A safety and pharmacodynamics study of temelimab, an antipathogenic human endogenous retrovirus type W envelope monoclonal antibody, in patients with type 1 diabetes.

AIM: To report the first study of temelimab, a monoclonal antibody neutralizing the pathogenic human endogenous retrovirus type W envelope, in patients with type 1 diabetes (T1D). MATERIALS AND METHODS: This double-blind, placebo-controlled, randomized clinical trial recruited adult patients with T1D within 4 years postdiagnosis and remaining C-peptide secretion. Sixty-four patients were randomized (2:1) to monthly temelimab 6 mg/kg or placebo during 24 weeks followed by a 24-week, open-label extension, during which all patients received temelimab. The primary objective was the safety and tolerability of temelimab. The secondary objective was to assess the pharmacodynamics response such as C-peptide levels, insulin use, HbA1c, hypoglycaemia and autoantibodies. RESULTS: Temelimab was well tolerated without any group difference in the frequency or severity of adverse events. Concerning exploratory endpoints, there was no difference in the levels of C-peptide, insulin use or HbA1c between treatment groups at weeks 24 and 48. The frequency of hypoglycaemia events was reduced with temelimab (P = 0.0004) at week 24 and the level of anti-insulin antibodies was lower with temelimab (P < 0.01); the other autoantibodies did not differ between groups. CONCLUSIONS: Temelimab appeared safe in patients with T1D. Pharmacodynamics signals (hypoglycaemia and anti-insulin antibodies) under temelimab were observed. Markers of ß-cell functions were not modified by treatment. These results need to be further explored in younger patients with T1D with earlier disease onset.

Amount and Type of Dietary Fat, Postprandial Glycemia, and Insulin Requirements in Type 1 Diabetes: A Randomized Within-Subject Trial.

OBJECTIVE: The American Diabetes Association recommends individuals with type 1 diabetes (T1D) adjust insulin for dietary fat; however, optimal adjustments are not known. This study aimed to determine 1) the relationship between the amount and type of dietary fat and glycemia and 2) the optimal insulin adjustments for dietary fat. RESEARCH DESIGN AND METHODS: Adults with T1D using insulin pump therapy attended the research clinic on 9-12 occasions. On the first six visits, participants consumed meals containing 45 g carbohydrate with 0 g, 20 g, 40 g, or 60 g fat and either saturated, monounsaturated, or polyunsaturated fat. Insulin was dosed using individual insulin/carbohydrate ratio as a dual-wave 50/50% over 2 h. On subsequent visits, participants repeated the 20-60-g fat meals with the insulin dose estimated using a model predictive bolus, up to twice per meal, until glycemic control was achieved. RESULTS: With the same insulin dose, increasing the amount of fat resulted in a significant dose-dependent reduction in incremental area under the curve for glucose (iAUCglucose) in the early postprandial period (0-2 h; P = 0.008) and increase in iAUCglucose in the late postprandial period (2-5 h; P = 0.004). The type of fat made no significant difference to the 5-h iAUCglucose. To achieve glycemic control, on average participants required dual-wave insulin bolus: for 20 g fat, +6% insulin, 74/26% over 73 min; 40 g fat, +6% insulin, 63/37% over 75 min; and 60 g fat, +21% insulin, 49/51% over 105 min. CONCLUSIONS: This study provides clinical guidance for mealtime insulin dosing recommendations for dietary fat in T1D.

Sydney Diabetes centre's experience of the Australian Government's roll out of subsidised continuous glucose monitoring for children with type 1 diabetes mellitus.

AIM: To determine patient/carer expectations of continuous glucose monitoring (CGM) and short-term satisfaction, to assess the efficacy of CGM in improving: fear of hypoglycaemia and glycaemic control (HbA1c , ketosis, hypoglycaemia) and to determine time requirements of diabetes clinic staff in commencing and administering CGM. METHODS: We assessed CGM-naïve patients starting on CGM at a Sydney Diabetes Centre following the introduction of a nationwide government subsidy for CGM. A standardised questionnaire was administered collecting demographic and glycaemic information in addition to Likert scale assessment of expectations and satisfaction. Clinic staff reported time dedicated to CGM education, commencement and follow-up. RESULTS: A total of 55 patients or parents/carers completed baseline questionnaires, with 37 completing a 3-month follow-up questionnaire. There were high expectations of CGM prior to commencement and high satisfaction ratings on follow-up. CGM improved fear of hypoglycaemia, and total daily insulin dose increased after commencement of CGM. There was a trend towards lower HbA1c that was not statistically significant and no statistically significant reduction in ketosis or hypoglycaemia. Comments were mostly positive, with some concern raised regarding technical issues and a lack of subsidy after 21 years of age. Staff time requirements were substantial, with an estimated average of 7.7 h per patient per year. CONCLUSIONS: Patients and families have high expectations of CGM, and satisfaction levels are high in the short term. Total insulin delivery increased after CGM commencement. Time requirements by staff are substantial but are worthwhile if families' overall satisfaction levels are high.

The effects of estradiol on mood and behavior in human female adolescents: a systematic review.

