.5% increase in the metformin group and 0.4% and 0.4% decrease in the placebo group, respectively. These effects were mostly driven by an increase in BMC and BMD in the legs and a loss of BMC and BMD in the arms. During 18 months, all participants increased in weight, fat mass (FM), FM%, and lean mass (LM), but decreased in LM%. The metformin group increased less in weight (subtotal weight (weight-head) - 2.4 [- 3.5, - 1.4] kg, p value < 0.001) and FM (- 1.5 [- 2.3, - 0.8] kg, p value < 0.001) and decreased less in LM% (0.6 [0.2, 1.1] %, p value < 0.001) compared with the placebo group. CONCLUSION: Metformin treatment had a small positive effect on BMC and BMD in the peripheral skeleton and reduced weight gain compared with placebo in insulin-treated patients with T2DM.

Metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes.

AIMS: To describe the metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes. METHODS: We performed a post hoc analysis using data from the Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial conducted across nine European countries (2012-2014). In women with a BMI ≥29 kg/m2 , insulin resistance and secretion were estimated from the oral glucose tolerance test values performed before 20 weeks, using homeostatic model assessment of insulin resistance and Stumvoll first-phase indices, respectively. Women with early gestational diabetes, defined by the International Association of Diabetes and Pregnancy Study Groups criteria, were classified into three groups: GDM-R (above-median insulin resistance alone), GDM-S (below-median insulin secretion alone), and GDM-B (combination of both) and the few remaining women were excluded. RESULTS: Compared with women in the normal glucose tolerance group (n = 651), women in the GDM-R group (n = 143) had higher fasting and post-load glucose values and insulin levels, with a greater risk of having large-for-gestational age babies [adjusted odds ratio 3.30 (95% CI 1.50-7.50)] and caesarean section [adjusted odds ratio 2.30 (95% CI 1.20-4.40)]. Women in the GDM-S (n = 37) and GDM-B (n = 56) groups had comparable pregnancy outcomes with those in the normal glucose tolerance group. CONCLUSIONS: In overweight and obese women with early gestational diabetes, higher degree of insulin resistance alone was more likely to be associated with adverse pregnancy outcomes than lower insulin secretion alone or a combination of both.

The effect of metformin versus placebo in combination with insulin analogues on bone mineral density and trabecular bone score in patients with type 2 diabetes mellitus: a randomized placebo-controlled trial.

Some antihyperglycemic medications have been found to affect bone metabolism. We assessed the long-term effects of metformin compared with placebo on bone mineral density (BMD) and trabecular bone score (TBS) in patients with type 2 diabetes. Metformin had no significant effect on BMD in the spine and hip or TBS compared with a placebo. INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures despite a high bone mass. Some antihyperglycemic medications have been found to affect bone metabolism. We assessed the long-term effects of metformin compared with placebo on bone mineral density (BMD) and trabecular bone score (TBS). METHODS: This was a sub-study of a multicenter, randomized, 18-month placebo-controlled, double-blinded trial with metformin vs. placebo in combination with different insulin regimens (the Copenhagen Insulin and Metformin Therapy trial) in patients with T2DM. BMD in the spine and hip and TBS in the spine were assessed by dual-energy X-ray absorptiometry at baseline and after 18 months follow-up. RESULTS: Four hundred seven patients were included in this sub-study. There were no between-group differences in BMD or TBS. From baseline to 18 months, TBS decreased significantly in both groups (metformin group, - 0.041 [- 0.055, - 0.027]; placebo group - 0.046 [- 0.058, - 0.034]; both p < 0.001). BMD in the spine and total hip did not change significantly from baseline to 18 months. After adjustments for gender, age, vitamin D, smoking, BMI, duration of T2DM, HbA1c, and insulin dose, the TBS between-group differences increased but remained non-significant. HbA1c was negatively associated with TBS (p = 0.009) as was longer duration of diabetes, with the femoral neck BMD (p = 0.003). Body mass index had a positive effect on the hip and femoral neck BMD (p < 0.001, p = 0.045, respectively). CONCLUSIONS: Eighteen months of treatment with metformin had no significant effect on BMD in the spine and hip or TBS in patients with T2DM compared with a placebo. TBS decreased significantly in both groups. TRIAL REGISTRATION: ClinicalTrials.gov (NCT00657943).

