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Background To estimate the incremental cost-effectiveness ratio (ICER) of the use of continuous subcutaneous insulin infusion (CSII) therapy versus multiple daily injections (MDI) therapy in adult patients with type 1 diabetes (T1D) at the Mexican Institute of Social Security (IMSS). Methods An analysis was developed using the internationally validated Core Diabetes Model (CDM) with which the incidence and progression of acute and chronic complications and the mortality of T1D was simulated throughout life. The baseline characteristics of the simulated cohorts were obtained from Mexican T1D adult patients aged ≥ 18 years that received care at two national IMSS medical centres in 2016. In the base case, the costs of the complications and treatment of the disease with both therapies were estimated in Mexican currency from the perspective of the institution, using Diagnosis Related Groups for outpatient and inpatient care. Utilities were taken from the international bibliography. In a secondary analysis, indirect costs were included using a human capital approach. The model used a lifetime time horizon, and a discount rate of 5% was applied for health outcomes and costs. A one-way sensitivity analysis was conducted on key variables and patient sub-groups; uncertainty was evaluated using a Cost-Effectiveness Acceptability Curve. Results The average age of the cohort was 32 years, with diabetes duration of 19 years, an average HbA1c of 9.2%; 29% were men. A gain of 0.614 Quality Adjusted Life Years (QALYs) was estimated with the use of CSII therapy. The estimated ICER was MXN$478,020 per QALY in the base case, and MXN$369,593 when indirect costs were considered. The sensitivity analysis showed that, in adult patients with HbA1c > 9.0%, the ICER was MXN$262,237. Conclusions This is the first economic evaluation study that compares CSII therapy versus MDI therapy for T1D adult patients in Mexico. The insulin pump therapy can be considered cost-effective in the context of the IMSS when considering a threshold of three GDPs per capita with 43.9% probability. Results improve substantially when patients have an HbA1c above 9%.

Debate exists as to whether the higher hemoglobin A1c (HbA1c) levels observed in black persons than in white persons are due to worse glycemic control or racial differences in the glycation of hemoglobin.To determine whether a racial difference exists in the relationship of mean glucose and HbA1c.Prospective, 12-week observational study.10 diabetes centers in the United States.104 black persons and 104 white persons aged 8 years or older who had had type 1 diabetes for at least 2 years and had an HbA1c level of 6.0% to 12.0%.Mean glucose concentration, measured by using continuous glucose monitoring and compared by race with HbA1c, glycated albumin, and fructosamine values.The mean HbA1c level was 9.1% in black persons and 8.3% in white persons. For a given HbA1c level, the mean glucose concentration was significantly lower in black persons than in white persons (P = 0.013), which was reflected in mean HbA1c values in black persons being 0.4 percentage points (95% CI, 0.2 to 0.6 percentage points) higher than those in white persons for a given mean glucose concentration. In contrast, no significant racial differences were found in the relationship of glycated albumin and fructosamine levels with the mean glucose concentration (P 0.20 for both comparisons).There were too few participants with HbA1c levels less than 6.5% to generalize the results to such individuals.On average, HbA1c levels overestimate the mean glucose concentration in black persons compared with white persons, possibly owing to racial differences in the glycation of hemoglobin. However, because race only partially explains the observed HbA1c differences between black persons and white persons, future research should focus on identifying and modifying barriers impeding improved glycemic control in black persons with diabetes.Helmsley Charitable Trust.

Obesity is associated with an increased risk of acute lymphoblastic leukemia (ALL) relapse. Using mouse and cell co-culture models, we investigated whether adipose tissue attracts ALL to a protective microenvironment. Syngeneically implanted ALL cells migrated into adipose tissue within ten days. In vitro, murine ALL cells migrated towards adipose tissue explants and 3T3-L1 adipocytes. Human and mouse ALL cells migrated toward adipocyte conditioned media, which was mediated by SDF-1α. In addition, adipose tissue explants protected ALL cells against daunorubicin and vincristine. Our findings suggest that ALL migration into adipose tissue could contribute to drug resistance and potentially relapse.

