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Andrade-Castellanos C.A.,Hospital Civil de Guadalajara Dr. Juan I. Menchaca | Colunga-Lozano L.E.,Hospital Civil de Guadalajara Fray Antonio Alcalde | Delgado-Figueroa N.,Hospital Civil de Guadalajara Dr. Juan I. Menchaca | Gonzalez-Padilla D.A.,Hospital Universitario 12 Of Octubre
Cochrane Database of Systematic Reviews

Background: Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of uncontrolled diabetes that mainly occurs in individuals with autoimmune type 1 diabetes, but it is not uncommon in some people with type 2 diabetes. The treatment of DKA is traditionally accomplished by the administration of intravenous infusion of regular insulin that is initiated in the emergency department and continued in an intensive care unit or a high-dependency unit environment. It is unclear whether people with DKA should be treated with other treatment modalities such as subcutaneous rapid-acting insulin analogues. Objectives: To assess the effects of subcutaneous rapid-acting insulin analogues for the treatment of diabetic ketoacidosis. Search methods: We identified eligible trials by searching MEDLINE, PubMed, EMBASE, LILACS, CINAHL, and the Cochrane Library. We searched the trials registers WHO ICTRP Search Portal and ClinicalTrials.gov. The date of last search for all databases was 27 October 2015. We also examined reference lists of included randomised controlled trials (RCTs) and systematic reviews, and contacted trial authors. Selection criteria: We included trials if they were RCTs comparing subcutaneous rapid-acting insulin analogues versus standard intravenous infusion in participants with DKA of any age or sex with type 1 or type 2 diabetes, and in pregnant women. Data collection and analysis: Two review authors independently extracted data, assessed studies for risk of bias, and evaluated overall study quality utilising the GRADE instrument. We assessed the statistical heterogeneity of included studies by visually inspecting forest plots and quantifying the diversity using the I2 statistic. We synthesised data using random-effects model meta-analysis or descriptive analysis, as appropriate. Main results: Five trials randomised 201 participants (110 participants to subcutaneous rapid-acting insulin analogues and 91 to intravenous regular insulin). The criteria for DKA were consistent with the American Diabetes Association criteria for mild or moderate DKA. The underlying cause of DKA was mostly poor compliance with diabetes therapy. Most trials did not report on type of diabetes. Younger diabetic participants and children were underrepresented in our included trials (one trial only). Four trials evaluated the effects of the rapid-acting insulin analogue lispro, and one the effects of the rapid-acting insulin analogue aspart. The mean follow-up period as measured by mean hospital stay ranged between two and seven days. Overall, risk of bias of the evaluated trials was unclear in many domains and high for performance bias for the outcome measure time to resolution of DKA. No deaths were reported in the included trials (186 participants; 3 trials; moderate- (insulin lispro) to low-quality evidence (insulin aspart)). There was very low-quality evidence to evaluate the effects of subcutaneous insulin lispro versus intravenous regular insulin on the time to resolution of DKA: mean difference (MD) 0.2 h (95% CI -1.7 to 2.1); P = 0.81; 90 participants; 2 trials. In one trial involving children with DKA, the time to reach a glucose level of 250 mg/dL was similar between insulin lispro and intravenous regular insulin. There was very low-quality evidence to evaluate the effects of subcutaneous insulin aspart versus intravenous regular insulin on the time to resolution of DKA: MD -1 h (95% CI -3.2 to 1.2); P = 0.36; 30 participants; 1 trial. There was low-quality evidence to evaluate the effects of subcutaneous rapid-acting insulin analogues versus intravenous regular insulin on hypoglycaemic episodes: 6 of 80 insulin lispro-treated participants compared with 9 of 76 regular insulin-treated participants reported hypoglycaemic events; risk ratio (RR) 0.59 (95% CI 0.23 to 1.52); P = 0.28; 156 participants; 4 trials. For insulin aspart compared with regular insulin, RR for hypoglycaemic episodes was 1.00 (95% CI 0.07 to 14.55); P = 1.0; 30 participants; 1 trial; low-quality evidence. Socioeconomic effects as measured by length of mean hospital stay for insulin lispro compared with regular insulin showed a MD of -0.4 days (95% CI -1 to 0.2); P = 0.22; 90 participants; 2 trials; low-quality evidence and for insulin aspart compared with regular insulin 1.1 days (95% CI -3.3 to 1.1); P = 0.32; low-quality evidence. Data on morbidity were limited, but no specific events were reported for the comparison of insulin lispro with regular insulin. No trial reported on adverse events other than hypoglycaemic episodes, and no trial investigated patient satisfaction. Authors' conclusions: Our review, which provided mainly data on adults, suggests on the basis of mostly low- to very low-quality evidence that there are neither advantages nor disadvantages when comparing the effects of subcutaneous rapid-acting insulin analogues versus intravenous regular insulin for treating mild or moderate DKA. © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Source

