Effect of a family and interdisciplinary intervention to prevent T2D: randomized clinical trial.

BACKGROUND: Lifestyle changes can reduce the risk of T2D; however, no study has evaluated the effect of a lifestyle intervention involving patients´ family. The aim of this study was to compare the impact of an interdisciplinary family (FI) Vs individual intervention (II) on glucose metabolism, insulin resistance (IR), pancreatic ß-cell function and cardiovascular risk markers in patients with prediabetes, as well as to measure the impact on their families' metabolic risk. METHODS: Randomized Clinical Trial (RCT) to compare the impact of FI and II on IR and pancreatic ß-cell function in subjects with prediabetes. There were 122 subjects with prediabetes (and 101 family members) randomized to FI or II. Data were collected in 2015-2016 and analyzed in 2017-2018. FI group had the support of their family members, who also received personalized diet and exercise recommendations; patients and their family members attended monthly a lifestyle enhancement program. II group received personalized diet and exercise recommendations. The follow-up was for 12 months. Glucose, IR, pancreatic ß-cell function and secondary outcomes (body composition and lipid profile) were assessed at baseline, 6 and 12 months. RESULTS: FI group improved area under the glucose curve (AUC) (from 18,597 ± 2611 to 17,237 ± 2792, p = 0.004) and the Matsuda index (from 3.5 ± 2.3 to 4.7 ± 3.5, p = 0.05) at 12 months. II group improved Disposition Index (from 1.5 ± 0.4 to 1.9 ± 0.73, p < .0001) at 12 months. The improvements achieved in weight and lipids at 6 months, were lost in II group at 12 moths, whereas in FI persisted. Adherence up to 12 months was not different between the study groups (FI 56% Vs II 60%). CONCLUSIONS: FI intervention was more effective by improving glucose AUC, insulin sensitivity and lipid profile, besides that, metabolic risk in family members of the FI group was maintained, while the risk of II group was increased. TRIAL REGISTRATION: This study was retrospectively registered at clinicaltrials.gov on December 15, 2015 (NTC026365646).

Chronic continuous exenatide infusion does not cause pancreatic inflammation and ductal hyperplasia in non-human primates.

In this study, we aimed to evaluate the effects of exenatide (EXE) treatment on exocrine pancreas of nonhuman primates. To this end, 52 baboons (Papio hamadryas) underwent partial pancreatectomy, followed by continuous infusion of EXE or saline (SAL) for 14 weeks. Histological analysis, immunohistochemistry, Computer Assisted Stereology Toolbox morphometry, and immunofluorescence staining were performed at baseline and after treatment. The EXE treatment did not induce pancreatitis, parenchymal or periductal inflammatory cell accumulation, ductal hyperplasia, or dysplastic lesions/pancreatic intraepithelial neoplasia. At study end, Ki-67-positive (proliferating) acinar cell number did not change, compared with baseline, in either group. Ki-67-positive ductal cells increased after EXE treatment (P = 0.04). However, the change in Ki-67-positive ductal cell number did not differ significantly between the EXE and SAL groups (P = 0.13). M-30-positive (apoptotic) acinar and ductal cell number did not change after SAL or EXE treatment. No changes in ductal density and volume were observed after EXE or SAL. Interestingly, by triple-immunofluorescence staining, we detected c-kit (a marker of cell transdifferentiation) positive ductal cells co-expressing insulin in ducts only in the EXE group at study end, suggesting that EXE may promote the differentiation of ductal cells toward a ß-cell phenotype. In conclusion, 14 weeks of EXE treatment did not exert any negative effect on exocrine pancreas, by inducing either pancreatic inflammation or hyperplasia/dysplasia in nonhuman primates.

Delta cell death in the islet of Langerhans and the progression from normal glucose tolerance to type 2 diabetes in non-human primates (baboon, Papio hamadryas).

AIMS/HYPOTHESIS: The cellular composition of the islet of Langerhans is essential to ensure its physiological function. Morphophysiological islet abnormalities are present in type 2 diabetes but the relationship between fasting plasma glucose (FPG) and islet cell composition, particularly the role of delta cells, is unknown. We explored these questions in pancreases from baboons (Papio hamadryas) with FPG ranging from normal to type 2 diabetic values. METHODS: We measured the volumes of alpha, beta and delta cells and amyloid in pancreatic islets of 40 baboons (Group 1 [G1]: FPG < 4.44 mmol/l [n = 10]; G2: FPG = 4.44-5.26 mmol/l [n = 9]; G3: FPG = 5.27-6.94 mmol/l [n = 9]; G4: FPG > 6.94 mmol/l [n = 12]) and correlated islet composition with metabolic and hormonal variables. We also performed confocal microscopy including TUNEL, caspase-3, and anti-caspase cleavage product of cytokeratin 18 (M30) immunostaining, electron microscopy, and immuno-electron microscopy with anti-somatostatin antibodies in baboon pancreases. RESULTS: Amyloidosis preceded the decrease in beta cell volume. Alpha cell volume increased ∼ 50% in G3 and G4 (p < 0.05), while delta cell volume decreased in these groups by 31% and 39%, respectively (p < 0.05). In G4, glucagon levels were higher, while insulin and HOMA index of beta cell function were lower than in the other groups. Immunostaining of G4 pancreatic sections with TUNEL, caspase-3 and M30 showed apoptosis of beta and delta cells, which was also confirmed by immuno-electron microscopy with anti-somatostatin antibodies. CONCLUSIONS/INTERPRETATION: In diabetic baboons, changes in islet composition correlate with amyloid deposition, with increased alpha cell and decreased beta and delta cell volume and number due to apoptosis. These data argue for an important role of delta cells in type 2 diabetes.

