Proteins and Peptides Studied In Silico and In Vivo for the Treatment of Diabetes Mellitus: A Systematic Review.

Bioinformatics has expedited the screening of new efficient therapeutic agents for diseases such as diabetes mellitus (DM). The objective of this systematic review (SR) was to understand naturally occurring proteins and peptides studied in silico and subsequently reevaluated in vivo for treating DM, guided by the question: which peptides or proteins have been studied in silico for the treatment of diabetes mellitus? The RS protocol was registered in the International Prospective Register of Systematic Reviews database. Articles meeting the eligibility criteria were selected from the PubMed, ScienceDirect, Scopus, Web of Science, Virtual Health Library (VHL), and EMBASE databases. Five studies that investigated peptides or proteins analyzed in silico and in vivo were selected. Risk of bias assessment was conducted using the adapted Strengthening the Reporting of Empirical Simulation Studies (STRESS) tool. A diverse range of assessed proteins and/or peptides that had a natural origin were investigated in silico and corresponding in vivo reevaluation demonstrated reductions in glycemia and/or insulin, morphological enhancements in pancreatic ß cells, and alterations in the gene expression of markers associated with DM. The in silico studies outlined offer crucial insights into therapeutic strategies for DM, along with promising leads for screening novel therapeutic agents in future trials.

Learning demands of diabetes self-management: a qualitative study with people who use insulin.

OBJECTIVE: to understand the experiences with diabetes mellitus management of people who use insulin, in order to identify possible factors that may influence adherence to self-care and thus define their learning demands for diabetes self-management. METHOD: this is a qualitative study carried out using individual semi-structured interviews online. The interviews were recorded, transcribed and evaluated using Atlas.ti® software by means of Thematic Content Analysis, using the Health Beliefs Model as a theoretical framework. RESULTS: 11 people living with diabetes and using insulin took part in the study. Four categories were identified: understanding diabetes, how to deal with diabetes, difficulties related to insulin use and emotional adaptation. CONCLUSION: the perception of the severity of the disease, its complications and the benefits of adhering to treatment positively influences adherence to self-care behaviors. Although the study participants have lived with diabetes for many years, they are not exempt from difficulties related to insulin use and disease management, reinforcing the importance of continuing health education. In this sense, the findings of this study guide important educational themes to be worked on by health professionals to promote autonomy in diabetes self-management. BACKGROUND: (1) Perceived severity of diabetes positively influences self-care. (2) Continued health education for people who use insulin is essential. (3) The importance of recognizing the benefits of insulin in adherence to treatment. (4) Emotional aspects in diabetes management should be considered in health education.

Mushrooms and Fungi and Their Biological Compounds with Antidiabetic Activity: A Review.

Mushrooms have been used by humans for centuries as food and medicine because they have been shown to affect certain diseases. Mushrooms for medicinal purposes have been consumed in the form of extracts and/or biomass of the mycelium or fruiting body. The beneficial health effects of mushrooms are due to their content of bioactive compounds (polysaccharides, proteins, ergosterol, lectins, etc.). On the other hand, diabetes is one of the metabolic diseases that affects the population worldwide, characterized by hyperglycemia that involves a defective metabolism of insulin, a hormone secreted by ß cells and that mainly stimulates glucose absorption by the cells. However, it also affects the metabolism of carbohydrates, fats and proteins; poor control of this disease leads to serious damage to eyesight, kidneys, bones, heart, skin, blood vessels, nerves, etc. It has been reported that the consumption of some mushrooms helps control and treat diabetes, since among other actions, they promote the secretion of insulin by the pancreas, help reduce blood glucose and have α-glucosidase inhibitory activity which improves glucose uptake by cells, which are effects that prescription medications have for patients with diabetes. In that sense, this manuscript shows a review of scientific studies that support the abilities of some mushrooms to be used in the control and/or treatment of diabetes.

Factors associated with poor adherence to medication in patients with diabetes and hypertension in Peru: findings from a pooled analysis of six years of population-based surveys.

