Structural modifications of INGAP-PP present in HTD4010 peptide potentiate its effect on rat islet gene expression and insulin secretion.

Type 2 diabetes (T2D) is characterized by peripheral insulin resistance and altered insulin secretion due to a progressive loss of ß-cell mass and function. Today, most antidiabetic agents are designed to resolve impaired insulin secretion and/or insulin resistance, and only GLP-1-based formulations contribute to stopping the decline in ß-cell mass. HTD4010, a peptide carrying two modifications of the amino acid sequence of INGAP-PP (N-terminus acetylation and substitution of Asn13 by Ala) showed greater plasma stability and could be a good candidate for proposal as a drug that could improve ß cell mass and function lost in T2D. In the present study, we showed that HTD4010 included in the culture media of normal rat islets at a dose 100 times lower than that used for INGAP-PP was able to modulate, in the same way as the original peptide, both insulin secretion in response to glucose and the expression of key genes related to insular function, insulin and leptin intracellular pathways, neogenesis, apoptosis, and inflammatory response. Our results confirm the positive effect of HTD4010 on ß-cell function and gene expression of factors involved in the maintenance of ß-cell mass. Although new assays in animal models of prediabetes and T2D must be performed to be conclusive, our results are very encouraging, and they suggest that the use of HTD4010 at a dose 100 times lower than that of INGAP-PP could minimize its side effects in a future clinical trial.

Transcriptional signature of islet neogenesis-associated protein peptide-treated rat pancreatic islets reveals induction of novel long non-coding RNAs.

Background: Diabetes mellitus is characterized by chronic hyperglycemia with loss of ß-cell function and mass. An attractive therapeutic approach to treat patients with diabetes in a non-invasive way is to harness the innate regenerative potential of the pancreas. The Islet Neogenesis-Associated Protein pentadecapeptide (INGAP-PP) has been shown to induce ß-cell regeneration and improve their function in rodents. To investigate its possible mechanism of action, we report here the global transcriptional effects induced by the short-term INGAP-PP in vitro treatment of adult rat pancreatic islets. Methods and findings: Rat pancreatic islets were cultured in vitro in the presence of INGAP-PP for 4 days, and RNA-seq was generated from triplicate treated and control islet samples. We performed a de novo rat gene annotation based on the alignment of RNA-seq reads. The list of INGAP-PP-regulated genes was integrated with epigenomic data. Using the new gene annotation generated in this work, we quantified RNA-seq data profiled in INS-1 cells treated with IL1ß, IL1ß+Calcipotriol (a vitamin D agonist) or vehicle, and single-cell RNA-seq data profiled in rat pancreatic islets. We found 1,669 differentially expressed genes by INGAP-PP treatment, including dozens of previously unannotated rat transcripts. Genes differentially expressed by the INGAP-PP treatment included a subset of upregulated transcripts that are associated with vitamin D receptor activation. Supported by epigenomic and single-cell RNA-seq data, we identified 9 previously unannotated long noncoding RNAs (lncRNAs) upregulated by INGAP-PP, some of which are also differentially regulated by IL1ß and vitamin D in ß-cells. These include Ri-lnc1, which is enriched in mature ß-cells. Conclusions: Our results reveal the transcriptional program that could explain the enhancement of INGAP-PP-mediated physiological effects on ß-cell mass and function. We identified novel lncRNAs that are induced by INGAP-PP in rat islets, some of which are selectively expressed in pancreatic ß-cells and downregulated by IL1ß treatment of INS-1 cells. Our results suggest a relevant function for Ri-lnc1 in ß-cells. These findings are expected to provide the basis for a deeper understanding of islet translational results from rodents to humans, with the ultimate goal of designing new therapies for people with diabetes.

Relación entre el Finnish Diabetes Risk Score, glucemia en ayunas y hemoglobina A1c / Relationship between the Finnish Diabetes Risk Score, fasting blood glucose and glycohemoglobin A1c