Pancreatic beta cell function and insulin resistance profiles in first-degree relatives of patients with prediabetes and type 2 diabetes.

AIMS: To evaluate insulin secretion and insulin resistance profiles in individuals with family history of prediabetes and type 2 diabetes. METHODS: This was a cross-sectional study to evaluate clinical and metabolic profiles between individuals with type 2 diabetes, prediabetes and their relatives. There were 911 subjects divided into five groups: (i) normoglycemic (NG), (ii) type 2 diabetes, (iii) prediabetes, (iv) first-degree relatives of patients with type 2 diabetes (famT2D), and (v) first-degree relatives of patients with prediabetes (famPD); anthropometrical, biochemical and nutritional evaluation, as well as insulin resistance and pancreatic beta cell function measurement was performed by oral glucose tolerance to compare between groups. RESULTS: The most prevalent type 2 diabetes risk factors were dyslipidemia (81%), family history of type 2 diabetes (76%), central obesity (73%), male sex (63%), and sedentary lifestyle (60%), and most of them were progressively associated to prediabetes and type 2 diabetes groups. Insulin sensitivity was lower in famT2D groups in comparison to NG group (p < 0.0001). FamPD and famT2D had a 10% lower pancreatic beta cell function (DI) than the NG group (NG group 2.78 ± 1.0, famPD 2.5 ± 0.85, famT2D 2.4 ± 0.75, p˂0.001). CONCLUSIONS: FamPD and famT2D patients had lower pancreatic beta cell function than NG patients, highlighting that defects in insulin secretion and insulin sensitivity appear long time before the development of hyperglycemia in patients genetically predisposed.

Correlation and comparison between different measurement sites of waist circumference and cardiovascular risk in children: a systematic review and meta-analysis.

BACKGROUND: waist circumference (WC) is a component of metabolic syndrome (MetS) and an excellent marker for the risk of cardiovascular disease (CVD) in children. This study aimed to provide information on the anatomical measurement sites of WC and their comparative correlation with MetS and its components in children. METHODS: the literature search included papers published between January 2005 and September 2023 that met the following criteria: pediatric patients (2-18 years), WC measurement at different anatomical sites (≥ 2), and CVD risk by MetS. The quality of each study was determined using the STROBE and modified GRADE scales. The meta-analysis evaluated the WCiliac-crest and WCmiddle. RESULTS: five observational studies (total population: 1,224) were included. WC was measured at 2-4 anatomical sites. In all studies, the correlations between different WC measurement sites and CVD risk were similar. The STROBE assessment ranged from 12-20/22 and the GRADE was A for all the articles. The meta-analysis showed that the heterogeneity (I2 test) of the WCiliac-crest and WCmiddle with CVD variables was substantial. CONCLUSION: All WC measurement sites showed adequate correlation with CVD risk, with some small individual differences. WCnarrow and WCumbilucus have adequate consistency and could be excellent alternatives in daily clinical practice because of their ease of measurement. Further studies are needed to evaluate the correlation between different WC measurement sites and CVD risk in children stratified according to pubertal stage and sex.

Effect of metformin and metformin/linagliptin on gut microbiota in patients with prediabetes.

Lifestyle modifications, metformin, and linagliptin reduce the incidence of type 2 diabetes (T2D) in people with prediabetes. The gut microbiota (GM) may enhance such interventions' efficacy. We determined the effect of linagliptin/metformin (LM) vs metformin (M) on GM composition and its relationship to insulin sensitivity (IS) and pancreatic ß-cell function (Pßf) in patients with prediabetes. A cross-sectional study was conducted at different times: basal, six, and twelve months in 167 Mexican adults with prediabetes. These treatments increased the abundance of GM SCFA-producing bacteria M (Fusicatenibacter and Blautia) and LM (Roseburia, Bifidobacterium, and [Eubacterium] hallii group). We performed a mediation analysis with structural equation models (SEM). In conclusion, M and LM therapies improve insulin sensitivity and Pßf in prediabetics. GM is partially associated with these improvements since the SEM models suggest a weak association between specific bacterial genera and improvements in IS and Pßf.

Safety of the oral methionine load test: effects on the clinical performance and laboratory tests.