OBJECTIVE: To evaluate the factors associated with poor medication adherence in patients with DM and HTN in Peru. STUDY DESIGN: A cross-sectional study. METHODS: We analyzed data from the Peruvian Demographic and Family Health Survey from 2014 to 2019. Adjusted prevalence ratios (aPR) and their respective 95% confidence intervals (CI) were estimated to determine the factors associated with poor medication adherence. RESULTS: We included 15,184 participants with a known diagnosis of DM and HTN. The frequency of poor medication adherence was 37.1%, with 36.7% among individuals with HTN and 29.2% among individuals with DM. Those belonging to age groups above 30 years (aPR: 0.77; 95% CI: 0.74-0.80, for the group ≥ 60 years) had a lower frequency of poor medication adherence. Meanwhile, being male (aPR: 1.03; 95% CI: 1.01-1.05), lacking health insurance (aPR: 1.08; 95% CI: 1.05-1.10), belonging to lower wealth quintiles (aPR: 1.12; 95% CI: 1.08-1.17, for the first quintile), and living in the mountain region (aPR: 1.09; 95% CI: 1.06-1.12) were associated with a higher frequency of poor medication adherence. These findings were consistent when stratifying by the type of disease. CONCLUSION: This study showed that poor medication adherence is common in patients with HTN and DM in Peru and is associated with sociodemographic factors, highlighting the importance of public health approaches to improve adherence.

Prescription drug coverage and effective coverage of three chronic conditions of high prevalence in Chile: Hypertension, diabetes and dyslipidemia.

BACKGROUND: Access to medicines is a serious problem globally and in Chile. Despite the creation of coverage policies, part of the population with chronic conditions of high prevalence, still does not have access to the medicines it requires and disease control continues to be low. The objective of the study was to estimate the medication use and effective coverage for diabetes, dyslipidemia and hypertension in Chile, analyzing them according to sociodemographic variables and social determinants of health. METHODS: Cross-sectional analytical study with information from the 2016-2017 National Health Survey (sample = 6,233 people aged 15 years or older, expanded = 14,518,969). Descriptive analyses of medication use and effective coverage for hypertension, diabetes and dyslipidemia were carried out, and multivariate logistic regression models were developed to analyze possible associations with variables of interest. RESULTS: 60% of people with hypertension or diabetes use medications and only 27.7% in dyslipidemia. While 54.2% of those with diabetes have their glycemia controlled, in hypertension and dyslipidemia the effective coverage drops to 33.3% and 6.6%, respectively. There are no differences in use by health system, but there are differences in the control of hypertension and diabetes, favoring beneficiaries of the private subsystem. Effective coverage of dyslipidemia and hypertension also increases in those using medications. The drugs coincide with the established protocols, although beneficiaries of the private sector report greater use of innovative drugs. CONCLUSION: A significant proportion of Chileans with hypertension, diabetes or dyslipidemia still do not use the required medications and do not control their conditions.

De-escalating treatment indications for patients who achieve metabolic goals.

INTRODUCTION: Robust evidence exists regarding initiation, intensification or modification of treatments. Recommendations to de-escalate therapy are lacking, specifically in diabetes. A successful treatment de-intensification reduces overtreatment, polypharmacy, and risk of adverse effects. OBJECTIVE: To encompass current recommendations for deprescribing common drugs and create a consensus among health professionals. METHODS: We reviewed four databases for deprescribing approaches published between 2010 and 2022. Articles were divided into different groups of drugs (for uric-acid, hypoglycemic, lipid-lowering, and psychotropic drugs). RESULTS: Hypoglycemic agents: strategies were limited to newer agents and insulin regimens for elderly individuals. Reducing insulin was associated with 1.1% reduction of A1c over time. SGLT2i and GLP-1RAs dose reduction depends on adverse events. Lipid-lowering agents: studies show that patients with very low cholesterol have fewer cardiovascular events without associated increased risk. Antihypertensive agents: Younger patients, lower systolic blood pressure, and few comorbidities are ideal characteristics for discontinuation. Uric acid therapy: we found no recommendation for dose de-escalation. Poor treatment adherence is associated with episodes of gout and deforming arthritis in the long term. CONCLUSION: Deprescribing hypoglycemic, statins, antihypertensives, and urate-lowering agents may be feasible in selected patients, but periodic surveillance is important. More evidence is necessary to support this decision entirely.

