Are third-trimester adipokines associated with higher metabolic risk among women with gestational diabetes?

AIM: This study aimed to determine whether third-trimester adipokines during gestational diabetes (GDM) are associated with higher metabolic risk. METHODS: A total of 221 women with GDM (according to IADPSG criteria) were enrolled between 2011/11 and 2013/6 into a prospective observational study (IMAGE), and categorized as having elevated fasting blood glucose (FBG) or impaired fasting glucose (IFG, n = 36) if levels were ≥ 92 mg/dL during a 75-g oral glucose tolerance test (OGTT), impaired glucose tolerance (IGT, n = 116) if FBG was < 92 mg/dL but with elevated 1-h or 2-h OGTT values, or impaired fasting and stimulated blood glucose (IFSG, n = 69) if both FBG was ≥ 92 mg/dL and 1-h or 2-h OGTT values were elevated. RESULTS: Pre-gestational body mass index (BMI) was higher in women with IFG or IFSG compared with IGT (P < 0.001), as were leptin levels in women with IFG vs IGT [34.7 (10.5-119.7) vs 26.6 (3.56-79.4) ng/L; P = 0.008]. HOMA2-IR scores were higher in women with IFG or IFSG vs IGT (1.87 ± 1.2 or 1.72 ± 0.9 vs 1.18 ± 0.8, respectively; P < 0.001). Also, those with IFSG vs those with IGT had significantly lower HOMA2-B scores (111.4 ± 41.3 vs 127.1 ± 61.6, respectively; P < 0.05) and adiponectin levels [5.00 (1.11-11.3) vs 6.19 (2.11-17.7) µg/mL; P < 0.001], and higher levels of IL-6 [1.14 (0.33-20.0) vs 0.90 (0.31-19.0); P = 0.012] and TNF-α [0.99 (0.50-10.5) vs 0.84 (0.45-11.5) pg/mL; P = 0.003]. After adjusting for age, parity, and pre-gestational and gestational BMI, the difference in adiponectin levels remained significant. CONCLUSION: Diagnosing GDM by IADSPG criteria results in a wide range of heterogeneity. Our study has indicated that adipokine levels in addition to FBG may help to select women at high metabolic risk for appropriate monitoring and post-delivery interventions (ClinicalTrials.gov number NCP02133729).

Telemedicine and type 1 diabetes: is technology per se sufficient to improve glycaemic control?

AIM: In the TELEDIAB-1 study, the Diabeo system (a smartphone coupled to a website) improved HbA1c by 0.9% vs controls in patients with chronic, poorly controlled type 1 diabetes. The system provided two main functions: automated advice on the insulin doses required; and remote monitoring by teleconsultation. The question is: how much did each function contribute to the improvement in HbA1c? METHODS: Each patient received a smartphone with an insulin dose advisor (IDA) and with (G3 group) or without (G2 group) the telemonitoring/teleconsultation function. Patients were classified as "high users" if the proportion of "informed" meals using the IDA exceeded 67% (median) and as "low users" if not. Also analyzed was the respective impact of the IDA function and teleconsultations on the final HbA1c levels. RESULTS: Among the high users, the proportion of informed meals remained stable from baseline to the end of the study 6months later (from 78.1±21.5% to 73.8±25.1%; P=0.107), but decreased in the low users (from 36.6±29.4% to 26.7±28.4%; P=0.005). As expected, HbA1c improved in high users from 8.7% [range: 8.3-9.2%] to 8.2% [range: 7.8-8.7%] in patients with (n=26) vs without (n=30) the benefit of telemonitoring/teleconsultation (-0.49±0.60% vs -0.52±0.73%, respectively; P=0.879). However, although HbA1c also improved in low users from 9.0% [8.5-10.1] to 8.5% [7.9-9.6], those receiving support via teleconsultation tended to show greater improvement than the others (-0.93±0.97 vs -0.46±1.05, respectively; P=0.084). CONCLUSION: The Diabeo system improved glycaemic control in both high and low users who avidly used the IDA function, while the greatest improvement was seen in the low users who had the motivational support of teleconsultations.

