Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies.

Psychosocial barriers to self -care among Hispanic women with type 2 diabetes mellitus

This cross-sectional survey-designed study investigated the presence and influence of psychosocial barriers to diabetes self-management practices among Hispanic women with type 2 diabetes mellitus. Women (n = 128) who were diagnosed and being treated for type 2 diabetes were recruited from the Miami-Dade area in South Florida. A Beck Depression Inventory-II, Diabetes Care Profile, Diabetes Knowledge Test, Diabetes Empowerment, Multidimensional Health Locus of Control, and Perceived Stress Scales were administered, along with assessment of diet through a 24-hour recall and anthropometric evaluation by body composition analysis and body mass index computation. ^ Mean (± SD) age for subjects was 50.15 ± 15.93 and age at diagnosis was 42.46 ± 14.69. Mean glycosylated hemoglobin (A 1C) was 8.55 ± 1.39. Diabetes education had not been received by 46.9% of subjects. Psychosocial status had previously been evaluated in only 4 participants. Forty percent of participants were assessed as depressed and 17% moderately to severely so. Depression correlated significantly (p < 0.01) with A1C (r = 0.242), perceived stress (r = 0.566), and self-rated health (r = −0.523). Perceived stress correlated significantly (p < 0.01) with A1C (r = 0.388), understanding of diabetes (r = 0.282), self-rated health (r = −0.372) and diabetes empowerment (r = −0.366). For Cuban women, perceived stress (β = 0.418, p = 0.033) was the only significant predictor of A1C, while among non-Cuban Hispanic women, self-reported health (β = −0.418, p = 0.003) and empowerment (β = 0.432, p = 0.004) were better predictors. The most desirable DM status among the women surveyed (high diet adherence, low exercise barriers, and A1C ≤ 7) was associated with superior self-rated health, more support from family and friends, and greater empowerment. ^ This study revealed the error in considering Hispanics a homogenous entity in treating disease, as their cultural backgrounds and concentration in a community can greatly influence management of a chronic disease like diabetes. The strong correlations found between diabetes-related health indicators and psychosocial factors such as depression and perceived stress suggest that psychosocial assessment of patients must be more strongly advocated in diabetes care. Psychosocial assessment of ethnically diverse diabetic populations is especially vital if greater knowledge is to be gained about their barriers to self-care so that diabetes treatment and thus outcomes are enhanced. ^

Importance of risk factor management in diabetic patients and reduction in Stage B heart failure

BACKGROUND: A number of studies have demonstrated the presence of a diabetic cardiomyopathy, increasing the risk of heart failure development in this population. Improvements in present-day risk factor control may have modified the risk of diabetes-associated cardiomyopathy.

AIM: We sought to determine the contemporary impact of diabetes mellitus (DM) on the prevalence of cardiomyopathy in at-risk patients with and without adjustment for risk factor control.

DESIGN: A cross-sectional study in a population at risk for heart failure.

METHODS: Those with diabetes were compared to those with other cardiovascular risk factors, unmatched, matched for age and gender and then matched for age, gender, body mass index, systolic blood pressure and low density lipoprotein cholesterol.

RESULTS: In total, 1399 patients enrolled in the St Vincent's Screening to Prevent Heart Failure (STOP-HF) cohort were included. About 543 participants had an established history of DM. In the whole sample, Stage B heart failure (asymptomatic cardiomyopathy) was not found more frequently among the diabetic cohort compared to those without diabetes [113 (20.8%) vs. 154 (18.0%), P = 0.22], even when matched for age and gender. When controlling for these risk factors and risk factor control Stage B was found to be more prevalent in those with diabetes [88 (22.2%)] compared to those without diabetes [65 (16.4%), P = 0.048].

CONCLUSION: In this cohort of patients with established risk factors for Stage B heart failure superior risk factor management among the diabetic population appears to dilute the independent diabetic insult to left ventricular structure and function, underlining the importance and benefit of effective risk factor control in this population on cardiovascular outcomes.

