Impaired endocrine-metabolic homeostasis: underlying mechanism of its induction by unbalanced diet.

To characterize the intrinsic mechanism by which sucrose induces ß-cell dysfunction. Normal rats received for 3 weeks a standard diet supplemented with 10% sucrose in the drinking water (high sucrose (HS)) with/out an antioxidant agent (R/S α-lipoic acid). We measured plasma glucose, insulin, triglyceride, leptin, and lipid peroxidation levels; homeostasis model assessment (HOMA)-insulin resistance (HOMA-IR) and HOMA for ß-cell function (HOMA-ß) indexes were also determined. Insulin secretion, ß-cell apoptosis, intracellular insulin and leptin mediators, and oxidative stress (OS) markers were also measured in islets isolated from each experimental group. HS rats had increased plasma triglyceride, insulin, leptin, and lipid peroxidation (OS marker) levels associated with an insulin-resistant state. Their islets developed an initial compensatory increase in glucose-induced insulin secretion and mRNA and protein levels of ß-cell apoptotic markers. They also showed a significant decrease in mRNA and protein levels of insulin and leptin signaling pathway mediators. Uncoupling protein 2 (UCP2), peroxisome proliferator-activated receptor (PPAR)-α and -δ mRNA and protein levels were increased whereas mRNA levels of Sirtuin-1 (Sirt-1), glutathione peroxidase, and catalase were significantly lower in these animals. Development of all these endocrine-metabolic abnormalities was prevented by co-administration of R/S α-lipoic acid together with sucrose. OS may be actively involved in the mechanism by which unbalanced/unhealthy diet induces ß-cell dysfunction. Since metabolic-endocrine dysfunctions recorded in HS rats resembled those measured in human pre-diabetes, knowledge of its molecular mechanism could help to develop appropriate strategies to prevent the progression of this metabolic state toward type 2 diabetes (T2D).

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.

Type 2 diabetes patients educated by other patients perform at least as well as patients trained by professionals.

BACKGROUND: Diabetes education can improve the quality of care of people with diabetes, but many organizations are not equipped to manage its implementation. Involving people with diabetes in the education process can overcome the problem. Thus, we compared clinical, metabolic and psychological outcomes in people with type 2 diabetes 1 year after attending a structured diabetes education programme implemented by professional educators versus the same programme implemented by trained peers with diabetes that also provided ongoing peer support. METHODS: People with type 2 diabetes (25-75 years) were randomly assigned to attend a 4-week structured diabetes education course delivered by professional educators (control) or previously trained peers (peer). Peers also received continuing psychological support, including examples on how to apply diabetes knowledge in daily life via weekly peer cellular phone calls and bimonthly face-to-face interviews in small groups (ten patients), using a structured questionnaire related to the patient's clinical, metabolic and psychological progress. Identical outcome data from both groups were used for follow-up. RESULTS: Both groups had a comparable positive effect on clinical, metabolic and psychological indicators immediately following the programme. Over the following year, peer-educated subjects had lower A(1C) and systolic blood pressure and showed higher adherence to physical activity and better control of hypoglycaemic episodes. CONCLUSION: The non-inferiority of the peer outcomes and the mentioned improvements in this group suggest that volunteer trained peer educators and ongoing support can be successful. This approach provides an effective alternative method of education, especially in areas with limited availability of professionals and economic resources.

Antioxidant treatment prevents the development of fructose-induced abdominal adipose tissue dysfunction.

In the present study, we tested the effect of OS (oxidative stress) inhibition in rats fed on an FRD [fructose-rich diet; 10% (w/v) in drinking water] for 3 weeks. Normal adult male rats received a standard CD (commercial diet) or an FRD without or with an inhibitor of NADPH oxidase, APO (apocynin; 5 mM in drinking water; CD-APO and FRD-APO). We thereafter measured plasma OS and metabolic-endocrine markers, AAT (abdominal adipose tissue) mass and cell size, FA (fatty acid) composition (content and release), OS status, LEP (leptin) and IRS (insulin receptor substrate)-1/IRS-2 mRNAs, ROS (reactive oxygen species) production, NADPH oxidase activity and LEP release by isolated AAT adipocytes. FRD-fed rats had larger AAT mass without changes in body weight, and higher plasma levels of TAG (triacylglycerol), FAs, TBARS (thiobarbituric acid-reactive substance) and LEP. Although no significant changes in glucose and insulin plasma levels were observed in these animals, their HOMA-IR (homoeostasis model assessment of insulin resistance) values were significantly higher than those of CD. The AAT from FRD-fed rats had larger adipocytes, higher saturated FA content, higher NADPH oxidase activity, greater ROS production, a distorted FA content/release pattern, lower insulin sensitivity together with higher and lower mRNA content of LEP and IRS-1-/2 respectively, and released a larger amount of LEP. The development of all the clinical, OS, metabolic, endocrine and molecular changes induced by the FRD were significantly prevented by APO co-administration. The fact that APO treatment prevented both changes in NADPH oxidase activity and the development of all the FRD-induced AAT dysfunctions in normal rats strongly suggests that OS plays an important role in the FRD-induced MS (metabolic syndrome) phenotype.

