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1.
Gac Med Mex ; 160(1): 23-31, 2024.
Article in English | MEDLINE | ID: mdl-38753572

ABSTRACT

BACKGROUND: Endothelial dysfunction (ED) suspicion will allow to prevent accelerated atherosclerosis and premature death. OBJECTIVE: To establish the usefulness of thermography for endothelial function screening in adults with cardiovascular risk factors. MATERIAL AND METHODS: Cross-sectional, analytical diagnostic test. A brachial arterial diameter (BAD) increase < 11% at one-minute post-ischemia meant probable ED and was confirmed if BAD was ≥ 11% post-sublingual nitroglycerin. Thermographic photographs of the palmar region were obtained at one minute. Descriptive statistics, ROC curve, Mann-Whitney's U-test, chi-square test, or Fisher's exact test were used. RESULTS: Thirty-eight subjects with a median age of 50 years, and with 624 thermographic measurements were included. Nine had ED (flow-mediated vasodilation [FMV]: 2.5%). The best cutoff point for normal endothelial function in subjects with cardiovascular risk factors was ≥ 36 °C at one minute of ischemia, with 85% sensitivity, 70% specificity, positive and negative predictive values of 78 and 77%, area under the curve of 0.796, LR+ 2.82, LR- 0.22. CONCLUSION: An infrared thermography-measured temperature in the palmar region greater than or equal to 36 °C after one minute of ischemia is practical, non-invasive, and inexpensive for normal endothelial function screening in adults with cardiovascular risk factors.


ANTECEDENTES: La sospecha de disfunción endotelial (DE) permitirá prevenir la aterosclerosis acelerada y la muerte prematura. OBJETIVO: Establecer la utilidad de la termografía en el cribado de la función endotelial en adultos con factores de riesgo cardiovascular. MATERIAL Y MÉTODOS: Estudio transversal analítico de prueba diagnóstica. El incremento del diámetro de la arteria braquial < 11 % a un minuto posisquemia significó probable DE, confirmada si el diámetro fue ≥ 11 % posnitroglicerina sublingual. Se obtuvieron fotografías termográficas al minuto de la región palmar. Se aplicó estadística descriptiva, curva ROC, pruebas U de Mann-Whitney, chi cuadrada o exacta de Fisher. RESULTADOS: Se incluyeron 38 sujetos, mediana de edad de 50 años, con 624 mediciones termográficas; nueve presentaron DE (vasodilatación mediada por flujo de 2.5 %). El mejor punto de corte para la función endotelial normal en sujetos con factores de riesgo cardiovascular fue ≥ 36 °C al minuto de isquemia, con sensibilidad de 85%, especificidad de 70%, valores predictivos positivo y negativo de 78 y 77%, área bajo la curva de 0.796, razón de verisimilitud positiva de 2.82 y razón de verisimilitud negativa de 0.22. CONCLUSIÓN: La medición de la temperatura en la región palmar mediante termografía infrarroja ≥ 36 °C tras un minuto de isquemia es práctica, no invasiva y económica para el cribado de la función endotelial normal en adultos con factores de riesgo cardiovascular.


Subject(s)
Endothelium, Vascular , Thermography , Humans , Thermography/methods , Middle Aged , Male , Female , Cross-Sectional Studies , Endothelium, Vascular/physiopathology , Adult , Aged , Heart Disease Risk Factors , Sensitivity and Specificity , Infrared Rays , Brachial Artery/physiology , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/physiopathology , Vasodilation/physiology , Predictive Value of Tests
2.
Acta Trop ; 249: 107047, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37866730

