The Finland-United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. II. An autosomal genome scan for diabetes-related quantitative-trait loci.

Type 2 diabetes mellitus is a complex disorder encompassing multiple metabolic defects. We report results from an autosomal genome scan for type 2 diabetes-related quantitative traits in 580 Finnish families ascertained for an affected sibling pair and analyzed by the variance components-based quantitative-trait locus (QTL) linkage approach. We analyzed diabetic and nondiabetic subjects separately, because of the possible impact of disease on the traits of interest. In diabetic individuals, our strongest results were observed on chromosomes 3 (fasting C-peptide/glucose: maximum LOD score [MLS] = 3.13 at 53.0 cM) and 13 (body-mass index: MLS = 3.28 at 5.0 cM). In nondiabetic individuals, the strongest results were observed on chromosomes 10 (acute insulin response: MLS = 3.11 at 21.0 cM), 13 (2-h insulin: MLS = 2.86 at 65.5 cM), and 17 (fasting insulin/glucose ratio: MLS = 3.20 at 9.0 cM). In several cases, there was evidence for overlapping signals between diabetic and nondiabetic individuals; therefore we performed joint analyses. In these joint analyses, we observed strong signals for chromosomes 3 (body-mass index: MLS = 3.43 at 59.5 cM), 17 (empirical insulin-resistance index: MLS = 3.61 at 0.0 cM), and 19 (empirical insulin-resistance index: MLS = 2.80 at 74.5 cM). Integrating genome-scan results from the companion article by Ghosh et al., we identify several regions that may harbor susceptibility genes for type 2 diabetes in the Finnish population.

Valine, isoleucine, and leucine. A new treatment for phenylketonuria.

Early treatment of phenylketonuria by dietary phenylalanine restriction prevents brain damage. Behavioral and cognitive deficits occur when serum phenylalanine levels increase. Administration of valine, isoleucine, and leucine to patients with phenylketonuria may inhibit entry of phenylalanine into the brain and reduce its toxic effects on the central nervous system. Sixteen adolescents and young adults with phenylketonuria participated in double-blind trials in which a valine, isoleucine, and leucine mixture or a control mixture was given for four 3-month periods. Biochemical and neuropsychologic tests were carried out before and at the end of each period. Time to completion of a test that required substantial attention with mental processing (Attention Diagnostic Method) was faster during the valine, isoleucine, and leucine periods than during the control mixture periods. Improvement with valine, isoleucine, and leucine on a less demanding task (Continuous Performance Test) approached significance. These data lent support to the hypothesis that a regimen of valine, isoleucine, and leucine may help individuals unable to maintain low serum phenylalanine levels.

Risk rate neglect in decisions involving invasive diagnostic procedures.

To investigate whether the risk of life-threatening complications influence the decisions involving invasive diagnostic procedures, a study was conducted that focused on the use of coronary angiography and endomyocardial biopsy with risk rates of either 1% or 2%. The participants included 38 physicians from two university-affiliated hospitals. Of their 76 pairs of decisions, 53% were of the "risk-avoidance" type and 26% were of the "risk-taking" type. Only 13% of decisions were of the "risk-conscious" type. The practical implication of these biases can be substantial in real-life decisions regarding events with low-probability, but high-consequence risks.

Phenylketonuria, adolescence, and diet.

The decision to continue treatment for phenylketonuria (PKU) patients into adolescence and adulthood presents a challenge to nutritionists and other professionals who must motivate patients to maintain the diet and give them support. Nutrition needs must be assessed and then met by commercial low-phenylalanine formula and low-protein foods, while at the same time the amount of phenylalanine in the diet is severely limited. Combinations of products can be used to tailor the diet to individual needs, e.g., weight reduction. The objective is to allow the intellectually normal PKU patient to develop as socially normal a life-style as possible.