Introducción: el Finnish Diabetes Risk Score (FINDRISC) mostró alta sensibilidad y especificidad para la detección de personas que evolucionarían a diabetes mellitus (DM) en las poblaciones estudiadas, por lo cual se decidió utilizarlo entre quienes concurrieron por diferentes motivos a realizarse análisis de laboratorio en centros de la Asociación de Laboratorios de Alta Complejidad (ALAC), con el objeto de identificar personas con diferentes niveles de riesgo de presentar alteraciones de la glucemia en ayunas (GA) y de la HbA1c. Objetivos: explorar la asociación entre la puntuación del FINDRISC con GA y HbA1c, estableciendo el punto de corte de mayor sensibilidad y especificidad para encontrar una GA ≥100 mg/dL y una HbA1c ≥5,7% (38,8 mmol/mol), en una población que concurrió a centros de la ALAC. Materiales y métodos: se incluyeron 1.175 individuos de 45 laboratorios de la ALAC, procesamiento local de glucemia y centralizado de HbA1c (high performance liquid chromatography, HPLC). Análisis estadístico: chi-cuadrado, Odds Ratio, ANOVA, test de Tukey, regresión logística binomial y curvas ROC. Resultados: los puntajes totales del FINDRISC se asociaron de manera positiva y estadísticamente significativa, tanto con los valores de GA como con los niveles de HbA1c. Entre sus variables, una edad mayor o igual a 45 años, un perímetro abdominal de alto riesgo, un índice de masa corporal mayor o igual a 25 Kg/m., la presencia de antecedentes familiares de DM (padres, hermanos o hijos) y la existencia de antecedentes de medicación antihipertensiva se asociaron de manera significativa con valores de GA iguales o superiores a 100 mg/dL y/o niveles de HbA1c iguales o mayores a 5,7% (38,8 mmol/mol). No se halló asociación significativa con la realización de actividad física (al menos 30 minutos diarios) ni con el registro de ingesta diario de frutas y verduras. Los valores medios de GA y HbA1c en individuos con puntajes totales del FINDRISC menores o iguales a 11 fueron de 89,9 mg/dL y 5,2% (33,0 mmol/mol), respectivamente, elevándose hasta valores medios de 116,1 mg/dL y 6,1% (43,0 mmol/mol) en los individuos con puntajes iguales o superiores a 21, siguiendo una asociación del tipo "dosis/respuesta". Por curvas ROC, un FINDRISC de 13 presenta una sensibilidad del 81,89%, especificidad del 67,60% y 70,55% de diagnósticos correctos de HbA1c ≥5,7% (38,8 mmol/mol), y una sensibilidad del 72,50%, especificidad del 70,62% y 71,20% de diagnósticos correctos para encontrar personas con una GA ≥100 mg/dL. Conclusiones: el puntaje del FINDRISC se relacionó con niveles crecientes de GA y HbA1c, resultando útil para encontrar personas con GA ≥100 mg/dL y HbA1c ≥5,7% (38,8 mmol/mol) en la población estudiada.

Introduction: the Finnish Diabetes Risk Score (FINDRISC) has high sensitivity and specificity for the identification of people at risk of diabetes mellitus (DM) in various populations. Therefore, we aimed to use this index to identify individuals at risk of having alterations in fasting glycemia (FG) and HbA1c among those who underwent laboratory analysis at ALAC, Argentina. Objectives: to explore the relationships of the FINDRISC score with the fasting blood glucose (FG) concentration and glycated hemoglobin (HbA1c) level, and to establish appropriate cut-off scores to predict FG ≥100 mg/dL and HbA1c ≥5.7% (38.8 mmol/mol) in this population. Materials and methods: we recruited 1,175 individuals from 45 ALAC laboratories for whom FG and HbA1c had been measured. We analyzed the data using the chi square test, odds ratios, ANOVA plus Tukey's post-hoc test, binomial logistic regression, and receiver operating characteristic (ROC) curves. Results: total FINDRISC score significantly positively correlated with both FG and HbA1c. Of the constituent variables, age ≥45 years, a large waist circumference, a body mass index ≥25 kg/m., a close family history of DM, and the use of antihypertensive medication were significantly associated with FG ≥100 mg/dL and/or HbA1c ≥5.7% (38.8 mmol/mol). However, no significant association was found with physical activity or the daily consumption of fruit and vegetables. The mean FG and HbA1c for individuals with total FINDRISC scores ≤11 were 89.9 mg/dL and 5.2% (33.0 mmol/mol), respectively, which increased to 116.1 mg/dL and 6.1% (43.0 mmol/mol) for individuals with scores ≥21, with a dose/response-type relationship. ROC analysis showed that a FINDRISC of 13 was associated with a sensitivity of 81.89%, a specificity of 67.60%, and a correct diagnosis rate of 70.55% for HbA1c ≥5.7% (38.8 mmol/mol); and a sensitivity of 72.50%, a specificity of 70.62%, and a correct diagnosis rate of 71.20% for FG ≥100 mg/dL. Conclusions: FINDRISC score increases with increasing FG and HbA1c, and is a useful means of identifying people with FG ≥100 mg/dL and HbA1c ≥5.7% (38.8 mmol/mol).

