Glycemic status and health-related quality of life (HRQOL) in populations at risk of diabetes in two Latin American cities.

PURPOSE: To estimate the health-related quality of life (HRQOL) according to glycemic status, and its relationship with sociodemographic and clinical factors in a population at risk of developing type 2 diabetes (T2D). METHODS: Cross-sectional study, using cluster sampling. Data were collected from 1135 participants over 30 years of age, at risk of developing T2D from the PREDICOL project. Participants' glycemic status was defined using an oral glucose tolerance test (OGTT). Participants were divided into normoglycemic subjects (NGT), prediabetes and diabetics do not know they have diabetes (UT2D). HRQOL was assessed using the EQ-5D-3L questionnaire of the EuroQol group. Logistic regression and Tobit models were used to examine factors associated with EQ-5D scores for each glycemic group. RESULTS: The mean age of participants was 55.6 ± 12.1 years, 76.4% were female, and one in four participants had prediabetes or unknown diabetes. Participants reported problems most frequently on the dimensions of Pain/Discomfort and Anxiety/Depression in the different glycemic groups. The mean EQ-5D score in NGT was 0.80 (95% CI 0.79-0.81), in prediabetes, 0.81 (95% CI 0.79-0.83), and in participants with UT2D of 0.79 (95% CI 0.76-0.82), respectively. Female sex, older age, city of residence, lower education, receiving treatment for hypertension, and marital status were significantly associated with lower levels of HRQOL in the Tobit regression analysis. CONCLUSIONS: HRQOL of NGT, prediabetes, and UT2D participants was statistically similar. However, factors such as gender, age. and place of residence were found to be significant predictors of HRQOL for each glycemic group.

Screening, prevalence, treatment and control of kidney disease in patients with type 1 and type 2 diabetes in low-to-middle-income countries (2005-2017): the International Diabetes Management Practices Study (IDMPS).

AIMS/HYPOTHESIS: Diabetes is the leading cause of kidney disease worldwide. There is limited information on screening, treatment and control of kidney disease in patients with diabetes in low-to-middle-income countries (LMICs). METHODS: The International Diabetes Management Practices Study is an ongoing, non-interventional study of clinical profiles and practices among patients receiving outpatient care mainly by internal medicine physicians and endocrinologists in LMICs. We examined screening, prevalence, treatment and control of kidney disease across seven waves (W) of data collection between 2005 and 2017. RESULTS: Among 15,079 patients with type 1 and 66,088 patients with type 2 diabetes, screening for kidney disease increased between W2 and W3 followed by a plateau (type 1 diabetes: W2, 73.7%; W3, 84.1%; W7, 83.4%; type 2 diabetes: W2, 65.1%; W3, 82.6%; W7, 86.2%). There were also decreasing proportions of patients with microalbuminuria (type 1 diabetes: W1, 27.1%; W3, 14.7%; W7, 13.8%; type 2 diabetes: W1, 24.5%; W3, 12.6%; W7, 11.9%) and proteinuria (type 1 diabetes: W1, 14.2%; W3, 8.7%; W7, 8.2%; type 2 diabetes: W1, 15.6%; W3, 9.3%; W7, 7.6%). Fewer patients were reported as receiving dialysis for both type 1 diabetes (W2, 1.4%; W7, 0.3%) and type 2 diabetes (W2, 0.9%; W7, 0.2%) over time. While there was no change in mean HbA1c or prevalence of diagnosed hypertension (type 1 diabetes: W1, 22.7%; W7, 19.9%; type 2 diabetes: W1, 60.9%; W7, 66.2%), the use of statins had increased among patients diagnosed with dyslipidaemia (type 1 diabetes: W1, 77.7%; W7, 90.7%; type 2 diabetes: W1, 78.6%; W7, 94.7%). Angiotensin II receptor blockers (type 1 diabetes: W1, 18.0%; W7, 30.6%; type 2 diabetes: W1, 24.2%; W7, 43.6%) were increasingly used over ACE inhibitors after W1 (type 1 diabetes: W1, 65.0%; W7, 55.9%; type 2 diabetes: W1, 55.7%, W7, 41.1%) among patients diagnosed with hypertension. CONCLUSIONS/INTERPRETATION: In LMICs, real-world data suggest improvement in screening and treatment for kidney disease in patients with type 1 and type 2 diabetes attending non-nephrology clinics. This was accompanied by decreasing proportions of patients with microalbuminuria and proteinuria, with fewer patients who reported receiving dialysis over a 12-year period.

