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.

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.

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.

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.

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.

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.

Increasing DNA Isolation Performance from Blood Cells Using a Modified Commercial Low-Cost Reagent.

BACKGROUND: Genomic studies facilitate comprehension of the pathophysiology, diagnosis, and treatment of chronic diseases. Such studies require sufficient and good quality DNA isolated from a large number of blood samples. This study attempts to obtain a high-quality genomic DNA isolated from a large number of blood samples using a simple and cheap method. METHODS: The EasyPure® Genomic DNA Kit (Transgen Biotech) was modified to increase the amount of DNA recovery: a few steps and two additional column elutions were added to the original manufacturer´s procedure. RESULTS: The amount of DNA isolated from frozen blood samples increased by an average of 56%. Its 260/280 ratio and electrophoretic mobility properties make it suitable for genomic studies. CONCLUSIONS: A relatively low-cost commercial column and a simple modification of the manufacturer´s protocol, provided a simple and cheap procedure to isolate high-quality DNA from a large number of blood samples suitable for genomic studies.

Diabetes management and treatment approaches outside of North America and West Europe in 2006 and 2015.

AIMS: The impact of introducing new classes of glucose-lowering medication (GLM) on diabetes management remains unclear, especially outside North America and Western Europe. Therefore, we aimed to analyse trends in glycaemic control and the usage of new and old GLMs in people with type 2 diabetes from 2006 to 2015. METHODS: Summary data from clinical services from nine countries outside North America and Western Europe were collected and pooled for statistical analysis. Each site summarized individual-level data from out-patient medical records for 2006 and 2015. Data included: demographics; HbA1c and fasting plasma glucose levels; and the proportions of patients taking GLM as monotherapy, combination therapy and/or insulin. RESULTS: Between 2006 and 2015, glycaemic control remained stable, although body mass index and duration of diabetes increased in most sites. The proportion of people on GLM increased, and the therapeutic regimens became more complex. There were increases in the use of insulin and triple therapy in most sites, while monotherapy, particularly in relation to sulphonylureas, decreased. Despite the introduction of new GLMs, such as DPP-4 inhibitors, insulin use increased over time. CONCLUSIONS: There was no clear evidence that the use of new classes of GLMs was associated with improvements in glycaemic control or reduced the reliance on insulin. These findings were consistent across a range of economic and geographic settings.

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.

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.

Diabetes primary prevention program: New insights from data analysis of recruitment period.

BACKGROUND: Primary Prevention of Diabetes Program in Buenos Aires Province evaluates the effectiveness of adopting healthy lifestyle to prevent type 2 diabetes (T2D) in people at high risk of developing it. We aimed to present preliminary data analysis of FINDRISC and laboratory measurements taken during recruitment of people for the Primary Prevention of Diabetes Program in Buenos Aires Province in the cities of La Plata, Berisso, and Ensenada, Argentina. METHODS: People were recruited through population approach (house-to-house survey by FINDRISC in randomized areas) and opportunistic approach (FINDRISC completed by participants during consultations for nonrelated prediabetes/diabetes symptoms in public and private primary care centres of cities involved). In people with FINDRISC score ≥ 13 points, we evaluated blood concentrations of HbA1c , creatinine, lipids, and an oral glucose tolerance test (OGTT). RESULTS: Approximately 3415 individuals completed the FINDRISC populational survey and 344 the opportunistic survey; 43% of the 2 groups scored over 13 points; 2.8 and 75.4% of them, respectively, took the prescribed OGTT. Approximately 53.7% of the OGTT showed normal values and 5.2% unknown T2D. The remaining cases showed 69.5% impaired fasting glucose, 13.6% impaired glucose tolerance, and 16.9% both impairments. HbA1c values showed significant differences compared with normal glucose tolerance (4.96 ± 0.43%), prediabetes (5.28 ± 0.51%), and T2D (5.60 ± 0.51%). Participants with prediabetes and T2D showed a predominant increase in low-density lipoprotein-cholesterol values. In prediabetes, >50% showed insulin resistance. CONCLUSIONS: People with prediabetes/T2D had dyslipidemia associated with insulin resistance, which promotes the development of T2D and cardiovascular disease. Thus, it merits its appropriate treatment.

Improving diabetes care at primary care level with a multistrategic approach: results of the DIAPREM programme.

AIM: To present results, 1 year postimplementation at primary care level, of an integrated diabetes care programme including systemic changes, education, registry (clinical, metabolic, and therapeutic indicators), and disease management (DIAPREM). METHODS: We randomly selected and trained 15 physicians and 15 nurses from primary care units of La Matanza County (intervention-IG) and another 15 physicians/nurses to participate as controls (control-CG). Each physician-nurse team controlled and followed up 10 patients with type 2 diabetes for 1 year; both groups used structured medical records. Patients in IG had quarterly clinical appointments, whereas those in CG received traditional care. Statistical data analysis included parametric/nonparametric tests according to data distribution profile and Chi-squared test for proportions. RESULTS: After 12 months, the dropout rate was significantly lower in IG than in CG. Whereas in IG HbA1c, blood pressure and lipid profile levels significantly decreased, no changes were recorded in CG. Drug prescriptions showed no significant changes in IG except a decrease in oral monotherapy. CONCLUSIONS: DIAPREM is an expedient and simple multistrategic model to implement at the primary care level in order to decrease patient dropout and improve control and treatment adherence, and quality of care of people with diabetes.