Continuous intraperitoneal insulin infusion does not increase the risk of organ-specific autoimmune disease in type 1 diabetic patients: results of a multicentric, comparative study.

AIM: The purpose of this national multicenter prospective study by the French EVADIAC group was to investigate the possibility that continuous intraperitoneal insulin infusion using an implanted pump (CIpii) increases the risk of autoimmune disease in type 1 diabetic patients as it increased anti-insulin immunogenicity. METHODS: Prevalence of clinical (Hashimoto's disease, hyperthyroidism, gastric atrophic disease and vitiligo) and subclinical (presence of anti-thyroperoxidase antibodies, anti-intrinsic factor antibodies, abnormal TSH levels) autoimmune diseases was estimated by comparing two groups of patients already treated by either CIpii (n=154) or external pump (CSII) (n=121) for an average of 6 years. Incidence of autoimmune disease was determined by comparing the same measurements one year after inclusion. RESULTS: No significant difference was observed for the total prevalence of clinical and subclinical auto-immune thyroid and gastric di-seases (35.6% and 3.2% respectively in the CIpii group versus 40.4% and 2.6% in the CSII group). No significant difference for the incidence of clinical and subclinical auto-immune diseases was observed: 7.2% and 0% in CIpii and 7.3% and 1.7% in CSII. CONCLUSION: As previously shown AIA (anti-insulin antibodies) levels were higher in CIpii than in CSII (32.9% vs 20.2%, P<0.0001) but no correlation was observed with either clinical or subclinical autoimmune disease. This large-scale study eliminates the possibility that CIpii increases the risk of autoimmune disease.

[Retrospective study of anorexia nervosa: reduced mortality and stable recovery rates]. / Diminution de la mortalité et stabilité du taux de guérison dans le suivi de l'anorexie mentale.

OBJECTIVES: Anorexia nervosa is an eating disorder that combines malnutrition, amenorrhea, and distorted body image. To learn more about the course of this disease we undertook a retrospective study of girls diagnosed with anorexia nervosa in the Saint Etienne Endocrinology Department between 1979 and 2004. METHODS: Patients were diagnosed according to DSMIV criteria. Data collected to complete the Morgan-Russell outcome assessment schedule included chronology of illness, patients' morphological features, anorexia type, treatment choice, patient's gynecological history, and social status. RESULTS: The study included 206 cases. The average follow-up period was 8.3 +/- 5.3 years. Defining recovery as stable BMI>17.5 kg/m2 for at least one year and recovery of normal menstruation, full recovery was observed in 55.8% and partial recovery in 25.7%, while 18.5% remained chronically ill. Early onset (i.e., during adolescence) was associated with good prognosis, and advanced emaciation and delayed or insufficient medical care with poor prognosis. CONCLUSIONS: The seriousness of this disease is due more to the incidence of cases that become chronic than to the mortality rate. Prediction of severity would be improved by taking into account underlying personality traits, such as addictive tendencies and depression.

Hypercorticism blunts circadian variations of osteocalcin regardless of nutritional status.