Health-related quality of life (HRQoL) in a population at risk of type 2 diabetes: a cross-sectional study in two Latin American cities.

PURPOSE: The purpose of this study was to describe the health-related quality of life (HRQoL) characteristics in a population at risk of developing type 2 diabetes in Barranquilla and Bogotá, Colombia. METHODS: A cross-sectional study with 1135 participants older than 30 years-of-age recruited in Bogotá D.C., and Barranquilla by cluster sampling in 2018 to 2019. The Finnish Diabetes Risk Score (FINDRISC) was used to detect participants at risk of developing type 2 diabetes (T2D). HRQoL was assessed using the EQ-5D-3L questionnaire. Unadjusted and adjusted logistic regression models were used to calculate odds ratios (OR) and their corresponding 95% confidence intervals CI). RESULTS: Moderate or extreme problems appeared more frequently in the dimensions of Pain/Discomfort (60.8%) and Anxiety/Depression (30.8%). The mean score of the EQ-VAS was 74.3 (± 17.3), significantly larger in the state of complete health (11111) compared with those with problems in more than one of the quality-of-life dimensions. Being female and living in Bogota D.C., were associated with greater odds of reporting problems in the Pain (OR 1.6; 95% CI 1.2-2.2) and Discomfort dimensions (OR 1.6; 95% CI 1.2-2.0) respectively and Anxiety/Depression (OR 1.9; 95% CI 1.3-2.7), (OR 9.1; 95% CI 6.6-12.4), respectively. CONCLUSIONS: As living place and sex were associated with dimensions of Pain/Discomfort and Anxiety/Depression in the HRQoL in people at risk of T2D, greater attention should be paid to these determinants of HRQoL to design and reorient strategies with a territorial and gender perspective to achieve better health outcomes. Diabetes is one of the four non-communicable diseases with increasing prevalence in the world, which has made it a serious public health problem. In Colombia, in 2019 diabetes affected 8.4% of the Colombian adult population and more than one million Colombian adults of this age group have hidden or undetected diabetes. This disease is not only characterized by increased premature mortality, loss of productivity, and economic impact, but it also involves a deterioration in the quality of life of people with diabetes with their respective families. However, very Little is known about health-related quality of life (HRQoL) in a population at risk or with prediabetes. This study has evaluated the quality of life in patients at risk of diabetes and their behavior with some variables as sociodemographic, lifestyle, history, and established their difference in two territories of the Colombian Caribbean. The results of this study indicate that the HRQoL of people at risk of type 2 diabetes is affected by factors such as gender, city, dysglycemia, medication for hypertension and education level. Therefore, greater attention should be paid to these determinants of HRQL to design and implement strategies that reduce this risk of developing type 2 diabetes, prevent prediabetes and improve the quality of life in prediabetic or diabetic patients.

Correction to: Persistent poor glycaemic control in individuals with type 2 diabetes in developing countries: 12 years of real-world evidence of the International Diabetes Management Practices Study (IDMPS).

Unfortunately, the standard deviations for 'last HbA1c measurement' in mmol/mol were miscalculated in Table 1 of this paper.

Persistent poor glycaemic control in individuals with type 2 diabetes in developing countries: 12 years of real-world evidence of the International Diabetes Management Practices Study (IDMPS).

AIMS/HYPOTHESIS: We evaluated the secular trend of glycaemic control in individuals with type 2 diabetes in developing countries, where data are limited. METHODS: The International Diabetes Management Practices Study provides real-world evidence of patient profiles and diabetes care practices in developing countries in seven cross-sectional waves (2005-2017). At each wave, each physician collected data from ten consecutive participants with type 2 diabetes during a 2 week period. The primary objective of this analysis was to evaluate trends of glycaemic control over time. RESULTS: A total of 66,088 individuals with type 2 diabetes were recruited by 6099 physicians from 49 countries. The proportion of participants with HbA1c <53 mmol/mol (<7%) decreased from 36% in wave 1 (2005) to 30.1% in wave 7 (2017) (p < 0.0001). Compared with wave 1, the adjusted ORs of attaining HbA1c ≤64 mmol/mol (≤8%) decreased significantly in waves 2, 5, 6 and 7 (p < 0.05). Over 80% of participants received oral glucose-lowering drugs, with declining use of sulfonylureas. Insulin use increased from 32.8% (wave 1) to 41.2% (wave 7) (p < 0.0001). The corresponding time to insulin initiation (mean ± SD) changed from 8.4 ± 6.9 in wave 1 to 8.3 ± 6.6 years in wave 7, while daily insulin dosage ranged from 0.39 ± 0.21 U/kg (wave 1) to 0.33 ± 0.19 U/kg (wave 7) for basal regimen and 0.70 ± 0.34 U/kg (wave 1) to 0.77 ± 0.33 (wave 7) U/kg for basal-bolus regimen. An increasing proportion of participants had ≥2 HbA1c measurements within 12 months of enrolment (from 61.8% to 92.9%), and the proportion of participants receiving diabetes education (mainly delivered by physicians) also increased from 59.0% to 78.3%. CONCLUSIONS: In developing countries, glycaemic control in individuals with type 2 diabetes remained suboptimal over a 12 year period, indicating a need for system changes and better organisation of care to improve self-management and attainment of treatment goals.

Association of obesity with cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease: Insights from TECOS.

BACKGROUND: Obesity is a risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). Whether obesity affects outcomes among those with T2D and atherosclerotic CVD (ASCVD) remains uncertain. Our objective was to investigate the relationship between body mass index (BMI) and ASCVD outcomes among TECOS participants with T2D and ASCVD. METHODS: BMI categories were defined as underweight/normal weight (BMI <25 kg/m2), overweight (25-29.9 kg/m2), obese class I (30-34.9 kg/m2), obese class II (35-39.9 kg/m2), and obese class III (≥ 40 kg/m2). Asian-specific BMI categories were applied to Asian participants. Kaplan-Meier survival analysis and Cox proportional hazards models were used to examine associations between baseline BMI and a composite CV outcome (CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina). RESULTS: For 14,534 TECOS patients with available BMI, mean age was 65.5 years; 29.3% were female, 32.0% non-White, and 23.1% insulin-treated, with median 3 years' follow-up. At baseline, 11.6% (n = 1686) were underweight/normal weight, 38.1% (n = 5532) overweight, 32.2% (n = 4683) obese class I, 12.4% (n = 1806) obese class II, and 5.7% (n = 827) obese class III. The composite CV outcome occurred in 11.4% (n = 1663) of participants; the outcome risk was lower, compared with under/normal weight, in overweight (HR 0.83, 95% CI 0.71-0.98) and obese class I (HR 0.79, 95% CI 0.67-0.93) individuals. Obesity was not associated with worse glycemic control. CONCLUSIONS: The majority of TECOS participants with ASCVD and T2D were overweight or obese, yet overweight or obese class I individuals had lower CV risk than those who were under/normal weight. These results suggest the presence of an obesity paradox, but this paradox may reflect an epidemiological artifact rather than a true negative association between normal weight and clinical outcomes.

Insulin Therapy in Type 2 Diabetes.