Visual functioning and health-related quality of life in diabetic patients about to undergo anti-vascular endothelial growth factor treatment for sight-threatening macular edema

Purpose To examine patient-reported outcome (PRO) in a selected group of Swedish patients about to receive anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). Material and methods In this cross-sectional study, 59 patients with diabetes mellitus, who regularly visited the outpatient eye-clinics, were included. Sociodemographic and clinical data were collected and the patients completed PRO measures before starting anti-VEGF treatment. PRO measures assessed eye-specific outcomes (NEI-VFQ-25) and generic health-related quality of life (SF-36). Results The participants consisted of 30 men and 29 women (mean age, 68.5 years); 54 (92 %) patients had type 2 diabetes; Five (9%) patients had moderate or severe visual impairment; 28 (47 %) were classified as having mild visual impairment. Some of the patients reported overall problems in their daily lives, such as with social relationships, as well as problems with impaired sight as a result of reduced distance vision. Conclusions Further studies are needed to investigate PRO factors related to low perceived general health in this patient population. It is important to increase our understanding of such underlying mechanisms to promote improvements in the quality of patient care.

Importância do conhecimento da diabetes mellitus pelo médico dentista

Este estudo tem como tema a “Importância do conhecimento da Diabetes Mellitus pelo médico dentista”, com o objetivo de através da revisão literária mostrar ao Médico Dentista a importância de uma boa anamnese e exame clínico para a detecção de doenças sistêmicas como a Diabetes Mellitus que interfere na saúde bucal do paciente e consequentemente no tratamento e em seu prognóstico. Devido a todos os transtornos que a diabetes provoca, a responsabilidade do médico dentista se torna cada vez maior tendo a responsabilidade de diminuir os focos de infecção de origem bucal que contribuem na descompensação e evitando condutas que possam comprometer o estado geral de saúde do paciente. Por isso, é de extrema importância que se estabeleça o planejamento dos cuidados especiais para o atendimento odontológico dos pacientes com diabetes, diminuindo o risco de intercorrências durante e após o atendimento.

Relevância no atendimento do idoso portador de diabetes mellitus tipo 2 em Medicina Dentária

A saúde oral na terceira idade é um fator indispensável para o envelhecimento saudável e uma boa qualidade de vida. O tratamento médico dentário não se resume apenas na cura de lesões já existentes, e é necessário promover um programa preventivo, que vise controlar a incidência de problemas médico dentários, um programa curativo para tratar os problemas presentes e também a procura de um programa educativo servindo de apoio para as demais ações. O paciente idoso requer uma atenção maior durante o tratamento, por isso é preciso que o Médico Dentista conheça adequadamente a saúde geral dos idosos, pois estes podem apresentar um quadro de saúde complexo e serem portadores de diversas patologias crónicas e serem poli-medicados. São necessários cuidados especiais na consulta e uma correta anamnese desses pacientes, realizando um exame clínico oral detalhado apoiada por exames complementares. O objetivo principal do presente estudo é analisar as condições clínicas dos idosos portadores de Diabetes Mellitus e as suas complicações orais e ainda a sistematização de procedimentos de forma protocolada para o atendimento médico dentário de idosos portadores desta patologia.

Impact of a community-based exercise programme on physical fitness in middle-aged and older patients with type 2 diabetes

Objectives: Physical fitness is related to all-cause mortality, quality of life and risk of falls in patients with type 2 diabetes. This study aimed to analyse the impact of a long-term community-based combined exercise program (aerobic + resistance + agility/balance + flexibility) developed with minimum and low-cost material resources on physical fitness in middle-aged and older patients with type 2 diabetes. Methods: This was a non-experimental pre-post evaluation study. Participants (N = 43; 62.92 ± 5.92 years old) were engaged in a community-based supervised exercise programme (consisting of combined aerobic, resistance, agility/balance and flexibility exercises; three sessions per week; 70 min per session) of 9 months' duration. Aerobic fitness (6-Minute Walk Test), muscle strength (30-Second Chair Stand Test), agility/balance (Timed Up and Go Test) and flexibility (Chair Sit and Reach Test) were assessed before (baseline) and after the exercise intervention. Results: Significant improvements in the performance of the 6-Minute Walk Test (Δ = 8.20%, p < 0.001), 30-Second Chair Stand Test (Δ = 28.84%, p < 0.001), Timed Up and Go Test (Δ = 14.31%, p < 0.001), and Chair Sit and Reach Test (Δ = 102.90%, p < 0.001) were identified between baseline and end-exercise intervention time points. Conclusions: A long-term community-based combined exercise programme, developed with low-cost exercise strategies, produced significant benefits in physical fitness in middle-aged and older patients with type 2 diabetes. This supervised group exercise programme significantly improved aerobic fitness, muscle strength, agility/balance and flexibility, assessed with field tests in community settings.

