Contraception use and knowledge related to pregnancy in diabetic women.

BACKGROUND: Diabetes mellitus prevalence is increasing among women of child-bearing age. Diabetic pregnancy is associated with major maternal and fetal risks, and these can be reduced by preconception care. Pregnancy can be planned using appropriate effective contraception. The objective of this study was to assess diabetic patients' knowledge about pregnancy and to describe their contraceptive use. STUDY DESIGN: An observational study was conducted from February to July 2020 at Reims University Hospital, France. Inclusion criteria were: women aged 18 to 40years, with type 1 (T1D) or type 2 diabetes (T2D). Patients filled out a survey about contraceptive use and knowledge regarding diabetic pregnancy and data were completed from medical records. RESULTS: Eighty-nine T1D and 33 T2D patients were included, with mean ages of 27.9±6.3 and 32.6±4.6years, respectively. Seventy-five percent reported that they had been informed about pregnancy-related risks and 67% about the need to plan pregnancy. The preconception HbA1c target was known by 33% of patients. Appropriate knowledge about pregnancy was greater in T1D patients (65.9%, versus 36.4% in T2D patients; P=0.003). The rate of patients using an effective contraceptive method was 66.4%. Fifteen percent patients for whom contraception was recommended reported having no contraceptive method; 12.5% of contraception users were using a contraindicated method. CONCLUSION: A large majority of diabetic women were aware of pregnancy-related risks and the importance of pregnancy planning, but there are still gaps, especially in T2D patients. We need to improve our practices by providing more information and better access to appropriate effective contraception. GOV NUMBER: NCT04350879.

Closed-loop insulin delivery in adults with type 1 diabetes in real-life conditions: a 12-week multicentre, open-label randomised controlled crossover trial.

BACKGROUND: Closed-loop insulin delivery systems are expected to become a standard treatment for patients with type 1 diabetes. We aimed to assess whether the Diabeloop Generation 1 (DBLG1) hybrid closed-loop artificial pancreas system improved glucose control compared with sensor-assisted pump therapy. METHODS: In this multicentre, open-label, randomised, crossover trial, we recruited adults (aged ≥18 years) with at least a 2 year history of type 1 diabetes, who had been treated with external insulin pump therapy for at least 6 months, had glycated haemoglobin (HbA1c) of 10% or less (86 mmol/mol), and preserved hypoglycaemia awareness. After a 2-week run-in period, patients were randomly assigned (1:1) with a web-based system in randomly permuted blocks of two, to receive insulin via the hybrid closed-loop system (DBLG1; using a machine-learning-based algorithm) or sensor-assisted pump therapy over 12 weeks of free living, followed by an 8-week washout period and then the other intervention for 12 weeks. The primary outcome was the proportion of time that the sensor glucose concentration was within the target range (3·9-10·0 mmol/L) during the 12 week study period. Efficacy analyses were done in the modified intention-to-treat population, which included all randomly assigned patients who completed both 12 week treatment periods. Safety analyses were done in all patients who were exposed to either of the two treatments at least once during the study. This trial is registered with ClinicalTrials.gov, number NCT02987556. FINDINGS: Between March 3, 2017, and June 19, 2017, 71 patients were screened, and 68 eligible patients were randomly assigned to the DBLG1 group (n=33) or the sensor-assisted pump therapy group (n=35), of whom five dropped out in the washout period (n=1 pregnancy; n=4 withdrew consent). 63 patients completed both 12 week treatment periods and were included in the modified intention-to-treat analysis. The proportion of time that the glucose concentration was within the target range was significantly higher in the DBLG1 group (68·5% [SD 9·4] than the sensor-assisted pump group (59·4% [10·2]; mean difference 9·2% [95% CI 6·4 to 11·9]; p<0·0001). Five severe hypoglycaemic episodes occurred in the DBLG1 group and three episodes occurred in the sensor-assisted pump therapy group, which were associated with hardware malfunctions or human error. INTERPRETATION: The DBLG1 system improves glucose control compared with sensor-assisted insulin pumps. This finding supports the use of closed-loop technology combined with appropriate health care organisation in adults with type 1 diabetes. FUNDING: French Innovation Fund, Diabeloop.

Continuous glucose monitoring and hypoglycemia unawareness in type 1 diabetes: a pilot study.