Mental health in early pregnancy is associated with pregnancy outcome in women with pregestational diabetes.

AIM: To explore the role of early pregnancy health-related quality of life, anxiety, depression and locus of control for pregnancy outcome in women with pregestational diabetes. METHODS: This was a cohort study of 148 pregnant women with pregestational diabetes (118 with Type 1 diabetes and 30 with Type 2 diabetes), who completed three internationally validated questionnaires: the 36-item Short-Form Health Survey, the Hospital Anxiety and Depression Scale and the Multidimensional Health Locus of Control survey at 8 weeks. Selected pregnancy outcomes were preterm delivery (< 37 weeks) and large for gestational age infants (birth weight > 90(th) percentile). Differences between groups in the questionnaires were analysed using an unpaired t-test. RESULTS: Women with preterm deliveries (n = 28) had lower (i.e. worse) mean (sd) quality-of-life scores for the two 36-item Short-Form Health Survey scales, Role-Emotional [58.3 (38.1) vs. 82.9 (31.3); P = 0.0005] and Mental Health [67.7 (20.4) vs. 75.2 (15.8), P = 0.04], and a lower score for the 36-item Short-Form Health Survey scale Mental Component Summary (42.8 (13.1) vs. 48.8 (9.7), P = 0.03) in early pregnancy, compared with women with term deliveries. Depression symptoms (Hospital Anxiety and Depression Scale depression score ≥ 8) were more frequent in women with preterm vs. term deliveries (seven (25%) vs. six women (5%); P = 0.003), while levels of anxiety and locus of control were similar in these two groups. No difference in early pregnancy scores for health-related quality of life, anxiety, depression and locus of control were seen in women delivering large or appropriate for gestational age infants. CONCLUSIONS: Poor mental quality of life and the presence of depressive symptoms in early pregnancy were associated with preterm delivery in women with pregestational diabetes.

Fetal growth in relation to gestational weight gain in women with type 2 diabetes: an observational study.

AIMS: To evaluate fetal growth in relation to gestational weight gain in women with Type 2 diabetes. METHODS: A retrospective cohort study of 142 consecutive pregnancies in 28 women of normal weight, 39 overweight women and 75 obese women with Type 2 diabetes (pre-pregnancy BMI < 25, 25-29.9, ≥ 30 kg/m2, respectively). Gestational weight gain was categorized as excessive (exceeding the US Institute of Medicine recommendations) or as non-excessive (within or below the Institute of Medicine recommendations). RESULTS: Excessive and non-excessive gestational weight gain were seen in 61 (43%) and 81 women (57%) with a median (range) gestational weight gain of 14.3 (9-32) vs. 7.0 (-5-16) kg (P < 0.001), respectively. Infants of women with excessive gestational weight gain were characterized by higher birth weight (3712 vs. 3258 g; P = 0.001), birth weight z-score (1.14 vs. -0.01, P = 0.001) and prevalence of large-for-gestational-age infants (48 vs. 20%; P < 0.001). In normal weight, overweight and obese women with non-excessive gestational weight gain, the median weight gain in the first half of pregnancy was 371, 114 and 81 g/week, and in the second half of pregnancy 483, 427 and 439 g/week, respectively. In multiple linear regression analysis, gestational weight gain was associated with a higher infant birth weight z-score independent of pre-pregnancy BMI, smoking, HbA1c and insulin dose at last visit, ethnicity and parity [ß=0.1 (95% CI 0.06-0.14), P < 0.001]. CONCLUSIONS: Infant birth weight was almost 0.5 kg higher in women with Type 2 diabetes and excessive gestational weight gain than in women with Type 2 diabetes and non-excessive weight gain.

Real-time continuous glucose monitoring as a tool to prevent severe hypoglycaemia in selected pregnant women with Type 1 diabetes - an observational study.