Apocynin administration prevents the changes induced by a fructose-rich diet on rat liver metabolism and the antioxidant system.

In the present study, we investigated the role of NADPH oxidase in F (fructose)-rich-diet-induced hepatic OS (oxidative stress) and metabolic changes, and their prevention by apocynin co-administration. Wistar rats were fed for 21 days on (i) a control diet, (ii) a control diet plus 10% F in the drinking water, (iii) a control diet with apocynin in the drinking water (CA) and (iv) F plus apocynin in the drinking water (FA). Glycaemia, triglyceridaemia, NEFAs (non-esterified fatty acids) and insulinaemia were determined. In the liver, we measured (i) NADPH oxidase activity, and gene and protein expression; (ii) protein carbonyl groups, GSH and TBARSs (thiobarbituric acid-reactive substances); (iii) catalase, CuZn-SOD (superoxide dismutase) and Mn-SOD expression; (iv) liver glycogen and lipid content; (v) GK (glucokinase), G6Pase (glucose-6-phosphatase) and G6PDH (glucose-6-phosphate dehydrogenase) activities; (vi) FAS (fatty acid synthase), GPAT (glycerol-3-phosphate acyltransferase), G6Pase and G6PDH, IL-1ß (interleukin-1ß), PAI-1 (plasminogen-activator inhibitor-1) and TNFα (tumour necrosis factor α) gene expression; and (vii) IκBα (inhibitor of nuclear factor κB α) protein expression. F-fed animals had high serum TAG (triacylglycerol), NEFA and insulin levels, high liver NADPH oxidase activity/expression, increased OS markers, reduced antioxidant enzyme expression, and increased glycogen, TAG storage and GK, G6Pase and G6PDH activities. They also had high G6Pase, G6PDH, FAS, GPAT, TNFα and IL-1ß gene expression and decreased IκBα expression. Co-administration of apocynin to F-fed rats prevented the development of most of these abnormalities. In conclusion, NADPH oxidase plays a key role in F-induced hepatic OS production and probably also in the mechanism of liver steatosis, suggesting its potential usefulness for the prevention/treatment of T2DM (Type 2 diabetes mellitus).

Glycated Hemoglobin Measurement: Comparison of Three Methods Versus High Performance Liquid Chromatography.

BACKGROUND: HbA1c result provide information on metabolic control in diabetes mellitus (DM) and could also be used for its diagnosis. For its determination, the laboratory must be certified by the National Glycohemoglobin Standardization Program (NGSP) or the International Federation of Clinical Chemistry (IFCC) and comply with a strict quality control program. AIMS: To determine the correlation and agreement between HbA1c results measured by three analytical methods (enzymatic, turbidimetric, and capillary electrophoresis) versus HPLC. METHODS: Method comparison-1245 samples from equal number of subjects at 45 Association of High Complexity Laboratories (Asociación de Laboratorios de Alta Complejidad-ALAC) centers, centralizing sample processing and operator. Statistical analysis-analysis of variance (ANOVA) and nonparametric Friedman ANOVA test for related samples, means, and medians. Correlation and concordance-Pearson's correlation and linear regression, intraclass correlation coefficient (Passing and Bablock and Bland and Altman). RESULTS: The comparison of mean values obtained by the four methods showed statistically significant, but clinically irrelevant, differences: HbA1c by HPLC versus Electrophoresis 0.06% (0.42 mmol/mol) P = .000 (± 1.96 DS -0.070 -0.047), Enzymatic 0.087% (1 mmol/mol) P = .000 (± 1.96 DS 0.077 0.098), Turbidimetric 0.056% (0.38 mmol/mol) P = 0.000 (± 1.96 DS -0.067 -0.044). Their concordance showed intraclass correlation of single measures of 0.982 P < .001 (95% CI 0.987 - 0.9838). CONCLUSIONS: The three methods present low variability and high correlation versus the HPLC.