INTRODUCTION: Hyperhomocysteinemia is a prothrombotic risk factor. Homocysteine is evaluated during fasting and after an oral methionine load (OML). AIM: To determine the safety of the OML test according to the general performance status and clinical laboratory tests. We studied healthy nonsmoking volunteers and patients with several thrombotic conditions. Before and after receiving an OML, blood samples were obtained to perform several laboratory tests. We also evaluated acute and subacute adverse effects and 30-day associated morbidity and mortality. Of 353 individuals, three were eliminated because they did not tolerate the OML. We studied 175 healthy individuals and 175 patients without age differences. After OML, mild to moderate clinical abnormalities were recorded in 78 subjects (22.1%): nausea (n = 69; 88.5%), dizziness (n = 13; 16.7%) and decreased or increased blood pressure (n = 8; 10.2%). Nausea always disappeared after breakfast in affected individuals. Prevalence of complications was similar in patients and controls. No patient required hospitalization and there was no mortality during the 30-day study period. In conclusion, OML test had no significant undesirable effects on the clinical status or the general laboratory tests of patients and healthy controls. Some mild and moderate symptoms associated with OML tests were observed, and OML test did not negatively affect general laboratory tests. OML test is a safe diagnostic procedure in patients with previous thrombotic events (and with the consequent associated risk factors such as diabetes mellitus or dyslipidemia) and in healthy subjects.

Doxycycline Prevents Preclinical Atherosclerosis, Pancreatic Islet Loss and Improves Insulin Secretion after Glycemic Stimulation: Preclinical Study in Individuals with a High-Fat Diet.

Doxycycline (Doxy) is an antibiotic, which has exhibited anti-inflammatory activity and glucose metabolism improvement. The present study was proposed to evaluate its effects on glucose metabolism and other associated processes, such as lipemia and adipogenesis, as well as, to evaluate its effects on the liver, pancreas, and aorta in subjects fed with an occidental high-fat diet (HFD). The trial followed three groups of BALB/c mice for 6 months: (1) Standard diet (SD); (2) HFD-placebo (saline solution); and (3) HFD-Doxy (10 mg/kg/day). Intrahepatic fat accumulation (steatohepatosis) and the epididymal fat pad, as well as the hepatic inflammatory infiltrate and ALT serum levels were higher in both groups with the HFD (with/without doxycycline) in comparison with the SD group. The thickness of the aorta (preclinic atherosclerosis) was significantly elevated in the HFD group with respect to the HFD + Doxy and SD group, these two being similar groups to each other. The HFD-Doxy group had pancreatic morphological parameters very similar to those of the SD group; on the contrary, the HFD group reduced the number of pancreatic islets and the number of ß cells per mm2, in addition to losing large islets. The index of ß cell function (∆Insulin0-30/∆Glucose0-30 ratio) was significantly higher in the HFD + Doxy group, compared to the rest of the groups.

Pancreatic islet amyloidosis, beta-cell apoptosis, and alpha-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons.

beta-Cell dysfunction is an important factor in the development of hyperglycemia of type-2 diabetes mellitus, and pancreatic islet amyloidosis (IA) has been postulated to be one of the main contributors to impaired insulin secretion. The aim of this study was to evaluate the correlation of IA with metabolic parameters and its effect on islets of Langerhans remodeling and relative endocrine-cell volume in baboons. We sequenced the amylin peptide, determined the fibrillogenic propensities, and evaluated pancreatic histology, clinical and biochemical characteristics, and endocrine cell proliferation and apoptosis in 150 baboons with different metabolic status. Amylin sequence in the baboon was 92% similar to humans and showed superimposable fibrillogenic propensities. IA severity correlated with fasting plasma glucose (FPG) (r = 0.662, P < 0.001) and HbA1c (r = 0.726, P < 0.001), as well as with free fatty acid, glucagon values, decreased homeostasis model assessment (HOMA) insulin resistance, and HOMA-B. IA severity was associated with a decreased relative beta-cell volume, and increased relative alpha-cell volume and hyperglucagonemia. These results strongly support the concept that IA and beta-cell apoptosis in concert with alpha-cell proliferation and hypertrophy are key determinants of islets of Langerhans "dysfunctional remodeling" and hyperglycemia in the baboon, a nonhuman primate model of type-2 diabetes mellitus. The most important determinants of IA were age and FPG (R(2) = 0.519, P < 0.0001), and different FPG levels were sensitive and specific to predict IA severity. Finally, a predictive model for islet amyloid severity was generated with age and FPG as required variables.

Sensitivity and specificity of body mass index and main risk factors for cardiovascular disease in middle-income urban participants in Guanajuato, Mexico.

