HighlightsPlacebo controls may be acceptable even when an efficacious vaccine exists, in the following four possible situations:When developing a locally affordable vaccine.When evaluating the local safety and efficacy of an existing vaccine.When testing a new vaccine when an existing vaccine is not considered appropriate locally.When determining the local burden of disease.

Background Recently, the absence of metabolic effects from nonnutritive sweeteners has been questioned. Objective The aim of this study was to evaluate the effects of sucralose consumption on glucose metabolism variables. Design We performed a randomized controlled trial involving healthy subjects without comorbidities and with a low habitual consumption of nonnutritive sweeteners (n = 33/group). Methods The intervention consisted of sucralose consumption as 15% of Acceptable Daily Intake every day for 14 d using commercial sachets. The control group followed the same procedures without any intervention. The glucose metabolism variables (insulin sensitivity, acute insulin response to glucose, disposition index, and glucose effectiveness) were evaluated by using a 3-h modified intravenous-glucose-tolerance test before and after the intervention period. Results Individuals assigned to sucralose consumption showed a significant decrease in insulin sensitivity with a median (IQR) percentage change of −17.7% (−29.3% to −1.0%) in comparison to −2.8% (−30.7% to 40.6%) in the control group (P= 0.04). An increased acute insulin response to glucose from 577 mU · L-1· min (350–1040 mU · L-1· min) to 671 mU · L-1· min (376–1010 mU · L-1· min) (P = 0.04) was observed in the sucralose group for participants with adequate adherence. Conclusions Sucralose may have effects on glucose metabolism, and our study complements findings previously reported in other trials. Further studies are needed to confirm the decrease in insulin sensitivity and to explore the mechanisms for these metabolic alterations. This trial was registered at www.clinicaltrials.gov as NCT02589002.

OBJECTIVE -To compare the carotid artery intima-media thickness in Hispanic pediatric type 1 diabetic patients against that in healthy control subjects matched for age, sex, height, and BMI.RESEARCH DESIGN AND METHODS -The evaluation consisted of anthropometric measurements, biochemical parameters, and a carotid Doppler and real-time ultrasound, in which carotid artery intima-media thickness (cIMT), peak systolic velocity, and end diastolic velocity were measured using standardized procedures.RESULTS -A total of 52 diabetic patients and 47 control subjects were included. No significant differences existed in the characteristics between case and control subjects (mean age 11.8 Ϯ 3.1 vs. 11.8 Ϯ 2.8 years, weight 42.2 Ϯ 15.3 vs. 44.2 Ϯ 14.4 kg, height 1.45 Ϯ 0.15 vs. 1.47 Ϯ 0.15 m, BMI 19.3 Ϯ 3.2 vs. 19.9 Ϯ 4.4 kg/m 2 , systolic blood pressure 99.1 Ϯ 9.9 vs. 99.6 Ϯ 9 mmHg, and diastolic blood pressure 63 Ϯ 6.4 vs. 62.0 Ϯ 5.7 mmHg, respectively). The mean duration of diabetes was 4.8 Ϯ 3.2 years (range 6 -144 months), and the mean A1C was 8.6 Ϯ 1.6%. A significantly higher cIMT was found in the patients with type 1 diabetes (0.463 Ϯ 0.04 vs. 0.441 Ϯ 0.04 mm; P ϭ 0.001). In contrast, both peak systolic velocity (107.1 Ϯ 22.8 vs. 119.3 Ϯ 19.2, P Ͻ 0.005) and end diastolic velocity (28.4 Ϯ 6.0 vs. 33.0 Ϯ 7.0, P Ͻ 0.001) were higher in the control subjects.CONCLUSIONS -Type 1 diabetes is associated with higher cIMT and decreased flow velocities in a Hispanic pediatric population. Diabetes Care 30:2599-2602, 2007A therosclerosis is a long-term process that begins early in life. During childhood, potentially reversible lesions have been shown in autopsy studies and in animal models; lesions progress during the first decade of life and become symptomatic usually after the fourth decade of life (1). Long-term follow-up studies have proven the importance of several cardiovascular risk factors during childhood. Their presence increased the likelihood for having cardiovascular complications in adult life (2). The association between type 1 diabetes and coronary heart disease (CHD) has become undisputed during recent years (3,4). It has been demonstrated that there is a dramatic increase in the morbidity and mortality risk caused by atherosclerotic cardiovascular disease in young adults with type 1 diabetes compared with the nondiabetic population (5,6). Carotid artery intima-media thickness (cIMT) is a prognostic factor for having cardiovascular disease in adults with type 1 diabetes.Recommendations for primary CHD prevention applicable to patients with type 1 and 2 diabetes were published recently (7). There is a growing interest to prevent the cardiovascular disease risk factors early in the course of the disease, even at pediatric stages (8). It is necessary to identify children with type 1 diabetes with the highest risk for CHD using objective and noninvasive studies; if clinically useful information is obtained from its use, it may help to establish additional measures for prevention.Advances in imaging techniques identif...