Association of Baseline Factors With Glycemic Outcomes in GRADE: A Comparative Effectiveness Randomized Clinical Trial.

OBJECTIVE: To describe the individual and joint associations of baseline factors with glycemia, and also with differential effectiveness of medications added to metformin. RESEARCH DESIGN AND METHODS: Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) participants (with type 2 diabetes diagnosed for <10 years, on metformin, and with HbA1c 6.8-8.5%; N = 5,047) were randomly assigned to a basal insulin (glargine), sulfonylurea (glimepiride), glucagon-like peptide 1 agonist (liraglutide), or dipeptidyl peptidase 4 inhibitor (sitagliptin). The glycemic outcome was HbA1c ≥7.0%, subsequently confirmed. Univariate and multivariate regression and classification and regression tree (CART) analyses were used to assess the association of baseline factors with the glycemic outcome at years 1 and 4. RESULTS: In univariate analyses at baseline, younger age (<58 years), Hispanic ethnicity, higher HbA1c, fasting glucose, and triglyceride levels, lower insulin secretion, and relatively greater insulin resistance were associated with the glycemic outcome at years 1 and/or 4. No factors were associated with differential effectiveness of the medications by year 4. In multivariate analyses, treatment group, younger age, and higher baseline HbA1c and fasting glucose were jointly associated with the glycemic outcome by year 4. The superiority of glargine and liraglutide at year 4 persisted after multiple baseline factors were controlled for. CART analyses indicated that failure to maintain HbA1c <7% by year 4 was more likely for younger participants and those with baseline HbA1c ≥7.4%. CONCLUSIONS: Several baseline factors were associated with the glycemic outcome but not with differential effectiveness of the four medications. Failure to maintain HbA1c <7% was largely driven by younger age and higher HbA1c at baseline. Factors that predict earlier glycemic deterioration could help in targeting patients for more aggressive management.

The Use of Rescue Insulin in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

OBJECTIVE: To describe rescue insulin use and associated factors in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). RESEARCH DESIGN AND METHODS: GRADE participants (type 2 diabetes duration <10 years, baseline A1C 6.8%-8.5% on metformin monotherapy, N = 5,047) were randomly assigned to insulin glargine U-100, glimepiride, liraglutide, or sitagliptin and followed quarterly for a mean of 5 years. Rescue insulin (glargine or aspart) was to be started within 6 weeks of A1C >7.5%, confirmed. Reasons for delaying rescue insulin were reported by staff-completed survey. RESULTS: Nearly one-half of GRADE participants (N = 2,387 [47.3%]) met the threshold for rescue insulin. Among participants assigned to glimepiride, liraglutide, or sitagliptin, rescue glargine was added by 69% (39% within 6 weeks). Rescue aspart was added by 44% of glargine-assigned participants (19% within 6 weeks) and by 30% of non-glargine-assigned participants (14% within 6 weeks). Higher A1C values were associated with adding rescue insulin. Intention to change health behaviors (diet/lifestyle, adherence to current treatment) and not wanting to take insulin were among the most common reasons reported for not adding rescue insulin within 6 weeks. CONCLUSIONS: Proportionately, rescue glargine, when required, was more often used than rescue aspart, and higher A1C values were associated with greater rescue insulin use. Wanting to use noninsulin strategies to improve glycemia was commonly reported, although multiple factors likely contributed to not using rescue insulin. These findings highlight the persistent challenge of intensifying type 2 diabetes treatment with insulin, even in a clinical trial.

BMI, insulin sensitivity, and cognition in early type 2 diabetes: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study.

OBJECTIVE: This study explored the association of BMI and insulin sensitivity with cognitive performance in type 2 diabetes. METHODS: A cross-sectional analysis of data from the baseline assessment of the Glycemia Reduction Approaches in Diabetes: a Comparative Effectiveness Study (GRADE) was conducted. BMI was used as a surrogate of adiposity and the Matsuda index as the measure of insulin sensitivity. Cognitive tests included the Spanish English Verbal Learning Test, the Digit Symbol Substitution Test, and the letter and animal fluency tests. RESULTS: Cognitive assessments were completed by 5018 (99.4%) of 5047 participants aged 56.7 ± 10.0 years, of whom 36.4% were female. Higher BMI and lower insulin sensitivity were related to better performance on memory and verbal fluency tests. In models including BMI and insulin sensitivity simultaneously, only higher BMI was related to better cognitive performance. CONCLUSIONS: In this study, higher BMI and lower insulin sensitivity in type 2 diabetes were cross-sectionally associated with better cognitive performance. However, only higher BMI was related to cognitive performance when both BMI and insulin sensitivity were considered simultaneously. The causality and mechanisms for this association need to be determined in future studies.

Evaluating the effect of a community score card among pregnant and breastfeeding women living with HIV in two districts in Malawi.