AIMS: Among women with Type 1 diabetes who have had severe hypoglycaemia the year before pregnancy, 70% also experience this complication in pregnancy, and particularly in the first half of pregnancy. We evaluated whether routine use of real-time continuous glucose monitoring from early pregnancy onwards could prevent severe hypoglycaemia in these women. METHODS: All 136 consecutive pregnant women with Type 1 diabetes referred to our centre were asked about severe hypoglycaemic events in the year before pregnancy and early in pregnancy at their first antenatal visit. Women with a relevant recent history were informed about their additional high risk of severe hypoglycaemia, their treatment was focused on restricted insulin doses during the first 16 gestational weeks, and they were offered real-time continuous glucose monitoring on top of self-monitored plasma glucose measurements. RESULTS: Among 28 women with a recent history of severe hypoglycaemia, 12 (43%) used real-time continuous glucose monitoring from a median (range) of 10 (7-13) gestational weeks for 10 (1-32) weeks. Among these 12 women, eight had experienced a total of 34 (range 1-11) severe hypoglycaemic events in the year before pregnancy and nine had experienced 23 (range 1-10) events early in pregnancy. After initiation of real-time continuous glucose monitoring, two (17%) women experienced one event each. The incidence rates of severe hypoglycaemia were 2.8,17.5 and 0.3 events/patient-year. Among the 16 women in the high risk group not using real-time continuous glucose monitoring, the corresponding figures were 1.6, 5.0 and 0.1 events/patient-year. CONCLUSIONS: Further evaluation is required to determine whether continuous real-time continuous glucose monitoring from early pregnancy onwards in highly selected women may reduce the risk of severe hypoglycaemia. Other elements of focused intervention probably also contribute to the risk reduction.

The incidence of severe hypoglycaemia in pregnant women with type 1 diabetes mellitus can be reduced with unchanged HbA1c levels and pregnancy outcomes in a routine care setting.

AIMS: To investigate whether the incidence of severe hypoglycaemia in pregnant women with type 1 diabetes can be reduced without deteriorating HbA1c levels or pregnancy outcomes in a routine care setting. METHODS: Two cohorts (2004-2006; n=108 and 2009-2011; n=104) were compared. In between the cohorts a focused intervention including education of caregivers and patients in preventing hypoglycaemia was implemented. Women were included at median 8 (range 5-13) weeks. Severe hypoglycaemia (requiring assistance from others) was prospectively reported in structured interviews. RESULTS: In the first vs. second cohort, severe hypoglycaemia during pregnancy occurred in 45% vs. 23%, p=0.0006, corresponding to incidences of 2.5 vs. 1.6 events/patient-year, p=0.04. Unconsciousness and/or convulsions occurred at 24% vs. 8% of events. Glucagon and/or glucose injections were given at 15% vs. 5% of events. At inclusion HbA1c was comparable between the cohorts while in the second cohort fewer women reported impaired hypoglycaemia awareness (56% vs. 36%, p=0.0006), insulin dose in women on multiple daily injections was lower (0.77 IU/kg (0.4-1.7) vs. 0.65 (0.2-1.4), p=0.0006) and more women were on insulin analogues (rapid-acting 44% vs. 97%, p<0.0001; long-acting 6% vs. 76%, p<0.0001) and insulin pumps (5% vs. 23%, p<0.0001). Pregnancy outcomes were similar in the two cohorts. CONCLUSIONS: A 36% reduction in the incidence of severe hypoglycaemia in pregnancy with unchanged HbA1c levels and pregnancy outcomes was observed after implementation of focused intervention against severe hypoglycaemia in a routine care setting. Improved insulin treatment, increased health professional education and fewer women with impaired hypoglycaemia awareness may contribute.

Real-time continuous glucose monitoring during labour and delivery in women with Type 1 diabetes - observations from a randomized controlled trial.