ABSTRACT

BACKGROUND AND AIM: Gonorrhea is a bacterial infection in the urogenital tract, transmitted by sexual or perinatal contact, caused by Neisseria gonorrhoeae, a gram-negative diplococcus. The present study evaluates the frequency of N. gonorrhoeae in women treated at Hospital Wladimir Arruda in poor area of São Paulo and also verifies the presence of genetic resistance against three antimicrobials of different classes: Tetracycline, Azithromycin and Ciprofloxacin. METHODS: This is an observational and descriptive study with a quantitative approach. Samples were collected at Hospital Escola Wladimir Arruda. The volunteers are women from 16 to 65 years of age. Sociodemographic, gynecological, sexual and health data are collected through a questionnaire, their symptoms/clinical manifestation were requested by the medical records, and then the participant is referred for collection of samples of cervical vaginal smear. The samples were screened for N. gonorrhoeae (dcmH gene) and tested for resistance genes to Tetracycline, Azithromycin and Ciprofloxacin through PCR. RESULTS: In the total of 127 samples analyzed by Real-Time PCR, 23 were positive and correspond to a general prevalence of a gonococcal infection in the studied population of 17% (CI:95%), and the participants were married (43.4%), had active sexual life (56.5%) and did not use any type of condom during sexual intercourse (52.1%). The resistance to the tetM ribosomal gene was found in 14 samples, prevalence of 60% (CI= 95%). CONCLUSIONS: We have described a concerning frequency of N. gonorrhoeae infection in females attended in an outcare patient. Also, most of the strains detected presented resistance to one or more antimicrobials.


Subject(s)
Anti-Infective Agents , Gonorrhea , Humans , Female , Male , Gonorrhea/epidemiology , Gonorrhea/drug therapy , Gonorrhea/microbiology , Azithromycin/therapeutic use , Brazil/epidemiology , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Neisseria gonorrhoeae/genetics , Ciprofloxacin/therapeutic use , Tetracycline , Anti-Infective Agents/therapeutic use
3.
Curr Diabetes Rev ; 17(8): e140421192834, 2021.
Article in English | MEDLINE | ID: mdl-33855947

ABSTRACT

BACKGROUND: Thousands of publications in recent years have addressed the induction of metabolic syndrome (MetS) in rodents. However, the criteria and the reference values for diagnosing this disease have not been defined. OBJECTIVE: Our main objective was to carry out a systematic review to gather evidence about the criteria for biochemical and anthropometric parameters in which scientific studies have relied on to report that rats developed MetS from a previous dietary manipulation. METHODS: We compiled characteristics and findings of diet-induced MetS with high-fat, high-carbohydrate, high-fat/high-carbohydrates, and cafeteria diet from PubMed and Science Direct databases published in the last 5 years. RESULTS: The results on the principal determinants for the syndrome, published in the reviewed articles, were chosen to propose reference values in the rat models of food induction. CONCLUSION: The values obtained will serve as reference cut-of points in the development of the disease; in addition, the compilation of data will be useful in planning and executing research protocols in animal models.


Subject(s)
Metabolic Syndrome , Animals , Diet/adverse effects , Humans , Metabolic Syndrome/diagnosis , Metabolic Syndrome/etiology , Rats , Rodentia
4.
Article in English | WPRIM (Western Pacific) | ID: wpr-902854

ABSTRACT

BACKGROUND/OBJECTIVES@#The exposure to sucrose in rats has mimic abnormalities attributed to metabolic syndrome (MetS). The effects of honey bee and “free” glucose and fructose, have not been explored in this context. The aim was to expose Wistar rodents to sucrose solution (SS), honey solution (HS) and fructose/glucose solution (GFS) at 30% to assess their effects. @*SUBJECTS/METHODS@#HS (n = 10), SS (n = 10) and GFS (n = 10) groups were formed.Solutions were ad libitum along 14-weeks. @*RESULTS@#Between solutions consumptions, honey was significantly 42% higher (P = 0.000), while similar consumption was observed among GFS and SS. The feeding pattern of HS consumption was irregular along experiment; while the food intake pattern showed the similar trend among groups along time. Non statistical differences were obtained in any biochemical and anthropometric measure, however, a higher concentration of leptin (721 ± 507 pg/mL), lower concentration of total cholesterol (TC; 48.87 ± 2.41 mg/100 mL), very low density lipoprotein (VLDL; 16.47 ± 6.55 mg/100 mL) and triglycerides (82.37 ± 32.77 mg/100 mL) was obtained in SS group. For anthropometric values, HS showed less total adipose tissue (AT; average 26 vs. 31–33 g) and adiposity index (average 6.11 vs. 7.6). Due to sugar-sweetened beverages consumption increases the risk for the development of chronic diseases; correlations between fluid intake and anthropometric and biochemical parameters were assessed. A moderate correlation was obtained in groups with the weight of total AT and solution intake; for the weight gain in GFS group and for triglycerides in HS and GFS.The highest hepatic tissue damage was observed in SS group with multiple intracytoplasmic vacuoles, atypia changes, moderate pleomorphism and hepatocellular necrosis. @*CONCLUSIONS@#In spite of the significantly higher consumption of HS, biochemical, anthropometrical and histological effects were not remarkably different in comparision to other sweeteners.