BACKGROUND: Since the discovery of insulin, it was the only drug available for the treatment of diabetes until the development of sulfonylureas and biguanides 50 years later. But even with the availability of oral glucose-lowering drugs, insulin supplementation was often needed to achieve good glucose control in type 2 diabetes. Insulin NPH became the basal insulin therapy of choice and adding NPH to metformin and/or sulfonylureas became the standard of care until basal insulin analogs were developed and new glucose-lowering drugs became available. AREAS OF UNCERTAINTY: The advantages in cost-benefit of insulin analogs and their combination with new glucose-lowering drugs are still a matter of debate. There is no general agreement on how to avoid inertia by prescribing insulin therapy in type 2 diabetes when really needed, as reflected by the diversity of recommendations in the current clinical practice guidelines. DATA SOURCES: When necessary for this review, a systematic search of the evidence was done in PubMed and Cochrane databases. THERAPEUTIC ADVANCES: Adding new oral glucose-lowering drugs to insulin such as DPP-4 inhibitors lead to a modest HbA1c reduction without weight gain and no increase in hypoglycemia. When SGLT-2 inhibitors are added instead, there is a slightly higher HbA1c reduction, but with body weight and blood pressure reduction. The downside is the increase in genital tract infections. GLP-1 receptor agonists have become the best alternative when basal insulin fails, particularly using fixed ratio combinations. Rapid-acting insulins via the inhaled route may also become an alternative for insulin supplementation and/or intensification. "Smart insulins" are under investigation and may become available for clinical use in the near future. CONCLUSIONS: Aggressive weight loss strategies together with the new glucose-lowering drugs which do not cause hypoglycemia nor weight gain should limit the number of patients with type 2 diabetes needing insulin. Nevertheless, because of therapeutic inertia and the progressive nature of the disease, many need at least a basal insulin supplementation and insulin analogs are the best choice as they become more affordable. Fixed ratio combinations with GLP1 receptor agonists are a good choice for intensification of insulin therapy.

Global status of diabetes prevention and prospects for action: A consensus statement.

Primary prevention of type 2 diabetes (T2D) should be achievable through the implementation of early and sustainable measures. Several randomized control studies that found success in preventing the progression to T2D in high-risk populations have identified early and intensive intervention based on an individualized prevention model as the key factor for participant benefit. The global prevalence of both overweight and obesity has now been widely recognized as the major epidemic of the 21st century. Obesity is a major risk factor for the progression from normal glucose tolerance to prediabetes and then to T2D. However, not all obese individuals will develop prediabetes or progress to diabetes. Intensive, multicomponent behavioural interventions for overweight and obese adults can lead to weight loss. Diabetes medications, including metformin, GLP-1 agonists, glitazones, and acarbose, can be considered for selected high-risk patients with prediabetes when lifestyle-based programmes are proven unsuccessful. Nutrition education is the cornerstone of a healthy lifestyle. Also, physical activity is an integral part of the prediabetes management plan and one of the main pillars in the prevention of diabetes. Mobile phones, used extensively worldwide, can facilitate communication between health professionals and the general population, and have been shown to be helpful in the prevention of T2D. Universal screening is needed. Noninvasive risk scores should be used in all countries, but they should be locally validated in all ethnic populations focusing on cultural differences around the world. Lifestyle interventions reduce the progression to prediabetes and diabetes. Nevertheless, many questions still need to be answered.

Effect of race on the glycaemic response to sitagliptin: Insights from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS).

AIM: Pooled efficacy studies suggest that glycaemic responses to dipeptidyl-peptidase 4 inhibitors in type 2 diabetes are greatest in Asians, who may also respond better to alpha-glucosidase inhibitors. We assessed the glycaemic impact of sitagliptin by race in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), and whether this was enhanced in Asians with concomitant acarbose therapy. MATERIALS AND METHODS: TECOS enrolled 14 671 patients with type 2 diabetes, cardiovascular disease and HbA1c of 48-64 mmol/mol (6.5%-8.0%), and randomized them, double-blind, to sitagliptin or placebo. There were 3265 patients (22.3%) from Asian countries. Background glucose-lowering therapies were unaltered for the first 4 months post randomization unless clinically essential, facilitating comparison of sitagliptin-associated effects in self-identified East Asian, Other (South) Asian, White Caucasian, Hispanic, Black and Indigenous groups. RESULTS: Median baseline HbA1c by race was 54 to 57 mmol/mol (7.1%-7.4%). Mean 4-month reduction in placebo-adjusted HbA1c was greatest in East Asians (-6.6 mmol/mol [-0.60%] vs ≤6.0 mmol/mol [≤0.55%] in other groups), with significantly greater reduction vs the 2 largest groups (White Caucasians, Other Asians; P < .0001) after adjustment for covariates. After the first 4 months, East and Other Asians were more likely to initiate additional oral therapy (metformin and/or sulfonylureas) than insulin vs White Caucasians (P < .0001). Acarbose use increased in the Asian patients, but no glycaemic interaction with allocated study medication was observed (adjusted P = .12). CONCLUSIONS: The greatest initial reduction in HbA1c with sitagliptin in the TECOS population was in East Asians. No enhanced glycaemic effect was seen when sitagliptin was given with acarbose.

