Core Standards of the EUBIROD Project. Defining a European Diabetes Data Dictionary for Clinical Audit and Healthcare Delivery.

BACKGROUND: A set of core diabetes indicators were identified in a clinical review of current evidence for the EUBIROD project. In order to allow accurate comparisons of diabetes indicators, a standardised currency for data storage and aggregation was required. We aimed to define a robust European data dictionary with appropriate clinical definitions that can be used to analyse diabetes outcomes and provide the foundation for data collection from existing electronic health records for diabetes. METHODS: Existing clinical datasets used by 15 partner institutions across Europe were collated and common data items analysed for consistency in terms of recording, data definition and units of measurement. Where necessary, data mappings and algorithms were specified in order to allow partners to meet the standard definitions. A series of descriptive elements were created to document metadata for each data item, including recording, consistency, completeness and quality. RESULTS: While datasets varied in terms of consistency, it was possible to create a common standard that could be used by all. The minimum dataset defined 53 data items that were classified according to their feasibility and validity. Mappings and standardised definitions were used to create an electronic directory for diabetes care, providing the foundation for the EUBIROD data analysis repository, also used to implement the diabetes registry and model of care for Cyprus. CONCLUSIONS: The development of data dictionaries and standards can be used to improve the quality and comparability of health information. A data dictionary has been developed to be compatible with other existing data sources for diabetes, within and beyond Europe.

A family history of diabetes determines poorer glycaemic control and younger age of diabetes onset in immigrants from the Middle East compared with native Swedes.

AIMS: Immigrant populations from the Middle East develop diabetes earlier than indigenous European populations; however, the underlying etiology is poorly understood. This study looked at the risk factors associated with early diabetes onset and, in non-diabetics, glycaemic control in immigrants from Iraq compared with native Swedes. METHODS: This cross-sectional population-based study comprised 1398 Iraqi immigrants and 757 Swedes (ages 30-75years) residing in the same area of Malmö, Sweden. Outcomes were age at diabetes onset and glycaemic control (HbA1c) as assessed by Cox proportional hazards and linear regression, respectively. RESULTS: In Iraqis vs Swedes, clustering in the family history (in two or more relatives) was more prevalent (23.2% vs 3.6%, P<0.001) and diabetes onset occurred earlier (47.6years vs 53.4years, P=0.001). Having an Iraqi background independently raised the hazard ratio (HR) for diabetes onset. Diabetes risk due to family history was augmented by obesity, with the highest HRs observed in obese participants with clustering in the family history (HR: 5.1, 95% CI: 3.2-8.2) after adjusting for country of birth and gender. In participants without previously diagnosed diabetes (Iraqis: n=1270; Swedes: n=728), HbA1c levels were slightly higher in Iraqis than in Swedes (4.5% vs 4.4%, P=0.038). This difference was explained primarily by clustering in the family history rather than age, obesity, lifestyle or socioeconomic status. CONCLUSION: The study shows that the greater predisposition to diabetes in Middle Eastern immigrants may be explained by a more extensive family history of the disorder; clinical interventions tailored to Middle Eastern immigrants with such a family history are thus warranted.

Ethnicity is an independent risk indicator when estimating diabetes risk with FINDRISC scores: a cross sectional study comparing immigrants from the Middle East and native Swedes.

AIMS: This study sought to compare type 2 diabetes (T2D) risk indicators in Iraqi immigrants with those in ethnic Swedes living in southern Sweden. METHODS: Population-based, cross-sectional cohort study of men and women, aged 30-75 years, born in Iraq or Sweden conducted in 2010-2012 in Malmö, Sweden. A 75g oral glucose tolerance test was performed and sociodemographic and lifestyle data were collected. T2D risk was assessed by the Finnish Diabetes Risk Score (FINDRISC). RESULTS: In Iraqi versus Swedish participants, T2D was twice as prevalent (11.6 vs. 5.8%, p<0.001). A large proportion of the excess T2D risk was attributable to larger waist circumference and first-degree family history of diabetes. However, Iraqi ethnicity was a risk factor for T2D independently of other FINDRISC factors (odds ratio (OR) 2.5, 95% CI 1.6-3.9). The FINDRISC algorithm predicted that more Iraqis than Swedes (16.2 vs. 12.3%, p<0.001) will develop T2D within the next decade. The total annual costs for excess T2D risk in Iraqis are estimated to exceed 2.3 million euros in 2005, not accounting for worse quality of life. CONCLUSIONS: Our study suggests that Middle Eastern ethnicity should be considered an independent risk indicator for diabetes. Accordingly, the implementation of culturally tailored prevention programs may be warranted.