BACKGROUND: Looking for strict normoglycemia in type 1 diabetes increases the risk of hypoglycemia, exposing to hypoglycemia unawareness. It has been shown that the early correction of hypoglycemia can help recovering the perception of hypoglycemia. The purpose of this prospective study was to assess the value of sensor-augmented insulin-pump therapy to treat hypoglycemia unawareness. METHODS: Eleven patients with type 1 diabetes and partial or total hypoglycemia unawareness received sensor-augmented insulin-pump therapy combined to the low blood glucose-suspend feature (Paradigm® Veo™ pump and Enlite® sensors) for three months. RESULTS: Eighty per cent of the patients improved their hypoglycemia unawareness with an increase in the hypoglycemia perception threshold of 31 mg/dL as evaluated by blinded continuous glucose monitoring. These results were correlated to a self-assessment quiz evaluation. Results were sustained at six months (three months after patients stopped using the system). Sensitive neuropathy, untreated hypoglycemia and the area under the curve for hypoglycemia events were associated with less chance of recovery. These devices were globally considered by the patients as simple to use, with no major disadvantages and only a single withdrawal occurred. CONCLUSIONS: Sensor-augmented insulin-pump therapy should be considered as a possible treatment of hypoglycemia unawareness.

Study of Insulin Requirement Modeling in Hospitalized Elderly Patients with Type 2 Diabetes at a Late Stage of Stepwise Escalation Therapy.

BACKGROUND: This study explored the relationships between exogenous insulin requirements and endogenous variables in elderly patients with type 2 diabetes (T2D). SUBJECTS AND METHODS: Patients with T2D 65 years of age or older were enrolled for a short hospitalization period in order to start or change their basal-bolus therapy. The following data were collected: age, sex, diabetes duration, body mass index, glycosylated hemoglobin, estimated glomerular filtration rate (eGFR), and triglyceride (TG) levels. RESULTS: Data from 71 elderly T2D patients (31 men/40 women; 75.7 ± 6 years of age) were analyzed by data mining techniques. The total daily dose of insulin (TDI) ranged from 0.24 U/kg to 2.5 U/kg (ratio >1:10). Three clusters of patients were identified: Cluster 1 (n = 22) consisted of older patients (age, 82.05 ± 3.6 years) (P < 0.0001) with a TDI of 0.59 ± 0.21 U/kg/day and lower TG level (1.1 ± 0.4 mmol/L) (P < 0.0001). Cluster 2 (n = 22) consisted of patients with a TDI of 0.71 ± 0.24 U/kg/day with a higher eGFR (75.3 ± 18.8 mL/min) (P < 0.001) and a shorter duration of diabetes (13.6 ± 6.4 years) (P < 0.001). Cluster 3 (n = 27) consisted of patients with a larger proportion of macroangiopathic complications (P < 0.05), having a TDI of 1.31 ± 0.54 U/kg/day, higher TG level (2.2 ± 0.7 mmol/L) (P < 0.001), and lower eGFR (46.3 ± 16 mL/min). The average basal-bolus ratio was 43%/57% with a maximum bolus requirement due to carbohydrate intake at breakfast. CONCLUSIONS: Insulin requirements in elderly T2D patients vary widely. Age, TG level, and eGFR appeared to be the most predictive factors of TDI. Because of the small sample size, further studies would be required to extrapolate these results.

Interferon-alpha-induced hyperthyroidism: a three-stage evolution from silent thyroiditis towards Graves' disease.

Autoimmune thyroid disease is a common side-effect of interferon-alpha (IFN-alpha) treatment of viral hepatitis C. We have described three patients with hepatitis C for whom IFN-alpha and ribavirin were prescribed and who developed two successive phases of silent thyroiditis followed by hyperthryroidism relapse due to Graves' disease. These three men had no known history of familial or personal thyroid disease. Destructive thyrotoxicosis appeared 4-6 months after starting IFN-alpha, followed by Graves' hyperthyroidism within 8 to 11 months. The thyrotropin (TSH) level was normal before IFN-alpha was started. The diagnosis of destructive thyroiditis was confirmed by anti-TSH receptor antibody (TSHRAb) negativity and the absence of radionuclide ((123)I or (99)Tc) uptake on thyroid scintiscans. Eight to eleven months after starting treatment, TSHRAb positivity and intense scintigraphic uptake confirmed the appearance of Graves' disease. IFN-alpha was continued in only one patient. Hence, hyperthyroidism induced by IFN-alpha could correspond to the first phase of silent thyroiditis, to Graves' disease or to the succession of both. Rigorous diagnostic procedures with repeated scintiscans and TSHRAb titering are necessary to avoid a false diagnosis and inappropriate therapy.