FEEDING AND DIABETES MELLITUS: PERCEPTION AND FOOD CONSUMPTION BY ELDERLY PEOPLE IN THE HINTERLANDS OF PERNAMBUCO

Objective: To evaluate the knowledge of diabetes diet and identify factors that may interfere with the adherence to nutritional therapy and food choices of participants in a Community Center for the Elderly in Sairé, PE. Methods: A quantitative, descriptive and cross-sectional study, which evaluated 39 attendees of that center, from July to August 2014, with or without diabetes mellitus. Two questionnaires were applied to assess socioeconomic data, nutrition knowledge and cultural factors, and check the consumption of food with high and low glycemic index. Data was analyzed using the Assistat Program 7.0 Beta version. Results: The majority of the respondents have knowledge about types of foods that may influence the treatment of diabetes mellitus, as 51.2% (n=20) reported knowing some food that can reduce the risk for diabetes onset or assist in its treatment. Most of the participants reported having acquired such knowledge through the television 35% (n=7) and conversation with peers 35% (n=7). Evaluation of the food intake evidenced higher consumption of foods with high glycemic index. However, among diabetic patients, foods with low glycemic index are consumed more times per week. Conclusion: The knowledge about nutrition and diabetes mellitus was considered adequate, but socioeconomic and cultural factors may interfere in the adherence to diet therapy for diabetes or in the food choices made by the individuals. However, food consumption was considered appropriate among diabetics.

Prevalence, types and factors associated with echocardiographic abnormalities among newly diagnosed diabetic patients at Mulago Hospital.

Background: The prevalence of Diabetes mellitus (DM) is on a rise in sub-Saharan Africa and will more than double by 2025. Cardiovascular disease (CVD) accounts for up to 2/3 of all deaths in the diabetic population. Of all the CVD deaths in DM, 3/4 occur in sub Saharan Africa (SSA). Non invasive identification of cardiac abnormalities, such as Left Ventricular Hypertrophy (LVH), diastolic and systolic dysfunction, is not part of diabetes complications surveillance programs in Uganda and there is limited data on this problem. This study sought to determine the prevalence, types and factors associated with echocardiographic abnormalities among newly diagnosed diabetic patients at Mulago National referral hospital in Uganda. Methods: In this cross sectional study conducted between June 2014 and December 2014, we recruited 202 newly diagnosed adult diabetic patients. Information on patients\' socio-demographics, bio-physical profile, biochemical testing and echocardiographic findings was obtained for all the participants using a pre-tested questionnaire. An abnormal echocardiogram in this study was defined as the presence of LVH, diastolic and/or systolic dysfunction and wall motion abnormality. Bivariate and multivariate logistic regression analyses were used to investigate the association of several parameters with echocardiographic abnormalities. Results: Of the 202 patients recruited, males were 102(50.5%) and the mean age was 46±15 years. Majority of patients had type 2 DM, 156(77.2%) and type 1 DM, 41(20.3%) with mean HbA1C of 13.9±5.3%. Mean duration of diabetes was 2 months. The prevalence of an abnormal echocardiogram was 67.8 % (95% CI 60%-74%). Diastolic dysfunction, systolic dysfunction, LVH and wall motion abnormalities were present in 55.0%, 21.8%, 19.3% and 4.0% of all the participants respectively. In bivariate logistic regression analysis, the factors associated with an abnormal echocardiogram were age (OR 1.09 [95% CI 1.06–1.12], P <0.0001), type 2 DM (OR 5.8[95% CI 2.77-12.07], P<0.0001), hypertension (OR 2.64[95% CI 1.44-4.85], P=0.002), obesity (OR 3.51[955 CI 1.25-9.84], P=0.017 and increased waist circumference (OR 1.02[95% CI 1.00-1.04], P=0.024. On Multiple logistic regression analysis, age was the only factor associated with an abnormal echocardiogram (OR 1.09[95%CI 1.05-1.15], P<0.0001). Conclusion: Echocardiographic abnormalities were common among newly diagnosed adults with DM. Traditional CVD risk factors were associated with an abnormal echocardiogram in this patient population. Due to a high prevalence of echocardiographic abnormalities among newly diagnosed diabetics, we recommend screening for cardiac disease especially in patients who present with traditional CVD risk factors. This will facilitate early diagnosis, management and hence better patient outcomes.

Biochemical parameters response to weight loss in patients with non-alcoholic steatohepatitis.

