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.

The association between glycated haemoglobin levels and P100 visual evoked potentials in diabetes mellitus

Diabetes mellitus (DM) is a metabolic disorder which is characterised by hyperglycaemia resulting from defects in insulin secretion, insulin action or both. The long-term specific effects of DM include the development of retinopathy, nephropathy and neuropathy. Cardiac disease, peripheral arterial and cerebrovascular disease are also known to be linked with DM. Type 1 diabetes mellitus (T1DM) accounts for approximately 10% of all individuals with DM, and insulin therapy is the only available treatment. Type 2 diabetes mellitus (T2DM) accounts for 90% of all individuals with DM. Diet, exercise, oral hypoglycaemic agents and occasionally exogenous insulin are used to manage T2DM. The diagnosis of DM is made where the glycated haemoglobin (HbA1c) percentage is greater than 6.5%. Pattern-reversal visual evoked potential (PVEP) testing is an objective means of evaluating impulse conduction along the central nervous pathways. Increased peak time of the visual P100 waveform is an expression of structural damage at the level of myelinated optic nerve fibres. This was an observational cross sectional study. The participants were grouped into two phases. Phase 1, the control group, consisted of 30 healthy non-diabetic participants. Phase 2 comprised of 104 diabetic participants of whom 52 had an HbA1c greater than 10% (poorly controlled DM) and 52 whose HbA1c was 10% and less (moderately controlled DM). The aim of this study was to firstly observe the possible association between glycated haemoglobin levels and P100 peak time of pattern-reversal visual evoked potentials (PVEPs) in DM. Secondly, to assess whether the central nervous system (CNS) and in particular visual function is affected by type and/or duration of DM. The cut-off values to define P100 peak time delay was calculated as the mean P100 peak time plus 2.5 X standard deviations as measured for the non-diabetic control group, and were 110.64 ms for the right eye. The proportion of delayed P100 peak time amounted to 38.5% for both diabetic groups, thus the poorly controlled group (HbA1c > 10%) did not pose an increased risk for delayed P100 peak time, relative to the moderately controlled group (HbA1c ≤ 10%). The P100 PVEP results for this study, do however, reflect significant delay (p < 0.001) of the DM group as compared to the non-diabetic group; thus, subclincal neuropathy of the CNS occurs in 38.5% of cases. The duration of DM and type of DM had no influence on the P100 peak time measurements.

Risk factors for type 2 diabetes mellitus and cardiovascular diseases in Hispanic adolescents

This cross-sectional study evaluated risk factors (RF) for type 2 diabetes (T2DM) and cardiovascular diseases (CVD) in 100 Hispanic adolescents(50 overweight, 50 non-overweight) aged 12-16 years, and their associations with body mass index (BMI), diet, physical activity (PA), gender, and birth weight (BW). The RF studied were fasting plasma glucose (FPG), insulin sensitivity (IS), total cholesterol (TC), triacylglycerols (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), acanthosis nigricans (AN), and blood pressure (BP). Dietary intakes were assessed using the Block Kids Questionnaire, fat-related intake behavior (FB) using the Fat-Related Diet Habits Questionnaire, and PA using the Modifiable Activity Questionnaire for Adolescents. Blood was collected after an overnight fast of 12 hours. All statistical analyses used SPSS 14.0. Overweight adolescents had presence of AN, higher BP, TC, TG, and LDL, and lower IS, ps < .001, as compared to non-overweight adolescents. Overweight adolescents were more likely to have 1 and 2 RF for T2DM and CVD as compared to having 0, ps < .001, and 2 RF as compared to having 1, p =.033. Adolescents with kilocalorie (Kcal) intake above requirements for age gender, and PA level were 4.6 times more likely to be overweight, p = .005. Overweight adolescents had worse FB, p = .011, and lower PA, p < .001. Adolescents with worse FB had higher BP, p = .016. Fiber below recommendations (14g/1,000 Kcal) was associated with being overweight, p = .012, and lower IS, p = .040. Adolescents with higher BW had higher FPG, p = .013. Our findings point to an association between being overweight and RF for T2DM and CVD, suggesting that overweight during adolescence may have serious health consequences for Hispanic adolescents. Also, our results indicate that Hispanic overweight adolescents eat more Kcal and less fiber than required, have worst FB, and less PA levels than their non-overweight counterparts. In addition, high BW and dietary habits of Hispanic adolescents, such as low fiber and FB, increase their risk for T2DM and CVD. We conclude that BMI can serve as a useful tool to identify Hispanic adolescents at risk for T2DM and CVD.

