Initially untreated fasting hyperglycaemia in early pregnancy: prognosis according to occurrence of gestational diabetes mellitus after 22 weeks' gestation: a case-control study.

AIMS: To evaluate the percentage of women with untreated fasting hyperglycaemia in early pregnancy who develop gestational diabetes mellitus after 22 weeks' gestation, the determinants of gestational diabetes development in such women and the prognosis of early fasting hyperglycaemia according to whether the women go on to develop gestational diabetes. METHODS: From a large cohort of women who delivered in our hospital between 2012 and 2016, we retrospectively selected all those who had untreated early fasting hyperglycaemia and separated them into a 'gestational diabetes' and a 'no-gestational diabetes' group according to oral glucose tolerance test results after 22 weeks' gestation. We compared the incidence of a predefined composite outcome (preeclampsia or large-for-gestational-age infant or shoulder dystocia or neonatal hypoglycaemia) in both groups. RESULTS: A total of 268 women (mean fasting plasma glucose 5.3 ± 0.3 mmol/l at a mean ± sd of 10.2 ± 4.2 weeks' gestation) were included. Gestational diabetes developed in 134 women and was independently associated with early fasting plasma glucose ≥ 5.5 mmol/l [odds ratio 3.16 (95% CI 1.57, 6.33)], age ≥ 30 years [odds ratio 2.78 (95% CI 1.46, 5.31)], preconception obesity [odds ratio 2.12 (95% CI 1.11, 4.02)], family history of diabetes [odds ratio 1.87 (95% CI 1.00, 3.50)] and current employment [odds ratio 0.46 (95% CI 0.26, 0.83)]. Despite treatment, gestational diabetes induced a significant increase in the composite outcome as compared to no gestational diabetes (odds ratio 2.16 [95% CI 1.08, 4.34]). The association disappeared after adjustment for risk factors. CONCLUSIONS: Only half of the women with early fasting hyperglycaemia and no specific care subsequently developed gestational diabetes, and these women had a poor prognosis despite gestational diabetes treatment. Poor prognosis was mostly attributable to risk factors. Our results suggest that only women with certain risk factors should be screened for early fasting hyperglycaemia.

Performance of a selective screening strategy for diagnosis of hyperglycaemia in pregnancy as defined by IADPSG/WHO criteria.

AIM: Our study evaluated the performance of a selective screening strategy for hyperglycaemia in pregnancy (HIP) based on the presence of risk factors (RFs; body mass index≥25kg/m2, age≥35years, family history of diabetes, personal history of HIP or macrosomic infant) to diagnose HIP and to predict HIP-related events. METHODS: Women with no known diabetes who had undergone complete universal screening (early, before 22weeks of gestation and, if normal, in the second part of pregnancy) at our department (2012-2016) were selected, resulting in four groups of women according to the presence of HIP and/or RFs, with a predefined composite endpoint (preeclampsia or large-for-gestational-age infant or shoulder dystocia). RESULTS: Included were 4518 women: 23.5% had HIP and 71.1% had at least one RF. The distribution among our four groups was: HIP-/RF- (n=1144); HIP-/RF+ (n=2313); HIP+/RF- (n=163); and HIP+/RF+ (n=898). HIP was more frequent when RFs were present rather than absent (33.1% vs 15.4%, respectively; P<0.001). Incidence of the composite endpoint differed significantly (P<0.0001) across groups [HIP-/RF- 6.3%; HIP-/RF+ 13.2%; HIP+/RF- 8.6%; and HIP+/RF+ 17.1% (HIP effect: P<0.05; RF effect: P<0.001; interaction HIP * RF: P=0.94)] and significantly increased with the number of RFs (no RF: 6.3%, 1 RF: 10.8%, 2 RFs: 14.7%, 3 RFs: 28.0%, 4-5 RFs: 25.0%; P<0.0001). CONCLUSION: RFs are predictive of HIP, although 15.4% of women with HIP have no RFs. Also, irrespective of HIP status, RFs are predictive of HIP-related events, suggesting that overweight/obesity, the only modifiable RFs, could be targets of interventions to improve pregnancy prognosis.

Early screening for gestational diabetes mellitus is not associated with improved pregnancy outcomes: an observational study including 9795 women.