AMCP Market Insights Health Plan Best Practice: Implementing continuous glucose monitoring to improve patient outcomes in diabetes.

Diabetes is a complex chronic condition that affects the body's ability to produce or use insulin effectively, resulting in elevated blood glucose levels. It is associated with various complications and comorbidities, significantly impacting both individuals and the health care system. Effective management involves a combination of lifestyle adjustments, medication adherence, monitoring, education, and support. The expanding use of continuous glucose monitoring (CGM) has been transformative in diabetes care, providing valuable real-time data and insights for better management. To understand the opportunity for health plans to support improved patient outcomes with CGM, AMCP sponsored a multifaceted approach to identify best practices consisting of expert interviews, a national payer survey, an expert panel workshop with clinical experts and managed care stakeholders, and a national webcast to communicate the program findings. This article summarizes current evidence for CGM to support managed care and payer professionals in making collaborative, evidence-based decisions to optimize outcomes among patients with diabetes. In addition, this review also presents the findings of a national payer survey and describes expert-supported health plan best practices around coverage and access to CGM.

Predictors of Trypanosoma cruzi PCR positivity in patients with chronic Chagas disease.

BACKGROUND: A positive Trypanosoma cruzi polymerase chain reaction (PCR) is associated with a worse prognosis in patients with chronic Chagas disease (CD). OBJECTIVES: To study the association of clinical, electrocardiographic, and echocardiographic characteristics and biomarker blood levels with positive T. cruzi PCR in chronic CD. METHODS: This is a single-centre observational cross-sectional study. Positive T. cruzi PCR association with clinical, electrocardiographic, and echocardiographic characteristics, and biomarker blood levels were studied by logistic regression analysis. p values < 0.05 were considered significant. FINDINGS: Among 333 patients with chronic CD (56.4% men; 62 ± 10 years), T. cruzi PCR was positive in 41.1%. Stepwise multivariate logistic regression showed an independent association between positive T. cruzi PCR and diabetes mellitus {odds ratio (OR) 0.53 [95% confidence interval (CI) 0.30-0.93]; p = 0.03}, right bundle branch block [OR 1.78 (95% CI 1.09-2.89); p = 0.02], and history of trypanocidal treatment [OR 0.13 (95% CI 0.04-0.38); p = 0.0002]. Among patients with a history of trypanocidal treatment (n = 39), only four (10%) patients had a positive T. cruzi PCR. MAIN CONCLUSIONS: Among several studied parameters, only diabetes mellitus, right bundle branch block, and history of trypanocidal treatment showed an independent association with positive T. cruzi PCR. History of trypanocidal treatment was a strong protective factor against a positive T. cruzi PCR.

Increase in antibiotic resistance in diabetic foot infections among peruvian patients: a single-center cross-sectional study.

Background: Diabetic foot is one of the most significant complications in individuals with diabetes and is closely associated with lower limb amputation. The antibiotic susceptibility patterns of these bacterial isolates play a critical role in guiding effective treatment strategies We aimed to determine the most common bacterial agents causing diabetic foot infections in a tertiary-care hospital in Peru. Methods: Clinical and microbiological data were collected from 181 patients diagnosed with diabetic foot infections and positive microbiological culture results. All the samples were analyzed with the Vitek 2 compact system and the cut-off points were defined with the CLSI M100 guide. The data were segregated based on mono-microbial or poly-microbial cultures, bacterial types, and antibiotic susceptibility profiles. Results: A total of 32 bacterial species were identified, predominantly Gram-negative (63%). The most frequent bacterial agents isolated were Staphylococcus aureus (19.9%), Escherichia coli (12.2%), Pseudomonas aeruginosa (8.3%), and Proteus vulgaris (6.6%). These bacteria commonly exhibited resistance to Ampicillin, Ciprofloxacin, Levofloxacin, Trimethoprim-sulfamethoxazole, and Cefuroxime. E. coli showed the highest antibiotic resistance (19 antibiotics), while Gentamicin, Tobramycin, and Levofloxacin demonstrated the highest sensitivity against the most prevalent bacteria. Gram-negative bacteria also exhibited notable antibiotic-susceptibility to Meropenem, Piperacillin/tazobactam, and Amikacin. Regarding the presence of Extended-Spectrum Beta-Lactamase, 54 isolates tested positive, with 35 (64.8%) and 14 (42.4%) of these being S. aureus and E. coli. Conclusions: Bacterial agents causing diabetic foot infections pose a constant concern, particularly due to the increasing antibiotic resistance observed. This difficulty in treating the condition contributes to a higher risk of amputation and mortality. Further research on bacterial susceptibility is necessary to determine appropriate dosages for pharmacological treatment and to prevent the overuse of antibiotics.