Salmon G.F.,National Autonomous University of Mexico | Sanchez-Reyes L.,National Autonomous University of Mexico | Chiquete E.,Hospital Civil de Guadalajara Fray Antonio Alcalde | De La Luz J.,Sanofi S.A. | Herrera A.E.,Instituto Mexicano del Seguro Social
Gaceta Medica de Mexico

Background: There is a lack of information on the characteristics of the medical attention delivered to Mexican patients with type 2 diabetes (T2D). Our aim was to describe the current state on the medical management of T2D in Mexico. Methods: Among 17,232 patients included in the International Diabetes Management Practices Study (IDMPS), 2,620 (15%) corresponded to Mexico. Information regarding clinical, demographics and management characteristics, as well as the impact of T2D in the patientís clinical and social condition was registered. The metabolic control and achievement of therapeutic goals were also analyzed. Results: Diagnosis of T2D was performed by the general practitioner in 76% of cases. Only about a quarter of the cohort had a blood pressure goal of < 130/80 mmHg, although 97% had anti-hypertensive treatment. Management of T2D was with diet and exercise exclusively in 5%, with oral glucoselowering drugs (OGLD) in 66% (alone or combined), with OGLD and insulin in 18%, and with insulin alone in 11%. Only 31% of patients reached the goal of HbA1c < 7. Self-monitoring was practiced in 50% of patients and 26% received education on diabetes. The managing physicianís personal impression about the quality of the metabolic control was not in accordance with HbA1c. Eight percent of patients had work absences in the last 3 months due to complications of T2D (mean of 15 days lost). Conclusions: In Mexico, quality of metabolic control of T2D patients could have important deficiencies. The personal impression of the physician on the patientís metabolic control is not consistent with objective data. Source

Reyes-Castillo Z.,University of Guadalajara | Palafox-Sanchez C.A.,University of Guadalajara | Parra-Rojas I.,Autonomous University of Guerrero | Martinez-Bonilla G.E.,Hospital Civil de Guadalajara Fray Antonio Alcalde | And 4 more authors.
Clinical and Experimental Immunology

Antibodies against cyclic citrullinated peptides (anti-CCP) are widely used for diagnosis of rheumatoid arthritis (RA). We performed a comparative analysis of antibodies targeting the citrullinating enzyme peptidylarginine deiminase type 4 (anti-PAD4) and mutated citrullinated vimentin (anti-MCV) with anti-CCP autoantibodies in RA patients and examined their relationships with clinical parameters, cytokine profiles and the PADI4 gene. Autoantibodies were examined by enzyme-linked immunosorbent assay (ELISA) in sera of 170 RA patients and 103 controls. Cytokine profiles were measured using a multiplex system. PADI4 polymorphisms (89G>A, 90T>C and 92G>C) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Anti-PAD4, anti-MCV and anti-CCP autoantibodies were detected in 24, 61 and 74% of RA patients, respectively. Positive correlations were observed between anti-PAD4 and disease duration; anti-CCP and erythrocyte sedimentation rate (ESR); anti-MCV and ESR and C-reactive protein. Anti-MCV antibodies were associated with high disease activity score 28 (DAS-28) in early RA. Concentrations of T helper type 1 (Th1) [tumour necrosis factor (TNF)-α, interleukin (IL)-12, IL-2, IL-1β], Th2 (IL-4, IL-6, IL-10, IL-13) and Th17 (IL-17) cytokines were higher in RA than in controls. Th2 and, to a lesser extent, Th1-related cytokines, showed positive correlations with anti-MCV and anti-CCP. The GTG haplotype in PADI4 was associated with anti-CCP and anti-MCV, but not anti-PAD4 antibodies. In conclusion, anti-PAD4 antibodies are detected mainly in established RA, which is in contrast to the early detection of antibodies against citrullinated peptide/proteins (ACPAs). Among autoantibodies, anti-MCV appear to perform better as markers of disease activity. Furthermore, anti-CCP and anti-MCV are associated genetically with the citrullinating enzyme PAD4 and are related strongly to Th1 and Th2 cytokines, suggesting a feed-forward loop between cytokines and ACPA production. © 2015 British Society for Immunology. Source

