Hypertensive disorders during pregnancy and 3 years after delivery in women with gestational hyperglycemia.

AIMS: Women with gestational hyperglycemia commonly experience hypertensive disorders during pregnancy. More information is needed about how hypertension develops in these patients over time. We investigated the prevalence of hypertension during and 3 years after pregnancy in Caucasian women with gestational hyperglycemia. We also investigated metabolic syndrome presence, glucose tolerance status, insulin sensitivity and insulin secretion levels in the follow-up period. METHODS: In a prospective longitudinal study with a 3-year follow-up, we assessed hypertension status and clinical-related characteristics of 103 consecutive women with gestational hyperglycemia sub-grouped according to their hypertensive status during and after pregnancy. RESULTS: Overall, 29 (28.1%) women had hypertension during pregnancy (24 gestational hypertension; 4 chronic hypertension; 1 preeclampsia). At follow-up 16 (15.5%) women were diagnosed as having hypertension (11 with hypertension in pregnancy; 5 with a normotensive pregnancy). Women with hypertension after pregnancy had higher BMI, metabolic syndrome rate and worse insulin resistance indexes than normotensive women. Weight increase at follow-up (OR 1.17, 95% CI 1.00-1.35) and hypertension in pregnancy (OR 6.72, 95% CI 1.17-38.64) were associated with hypertension after pregnancy. CONCLUSIONS: Women with gestational hyperglycemia should undergo regular monitoring during and after pregnancy to detect metabolic and clinical impairments and to prevent cardiovascular harm.

Efficacy, safety and acceptability of the new pen needle 33G × 4 mm. AGO 01 study.

OBJECTIVES: Adherence to insulin therapy can be threatened by pain and needle fear. This cross-over randomized non-inferiority trial evaluated a new Pic Insupen 33G × 4 mm needle vs. a 32G × 4 mm needle in terms of metabolic control, safety and acceptability in patients with diabetes treated with insulin. RESEARCH DESIGN AND METHODS: We used a centralized, permuted block randomization, stratified by center and maximum insulin dose per single injection. Subjects used the two needles in two 3 week treatment periods. The primary endpoint was the absolute percentage variation of the blood fructosamine between the two treatments (% |ΔFru|). Additional endpoints were: glycemic variability, total insulin doses, body weight, severe hypoglycemic episodes, leakage at injection sites and pain measured by visual analogue scale. Equivalent glycemic control was defined a priori as % |ΔFru| (including 95% CI) within 20%. RESULTS: Of 87 subjects randomized, 77 completed the study (median age 53.1 [IR 42.3-61.2], median BMI 24.3 Kg/m(2) [IR 21.3-28.5], median duration of insulin therapy [in months] 141.4 (IR 56.3-256.9), median baseline HbA1c 7.9% [IR 7.2-8.8]). The % |ΔFru| was 7.93% (95% CI 6.23-9.63), meeting the non-inferiority criterion. The fasting blood glucose standard deviation was 46.2 (mean 154.6) with the 33G needle and 42.8 (mean 157.3) with the 32G needle (p=0.42). Insulin daily dose and patients' weight did not show any statistically significant variation. We observed 95 episodes of symptomatic hypoglycemia with the 33G needle and 96 with the 32G needle. One episode of severe hypoglycemia was documented in the latter group. As for insulin leakage we observed 37.55 episodes per 100 patient-days with the 33G needle and 32.21 episodes per 100 patient-days with the 32G needle (p=0.31). Patients reported less pain with the 33G × 4 mm needle (p=0.05). STUDY LIMITATIONS: Study sample was mainly composed of adults with type 1 diabetes and study was not blinded. CONCLUSIONS: The 33G needle is not inferior to the 32G needle in terms of efficacy and safety, with reduced pain and no difference in insulin leakage. CLINICAL TRIAL REGISTRATION: NCT01745549.

Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study.

BACKGROUND: Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. AIM: To evaluate the efficacy and tolerability of larazotide acetate during gluten challenge. METHODS: This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. RESULTS: No significant differences in LAMA ratios were observed between larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between larazotide acetate and placebo groups. CONCLUSIONS: Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.

A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge.

