A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

Increased registration of hypertension and cancer diagnoses after the introduction of a new reimbursement system

Objective. To investigate the impact on ICD coding behaviour of a new case-mix reimbursement system based on coded patient diagnoses. The main hypothesis was that after the introduction of the new system the coding of chronic diseases like hypertension and cancer would increase and the variance in propensity for coding would decrease on both physician and health care centre (HCC) levels. Design. Cross-sectional multilevel logistic regression analyses were performed in periods covering the time before and after the introduction of the new reimbursement system. Setting. Skaraborg primary care, Sweden. Subjects. All patients (n = 76 546 to 79 826) 50 years of age and older visiting 468 to 627 physicians at the 22 public HCCs in five consecutive time periods of one year each. Main outcome measures. Registered codes for hypertension and cancer diseases in Skaraborg primary care database (SPCD). Results. After the introduction of the new reimbursement system the adjusted prevalence of hypertension and cancer in SPCD increased from 17.4% to 32.2% and from 0.79% to 2.32%, respectively, probably partly due to an increased diagnosis coding of indirect patient contacts. The total variance in the propensity for coding declined simultaneously at the physician level for both diagnosis groups. Conclusions. Changes in the healthcare reimbursement system may directly influence the contents of a research database that retrieves data from clinical practice. This should be taken into account when using such a database for research purposes, and the data should be validated for each diagnosis

The prognosis of diabetic retinopathy in patients with type 2 diabetes since 1996-1998: the Skaraborg Diabetes Register

Diabetes mellitus is the main reason for visual impairment among patients of working ages. The aim of this paper was to investigate the prognosis of eye complications in patients with diabetes during 10 years of follow-up and contributing risk factors. Data from ophthalmological records (occurrence of retinopathy and laser treatment and visual acuity), and clinical data (blood pressure, glycosylated hemoglobin (HbA1c), body mass index (BMI), and antihypertensive treatment) from the Skaraborg Diabetes Register were retrieved in the Skaraborg Screening Program of 1,258 patients diagnosed during 1996-1998. Kaplan Meyer survival analysis and Log Rank test were used to analyze eye complications in 773 patients with type 2 diabetes and a parts per thousand currency sign70 years at diagnosis. Visual acuity was above the limit for driving license in 96 % of 548 patients and only nineteen patients were treated by laser. At diagnosis of diabetes, mean HbA1c was 6.7 +/- A 1.7 % (59 +/- A 7.1 mmol/mol), and systolic blood pressure was 142.9 +/- A 0.7 mmHg; neither changed significantly during follow-up. Retinopathy appeared about 1 year, and maculopathy 2 years earlier, if HbA1c a parts per thousand yen 7 % (63 mmol/mol) at diagnosis (p < 0.001 and p < 0.006). Antihypertensive treatment, higher BMI, and higher age at diagnosis were associated with less retinopathy during follow-up. Most patients with diabetes develop little retinopathy for the first 10 years after diagnosis. High HbA1c at baseline was associated with retinopathy and maculopathy during follow-up. Antihypertensive treatment, probably a proxy for regular controls and early detection of diabetes, was associated with less retinopathy

Understanding adherence to therapeutic guidelines: a multilevel analysis of statin prescription in the Skaraborg Primary Care Database

In Skaraborg, Sweden, the economic responsibility for tax-financed prescription drug costs was transferred from the regional administrative level to the local level (health care centre; HCC) in 2003. The aim of this study was to investigate the impact of this decentralization of economic responsibility on adherence to guidelines for prescribing lipid-lowering drugs. Data from all 24 public HCCs in Skaraborg on prescriptions for lipid-lowering drugs during 2003 and 2005 were extracted from the Skaraborg Primary Care Database (SPCD). Multilevel regression analysis (MLRA) was used to disentangle the variances at different levels of data (patient, physician, HCC). The outcome variable on the patient level was the prescription of the recommended statin (yes/no). Sex and age of the patients and sex, age and occupational status of the physician were included as fixed effects. The variance was expressed as the median odds ratio (MOR). The prevalence of adherence to guidelines for the prescription of statins increased from 77% in 2003 to 84% in 2005. The MLRA showed that in 2003 the variance was equally distributed between the HCC and physician levels (MORHCC2003 = 1.89 vs. MORPHYSICIAN2003 = 1.88). The variance between physicians and between HCCs decreased considerably between 2003 and 2005. The inclusion of individual and physician characteristics did not explain any of the remaining variance. The decentralized budget appears to have increased adherence to guidelines and reduced inefficient variation in prescribing

The impact of diabetes, education and income on mortality and cardiovascular events in hypertensive patients : A cohort study from the Swedish Primary Care Cardiovascular Database (SPCCD)