Worse glycaemic control in LADA patients than in those with type 2 diabetes, despite a longer time on insulin therapy.

AIMS/HYPOTHESIS: Our aim was to study whether glycaemic control differs between individuals with latent autoimmune diabetes in adults (LADA) and patients with type 2 diabetes, and whether it is influenced by time on insulin therapy. METHODS: We performed a retrospective study of 372 patients with LADA (205 men and 167 women; median age 54 years, range 35-80 years) from Swedish cohorts from Skåne (n = 272) and Västerbotten (n = 100). Age- and sex-matched patients with type 2 diabetes were included as controls. Data on the use of oral hypoglycaemic agents (OHAs), insulin and insulin-OHA combination therapy was retrieved from the medical records. Poor glycaemic control was defined as HbA(1c) ≥7.0% (≥53 mmol/mol) at follow-up. RESULTS: The individuals with LADA and with type 2 diabetes were followed for an average of 107 months. LADA patients were leaner than type 2 diabetes patients at diagnosis (BMI 27.7 vs 31.0 kg/m(2); p < 0.001) and follow-up (BMI 27.9 vs 30.2 kg/m(2); p < 0.001). Patients with LADA had been treated with insulin for longer than those with type 2 diabetes (53.3 vs 28.8 months; p < 0.001). There was no significant difference between the patient groups with regard to poor glycaemic control at diagnosis, but more patients with LADA (67.8%) than type 2 diabetes patients (53.0%; p < 0.001) had poor glycaemic control at follow-up. Patients with LADA had worse glycaemic control at follow-up compared with participants with type 2 diabetes (OR = 1.8, 95% CI 1.2, 2.7), adjusted for age at diagnosis, HbA(1c), BMI at diagnosis, follow-up time and duration of insulin treatment. CONCLUSIONS/INTERPRETATION: Individuals with LADA have worse glycaemic control than patients with type 2 diabetes despite a longer time on insulin therapy.

Feasibility of the FINDRISC questionnaire to identify individuals with impaired glucose tolerance in Swedish primary care. A cross-sectional population-based study.

AIM: To evaluate the performance of the FINDRISC questionnaire as a tool to recruit individuals with impaired glucose tolerance for lifestyle intervention programmes. METHODS: A cross-sectional population-based study in primary Health Care Centres in a middle-sized Swedish town. All 9734 individuals, aged 35-75 years, living within a defined area, were invited by mail to fill in and return the FINDRISC questionnaire. Participants with a risk score ≥ 15 (n = 525) were invited to perform an oral glucose tolerance test while those with known diabetes were excluded. RESULTS: In total, 5452 questionnaires (58%) were returned and revealed a mean risk-score of 8.5 ± 4.5 (mean ± SD). We found that 525 participants had a risk-score ≥ 15 and 302 (58%) were further examined with an oral glucose tolerance testing (OGTT). Among them we detected 11% with previously undiagnosed Type 2 diabetes, 16% with impaired glucose tolerance and 29% with impaired fasting glucose. A FINDRISC score ≥ 15 was associated with a positive predictive value of 55% for impaired glucose metabolism (impaired fasting glucose + impaired glucose tolerance + Type 2 diabetes) and of 16% for impaired glucose tolerance, respectively. The positive predictive value for impaired glucose tolerance did not increase to more than 17% when choosing the cut-point 17, while there was a significant increase in the positive predictive value for impaired glucose metabolism (70%). CONCLUSIONS: The FINDRISC questionnaire is a useful instrument for identification of individuals with impaired glucose metabolism but seems less effective for detection of individuals with impaired glucose tolerance. Strategies to find individuals with impaired glucose tolerance for implementation of lifestyle changes in primary care should therefore be developed further.