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.

One in Seven Insulin-Treated Patients in Developing Countries Reported Poor Persistence with Insulin Therapy: Real World Evidence from the Cross-Sectional International Diabetes Management Practices Study (IDMPS).

INTRODUCTION: Although poor adherence to insulin is widely recognised, periodic discontinuation of insulin may cause more severe hyperglycaemia than poor adherence. We assessed persistence with insulin therapy in patients with type 1 (T1D) or type 2 diabetes (T2D) in developing countries and the reasons for insulin discontinuation. METHODS: The International Diabetes Management Practices Study collected real-world data from developing countries in seven waves between 2005 and 2017. In Wave 7 (2016-2017), we asked adult patients with T1D and insulin-treated T2D to report whether they had ever discontinued insulin, the estimated duration of discontinuation and underlying reasons. RESULTS: Among 8303 patients recruited from 24 countries by 620 physicians, 4596 were insulin-treated (T1D: 2000; T2D: 2596). In patients with T1D, 14.0% (95% CI: 12.5-15.6) reported having self-discontinued insulin for a median duration of 1.0 month (IQR: 0.5, 3.5). The respective figures in patients with T2D were 13.7% (12.4-15.1) and 2.0 months (IQR: 1.0, 6.0). The main reasons for discontinuation were impact on social life (T1D: 41.0%; T2D: 30.5%), cost of medications and test strips (T1D: 34.4%; T2D: 24.5%), fear of hypoglycaemia (T1D: 26.7%; T2D: 28.0%) and lack of support (T1D: 26.4%; T2D: 25.9%). Other factors included age < 40 years, non-university education and short disease duration (T1D: ≤ 1 year; T2D: > 1-≤ 5 years). Patients with T1D who did not perform self-monitoring of blood glucose (SMBG) or self-adjust their insulin dosage, and patients with T1D or T2D without glucose meters were less likely to persist with insulin. Nearly 50% of patients who reported poor persistence had HbA1c > 75 mmol/mol (> 9%) and > 50% of physicians recommended diabetes education programmes to improve treatment persistence. CONCLUSION: In developing countries, poor persistence with insulin is common among insulin-treated patients, supporting calls for urgent actions to ensure easy access to insulin, tools for SMBG and education.

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.

Impact of diabetes education and self-management on the quality of care for people with type 1 diabetes mellitus in the Middle East (the International Diabetes Mellitus Practices Study, IDMPS).

AIMS: Self-management (self-monitoring of blood glucose, plus self-adjustment of insulin dose) is important in diabetes care, but its complexity presents a barrier to wider implementation, which hinders attainment and maintenance of glycemic targets. More evidence on self-management is needed to increase its implementation and improve metabolic outcomes. METHODS: Data from 1316 participants with type 1 diabetes mellitus who were enrolled from Middle East countries into the International Diabetes Management Practices Study (IDMPS), a multinational observational survey, were analyzed to assess the impact of education on disease management and outcomes. RESULTS: A majority (78%) of participants failed to achieve glycemic target (HbA1c < 7.0% [<53 mmol/mol]). Participants who had received diabetes education (59%) were more likely to practice self-management than those who had not (odds ratio [OR]: 2.51; 95% confidence interval [CI]: 1.7-3.69; p < 0.001), and those who practiced self-management were more likely to attain target HbA1c than those who did not (OR: 1.49; 95% CI: 1.06-2.09; p = 0.023). CONCLUSIONS: These relationships between diabetes education, self-management and glycemic control suggest that diabetes education provides knowledge and skills to optimize self-management, favoring HbA1c target attainment. Middle East health authorities should search for ways to facilitate access to diabetes education to optimize treatment outcomes.

Diabetes education and health insurance: How they affect the quality of care provided to people with type 1 diabetes in Latin America. Data from the International Diabetes Mellitus Practices Study (IDMPS).