Background: Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that is capable of progressing to end-stage liver disease, but generally has a benign course. Non-alcoholic steatohepatitis (NASH) is a growing public health problem with no approved therapy. NASH projected to be the leading cause of liver transplantation in the United States by 2020. Obesity, non-insulin-dependent diabetes mellitus and hyperlipidaemia are the most common associations of the disease. Global prevalence of NASH is 10-24% amongst general population but increases to 25-75% in obese diabetic individuals. Objective: There is an urgent need for efficient therapeutic options as there is still no approved medication. The aim of this study was to detect changes in biochemical parameters including insulin resistance, cytokines, blood lipid profile and liver enzymes following weight loss in patients with non-alcoholic steatohepatitis. Materials and methods: One hundred obese patients with NASH, their age between 35-50 years, body mass index (BMI) from 30 to 35 Kg/m2 were included in the study in two subgroups; the first group (A) received moderate aerobic exercise training in addition to diet regimen , where the second group (B) received no treatment intervention. Results: The mean values of leptin, TNF-α, IL6, IL8, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Homeostasis Model Assessment-Insulin Resistance- index (HOMA-IR), Total Cholesterol (TC), Low Density Lipoprotein Cholesterol (LDL-c) , Triglycerides (TG) and BMI were significantly decreased in group (A), where the mean value of Adiponectin and High Density Lipoprotein Cholesterol (HDL-c) were significantly increased, while there were no significant changes in group (B). Also, there was a significant difference between both groups at the end of the study. Conclusion: Weight loss modulates insulin resistance, adiponectin, leptin, inflammatory cytokine levels and markers of hepatic function in patients with nonalcoholic steatohepatitis.

Stable Incretin Mimetics Counter Rapid Deterioration of Bone Quality in Type 1 Diabetes Mellitus.

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Modulation of immune cells and Th1/Th2 cytokines in insulin-treated type 2 diabetes mellitus.

Background: The role of the immune system in insulin resistance associated with type 2 diabetes has been suggested. Objectives: We assessed the profile of Th1/Th2 cytokines along with the frequencies of immune cells in insulin-treated type 2 diabetic patients (T2DP). Methods: 45 T2D patients and 43 age-matched healthy subjects were selected. Serum concentrations of T-helper type 1 (Th1) and Th2 cytokines and the frequencies of innate and adaptive immunity cells were assessed. Results: T2DP were hyperglycemic and showed high level of insulin, normal levels of triglycerides and total-cholesterol and without any change in HDL-cholesterol.Compared to healthy subjects, T2DP exhibited significant decreased frequencies of neutrophils, without any change in monocytes, eosinophils and natural killer cells. The percentages of total lymphocytes (CD3+) and CD8+-T-cells decreased whereas those of regulatory T-cells increased without any change in CD4+ T-cells in T2DP. Interestingly, the frequencies of effector CD4+-T and B-cells increased in T2DP. Serum concentrations of IL-2, IFN-γ and IL-4 decreased while IL-10 significantly enhanced in T2DP, suggesting a differentiation of CD4+T helper cells towards IL-10-producing- Teff-cells in these patients. Conclusion: Insulin-treated type 2 diabetes is associated with anti-inflammatory profile consistent with differentiation of CD4+-Th-cells towards IL-10-producing-Teff-cells, concomitant with increased frequencies of Treg and B-cells, and this may probably offer prevention against certain infections or autoimmune/inflammatory diseases.

Impact of weight loss on oxidative stress and inflammatory cytokines in obese type 2 diabetic patients.

Background: Type 2 diabetes mellitus is associated with abnormal markers of inflammatory cytokines and oxidative stress markers. Although, these abnormalities could be modulated with weight reduction; there is limitation in clinical studies that have addressed the beneficial effects of weight reduction in modulating biomarkers of inflammatory cytokines and oxidative stress for obesity associated with type 2 diabetes mellitus. Objective: This study was designed to detect the effects of weight loss on the inflammatory cytokines, oxidative stress markers in obese type 2 diabetic patients. Material and Methods: Eighty obese patients with type 2 diabetes mellitus, their age ranged from 35-57 years and their body mass index ranged from 31-35 kg/m2 were equally assigned into 2 groups: the weight reduction group received aerobic exercises, diet regimen, where as the control group received medical treatment only for 12 weeks. Results: The mean values of body mass index (BMI), tumor necrosis factor–alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (sCRP), conjugated dienes (CD) and malondialdehyde (MDA) were significantly decreased, while the mean values of glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione (GSH) were significantly increased in patients of group (A), while changes were not significant in group (B). Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) at the end of the study. Conclusion: Weight loss ameliorates inflammatory cytokines and oxidative stress markers in obese type 2 diabetic patients.