Changes in lifestyle behaviors during COVID-19 isolation in Argentina: A cross-sectional study.

OBJECTIVE: Our aim was to identify changes in population habits induced by COVID-19 confinement in Argentina. METHODS: An internet-based cross-sectional survey was conducted among adults in Argentina on December 2020, requesting possible changes occurring during the COVID-19 outbreak. It included 26 questions regarding general information (age, gender, location), eating habits, desire/anxiety for food or to eat between meals, weight gain, physical activity, and hours of sleep. We ran a descriptive statistical analysis of changes in habits and lifestyle during the confinement, followed by a logistic regression analysis to explore the relation between these changes and weight gain. Results: Out of 1536 survey participants, 57.1% were female, aged 38.8 ± 13.1 years. Data showed that during the outbreak, people experienced significant changes in food intake, physical activity, nutritional supplement consumption, anxiety, and sleeping disorders. These changes in behavior resulted in an elevated percentage of people (39.7%) that gained weight (average 4.8 ± 2.8 kg). Weight gain was associated with more food consumption (OR: 9.398), increased snacking between meals (OR: 1.536), anxiety about food (OR: 3.180), less practice of physical activity (OR: 0.586) and less consumption of nutritional supplements (OR: 0.762). Conclusions: COVID-19 outbreak was associated with unhealthy lifestyle changes and body weight increase. These adverse side effects could be prevented by active promotion of nutritional advice and physical activity, implementing virtual activities associated with regular mass promotion campaigns.

Visión epidemiológica, psicosocial y terapéutica de la diabetes mellitus en Argentina desde las perspectivas del equipo de salud y de las personas con diabetes / Epidemiological, psychosocial and therapeutic vision of diabetes mellitus in Argentina from the perspectives of health team and people with diabetes

Introducción: la diabetes mellitus (DM) genera una pesada carga socioeconómica, y para su abordaje es necesario indagar sobre sus posibles condicionantes para lograr su control, prevención y tratamiento efectivo. Objetivos: entender la problemática de la DM en Argentina y las estrategias para mejorarla según la perspectiva de los profesionales de la salud y de las personas con DM. Materiales y métodos: se implementó un estudio descriptivo con metodología cualitativa basado en la técnica del Metaplan. Se diseñó un cuestionario con dos preguntas (¿Cuáles son a su criterio los problemas que enfrenta la DM en nuestro país?, ¿Qué estrategias emplearía para solucionarlos?), que se distribuyó entre los profesionales de la salud y las personas con DM vía Internet a través de sus respectivas Sociedades, durante junio-julio de 2021. Los participantes (adultos, residentes en Argentina) debían responder hasta cuatro alternativas en cada pregunta. Se revisaron todas las respuestas recibidas, se las agrupó por temas y se las analizó/cuantificó mediante técnicas descriptivas expresando los resultados como porcentajes. Resultados: la muestra final incluyó 404 profesionales del equipo de salud y 272 personas con DM, mayoritariamente con DM1. El análisis demostró que existe: a) una organización deficiente de la cobertura; b) un predominio de hábitos no saludables; c) escasa provisión de educación diabetológica estructurada que dificulta el diagnóstico y el tratamiento adecuado, y falta de capacitación al paciente para participar activa y eficientemente en el control y tratamiento de su enfermedad; d) deficiente calidad de atención. Conclusiones: los resultados, similares a los obtenidos en otros países, sugieren que las estrategias de solución implicarían la restructuración de la formación médica para lograr un balance armónico entre el nivel primario de atención y las especialidades, disminuyendo además la carga psicológica del paciente, la cual se vería facilitada mediante la cooperación armónica de las instituciones educativas y las sociedades científicas, al igual que con una intervención consensuada de diferentes sectores de la sociedad.