AIMS: This study aimed to evaluate the impact of diabetes education and access to healthcare coverage on disease management and outcomes in Latin America. METHODS: Data were obtained from a sub-analysis of 2693 patients with type 1 diabetes mellitus recruited from 9 Latin American countries as part of the International Diabetes Mellitus Practices Study (IDMPS), a multinational, observational survey of diabetes treatment in developing regions. RESULTS: Results from the Latin American cohort show that only 25% of participants met HbA1c target value (< 7% [53 mmol/mol]). Attainment of this target was significantly higher among participants who had received diabetes education than those who hadn't (28% vs. 19%, p < 0.001), and among those who practiced self-management (27% vs. 21% no self-management, p = 0.001). Multivariate analysis showed that participants who had received diabetes education were more likely to manage their diabetes (OR:1.65 [95% CI: 1.24, 2.19]; p = 0.001), and to attain HbA1c target values (OR:1.48 [95% CI: 1.14, 1.93]; p = 0.003). CONCLUSIONS: Given the association between uncontrolled diabetes and long-term complications, health authorities and care providers should increase efforts to ensure widespread healthcare coverage and access to self-management education to reduce the socioeconomic and humanistic burden of type 1 diabetes.

INGAP-PP effects on ß-cell mass and function are related to its positive effect on islet angiogenesis and VEGFA production.

Our aim was to determine whether islet angiogenesis and VEGFA production/release participate in the mechanism by which INGAP-PP enhances ß-cell function and mass. We used two models: a) in vivo (normal rats injected with INGAP-PP for 10 days) and b) in vitro (normal islets cultured for 4 days with INGAP-PP, VEGFA, Rapamycin, and the specific VEGF-Receptor inhibitor, SU5416). INGAP-PP administration enhanced insulin secretion, ß-cell mass, islet vascularization, and angiogenesis without affecting glucose homeostasis. Normal islets cultured with INGAP-PP and VEGFA increased insulin and VEGFA secretion while apoptosis decreased. INGAP-PP-induced effects were prevented by both Rapamycin and SU5416. INGAP-PP effects on ß-cell mass and function were significantly associated with a positive effect on islet angiogenesis and VEGFA production/release. VEGF-A possibly potentiates INGAP-PP effect through mTORC pathway.

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).

Liver carbohydrates metabolism: A new islet-neogenesis associated protein peptide (INGAP-PP) target.

Islet-Neogenesis Associated Protein-Pentadecapeptide (INGAP-PP) increases ß-cell mass and enhances glucose and amino acids-induced insulin secretion. Our aim was to demonstrate its effect on liver metabolism. For that purpose, adult male Wistar rats were injected twice-daily (10 days) with saline solution or INGAP-PP (250 µg). Thereafter, serum glucose, triglyceride and insulin levels were measured and homeostasis model assessment (HOMA-IR) and hepatic insulin sensitivity (HIS) were determined. Liver glucokinase and glucose-6-phosphatase (G-6-Pase) expression and activity, phosphoenolpyruvate carboxykinase (PEPCK) expression, phosphofructokinase-2 (PFK-2) protein content, P-Akt/Akt and glycogen synthase kinase-3ß (P-GSK3/GSK3) protein ratios and glycogen deposit were also determined. Additionally, glucokinase activity and G-6-Pase and PEPCK gene expression were also determined in isolated hepatocytes from normal rats incubated with INGAP-PP (5 µg/ml). INGAP-PP administration did not modify any of the serum parameters tested but significantly increased activity of liver glucokinase and the protein level of its cytosolic activator, PFK-2. Conversely, INGAP-PP treated rats decreased gene expression and enzyme activity of gluconeogenic enzymes, G-6-Pase and PEPCK. They also showed a higher glycogen deposit and P-GSK3/GSK3 and P-Akt/Akt ratio. In isolated hepatocytes, INGAP-PP increased GK activity and decreased G-6-Pase and PEPCK expression. These results demonstrate a direct effect of INGAP-PP on the liver acting through P-Akt signaling pathway. INGAP-PP enhances liver glucose metabolism and deposit and reduces its production/output, thereby contributing to maintain normal glucose homeostasis. These results reinforce the concept that INGAP-PP might become a useful tool to treat people with impaired islet/liver glucose metabolism as it occurs in T2D.

Aspects of Multicomponent Integrated Care Promote Sustained Improvement in Surrogate Clinical Outcomes: A Systematic Review and Meta-analysis.