UNLABELLED: Mood disorders and health risk behaviors increase in adolescence. Puberty is considered to contribute to these events. However, the precise impact of pubertal hormone changes to the emergence of mood disorders and risk behaviors is relatively unclear. It is important that inappropriate attribution is not made. Our aim was to determine what is known about the effect of endogenous estradiol on human adolescent girls' mood and behavior. The databases searched were MEDLINE, Embase, PsycINFO, Education Resources Information Center (ERIC), Pre-MEDLINE, Web of Science, and Scopus for all dates to October 2014. For inclusion, contemporaneous hormone and mood or behavioral assessment was required. Data were extracted following a template created by the authors. Fourteen studies met our inclusion criteria. There was some consistency in findings for mood and estradiol levels, with associations between estradiol and depression and emotional tone and risk taking. Results were less consistent for studies assessing other mood and behavioral outcomes. Most studies were cross-sectional in design; assay methodologies used in older studies may lack the precision to detect early pubertal hormone levels. CONCLUSION: Three longitudinal and several cross-sectional studies indicate potential associations between estradiol and certain mood or affective states, especially depression and mood variability though there are insufficient data to confirm that the rise in estradiol during puberty is causative. We believe that it is important for health professionals to take care when attributing adolescent psychopathology to puberty hormones, as the current data supporting these assertions are limited.

Testosterone and its effects on human male adolescent mood and behavior: a systematic review.

PURPOSE: During human puberty, there is an approximate 30-fold increase in testosterone production in boys. This increase is often linked to changes in mood and behavior in adolescence such as aggression, an increase in risk taking, and depression. The aim of this systematic review was to determine what evidence exists on the effects of endogenous testosterone on behavior and mood in males during adolescence. METHODS: The following databases were searched: MEDLINE, Pre-MEDLINE, Education Resources Information Centre, PsycINFO, EMBASE, Scopus, and Web of Science. Only human studies were included. The study is community based, and the participants were healthy male adolescents within the age range of 9-18 years. Studies were required to have a validated mood and/or behavior assessment contemporaneous with a timed testosterone measurement. RESULTS: A total of 27 studies met the inclusion criteria of which only one was a longitudinal study. The remaining 26 studies were cross sectional in their analysis. As a variety of measurement tools were used, no meta-analysis was possible. Most studies focused on aggression. The one longitudinal study looking at testosterone and aggression showed little relationship with concurrent changes in aggression. Most of the cross-sectional studies of adolescent males observed relationships between aggression and testosterone levels. With respect to other behaviors and moods and/or affect, no consistent relationships with testosterone were observed in cross-sectional studies. CONCLUSIONS: This systematic review concludes that there are insufficient longitudinal data of high methodological quality to currently confirm that changing testosterone levels during puberty are significantly associated with mood and behavior in adolescent males. To discount these findings is to risk apportioning blame inappropriately and missing other important diagnoses in adolescent males.

Individual patient education for people with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes is a common and costly chronic disease which is associated with significant premature mortality and morbidity. Although patient education is an integral component of diabetes care, there remain uncertainties regarding the effectiveness of different methods and modes of education. OBJECTIVES: To evaluate the effectiveness of individual patient education on metabolic control, diabetes knowledge and psychosocial outcomes. SEARCH STRATEGY: Multiple electronic bibliographic databases were searched, including The Cochrane Library, MEDLINE, Premedline, ERIC, Biosis, AMED, Psychinfo, EMBASE, CINAHL, APAIS-health, Australian Medical Index, Web of Science, dissertation abstracts and Biomed Central. SELECTION CRITERIA: Randomized controlled and controlled clinical trials which evaluated individual education for adults with type 2 diabetes. The intervention was individual face-to-face patient education while control individuals received usual care, routine treatment or group education. Only studies that assessed outcome measures at least six months from baseline were included. DATA COLLECTION AND ANALYSIS: Information was extracted by two reviewers who summarized both study characteristics and outcome statistics. A meta-analysis using a fixed-effect model was performed if there were adequate studies with a specified outcome of sufficient homogeneity. For outcomes where there were too few studies or the assessment measurements were not standardized or variable, the results were summarised qualitatively. MAIN RESULTS: Nine studies involving 1359 participants met the inclusion criteria. Six studies compared individual education to usual care and three compared individual education to group education (361 participants). There were no long-term studies and overall the quality of the studies was not high. In the six studies comparing individual face-to-face education to usual care, individual education did not significantly improve glycaemic control (weighted mean difference (WMD) in HbA1c -0.1% (95% confidence interval (CI) -0.3 to 0.1, P = 0.33) over a 12 to 18 month period. However, there did appear to be a significant benefit of individual education on glycaemic control in a subgroup analysis of three studies involving participants with a higher mean baseline HbA1c greater than 8% (WMD -0.3% (95% CI -0.5 to -0.1, P = 0.007). In the two studies comparing individual to group education, there was no significant difference in glycaemic control between individual or group education at 12 to 18 months with a WMD in HbA1c of 0.03% (95% CI -0.02 to 0.1, P = 0.22). There was no significant difference in the impact of individual versus usual care or group education on body mass index systolic or diastolic blood pressure. There were too few studies to perform a meta-analysis on the effect of individual education on dietary self management, diabetes knowledge, psychosocial outcomes and smoking habits. No data were available on the other main outcome measures of diabetes complications or health service utilization and cost analysis in these studies. AUTHORS' CONCLUSIONS: This systematic review suggests a benefit of individual education on glycaemic control when compared with usual care in a subgroup of those with a baseline HbA1c greater than 8%. However, overall there did not appear to be a significant difference between individual education and usual care. In the small number of studies comparing group and individual education, there was an equal impact on HbA1c at 12 to 18 months. Additional studies are needed to delineate these findings further.