AIMS: In addition to screening for hyperglycaemia during pregnancy after 24 weeks of gestation (WG), the current guidelines also suggest screening in early pregnancy and referring women with early gestational diabetes mellitus (eGDM) or overt diabetes (OD) for immediate care. Our aim was to evaluate this strategy. METHODS: This study evaluated, at our hospital (2012-2016), whether the incidence of a predefined composite outcome (preeclampsia, large-for-gestational-age infant, shoulder dystocia) and secondary outcomes was different when women were screened only after 22WG ('late screening only') or before 22WG and treated for eGDM or OD if present, with repeat screening after 22WG if absent ('early ± late screening'). RESULTS: Early ± late screening (n = 4605, 47.0%) increased between 2012 and 2016 (P < 0.0001) and was associated with more risk factors for GDM than late screening only. Glycaemic status differed in both groups (early ± late screening: eGDM 10.3%, GDM 12.1%, OD 0.9% vs. late screening only: GDM 16.8%, OD 1.2%; P < 0.001), with a higher rate of insulin therapy (8.9% vs. 6.0%; P < 0.001) and less gestational weight gain (11.1 ± 5.4 kg vs. 11.4 ± 5.5 kg; P = 0.013) in the early ± late screening group. Rates of those meeting the composite criterion were similar in both groups [11.6% vs. 12.0%, respectively; odds ratio (OR): 1.040, 95% confidence interval (CI): 0.920-1.176; P = 0.53] and remained comparable after adjusting for Propensity Scores (OR: 1.046, 95% CI: 0.924-1.185; P = 0.4790). Rates for secondary outcomes were also similar in both groups. CONCLUSION: While a strategy including early measurement of fasting plasma glucose during pregnancy increases the incidence and care of hyperglycaemia during pregnancy, it may not significantly improve pregnancy outcomes.

Fetal gender is not associated with either gestational diabetes mellitus or placental weight: A cohort study.

AIM: This study assessed whether male fetal gender increases the risk of maternal gestational diabetes mellitus (GDM) and investigated the association with placental weight. METHODS: The study included 20,149 women without pregestational diabetes who delivered singletons at our hospital between January 2002 and December 2010. There was universal screening for GDM, and all placentas were weighed at delivery. RESULTS: GDM (affecting 14.2% of women) was not associated with fetal gender (male fetuses in women without and with GDM: 51.8% vs. 51.7%, respectively; P=0.957), and remained likewise after logistic-regression analysis of risk factors for GDM (OR: 1.007, 95% CI: 0.930-1.091; P=0.858). Placental weights were 600±126g, 596±123g, 584±118g and 587±181g in women with GDM/female, GDM/male, no GDM/female and no GDM/male fetuses, respectively (GDM effect: P=0.017; gender effect: P=0.41; GDM * gender effect: P=0.16). CONCLUSION: The present results suggest that fetal gender is not associated with GDM and, while placental weights were higher in cases of GDM, there were still no gender effects.

Multicenter randomized evaluation of a nutritional education software in obese patients.

OBJECTIVE: To study the efficacy of the nutritional education software, Nutri-Expert, in the management of obese adult patients. MATERIAL AND METHODS: Two groups of obese patients were followed up over one year in a randomized study: the first group received close traditional management (seven nutritional visits over the year, with physicians and dietitians conjointly) and the second one also used at home by Minitel the Nutri-Expert system. 557 patients were enrolled in the study by 16 French centers of diabetology and nutrition. Body mass index (BMI), tests of dietetic knowledge, dietary records and centralized biological measurements were assessed at inclusion, 6 and 12 months. 341 patients were evaluable at the end of the year. RESULTS: The group using Nutri-Expert scored significantly better in the tests of dietetic knowledge than the control group. For all patients, nutritional education led to a significant improvement in BMI, dietary records and biological measurements, without significant difference between the two groups. Five years after the end of the study, the weight of 148 patients was recorded; mean BMI was significantly lower than the initial value but there was no significant difference between the two groups. CONCLUSION: In the management of obese patients, Nutri-Expert system has a role to play in reinforcing nutritional knowledge; if regular follow-up is not possible, or if a large series of obese patients is to be treated, Nutri-Expert could partly replace traditional management, for example between visits.

Extra cellular water and increase in capillary permeability to albumin in overweight women with swelling syndrome.

OBJECTIVE: To evaluate extracellular water (ECW) in the recumbent and the upright position, in overweight and lean women with swelling syndrome, and to correlate the excess in ECW with an increase in capillary filtration of albumin (CFA). PATIENTS: Fifty-one women with a swelling syndrome were investigated, 26 of whom were overweight. MEASUREMENTS: ECW was measured by the bioelectrical impedance method, in the recumbent position and again after a postural test which consisted of walking around for 30 min. CFA was studied by an isotopic test using 99m technetium-labelled albumin. RESULTS: ECW increased (>107% of the theoretical value) in 22 of the 26 overweight patients and 23 of the 25 lean patients. The CFA isotopic test was abnormal in half (11/22) of the overweight patients with increased ECW and in three of the four overweight patients with a normal ECW value. It was abnormal in 18 of the 23 lean patients with increased ECW and in the two lean patients with a normal ECW value. During the postural test, a significant (by> or =4%) increase in ECW occurred in a higher proportion of overweight patients tested (14/22) than among the lean women tested (0/5; P=0. 04). CONCLUSIONS: The swelling syndrome is indeed related to an increase in ECW in lean and overweight subjects and to a further increase in ECW after a postural test only in the overweight patients. It is also associated with microcirculatory disorders in most of the lean patients who complain of swelling and in only half of the overweight patients with the same complaints, which suggests that other factors (e.g. hormonal disorders) may be involved in the overweight patients. International Journal of Obesity (2000)24, 126-130

Effect of insulin concentration on bioavailability during nasal spray administration.