Anorexia nervosa (AN) and Cushing's syndrome (CS) are both responsible for osteoporosis. The mechanisms leading to osteoporosis in AN include hypogonadism, nutritional depletion, and in some cases hypercorticism. Osteocalcin circulating level is a serum marker of osteoblastic activity that follows a circadian rhythm (OCR). Serum osteocalcin is decreased in both CS and AN and can be increased with treatment. In this study we analyzed the influence of combined cortisol and nutritional status on osteocalcin levels and its circadian rhythm in these two different models of hypercorticism, one nutritionally replete (CS) and one nutritionally deplete (AN), and we evaluated the effects of their treatment (surgical cure and weight gain, respectively). Before treatment, osteocalcin levels were lower in CS (n = 16) and AN (n = 42) than in controls and in the AN patient subgroup with hypercorticism (n = 13) compared to those without (n = 29). OCR was absent in CS and in AN patients with hypercorticism, whereas their circadian cortisol cycle was maintained. In CS, successful surgical treatment increased osteocalcin levels (n = 5) and restored OCR. In AN, weight gain (n = 13) induced a significant decrease in cortisol levels in hypercortisolic AN patients, and restored normal osteocalcin levels and OCR. In conclusion, we found that hypercorticism was associated with a decrease in osteocalcin levels in nutritionally replete or deplete patients and that OCR was more affected by cortisol levels than by cortisol cycle.

Initiating insulin treatment in insulin-requiring type 2 diabetic patients: comparative efficiency and cost of outpatient and inpatient management. INNOV Study Group.

The main objective of this randomised study was to compare glycaemic control (as determined by HbA1c levels) in two groups of insulin-requiring Type 2 diabetic patients three months after initiation of insulin therapy either on an inpatient (group A, n = 58) or outpatient (group B, n = 56) basis. Evaluation of the safety and cost of both methods was a secondary objective. Although HbA1c level at inclusion was slightly but significantly lower in group A than group B (10.17 +/- 0.19% vs. 10.87 +/- 0.22% respectively, P = 0.019), covariance analysis showed equivalent glycaemic control at 3 months in both groups (adjusted means with respect to inclusion values: 9.00 +/- 1.14% vs. 9.37 +/- 1.14% respectively; equivalence hypothesis: P = 0.01). A low and similar incidence of episodes of hypoglycaemia and hyperglycaemia with ketonuria was observed. Clinical tests, paramedical care and the cost of hospitalisation itself resulted in a direct cost of initiating treatment that was more than four times higher in group A than in group B (mean total cost per patient: FF 15,231 and FF 3,296 respectively). Insulin-requiring Type 2 diabetic patients can be efficiently and safely started on insulin as outpatients, and this approach to initiating insulin therapy is cost-effective.

Are depression and denutrition good predictors of dexamethasone suppression test (DST) in anorexia nervosa?

This study was conducted to investigate the corticotropic axis in anorexia nervosa. In 93 female inpatients who met DSM-III-R criteria for anorexia nervosa, subsample (n = 64) with DSM-III criteria was also considered. Using stepwise regression analysis, this study examined the relationship between independent variables ie, age, body mass index, scores on depression scales and postdexamethasone serum cortisol, considered as a dependent variable. In patients who met DSM-III criteria, 16.7% of the variance of serum cortisol can be explained. The main predictors are depressive retardation, emaciation and age. Using stepwise logistic regression the main categorical predictors of the test suppression vs non suppression are of the same nature. The condition of realisation of DST are discussed.

Efficacy of low doses of radioiodine in the treatment of autonomous thyroid nodules: importance of dose/area ratio.

Radioiodine (131I) represents an interesting alternative to surgery in the treatment of autonomously functioning thyroid nodules (AFTN), but leads to a significant incidence of hypothyroidism when high doses are used. Over 4 years, we have treated 40 patients (hyperthyroid [Plummer's disease]: 6, single hot nodules with undetectable thyrotropin [TSH] and normal serum free thyroxine [FT4]: 34), 34 single hot nodules with undetectable thyrotropin TSH and normal serum free thyroxine [FT4] with 131I. The dose level was neither related to the concentration of FT4 nor to the iodine uptake on thyroid scintigram. Retrospectively we measured the nodule's area on the scan and calculated the dose/area ratio (DAR). Three months after treatment, 30 patients were euthyroid, 9 were still hyperthyroid, and 1 was hypothyroid. The mean DAR of the euthyroid patients was twofold higher than for the hyperthyroid subjects (1.4 +/- 0.8 vs. 0.7 +/- 0.3 mCi/cm2; p = .003) and one-half the DAR for the hypothyroid patient (2.82 mCi/cm2). Twenty of the 30 euthyroid patients had received a dose higher than 1 mCi/cm2 and 7 of 9 hyperthyroid patients had received a dose lower than 1 mCi/cm2. (chi2 = 12.9; p = .02). The initial values of T4, TSH, and dose level of patients who were euthyroid or hyperthyroid at 3 months were not different. These data suggest that the efficacy of 131I for treating AFTN depends on the DAR, rather than the initial T4 value or the 131I uptake. A DAR between 1 and 1.5 mCi/cm2 seems to be optimal and avoids hypothyroidism.