AIMS: To explore whether real-time continuous glucose monitoring during labour and delivery supplementary to hourly self-monitored plasma glucose in women with Type 1 diabetes reduces the prevalence of neonatal hypoglycaemia. METHODS: Women with Type 1 diabetes participating in a randomized controlled trial on the effect of real-time continuous glucose monitoring in pregnancy were included in this study. Twenty-seven of 60 (45%) women in the intervention arm used real-time continuous glucose monitoring during labour and delivery, supplementary to hourly self-monitored plasma glucose. Real-time continuous glucose monitoring glucose data covering the last 8 h prior to delivery were retrospectively evaluated, and maternal hypo- and hyperglycaemia were defined as glucose values ≤ 3.9 mmol/l and > 7.0 mmol/l, respectively. Women in the control arm (n = 59) solely used self-monitored plasma glucose. Neonatal hypoglycaemia was defined as a 2-h plasma glucose < 2.5 mmol/l. RESULTS: In infants of women using real-time continuous glucose monitoring during labour and delivery, 10 (37%) developed neonatal hypoglycaemia vs. 27 (46%) infants in the control arm (P = 0.45). Among 10 infants with and 17 infants without neonatal hypoglycaemia within the real-time continuous glucose monitoring arm, median maternal self-monitored plasma glucose was 6.2 (range 4.2-7.8) vs. 5.6 (3.3-8.5) mmol/l (P = 0.26) during labour and delivery, with maternal hyperglycaemia present in 17 (0-94) vs. 4 (0-46)% of the time (P = 0.02), and birthweight was 4040 (3102-4322) vs. 3500 (1829-4320) g (P = 0.04). Maternal hypoglycaemia up to delivery was relatively rare. CONCLUSIONS: The prevalence of neonatal hypoglycaemia was comparable between infants of women using real-time continuous glucose monitoring supplementary to self-monitored plasma glucose during labour and delivery and infants of women solely using self-monitored plasma glucose.

Hypoglycaemia during pregnancy in women with Type 1 diabetes.

AIMS: To explore incidence, risk factors, possible pathophysiological factors and clinical management of hypoglycaemia during pregnancy in women with Type 1 diabetes. METHODS: Literature review. RESULTS: In women with Type 1 diabetes, severe hypoglycaemia occurs three to five times more frequently in early pregnancy than in the period prior to pregnancy, whereas in the third trimester the incidence of severe hypoglycaemia is lower than in the year preceding pregnancy. The frequency distribution of severe hypoglycaemia is much skewed, as 10% of the pregnant women account for 60% of all recorded events. Risk factors for severe hypoglycaemia during pregnancy include a history with severe hypoglycaemia in the year preceding pregnancy, impaired hypoglycaemia awareness, long duration of diabetes, low HbA(1c) in early pregnancy, fluctuating plasma glucose values (≤ 3.9 mmol/l or ≥ 10.0 mmol/l) and excessive use of supplementary insulin injections between meals. Pregnancy-induced nausea and vomiting seem not to be contributing factors. CONCLUSIONS: Striving for near-normoglycaemia with focus on reduction of plasma glucose fluctuations during pregnancy should have high priority among clinicians with the persistent aim of improving pregnancy outcome among women with Type 1 diabetes. Pre-conception counselling, carbohydrate counting, use of insulin analogues, continuous subcutaneous insulin infusion (insulin pump) therapy and real-time continuous glucose monitoring with alarms for low glucose values might be relevant tools to obtain near-normoglycaemia without episodes of severe hypoglycaemia.

Patient satisfaction and barriers to initiating real-time continuous glucose monitoring in early pregnancy in women with diabetes.

AIM: To evaluate self-reported satisfaction and barriers to initiating real-time continuous glucose monitoring in early pregnancy among women with pregestational diabetes. METHODS: Fifty-four women with Type 1 diabetes and 14 women with Type 2 diabetes were offered continuous glucose monitoring for 6 days at median 9 (range 6-14) gestational weeks and were asked to answer a semi-structured questionnaire on patient satisfaction. RESULTS: Median HbA1c was 49 (range 34-86) mmol/mol) [6.6 (5.3-10.0) %] and duration of diabetes was 12 (0.5-37) years. Continuous glucose monitoring was used for 6 (0.5-7) days, with 43 (65%) women using continuous glucose monitoring for at least 5 days. The women experienced 2.7 (0-12) alarms per 24 h, of which approximately one third was technical alarms and one third disturbed their sleep. Sixteen women (24%) reported discomfort with continuous glucose monitoring during daytime and twelve (18%) during sleep. Many women reported improved diabetes understanding (52%) and would recommend continuous glucose monitoring to others (83%). Twenty-four patients (36%) had continuous glucose monitoring removed earlier than planned ( before the intended 6 days of initial monitoring). Ten women (15%) did not wish to use continuous glucose monitoring again in pregnancy. Main causes behind early removal of continuous glucose monitoring were self-reported skin irritation, technical problems and continuous glucose monitoring inaccuracy. No differences were found in continuous glucose monitoring use, inconvenience or compliance with respect to diabetes type. CONCLUSIONS: The majority of pregnant women with diabetes found real-time continuous glucose monitoring useful and the intervention was equally tolerated regardless of diabetes type. Nevertheless, continuous glucose monitoring was frequently removed earlier than planned, primarily because of skin irritation, technical problems and inaccuracy.

