Genetic and environmental effects on fasting and postchallenge plasma glucose and serum insulin values in Finnish twins

The aim of this study was to evaluate genetic and environmental effects on plasma glucose, insulin secretion, and resistance in Finnish twins. Altogether 151 randomly selected twin pairs were examined by the oral glucose tolerance test; 66 twin pairs were monozygotic and 85 like-sexed dizygotic. We estimated the intraclass correlation coefficients and variance components of genetic and environmental effects on waist circumference, plasma glucose, and serum insulin. For fasting insulin, the proportion of total variation accounted for by additive genetic effects (A) and nonshared environmental effects (E) were 43 and 57%, respectively. As to postchallenge insulin and waist circumference, A effects were stronger in female twins (51 and 70%, respectively) than male twins in whom no significant evidence for genetic variance was found. Of the variation in fasting glucose, A and E effects accounted for 45 and 55%, respectively. Of the variation in postchallenge glucose, E effects had a greater role (65%), compared with A effects (35%); A effects on pre- and postchallenge insulin levels were highly correlated (genetic correlation coefficient = 0.81). In conclusion, additive genetic effects are important for the insulin secretion, whereas nonshared environmental effects contribute strongly to peripheral insulin resistance.     

Targeted postoperative care improves discharge outcome after hip or knee arthroplasty

OBJECTIVE: To determine whether targeted postoperative care, based on preoperative risk assessment, can increase the number of patients who are discharged home directly from acute care after elective hip or knee arthroplasty. DESIGN: Quasiexperimental with historical control. SETTING: A public university teaching hospital. PARTICIPANTS: One hundred patients who had an elective hip or knee arthroplasty. INTERVENTIONS: Between January and July 2001, 50 patients had their risk of discharge to extended inpatient rehabilitation assessed preoperatively with a newly developed Risk Assessment and Prediction Tool (RAPT). Postoperative management was targeted on the basis of the identified level of risk. Results were compared with those of a similar group of 50 patients treated between January and July 2000. MAIN OUTCOME MEASURES: Discharge destination, length of stay (LOS), and readmission rates. RESULTS: The percentage of patients discharged directly home increased significantly, from 34% during 2000 to 64% in 2001 (P=.002), with no increase in readmission rates in the 12 months postdischarge. In addition, the mean acute hospital LOS decreased by 1.1 days to 7.5 days in 2001 (P=.02). CONCLUSIONS: Use of the RAPT and targeted postoperative care resulted in more patients being discharged directly home after hip or knee arthroplasty while hospital LOS further decreased.     

Novel Linkage Peaks Discovered for Diabetic Nephropathy in Individuals With Type 1 Diabetes

Genome-wide association studies (GWAS) and linkage studies have had limited success in identifying genome-wide significantly linked regions or risk loci for diabetic nephropathy (DN) in individuals with type 1 diabetes (T1D). As GWAS cohorts have grown, they have also included more documented and undocumented familial relationships. Here we computationally inferred and manually curated pedigrees in a study cohort of >6,000 individuals with T1D and their relatives without diabetes. We performed a linkage study for 177 pedigrees consisting of 452 individuals with T1D and their relatives using a genome-wide genotyping array with >300,000 single nucleotide polymorphisms and PSEUDOMARKER software. Analysis resulted in genome-wide significant linkage peaks on eight chromosomal regions from five chromosomes (logarithm of odds score >3.3). The highest peak was localized at the HLA region on chromosome 6p, but whether the peak originated from T1D or DN remained ambiguous. Of other significant peaks, the chromosome 4p22 region was localized on top of ARHGAP24, a gene associated with focal segmental glomerulosclerosis, suggesting this gene may play a role in DN as well. Furthermore, rare variants have been associated with DN and chronic kidney disease near the 4q25 peak, localized on top of CCSER1.     