Introduction: diabetes mellitus (DM) generates a heavy socioeconomic burden, and to address it, it is necessary to investigate its possible conditioning factors to achieve effective control, prevention, and treatment. Objectives: to understand the problem of diabetes in Argentina, from the perspective of health professionals and people with DM and the strategies to improve it. Materials and methods: it was implemented a descriptive study with qualitative methodology based on the metaplan technique. A questionnaire was designed with two questions (What are, in your opinion, the problems faced by diabetes in our country?, What strategies would you use to solve them?), which was distributed to health professionals and people with DM via the Internet of their respective Societies during JuneJuly 2021. The participants (adults, residents of Argentina) had to answer up to 4 alternatives in each question. All the responses received were reviewed, grouped by topic and analyzed/ quantified using descriptive techniques, expressing the results as percentages. Results: the final sample included 404 professionals from the health team and 272 people with DM: mostly with type 1 DM. The analysis shows that there is: a) a poor organization of coverage; b) a predominance of unhealthy habits; c) scarce provision of structured diabetes education, which makes it difficult to diagnose and adequately treat, and train patients to participate actively and efficiently in the control and treatment of their disease; d) there is a deficient quality of care. Conclusions: our results, similar to those obtained in other countries, suggest that the solution strategies would go through the restructuring of medical training, achieving a harmonious balance between the primary level of care and the specialties, adding a decrease in the psychological burden of the patient. It would be facilitated by the harmonious cooperation of educational institutions and scientific societies. Likewise, through a consensual intervention of different sectors of society.

Aislamiento por Covid-19 en el Amba y en el resto del pais: estudio transversal de cambios en el hábitos y estilo de vida / Isolation by Covid-19 in the Amba and the rest of the country: cross-sectional study of changes in habits and lifestyle

Introducción: el confinamiento impuesto para disminuir la propagación de la COVID-19 induce cambios de hábitos y estilos de vida no saludables. Objetivos: verificar cambios asociados al confinamiento en los hábitos alimentarios y estilo de vida en la población argentina, y sus diferencias entre el área metropolitana de Buenos Aires (AMBA) y el resto del país. Materiales y métodos: estudio transversal, descriptivo y analítico, mediante una encuesta "en línea" (diciembre de 2020) realizada a adultos residentes en Argentina. Se relevó edad, género y lugar de residencia, así como los cambios registrados respecto del peso, hábitos alimentarios, actividad física, deseo por comer y calidad del sueño. Se realizó un análisis descriptivo de las encuestas válidas recibidas (N=1.536), y se verificaron diferencias entre las regiones mediante pruebas paramétricas y no paramétricas, considerando significativo p<0,05.Resultados: el 75,1% de los participantes fue mujer (38,8±13,1 años), el 60,5% del AMBA y 39,5% del resto del país. El aislamiento se asoció a cambios que impactaron en lo psicológico, estrés, hábitos saludables y sueño, con algunas diferencias regionales significativas. Sin embargo, la resultante final común entre AMBA y el resto del país fue el mayor aumento de la ingesta calórica y la disminución de actividad física que condujo a que el 39,7% de los participantes aumentara su peso (media 4,8±2,8 kg). Conclusiones: el aislamiento se asoció con efectos secundarios indeseables que podrían disminuirse mediante la promoción virtual de hábitos saludables que, simultáneamente, disminuirían el aumento de la obesidad y la diabetes

Introduction: the confinement imposed to reduce the spread of COVID-19 induces changes in habits and unhealthy lifestyles. Objectives: to verify changes associated with confinement in eating habits and lifestyle in the Argentine population and their differences between the metropolitan area of Buenos Aires (AMBA) and the rest of the country. Materials and methods: cross-sectional, descriptive, and analytical study, through an "online" survey (December 2020) carried out on adults residing in Argentina. Age, gender and place of residence were surveyed, as well as the changes registered regarding weight, eating habits, physical activity, desire to eat and quality of sleep. A descriptive analysis of the valid surveys received (N=1,536) was carried out, verifying differences between the regions using parametric and nonparametric tests, considering significant p<0.05. Results: 75.1% of the participants were women (38.8±13.1 years), 60.5% from the AMBA and 39.5% from the rest of the country. Isolation was associated with changes that impacted on the psychological, stress, healthy habits, and sleep, with some significant regional differences. However, the common end result between AMBA and the rest of the country was the greater increase in caloric intake and the decrease in physical activity that led to 39.7% of the participants increasing their weight (mean 4.8±2,8 kg). Conclusions: isolation was associated with undesirable side effects, which could be diminished through the virtual promotion of healthy habits that would simultaneously decrease the growth of obesity and diabetes

Arterial Stiffness: Its Relation with Prediabetes and Metabolic Syndrome and Possible Pathogenesis.