Introduction: Introduction: several studies have questioned body mass index (BMI) as an accurate diagnostic tool for obesity and therefore a predictor of cardiovascular risk. But BMI is widely used currently. Objective: we analyzed the sensitivity and specificity of BMI and compared cardiovascular risk factors in middle-income urban participants in Guanajuato, Mexico, at different ages. Design: an analytical and cross-sectional study was carried out in 385 apparently healthy subjects, stratified by age ranges (20 to 59 years old). A high global CVD risk was obtained with the Framingham risk score (Framingham Risk Score > 20 %). The odds ratio was used to assess the association between high global CVD risk and the dietetic and anthropometric variables. Sensitivity, specificity, and correlation statistical analyses were carried out between BMI and other anthropometric variables with high cardiovascular risk, and this was integrated to derive recommendations to improve risk factor detection (p < 0.05 and power of 80 %). Results: a high global CVD risk was found in 4 % of the sample. BMI ≥ 30 kg/m2 had a sensitivity of 77 % for the detection of high cardiovascular risk; waist circumference ≥ 90 cm (men) or ≥ 80 cm (women) and body fat percentage ≥ 2 5% (men) or ≥ 35 % (women) had a sensitivity of 100 %. BMI showed a significant association with high global CVD risk (OR = 6.1; 95 % CI, 1.6-22.6, p < 0.01), but was not able to predict high global CVD risk in at least 30 % of the cases. There was not significative difference by age group for waist circumference, body fat percentage, total cholesterol, and low-density lipoprotein. Regarding the comparison of dietary intake of the stratified population by age group, intake of cholesterol, added sugars, fiber, sodium were highest in the 20 years group. Conclusions: a higher intake of cholesterol, simple sugars, and sodium was observed in the 20-year-old age group. The use of BMI with waist circumference and percentage of body fat used together allow a better assessment of cardiovascular risk. We need to integrate this new recommendation to increase early detection of main risk factors for cardiovascular disease.

Introducción: Introducción: diversos estudios han cuestionado el índice de masa corporal (IMC) como herramienta diagnóstica certera de la obesidad y por tanto predictor de riesgo cardiovascular. Pero el IMC es ampliamente utilizado actualmente. Objetivo: se analizó la sensibilidad y especificidad del IMC y se compararon factores de riesgo cardiovascular en participantes de diferentes edades de zonas urbanas de ingresos medios en Guanajuato, México. Diseño: se realizó un estudio analítico y transversal en 385 participantes, aparentemente sanos, estratificados por rangos de edad (20 a 59 años). El riesgo de CVD global alto se obtuvo con la puntuación de riesgo de Framingham (puntuación de riesgo de Framingham > 20 %). Se calculó la odds ratio para evaluar la asociación entre el alto riesgo global de ECV y las variables dietéticas y antropométricas. Se realizó un análisis estadístico de sensibilidad, especificidad y correlación entre el IMC y otras variables antropométricas con el alto riesgo cardiovascular, y se integró para derivar recomendaciones para mejorar la detección de factores de riesgo (p < 0,05 y potencia del 80 %). Resultados: se encontró un alto riesgo global de ECV en el 4 % de la muestra. El IMC ≥ 30 kg/m2 tuvo una sensibilidad del 77 % para la detección del alto riesgo cardiovascular; la circunferencia de la cintura ≥ 90 cm (hombre) o ≥ 80 cm (mujer) y el porcentaje de grasa corporal ≥ 25 % (hombre) o ≥ 35 % (mujer) tuvo una sensibilidad del 100 %. El IMC mostró una asociación significativa con un alto riesgo global de ECV (OR = 6,1; IC 95 % 1,6-22,6; p < 0,01) pero no fue capaz de predecir un alto riesgo global de ECV en al menos el 30 % de los casos. No hubo diferencia significativa por grupo de edad para circunferencia de cintura, porcentaje de grasa corporal, colesterol total y lipoproteínas de baja densidad. Con respecto a la comparación de la ingesta dietética de la población estratificada por grupos de edad, la ingesta de colesterol, azúcares añadidos y sodio fue mayor en el grupo de 20 años. Conclusiones: se observó una mayor ingesta de colesterol, azúcares simples y sodio en el grupo de edad de 20 años. El uso del IMC con la circunferencia de la cintura y el porcentaje de grasa corporal utilizados conjuntamente permiten lograr una mejor evaluación del riesgo cardiovascular. Necesitamos contar con herramientas para aumentar la detección temprana de los principales factores de riesgo de enfermedad cardiovascular.

Type 2 diabetes, gut microbiome, and systems biology: A novel perspective for a new era.

The association between the physio-pathological variables of type 2 diabetes (T2D) and gut microbiota composition suggests a new avenue to track the disease and improve the outcomes of pharmacological and non-pharmacological treatments. This enterprise requires new strategies to elucidate the metabolic disturbances occurring in the gut microbiome as the disease progresses. To this end, physiological knowledge and systems biology pave the way for characterizing microbiota and identifying strategies in a move toward healthy compositions. Here, we dissect the recent associations between gut microbiota and T2D. In addition, we discuss recent advances in how drugs, diet, and exercise modulate the microbiome to favor healthy stages. Finally, we present computational approaches for disentangling the metabolic activity underlying host-microbiota codependence. Altogether, we envision that the combination of physiology and computational modeling of microbiota metabolism will drive us to optimize the diagnosis and treatment of T2D patients in a personalized way.

[Delta of neutrophil lymphocyte index and mortality in covid-19 disease]. / Delta del índice neutrófilo linfocito y mortalidad en infección COVID-19.