VMP1-related autophagy induced by a fructose-rich diet in ß-cells: its prevention by incretins.

The aim of the present study was to demonstrate the role of autophagy and incretins in the fructose-induced alteration of ß-cell mass and function. Normal Wistar rats were fed (3 weeks) with a commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrine parameters, ß-cell mass, morphology/ultrastructure and apoptosis, vacuole membrane protein 1 (VMP1) expression and glucose-stimulated insulin secretion (GSIS) were studied. Complementary to this, islets isolated from normal rats were cultured (3 days) without (C) or with F and F + exendin-4 or chloroquine. Expression of autophagy-related proteins [VMP1 and microtubule-associated protein light chain 3 (LC3)], apoptotic/antiapoptotic markers (caspase-3 and Bcl-2), GSIS and insulin mRNA levels were measured. F rats developed impaired glucose tolerance (IGT) and a significant increase in plasma triacylglycerols, thiobarbituric acid-reactive substances, insulin levels, homoeostasis model assessment (HOMA) for insulin resistance (HOMA-IR) and ß-cell function (HOMA-ß) indices. A significant reduction in ß-cell mass was associated with an increased apoptotic rate and morphological/ultrastructural changes indicative of autophagic activity. All these changes were prevented by either sitagliptin or exendin-4. In cultured islets, F significantly enhanced insulin mRNA and GSIS, decreased Bcl-2 mRNA levels and increased caspase-3 expression. Chloroquine reduced these changes, suggesting the participation of autophagy in this process. Indeed, F induced the increase of both VMP1 expression and LC3-II, suggesting that VMP1-related autophagy is activated in injured ß-cells. Exendin-4 prevented islet-cell damage and autophagy development. VMP1-related autophagy is a reactive process against F-induced islet dysfunction, being prevented by exendin-4 treatment. This knowledge could help in the use of autophagy as a potential target for preventing progression from IGT to type 2 diabetes mellitus.

Resource use associated with type 2 diabetes in Africa, the Middle East, South Asia, Eurasia and Turkey: results from the International Diabetes Management Practice Study (IDMPS).

OBJECTIVE: Type 2 diabetes (T2D) and its complications form a global healthcare burden but the exact impact in some geographical regions is still not well documented. We describe the healthcare resource usage (HRU) associated with T2D in Africa, the Middle East, South Asia, Eurasia and Turkey. RESEARCH DESIGN AND METHODS: In the fifth wave of the International Diabetes Management Practices Study (IDMPS; 2011-2012), we collected self-reported and physician-reported cross-sectional data from 8156 patients from 18 countries across 5 regions, including different types of HRU in the previous 3-6 months. Negative binomial regression was used to identify parameters associated with HRU, using incidence rate ratios (IRRs) to express associations. RESULTS: Patients in Africa (n=2220), the Middle East (n=2065), Eurasia (n=1843), South Asia (n=1195) and Turkey (n=842) experienced an annual hospitalization rate (mean±SD) of 0.6±1.9, 0.3±1.2, 1.7±4.1, 0.4±1.5 and 1.3±2.7, respectively. The annual number of diabetes-related inpatient days (mean±SD) was 4.7±22.7, 1.1±6.1, 16.0±30.0, 1.5±6.8 and 10.8±34.3, respectively. Despite some inter-regional heterogeneity, macrovascular complications (IRRs varying between 1.4 and 8.9), microvascular complications (IRRs varying between 3.4 and 4.3) and, to a large extent, inadequate glycemic control (IRRs varying between 1.89 and 10.1), were independent parameters associated with hospitalization in these respective regions. CONCLUSIONS: In non-Western countries, macrovascular/microvascular complications and inadequate glycemic control were common and important parameters associated with increased HRU.

White Adipose Tissue and Circadian Rhythm Dysfunctions in Obesity: Pathogenesis and Available Therapies.

A combined neuroendocrine, metabolic, and chronobiological view can help to better understand the multiple and complex mechanisms involved in obesity development and maintenance, as well as to provide new effective approaches for its control and treatment. Indeed, we have currently updated data on the whole adipogenic process involved in white adipose tissue (WAT) mass expansion, namely due to a mechanism whereby WAT cells become hypertrophic, thus inducing a serious local (WAT) inflammatory condition that in turn, will impair not only the cross-talk between the hypothalamus and the WAT, but also favoring the development of deep and widespread neuroendocrine-metabolic dysfunction. Moreover, we also have revisited the circadian clock genes involved in dysfunctional WAT mass expansion and the mechanisms that may lead to obesity development, including early metabolic dysfunctions, enhanced oxidative stress and distorted energy homeostasis. The epigenetic changes of clock genes driving metabolic disease and obesity development have also been included in this review. Finally, we have also underlined the relevance of metabolic homeostasis regulation by central and peripheral organ clocks, sleep disturbances, nutrients, and feeding time, as key factors in obesity development as well as both, classical and chronotherapeutic approaches for its prevention and treatment.