Cognitive function in adult offspring of women with Type 1 diabetes.

AIMS: Maternal diabetes may affect offspring cognitive function. The objective of the study was to evaluate cognitive function and potential predictors hereof in adult offspring of women with Type 1 diabetes. METHODS: We conducted a follow-up study of adult offspring of women with Type 1 diabetes (n = 158) and a reference group from the background population (n = 118). The main outcome measure was offspring cognitive function measured by global cognitive score, derived from Raven's Progressive Matrices and three verbal subtests from the Weschler Adult Intelligence Scale. RESULTS: Offspring of women with Type 1 diabetes obtained lower global cognitive scores (94.8 vs. 100.0, P = 0.004) than offspring from the background population. When adjusted for confounders, the groups no longer differed significantly (difference 0.4, 95% CI -3.3 to 4.). Positive predictors of cognitive function in offspring of women with diabetes were family social class, parental educational level, maternal diabetes duration, male gender and offspring age, whereas parity ≥ 1 and gestational age < 34 weeks were negative predictors. We found no association with maternal glycaemia during pregnancy or with neonatal hypoglycaemia. CONCLUSIONS: Impaired cognitive function in adult offspring of women with Type 1 diabetes compared with the background population apparently reflects differences with respect to well-known confounders. However, harmful effects of maternal hyperglycaemia may be mediated through delivery at < 34 weeks.

A high concentration of prorenin in early pregnancy is associated with development of pre-eclampsia in women with type 1 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether components of the renin-angiotensin system and semicarbazide-sensitive amine oxidase (SSAO) are associated with the development of pre-eclampsia in women with type 1 diabetes. METHODS: This was an observational study of 107 consecutive pregnant women with type 1 diabetes (median duration 16 years [range 1-36 years], HbA(1c) 6.6% [range 4.9-10.5%]) in early pregnancy. At 8, 14, 21, 27 and 33 weeks and once within 5 days postpartum, blood was sampled for measurements of prorenin, renin, angiotensinogen, ACE and SSAO. HbA(1c), blood pressure and urinary albumin excretion were recorded. Pre-eclampsia was defined as blood pressure >140/90 mmHg and proteinuria ≥300 mg/24 h after 20 weeks. RESULTS: Pre-eclampsia developed in nine women (8%) with longer diabetes duration (median 20 [range 10-32] vs 16 [range 1-36] years, p = 0.04), higher SSAO concentrations (592 [range 372-914] vs 522 [range 264-872] mU/l, p = 0.04) and a tendency towards higher prorenin levels (136 [range 50-296] vs 101 [range 21-316] ng angiotensin I ml(-1) h(-1), p = 0.06) at 8 weeks compared with women without pre-eclampsia. Levels of renin, angiotensinogen and ACE did not differ in the two groups. Throughout pregnancy, prorenin and SSAO levels were 30% (p = 0.004) and 16% (p = 0.04) higher, respectively, in women developing pre-eclampsia. Using multivariate logistic regression analysis, prorenin concentration at 8 weeks was associated with pre-eclampsia (OR 4.4 [95% CI 1.5-13.0], p = 0.007), i.e. an increase of prorenin of 100 ng angiotensin I ml(-1) h(-1) implies a 4.4 times higher risk of subsequent pre-eclampsia. CONCLUSIONS/INTERPRETATION: In type 1 diabetic women with pre-eclampsia, a higher concentration of prorenin in early pregnancy and higher levels of prorenin and SSAO throughout pregnancy were seen.