Malawi faces challenges with retaining women in prevention of mother-to-child HIV transmission (PMTCT) services. We evaluated Cooperative for Assistance and Relief Everywhere, Inc. (CARE's) community score card (CSC) in 11 purposively selected health facilities, assessing the effect on: (1) retention in PMTCT services, (2) uptake of early infant diagnosis (EID), (3) collective efficacy among clients, and (4) self-efficacy among health care workers (HCWs) in delivering quality services. The CSC is a participatory community approach. In this study, HCWs and PMTCT clients identified issues impacting PMTCT service quality and uptake and implemented actions for improvement. A mixed-methods, pre- and post-intervention design was used to evaluate the intervention. We abstracted routine clinical data on retention in PMTCT services for HIV-positive clients attending their first antenatal care visit and EID uptake for their infants for 8-month periods before and after implementation. To assess collective efficacy and self-efficacy, we administered questionnaires and conducted focus group discussions (FGDs) pre- and post-intervention with PMTCT clients recruited from CSC participants, and HCWs providing HIV care from facilities. Retention of HIV-positive women in PMTCT services at three and six months and EID uptake was not significantly different pre- and post-implementation. For the clients, the collective efficacy scale average improved significantly post-intervention, (p = 0.003). HCW self-efficacy scale average did not improve. Results from the FGDs highlighted a strengthened relationship between HCWs and PMTCT clients, with clients reporting increased satisfaction with services. However, the data indicated continued challenges with stigma and fear of disclosure. While CSC may foster mutual trust and respect between HCWs and PMTCT clients, we did not find it improved PMTCT retention or EID uptake within the short duration of the study period. More research is needed on ways to improve service quality and decrease stigmatized behaviors, such as HIV testing and treatment services, as well as the longer-term impacts of interventions like the CSC on clinical outcomes.

Willingness to use HIV self-test kits and willingness to pay among urban antenatal clients in Cote d'Ivoire and Tanzania: a cross-sectional study.

OBJECTIVES: To generate evidence on willingness to use HIV self-test kits and willingness to pay among antenatal care clients in public and private facilities in Cote d'Ivoire and Tanzania. METHODS: Cross-sectional survey data were collected from 414 clients recruited from 35 high-volume facilities in Cote d'Ivoire and from 385 clients in 33 high-volume facilities in Tanzania. Surveys covered willingness to use HIV self-test kits, prices clients were willing to pay, advantages and disadvantages and views on specific qualities of HIV self-tests. Market data on availability of proxy self-testing products (e.g. pregnancy and malaria tests) and attitudes of pharmacists towards HIV self-test kits were collected from 51 pharmacies in Cote d'Ivoire and 59 in Tanzania. RESULTS: Willingness to use HIV self-test kits was 65% in Cote d'Ivoire and 69% in Tanzania. Median ideal prices women would pay ranged from USD 1.77 in Cote d'Ivoire to USD 0.87 in Tanzania. Proxy self-test kits were available in pharmacies, and interest was high in stocking HIV self-test kits. CONCLUSIONS: Implications for national HIV self-test policy and planning include keeping prices low, providing psychological and HIV counselling, and ensuring linkage to HIV care and treatment services. Private pharmacies will play a key role in providing access to HIV self-test kits.

OBJECTIFS: Générer des données sur la volonté d'utiliser des kits d'auto-dépistage du VIH et la volonté de payer chez les clients des soins prénatals dans les établissements publics et privés en Côte d'Ivoire et en Tanzanie. MÉTHODES: Les données de l'enquête transversale ont été recueillies auprès de 414 patientes enrôlées dans 35 établissements de santé à volume élevé en Côte d'Ivoire et de 385 patientes dans 33 établissements de santé à volume élevé en Tanzanie. Les enquêtes ont porté sur la volonté d'utiliser des kits d'auto-dépistage du VIH, les prix que les clients étaient prêts à payer, les avantages et les inconvénients et les opinions sur les qualités spécifiques des auto-tests du VIH. Les données du marché sur la disponibilité des proxyse des produits d'auto-test (par exemple, les tests de grossesse et du paludisme) et les attitudes des pharmaciens envers les kits d'auto-test du VIH ont été collectées dans 51 pharmacies en Côte d'Ivoire et 59 en Tanzanie. RÉSULTATS: La volonté d'utiliser des kits d'auto-test VIH était de 65% en Côte d'Ivoire et de 69% en Tanzanie. Le prix médian idéal que les femmes paieraient allait de 1,77 USD en Côte d'Ivoire à 0,87 USD en Tanzanie. Des proxys de kits d'auto-test étaient disponibles dans les pharmacies et l'intérêt pour le stockage des kits d'auto-test du VIH était élevé. CONCLUSIONS: Les implications pour la politique et la planification nationales d'auto-test du VIH incluent le maintien de prix bas, la fourniture de conseils psychologiques et sur le VIH, et la garantie d'un lien avec les services de soins et de traitement du VIH. Les pharmacies privées joueront un rôle clé en donnant accès aux kits d'autotest du VIH.