Electrophysiological studies in newly onset type 2 diabetes without visible vascular retinopathy.

The purpose of this study was to investigate the early alterations of retinal function, assessed with electrophysiology, in newly onset type 2 diabetes patients without vascular retinopathy. Seventeen patients with newly diagnosed type 2 diabetes (duration 7±3 months), without any vascular retinopathy in fundus photographs, were examined with full-field electroretinogram (ERG) and multifocal ERG (mfERG). The results were compared with those of age-matched subjects without diabetes. In the dark-adapted full-field ERG, the a-wave and the 30-Hz flicker implicit times were delayed in diabetes patients compared to controls, P=0.001 and P=0.020. In the first-order kernel of the mfERG, the first positive wave, P1, was delayed in all areas measured. The electrophysiological examinations demonstrate early alterations of retinal function characterised by a delayed a-wave implicit time in the dark-adapted full-field ERG, representing the rod signalling, and alterations in the multifocal ERG reflecting cone and/or postreceptoral function.

Can sulphonylurea addition to lifestyle changes help to delay diabetes development in subjects with impaired fasting glucose? The Nepi ANtidiabetes StudY (NANSY).

The Nepi ANtidiabetes StudY (NANSY) is a 5-year randomized, double-blind, placebo-controlled trial in Swedish primary care, examining whether the development of type 2 diabetes (T2D) and retinopathy (separately reported) would be delayed in 40- to 70-year-old subjects with impaired fasting glucose (IFG) who, in addition to lifestyle changes, were treated with either placebo or low-dosage sulphonylurea (SU) (1-mg glimepiride; Amaryl). Of 274 subjects (163 men, 111 women), 138 were allocated to placebo (46.0% men, 56.8% women) and 136 to glimepiride (54.0% men, 43.2% women). The primary endpoint was conversion to diabetes. Average follow-up time was 3.71 years; 96 subjects converted to diabetes, 55 allocated to placebo and 41 to glimepiride (absolute difference 9.8%; p = 0.072). In conclusion, the study failed to support the notion that low-dose SU added to lifestyle changes in IFG subjects would help to delay the conversion to diabetes.

Evaluation and comparison of guidelines for the management of people with type 2 diabetes from eight European countries.

METHODS: The most recent nationally recognised guidelines for type 2 diabetes from eight European countries (Belgium, England/Wales, France, Germany, Ireland, Italy, the Netherlands and Sweden) were compared. The Appraisal of Guidelines for Research and Evaluation (AGREE) instrument was used for quality assessment. Details of recommendations for key process and outcome indicators were also extracted. Appraisal and data extraction were conducted independently by two researchers. RESULTS: AGREE domain scores varied between guidelines, including a range of 31-95% for rigour of development. The highest mean domain scores were for Scope and Purpose (81%) and Clarity and Presentation (85%); the lowest was for Stakeholder Involvement (49%). Specific recommendations, including targets relating to intermediate outcomes, were broadly similar. However, at detailed level, there were variations, particularly in terms of the level of information provided, for example, only two countries' guidelines provided cut-off points in relation to risk associated with waist circumference. IMPLICATIONS: Our findings suggest that there are some areas of good practice relating to guideline development where more attention is needed. Despite a substantial degree of consensus for specified targets, observed differences at detailed level suggest a lack of consistency in relation to some aspects of the information provided to clinicians across Europe.

A variation in the cerebroside sulfotransferase gene is linked to exercise-modified insulin resistance and to type 2 diabetes.

