Metformin in patients with type 2 diabetes and kidney disease:a systematic review

IMPORTANCE: Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis. OBJECTIVE: To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. EVIDENCE ACQUISITION: In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining tometformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014.We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial. RESULTS: Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety ofmetformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus-use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use. CONCLUSIONS AND RELEVANCE: Available evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function.

Overweight/Obesity and HIV Disease Progression in HIV+ Adults in Botswana

Studies indicate that overweight and obesity protect against HIV-disease progression in antiretroviral therapy (ART)-naïve patients. We examined retrospectively the relationship of overweight/obesity with HIV-disease progression in ART-naïve HIV+ adults in Botswana in a case-control study with 18-month follow-up, which included 217 participants, 139 with BMI 18.0-24.9 kg/m2 and 78 with BMI ≥25 kg/m2. Archived plasma samples were used to determine inflammatory markers: leptin and bacterial endotoxin lipopolysaccharide (LPS), and genotype single nucleotide polymorphisms (SNPs) of the Fat Mass and Obesity Associated Gene (FTO). At baseline, BMI was inversely associated with risk for AIDS-defining conditions (HR=0.218; 95%CI=0.068, 0.701, P=0.011), and higher fat mass was associated with reduced risk of the combined outcome of CD4+cell count ≤250/µL and AIDS-defining conditions, whichever occurred earlier (HR=0.918; 95%CI=0.847, 0.994, P=0.036) over 18 months, adjusting for age, gender, marriage, children, and baseline CD4+cell count and HIV-viral load. FTO-SNP rs17817449 was associated with BMI (OR=1.082; 95%CI=1.001, 1.169; P=0.047). Fat mass was associated with the risk alleles of rs1121980 (OR=1.065; 95%CI=1.009, 1.125, P=0.021), rs8050136 (OR=1.078; 95%CI=1.021, 1.140; P=0.007), and rs17817449 (OR=1.086; 95%CI=1.031, 1.145; P=0.002), controlling for age, gender, tribe, total energy intake, and activity. There were no associations of SNPs with markers of disease progression. Leptin levels were positively associated with BMI (β=1.764; 95%CI=0.788, 2.739; P=0.022) and fat mass (β=0.112; 95%CI=0.090, 0.135; P<0.001), but inversely with viral load (β=-0.305; 95%CI=-0.579, -.031; P=0.030). LPS levels were inversely associated with BMI (OR=0.790, 95%CI=0.630, 0.990; P=0.041), and fat mass (OR=0.852, 95%CI=0.757, 0.958; P=0.007) and directly with viral load (OR=2.608, 95%CI=1.111, 6.124; P=0.028), adjusting for age, gender, smoking and %fat mass. In this cohort, overweight/obesity predicted slower HIV-disease progression. Obesity may confer an advantage in maintaining fat stores to support the overactive immune system. FTO-SNPs may contribute to the variation in fat mass; however, they were not associated with HIV-disease progression. Our findings suggest that the obesity paradox may be explained by the association of increased LPS with lower BMI and higher viral load; while viral load decreased with increasing leptin levels. Studies in African populations are needed to clarify whether genetic variation and inflammation mediate the obesity paradox in HIV-disease progression.

Association between miscarriage and cardiovascular disease in a Scottish cohort

Funding This work was supported by a grant from the ‘Merel Foundation’, the Netherlands. The AMND receives support from the University of Aberdeen.

Association between osteoarthritis and cardiovascular disease : Systematic review and meta-analysis

© The European Society of Cardiology 2015.

Association between miscarriage and cardiovascular disease in a Scottish cohort

Funding This work was supported by a grant from the ‘Merel Foundation’, the Netherlands. The AMND receives support from the University of Aberdeen.

Association between osteoarthritis and cardiovascular disease : Systematic review and meta-analysis

© The European Society of Cardiology 2015.