AMH/MIS: what we know already about the gene, the protein and its regulation.

(AMH/MIS) was first suggested by Jost, more than Four decades before this gonadal glycoprotein was purified and its gene and promoter sequenced. In mammals, AMH expression is triggered by SOX9 in Sertoli cells at the onset of testicular differentiation, and regulated by SF1, GATA factors, WT1, DAX1 and FSH. Ovarian granulosa cells also secrete AMH from late foetal life. In males, AMH is secreted into the bloodstream at high levels until puberty when it is down-regulated by androgens and meiotic germ cells and its directional secretion switches from the basal compartment to the seminiferous tubule lumen. In birds and reptiles, AMH expression shows particular features. Serum AMH determination is useful to study testicular function in boys and in patients with gonadal tumours. AMH levels in seminal and follicular fluid may also be of clinical use.

Follicle-stimulating hormone increases testicular Anti-Mullerian hormone (AMH) production through sertoli cell proliferation and a nonclassical cyclic adenosine 5'-monophosphate-mediated activation of the AMH Gene.

Anti-Müllerian hormone (AMH) production by testicular Sertoli cells is high before puberty and can be further induced by FSH. Our objective was to delineate the mechanisms by which FSH stimulates AMH production. Assay of serum AMH levels and histological morphometric analysis in prepubertal FSH-deficient transgenic mice showed that serum AMH and testicular mass were decreased owing to reduced Sertoli cell number. All parameters resumed normal values in mice treated with recombinant FSH. We also analyzed the ability of FSH and the factors involved in its signaling pathway to activate AMH transcription by transfecting AMH promoter-luc reporter constructs of different lengths in a prepubertal Sertoli cell line. Our results showed that FSH activates AMH transcription via adenylate cyclase, cAMP, and protein kinase A but involving a nonclassical cAMP-response pathway requiring nuclear factor-kappaB and activating protein 2 binding sites, which lie more than 1.9 kb upstream of the AMH transcription start site. This is the first report showing the importance of distant sequences in the regulation of AMH expression. We conclude that prepubertal testicular AMH production is increased by FSH stimulation through Sertoli cell proliferation and an enhancement of AMH gene transcription.

Study of diurnal fluctuations of plasma methoxyamines in healthy volunteers.

OBJECTIVE: We studied the diurnal fluctuations of plasma concentrations of methoxyamines (metanephrine and normetanephrine) and of their parent amines (epinephrine and norepinephrine) in normotensive subjects. DESIGN: Serial blood sampling at 09.00 h, 11.00 h, 12.00 h, 14.00 h, 16.00 h, 18.00 h and 20.00 h in 28 healthy volunteers at rest. Determination of plasma concentrations of free catecholamines and total methoxyamines (free and sulpho-conjugates) was carried out by high-performance liquid chromatography with electrochemical detection. RESULTS: Mean (+/- SD) plasma concentrations of total metanephrine (MN) and normetanephrine (NMN) were 4.31 +/- 1.73 nmol/l (range: 0.96-9.3 nmol/l) and 8.13 +/- 2.54 nmol/l (range: 3.14-17.0 nmol/l), respectively. The NMN/MN ratio ranged between 0.8 and 7.8 (mean +/- SD 2.1 +/- 1.0). Mean plasma concentrations of free epinephrine and norepinephrine were 0.21 +/- 0.12 nmol/l (range: 0.06-1.39 nmol/l) and 1.61 +/- 0.62 nmol/l (range: 0.47-4.01 nmol/l), respectively. Despite marked intraindividual fluctuations, mean methoxyamine and catecholamine levels remained constant over the entire duration of the experiment. CONCLUSIONS: The absence of fluctuations of plasma levels of total methoxyamines suggests that their measurement could be carried out at any time within the diurnal time frame. Further investigations, however, remain necessary to validate these findings in patients with hypertension and/or pheochromocytoma, and to explain the ever important intraindividual variation in plasma concentrations of methoxyamines and of their parent compounds.