AIMS: The glycosphingolipid beta-galactosylceramide-3-O-sulfate (sulfatide) is present in the secretory granules of the insulin producing beta-cells and may act as a molecular chaperone of insulin. The final step in sulfatide synthesis is performed by cerebroside sulfotransferase (CST) (EC 2.8.2.11). The aim of this study was to investigate whether two single nucleotide polymorphisms (SNP), rs2267161 located in an exon or rs42929 located in an intron, in the gene encoding CST are linked to type 2 diabetes (T2D). METHODS: As a population survey, 265 male and female patients suffering from T2D and 291 gender matched controls were examined. RESULTS: A higher proportion of T2D patients were heterozygous at SNP rs2267161 with both T (methionine) and C (valine) alleles present (49.8% versus 41.3%, P = .04). The calculated odd risk for T2D was 1.47 (1.01-2.15, P = .047). Among female controls, the homozygous CC individuals displayed lower insulin resistance measured by HOMA-IR (P = .05) than the C/T or TT persons; this was particularly prevalent in individuals who exercise (P = .03). CONCLUSION: Heterozygosity at SNP rs2267161 in the gene encoding the CST enzyme confers increased risk of T2D. Females with the CC allele showed lower insulin resistance.

Higher education and more physical activity limit the development of obesity in a Swedish rural population. The Skaraborg Project.

OBJECTIVE: To investigate the prevalence and the secular trends of obesity in a rural Swedish community with emphasis on the association with socioeconomic status and lifestyle. DESIGN: The Skaraborg Project cross-sectional population surveys were conducted in Vara, a rural community in the southwest of Sweden, every fifth year between 1977 and 2002. SUBJECTS: A total of 3365 residents (1634 men and 1731 women) aged 30-60 years. MEASUREMENTS: Obesity was defined as body mass index> or =30 kg m(-2). Information on ethnicity, marital status, socioeconomic status and lifestyle was collected by a questionnaire. RESULTS: In 1977-1982, the average prevalence of obesity was 14% in both men and women, and in 2002, the prevalence of obesity was 19% in men and 21% in women. The age-adjusted odds ratio (OR) of obesity in 2002 was 1.48 (1.00, 2.20) in men and 1.41 (0.97, 2.05) in women. Without the simultaneous increase in the level of education and leisure-time physical activity (LTPA), the risk of developing obesity could have been considerably higher; in men OR=3.08 (1.88, 5.03) and in women OR=2.72 (1.66, 4.44). In multivariate models, higher levels of education and LTPA were associated with protective effects on obesity in both men (OR=0.60 (0.43, 0.83) and OR=0.50 (0.45, 0.79)) and women (OR=0.73 (0.54, 0.98) and OR=0.57 (0.42, 0.78)), respectively. CONCLUSIONS: This study revealed an upward secular trend in the prevalence of obesity in a rural community in Sweden. Increasing levels of education and LTPA limit this ongoing development of obesity. Public health strategies for the prevention of obesity should consider the special condition in rural environments.

Detection of hydrogen peroxide using photofragmentation laser-induced fluorescence.

Photofragmentation laser-induced fluorescence (PF-LIF) is for the first time demonstrated to be a practical diagnostic tool for detection of hydrogen peroxide. Point measurements as well as two-dimensional (2D) measurements in free-flows, with nitrogen as bath gas, are reported. The present application of the PF-LIF technique involves one laser, emitting radiation of 266 nm wavelength, to dissociate hydrogen peroxide molecules into OH radicals, and another laser, emitting at 282.25 nm, to electronically excite OH, whose laser-induced fluorescence is detected. The measurement procedure is explained in detail and a suitable time separation between photolysis and excitation pulse is proposed to be on the order of a few hundred nanoseconds. With a separation time in that regime, recorded OH excitation scans were found to be thermal and the signal was close to maximum. The PF-LIF signal strength was shown to follow the same trend as the vapor pressure corresponding to the hydrogen peroxide liquid concentration. Thus, the PF-LIF signal appeared to increase linearly with hydrogen peroxide vapor-phase concentration. For 2D single shot measurements, a conservatively estimated value of the detection limit is 30 ppm. Experiments verified that for averaged point measurements the detection limit was well below 30 ppm.

Retinopathy in subjects with impaired fasting glucose: the NANSY-Eye baseline report.