Pregnancy-induced sight-threatening diabetic retinopathy in women with Type 1 diabetes.

AIMS: To determine the progression of diabetic retinopathy in pregnant women with diabetes offered tight glycaemic and blood pressure control. METHODS: A prospective study of 102 (87%) out of 117 consecutive pregnant women with Type 1 diabetes for median 16 years (range 1-36) and HbA(1c) 6.7% (4.9-10.8) in early pregnancy. Fundus photography was performed at 8 and 27 weeks. Retinopathy was classified in five stages. Diabetic macular oedema was classified as present in a mild form or as clinically significant macular oedema (CSMO). Progression was defined as at least one stage of deterioration of retinopathy and/or development of macular oedema in at least one eye. Sight-threatening progression was defined as loss of visual acuity>or=0.2 on Snellen's chart or laser treatment performed during pregnancy due to proliferative retinopathy or CSMO. RESULTS: Diabetic retinopathy was present at inclusion in at least one eye in 64 (63%) women and proliferative retinopathy and macular oedema were present in nine and 16 women, respectively. Progression of retinopathy occurred in 28 (27%) women. Sight-threatening progression occurred in six women; in three, visual acuity deteriorated and four required laser treatment. Sight-threatening progression was associated with presence of macular oedema (P=0.007), impaired visual acuity (P=0.03) and higher blood pressure (P=0.016) in early pregnancy, but not with HbA1c, decline in HbA1c, or prevalence of severe hypoglycaemia. CONCLUSIONS: Loss of visual acuity and the need for laser treatment during diabetic pregnancy remain clinical problems associated with presence of macular oedema, visual impairment and higher blood pressure in early pregnancy.

Diabetic mothers and their newborn infants - rooming-in and neonatal morbidity.

AIM: As a result of increased neonatal morbidity, the infants of diabetic mothers have routinely been admitted to a neonatal special care unit (NSCU). We therefore investigated whether the offer of rooming-in diabetic mothers and their newborn infants has an effect on neonatal morbidity. METHODS: The records of an old cohort of 103 infants routinely admitted to the NSCU, and a new cohort (N = 102), offered rooming-in were assessed for neonatal morbidity. RESULTS: Eighty-four (82%) of the new cohort infants followed their mothers to the maternity ward; whereas 19 (18%) were transferred to the NSCU chiefly because of prematurity. Ten infants were later transferred to the NSCU for minor problems. Neonatal morbidity and neonatal hypoglycaemia were significantly less common in the new cohort than in the old cohort [27 (26%) vs. 55 (54%), p < 0.001 and 42 (41%) vs. 64 (63%), p = 0.0027 respectively]. Maternal HbA1c in late pregnancy was significantly lower in the new cohort, but the only independent predictors of neonatal morbidity were belonging to the old cohort and preterm delivery. CONCLUSION: Neonatal care with rooming-in mothers with type 1 diabetes and their newborn infants seems safe and is associated with reduced neonatal morbidity, when compared with routine separation of infants from their mothers.

Progression of diabetic retinopathy during pregnancy in women with type 2 diabetes.