The bioavailability of rapid-acting insulin administered as a nasal spray was studied in 6 type 1 (insulin-dependent) diabetic patients. They received long-acting bovine insulin (Ultratardum 40 U/ml, Organon) as basal treatment at 8 a.m. Rapid-acting insulin was also administered at 8 a.m., then at noon and 6 p.m, subcutaneously on day 1 as a 100 U/ml solution and intranasally by aerosol spray as a 100 U/ml and 500 U/ml with 1% (w/v) 9 lauryl ether solution on day 2 and day 3 respectively. On days 2 and 3, the dose of insulin was at least nine times higher than the subcutaneous dose on day 1. Free and total plasma insulin concentrations were assayed after the noon insulin administration. The peaks of the free and total plasma insulin levels were reached earlier and the return to basal levels was obtained earlier after nasal insulin administration than after insulin injected subcutaneously. The bioavailability of nasal spray insulin versus subcutaneous insulin with a 100 U/ml insulin solution was similar to that with a 500 U/ml insulin solution: 5.14 +/- 0.38% (m +/- SEM) and 4.64 +/- 0.46% according to the total plasma insulin level. This study suggests that the bioavailability of nasal spray insulin is not increased by increasing insulin concentration in our experimental conditions.

[Multicenter evaluation of the Nutri-Expert Telematic System in diabetic patients]. / Evaluation multicentrique du Système Télématique Nutri-Expert aupres de patients diabétiques.

Nutri-Expert is a system for self-monitoring and dietetic education, accessible through Minitel. A preliminary randomised evaluation of one hundred diabetic patients in the Midi-Pyrénées region showed that Nutri-Expert improved dietetic knowledge, dietary habits and metabolic balance. The aim of the present study was to show that the system can be successfully prescribed to patients by physicians outside the center which originated it, indicating the benefit of a wider use of Nutri-Expert, among the diabetic population. One hundred and fifty-five patients, recruited by six French centres of diabetology, used Nutri-Expert from their homes for six months. Clinical examination, tests of dietetic knowledge and biological tests, including lipid fractions, were carried out before and after six months of use. After six months, there was a significant improvement in the patients' dietetic knowledge and in some biological parameters. Nutri-Expert is thus useful even when prescribed by a centre other than the hospital which devised the system. It is an additional beneficial tool in the ambulatory management of diabetic patients.

Thyroid stimulating antibodies in sarcoidosis.

OBJECTIVES: Thyroid disorders, particularly euthyroid goiters and hyperthyroidism, can be observed in sarcoidosis. The aim of this study was to analyze the presence of thyroid stimulating antibodies (TSAb) in 21 patients with sarcoidosis. 12 patients out of 21 had simultaneous euthyroid goiter. The others were euthyroid and free of goiter. METHODS: The TSAb testing was carried out using the rat thyroid fragment perifusion technique. Thyroid response to IgG was determined by the mean rate of T4 release (R) during a 30-min perifusion and the secretion peak (Imax). Antibodies inhibiting TSH binding to its receptors were also looked for. RESULTS: Ten patients were TSAb+ and eleven were TSAb-. There was no difference between the TSAb+ and TSAb- groups in the clinical parameters for sarcoidosis, nor in the number of goiters found (n = 6 for both groups). In 5 out of the 6 cases where goiter was present in the TSAb+ group it was homogeneous and diagnosed at the same time as or after the first signs of sarcoidosis, whereas in 5 out of the 6 cases of goiter in TSAb- patients, it was nodular, diagnosed before sarcoidosis in 3 of them, endemic in one of them, and familial in another. The search for antibodies inhibiting TSH binding to its receptors was negative in 10 out of 21 patients tested. CONCLUSION: Although the presence of thyroid-stimulating antibodies in the serum of patients with sarcoidosis, found here for the first time, remains to be explained, it pleads in favor of the immunologic nature of the association of sarcoidosis with thyroid disorders.

Stimulating effect of forskolin on thyroxine secretion. Influence of calcium.

The aim of this study was to determine, with a rat thyroid fragment perifusion system, the short-term (20 min) effect of forskolin (FK), an adenylate cyclase activator, on T4 secretion, the effect of forskolin on T4 secretion stimulated by theophylline and TSH, and the role played by calcium in the forskolin effect. A dose-dependent effect on T4 secretion was obtained with forskolin, from 10(-8) to 10(-4) mol/l, with a maximal effect between 10(-6) and 10(-5) mol/l. The effect of forskolin was not increased by theophylline. The combined stimulation with forskolin and theophylline induced a T4 release which remained significantly lower than the effect of 22 or 65 mIU/ml TSH. Forskolin slightly increased the stimulating effect of 22 mIU/ml TSH but significantly decreased the effect of 65 mIU/ml TSH. A reduction in the buffer calcium concentration slightly decreased the effect of the forskolin and theophylline stimulations and the effect of the combined stimulation with forskolin and theophylline without suppressing completely the effect of these stimulations. This study demonstrates that 1) low concentrations of forskolin are able to induce a significant T4 release during short-term stimulations; 2) calcium is necessary in order to obtain a maximum effect of adenylate cyclase activation on T4 release; 3) the part of the thyroid hormone response to TSH which is mediated by adenylate cyclase activation is relatively small.