AIMS: Network for Pharmacoepidemiology (NEPI) Antidiabetes Study-Eye is a randomized placebo-controlled Swedish trial investigating if treatment with sulphonylurea, in addition to dietary regulation and increased exercise, delays the development of retinopathy in subjects with impaired fasting glucose (IFG). METHODS: Subjects were surveyed in primary care with repeated fasting blood glucose measurements. Those with a mean of two consecutive values >or=5.6 and <6.1 mmol/l were invited to participate. Baseline physical examination included blood pressure and body mass index (BMI). Fundus photos were taken in two fields using 35-mm diafilm. The alternative classification of the Wisconsin Epidemiologic Study of Diabetic Retinopathy was used to classify the retinopathy level. RESULTS: At baseline, 90 men and 64 women with IFG were photographed. Of these, 16 subjects (10%) had mild or very mild retinopathy. There was no difference in occurrence of retinopathy between subjects with known diagnosis of hypertension or not. However, subjects with retinopathy had significantly higher systolic (154 vs. 141 mmHg, p = 0.013) and diastolic (86 vs. 81 mmHg, p = 0.008) blood pressure levels independent of differences in age, sex and known hypertension. There was a corresponding difference in BMI, being greater in subjects with than in those without retinopathy (32.4 vs. 29.2 kg/m(2), p = 0.013). There were no associations between levels of fasting blood glucose or haemoglobin A1c, on the one hand, and retinopathy, on the other. CONCLUSION: Retinopathy may be present even before type 2 diabetes is manifest. It is associated with higher blood pressure levels and higher BMI values, that is, with predominant features of the metabolic syndrome.

Association testing of common variants in the insulin receptor substrate-1 gene (IRS1) with type 2 diabetes.

AIMS/HYPOTHESIS: Activation of the insulin receptor substrate-1 (IRS1) is a key initial step in the insulin signalling pathway. Despite several reports of association of the G972R polymorphism in its gene IRS1 with type 2 diabetes, we and others have not observed this association in well-powered samples. However, other nearby variants might account for the putative association signal. SUBJECTS AND METHODS: We characterised the haplotype map of IRS1 and selected 20 markers designed to capture common variations in the region. We genotyped this comprehensive set of markers in several family-based and case-control samples of European descent totalling 12,129 subjects. RESULTS: In an initial sample of 2,235 North American and Polish case-control pairs, the minor allele of the rs934167 polymorphism showed nominal evidence of association with type 2 diabetes (odds ratio [OR] 1.25, 95% CI 1.03-1.51, p = 0.03). This association showed a trend in the same direction in 7,659 Scandinavian samples (OR 1.16, 95% CI 0.96-1.39, p = 0.059). The combined OR was 1.20 (p = 0.008), but statistical correction for the number of variants examined yielded a p value of 0.086. We detected no differences across rs934167 genotypes in insulin-related quantitative traits. CONCLUSIONS/INTERPRETATION: Our data do not support an association of common variants in IRS1 with type 2 diabetes in populations of European descent.

The influence of patent foramen ovale on oxygen desaturation in obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is associated with oxygen desaturation to a varying degree. A patent foramen ovale (PFO) may allow interatrial right-to-left shunting. The hypothesis of the current study was that oxygen desaturation will occur more often, in proportion to the frequency of respiratory disturbances, in OSA subjects with PFO than in those without. In a group of 209 subjects diagnosed with OSA, the proportion of desaturation to respiratory events was calculated as the ratio of oxygen desaturation index (ODI)/apnoea-hypopnoea index (AHI). A total of 15 cases with high proportional desaturation (ODI/AHI >or=0.66) were individually matched with 15 controls with low proportional desaturation (ODI/AHI or=20 bubbles passed over from the right to the left atrium after a single injection. The prevalence of large PFO was nine out of 15 (60%) in the high proportional desaturation group versus two out of 15 (13%) in the low proportional desaturation group. The median number of passing bubbles was positively correlated to minimum oxygen saturation among those with PFO. In conclusion, oxygen desaturation occurs more often, in proportion to the frequency of respiratory disturbances, in obstructive sleep apnoea subjects with a patent foramen ovale than in those without.