Background: Acute respiratory distress syndrome, due to SARS-CoV-2, is a worldwide health problem. The neutrophil-lymphocyte index allows risk stratification in patients with severe and poor prognostic data, since it reflects the inflammatory state. Objective: To determine whether the Neutrophil-Lymphocyte Index delta predicts mortality in patients with COVID-19. Material and methods: We conducted a longitudinal, comparative study in patients with COVID-19, older than 18 years, admitted to the ICU. We evaluated HAS, DM, obesity, COPD, asthma, PaO2/FiO2, tomographic severity. On admission and on days 3 and 7 we measured Neutrophil-Lymphocyte Index, SOFA and APACHE score. For statistical analysis, we performed ROC and Kaplan-Meyer curves. Results: We included 180 patients with COVID-19, 63 died (35%). Delta INL1(Day1-day3)>4.11 was associated with mortality (AUC:0.633); sensitivity 55.56% and specificity 77.78%, CI95 0.55-0.70, for delta INL2 (Day1-day7)>8.95 (AUC:0.623); sensitivity 44.44% and specificity 84.62%, CI95 0.54-0.69. Difference in survival was observed for Delta1. SOFA scale >6, was associated with more days of mechanical ventilation and lower PaO2/FiO2 (p<0.001). Conclusions: INL delta between the day of ICU admission and the 3rd day of evolution is a predictor of mortality in critically ill patients.

Introducción: El síndrome de dificultad respiratoria aguda, por SARS-CoV-2, es un problema mundial de salud. El índice neutrófilo-linfocito, permite estratificar el riesgo en pacientes con datos de severidad y mal pronóstico, ya que refleja el estado inflamatorio. Objetivo: Determinar si el delta del Índice Neutrófilo-Linfocito predice mortalidad en pacientes con COVID-19. Material y métodos: Se realizó un estudio longitudinal, comparativo en pacientes con COVID-19, mayores de 18 años, ingresados a UCI. Evaluamos HAS, DM, Obesidad, EPOC, asma, PaO2/FiO2, severidad tomográfica., A su ingreso y los días 3 y 7 medimos Índice Neutrófilo-Linfocito, puntaje SOFA y APACHE. En el análisis estadístico, realizamos curvas ROC y Kaplan-Meyer. Resultados: Incluimos 180 pacientes con COVID-19, 63 fallecieron (35%). Se asoció delta INL1(Día1-día3)>4.11 con mortalidad (AUC:0.633); sensibilidad 55.56% y especificidad 77.78%, IC95 0.55-0.70, para delta INL2 (Día1-día7)>8.95 (AUC:0.623); sensibilidad 44.44% y especificidad 84.62%, IC95 0.54-0.69. Se observó diferencia en la sobrevida para delta1. La escala SOFA >6, se asoció a más días de ventilación mecánica y PaO2/FiO2 menor (p<0.001). Conclusiones: El delta de INL entre el día de ingreso a UCI y el 3er día de evolución es predictor de mortalidad en pacientes críticamente enfermos.

Effect of linagliptin plus insulin in comparison to insulin alone on metabolic control and prognosis in hospitalized patients with SARS-CoV-2 infection.

To evaluate the effect of the combination of linagliptin and insulin on metabolic control and prognosis in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hyperglycemia. A parallel double-blind randomized clinical trial including hospitalized patients with SARS-CoV-2 infection and hyperglycemia, randomized to receive 5 mg linagliptin + insulin (LI group) or insulin alone (I group) was performed. The main outcomes were the need for assisted mechanical ventilation and glucose levels during hospitalization. Subjects were screened for eligibility at hospital admission if they were not with assisted mechanical ventilation and presented hyperglycemia, and a total of 73 patients with SARS-CoV-2 infection and hyperglycemia were randomized to the LI group (n = 35) or I group (n = 38). The average hospital stay was 12 ± 1 vs 10 ± 1 days for the I and LI groups, respectively (p = 0.343). There were no baseline clinical differences between the study groups, but the percentage of males was higher in the LI group (26 vs 18, p = 0.030). The improvements in fasting and postprandial glucose levels were better in the LI group that the I group (122 ± 7 vs 149 ± 10, p = 0.033; and 137 ± 7 vs 173 ± 12, p = 0.017, respectively), and insulin requirements tended to be lower in the LI group than the I group. Three patients in the LI group and 12 in the I group required assisted mechanical ventilation (HR 0.258, CI 95% 0.092-0.719, p = 0.009); 2 patients in the LI group and 6 in the I group died after a follow-up of 30 days (p = 0.139). No major side effects were observed. The combination of linagliptin and insulin in hospitalized patients with SARS-CoV-2 infection and hyperglycemia reduced the relative risk of assisted mechanical ventilation by 74% and improved better pre and postprandial glucose levels with lower insulin requirements, and no higher risk of hypoglycemia.This study is registered at clinicaltrials.gov, number NCT04542213 on 09/03/2020.

Trends, structural changes, and assessment of time series models for forecasting hospital discharge due to death at a Mexican tertiary care hospital.