Forecasting future prevalence of type 2 diabetes mellitus in Syria

Background Type 2 diabetes mellitus (T2DM) is increasingly becoming a major public health problem worldwide. Estimating the future burden of diabetes is instrumental to guide the public health response to the epidemic. This study aims to project the prevalence of T2DM among adults in Syria over the period 2003–2022 by applying a modelling approach to the country’s own data. Methods Future prevalence of T2DM in Syria was estimated among adults aged 25 years and older for the period 2003–2022 using the IMPACT Diabetes Model (a discrete-state Markov model). Results According to our model, the prevalence of T2DM in Syria is projected to double in the period between 2003 and 2022 (from 10% to 21%). The projected increase in T2DM prevalence is higher in men (148%) than in women (93%). The increase in prevalence of T2DM is expected to be most marked in people younger than 55 years especially the 25–34 years age group. Conclusions The future projections of T2DM in Syria put it amongst countries with the highest levels of T2DM worldwide. It is estimated that by 2022 approximately a fifth of the Syrian population aged 25 years and older will have T2DM.

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. ^

Ethnic Differences in Insulin Resistance, Adiponectin Levels and Abdominal Obesity: Haitian Americans and African Americans, with and without Type 2 Diabetes Mellitus

Background: Metabolic outcomes of obesity and its associated disorders may not be equivalent across ethnicity and diabetes status. Aim: In this paper, we examined the association of abdominal obesity, by ethnicity and diabetes status, for indicators of glucose metabolism in Blacks. Methods: A cross sectional study was conducted in Haitian Americans (n= 186) and African Americans (n= 148) with and without type 2 diabetes mellitus (T2DM). Student’s t-test and Chi-squared test were used to assess differences in mean and proportion values between ethnicities with and without type 2 diabetes mellitus. Relationship between insulin resistance, ethnicity, diabetes status, abdominal obesity, and adiponectin levels were analyzed by analysis of covariance while controlling for confounding variables. Results:Haitian American participants were older (P = .032), had higher fasting plasma glucose (P = .036), and A1C (P = .016), but had lower levels of Hs-CRP (P < .001), insulin and HOMA2-IR and lower abdominal obesity (P = .030), than African Americans. Haitian Americans had significantly lower HOMA2-IR (P = .008) than African Americans when comparing both ethnicities with T2DM, high abdominal obesity, and adiponectin levels lower than the median ( Conclusion: The clinical significance of observed differences in insulin resistance, abdominal obesity, and adiponectin levels between Haitian Americans and African Americans could assist in forming public health policies that are ethnic specific.

Estudo da influência dos genes LRP5, TGFB1, IGF1 e IGF1R no metabolismo ósseo de pacientes com diabetes mellitus tipo 1

Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq

Perspetiva do fisioterapeuta sobre o Core Set da Classificação Internacional de Funcionalidade, Incapacidade e Saúde da Diabetes Mellitus

Introdução: Os core sets são desenvolvidos com o objetivo de identificar e agrupar categorias da Classificação Internacional de Funcionalidade, Incapacidade e Saúde (CIF) e que caraterizam os principais problemas de funcionalidade dos indivíduos com uma condição clinica específica. Ao simplificar o número de categorias da CIF, facilita-se a sua aplicação na prática clínica. Objetivos: O comprehensive core set da CIF para a Diabetes Mellitus (DM) representa o conjunto típico de problemas de funcionalidade em utentes com DM. O objetivo deste estudo visa a exploração da validade do conteúdo deste core set e identificar os problemas mais comuns de utentes com DM a partir da perspetiva do fisioterapeuta através da utilização da CIF. Metodologia: Foi realizado um estudo qualitativo, com fisioterapeutas com experiência no tratamento de utentes com DM. Os dados foram recolhidos segundo o método de Delphi, através da realização de três questionários. As respostas foram analisadas por dois investigadores que procederam ao linking para as categorias da CIF. O grau de concordância foi efetuado utilizando a estatística de kappa. Resultados: Sete fisioterapeutas de 5 centros de saúde da região centro de Portugal foram questionados na primeira e segunda ronda; seis completaram a terceira ronda. Os fisioterapeutas chegaram ao consenso sobre o total de 26 categorias da CIF, sendo que 19 correspondem às categorias presentes no core set e 7 às não incluídas no core set da CIF para a DM. Seis componentes foram identificados como fatores pessoais. Conclusões: As categorias presentes no comprehensive core set da CIF para a DM pela perspetiva dos fisioterapeutas foram apoiadas. Contudo, algumas categorias adicionais foram propostas para inclusão no comprehensive core set da CIF para a DM.

Fear of Falling and Balance Confidence in Older Adults with Diabetes Mellitus

Several determinants of fear of falling (FoF) and low balance confidence overlap with the consequences/complications of diabetes mellitus (DM). FoF is strongly associated with low balance confidence, and balance confidence mediates the relationship between FoF and balance and physical function. The purpose of this thesis was two-fold: (1) to examine the prevalence, severity and determinants of FoF in older adults (aged≥65) with DM, and (2) to evaluate the validity of the short version of the Activities-specific Balance Confidence scale (ABC-6) and its association with balance and postural control in older adults with DM. Three separate studies were conducted of older adults with DM (DM-group) and without DM (noDM-group). Study I revealed that although FoF prevalence adjusted for age and sex was not different between-groups, the DM-group had 8.8% fewer participants in the low and 8.4% more in the high Falls-Efficacy Scale International categories when compared to the noDM-group. Higher FoF severity in the DM-group was associated with poor physical performance, being female, fall history and clinical depressive symptoms. Study II provided evidence of convergent, discriminant and concurrent validity of the ABC-6 for use in older adults with DM with and without diabetic peripheral neuropathy (DPN). Notably, the ABC-6 was more sensitive in detecting subtle differences in balance confidence between the DM-group and noDM-group when compared to the original ABC scale (ABC-16), and can be administered in less time. Study III explored balance confidence (ABC-6) and its association with balance and postural control in older adults with DM. Subtle differences in axial segmental control (i.e., lower trunk roll velocity and higher head-trunk correlations) while walking and lower balance confidence were apparent in the DM-group, even in the absence of DPN, when compared to the noDM-group. Balance confidence partially explained the variance in head-trunk stiffening between-groups, and consequently low balance confidence in older adults with DM may contribute to the dependence on postural control strategies that are normally only utilized in high-risk situations. Findings from this thesis will help to guide the development of protocols for screening and intervention recommendations of patient education and targeted rehabilitation programs for older adults with DM.

Alleles that increase risk for type 2 diabetes mellitus are not associated with increased risk for Alzheimer's disease

Although epidemiological studies suggest that type 2 diabetes mellitus (T2DM) increases the risk of late-onset Alzheimer's disease (LOAD), the biological basis of this relationship is not well understood. The aim of this study was to examine the genetic comorbidity between the 2 disorders and to investigate whether genetic liability to T2DM, estimated by a genotype risk scores based on T2DM associated loci, is associated with increased risk of LOAD. This study was performed in 2 stages. In stage 1, we combined genotypes for the top 15 T2DM-associated polymorphisms drawn from approximately 3000 individuals (1349 cases and 1351 control subjects) with extracted and/or imputed data from 6 genome-wide studies (>10,000 individuals; 4507 cases, 2183 controls, 4989 population controls) to form a genotype risk score and examined if this was associated with increased LOAD risk in a combined meta-analysis. In stage 2, we investigated the association of LOAD with an expanded T2DM score made of 45 well-established variants drawn from the 6 genome-wide studies. Results were combined in a meta-analysis. Both stage 1 and stage 2 T2DM risk scores were not associated with LOAD risk (odds ratio = 0.988; 95% confidence interval, 0.972-1.004; p = 0.144 and odds ratio = 0.993; 95% confidence interval, 0.983-1.003; p = 0.149 per allele, respectively). Contrary to expectation, genotype risk scores based on established T2DM candidates were not associated with increased risk of LOAD. The observed epidemiological associations between T2DM and LOAD could therefore be a consequence of secondary disease processes, pleiotropic mechanisms, and/or common environmental risk factors. Future work should focus on well-characterized longitudinal cohorts with extensive phenotypic and genetic data relevant to both LOAD and T2DM.