Objective In this study we aimed to estimate the effect of diabetes, educational level and income on the risk of mortality and cardiovascular events in primary care patients with hypertension. Methods We followed 62,557 individuals with hypertension diagnosed 2001-2008, in the Swedish Primary Care Cardiovascular Database. Study outcomes were death, myocardial infarction, and ischemic stroke, assessed using national registers until 2012. Cox regression models were used to estimate adjusted hazard ratios of outcomes according to diabetes status, educational level, and income. Results During follow-up, 13,231 individuals died, 9981 were diagnosed with diabetes, 4431 with myocardial infarction, and 4433 with ischemic stroke. Hazard ratios (95% confidence intervals) for diabetes versus no diabetes: mortality 1.57 (1.50-1.65), myocardial infarction 1.24 (1.14-1.34), and ischemic stroke 1.17 (1.07-1.27). Hazard ratios for diabetes and ≤9 years of school versus no diabetes and >12 years of school: mortality 1.56 (1.41-1.73), myocardial infarction 1.36 (1.17-1.59), and ischemic stroke 1.27 (1.08-1.50). Hazard ratios for diabetes and income in the lowest fifth group versus no diabetes and income in the highest fifth group: mortality 3.82 (3.36-4.34), myocardial infarction 2.00 (1.66-2.42), and ischemic stroke 1.91 (1.58-2.31). Conclusions Diabetes combined with low income was associated with substantial excess risk of mortality, myocardial infarction and ischemic stroke among primary care patients with hypertension

Association of dairy consumption with metabolic syndrome, hypertension and diabetes in 147 812 individuals from 21 countries

Objective Our aims were to assess the association of dairy intake with prevalence of metabolic syndrome (MetS) (cross-sectionally) and with incident hypertension and incident diabetes (prospectively) in a large multinational cohort study.Methods The Prospective Urban Rural Epidemiology (PURE) study is a prospective epidemiological study of individuals aged 35 and 70 years from 21 countries on five continents, with a median follow-up of 9.1 years. In the cross-sectional analyses, we assessed the association of dairy intake with prevalent MetS and its components among individuals with information on the five MetS components (n=112 922). For the prospective analyses, we examined the association of dairy with incident hypertension (in 57 547 individuals free of hypertension) and diabetes (in 131 481 individuals free of diabetes).Results In cross-sectional analysis, higher intake of total dairy (at least two servings/day compared with zero intake; OR 0.76, 95% CI 0.71 to 0.80, p-trend&lt;0.0001) was associated with a lower prevalence of MetS after multivariable adjustment. Higher intakes of whole fat dairy consumed alone (OR 0.72, 95% CI 0.66 to 0.78, p-trend&lt;0.0001), or consumed jointly with low fat dairy (OR 0.89, 95% CI 0.80 to 0.98, p-trend=0.0005), were associated with a lower MetS prevalence. Low fat dairy consumed alone was not associated with MetS (OR 1.03, 95% CI 0.77 to 1.38, p-trend=0.13). In prospective analysis, 13 640 people with incident hypertension and 5351 people with incident diabetes were recorded. Higher intake of total dairy (at least two servings/day vs zero serving/day) was associated with a lower incidence of hypertension (HR 0.89, 95% CI 0.82 to 0.97, p-trend=0.02) and diabetes (HR 0.88, 95% CI 0.76 to 1.02, p-trend=0.01). Directionally similar associations were found for whole fat dairy versus each outcome.Conclusions Higher intake of whole fat (but not low fat) dairy was associated with a lower prevalence of MetS and most of its component factors, and with a lower incidence of hypertension and diabetes. Our findings should be evaluated in large randomized trials of the effects of whole fat dairy on the risks of MetS, hypertension, and diabetes

Association of dairy consumption with metabolic syndrome, hypertension and diabetes in 147 812 individuals from 21 countries

Objective: Our aims were to assess the association of dairy intake with prevalence of metabolic syndrome (MetS) (cross-sectionally) and with incident hypertension and incident diabetes (prospectively) in a large multinational cohort study. Methods: The Prospective Urban Rural Epidemiology (PURE) study is a prospective epidemiological study of individuals aged 35 and 70 years from 21 countries on five continents, with a median follow-up of 9.1 years. In the cross-sectional analyses, we assessed the association of dairy intake with prevalent MetS and its components among individuals with information on the five MetS components (n=112 922). For the prospective analyses, we examined the association of dairy with incident hypertension (in 57 547 individuals free of hypertension) and diabetes (in 131 481 individuals free of diabetes). Results: In cross-sectional analysis, higher intake of total dairy (at least two servings/day compared with zero intake; OR 0.76, 95% CI 0.71 to 0.80, p-trend\u3c0.0001) was associated with a lower prevalence of MetS after multivariable adjustment. Higher intakes of whole fat dairy consumed alone (OR 0.72, 95% CI 0.66 to 0.78, p-trend\u3c0.0001), or consumed jointly with low fat dairy (OR 0.89, 95% CI 0.80 to 0.98, p-trend=0.0005), were associated with a lower MetS prevalence. Low fat dairy consumed alone was not associated with MetS (OR 1.03, 95% CI 0.77 to 1.38, p-trend=0.13). In prospective analysis, 13 640 people with incident hypertension and 5351 people with incident diabetes were recorded. Higher intake of total dairy (at least two servings/day vs zero serving/day) was associated with a lower incidence of hypertension (HR 0.89, 95% CI 0.82 to 0.97, p-trend=0.02) and diabetes (HR 0.88, 95% CI 0.76 to 1.02, p-trend=0.01). Directionally similar associations were found for whole fat dairy versus each outcome. Conclusions: Higher intake of whole fat (but not low fat) dairy was associated with a lower prevalence of MetS and most of its component factors, and with a lower incidence of hypertension and diabetes. Our findings should be evaluated in large randomized trials of the effects of whole fat dairy on the risks of MetS, hypertension, and diabetes

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P&lt;0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P&lt;0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P&lt;2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P&lt;0.05) and reached more nominal levels of significance (P&lt;2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations