Skin autofluorescence improves the Finnish Diabetes Risk Score in the detection of diabetes in a large population-based cohort: The LifeLines Cohort Study.

AIM: The aim of the present study was to investigate whether skin autofluorescence would improve the Finnish Diabetes Risk Score (FINDRISC) in detecting undiagnosed diabetes in a large population-based cohort. METHODS: Included were participants from the Dutch LifeLines Cohort Study. Skin autofluorescence was assessed in an unselected subset of participants using the AGE Reader. After the exclusion of participants with previously diagnosed diabetes (n=1635), pregnant women (n=58) and those using corticosteroids (n=345), 79,248 subjects were eligible for analysis. Diabetes was defined as fasting plasma glucose ≥7.0mmol/L, non-fasting plasma glucose ≥11.1mmol/L or HbA1c ≥6.5% (48mmol/mol). RESULTS: Diabetes was detected in 1042 participants (aged 55±12 years; 54% male). Skin autofluorescence improved the area under the receiver operating characteristic (AUROC) curve of the FINDRISC model from 0.802 to 0.811 (P<0.001). Furthermore, the addition of skin autofluorescence to FINDRISC reclassified 8-15% of all participants into more accurate risk categories (NRI: 0.080, 95% CI: 0.052-0.110). The proportion of reclassified participants was especially high (>30%) in the intermediate (1% to <5% and 5% to<10%) risk categories. When skin autofluorescence was added to a simplified model (age+body mass index), its discriminatory performance was similar to the full model+skin autofluorescence (AUROC: 0.806, P=0.062). CONCLUSION: Skin autofluorescence is a non-invasive tool that can be used to further improve the FINDRISC for diabetes detection. The new resultant model is especially useful for reclassifying people in the intermediate-risk categories, where additional blood glucose testing is needed to confirm the presence of diabetes.

Withdrawal of fluticasone propionate from combined salmeterol/fluticasone treatment in patients with COPD causes immediate and sustained disease deterioration: a randomised controlled trial.

BACKGROUND: Guidelines recommend inhaled corticosteroids (ICS) as maintenance treatment for patients with chronic obstructive pulmonary disease (COPD) with a post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted and frequent exacerbations, although they have only a small preventive effect on the accelerated decline in lung function. Combined treatment with ICS and long acting beta2 agonists (LABA) may provide benefit to the stability of COPD, but it is unknown if withdrawal of ICS will result in disease deterioration. METHODS: The effects of 1 year withdrawal of the ICS fluticasone propionate (FP) after a 3 month run-in treatment period with FP combined with the LABA salmeterol (S) (500 microg FP + 50 microg S twice daily; SFC) were investigated in patients with COPD in a randomised, double blind study. 497 patients were enrolled from 39 centres throughout the Netherlands; 373 were randomised and 293 completed the study. RESULTS: The drop out rate after randomisation was similar in the two groups. Withdrawal of FP resulted in a sustained decrease in FEV1: mean (SE) change from baseline -4.4 (0.9)% (S) v -0.1 (0.9)% (SFC); adjusted difference 4.1 (95% CI 1.6 to 6.6) percentage points (p<0.001). Corresponding figures for the FEV1/FVC ratio were -3.7 (0.8)% (S) v 0.0 (0.8)% (SFC) (p = 0.002). The annual moderate to severe exacerbation rate was 1.6 and 1.3 in the S and SFC groups, respectively (adjusted rate ratio 1.2; 95% CI 0.9 to 1.5; p = 0.15). The mean annual incidence rate of mild exacerbations was 1.3 (S) v 0.6 (SFC), p = 0.020. An immediate and sustained increase in dyspnoea score (scale 0-4; mean difference between groups 0.17 (0.04), p<0.001) and in the percentage of disturbed nights (6 (2) percentage points, p<0.001) occurred after withdrawal of fluticasone. CONCLUSIONS: Withdrawal of FP in COPD patients using SFC resulted in acute and persistent deterioration in lung function and dyspnoea and in an increase in mild exacerbations and percentage of disturbed nights. This study clearly indicates a key role for ICS in the management of COPD as their discontinuation leads to disease deterioration, even under treatment with a LABA.

Cord blood apolipoprotein-E genotype distribution and plasma lipid indices in newborns of different ethnicity.

We hypothesized that apolipoprotein-E (apo-E) genotypes would be associated with plasma lipid indices in newborns of South Asian (SA) ancestry but not in newborns of African (Afr) ancestry. Cord blood was obtained by consecutive sampling at maternity hospitals in the Caribbean Islands of Trinidad and Curaçao. Apolipoprotein-E genotypes, cholesterol, triglycerides, apo-A, apo-B and Lipoprotein (a) (Lp(a)) were measured in 294 newborns in Trinidad and 234 in Curaçao. The apo-B/apo-AI ratio and an adapted lipid tetrad index (i.e. cholesterol x triglycerides x Lp(a)/apo-AI) were calculated. In Trinidad, apo-E allele frequencies and genotype distributions of Afr and SA were significantly (p < 0.001) different (Afr: n = 71: apo-e2 : e3 : e4 = 10.4 : 66.4 : 23.2%; SA: n = 98; e2 : e3 : e4 = 3.5 : 83.1: 13.4%). The Mixed group (SA + Afr) had apo-E allele frequencies in between those of SA and Afr groups (n = 115; e2 : e3 : e4 = 7 : 76 : 17%). Lipid indices of appropriate for gestational age and term newborns were comparable, except for lower Lp(a) (SA = 29+/-4; Afr = 46+/-5; Mixed = 41+/-5 mg L(-1)) and lower adapted lipid tetrad index (29.4+/-4.8; 41.9+/-5.4; 41.4+/-7.0) in SA. Apo-E allele frequencies of Curaçao newborns were: apo-e2 : e3 : e4 = 10.5 : 72.6 : 16.9%. Their Lp(a) levels were significantly higher (68+/-3 mg L(-1)) than that of the Trinidadian sample (38+/-3; p < 0.0001). Apolipoprotein-E4 had an apo-B-increasing effect and apo-E2 an apo-B-decreasing effect in Afr (r = 0.192, p = 0.003). Among Africans from Trinidad and Curaçao variations in apo-E4 and apo-E2 are associated with an apo-B-increasing effect and an apo-B-decreasing effect, respectively. There was no relationship between apo-E polymorphism and lipids among South Asians.

Apolipoprotein-E genotype distribution in consecutive Trinidadian newborns of African and Indian descent: comparisons with other populations and relations of the apolipoprotein-E genotype with plasma lipid indices

Trinidadian Indians and Africans have different coronary artery disease (CAD) incidences. We determined apolipoprotein-E (apo-E) genotypes, and umbilical plasma cholesterol, triglycerides, apo-A1, apo-B and lipoprotein(a) [Lp(a) in 294 consecutive newborns in Trinidad. We calculate the apo-B/apo-A1 ratio and an adapted "lipid tetrad index" (i.e cholesterol*triglycerides*Lp(a)/apo-A1). Apo-E genotype distributions of Trinidadian Africans (allele frequencies: apo-e2:e3:e4=10.4:66.4:23.2 percent) and Indians(e2:e3:e4=3.5:83.1:13.4 percent) were different. The apo-E genotype distribution of Trinidadian Africans resembles to a certain extent that of their counterpart in Curacao and Sudan, but not that of cuonterparts in Nigeria and the USA.(AU)