Interleukin-4 receptor alpha gene variants and allergic disease

The interleukin-4 (IL-4) signalling cascade has been identified as a pathway potentially important in the development of asthma. Genetic variants within this signalling pathway might contribute to the risk of developing asthma in a given individual. A number of polymorphisms have been described within the IL-4 receptor alpha (IL-4Ralpha) gene. In addition polymorphism occurs in the promoter for the IL-4 gene itself. This commentary accompanies a paper by C Ober et al describing the contribution of IL-4Ralpha polymorphism to susceptibility to asthma and atopy in the Hutterite population and other outbred populations collected during the collaborative studies on the genetics of asthma (CSGA) programme

Pharmacogenetics, pharmacogenomics and airway disease

The availability of a draft sequence for the human genome will revolutionise research into airway disease. This review deals with two of the most important areas impinging on the treatment of patients: pharmacogenetics and pharmacogenomics. Considerable inter-individual variation exists at the DNA level in targets for medication, and variability in response to treatment may, in part, be determined by this genetic variation. Increased knowledge about the human genome might also permit the identification of novel therapeutic targets by expression profiling at the RNA (genomics) or protein (proteomics) level. This review describes recent advances in pharmacogenetics and pharmacogenomics with regard to airway disease

Good Practices in the field of Health Promotion and Chronic Disease Prevention

Background; Approach and Concept; Methods (Country reviews; Definition of Good Practice Criteria; Identification of Good Practice Examples; Identification of transferable practices / elements); Outputs

Joint Action CHRODIS Work Package 5 - Good practices in the field of health promotion and chronic disease prevention across the life cycle: outcomes at a glance

Associated Partners in the Work Package 5: National Health Institute Doutor Ricardo Jorge (INSA), Portugal (Luciana Costa)

Patatin-like phospholipase domain-containing protein 3 and Liver Disease: Opportunities to Unravel Mechanisms Underlying Statistical Associations

International audience

Provision of care services for rheumatic and musculoskeletal diseases-related foot and ankle problems: a survey from sixteen european countries

Background: The increased prevalence of foot and ankle pathologies in Rheumatic and Musculoskeletal diseases (RMDs) is well documented1, however the provision of foot & ankle (F&A) healthcare services for people with RMDs in Europe has not been evaluated. Objectives: To assess the current healthcare systems for providing foot & ankle healthcare services for people with RMDs in Europe. Methods: A survey was undertaken to evaluate current provision of F&A health care services for people with RMDs across Europe. A questionnaire was distributed to all 22 country presidents representing HP associations within EULAR. The questionnaire used was developed and piloted (in 7 countries) by the EULAR F&A Study Group, and structured to capture the provision and type of F&A services for people with RMDs. When the HP presidents felt unable to answer specific questions they were encouraged to consult a colleague who may be better placed to provide the answers. Results: Sixteen questionnaires were completed (Norway, Ireland, Sweden, Hungary, Netherlands, UK, Denmark, Portugal, Italy, Switzerland, Austria, France, Czech Republic, Spain, Belgium, Malta). Of the 16, 13 respondents indicated provision of F&A health care services in their country, but only three countries had services specialising in RMD-related F&A problems (Netherlands, UK, Malta). The professions providing the care for patients with RMD-related F&A problems were different depending on the pathology and the country (Table1). Podiatrists provided care for F&A pain and deformity problems in 11 countries, but provided F&A ulcer care in only 8 countriesConclusions: Only 3 countries have F&A health care services specialised to the needs of people with RMDs. The professions providing the care varied between countries, and also depended on the F&A pathology. Interestingly, F&A healthcare services were provided by professions that do not solely specialised in F&A care. Further research is needed to assess the variation of F&A healthcare services between and within European countries and the impact on healthcare of various F&A healthcare service designs. References: Woodburn, J. & Helliwell, P. Foot problems in rheumatology. Rheumatology 36, 932-934 (1997).

Relationship between menopause and periodontal disease: a cross-sectional study in a Portuguese population

Article published under a “Creative Commons Attribution Noncommercial License”, enabling the unrestricted non-commercial use, distribution, and reproduction of the published article in any medium, provided that the original work is properly cited.

Overweight/obesity and HIV disease progression in HIV+ adults in Botswana

Studies indicate that overweight and obesity protect against HIV-disease progression in antiretroviral therapy (ART)-naïve patients. We examined retrospectively the relationship of overweight/obesity with HIV-disease progression in ART-naïve HIV+ adults in Botswana in a case-control study with 18-month follow-up, which included 217 participants, 139 with BMI 18.0-24.9 kg/m 2 and 78 with BMI ≥25 kg/m2. Archived plasma samples were used to determine inflammatory markers: leptin and bacterial endotoxin lipopolysaccharide (LPS), and genotype single nucleotide polymorphisms (SNPs) of the Fat Mass and Obesity Associated Gene (FTO). ^ At baseline, BMI was inversely associated with risk for AIDS-defining conditions (HR=0.218; 95%CI=0.068, 0.701, P=0.011), and higher fat mass was associated with reduced risk of the combined outcome of CD4+cell count ≤250/µL and AIDS-defining conditions, whichever occurred earlier (HR=0.918; 95%CI=0.847, 0.994, P=0.036) over 18 months, adjusting for age, gender, marriage, children, and baseline CD4+cell count and HIV-viral load. ^ FTO-SNP rs17817449 was associated with BMI (OR=1.082; 95%CI=1.001, 1.169; P=0.047). Fat mass was associated with the risk alleles of rs1121980 (OR=1.065; 95%CI=1.009, 1.125, P=0.021), rs8050136 (OR=1.078; 95%CI=1.021, 1.140; P=0.007), and rs17817449 (OR=1.086; 95%CI=1.031, 1.145; P=0.002), controlling for age, gender, tribe, total energy intake, and activity. There were no associations of SNPs with markers of disease progression. ^ Leptin levels were positively associated with BMI (β=1.764; 95%CI=0.788, 2.739; P=0.022) and fat mass (β=0.112; 95%CI=0.090, 0.135; P<0.001), but inversely with viral load (β=-0.305; 95%CI=-0.579, -.031; P=0.030). LPS levels were inversely associated with BMI (OR=0.790, 95%CI=0.630, 0.990; P=0.041), and fat mass (OR=0.852, 95%CI=0.757, 0.958; P=0.007) and directly with viral load (OR=2.608, 95%CI=1.111, 6.124; P=0.028), adjusting for age, gender, smoking and %fat mass. ^ In this cohort, overweight/obesity predicted slower HIV-disease progression. Obesity may confer an advantage in maintaining fat stores to support the overactive immune system. FTO-SNPs may contribute to the variation in fat mass; however, they were not associated with HIV-disease progression. Our findings suggest that the obesity paradox may be explained by the association of increased LPS with lower BMI and higher viral load; while viral load decreased with increasing leptin levels. Studies in African populations are needed to clarify whether genetic variation and inflammation mediate the obesity paradox in HIV-disease progression.^

Quality of life and chronic disease in patients receiving primary health care

Problem Statement: Chronic disease entails physical, psychological and social issues with a decrease in the quality of life. The assessment of QoL has been applied as indicator in patients with chronic diseases. Research Questions: What is the quality of life in patients with chronic disease? What are the socio-demographic variables that influence the quality of life in patients? Purpose: To assess the quality of life in patients suffering from chronic disease and identify socio-demographic variables which influence the quality of life of patients suffering from chronic disease. Research Methods: We conducted a cross-sectional analytical study using a sample composed of 228 users (134 females) from a Family Health Unit in the municipality of Viseu. Data collection was made by means of a questionnaire, consisting of sociodemographic variables, the SF-12 scale and the existence of chronic disease was assessed through the questions – “Do you currently suffer from any chronic disease?”; “If so, which one(s)?”. Findings: The most common chronic diseases were hypertension (59.9%). Female patients with a chronic disease reported worse physical functioning, role-physical and role-emotional; increased bodily pain and better quality of life regarding general health. Male patients showed worse role-physical, increased bodily pain and vitality. Sociodemographic variables which were associated with quality of life were area of residence, academic qualifications and work situation. Conclusion: Chronic disease affects quality of life negatively. Quality of life in both patients groups was associated with socio-demographic variables. Health-related quality of life is an essential issue and should be considered as a priority in health policies.