Cardio-Metabolic Health Venezuelan Study (EVESCAM): Design and Implementation.

The EVESCAM (EstudioVenezolano de Salud Cardio-Metabólica) is the first national, population survey in Venezuela, designed to examine the prevalence of diabetes and cardio-metabolic risk factors and its relationship with lifestyle. It is a cross-sectional, cluster sampling study, which recruited 4454 participants aged ≥ 20 years. The data were collected in community health-care centers by trained health professionals and medical students. The data collected from each subject included, after informed consent, structured questionnaires (clinical, demographic, physical activity, nutritional and psychological), anthropometric measurements (weight, height and waist circumference), body fat by bioelectrical impedance, hand grip, blood pressure, electrocardiogram, and biochemical measurements (standard 75 g oral glucose tolerance test, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). The data will be used to estimate the prevalence of overweight, obesity, prediabetes, diabetes, hypertension, dyslipidemias, sarcopenia and metabolic syndrome; and to examine their relationships with lifestyle factors. The risk of coronary heart disease and impaired glucose regulation will be estimated using the Framingham Coronary Heart Disease Risk Score and the Latin America adaptation of the Finnish Diabetes Risk Score (LA-FINDRISC), respectively. These results will guide national cardiovascular and diabetes prevention strategies, and will be available for government agencies to help in the implementation of public health policies.

TRANSCULTURALIZATION RECOMMENDATIONS FOR DEVELOPING LATIN AMERICAN CLINICAL PRACTICE ALGORITHMS IN ENDOCRINOLOGY--PROCEEDINGS OF THE 2015 PAN-AMERICAN WORKSHOP BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY.

The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) convened their first Workshop for recommendations to optimize Clinical Practice Algorithm (CPA) development for Latin America (LA) in diabetes (focusing on glycemic control), obesity (focusing on weight loss), thyroid (focusing on thyroid nodule diagnostics), and bone (focusing on postmenopausal osteoporosis) on February 28, 2015, in San Jose, Costa Rica. A standardized methodology is presented incorporating various transculturalization factors: resource availability (including imaging equipment and approved pharmaceuticals), health care professional and patient preferences, lifestyle variables, socio-economic parameters, web-based global accessibility, electronic implementation, and need for validation protocols. A standardized CPA template with node-specific recommendations to assist the local transculturalization process is provided. Participants unanimously agreed on the following five overarching principles for LA: (1) there is only one level of optimal endocrine care, (2) hemoglobin A1C should be utilized at every level of diabetes care, (3) nutrition education and increased pharmaceutical options are necessary to optimize the obesity care model, (4) quality neck ultrasound must be part of an optimal thyroid nodule care model, and (5) more scientific evidence is needed on osteoporosis prevalence and cost to justify intervention by governmental health care authorities. This 2015 AACE/ACE Workshop marks the beginning of a structured activity that assists local experts in creating culturally sensitive, evidence-based, and easy-to-implement tools for optimizing endocrine care on a global scale.

The association between sociodemographic characteristics, clinical indicators and body mass index in a population at risk of type 2 diabetes: A cross-sectional study in two Colombian cities.

AIMS: To assess the association between sociodemographic and clinical factors with body mass index (BMI) in a population at risk of type 2 diabetes (T2D) in Bogotá and Barranquilla, Colombia. METHODS: This cross-sectional study used data from the PREDICOL Study. Participants with a FINDRISC ≥ 12 who underwent an Oral Glucose Tolerance Test (OGTT) were included in the study (n=1166). The final analytical sample size was 1101 participants. Those with missing data were excluded from the analysis (n=65). The main outcome was body mass index (BMI), which was categorized as normal, overweight, and obese. We utilized unadjusted and adjusted ordinal logistic regression analysis to calculate odds ratios (OR) and 95 % confidence intervals (CI). RESULTS: The prevalence of overweight and obesity was 41 % (n=449) and 47 % (n=517), respectively. Participants with a 2-hour glucose ≥139 mg/dl had 1.71 times higher odds of being overweight or obese (regarding normal weight) than participants with normal 2-hour glucose values. In addition, being a woman, waist circumference altered, and blood pressure >120/80 mmHg were statistically significantly associated with a higher BMI. CONCLUSION: Strategies to control glycemia, blood pressure, and central adiposity are needed in people at risk of T2D. Future studies should be considered with a territorial and gender focus, considering behavioral, and sociocultural patterns.