AIMS: To evaluate arterial stiffness indicators in people with prediabetes (PreD) and its possible pathogenesis. MATERIALS AND METHODS: Pulse wave velocity (PWV) was measured in 208 people with FINDRISC ≥ 13 (57 ± 8 years old, 68.7% women) and thereafter divided into those having either normal glucose tolerance (NGT) or PreD. In each subgroup we also identified those with/out insulin resistance (IR) measured by the triglyceride/HDL-c ratio (normal cut off values previously established in our population). Clinical and metabolic data were collected for all participants. PWV was compared between subgroups using independent t test. RESULTS: Women and men had comparable clinical and metabolic characteristics with obesity (BMI ≥ 30) and antihypertensive-statin treatment, almost half with either NGT or PreD. Whereas 48% of NGT people presented IR (abnormally high TG/HDL-c ratio), 52% had PreD. PWV was significantly higher only in those with a complete picture of metabolic syndrome (MS). CONCLUSIONS: Since PWV was significantly impaired in people with a complete picture of MS, clinicians must carefully search for early diagnosis of this condition and prescribe a healthy life-style to prevent development/progression of CVD. This proactive attitude would provide a cost-effective preventive strategy to avoid CVD's negative impact on patients' quality of life and on health systems due to their higher care costs.

High Prevalence of Depressive Symptoms in Patients With Type 1 and Type 2 Diabetes in Developing Countries: Results From the International Diabetes Management Practices Study.

OBJECTIVE: Depression is common in people with diabetes, but data from developing countries are scarce. We evaluated the prevalence and risk factors for depressive symptoms in patients with diabetes using data from the International Diabetes Management Practices Study (IDMPS). RESEARCH DESIGN AND METHODS: IDMPS is an ongoing multinational, cross-sectional study investigating quality of care in patients with diabetes in real-world settings. Data from wave 5 (2011), including 21 countries, were analyzed using the 9-item Patient Health Questionnaire (PHQ-9) to evaluate depressive symptoms. Logistic regression analyses were conducted to identify risk factors of depressive symptoms. RESULTS: Of 9,865 patients eligible for analysis, 2,280 had type 1 and 7,585 had type 2 diabetes (treatment: oral glucose-lowering drugs [OGLD] only, n = 4,729; OGLDs plus insulin, n = 1,892; insulin only, n = 964). Depressive symptoms (PHQ-9 score ≥5) were reported in 30.7% of those with type 1 diabetes. In patients with type 2 diabetes, the respective figures were 29.0% for OGLDs-only, 36.6% for OGLDs-plus-insulin, and 46.7% for insulin-only subgroups. Moderate depressive symptoms (PHQ-9 score 10-19) were observed in 8-16% of patients with type 1 or type 2 diabetes. Female sex, complications, and low socioeconomic status were independently associated with depressive symptoms. In type 1 diabetes and in the type 2 diabetes OGLDs-only group, depression was associated with poor glycemic control. CONCLUSIONS: Depressive symptoms are common in patients with diabetes from developing countries, calling for routine screening, especially in high-risk groups, to reduce the double burden of diabetes and depression and their negative interaction.

Integrative transcriptomic analysis of pancreatic islets from patients with prediabetes/type 2 diabetes.

AIM: To identify new transcriptomic alterations in pancreatic islets associated with metabolic dysfunctions in people with prediabetes (PD)/type 2 diabetes (T2D). MATERIALS AND METHODS: We collected information from public data repositories T2D related microarray datasets from pancreatic islets. We identified Differential Expressed Genes (DEGs) in non-diabetic (ND) vs people with T2D in each study. To identify relevant DEGs in T2D, we selected those that varied consistently in the different studies for further meta-analysis and functional enrichment analysis. DEGs were also evaluated at the PD stage. RESULTS: A total of seven microarray datasets were collected and analysed to find the DEGs in each study and meta-analysis was performed with 245 ND and 96 T2D cases. We identified 55 transcriptional alterations potentially associated with specific metabolic dysfunctions in T2D. Meta-analysis showed that 87% of transcripts identified as DEGs (48 out of 55) were confirmed as having statistically significant up- or down-modulation in T2D compared to ND. Notably, nine of these DEGs have not been previously reported as dysregulated in pancreatic islets from people with T2D. Consistently, the most significantly enriched pathways were related to the metabolism and/or development/maintenance of ß-cells. Eighteen of the 48 selected DEGs (38%) showed an altered expression in islets from people with PD. CONCLUSIONS: These results provide new evidence to interpret the pathogenesis of T2D and the transition from PD to T2D. Further studies are necessary to validate its potential use for the development/implementation of efficient new strategies for the prevention, diagnosis/prognosis and treatment of T2D.