BACKGROUND: Data on hospital discharges can be used as a valuable instrument for hospital planning and management. The quantification of deaths can be considered a measure of the effectiveness of hospital intervention, and a high percentage of hospital discharges due to death can be associated with deficiencies in the quality of hospital care. OBJECTIVE: To determine the overall percentage of hospital discharges due to death in a Mexican tertiary care hospital from its opening, to describe the characteristics of the time series generated from the monthly percentage of hospital discharges due to death and to make and evaluate predictions. METHODS: This was a retrospective study involving the medical records of 81,083 patients who were discharged from a tertiary care hospital from April 2007 to December 2019 (first 153 months of operation). The records of the first 129 months (April 2007 to December 2017) were used for the analysis and construction of the models (training dataset). In addition, the records of the last 24 months (January 2018 to December 2019) were used to evaluate the predictions made (test dataset). Structural change was identified (Chow test), ARIMA models were adjusted, predictions were estimated with and without considering the structural change, and predictions were evaluated using error indices (MAE, RMSE, MAPE, and MASE). RESULTS: The total percentage of discharges due to death was 3.41%. A structural change was observed in the time series (March 2009, p>0.001), and ARIMA(0,0,0)(1,1,2)12 with drift models were adjusted with and without consideration of the structural change. The error metrics favored the model that did not consider the structural change (MAE = 0.63, RMSE = 0.81, MAPE = 25.89%, and MASE = 0.65). CONCLUSION: Our study suggests that the ARIMA models are an adequate tool for future monitoring of the monthly percentage of hospital discharges due to death, allowing us to detect observations that depart from the described trend and identify future structural changes.

Effect of linagliptin on glucose metabolism and pancreatic beta cell function in patients with persistent prediabetes after metformin and lifestyle.

The goal of the study was to evaluate the effect of adding linagliptin to metformin and lifestyle on glucose levels and pancreatic ß-cell function in patients with persistent impaired glucose tolerance (IGT) after 12 months of metformin and lifestyle. A single center parallel double-blind randomized clinical trial with 6 months of follow-up was performed in patients with persistent IGT after 12 months of treatment with metformin and lifestyle; patients were randomized to continue with metformin 850 mg twice daily (M group, n = 12) or linagliptin/metformin 2.5/850 mg twice daily (LM group, n = 19). Anthropometric measurements were obtained by standard methods and by bioelectrical impedance; glucose was measured by dry chemistry, insulin by chemiluminescence, and pancreatic ß-cell function was calculated with the disposition index using glucose and insulin values during oral glucose tolerance test (OGTT) and adjusting by insulin sensitivity. The main outcomes were glucose levels during OGTT and pancreatic ß-cell function. Patients in the LM group had a reduction in weight (-1.7 ± 0.6, p < 0.05) and body mass index (BMI, -0.67 ± 0.2, p < 0.05). Glucose levels significantly improved in LM group with a greater reduction in the area under the glucose curve during OGTT (AUCGluc0_120min) as compared to the M group (-4425 ± 871 vs -1116 ± 1104 mg/dl/120 min, p < 0.001). Pancreatic ß-cell function measured with the disposition index, improved only in LM group (2.3 ± 0.23 vs 1.7 ± 0.27, p 0.001); these improvements persisted after controlling for OGTT glucose levels. The differences in pancreatic ß-cell function persisted also after pairing groups for basal AUCGluc0_120min. The addition of linagliptin to patients with persistent IGT after 12 months of treatment with metformin and lifestyle, improved glucose levels during OGTT and pancreatic ß-cell function after 6 months of treatment.Trial registration: Clinicaltrials.gov with the ID number NCT04088461.

Comparison between metabolically healthy obesity and metabolically unhealthy obesity by different definitions among Mexican children.

Background There is no consensus on the definition of metabolically healthy obesity (MHO) and the diagnostic criteria in children. Objectives To estimate the prevalence of MHO and compare clinical and biochemical characteristics between MHO and metabolically unhealthy obesity (MUO), and to evaluate the association between MUO and cardiovascular disease (CVD) risk, anthropometrics and family background using different definitions in children. Methods This was a cross-sectional study. Participants included 224 obese children between the years 2007 and 2017. MHO was defined by three different criteria: (i) absence of metabolic syndrome (MHO-MS), (ii) no insulin resistance (IR) by homeostatic model assessment (HOMA) <3.16 cut-off (MHO-IR3.16) and (iii) absence of IR at <95th percentile for Mexican children (MHO-95th). Results The prevalence of MHO-MS, MHO-IR3.16 and MHO-IR95th was 12.9%, 56.3% and 41.5%, respectively. The prevalence of simultaneous MHO-MS plus MHO-IR95th was 5.36%. Children with MHO-MS vs. MUO-MS showed lower height, weight and body mass index (BMI) percentiles; MHO-IR3.16 vs. MUO-IR3.16 showed lower age, acanthosis, Tanner, waist circumference (WC), waist-to-height ratio (WHtR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and glucose; and MHO-IR95th vs. MUO-IR95th showed lower acanthosis, WC, DBP, glucose and high high-density lipoprotein cholesterol (HDL-C). MUO-MS was associated with WC > 90th, type 2 diabetes mellitus (T2DM) in first-degree relatives and obesity in siblings. MUO-IR3.16 was associated with pubertal stages, WC > 90th, WHtR > 0.55 and fasting hyperglycemia. MUO-IR95th was associated with WHtR > 0.55 and HDL < 10th. MHO-MS and MHO-IR3.16 or MHO-IR95th did not have agreement. Conclusions The prevalence of MHO varied depending on the definition, although the real MHO with no MS or IR is very low. Low DBP and high HDL-C in MHO were present in any definition. Association of MUO with anthropometric, biochemical and family background differs across definitions.