5.
Article in English | WPRIM (Western Pacific) | ID: wpr-895150

ABSTRACT

BACKGROUND/OBJECTIVES@#The exposure to sucrose in rats has mimic abnormalities attributed to metabolic syndrome (MetS). The effects of honey bee and “free” glucose and fructose, have not been explored in this context. The aim was to expose Wistar rodents to sucrose solution (SS), honey solution (HS) and fructose/glucose solution (GFS) at 30% to assess their effects. @*SUBJECTS/METHODS@#HS (n = 10), SS (n = 10) and GFS (n = 10) groups were formed.Solutions were ad libitum along 14-weeks. @*RESULTS@#Between solutions consumptions, honey was significantly 42% higher (P = 0.000), while similar consumption was observed among GFS and SS. The feeding pattern of HS consumption was irregular along experiment; while the food intake pattern showed the similar trend among groups along time. Non statistical differences were obtained in any biochemical and anthropometric measure, however, a higher concentration of leptin (721 ± 507 pg/mL), lower concentration of total cholesterol (TC; 48.87 ± 2.41 mg/100 mL), very low density lipoprotein (VLDL; 16.47 ± 6.55 mg/100 mL) and triglycerides (82.37 ± 32.77 mg/100 mL) was obtained in SS group. For anthropometric values, HS showed less total adipose tissue (AT; average 26 vs. 31–33 g) and adiposity index (average 6.11 vs. 7.6). Due to sugar-sweetened beverages consumption increases the risk for the development of chronic diseases; correlations between fluid intake and anthropometric and biochemical parameters were assessed. A moderate correlation was obtained in groups with the weight of total AT and solution intake; for the weight gain in GFS group and for triglycerides in HS and GFS.The highest hepatic tissue damage was observed in SS group with multiple intracytoplasmic vacuoles, atypia changes, moderate pleomorphism and hepatocellular necrosis. @*CONCLUSIONS@#In spite of the significantly higher consumption of HS, biochemical, anthropometrical and histological effects were not remarkably different in comparision to other sweeteners.

6.
Rev Assoc Med Bras (1992) ; 65(7): 1022-1031, 2019 Aug 05.
Article in English | MEDLINE | ID: mdl-31389518

ABSTRACT

OBJECTIVE: The energy imbalance produced by an increase in caloric intake and/or decrease in energy expenditure induces obesity. However, the fatty acid composition of a diet can affect the metabolism in different ways, having a role in the development of obesity. AIM: To determine the effect of different fatty acids types and composition on Diet-Induced Thermogenesis (DIT) and postprandial energy expenditure in humans. METHODS: A search in the PubMed and Web of Science databases, yielded a total of 269 potential articles as a first result; 254 were excluded according to the criteria. RESULTS: Fifteen articles were used for this systematic review. The studies analyzed report different effects of the fatty acids of the treatment on the diet-induced thermogenesis. Evidence indicates that the consumption of polyunsaturated fatty acids causes a greater DIT than saturated fatty acids. Also, the consumption of medium-chain fatty acids compared to long-chain fatty acids has been shown to increase DIT. Likewise, the use of certain oils has shown positive effects on postprandial energy expenditure, as is the case of olive oil, compared to rapeseed oil. CONCLUSIONS: The use of specific types of fatty acids in the everyday diet can increase postprandial energy expenditure in humans. Nevertheless, longer-term studies are required.