A new analogue of islet neogenesis associated protein with higher structural and plasma stability.

Islet Neogenesis Associated Protein pentadecapeptide (INGAP-PP) increases ß-cell mass and function in experimental animals. A short clinical trial also yielded promising results. However, HTD4010, a new peptide derived from INGAP-PP, was developed in order to optimize its specific effects by minimizing its side effects. To study and compare the tertiary structure, stability dynamics, and plasma stability of HTD4010, an INGAP-PP analogue. Both peptides were pre-incubated in human, rat and mouse plasma at 37 °C, and their presence was identified and quantified by high performance liquid chromatography at different time-points. GROMACS 2019 package and the Gromos 54A7 force field were used to evaluate overall correlated motion of the peptide molecule during molecular dynamics simulation by essential dynamics. HTD4010 exhibited significantly larger plasma stability than INGAP-PP, and its structural stability was almost 3.36-fold higher than INGAP-PP. These results suggest that HTD4010 may facilitate longer tissue interaction, thereby developing higher potential biological effects. If so, HTD4010 may become a promising therapeutic agent to treat people with diabetes. Communicated by Ramaswamy H. Sarma.

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.

The triad macrosomia, obesity, and hypertriglyceridemia in gestational diabetes.

AIMS: Offspring of women with gestational diabetes (GD) have more macrosomia than newborns of normal mothers. We studied macrosomia frequency, possible pathogenesis, and main predictors of its appearance at different gestational ages. MATERIALS AND METHODS: A total of 1870 pregnant women with GD were recruited in primary care centres and maternity hospitals in the Argentine provinces of Corrientes, Chaco, Buenos Aires, and in Buenos Aires City; 1088 completed gestation and delivered an infant. We collected clinical and metabolic data, personal and obstetric history, and gestational and delivery characteristics. Presence of macrosomia was analysed in the whole population, the entire pregnancy, and in each trimester of gestation. Data were statistically analysed and values were expressed as mean ± SD and percentages. The study protocol was approved by the Ethics Committee and all participants signed informed consent. RESULTS: Macrosomia was found in 12.9% of newborns and obesity in all mothers with no significant differences between mothers with/without macrosomic offspring. In early pregnancy, the main significant indicators of macrosomia were: history of dyslipidaemia (5.6% vs 1.2%, respectively) and macrosomia in previous pregnancies (27% vs 13%, respectively). However, the third trimester showed a significant combination of higher BMI, FBG, and triglycerides. CONCLUSIONS: Offspring of women with GD presented macrosomia in 12.9% of cases, maternal history of dyslipidaemia and macrosomia in previous pregnancies being early predictors. The combination of maternal obesity, FBG, and hypertriglyceridemia became significant during the last trimester of pregnancy.

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.

Type 2 diabetes: Prescription patterns and treatment outcomes of IDMPS survey in Argentina.

AIM: To assess prescription patterns for treatment of type 2 diabetes (T2D) and their outcomes in the IDMPS survey in Argentina. METHODS: Data from 2551 people with T2D recruited from 210 physicians participating in IDMPS surveys in Argentina (2006 to 2012 waves) were recorded, including medical history, medications, glycemic control, blood pressure, and lipid status. RESULTS: Most people were treated with oral glucose-lowering drugs (OGLDs) (65%), followed by combinations of these drugs plus insulin (22%) and only insulin (13%). These percentages varied according to T2D duration, the frequency of OGLDs decreasing while contrastingly and only insulin increasing (under 5 years versus over 10 years of disease duration, respectively). Average systolic blood pressure (SBP), HbA1c and LDL-c were significantly higher in patients treated with insulin either alone or associated with OGLDs. The percentage of people at target values for these parameters was also lower in these two groups. The percentage of people that reached simultaneous goal treatment values for BP, HbA1c and LDL-c levels was markedly low. CONCLUSION: Prescription patterns for treatment of T2D follows a chronological trend and the percentage of people at goal values (HbA1c, BP and LDL-c values) was significantly lower in people receiving insulin. These data must be carefully considered by health and academic authorities in order to implement effective strategies to modify this situation.

Treat-to-target HbA1c and lipid profile to prolong ß-cell mass/function and optimize treatment goal attainment.