Awareness of the diagnosis, treatment, and control of diabetes mellitus in Brazil.

OBJECTIVE: To estimate the proportions of awareness, treatment, and control of diabetes mellitus (DM) in the Brazilian adult population. METHOD: This is a cross-sectional study, with data from a representative sample of the Brazilian population, taken from the National Health Survey(PNS 2014/2015). Outcomes were defined based on glycated hemoglobin (HbA1c) measurements, self-reported DM diagnosis, and use of hypoglycemic agents or insulin. The proportion of DM awareness, treatment, and control was estimated according to sociodemographic characteristics, health conditions, and access to health services, and their respective 95% confidence intervals. RESULTS: DM prevalence in the Brazilian population was of 8.6% (95%CI: 7.8-9.3): 68.2% (95%CI: 63.9-72.3) were aware of their diagnosis, 92.2% (95%CI: 88.6-94.7) of those who were aware were undergoing drug treatments, and, of these, 35.8% (95%CI: 30.5-41.6) had controlled HbA1c levels. The proportions of DM awareness, control, and treatment were lower in men aged 18 to 39 years, individuals with low education, without health insurance, and beneficiaries of the Bolsa Família program. CONCLUSION: Approximately one in ten Brazilians has DM. A little more than half of this population is aware of their diagnosis, a condition measured by HbA1c dosage and clinical diagnosis. Among those who know, the vast majority are undergoing drug treatments. However, less than half of these have their HbA1c levels controlled. Worse scenarios were found in subgroups with high social vulnerability.

Impact of Guideline-Directed Statin Intervention for Primary Prevention in Patients With Diabetes.

OBJECTIVE: We examined guideline-directed statin intensity (GDSI) use and atherosclerotic cardiovascular disease (ASCVD) outcomes in patients with diabetes across a contemporary health care system. RESEARCH DESIGN AND METHODS: Patients without preexisting ASCVD were categorized by diabetes status and 10-year ASCVD risk (borderline [5-7.4%], intermediate [7.5-19.9%], high [≥20%]). Mean ±SD time to start of or change to GDSI was calculated. Incident ASCVD and all-cause mortality association, stratified by ASCVD risk, was calculated using Cox regression. RESULTS: Among 282,298 patients, 28,807 (10.2%) had diabetes and 253,491 (89.8%) did not. Only two-thirds of intermediate- and high-risk patients with diabetes were receiving GDSI therapy at 5-year follow-up. In fully adjusted models, patients with diabetes not taking a statin (vs. GDSI) had a significantly higher risk of stroke and mortality in the intermediate- and high-risk groups (hazard ratio for mortality 1.81 [95% CI 1.58-2.07] vs. 1.41 [1.26-1.57]; P for interaction < 0.01). CONCLUSIONS: Significant gaps remain in GDSI use for high-risk patients with diabetes, conferring an increased risk of ASCVD outcomes and all-cause mortality.