Subject(s)
Energy Metabolism/physiology , Fatty Acids/chemistry , Meals/physiology , Postprandial Period/physiology , Diet , Female , Humans , Male , Thermogenesis/physiology
7.
Rev. Assoc. Med. Bras. (1992, Impr.) ; 65(7): 1022-1031, July 2019. tab, graf
Article in English | LILACS | ID: biblio-1013010

ABSTRACT

SUMMARY The energy imbalance produced by an increase in caloric intake and/or decrease in energy expenditure induces obesity. However, the fatty acid composition of a diet can affect the metabolism in different ways, having a role in the development of obesity. AIM To determine the effect of different fatty acids types and composition on Diet-Induced Thermogenesis (DIT) and postprandial energy expenditure in humans. METHODS A search in the PubMed and Web of Science databases, yielded a total of 269 potential articles as a first result; 254 were excluded according to the criteria. RESULTS Fifteen articles were used for this systematic review. The studies analyzed report different effects of the fatty acids of the treatment on the diet-induced thermogenesis. Evidence indicates that the consumption of polyunsaturated fatty acids causes a greater DIT than saturated fatty acids. Also, the consumption of medium-chain fatty acids compared to long-chain fatty acids has been shown to increase DIT. Likewise, the use of certain oils has shown positive effects on postprandial energy expenditure, as is the case of olive oil, compared to rapeseed oil. CONCLUSIONS The use of specific types of fatty acids in the everyday diet can increase postprandial energy expenditure in humans. Nevertheless, longer-term studies are required.


RESUMO O desequilíbrio energético produzido pelo aumento da ingestão calórica e/ou diminuição do gasto energético provoca obesidade. Sem embargo, a composição de ácidos graxos da dieta pode afetar diferencialmente o metabolismo, tendo um papel no desenvolvimento da obesidade. OBJETIVO Determinar os efeitos de diferentes tipos de ácidos graxos e sua composição na termogênese induzida por dieta e no gasto energético pós-prandial em humanos. MÉTODOS Uma busca nas bases de dados da PubMed e da Web of Science gerou um total de 269 artigos potenciais como primeiro resultado; 254 foram excluídos de acordo com os critérios. RESULTADOS Quinze artigos foram utilizados para esta revisão sistemática. Os estudos analisados informam os efeitos diferenciais dos ácidos graxos no tratamento da termogênese induzida pela dieta. As evidências indicam que o consumo dos ácidos graxos poli-insaturados ocasiona maior DIT que os ácidos graxos saturados. Além disso, demonstra-se que o consumo dos ácidos graxos da cadeia média, em comparação com os ácidos graxos da cadeia longa, aumenta o DIT. Do mesmo modo, o uso de certos azeites demonstra os efeitos positivos sobre o gasto de energia pós-prandial, como é o caso do azeite de oliva, em comparação com o azeite de colza. CONCLUSÃO O uso de tipos específicos de ácidos graxos na dieta habitual pode aumentar o gasto de energia pós-prandial nos seres humanos. Sem embargo, é necessária maior investigação no longo prazo.


Subject(s)
Humans , Male , Female , Postprandial Period/physiology , Energy Metabolism/physiology , Fatty Acids/chemistry , Meals/physiology , Thermogenesis/physiology , Diet
8.
Article in English | WPRIM (Western Pacific) | ID: wpr-742307

ABSTRACT

In the indeterminate chronic period of Chagas disease (ChD) the treatment has not been conclusive, because the serological negativization requires many years. This study aims to evaluate the efficacy of nifurtimox (NF) in the treatment of chronic ChD in prolonged follow-up by serological techniques of indirect immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA) IgG comparing 2 groups of patients, treated and non treated. Mann-Whitney test was performed for ELISA and IFA, with significant difference between the groups (P < 0.05). IgG levels were lower in individuals treated compared with untreated patients, indicating chemotherapeutic efficacy in prolonged follow-up.