BACKGROUND: To evaluate the relation between different serum lipid fractions and other known barriers to attain the HbA1c  ≤ 7.0% (53 mmol/mol) target. METHODS: Data on 2719 patients with type 2 diabetes were collected from the five waves of the International Diabetes Mellitus Practice Study implemented in Argentina (2006 to 2012) including demographic/socioeconomic profile, clinical, metabolic (HbA1c and serum lipids) data, and treatment type and also, percentage of treatment goal attainment. Descriptive statistical analyses included ANOVA, χ2 test, and Fisher exact test and univariate and multivariate logistic regression analyses, which identified predictive factors for HbA1c  ≤ 7% (53 mmol/mol). RESULTS: The average age was 63 years, primary/secondary education, health insurance, 10-year type 2 diabetes duration, most associated with cardiovascular risk factors and some microvascular/macrovascular complications; 94.5% received antihyperglycaemic drugs. Percentage of people on target: HbA1c 51.2%, blood pressure 23.5%, total cholesterol 62.6%, low-density lipoprotein (LDL) cholesterol 38.9%, and triglycerides 61.1%. HbA1c on target depended markedly on treatment type: more of those treated with lifestyle changes and significantly fewer of those receiving insulin. Only 4.1% had all parameters simultaneously on target. Multivariate logistic regression analyses showed that achieving HbA1c  ≤ 7.0% (53 mmol/mol) was associated with higher educational level, shorter diabetes duration, and having reached goals for LDL cholesterol and triglycerides, whereas opposite results were obtained with insulin treatment and longer diabetes duration. CONCLUSIONS: High LDL cholesterol and triglyceride levels simultaneously potentiate development/progression of chronic complications, exerting this effect in the long term by decreasing ß-cell mass/function, thereby making it more difficult to reach HbA1c values able to prevent complications.

Dyslipidemia: The untreated metabolic dysfunction in people with type 2 diabetes in Latin America. ARETAEUS study outcomes.

OBJECTIVE: To assess oral antihyperglycemic agents (OAHA) and/or statin treatment initiation in patients with type 2 diabetes (T2D) and time from diagnosis to both types of treatment initiation and intensification. RESEARCH DESIGN AND METHODS: We reviewed 662 retrospective medical records of patients with T2D diagnosed by 31 general practitioner or specialist sites across Mexico, Argentina, and Brazil. Demographic and clinical information was abstracted from patients' medical records and summarized using descriptive statistics. Between-group differences were assessed with Student's t-test for continuous variables and Fisher's exact test for categorical variables. The starting time of each therapy (OAHA and statins, separately) was assessed using Kaplan-Meier estimates. RESULTS: At diagnosis, patients' mean age was 53 years; 44% had hypertension, 42% were obese, and 23% had dyslipidemia. During the 2-year follow-up, 95% of patients received OAHAs but only 29% of those eligible for statins received this prescription. Mean ±â€¯SD and median (Q1, Q3) time to first OAHA was 59 ±â€¯141 days and 1 (1, 31) day, respectively, and 230 ±â€¯232 days and 132 (30, 406) days, respectively, for a statin. During follow-up, 51-53% of patients with HbA1c/FPG values above target did not intensify hyperglycemia treatment. CONCLUSION: Dyslipidemia treatment in patients with T2D was delayed despite its known deleterious effect on atherosclerosis development and ß-cell mass/function. Anti-hyperglycemic treatment was not intensified when targets were not attained. This prescriptive inertia needs to be corrected because attainment of HbA1c treatment goals becomes more difficult, favoring the development of diabetes complications.

Drug treatment of type 2 diabetes: Its cost is significantly associated with HbA1c levels.

AIMS: To examine the relationship between costs of hyperglycaemia drug treatment and glycemic control amongst people with type 2 diabetes (T2D). METHODS: This observational study utilised data from the QUALIDIAB database on 3,452 T2D patients seen in Diabetes Centers in Argentina. Patients were classified according to their HbA1c value into two groups: on target (OT; HbA1c ≤ 7%), and not on target (NOT; HbA1c > 7%); within each category we considered clinical and metabolic indicators, as well as type of hyperglycaemia treatment. Monthly expenditure on drugs was estimated by micro-costing. Multivariable regression analysis was used to evaluate the association between cost of hyperglycaemia treatment and HbA1c values. RESULTS: In total, 48.9% of the participants have HbA1c OT values. Overall monthly per capita costs of this treatment increased significantly (134%) in the NOT group. Multivariable regression analysis showed that expenditure for hyperglycaemia drugs treatment was significant associated with glycemic control (OR: 0.705), diabetes duration (OR: 1.017), systolic blood pressure (OR: 1.006) and treatment of T2D (OR: 2.622). CONCLUSIONS: HbA1c NOT significantly increases drugs monthly cost of hyperglycaemia treatment in people with T2D in a country with an emerging market economy.