Sjuksköterskans omvårdnadsåtgärder och råd till egenvård för att förebygga fotkomplikationer hos personer med diabetes mellitus typ II : En litteraturstudie

Bakgrund: Diabetes mellitus typ 2 (DMT2) ökar i världen och kan leda till allvarliga fotkomplikationer. Det har påvisats brister i den förbyggande vården för att undvika fotkomplikationer. Sjuksköterskan ansvarar för att stötta personer med DMT2 och målet är att få dem att känna sig självständiga och delaktiga i sin egenvård. Syfte: Syftet med studien var att belysa omvårdnadsåtgärder och egenvård som förebygger fotkomplikationer för personer med DMT2 Metod: En litteraturstudie som utgår ifrån 20 vetenskapliga artiklar med kvantitativ uppbyggnad. Sökningarna av Artiklarna är sökta i databaserna Cinahl och Pubmed. Samtliga artiklar är kvalitetsgranskade. Resultat: Identifiering av risker är en viktig faktor i förebyggandet av fotkomplikationer. Dagliga inspektioner och undersökningar av fötterna är viktiga egenvårdsråd som sjuksköterskan bör tilldela genom individuell undervisning. Sjuksköterskan skall efter bästa förmåga stötta och motivera personer med DMT2 till god egenvård. Slutsats: Sjuksköterskan bör undervisa och ge personer med DMT2 tillräcklig kunskap, för att självständigt kunna utföra förebyggande egenvård.

A systematic review of the effectiveness of lifestyle interventions for the prevention of type 2 diabetes mellitus (T2DM) in routine practice.

This document updates and extends a previously conducted systematic review and meta-analysis assessing the effectiveness of ‘real-world’ interventions for the prevention of type 2 diabetes mellitus (T2DM) in high risk populations.

Type 2 Diabetes Mellitus: Risk Evaluation and Advice in Undergraduate Students in Ashrafieh, Lebanon

Type 2 diabetes mellitus (T2DM) is a chronic lifestyle disease. It has become evident that T2DM occurs even among the younger age groups.1 In Lebanon, T2DM has a major public health impact through high disease prevalence, significant downstream pathophysiologic effects, and enormous financial liabilities.2

Cost-effectiveness Study of Antidiabetic Drugs in Type 2 Diabetes Mellitus Patients From Mumbai, India

Diabetes is fast gaining the status of a potential epidemic in India, with >62 million individuals currently diagnosed with the disease.1 India currently faces an uncertain future in relation to the potential burden that diabetes may impose on the country. An estimated US$ 2.2 billion would be needed to sufficiently treat all cases of type 2 diabetes mellitus (T2DM) in India.2 Many interventions can reduce the burden of this disease. However, health care resources are limited; thus, interventions for diabetes treatment should be prioritized.

Autocuidado dos adolescentes com diabetes mellitus tipo 1: responsabilidade no controlo da doença

Enquadramento: A diabetes mellitus tipo 1 (DM1) é uma doença cada vez mais prevalente na adolescência. Intervir no autocuidado é determinante para a gestão da doença. Objetivos: Determinar a responsabilidade dos adolescentes com DM1 nos papéis de autocuidado; analisar a relação da responsabilidade dos adolescentes com DM1 nos papéis de autocuidado com a idade e o género. Metodologia: Estudo descritivo-analítico e transversal. Participaram 51 adolescentes entre os 12 e os 18 anos seguidos em hospitais distritais da zona centro de Portugal. Foi aplicada uma escala de responsabilidade nos papéis de autocuidado, constituída por 15 itens distribuídos por 4 dimensões: manutenção da saúde; controlo da doença; diagnóstico, tratamento e medicação na DM1; e participação em serviços de saúde. Resultados: A maioria dos adolescentes assume responsabilidade própria elevada. O género não influencia a responsabilidade global, os rapazes evidenciam maior nível de responsabilidade na gestão de administração de insulina. Conclusão: Os adolescentes assumem responsabilidade própria no controlo da doença, evidencia-se responsabilidade partilhada com os pais ou outros no global e na participação em serviços de saúde.