To examine the current extent of the obesity problem in 2 large pediatric clinical registries in the US and Europe and to examine the hypotheses that increased body mass index (BMI) z-scores (BMIz) are associated with greater hemoglobin A1c (HbA1c) and increased frequency of severe hypoglycemia in youth with type 1 diabetes (T1D).International (World Health Organization) and national (Centers for Disease Control and Prevention/German Health Interview and Examination Survey for Children and Adolescents) BMI references were used to calculate BMIz in participants (age 2-18 years and ≥ 1 year duration of T1D) enrolled in the T1D Exchange (n = 11,435) and the Diabetes Prospective Follow-up (n = 21,501). Associations between BMIz and HbA1c and severe hypoglycemia were assessed.Participants in both registries had median BMI values that were greater than international and their respective national reference values. BMIz was significantly greater in the T1D Exchange vs the Diabetes Prospective Follow-up (P.001). After stratification by age-group, no differences in BMI between registries existed for children 2-5 years, but differences were confirmed for 6- to 9-, 10- to 13-, and 14- to 17-year age groups (all P.001). Greater BMIz were significantly related to greater HbA1c levels and more frequent occurrence of severe hypoglycemia across the registries, although these associations may not be clinically relevant.Excessive weight is a common problem in children with T1D in Germany and Austria and, especially, in the US. Our data suggest that obesity contributes to the challenges in achieving optimal glycemic control in children and adolescents with T1D.

Vitamin D deficiency has been linked with increased cancer risk, and vitamin D has been shown to be cytotoxic to some cancer cells in vitro. In the present study we evaluated whether vitamin D would have antiproliferative or cytotoxic effects on human pre-B acute lymphoblastic leukemia cells. Contrary to our hypotheses, calcitriol, the active form of vitamin D, had no effect on leukemia cell proliferation. Calcitriol actually had a modest effect to impair dexamethasone cytotoxicity and induction of apoptosis. Further studies are needed to evaluate the effects of vitamin D on leukemia cells in vivo.

Vitamin D deficiency has been associated with increased incidence and mortality in several types of cancer. Vitamin D has been shown to be cytotoxic to cancer cells in vitro, and may act synergistically with chemotherapy to kill cancer cells. Although vitamin D deficiency is common in children with cancer, the clinical implications of this remain unclear. Since acute lymphoblastic leukemia (ALL) is the most common type of cancer in children and relapsed leukemia remains a major problem, the present study was designed to test our hypothesis that active Vitamin D (Calcitriol) would induce apoptosis in ALL cells and potentiate the effect of chemotherapy on ALL cells. We cultured several human ALL cell lines and primary human ALL cells with and without Calcitriol, and quantified survival using trypan blue exclusion. Contrary to our hypothesis, Calcitriol did not negatively affect the viability or impair proliferation in the human ALL cell lines RS4; 11, SD1, BV173, or RCH-ACV, or in primary human ALL cells US7 or TXL 2. We then tested whether Calcitriol would synergize with dexamethasone, a glucocorticoid used almost universally in the treatment of childhood ALL. Again, contrary to our hypothesis, we found that rather than augment dexamethasone-induced cytotoxicity, supraphysiological doses of Calcitriol protected RS4;11 cells from the cytotoxic effect of 72 hour exposure to 100 nM dexamethasone (dexamethasone alone: 10±5% of initially plated cells viable; dexamethasone plus 300 nM Calcitriol: 27±14% of initially plated cells viable, n=4, p=0.04). More physiological doses of Calcitriol (10nM) showed similar protection (12.5±5% vs 31.5±19% of initially plated cells were viable at 72 hrs, n=4, p=0.05). Preliminary flow cytometry using Annexin/7AAD suggests that Calcitriol decreases dexamethasone-induced apoptosis in RS4;11 cells (dexamethasone alone: 94% of cells in apoptosis; dexamethasone plus 100 nM Calcitriol: 75% of cells in apoptosis, n=1) In summary, the active form of vitamin D appears to protect ALL cells from dexamethasone. This finding could be important, since glucocorticoid sensitivity of ALL cells is highly predictive of outcome and likelihood of relapse. Our findings could have major health implications given the high prevalence of Vitamin D deficiency in children and adolescents worldwide. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4684. doi:10.1158/1538-7445.AM2011-4684