OBJECTIVES: In patients with celiac disease, enteropathy is caused by the entry of gluten peptides into the lamina propria of the intestine, in which their immunogenicity is potentiated by tissue transglutaminase (tTG) and T-helper type 1-mediated immune responses are triggered. Tight junction disassembly and paracellular permeability are believed to have an important role in the transport of gluten peptides to the lamina propria. Larazotide acetate is a tight-junction regulator peptide that, in vitro, prevents the opening of intestinal epithelial tight junctions. The aim of this study was to evaluate the efficacy and tolerability of larazotide acetate in protecting against gluten-induced intestinal permeability and gastrointestinal symptom severity in patients with celiac disease. METHODS: In this dose-ranging, placebo-controlled study, 86 patients with celiac disease controlled through diet were randomly assigned to larazotide acetate (0.25, 1, 4, or 8 mg) or placebo three times per day with or without gluten challenge (2.4 g/day) for 14 days. The primary efficacy outcome was the urinary lactulose/mannitol (LAMA) fractional excretion ratio. Secondary endpoints included gastrointestinal symptom severity, quality-of-life measures, and antibodies to tTG. RESULTS: LAMA measurements were highly variable in the outpatient setting. The increase in LAMA ratio associated with the gluten challenge was not statistically significantly greater than the increase in the gluten-free control. Among patients receiving the gluten challenge, the difference in the LAMA ratios for the larazotide acetate and placebo groups was not statistically significant. However, larazotide acetate appeared to limit gluten-induced worsening of gastrointestinal symptom severity as measured by the Gastrointestinal Symptom Rating Scale at some lower doses but not at the higher dose. Symptoms worsened significantly in the gluten challenge-placebo arm compared with the placebo-placebo arm, suggesting that 2.4 g of gluten per day is sufficient to induce reproducible gluten toxicity. Larazotide acetate was generally well tolerated. No serious adverse events were observed. The most common adverse events were headache and urinary tract infection. CONCLUSIONS: LAMA variability in the outpatient setting precluded accurate assessment of the effect of larazotide acetate on intestinal permeability. However, some lower doses of larazotide acetate appeared to prevent the increase in gastrointestinal symptom severity induced by gluten challenge.

Eating disorders and diabetic ketoacidosis in a pregnant woman with type 1 diabetes: a case report.

OBJECTIVE: To describe a case of diabetic ketoacidosis (DKA) in a pregnant woman with type 1 diabetes (T1DM) and disordered eating behaviour treated with a continuous subcutaneous insulin infusion, and to discuss some aspects of the monitoring and management of DKA in pregnancy and whether a pump is the safest therapeutic choice in the presence of some eating disorders. CASE REPORT: This 26-year-old Caucasian woman affected by T1DM was hospitalised during the last weeks of her fourth pregnancy because of DKA due to disordered eating. She was treated with a fluid infusion, intravenous insulin, and her electrolyte imbalance was carefully corrected. An elective cesarean section was performed after the correction of DKA in the 34th week (+6 days) of gestation. CONCLUSIONS: We suggest that pregnancy in T1DM women with eating disorders may not be rare. The prevention, early recognition and aggressive management of DKA can minimise the possible complications, and is mandatory for the safety of the fetus and mother.

Hypertensive disorders in normal/over-weight and obese type 2 diabetic pregnant women.

BACKGROUND: Hypertension is one of the major complications of pregnancy. Its impact in type 2 diabetic pregnant women could be understimated because it is generally evaluated by retrospective studies and as one of the outcome measures. OBJECTIVE: Our aims were: 1) to evaluate the prevalence of hypertensive disease between type 2 diabetic and normal pregnancies; 2) to relate hypertensive disease to body weight in type 2 diabetic pregnancies; 3) to assess the impact of different types of hypertension on pregnancy outcome in type 2 diabetic women. STUDY DESIGN: Seventy-six type 2 diabetic (23 normal-weight, 26 overweight and 27 obese) and sixty normal (43, 15 and 2 respectively; x (2) 0.0001) pregnancies, matched for age and smoking habit. Hypertension was defined as >/=140/90 mmHg and classified in chronic, gestational and pre-eclampsia. STATISTICAL ANALYSIS: Student's t-test, chi (2), simple, and/or multiple and logistic regression analysis were used when appropriate. Odds ratio was calculated for hypertension. p significant <0.05. RESULTS: The overall prevalence of hypertension was 40.8% (18.4% chronic, 17.1% gestational and 5.3% pre-eclampsia) in type 2 diabetic pregnancies and 10% (8.3% gestational and 1.7% pre-eclampsia) in normal pregnancies (p<0.0001), with an odds ratio of 6.2. All the types of hypertension, significantly chronic, contributed to the higher prevalence. Only in diabetic pregnancies, hypertension was associated with a higher pregestational BMI; whenever BMI increased, chronic and gestational hypertension increased by contrast of pre-eclampsia (chi (2), 0.02). Hypertensive disorders did not affect maternal-fetal outcome. CONCLUSIONS: The prevalence of hypertension was 40.8% in type 2 diabetic pregnant women whilst it was 10.0% in non diabetic controls. All hypertensive disorders, significantly chronic, were more frequent. Increasing BMI was a crucial factor for chronic and gestational but not for pre-eclampsia. Hypertensive diseases did not seem to affect pregnancy outcome.