OBJECTIVE: The implementation of the Chronic Care Model (CCM) improves health care quality. We examined the sustained effectiveness of multicomponent integrated care in type 2 diabetes. RESEARCH DESIGN AND METHODS: We searched PubMed and Ovid MEDLINE (January 2000-August 2016) and identified randomized controlled trials comprising two or more quality improvement strategies from two or more domains (health system, health care providers, or patients) lasting ≥12 months with one or more clinical outcomes. Two reviewers extracted data and appraised the reporting quality. RESULTS: In a meta-analysis of 181 trials (N = 135,112), random-effects modeling revealed pooled mean differences in HbA1c of -0.28% (95% CI -0.35 to -0.21) (-3.1 mmol/mol [-3.9 to -2.3]), in systolic blood pressure (SBP) of -2.3 mmHg (-3.1 to -1.4), in diastolic blood pressure (DBP) of -1.1 mmHg (-1.5 to -0.6), and in LDL cholesterol (LDL-C) of -0.14 mmol/L (-0.21 to -0.07), with greater effects in patients with LDL-C ≥3.4 mmol/L (-0.31 vs. -0.10 mmol/L for <3.4 mmol/L; Pdifference = 0.013), studies from Asia (HbA1c -0.51% vs. -0.23% for North America [-5.5 vs. -2.5 mmol/mol]; Pdifference = 0.046), and studies lasting >12 months (SBP -3.4 vs. -1.4 mmHg, Pdifference = 0.034; DBP -1.7 vs. -0.7 mmHg, Pdifference = 0.047; LDL-C -0.21 vs. -0.07 mmol/L for 12-month studies, Pdifference = 0.049). Patients with median age <60 years had greater HbA1c reduction (-0.35% vs. -0.18% for ≥60 years [-3.8 vs. -2.0 mmol/mol]; Pdifference = 0.029). Team change, patient education/self-management, and improved patient-provider communication had the largest effect sizes (0.28-0.36% [3.0-3.9 mmol/mol]). CONCLUSIONS: Despite the small effect size of multicomponent integrated care (in part attenuated by good background care), team-based care with better information flow may improve patient-provider communication and self-management in patients who are young, with suboptimal control, and in low-resource settings.

Health inequalities and the impact on the prevalence of cardiovascular risk factors and chronic complications in Argentina: a study on national risk factors surveys. / Desigualdades en salud, su impacto sobre la prevalencia de factores de riesgo cardiovascular y el desarrollo de sus complicaciones crónicas en Argentina: estudio sobre Encuesta Nacional de Factores de Riesgo.

BACKGROUND: In Argentina, there is evidence of health inequalities, measured both at the general level and also using income as a parameter of social status. However, few studies address the issue of health equality in chronic diseases such as cardiovascular risk factors. OBJECTIVE: To describe health inequalities, using cardiovascular risk factors as a tracer for chronic diseases in different areas of the country and over time. In addition, we aim to identify differences in the quality of care provided to people with cardiovascular risk factors, between 2005 and 2009. METHODS: This is an observational study, which used descriptive and quantitative methods. Data from the National Risk Factors Survey from 2005 and 2009 in the cohorts who have chronic diseases (hypertension, diabetes, dyslipidemia and overweight/obesity) were analyzed to assess associations between health status and several demographic, epidemiological and socioeconomic variables. Additionally, clinical and metabolic characteristics of people with diabetes and other cardiovascular risks factors were analyzed in 2005 and 2009 using the database Quality of Diabetes Care (QUALIDIAB). RESULTS: Cardiovascular risk factors are more frequent in people with lower socioeconomic status, regardless of the indicator. The inequalities detected showed the worst indicators in strata with lower education and income, with the same results both nationwide and separated by region. This inequalities were more pronounced in 2009, and their magnitude changed by region and cardiovascular risk factor. From 2005 to 2009, body mass index, blood glucose and HbA1c value increased. In contrast, both systolic blood pressure and triglycerides decreased, with no significant changes in total cholesterol and diastolic blood pressure. CONCLUSION: Cardiovascular risk factors present inequalities attributed to social status manifesting at both national and regional levels.