Transient hyperglycemia in patients with tuberculosis in Tanzania: implications for diabetes screening algorithms.

BACKGROUND: Diabetes mellitus (DM) increases tuberculosis risk while tuberculosis, as an infectious disease, leads to hyperglycemia. We compared hyperglycemia screening strategies in controls and patients with tuberculosis in Dar es Salaam, Tanzania. METHODS: Consecutive adults with tuberculosis and sex- and age-matched volunteers were included in a case-control study between July 2012 and June 2014. All underwent DM screening tests (fasting capillary glucose [FCG] level, 2-hour CG [2-hCG] level, and glycated hemoglobin A1c [HbA1c] level) at enrollment, and cases were tested again after receipt of tuberculosis treatment. Association of tuberculosis and its outcome with hyperglycemia was assessed using logistic regression analysis adjusted for sex, age, body mass index, human immunodeficiency virus infection status, and socioeconomic status. Patients with tuberculosis and newly diagnosed DM were not treated for hyperglycemia. RESULTS: At enrollment, DM prevalence was significantly higher among patients with tuberculosis (n = 539; FCG level > 7 mmol/L, 4.5% of patients, 2-hCG level > 11 mmol/L, 6.8%; and HbA1c level > 6.5%, 9.3%), compared with controls (n = 496; 1.2%, 3.1%, and 2.2%, respectively). The association between hyperglycemia and tuberculosis disappeared after tuberculosis treatment (adjusted odds ratio [aOR] for the FCG level: 9.6 [95% confidence interval {CI}, 3.7-24.7] at enrollment vs 2.4 [95% CI, .7-8.7] at follow-up; aOR for the 2-hCG level: 6.6 [95% CI, 4.0-11.1] vs 1.6 [95% CI, .8-2.9]; and aOR for the HbA1c level, 4.2 [95% CI, 2.9-6.0] vs 1.4 [95% CI, .9-2.0]). Hyperglycemia, based on the FCG level, at enrollment was associated with tuberculosis treatment failure or death (aOR, 3.3; 95% CI, 1.2-9.3). CONCLUSIONS: Transient hyperglycemia is frequent during tuberculosis, and DM needs confirmation after tuberculosis treatment. Performance of DM screening at tuberculosis diagnosis gives the opportunity to detect patients at risk of adverse outcome.

The quality of care of diabetic patients in rural Malawi: A case of Mangochi district

Background Diabetes mellitus is a global public health problem. In Malawi, the prevalence of diabetes is 5.6% but the quality of care has not been well studied. Objective The aim of this study was to assess the quality of care offered to diabetic patients in Mangochi district. Methods This was a cross sectional descriptive study. Quantitative data were collected using a questionnaire from a sample of 75 diabetic patients (children and adults) who attended the Diabetes Clinic at Mangochi District Hospital between 20012 and 2013. Qualitative data were also collected using semi-structured interviews with eight Key Informants from among the District Health Management Team. Frequencies and cross-tabulation were obtained from the quantitative data. Patients’ master cards were checked to validate results. Clinical knowledge about diabetes, care practices and resources were the themes analysed from the qualitative data. Results Among the 75 participants interviewed, 46 were females and 29 males. The overall mean age was 48.3 years (45.6 for females and 53.3 for males). More than half of patients had little or no information about diabetes (40.0 % (n=30) and 22.7 (n=17) respectively. The majority of patients were taking their medicines regularly 98.7% (n=74). Only 17.3% (n=13) reported having their feet inspected regularly. Fifty-six percent of patients were satisfied about services provision. Some nurses and clinicians were trained on diabetes care but most of them left. Guidelines on diabetes management were not accessible. There were shortages in medicines (e.g. soluble insulin) and reagents. Information Education and Communication messages were offered through discussions, experiences sharing and posters. Conclusion Quality of diabetes care provided to diabetic patients attended to Mangochi hospital was sub-optimal due to lack of knowledge among patients and clinicians and resources. More efforts are needed towards retention of trained staff, provision of pharmaceutical and laboratory resources and health education.