Subject(s)
Humans , Chagas Disease , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique, Indirect , Follow-Up Studies , Immunoglobulin G , Immunoglobulins , Nifurtimox , Trypanosoma cruzi , Trypanosoma
9.
Mol Cancer Ther ; 16(8): 1717-1726, 2017 08.
Article in English | MEDLINE | ID: mdl-28416604

ABSTRACT

Fibroblast growth factor receptor (FGFR) genetic alterations are frequently observed in cancer, suggesting that FGFR inhibition may be a promising therapy in patients harboring these lesions. Identification of predictive and pharmacodynamic biomarkers to select and monitor patients most likely to respond to FGFR inhibition will be the key to clinical development of this class of agents. Sensitivity to FGFR inhibition and correlation with FGFR pathway activation status were determined in molecularly annotated panels of cancer cell lines and xenograft models. Pathway inhibition in response to FGFR inhibitor treatment was assessed in cell lines (both in vitro and in vivo) and in samples from patients treated with the FGFR inhibitor JNJ-42756493 (erdafitinib). Frequency of FGFR aberrations was assessed in a panel of NSCLC, breast, prostate, ovarian, colorectal, and melanoma human tumor tissue samples. FGFR translocations and gene amplifications present in clinical specimens were shown to display potent transforming activity associated with constitutive pathway activation. Tumor cells expressing these FGFR activating mutants displayed sensitivity to the selective FGFR inhibitor erdafitinib and resulted in suppression of FGFR phosphorylation and downstream signal transduction. Clinically, patients receiving erdafitinib showed decreased Erk phosphorylation in tumor biopsies and elevation of serum phosphate. In a phase I study, a heavily pretreated bladder cancer patient with an FGFR3-TACC3 translocation experienced a partial response when treated with erdafitinib. This preclinical study confirmed pharmacodynamics and identified new predictive biomarkers to FGFR inhibition with erdafitinib and supports further clinical evaluation of this compound in patients with FGFR genetic alterations. Mol Cancer Ther; 16(8); 1717-26. ©2017 AACR.


Subject(s)
Oncogenes , Pyrazoles/pharmacology , Quinoxalines/pharmacology , Receptors, Fibroblast Growth Factor/antagonists & inhibitors , Receptors, Fibroblast Growth Factor/genetics , Animals , Biomarkers, Tumor/metabolism , Male , Oncogene Proteins, Fusion/genetics , Pyrazoles/therapeutic use , Quinoxalines/therapeutic use , Rats, Nude , Tomography, X-Ray Computed , Urinary Bladder Neoplasms/diagnostic imaging , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology
10.
Agenda ; 30(1): 85-95, 2016 01 02.
Article in English | MEDLINE | ID: mdl-28058030

ABSTRACT

South Africa's Constitution, Bill of Rights, and Freedom Charter are globally ground-breaking for providing provisions of non-discrimination, and, of particular note, on the basis of sexual orientation. Since the introduction of these protective frameworks, lesbian, gay, bisexual, transgender, intersex, and queer (LGBTIQ) communities, allies, and advocates in the country have won major legal battles on these issues; however, in spite of these successes, LGBTIQ communities continue to face hostility and violence. As a result, South African LGBTIQ individuals often travel to urban centres, such as Johannesburg, in the hope that these spaces will be more tolerant of their sexual orientation and gender identity; the reality, however, suggests otherwise. Moreover, despite South Africa's designation as a safe haven for LGBTIQ communities, migrants from other African countries - where same-sex relationships are criminalised - are overwhelmingly met with xenophobic verbal, emotional, physical, and political violence. This article describes the authors' engagement with nine lesbian, gay and bisexual (LGB) migrants and asylum seekers from Zimbabwe, Malawi, and elsewhere in South Africa during a weeklong poetry workshop exploring their lived experiences in Johannesburg. This workshop followed a body mapping and narrative writing workshop held previously with the same participants. This article investigates the themes identified from the body mapping process that guided the poems produced: migration, violence, citizenship, and freedom. The poetry created during the workshop illuminates how lesbian, gay, and bisexual migrants in Johannesburg work on a daily basis to build social trust as they demand to be seen and recognised, to enact their rights, to make and remake homes, to show up in public as Black people, as LGB individuals, and as human beings. We explore these strategies of citizen-making as informed by the LGB poets with whom we had the opportunity to work.