INTRODUCCIÓN: Argentina muestra evidencia de desigualdades en salud medida, tanto a nivel general como utilizando el ingreso como parámetro de posición social. Sin embargo, pocos estudios abordan la problemática de la equidad en salud a nivel de enfermedades crónicas como los factores de riesgo cardiovascular. OBJETIVO: Describir las desigualdades en salud utilizando como trazador de enfermedades crónicas a los factores de riesgo cardiovascular a nivel subnacional y su evolución temporal. Para complementar, se busca identificar las diferencias en la calidad de atención brindada a personas con factores de riesgo cardiovascular entre 2005 y 2009. MÉTODOS: Estudio observacional y cuantitativo basado en métodos descriptivos. Se analizó la Encuesta Nacional de Factores de Riesgo 2005 y 2009 para evaluar hipertensión, diabetes, dislipemia y sobrepeso/obesidad en las cohortes correspondientes, las asociaciones entre el estado de salud y diversas variables demográficas, epidemiológicas y socioeconómicas. Adicionalmente, y utilizando la base de datos del registro Quality of Diabetes Care (QUALIDIAB), se analizaron las características clínicas y metabólicas de las personas con diabetes y otros factores de riesgo cardiovascular en los años 2005 y 2009. RESULTADOS: Los factores de riesgo cardiovascular se presentan más frecuentemente en personas con menor posición socioeconómica, independientemente del indicador considerado. Las desigualdades detectadas mostraron peores indicadores en los estratos con educación e ingreso más bajo, manifestándose tanto a nivel nacional como regional. En general, son más acentuadas en el año 2009. Su magnitud varió según región y factor de riesgo cardiovascular considerado. De 2005 a 2009, se incrementan los valores de índice de masa corporal, glucemia y hemoglobina glicosilada, disminuyeron los de presión arterial sistólica y los triglicéridos, sin cambios significativos en el colesterol total y presión arterial diastólica. CONCLUSIONES: En nuestro medio, los factores de riesgo cardiovascular presentan desigualdades condicionadas por su posición social, manifestándose tanto a nivel nacional como regional.

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.

Relation between cost of drug treatment and body mass index in people with type 2 diabetes in Latin America.

AIMS: Despite the frequent association of obesity with type 2 diabetes (T2D), the effect of the former on the cost of drug treatment of the latest has not been specifically addressed. We studied the association of overweight/obesity on the cost of drug treatment of hyperglycemia, hypertension and dyslipidemia in a population with T2D. METHODS: This observational study utilized data from the QUALIDIAB database on 3,099 T2D patients seen in Diabetes Centers in Argentina, Chile, Colombia, Peru, and Venezuela. Data were grouped according to body mass index (BMI) as Normal (18.5≤BMI<25), Overweight (25≤BMI<30), and Obese (BMI≥30). Thereafter, we assessed clinical and metabolic data and cost of drug treatment in each category. Statistical analyses included group comparisons for continuous variables (parametric or non-parametric tests), Chi-square tests for differences between proportions, and multivariable regression analysis to assess the association between BMI and monthly cost of drug treatment. RESULTS: Although all groups showed comparable degree of glycometabolic control (FBG, HbA1c), we found significant differences in other metabolic control indicators. Total cost of drug treatment of hyperglycemia and associated cardiovascular risk factors (CVRF) increased significantly (p<0.001) with increment of BMI. Hyperglycemia treatment cost showed a significant increase concordant with BMI whereas hypertension and dyslipidemia did not. Despite different values and percentages of increase, this growing cost profile was reproduced in every participating country. BMI significantly and independently affected hyperglycemia treatment cost. CONCLUSIONS: Our study shows for the first time that BMI significantly increases total expenditure on drugs for T2D and its associated CVRF treatment in Latin America.

Multistrategic approach to improve quality of care of people with diabetes at the primary care level: Study design and baseline data.

AIM: To test the one year-post effect of an integrated diabetes care program that includes system changes, education, registry (clinical, metabolic and therapeutic indicators) and disease management (DIAPREM), implemented at primary care level, on care outcomes and costs. METHODS: We randomly selected 15 physicians and 15 nurses from primary care units of La Matanza County to be trained (Intervention-IG) and another 15 physicians/nurses to use as controls (Control-CG). Each physician-nurse team controlled and followed up 10 patients with type 2 diabetes for one year; both groups use structured medical data registry. Patients in IG had quarterly clinical appointments whereas those in CG received traditional care. DIAPREM includes system changes (use of guidelines, programmed quarterly controls and yearly visits to the specialist) and education (physicians' and nurses' training courses). Statistical data analysis included parametric/nonparametric tests according to data distribution profile and Chi-squared test for proportions. RESULTS: Baseline data from both groups showed comparable values and 20-30% of them did not perform HbA1c and lipid profile measurements. Majority were obese, 59% had HbA1C ≥7%, 86% fasting blood glucose ≥100mg/dL, 45%, total cholesterol ≥200mg/dL, and 92% abnormal HDL- and LDL-cholesterol values. Similarly, micro and macroangiopathic complications had not been detected in the previous year. Most patients received oral antidiabetic agents (monotherapy), and one third was on insulin (mostly a single dose of an intermediate/long-acting formulation). Most people with hypertension received specific drug treatment but only half of them reached target values; dyslipidemia treatment showed similar data. CONCLUSIONS: Baseline data demonstrated the need of implementing an intervention to improve diabetes care and treatment outcomes.