Visual evoked potentials in infants of diabetic mothers: relations to clinical and metabolic status during pregnancy and delivery.

OBJECTIVE: To evaluate Visual Evoked Potentials (VEPs) and psychomotor development of infants of diabetic mothers (IDMs) in relation to clinical and metabolic data during pregnancy and delivery. METHODS: VEPs and psychomotor development (Brunet-Lézine) were analysed in 40 two-month-old IDMs (21 males, 19 females), 24 from mothers with type-1 diabetes, 13 gestational diabetes, and 3 type-2 diabetes. Normative VEP data were obtained from 63 age matched controls. RESULTS: VEP latencies were significantly longer in IDMs than in controls (O1 wave IV=197.9+/-35.5 vs 155.3+/-30.3; P<0.001; O2 wave IV=200.2+/-33.8 vs 155.6+/-29.0; P<0.001). The mean developmental quotient was normal. In IDMs with type-1 diabetes delayed VEPs were related to increased weight during pregnancy (r 0.516; P 0.009), 1st trimester fasting blood glucose (r 0.458; P 0.037), insulin requirement during the 2nd (r 0.441; P 0.035) and 3rd trimester (r 0.422; P 0.039); in IDMs with gestational diabetes, VEP latency showed negative relation to Apgar scores (r -0.748; P 0.008). CONCLUSIONS: IDMs have delayed VEPs, which may possibly be related to poor metabolic control in pre-gestational diabetes, and to delivery complications in gestational diabetes. SIGNIFICANCE: IDMs show subtle neurophysiologic changes detectable by VEPs.

A lower level of entropy in circadian rhythm of the sinus R-R intervals suggests a prevalence of the cardiac sympathetic regulation in early physiological pregnancy.

The study estimates the unpredictable disorder (chaos) within the 24 h pattern of sinus R-R intervals (SRRI) in clinically healthy pregnant women (CHPW) and clinically healthy non-pregnant women (CHNPW), in order to evaluate the early gestational changes in neurovegetative cardiac pacing. SRRI were provided by the 24-h Holter ECG of 10 CHPW and 10 CHNPW. SRRI were investigated by descriptive conventional statistics by means of the Time and Frequency Domain Analysis, and subsequently, in their chaotic component by means of entropy analysis. Both the SRRI and entropy were tested via the Cosinor method to better decipher whether or not the periodic disorder in heart rate variability is modified in pregnancy as a result of a gestational tonic resetting of the cardiac sympatho-vagal regulation. Cosinor analysis documented that the circadian rhythm of both the SRRI and entropy were preserved in CHNPW and CHPW. However, the circadian rhythm of SRRI and entropy in CHPW exhibited a significantly decreased 24 h mean. Via the analysis of the rhythmicity of entropy, this study has documented that the chaos in the 24 h pattern of SRRI is less prominent in CHPW than in CHNPW. Such a reduction of level in the deterministic periodic chaos of heart rate variability provides evidence that, in early pregnancy, a tonic elevation of the sympathetic activity regulates cardiac pacing.

Contraception in diabetic women: an Italian study.

Over 1 year, a survey on contraception and obstetric history was performed on a cohort of 667 Caucasian fertile diabetic women (446, type 1 and 201, type 2) living in Italy. RESULTS: Of these women, 30.4% used hormonal contraceptives, 12.0% intra-uterine device (IUD), 10.7% declared they used no contraception, 47.0% only utilised barrier and/or natural methods. However, irrespective of their previous contraceptive strategy, 7.2% of all the studied population was surgically sterilized during caesarean section. HORMONAL CONTRACEPTION: Of these women, 60.4% was prescribed by a gynaecologist, 11.2% by a diabetologist, 15% by both of them and 13.4% by others. The proportion using oral contraception was similar among types 1 and 2 women (29.4% versus 27.8%, chi(2) = ns). SMOKING HABITS: Of women taking hormonal contraception, 30.0% were smokers. EDUCATIONAL LEVEL: University graduates (37.1%), high school leaves (32.2%), secondary school (28.2%) and primary school leaves (15.5%) used oral contraceptives (OC). OBSTETRIC HISTORY: The mean number of deliveries was 1.14 +/- 1.1, of miscarriages was 1.3 +/- 0.7 and of induced abortions 0.17 +/- 0.5. Planning of at least one pregnancy was reported in 29.4% of patients.