Progressive Shifts in the Gut Microbiome Reflect Prediabetes and Diabetes Development in a Treatment-Naive Mexican Cohort.

Type 2 diabetes (T2D) is a global epidemic that affects more than 8% of the world's population and is a leading cause of death in Mexico. Diet and lifestyle are known to contribute to the onset of T2D. However, the role of the gut microbiome in T2D progression remains uncertain. Associations between microbiome composition and diabetes are confounded by medication use, diet, and obesity. Here we present data on a treatment-naive cohort of 405 Mexican individuals across varying stages of T2D severity. Associations between gut bacteria and more than 200 clinical variables revealed a defined set of bacterial genera that were consistent biomarkers of T2D prevalence and risk. Specifically, gradual increases in blood glucose levels, beta cell dysfunction, and the accumulation of measured T2D risk factors were correlated with the relative abundances of four bacterial genera. In a cohort of 25 individuals, T2D treatment-predominantly metformin-reliably returned the microbiome to the normoglycemic community state. Deep clinical characterization allowed us to broadly control for confounding variables, indicating that these microbiome patterns were independent of common T2D comorbidities, like obesity or cardiovascular disease. Our work provides the first solid evidence for a direct link between the gut microbiome and T2D in a critically high-risk population. In particular, we show that increased T2D risk is reflected in gradual changes in the gut microbiome. Whether or not these T2D-associated changes in the gut contribute to the etiology of T2D or its comorbidities remains to be seen.

Impact of nutritional risk on 28-day mortality and the prevalence of underfeeding in critically ill patients: A prospective cohort study.

INTRODUCTION: Introduction: nutritional risk is an important prognostic factor in hospitalized patients, but frequently it is underappreciated and not considered as a part of the prognostic evaluation in patients from intensive care units. Objective: to evaluate the association between nutritional risk and 28-day mortality and characterize the nutritional support in critically ill patients. Methods: this was a single-center, prospective cohort study was performed over 7 months in a Medical-surgical ICU of a tertiary hospital in Mexico. From 352 admissions a consecutive sample of 110 patients was included. All of them were ≥ 18 years old, with ≥ 48 h of stay in ICU and with the consent to participate. Nutritional risk assessed by the modified NUTRIC score (mNUTRIC score), 28-day mortality and nutritional support characteristics were recorded. Results: the patient characteristics: mean age 50.7 ± 16.8 years, APACHE II score 15.5 ± 5.8, SOFA score 6.9 ± 3, invasive mechanical ventilation (IMV) 65.5 % and 28-day mortality 23.6 %. High nutritional risk (31.8 %) was associated with 28-day mortality (RR 5.81, 95 % CI 2.69-12.53). In the surviving group, the mNUTRIC score correlated with the length of stay (LOS) in the ICU (r = 0.216, p = 0.049), LOS in the hospital (r = 0.230, p = 0.036) and IMV duration (r = 0.306, p = 0.037). Nutritional support was administered in 55.4 % of the patients, reaching only 52.9 % and 46 % of the energy and protein requirements, respectively. Only 18 % and 21.3 % of the patients achieved the energy and protein requirements, respectively. Conclusions: high nutritional risk was associated with a higher risk of 28-day mortality. Less than a quarter of the patients receiving nutritional support reached the energy and protein requirements.

INTRODUCCIÓN: Introducción: el riesgo nutricional es un factor pronóstico importante en pacientes hospitalizados, pero frecuentemente es infravalorado y no se considera dentro de la evaluación de los pacientes en unidades de cuidados intensivos. Objetivo: evaluar la asociación del riesgo nutricional con la mortalidad al día 28 en pacientes críticos y caracterizar el soporte nutricional. Métodos: se desarrolló un estudio de cohorte prospectivo durante 7 meses en una UCI de tercer nivel en México. Se obtuvo una muestra consecutiva con 110 pacientes de 352 elegibles, con edad ≥ 18 años, estancia ≥ 48 h en UCI, datos completos y consentimiento para participar. El riesgo nutricional fue evaluado con NUTRIC score modificado (mNUTRIC score) y se registró la mortalidad al día 28 y las características del soporte nutricional. Resultados: los pacientes tenían una edad de 50,7 ± 16,8 años; APACHE II, 15,5 ± 5,8; SOFA, 6,9 ± 3; ventilación mecánica invasiva (VMI) en 65,5 % y el 23,6 % de los pacientes falleció al día 28. El alto riesgo nutricional (31,8 %) se asoció con la mortalidad al día 28 (RR 5,81, IC 95 %, 2,69-12,53). En los supervivientes, el mNUTRIC score tuvo correlación con las duraciones de la estancia en UCI (ℓ = 0,216, p = 0,049), estancia hospitalaria (ℓ = 0,230, p = 0,036) y VMI (ℓ = 0,306, p = 0,037). El 55,4 % de los pacientes recibió soporte nutricional. Lograron el 52,9 % y 46 % de las metas energéticas y proteicas, respectivamente. Solo el 18 % alcanzó la meta energética y el 21,3 %, la meta proteica. Conclusiones: los pacientes con alto riesgo nutricional tienen mayor riesgo de morir al día 28. Menos de un cuarto de los pacientes con soporte nutricional alcanzó las metas nutricionales.