Evaluation of the acute toxicity and antidiabetic activity of Coutoubea spicata "nicolau" ethanolic extract and ethyl acetate fraction / Evaluación de la toxicidad aguda y la actividad antidiabética del extracto etanólico y la fracción de acetato de etilo de Coutoubea spicata "nicolau"

In order to understand antidiabetic potential and toxicity, this study aimed to evaluate the acute toxicity and antidiabetic activity of ethanolic extract and ethyl acetate fraction obtained from Coutoubea spicata "nicolau" shoots. Chemical constituents and acute toxicity were investigated. In alloxan-induced diabetic rats, extract and fraction were tested at dose of 100 mg/kg, p.o. Body weight gain, glucose, lipid profile and oxidative stress markers in serum and tissues were determined. In vitro antioxidant activity was performed. Swertiamarin, gentiopicrin, deoxyloganic acid, clovin and robinin, and their p-coumaric ester were identified. Extract and fraction were classified as safe (category 5). In diabetic rats, Coutoubea spicata reduced glycaemia, which was accompanied by body weight recovery gain and attenuation in oxidative stress markers. Fraction showed scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical (ABTS) radicals and reducing power higher than that of the extract. Extract and fraction of Coutoubea spicata didn't present significant toxicity and it can be investigated as a therapeutic alternative in diabetes.

Con el fin de conocer el potencial antidiabético y la toxicidad, este estudio tuvo como objetivo evaluar la toxicidad aguda y la actividad antidiabética del extracto etanólico y la fracción de acetato de etilo obtenidos de los brotes de Coutoubea spicata "Nicolau". Se investigaron los componentes químicos y la toxicidad aguda. En ratas diabéticas inducidas por alloxan, se probaron el extracto y la fracción en dosis de 100 mg/kg, p.o. Se determinó el aumento de peso corporal, la glucosa, el perfil lipídico y los marcadores de estrés oxidativo en suero y tejidos. Se realizó una actividad antioxidante in vitro. Se identificaron la suertiamarina, la gentiopicrina, el ácido desoxilogánico, la clovina y la robinina, así como su éster p-cumárico. El extracto y la fracción se clasificaron como seguros (categoría 5). En ratas diabéticas, Coutoubea spicata redujo la glicemia, lo que se acompañó de una recuperación del peso corporal y de la atenuación de los marcadores de estrés oxidativo. La fracción mostró una actividad de barrido contra los radicales 1,1-difenil-2-picrilhidrazilo (DPPH) y 2,2'-azino-bis (ácido 3-etilbenzotiazolina-6-sulfónico) y un poder reductor superior al del extracto. El extracto y la fracción de Coutoubea spicata no presentaron una toxicidad significativa y pueden ser investigados como alternativa terapéutica en la diabetes.

Update on current pharmacologic therapies for diabetic retinopathy.

INTRODUCTION: Diabetic retinopathy is a major cause of visual loss worldwide. The most important clinical findings include diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). AREAS COVERED: PubMed was used for our literature review. Articles from 1995 to 2023 were included. Pharmacologic treatment of diabetic retinopathy generally involves the use of intravitreal anti-vascular endothelial growth factor (VEGF) therapy for DME and PDR. Corticosteroids remain important second-line therapies for patients with DME. Most emerging therapies focus on newly identified inflammatory mediators and biochemical signaling pathways involved in disease pathogenesis. EXPERT OPINION: Emerging anti-VEGF modalities, integrin antagonists, and anti-inflammatory agents have the potential to improve outcomes with reduced treatment burdens.

Medicinal plants with antidiabetic activity used in the traditional medicine in Bolivia: a review / Plantas medicinales con actividad antidiabética utilizadas en la medicina tradicional de Bolivia: una compilación

The present study aimed to document the traditional use of medicinal plants used to treat Diabetes mellitus Type II in Bolivia. Based on the scientific literature were identified 35 medicinal plant species distributed in 21 botanical families, of which 52 % are native to Bolivia and 48 % are introduced. The botanical families with the highest representation of species were Asteraceae (7 species, 19%) and Fabaceae (17%). The most frequented growth forms were herbs (34%) and trees (29%). Leaves (30%) were the most frequently used plant parts, followed by roots (14%), and bark (9%), mostly prepared as an infusion (40%) and decoction (33%). From the available scientific studies, 25 medicinal species were verified for their antidiabetic properties with positive results, but it is necessary provide more biochemical and clinical analysis of medicinal plants to make better use of their potential.