Personas con diabetes: adherencia al tratamiento, calidad de vida y educación / People with diabetes: adherence to treatment, quality of life and education

La evidencia disponible en la literatura muestra que la calidad de atención de las personas con diabetes, tanto a nivel nacional como internacional, dista mucho de ser la ideal, lo que determina el desarrollo y progresión de las complicaciones crónicas prevenibles de la enfermedad. Esto redunda en un aumento de los costos de su atención y disminución de la calidad de vida de quienes la padecen. Lograr un cambio efectivo de esta situación implica, entre otros objetivos, identificar las causas subyacentes que la determinan. En este sentido en la diabetes y los factores de riesgo asociados, al igual que toda enfermedad crónica, la calidad de atención depende en gran parte de la interacción efectiva entre el médico y el paciente, es decir de un correcto diagnóstico y prescripción apropiada, además de una correcta implementación de la misma

Educación terapéutica de mujeres con diabetes gestacional (EDUGEST): datos correspondientes al período de reclutamiento / Education of pregnant women with gestational diabetes (EDUGEST): data collected in the recruitment period

Introducción: la prevalencia de diabetes gestacional (DG) en Argentina es de 4,7%, lo que implica mayor riesgo de desarrollar complicaciones tanto maternas como del recién nacido, prevenibles mediante un diagnóstico precoz y un tratamiento oportuno. Objetivos: promover la consulta precoz, el diagnóstico oportuno y el tratamiento adecuado mediante un programa de educación estructurado y multidisciplinario a nivel de Centros de Atención Primaria de la Salud (CAPs) y maternidades. Materiales y métodos: se reclutaron embarazadas con DG en CAPs y maternidades de Buenos Aires, Corrientes, Chaco y Ciudad Autónoma de Buenos Aires (CABA), con la participación de obstetras, diabetólogos, enfermeras, asistentes sociales, educadores, nutricionistas y médicos comunitarios. Para el diagnóstico de DG se aplicaron los criterios de la Asociación Latinoamérica de Diabetes (ALAD) y se relevaron simultáneamente hábitos nutricionales y parámetros clínicos, metabólicos y terapéuticos. También se desarrollaron cursos de educación y seguimiento durante el embarazo, parto, postparto y lactancia. Resultados: las embarazadas con DG consultaron tardíamente (la mayoría en el tercer trimestre de embarazo) y presentaron factores de riesgo para DG no prevenibles (el más frecuente fue el antecedente familiar de diabetes) y prevenibles (obesidad, hipertrigliceridemia y macrosomía) en embarazos previos. Conclusiones: el EduGest pretende interrumpir el círculo vicioso generado por la DG sobre la futura diabetes mellitus tipo 2 en la madre y el niño al promover la adopción de hábitos saludables

Introduction: in Argentina the prevalence of gestational diabetes (GD) is 4.7%, accounting for a higher risk of developing complications in both the mother and the baby which could be prevented by early diagnosis and timely treatment. Objectives: to promote early consultation, timely diagnosis and adequate treatment through a structured and multidisciplinary education Program in Primary Healthcare (PHU) and maternity (PMU) units. Materials and methods: pregnant women with DG were recruited in PHU and PMU from Buenos Aires, Corrientes, Chaco and CABA, Argentina. The program included the participation of obstetricians, diabetologists, nurses, social workers, educators, nutritionists and community doctors. The ALAD diagnostic criteria for DG were applied. Simultaneously, nutritional habits, clinical, metabolic and therapeutic parameters were recorded. Education and follow-up courses were developed during pregnancy, delivery, after delivery and breastfeeding. Results: late consultation was frequent in pregnant women with GD (mainly during the third trimester), who presented both non-preventable (the most frequent being family history of diabetes) and preventable (obesity, hypertriglyceridemia and macrosomia) risk factors for GD in previous pregnancies. Conclusions: EduGest is aimed at breaking the vicious circle of DG on the future development of type 2 diabetes in the mother and the baby by promoting the adoption of healthy habits