The combination of linagliptin, metformin and lifestyle modification to prevent type 2 diabetes (PRELLIM). A randomized clinical trial.

BACKGROUND: Prediabetes is a highly prevalent health problem with a high risk of complications and progression to type 2 diabetes (T2D). The goals of this study were to evaluate the effect of the combination of lingaliptin + metformin + lifestyle on glucose tolerance, pancreatic ß-cell function and T2D incidence in patients with prediabetes. METHODS: A single center parallel double-blind randomized clinical trial with 24 months of follow-up in patients with impaired glucose tolerance plus two T2D risk factors which were randomized to linagliptin 5 mg + metformin 1700 mg daily + lifestyle (LM group) or metformin 1700 mg daily + lifestyle (M group). Primary outcomes were regression to normoglycemia and T2D incidence; glucose levels and pancreatic ß-cell function were secondary outcomes. RESULTS: Subjects were screened for eligibility by OGTT and 144 patients with prediabetes were randomized to LM group (n = 74) or M group (n = 70); 52 and 36 participants in the LM group and 52 and 27 participants in the M group, completed the 12 and 24 months of treatment, respectively; average follow-up was 17 ±â€¯6 and 18 ±â€¯7 months in M and LM group, respectively. Glucose levels during OGTT improved more in LM group. OGTT disposition index (DI) improved significantly better during the first months in LM group, increasing from 1·31 (95% CI: 1·14-1·49) to 2·41 (95% CI: 2.10-2.72) and to 2.07 (95% CI: 1.82-2.31) at 6 and 24 months in LM group vs from 1.21 (95% CI: 0.98-1.34) to 1.56 (95% CI: 1.17-1.95) and to 1.72 (95% CI: 1.45-1.98) at 6 and 24 months in M group (p < .05). T2D incidence was higher in M group in comparison to LM group (HR 4.0, 95% CI: 1.24-13.04, p = .020). The probability of achieving normoglycemia was higher in LM group (OR 3.26 CI 95% 1.55-6.84). No major side effects were observed during the study. CONCLUSIONS: The combination of linagliptin, metformin and lifestyle improved significantly glucose metabolism and pancreatic ß-cell function, and reduced T2D incidence in subjects with prediabetes as compared to metformin and lifestyle.

Predictive models of insulin resistance derived from simple morphometric and biochemical indices related to obesity and the metabolic syndrome in baboons.

BACKGROUND: Non-human primates are valuable models for the study of insulin resistance and human obesity. In baboons, insulin sensitivity levels can be evaluated directly with the euglycemic clamp and is highly predicted by adiposity, metabolic markers of obesity and impaired glucose metabolism (i.e. percent body fat by DXA and HbA1c). However, a simple method to screen and identify obese insulin resistant baboons for inclusion in interventional studies is not available. METHODS: We studied a population of twenty baboons with the euglycemic clamp technique to characterize a population of obese nondiabetic, insulin resistant baboons, and used a multivariate linear regression analysis (adjusted for gender) to test different predictive models of insulin sensitivity (insulin-stimulated glucose uptake = Rd) using abdominal circumference and fasting plasma insulin. Alternatively, we tested in a separate baboon population (n = 159), a simpler model based on body weight and fasting plasma glucose to predict the whole-body insulin sensitivity (Rd/SSPI) derived from the clamp. RESULTS: In the first model, abdominal circumference explained 59% of total insulin mediated glucose uptake (Rd). A second model, which included fasting plasma insulin (log transformed) and abdominal circumference, explained 64% of Rd. Finally, the model using body weight and fasting plasma glucose explained 51% of Rd/SSPI. Interestingly, we found that percent body fat was directly correlated with the adipocyte insulin resistance index (r = 0.755, p < 0.0001). CONCLUSION: In baboons, simple morphometric measurements of adiposity/obesity, (i.e. abdominal circumference), plus baseline markers of glucose/lipid metabolism, (i.e. fasting plasma glucose and insulin) provide a feasible method to screen and identify overweight/obese insulin resistant baboons for inclusion in interventional studies aimed to study human obesity, insulin resistance and type 2 diabetes mellitus.