Lavalle-Gonzalez F.J.,Hospital Universitario Dr Jose Eleuterio Gonzalez | de la Luz J.,Sanofi S.A. | Sanchez-Orozco L.V.,University of Guadalajara | Godinez-gutierrez S.A.,Hospital Civil de Guadalajara Fray Antonio Alcalde
Endocrinologia y Nutricion

Background and aim: Complications of diabetes comprise the leading cause of death in Mexico. We aimed to describe the characteristics of management and achievement of therapeutic targets in Mexican patients with diabetes mellitus. Methods: We analyzed data from 2642 Mexican patients with type 1 (T1D, n=203, 7.7%) and type 2 diabetes (T2D, n=2439, 92.3%) included in the third wave of the International Diabetes Management Practices Study. Results: Of T2D patients, 63% were on oral glucose-lowering drugs (OGLD) exclusively (mostly metformin), 11% on insulin, 22% on OGLD plus insulin, and 4% on diet and exercise exclusively. T2D patients on insulin were more likely to be trained on diabetes, but they were older, had worse control, longer disease duration and more chronic complications than patients on OGLD only. Glycated hemoglobin (HbA1c) < 7% was achieved by 21% and 37% of T1D and T2D patients, respectively. Only 5% of T1D and 3% of T2D attained the composite target of HbA1c < 7%, blood pressure < 130/80. mmHg and low-density lipoprotein cholesterol < 100. mg/dl. T1D patients had less macrovascular but more microvascular complications, compared with T2D patients. Late complications increased with disease duration, so that about 80% of patients after 20 years of diagnosis have at least one late complication. Reaching the target HbA1c < 7% was associated with a reduced number of microvascular but not with less macrovascular complications. Conclusion: A great proportion of these Mexican patients with diabetes did not reach therapeutic targets. Insulin was used mostly in complicated cases with advanced disease. © 2011 SEEN. Source

Chiquete E.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran | Ruiz-Sandoval J.L.,Hospital Civil de Guadalajara Fray Antonio Alcalde | Murillo-Bonilla L.M.,Autonomous University of Guadalajara | Arauz A.,Instituto Nacional Of Neurologia Y Neurocirugia | And 7 more authors.
Cerebrovascular Diseases

Background: Current evidence shows that uric acid is a potent antioxidant whose serum concentration increases rapidly after acute ischemic stroke (AIS). Nevertheless, the re-lationship between serum uric acid (SUA) levels and AIS outcome remains debatable. We aimed to describe the prognostic significance of SUA in AIS. Methods: We studied 463 patients (52% men, mean age 68 years, 13% with glomerular filtration rate <60 ml/min at hospital arrival) with AIS pertaining to the multicenter registry PREMIER, who had SUA measurements at hospital presentation. Multivariate models were constructed to analyze the association of SUA with functional outcome as assessed by the modified Rankin scale (mRS) at 30-day, 3-, 6- and 12-month follow-up. A mRS 0-1 was regarded as a very good outcome. Results: Mean SUA concentration at hospital arrival was 6.1 ± 3.7 mg/dl (362.8 ± 220.0 μmol/l). Compared with cases with higher SUA levels at hospital admission, patients with ≤4.5 mg/dl (≤267.7 μmol/l; the lowest tertile of the sample) had more cases of a very good 30-day outcome (30.5 vs. 18.9%, respectively; p = 0.004). SUA was not associated with mortality or functional dependence (mRS >2) at 30 days, or with any outcome measure at 3, 6 or 12 months poststroke. After adjustment for age, gender, stroke type and severity (NIHSS <9), time since event onset, serum creatinine, hypertension, diabetes and smoking, a SUA ≤4.5 mg/dl (≤267.7 μmol/l) was positively associated with a very good short-term outcome (odds ratio: 1.76, 95% confidence interval: 1.05-2.95; negative predictive value: 81.1%), but not at 3, 6 or 12 months of follow-up. When NIHSS was entered in the multivariate model as a continuous variable, the independent association of SUA with outcome was lost. Compared with cases with higher levels, patients with SUA ≤4.5 mg/dl (≤267.7 μmol/l) were more frequently younger than 55 years, women, with mild strokes, with normal serum creatinine and fewer had hypertension. The time since event onset to hospital arrival was not significantly associated with AIS severity or SUA levels; nevertheless, a nonsignificant tendency was observed for patients with severe strokes and high SUA levels arriving in <24 h. Conclusions: A low SUA concentration is modestly associated with a very good short-term outcome. Our findings support the hypothesis that SUA is more a marker of the magnitude of the cerebral infarction than an independent predictor of stroke outcome. Copyright © 2013 S. Karger AG, Basel. Source

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