Patient-reported outcomes and treatment adherence in type 2 diabetes using natural language processing: Wave 8 of the Observational International Diabetes Management Practices Study.

AIMS/INTRODUCTION: We analyzed patient-reported outcomes of people with type 2 diabetes to better understand perceptions and experiences contributing to treatment adherence. MATERIALS AND METHODS: In the ongoing International Diabetes Management Practices Study, we collected patient-reported outcomes data from structured questionnaires (chronic treatment acceptance questionnaire and Diabetes Self-Management Questionnaire) and free-text answers to open-ended questions to assess perceptions of treatment value and side-effects, as well as barriers to, and enablers for, adherence and self-management. Free-text answers were analyzed by natural language processing. RESULTS: In 2018-2020, we recruited 2,475 patients with type 2 diabetes (43.3% insulin-treated, glycated hemoglobin (HbA1c) 8.0 ± 1.8%; 30.9% with HbA1c <7%) from 13 countries across Africa, the Middle East, Europe, Latin America and Asia. Mean ± standard deviation scores of chronic treatment acceptance questionnaire (acceptance of medication, rated out of 100) and Diabetes Self-Management Questionnaire (self-management, rated out of 10) were 87.8 ± 24.5 and 3.3 ± 0.9, respectively. Based on free-text analysis and coded responses, one in three patients reported treatment non-adherence. Overall, although most patients accepted treatment values and side-effects, self-management was suboptimal. Treatment duration, regimen complexity and disruption of daily routines were major barriers to adherence, whereas habit formation was a key enabler. Treatment-adherent patients were older (60 ± 11.6 vs 55 ± 11.7 years, P < 0.001), and more likely to have longer disease duration (12 ± 8.6 vs 10 ± 7.7 years, P < 0.001), exposure to diabetes education (73.1% vs 67.8%, P < 0.05), lower HbA1c (7.9 ± 1.8% vs 8.3 ± 1.9%, P < 0.001) and attainment of HbA1c <7% (29.7% vs 23.3%, P < 0.01). CONCLUSIONS: Patient perceptions/experiences influence treatment adherence and self-management. Patient-centered education and support programs that consider patient-reported outcomes aimed at promoting empowerment and developing new routines might improve glycemic control.

Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): a multicentre, randomised open-label trial.

BACKGROUND: In people with type 2 diabetes, a dipeptidyl peptidase-4 (DPP-4) inhibitor is one choice as second-line treatment after metformin, with basal insulin recommended as an alternative. We aimed to compare the efficacy, tolerability, and safety of insulin glargine and sitagliptin, a DPP-4 inhibitor, in patients whose disease was uncontrolled with metformin. METHODS: In this comparative, parallel, randomised, open-label trial, metformin-treated people aged 35-70 years with glycated haemoglobin A(1c) (HbA(1c)) of 7-11%, diagnosis of type 2 diabetes for at least 6 months, and body-mass index of 25-45 kg/m(2) were recruited from 17 countries. Participants were randomly assigned (1:1) to 24-week treatment with insulin glargine (titrated from an initial subcutaneous dose of 0·2 units per kg bodyweight to attain fasting plasma glucose of 4·0-5·5 mmol/L) or sitagliptin (oral dose of 100 mg daily). Randomisation (via a central interactive voice response system) was by random sequence generation and was stratified by centre. Patients and investigators were not masked to treatment assignment. The primary outcome was change in HbA(1c) from baseline to study end. Efficacy analysis included all randomly assigned participants who had received at least one dose of study drug and had at least one on-treatment assessment of any primary or secondary efficacy variable. This trial is registered at ClinicalTrials.gov, NCT00751114. FINDINGS: 732 people were screened and 515 were randomly assigned to insulin glargine (n=250) or sitagliptin (n=265). At study end, adjusted mean reduction in HbA(1c) was greater for patients on insulin glargine (n=227; -1·72%, SE 0·06) than for those on sitagliptin (n=253; -1·13%, SE 0·06) with a mean difference of -0·59% (95% CI -0·77 to -0·42, p<0·0001). The estimated rate of all symptomatic hypoglycaemic episodes was greater with insulin glargine than with sitagliptin (4·21 [SE 0·54] vs 0·50 [SE 0·09] events per patient-year; p<0·0001). Severe hypoglycaemia occurred in only three (1%) patients on insulin glargine and one (<1%) on sitagliptin. 15 (6%) of patients on insulin glargine versus eight (3%) on sitagliptin had at least one serious treatment-emergent adverse event. INTERPRETATION: Our results support the option of addition of basal insulin in patients with type 2 diabetes inadequately controlled by metformin. Long-term benefits might be expected from the achievement of optimum glycaemic control early in the course of the disease. FUNDING: Sanofi.