Residual risk for acute stroke in patients with type 2 diabetes and hypertension in primary care: Skaraborg Hypertension and Diabetes Project.

AIM: The aim of this study was to investigate the risk of acute stroke in subgroups of patients treated for hypertension and type 2 diabetes in primary care. METHODS: Patients with hypertension only (n = 695), type 2 diabetes only (n = 181) or both (n = 240), who consecutively attended an annual control in primary care in Skara, Sweden during 1992-1993, were evaluated for cardiovascular disease risk factors and enrolled in this study. Subjects with neither hypertension nor type 2 diabetes (n = 824) who participated in a population survey in the same community served as controls. Possible events of acute stroke through 2002 were validated using hospital records and death certificates. RESULTS: During a mean follow-up time of 8.4 years, 190 first events of acute stroke, fatal or non-fatal, were ascertained. Risk factor levels were generally higher in all patient categories than in controls. Stroke risk was significantly increased in all male patients: hazard ratio 4.2 (95% CI 2.1-8.4) in patients with both conditions, 3.3 (1.5-7.0) in those with type 2 diabetes alone and 2.8 (1.5-5.3) in those with hypertension alone (adjusted for age, total cholesterol, current smoking, BMI and physical activity). Corresponding findings in women were 2.9 (1.5-5.8) in patients with type 2 diabetes only and 2.4 (1.2-4.7) in those with both conditions. However, in women with hypertension only, a significant risk was seen first when subjects were truncated at 85 years of age. There were too few fatal stroke events for conclusive results on stroke mortality. CONCLUSIONS: A considerable risk of acute stroke remains in patients with type 2 diabetes and hypertension. Strategies for stricter multiple risk factor interventions should be implemented in primary care.

Utilisation of antihyperglycaemic drugs in ten European countries: different developments and different levels.

AIMS/HYPOTHESIS: The aim of this study was to compare developments in the utilisation of antihyperglycaemic drugs (AHGDs) in ten European countries. SUBJECTS AND METHODS: Data on the yearly utilisation of insulin and oral AHGDs were collected from public registers in Denmark, Finland, Norway, Sweden, Belgium, England, Germany, Italy, Portugal and Spain, and were expressed as defined daily doses per 1,000 inhabitants per day. RESULTS: Total AGHD utilisation increased everywhere, but at different rates and levels. Insulin utilisation doubled in England and Germany, but hardly changed in Belgium, Portugal or Italy. Sulfonylurea utilisation doubled in Spain, England and Denmark but was reduced in Germany and Sweden. Metformin utilisation increased greatly everywhere. There were two- to three-fold differences in AHGD utilisation even between neighbouring countries. In Finland, there were more users of both insulin (+120%) and oral AHGDs (+80%) than in Denmark, and the daily oral AHGD doses were higher. In Denmark and Sweden, AHGD utilisation was equal in subjects aged <45 years, but in those >or=45 years of age, both insulin and oral AHGD utilisation were twice as high in Sweden. CONCLUSIONS/INTERPRETATION: The ubiquitous increase in AHGD utilisation, particularly metformin, seems logical, considering the increasing prevalence of type 2 diabetes and the results of the UK Prospective Diabetes Study. However, the large differences even between neighbouring countries are more difficult to explain, and suggest different habits and attitudes in terms of screening and management of type 2 diabetes.

Hypertension prevalence in obstructive sleep apnoea and sex: a population-based case-control study.