[Acute pituitary necrosis after multiple pituitary stimulation test]. / Nécrose hypophysaire aiguë après test de multistimulation hypophysaire.

Iatrogenic necrosis of the pituitary gland is well-known but rarely caused by stimulation tests used to investigate pituitary adenomas; 26 cases have been reported in the literature. We report 2 new cases where the chronology of the events suggests the sudden necrosis resulted from stimulation tests. Several mechanisms have been proposed. It is not possible to define increased risk as a function of the adenoma histology. In most cases, voluminous tumors are revealed by visual dysfunction. These accidents should not overshadow the role of function tests in neurosurgical situations. Outcome is usually favorable after acute necrosis.

[Theoretical aspects of the treatment with antithyroid drugs]. / Aspects théoriques du traitement par les antithyroïdiens.

Antithyroid drugs (thionamides such as carbimazole and its active metabolite methimazole, and propyl thiouracile) are taken up by the thyroid gland just as the other anions similar to iodide (perchlorate, thiocyanate, pertechnetate). Their target is the thyroid peroxidase. They block the iodation of tyrosine residues and the coupling of iodotyrosines into iodothyronines. However, beyond the inhibition of thyroid hormone synthesis, antithyroid drugs appear to have the capacity of interfering with the immunological abnormalities involved in Graves' hyperthyroidism: they cure 50% of the patients provided they are maintained for at least 12 months and they significantly decrease the titers of antithyroid antibodies in most of the patients. Potential immunomodulatory effects of antithyroid drugs seem to involve thyroid depletion of iodine which might reduce antigen expression, and scavenging of reactive free radicals generated from oxygen and/or iodide during peroxidation. A direct toxic effect of thionamides on immuno-competent cells seems unlikely. Whatever the mechanisms, more accurate elucidation of the immunomodulatory action of antithyroid drugs might contribute to a better understanding of the thyroid-immune derangements involved in the initiation or perpetuation of Graves' hyperthyroidism.

[Standardized ambulatory insulin therapy of initial moderate ketoacidosis in type 1 diabetes. A pilot project]. / Insulinothérapie standardisée ambulatoire de l'acidocétose modérée inaugurale du diabéte de type 1. Etude pilote.

Most textbooks advise that newly diagnosed insulin dependent mellitus be admitted to the hospital for starting carefully insulin treatment. We report a pilot study for starting an outpatient insulin using continuous subcutaneous insulin infusion. In 40 newly IDDM (glycaemia over 16.5 mM/l, CO2 over 15 mM/l), intensive therapy was done by CSII = basal rate 1 unit/hour, bolus 5 units per meal. After a long explanatory talk (4 hours) with the physician and the nurse on hypo, hyperglycaemia, on blood glucose sensor and pump, 21 patients agreed to start insulin at home and 19 remained in hospital for 2 or 7 days. At days 3, 30 and 365, clinical and biological evaluation was done and at D30 patient education program for 5 days was undergone. Never emergency even was reported in any patient, and no difference appeared between the in and out patient in D1, D3 and D365 normalisation of blood glucose (3 days) or level cetone body (2 days) and total insulin dose. Our results suggest that outpatient is a safe and cost effective IDDM onset therapy.