AIMS/HYPOTHESIS: We studied the progression of diabetic retinopathy during pregnancy in women with type 2 diabetes. METHODS: Fundus photography was performed at median 10 (range 6-21) and 28 (27-37) gestational weeks in 80 of 110 (73%) consecutively referred pregnant women with type 2 diabetes. Diabetic retinopathy was classified in five stages. Progression was defined as at least one stage of deterioration of diabetic retinopathy and/or development of macular oedema on at least one eye between the two examinations. Macular oedema was defined as retinal thickening and/or hard exudates within a diameter of 1,500 microm in the macula area. RESULTS: Diabetic retinopathy, mainly mild, was present in 11 (14%) women in early pregnancy. Median duration of diabetes was 3 years (range 0-16 years). At baseline, HbA(1c) was 6.4% (1.0) (mean [SD]), systolic BP 121 (13) and diastolic BP 72 (9) mmHg. Prior to pregnancy, 22 (28%) women had been on insulin treatment. During pregnancy 74 women (93%) were treated with insulin and 11 (14%) with antihypertensive medication. Progression of diabetic retinopathy was observed in 11 (14%) women. Progression was mainly mild, but one woman with poor glycaemic control and uncontrolled hypertension progressed from mild retinopathy to sight-threatening retinopathy with proliferations, clinically significant macular oedema and impaired vision in both eyes. Progression of diabetic retinopathy was associated with a longer duration of diabetes (p = 0.03) and insulin treatment before pregnancy (p = 0.004). CONCLUSIONS/INTERPRETATION: Despite a low risk of progression of retinopathy in pregnant women with type 2 diabetes, sight-threatening deterioration did occur.

Severe hypoglycaemia during pregnancy in women with type 1 diabetes: possible role of renin-angiotensin system activity?

AIMS: To investigate whether increased risk of severe hypoglycaemia in early pregnancy is related to pregnancy-induced changes in renin-angiotensin system (RAS) activity in women with type 1 diabetes (T1DM). METHODS: Severe hypoglycaemic events the year preceding pregnancy were recorded retrospectively in 107 consecutive pregnant women with T1DM. Events during pregnancy were recorded prospectively. Measurements of ACE, renin and angiotensinogen were determined at 8, 14, 21, 27 and 33 weeks and postpartum. RESULTS: The rate of severe hypoglycaemia was 1.1 and 5.3 events/patient-year the year preceding pregnancy and in first trimester, respectively (p<0.0001). Levels of ACE, renin or angiotensinogen did not differ between women with and without severe hypoglycaemia during pregnancy. Multivariate regression analysis identified a positive association between rate of severe hypoglycaemia the year preceding pregnancy and postpartum ACE activity (relative rate of severe hypoglycaemia above versus below median ACE activity: 4.4 (CI: 1.7-11.9), p=0.003). No association was found between severe hypoglycaemia during pregnancy and renin angiotensin system activity at 8 weeks. CONCLUSIONS: In early pregnancy increased RAS activity does not explain the 5-fold increase in severe hypoglycaemia in women with T1DM. A positive association between occurrence of severe hypoglycaemia and ACE activity outside pregnancy was demonstrated.

Lower levels of circulating IGF-I in Type 1 diabetic women with frequent severe hypoglycaemia during pregnancy.

AIMS: Severe hypoglycaemia is a significant problem in pregnant women with Type 1 diabetes. We explored whether frequent severe hypoglycaemia during pregnancy in women with Type 1 diabetes is related to placental growth hormone (GH) and insulin-like growth factor I (IGF-I) levels. METHODS: A prospective, observational study of 107 consecutive pregnant women with Type 1 diabetes. Blood samples were drawn for IGF-I and placental GH analyses at 8, 14, 21, 27 and 33 weeks. Severe hypoglycaemic events were reported within 24 h. RESULTS: Eleven women (10%) experienced frequent severe hypoglycaemia (> or = 5 events), accounting for 60% of all events. Throughout pregnancy, IGF-I levels were 25% lower in these women (P < 0.005) compared with the remaining women, despite similar placental GH levels. Eighty per cent of the severe hypoglycaemic events occurred before 20 weeks when IGF-I levels were at their lowest. This finding was not explained by differences in insulin dose, median plasma glucose levels or glycated haemoglobin. History of severe hypoglycaemia the year preceding pregnancy and impaired hypoglycaemia awareness-being the only predictors of frequent severe hypoglycaemia in a logistic regression analysis-were not associated with IGF-I or placental GH levels at 8 weeks. CONCLUSIONS: In women with Type 1 diabetes experiencing frequent severe hypoglycaemia during pregnancy, IGF-I levels are significantly lower compared with the remaining women despite similar placental GH levels. IGF-I levels are lowest in early pregnancy where the incidence of severe hypoglycaemia is highest. IGF-I may be a novel factor of interest in the investigation of severe hypoglycaemia in patients with Type 1 diabetes.