Obstructive sleep apnoea (OSA) is a recognised risk factor for hypertension (HT). The current authors investigated confounders of this association in a sex-balanced community-based sample of patients with HT (n=161) from the Skaraborg Hypertension and Diabetes Project (n=1,149) and normotensive controls (n=183) from an age and sex stratified community-based population sample (n=1,109). All participants underwent ambulatory home polysomnography. Severe OSA (apnoea-plus-hypopnoea index (AHI)>or=30 events.h-1) was found in 47 and 25% of hypertensive and normotensive males, respectively. The corresponding numbers in females were 26 and 24%, respectively. The odds ratio (OR) for HT increased across AHI tertiles from 1.0 to 2.1 (95% confidence interval: 0.9-4.5) and 1.0 to 3.7 (95% CI: 1.7-8.2) in males, but not in females where the OR increased from 1.0 to 1.8 (95% CI: 0.8-3.9) and 1.0 to 1.6 (95% CI: 0.7-3.5). Regression analysis correcting for age, body mass index (or waist-hip ratio) and smoking did not eliminate the association between OSA and HT in males. The present data suggest that obstructive sleep apnoea is highly prevalent in both the general population and in patients with known hypertension. The contribution of obstructive sleep apnoea to hypertension risk may be sex dependent and higher in males than in females.

Increased risk of obesity associated with the variant allele of the PPARGC1A Gly482Ser polymorphism in physically inactive elderly men.

AIMS/HYPOTHESIS: The variant allele of the Gly482Ser polymorphism in peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PPARGC1A or PGC1alpha), a critical determinant of skeletal muscle metabolism, has been associated with obesity and type 2 diabetes. Previous studies indicate that these risks depend on sex and environmental triggers such as age. The aim of the present study was to investigate the possible interactions between genotype and age and physical activity on risk of obesity. METHODS: We genotyped PPARGC1A Gly482Ser, in a population-based study comprising 899 women and 902 men aged between 30 and 75 years in Vara, Sweden. RESULTS: Genotyping revealed that 56% of the males and 57% of the females carried the PPARGC1A 482Ser variant allele. Elderly males (>or=50 years) carrying 482Ser had an increased risk of obesity compared with subjects who were homozygous for the wild-type allele (odds ratio [OR]=1.99, 95% CI 1.14-3.47, p=0.015). The risk was restricted to males with a low leisure-time physical activity level, and was significantly weaker (OR=0.44, 95% CI 0.22-0.87, p=0.018) for the homozygous 482Gly carriers among this subgroup. No association with obesity was found in elderly males with a high level of physical activity, in younger males, or in females of any age group or level of physical activity. CONCLUSIONS/INTERPRETATION: Our findings confirm that sex and age should be considered when investigating the influence of the PPARGC1A Gly482Ser polymorphism on metabolic disease. The risk of obesity associated with 482Ser is evident only in physically inactive elderly male subjects. Whenever possible, the level of physical activity should be addressed in future studies on disease risk associated with PPARGC1A Gly482Ser.

Understanding adherence to official guidelines on statin prescribing in primary health care--a multi-level methodological approach.

OBJECTIVE: The aim was to investigate the role that municipalities and out-patient health care centres (HCCs) have in understanding adherence to official guidelines on statin prescribing. Our hypothesis was that after guideline publication, adherence to recommended statin prescription would increase and variance among HCCs and municipalities would decrease. Since multi-level regression analysis (MLRA) is a relatively new methodology in pharmacoepidemiology, we also aimed to explore the application of MLRA in our investigation. METHODS: We obtained data from the Swedish Corporation of Pharmacies record of sales regarding all initial prescriptions of statins issued between April and December 2003. We applied multi-level analysis on 34,514 individual prescriptions (level 1) nested within 226 HCCs (level 2), which in turn were nested within 33 municipalities (level 3). Temporal trends and gender differences were investigated by means of random slope analysis. Variance was expressed using median odds ratio (MOR) and interval odds ratio. RESULTS: HCCs appeared to be more relevant than municipalities for understanding the physicians' propensity to prescribe a recommended statin (MOR(HCC) = 1.96 and MOR(Municipality) = 1.41). Overall prevalence of adherence was very low (about 20%). After publication of the guidelines, prescription of recommended statins increased, and variance among HCCs decreased but only during the first 4 months of the observation period. CONCLUSION: The publication of official guidelines in the county of Scania exerted a positive influence on statin prescription but, at the end of the observation period, adherence was still low and practice variation high. These facts may reflect inefficient therapeutic traditions and suggest that more intensive interventions may be necessary to promote rational statin prescription.