El objetivo del presente estudio fue documentar el uso tradicional de plantas medicinales para el tratamiento de la Diabetes mellitus tipo II en Bolivia. Con base en la literatura científica se identificaron 35 especies medicinales, distribuidas en 21 familias botánicas, de las cuales el 52% son nativas de Bolivia y el 48% son introducidas. Las familias botánicas con mayor representación de especies fueron Asteraceae (7 especies, 19%) y Fabaceae (17%). Las formas de crecimiento más frecuentes fueron hierbas (34%) y árboles (29%). Las hojas (30%) fueron la parte de la planta más utilizada, seguidas de las raíces (14%) y la corteza (9%), preparadas especialmente como infusión (40%) y decocción (33%). Así mismo, con base en estudios científicos disponibles, se confirmó la actividad antidiabética de 25 especies medicinales. Sin embargo, es necesario aportar más análisis bioquímicos y clínicos de las plantas medicinales para aprovechar mejor su potencial.

Obesity, diabetes, and cancer: epidemiology, pathophysiology, and potential interventions.

The proportion of deaths attributable to cancer is rising, and malignant neoplasms have become the leading cause of death in high-income countries. Obesity and diabetes are now recognized as risk factors for several types of malignancies, especially endometrial, colorectal, and postmenopausal breast cancers. Mechanisms implicated include disturbances in lipid-derived hormone secretion, sex steroids biosynthesis, hyperinsulinemia, and chronic inflammation. Intentional weight loss is associated with a mitigation of risk for obesity-related cancers, a phenomenon observed specially with bariatric surgery. The impact of pharmacological interventions for obesity and diabetes is not uniform: while metformin seems to protect against cancer, other agents such as lorcaserin may increase the risk of malignancies. However, these interpretations must be carefully considered, since most data stem from bias-prone observational studies, and high-quality randomized controlled trials with appropriate sample size and duration are needed to achieve definite conclusions. In this review, we outline epidemiological and pathophysiological aspects of the relationship between obesity, diabetes, and malignancies. We also highlight pieces of evidence regarding treatment effects on cancer incidence in these populations.

Point-of-care testing de hemoglobina glicada para pacientes diabéticos / Point-of-care glycated hemoglobin testing for diabetic patients

INTRODUÇÃO: O diabetes mellitus (DM) é uma doença endócrina-metabólica de etiologia heterogênea, decorrente de deficiência na produção de insulina ou na sua ação, ou em ambos os mecanismos. Pode evoluir com complicações agudas (hipoglicemia, cetoacidose e síndrome hiperosmolar hiperglicêmica não cetótica) e crônicas - microvasculares (retinopatia, nefropatia, neuropatia) e macrovasculares (doença arterial coronariana, doença arterial periférica e doença cerebrovascular). O diagnóstico de DM deve ser estabelecido pela identificação de hiperglicemia. Para isto, podem ser usados a glicemia plasmática de jejum, o teste de tolerância oral à glicose (TOTG) e a hemoglobina glicada (HbA1c). A HbA1c oferece vantagens ao refletir níveis glicêmicos dos últimos três a quatro meses e sofrer menor variabilidade dia a dia, além de não estar relacionada ao estado de jejum para sua determinação, sendo uma medida indireta da glicemia. O tratamento do DM1 e 2 inclui medidas não farmacológicas e farmacológicas. POCT, point-of-care testing é a testagem conduzida próximo ao local de cuidado ao paciente, inclusive em consultórios e locais fora da área técnica de um laboratório, sendo um dispositivo para medir HbA1c considerado simples. PERGUNTA: Existe evidência científica quanto a utilidade clínica de point-of-care testing de Hba1c em pacientes com DM1 ou DM2 na atenção primária? Existe evidência científica quanto a validade clínica de pointof-care testing de Hba1c em pacientes com DM1 ou DM2 na atenção primária? EVIDÊNCIAS CLÍNICAS: Trinta estudos forneceram evidências sobre a utilidade e a validade clínica de point-ofcare testing de Hba1c em pacientes com DM1 ou DM2. Estudos que realizaram a comparação de mais de um POCT de HbA1c versus o teste laboratorial convencional, observaram uma diferença ampla no coeficiente de correlação, destacando os aparelhos DCA Vantage Analyzer e A1CNow+, sendo que em um dos estudos, os valores foram, respectivamente 0,95 e 0,70. Este resultado concorda com alguns achados mencionados em uma revisão sistemática, que mostrou importante heterogeneidade nos resultados dos estudos, além de alto risco de viés na seleção dos pacientes. O grau de satisfação com uso de POCT foi alto, com estudos mostrando que pacientes consideraram a utilização de POCT menos dolorosa do que a punção venosa realizada para os testes laboratoriais. Os estudos selecionados para avaliar os dois desfechos analisados (utilidade clínica e validade clínica), apresentaram uma qualidade moderada de evidência, considerando-se as recomendações GRADE. AVALIAÇÃO ECONÔMICA: o demandante apresentou uma análise de custo-efetividade, considerando-se o horizonte temporal de um ano, empregando-se um modelo de árvore de decisão simples, avaliando os desfechos utilidade clínica (controle glicêmico) e satisfação do paciente, com base em custos diretos. A razão de custo-efetividade incremental, foi de R$ 403,11 e de R$ 134,70 para os desfechos controle glicêmico e satisfação do paciente, respectivamente. Importante salientar que neste cenário, não foram imputados no modelo o custo direto com aquisição do aparelho de realização da HbA1c em "point of care". Os cálculos para RCEI com inclusão deste custo, foram incluídos pelos pareceristas, e foram respectivamente de R$ 778.181,11 e R$ 259.393,70, para o primeiro ano, sendo projetados valores finais em 10 anos com taxa de desconto de 5%/ano. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: O demandante apresentou uma AIO, considerando-se um horizonte temporal de cinco anos e um "market-share" final de 15% no cenário de serviços de Atenção Primária em Saúde, com uma população elegível superestimada (prevalência de DM em todo o Brasil - usuários do SUS) e sem inclusão do valor de aquisição do aparelho para realização da HbA1c em "point of care". O IO incremental, em tal cenário, variou de R$ 13.535.412,00 no primeiro ano a R$ 41.743.136,00 no quinto ano, sendo de R$ 137.757.277,00 nos cinco anos. Na presente análise crítica, os pareceristas projetaram um cenário com "market-share" atingindo 50% ao final de cinco anos, considerando-se uma população elegível ao número proporcional de unidades de APS, o qual apresentou IO incremental de R$ 749.811.611,95 no período. Outro cenário considerando o custo de aquisição do hemoglobinômetro foi apresentado, e o IO incremental foi de R$ 2.124.262.267,9, para um market-share de 50% e de R$ 899.262.267,91, para market-share de 15%. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foram detectadas sete tecnologias nas pesquisas realizadas nas bases de dados ClinicalTrials.gov e Cortellis™, sendo que cinco encontram-se registradas na ANVISA e uma na FDA. CONSIDERAÇÕES FINAIS: A realização de teste de HbA1c em "point of care" para monitoramento de pacientes com diabetes melito no cenário dos serviços de Atenção Primária à Saúde, por fornecer resultados imediatos em comparação aos métodos laboratoriais convencionais, pode trazer benefícios clínicos para os pacientes acometidos por esta doença crônica com ganhos no controle dos níveis glicêmicos e consequentemente melhorando o prognóstico da enfermidade, interferindo positivamente na sua história natural diminuindo as sequelas e consequências danosas como a neuropatia periférica, a retinopatia, as nefropatias, além das repercussões no sistema cardiovascular e cerebrovascular, entre outras. Entretanto, há que se considerar análises de custo-efetividade com modelos apropriados para doenças crônicas como simulação de eventos discretos e Markov, capazes de capturar estados de transição clínica próprios da evolução destes pacientes. Seria adequado também considerar análise de impacto orçamentário baseado em cenários de market-share com potencial de efetivamente modificar o padrão epidemiológico da doença e que estejam em consonância com a distribuição quantitativa e geográfica dos serviços de Atenção Primária em Saúde. O uso de população elegível não representativa quantitativamente ao cenário apresentado, bem como a desconsideração de custo de aquisição de hemoglobinômetro para teste em POCT, trouxe incertezas nos resultados econômicos. RECOMENDAÇÃO PRELIMINAR DA CONITEC: O Plenário da CONITEC, em sua 114ª Reunião Ordinária, realizada no dia 09 de novembro de 2022, deliberou que a matéria fosse disponibilizada em Consulta Pública com recomendação preliminar desfavorável à incorporação do Point-of-care testing de hemoglobina glicada para pacientes diabéticos com indicação de uso no SUS, sendo considerado de elevado custo e impacto orçamentário. CONSULTA PÚBLICA: Foram recebidas 75 contribuições, sendo nove pelo Formulário para Contribuições Técnicocientíficas e 66 pelo Formulário para Contribuições sobre Experiência e Opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. Foram consideradas apenas as contribuições encaminhadas no período estipulado e por meio do site da CONITEC, em formulário próprio. A empresa Siemens Healthineers enviou documento propondo alterações quanto à população-alvo, com foco em pacientes com DM I ou II com complicações micro ou macrovasculares e HbA1c maior igual a 6,5%, destacando que o modelo comercial é baseado no comodato do equipamento e, nos valores dos custos do POCT estão inclusos o teste em si, o treinamento com o equipamento e a manutenção do equipamento, assim não há outros custos extras para o SUS. A empresa apresentou novos cálculos de RCEI para os desfechos "controle glicêmico" e "satisfação do cliente", respectivamente de R$ 803,33 e R$ 267,78. RECOMENDAÇÃO FINAL DA CONITEC: o Comitê de Produtos e Procedimentos, na 119ª Reunião Ordinária da Conitec, no dia 1º de junho de 2023, deliberou, por unanimidade, recomendar a não incorporação do pointof-care testing de hemoglobina glicada para pacientes diabéticos no SUS. Os membros do Comitê de Produtos e Procedimentos consideraram que a implementação do point-of-care de hemoglobina glicada estaria relacionada a barreiras importantes devido à grande escala prevista para atendimento e às incertezas de que a utilização desse produto no contexto do SUS estaria relacionada à melhoria em desfechos clínicos importantes para a doença. Por fim, foi assinado o Registro de Deliberação nº 831/2023. DECISÃO: Não incorporar, no âmbito do Sistema Único de Saúde - SUS, o point-of-care testing de hemoglobina glicada para pacientes diabéticos, publicada no Diário Oficial da União nº 177, seção 1, página 190, em 15 de setembro de 2023.

Insulin-loaded nanoparticles based on acetylated cashew gum/chitosan complexes for oral administration and diabetes treatment.

Insulin is one of the most important drugs in the clinical treatment of diabetes. There is growing interest in oral insulin administration as it mimics the physiological pathway and potentially reduces side effects associated with subcutaneous injection. In this study, a nanoparticulate system was developed using acetylated cashew gum (ACG) and chitosan by the polyelectrolyte complexation method, for oral administration of insulin. The nanoparticles were characterized by size, zeta potential and encapsulation efficiency (EE%). And they had a particle size of 460 ± 11.0 nm, PDI of 0.2 ± 0.021, zeta potential of 30.6 ± 0.48 mV, and an EE% of 52.5 %. Cytotoxicity assays were performed for HT-29 cell lines. It was observed that ACG and nanoparticles did not have a significant effect on cell viability, verifying their biocompatibility. Hypoglycemic effects of the formulation were analyzed in vivo, noting that the nanoparticles reduced blood glucose by 51.0 % of baseline levels after 12 h, not inducing signs of toxicity or death. Biochemical and hematological profiles were not clinically modified. Histological study indicated no signs of toxicity. Results showed that the nanostructured system presented itself as a potential vehicle for oral insulin release.