Hospital stay and discharge outcomes after knee arthroplasty: implications for physiotherapy practice

Patient outcomes at discharge from acute care after knee arthroplasty were investigated in a prospective observational outcome study at three Melbourne public acute care hospitals during a five-month period from November 1999 to March 2000. The participants were 105 consecutive patients (35 at each hospital), with a mean age of 71 years. Outcome measures were length of stay, destination (home or rehabilitation), knee range of movement, and functional mobility at discharge from the acute care facility. During the study period, mean hospital length of stay across the three hospitals was 6.5 days, more than 30% less than the Victorian average for the preceding year. In that time, 56% of patients had achieved functional independence sufficient for discharge directly home, however only 36% were actually discharged home. The reasons identified for discharge to rehabilitation despite the achievement of sufficient functional independence included pressure on clinicians to decrease length of stay and the need to make decisions regarding discharge early in the post-operative recovery when the eventual patient outcome may still be unclear. Unnecessary discharges to rehabilitation increase the overall length of stay in the health care system and costs per patient. This finding suggests a method of risk screening is required to assist clinical decision making with regard to discharge.     

Long-term mortality in nationwide cohorts of childhood-onset type 1 diabetes in Japan and Finland

OBJECTIVE: This study compares mortality from type 1 diabetes in Japan and Finland and examines the effects of sex, age at diagnosis, and calendar time period of diagnosis on mortality. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes from Japan (n = 1,408) and Finland (n = 5,126), diagnosed from 1965 through 1979, at age <18 years, were followed until 1994. Mortality was estimated with and without adjustment for that of the general population to assess absolute and relative mortality using Cox proportional hazard models. RESULTS: Overall mortality rates in Japan and Finland were 607 (95% CI 510-718) and 352 (315-393), respectively, per 100,000 person-years; standardized mortality ratios were 12.9 (10.8-15.3) and 3.7 (3.3-4.1), respectively. Absolute mortality was higher for men than for women in Finland, but relative mortality was higher for women than for men in both cohorts. Absolute mortality was higher in both cohorts among those whose diabetes was diagnosed during puberty, but relative mortality did not show any significant difference by age at diagnosis in either cohort. In Japan, both absolute and relative mortality were higher among those whose diagnosis was in the 1960s rather than the 1970s. CONCLUSIONS: Mortality from type 1 diabetes was higher in Japan compared with Finland. The increased risk of death from type 1 diabetes seems to vary by sex, age at diagnosis, and calendar time period of diagnosis. Further investigation, especially on cause-specific mortality, is warranted in the two countries.     

Osteoprotegerin Is an Independent Predictor of Vascular Events in Finnish Adults With Type 1 Diabetes

OBJECTIVEOsteoprotegerin (OPG) is involved in the process of vascular calcification. We investigated whether OPG is associated with the development and progression of diabetes complications in adults with type 1 diabetes (T1D).RESULTSOnly patients with macroalbuminuria and/or renal impairment had elevated OPG concentrations, when compared with participants without overt kidney disease. Patients with retinopathy or CV disease also had higher OPG concentrations, but this was attributable to their higher frequency of chronic kidney disease. OPG predicted an incident CV event (hazard ratio 1.21 [95% CI 1.01–1.45]; P = 0.035) and peripheral vascular disease/amputation events (1.46 [1.13–1.88]; P = 0.004) during follow-up.CONCLUSIONSWe showed that serum OPG is an independent predictor of CV complications. OPG may be directly involved in extraosseous calcification, resulting in stiffening of the arteries and subsequent vascular insufficiency in patients with T1D.Arterial calcification is strongly associated with the development and progression of vascular stiffening and arteriosclerosis leading to cardiovascular disease (CVD). This process is accelerated in patients with diabetes or chronic kidney disease (CKD) and especially in those with both (1). Many of the key regulators of bone mineralization also appear to be key mediators of osteogenic transformation of vascular smooth muscle cells and arterial calcification in diabetes (2,3). One of the most well known is osteoprotegerin (OPG) (4,5). OPG concentrations are positively correlated with coronary calcification (6), vascular stiffness (7), and the presence of unstable plaque (8) in nondiabetic individuals and an increased risk of cardiovascular (CV) mortality in patients with diabetes (9,10). In this study, we further explore the association between circulating concentrations of OPG and CV outcomes in a large well-characterized cohort of patients with type 1 diabetes (T1D) exploring mortality, coronary, stroke, and amputation events.