Safety and efficacy of P2Et extract from Caesalpinia spinosa in breast cancer patients: study protocol for a randomized double blind phase II clinical trial (CS003-BC).

BACKGROUND: Chemotherapy in breast cancer is effective but can generate significant toxicity and lead to tumor resistance. Joint treatment with standardized plant extracts can be an alternative to improve the response and allow an effective activation of the antitumor immune response that favors recovery in the short and long term. The P2Et extract of Caesalpinia spinosa presents antitumor activity in cells and animal models of breast cancer, improves the tumor microenvironment, and induces activation of the specific immune response against the tumor and is synergistic when used together with anthracyclines, which makes it a good candidate for evaluation in patients. METHODS: Conducted at a single center, this phase II study is a randomized, double-blind, placebo-controlled trial aimed at assessing the safety and efficacy of P2Et extract in patients diagnosed with stage II and III breast cancer, who are eligible for neoadjuvant treatment. The study aims to determine the safety profile at the previously established optimal biological dose from phase I trial while investigating various efficacy outcomes. These outcomes include improvements in quality of life, immunomodulation, metabolic profile, microbiome, as well as clinical indicators such as tumor reduction, disease-free survival, and pathological response, assessed at different stages of the treatment regimen. DISCUSSION: Treatment with the P2Et extract in breast cancer patients is hypothesized to enhance overall well-being, positively influencing their quality of life, while also triggering an antitumor immune response and enhancing immune infiltration. These combined effects have the potential to contribute to improved long-term survival outcomes for patients receiving the phytomedicine alongside neoadjuvant chemotherapy treatment. TRIAL REGISTRATION: This trial was registered in the US National Library of Medicine with identifier NCT05007444. First Registered August 16th, 2021. Last Updated: August 9th, 2022.

Exploring the safety and efficacy of phytomedicine Petiveria alliacea extract (Esperanza) in patients with metastatic gastrointestinal tumors and acute leukemias: study protocol for a phase Ib/randomized double blind phase II trial (PA001).

BACKGROUND: The energy metabolism of drug-resistant tumor cells can provide a survival advantage during therapy, and treatment itself may influence metabolic reprogramming. Petiveria alliacea (Traditional name: Anamu) could inhibit glycolysis and OXPHOX modulating tumor metabolism, making it a potential treatment for tumors with altered metabolism. This clinical study aims to evaluate the safety and efficacy of a standardized Anamu phytomedicine called Esperanza in treating gastric tumors and acute leukemias. METHODS: This is a prospective, open label, phase I/ randomized, double-blind single-center phase II study designed to evaluate the safety and efficacy of Esperanza extract in patients with metastatic gastrointestinal tumors and acute leukemias. In stage 1, the study will determine the MTD and assess safety. In stage 2, safety at the MTD will be evaluated, and the efficacy of Esperanza extract will be explored in both metastatic gastric tumors and acute leukemias. Quality of life improvement will be the primary outcome in the gastric tumor group, while different efficacy outcomes will be assessed in the acute leukemia group. A placebo group will be used for comparison in the gastric tumor group, and a historical control group will be used in the acute leukemia arm. DISCUSSION: This clinical trial aims to evaluate the safety profile of the Esperanza extract in patients with metastatic gastrointestinal tumors and acute leukemias, while exploring its potential efficacy in conjunction with standard treatment for these pathologies. TRIAL REGISTRATION: This trial was registered in the US National Library of Medicine with identifier NCT05587088. Registered October 19th, 2022.

The impact of the COVID-19 pandemic on diabetes services: planning for a global recovery.

The COVID-19 pandemic has disproportionately affected certain groups, such as older people (ie, >65 years), minority ethnic populations, and people with specific chronic conditions including diabetes, cardiovascular disease, kidney disease, and some respiratory diseases. There is now evidence of not only direct but also indirect adverse effects of COVID-19 in people with diabetes. Recurrent lockdowns and public health measures throughout the pandemic have restricted access to routine diabetes care, limiting new diagnoses, and affecting self-management, routine follow-ups, and access to medications, as well as affecting lifestyle behaviours and emotional wellbeing globally. Pre-pandemic studies have shown that short-term delays in delivery of routine care, even by 12 months, are associated with adverse effects on risk factor control and worse microvascular, macrovascular, and mortality outcomes in people with diabetes. Disruptions within the short-to-medium term due to natural disasters also result in worse diabetes outcomes. However, the true magnitude of the indirect effects of the COVID-19 pandemic on long-term outcomes and mortality in people with diabetes is still unclear. Disasters tend to exacerbate existing health disparities; as we recover ambulatory diabetes services in the aftermath of the pandemic, there is an opportunity to prioritise those with the greatest need, and to target resources and interventions aimed at improving outcomes and reducing inequality.

Randomized double-blind clinical study in patients with COVID-19 to evaluate the safety and efficacy of a phytomedicine (P2Et).

Background: It has been proposed that polyphenols can be used in the development of new therapies against COVID-19, given their ability to interfere with the adsorption and entrance processes of the virus, thus disrupting viral replication. Seeds from Caesalpinia spinosa, have been traditionally used for the treatment of inflammatory pathologies and respiratory diseases. Our team has obtained an extract called P2Et, rich in polyphenols derived from gallic acid with significant antioxidant activity, and the ability to induce complete autophagy in tumor cells and reduce the systemic inflammatory response in animal models. Methods: In this work, a phase II multicenter randomized double-blind clinical trial on COVID-19 patients was designed to evaluate the impact of the P2Et treatment on the clinical outcome and the immunological parameters related to the evolution of the disease. The Trial was registered with the number No. NCT04410510*. A complementary study in an animal model of lung fibrosis was carried out to evaluate in situ lung changes after P2Et in vivo administration. The ability of P2Et to inhibit the viral load of murine and human coronaviruses in cellular models was also evaluated. Results: Patients treated with P2Et were discharged on average after 7.4 days of admission vs. 9.6 days in the placebo group. Although a decrease in proinflammatory cytokines such as G-CSF, IL-15, IL-12, IL-6, IP10, MCP-1, MCP-2 and IL-18 was observed in both groups, P2Et decreased to a greater extent G-CSF, IL-6 and IL-18 among others, which are related to lower recovery of patients in the long term. The frequency of T lymphocytes (LT) CD3+, LT double negative (CD3+CD4-CD8-), NK cells increased in the P2Et group where the population of eosinophils was also significantly reduced. In the murine bleomycin model, P2Et also reduced lung inflammation and fibrosis. P2Et was able to reduce the viral replication of murine and human coronaviruses in vitro, showing its dual antiviral and anti-inflammatory role, key in disease control. Conclusions: Taken together these results suggest that P2Et could be consider as a good co-adjuvant in the treatment of COVID-19. Clinical trail registration: https://clinicaltrials.gov/ct2/show/NCT04410510, identifier: NCT04410510.

Comparative efficacy and safety of basal insulins: A review.

BACKGROUND AND AIM: To provide an update on the usefulness of basal insulin in patients with type 2 diabetes mellitus. METHODS: We conducted a literature search using PubMed and MEDLINE, BIOSIS, Scopus, EMBASE, ClinicalTrials.gov, Google Scholar, and Springer Online Archives Collection until June 2021. RESULTS: All basal insulins are similar in efficacy, with only small differences among them in terms of the risk of hypoglycemia. CONCLUSIONS: For type 2 diabetes mellitus, all basal insulins have a similar efficacy, with some advantage of Glar-300 and Deg-100 in reducing the risk of hypoglycemia compared to Glar-100.