11.
Invest Clin ; 54(1): 20-33, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23781710

ABSTRACT

The purpose of this research was to investigate how the knowledge and attitudes have influence in Cervical Cancer (CC) screening among Venezuelan women, by realizing a cross-sectional descriptive study based on a structured non disguised questionnaire with closed ended questions: yes/no questions and multiple choices. The survey was performed on 691 volunteers, of which 595 were analyzed. Each patient was asked to fill in the questionnaire. Four hundred ninety three of 522 (94.4%) answered that they knew that Pap smear is for screening CC. Knowledge of Pap smear was statistically significant when it was compared to high educational level (p < 0.0001) although 185 (76%) of 244 low educational level interviewees answered that they had the knowledge that the Pap smear is used for screening of CC. Four hundred four of 504 (84.7%; p < 0.001) mentioned that they had a Pap smear at least once. One hundred ninety two (38.1%) of 504 women were adherent to an annual Pap smear test and more than half of the women (n = 337, 67%) had the last Pap smear in the last 1-3 years. Women with a high educational level showed higher adherence to the annual Pap smear screening (68.2%). Two hundred fifty seven (87.4%) of 294 said that they remembered when they got the information about Pap smear. The conclusions of this investigation were that our women were aware about Pap smear, had a good attitude to have a Pap smear and to be adherent to a regularly performed screening.


Subject(s)
Early Detection of Cancer/psychology , Health Knowledge, Attitudes, Practice , Papanicolaou Test , Patient Acceptance of Health Care/statistics & numerical data , Uterine Cervical Neoplasms/prevention & control , Vaginal Smears/psychology , Adolescent , Adult , Aged , Aged, 80 and over , Attitude to Health , Cross-Sectional Studies , Early Detection of Cancer/statistics & numerical data , Educational Status , Female , Guideline Adherence , Health Care Surveys , Health Promotion , Humans , Information Dissemination , Marital Status/statistics & numerical data , Middle Aged , Parity , Patient Acceptance of Health Care/psychology , Pregnancy , Surveys and Questionnaires , Urban Population , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/psychology , Vaginal Smears/statistics & numerical data , Venezuela/epidemiology , Young Adult
12.
Neurosci Lett ; 451(3): 257-60, 2009 Feb 27.
Article in English | MEDLINE | ID: mdl-19146920

ABSTRACT

Attention-deficit hyperactivity disorder (ADHD) is a clinically complex and multifactorial psychiatric disorder of inattention, hyperactivity and impulsivity. Family, twin and adoption studies suggest a genetic influence in the etiology of ADHD. Two variable number of tandem repeats (VNTR) polymorphic systems have been frequently associated with this disorder: the 7 repeat (R) allele in exon 3 of the dopamine receptor D4 (DRD4) and the 10R allele located in the 3' untranslated region (UTR) of the dopamine transporter (DAT1). We conducted a case-control association study between ADHD and these polymorphisms in a group of adolescent inhabitants of the metropolitan area of Mexico City. In addition, we evaluated the interaction between these genes, the disorder and its associated psychiatric comorbidities. No positive association between ADHD and the 7R allele of DRD4 or the 10R allele of DAT1 was observed; however, compared to controls, patients with internalized comorbidities had a lesser frequency of genotypes with the 7R allele of DRD4 and the 10/10 genotype of DAT1. A logistic regression analysis showed that the simultaneous absence of the 10/10 DAT1 and 7/7 DRD4 genotypes predicts membership to the group of ADHD patients with internalized comorbidities (e.g. anxiety, depression). Our results highlight the importance of cross-ethnic research and the possibility of a distinct genetic basis that underlies the type of comorbidities associated with ADHD. This result should be considered in terms of the study design, and further replication is necessary in an independent sample.


Subject(s)
Attention Deficit Disorder with Hyperactivity/genetics , Dopamine Plasma Membrane Transport Proteins/genetics , Dopamine/metabolism , Genetic Predisposition to Disease/genetics , Polymorphism, Genetic/genetics , Receptors, Dopamine D4/genetics , Adolescent , Anxiety Disorders/genetics , Attention Deficit Disorder with Hyperactivity/ethnology , Attention Deficit Disorder with Hyperactivity/metabolism , Brain/metabolism , Brain/physiopathology , Brain Chemistry/genetics , Case-Control Studies , Child , Comorbidity , DNA Mutational Analysis , Depressive Disorder/genetics , Gene Frequency , Genetic Testing , Genotype , Humans , Logistic Models , Mexico/ethnology
13.
Clin Ther ; 28(10): 1569-81, 2006 Oct.
Article in English | MEDLINE | ID: mdl-17157113

ABSTRACT

BACKGROUND: Many patients with poorly controlled type 2 diabetes mellitus (DM) receive, as initial insulin treatment, the addition of a basal formulation to an existing regimen of oral antidiabetic drug (OAD) therapy. Used this way, the insulin analogue detemir has been associated with improved glycemic control of a magnitude similar to neutral protamine Hagedorn (NPH), with lower rates of hypoglycemia and weight gain. Initial studies investigated detemir administered BID, but pharmacologic data suggest that detemir might be effective with QD administration. OBJECTIVES: The aims of this study were to compare the effectiveness and tolerability of detemir versus NPH administered QD together with > or =1 OAD in poorly controlled type 2 DM, and to compare different administration times of detemir. METHODS: This 20-week, multicenter, randomized, open-label, 3-arm, parallel-group trial was conducted at 91 centers across Europe and the United States. Men and women were eligible for participation if they were aged > or =18 years, had a body mass index (BMI) < or =40 kg/m(2), had a diagnosis of type 2 DM of at least 12 months' duration, and were insulin naive. Eligible patients also had a glycosylated hemoglobin (HbA(1c)) concentration value not outside the range of 7.5% to 11.0% following at least 3 months' treatment with > or =10 AD. Patients were randomly assigned to receive an evening SC injection of detemir, a prebreakfast injection of detemir, or an evening injection of NPH insulin (1:1:1), administered at initial doses of 10 IU (U). RESULTS: A total of 504 patients were enrolled 5 men, 219 women; mean [SD] age, 59 [11] years; mean [SD] BMI, 30 [5] kg/m2; insulin detemir before breakfast, 168; insulin detemir evening, 170; NPH insulin evening, 166). The intent-to-treat population comprised 498 patients. Morning and evening detemir were associated with reductions in HbA(1c) similar to those with evening NPH (raw mean decreases, -1.58%, -1.48%, and -1.74%, respectively). Nine-point profile and fasting and predinner plasma glucose data found morning detemir to be associated with a different diurnal glycemic profile compared with the evening regimens. Compared with evening NPH, 24-hour and nocturnal hypoglycemia were reduced by 53% (P = 0.019) and 65% (P = 0.031), respectively, with evening detemir. Incidences of hypoglycemia did not differ significantly between groups that received morning and evening detemir, but nocturnal hypoglycemia was reduced further, by 87%, with morning detemir compared with evening NPH (P < 0.001). Weight gain was 1.2, 0.7, and 1.6 kg with morning detemir, evening detemir, and NPH, respectively (P = 0.005 for evening detemir vs NPH). No between-treatment differences were seen in other tolerability end points. CONCLUSIONS: The results of this study in patients whose type 2 DM was poorly controlled with > or =1 OAD suggest that insulin detemir QD in the morning or evening can be used to improve glycemic control. Compared with NPH, insulin detemir may offer some tolerability advantages in this role.


Subject(s)
Insulin/administration & dosage , Administration, Oral , Aged , Diabetes Mellitus, Type 2/drug therapy , Drug Administration Schedule , Female , Glycated Hemoglobin/analysis , Humans , Insulin/therapeutic use , Male , Middle Aged , Treatment Outcome
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