Development of a nutrition knowledge questionnaire for young endurance athletes and their coaches.

Both athletes and coaches should have adequate nutrition knowledge to understand the importance of diet on athletic performance, recovery, and health. Nutrition knowledge can be assessed reliably only by validated knowledge questionnaires. The aim of this study was to develop a reliable and valid questionnaire for assessing the nutrition knowledge of young endurance athletes and their coaches. The questionnaire was developed with an expert panel and pilot tested by athletes, coaches, and students. Content, face, and construct validities both as test-retest reliability and internal consistency reliability were ensured when the current questionnaire was developed. Athletes (n = 16) and coaches (n = 13) pilot tested the 127-item questionnaire. After item analysis and proposals from the expert panel, 41 items were removed. Internal consistency of the 86-item questionnaire in the pilot study was 0.87, measured using Cronbach's α. Construct validity was evaluated by the difference in knowledge between nutrition (n = 20) and humanities students (n = 22). Nutrition students had significantly higher knowledge scores (P < .001). Test-retest reliability for all knowledge sections between those groups was 0.85 measured using Pearson's r. Final adjustments to the questionnaire were made on the grounds of feedback from the respondents and proposals from the experts (n = 6). These adjustments resulted in minor changes in the construct of the items, the layout of the questionnaire, and the removal of 7 items. The final questionnaire had 79 items. The questionnaire can be used to measure the overall nutrition knowledge of endurance athletes and their coaches and to find potential gaps in nutrition knowledge.

Heritability and familiality of type 2 diabetes and related quantitative traits in the Botnia Study.

AIMS/HYPOTHESIS: To study the heritability and familiality of type 2 diabetes and related quantitative traits in families from the Botnia Study in Finland. METHODS: Heritability estimates for type 2 diabetes adjusted for sex, age and BMI are provided for different age groups of type 2 diabetes and for 34 clinical and metabolic traits in 5,810 individuals from 942 families using a variance component model (SOLAR). In addition, family means of these traits and their distribution across families are calculated. RESULTS: The strongest heritability for type 2 diabetes was seen in patients with age at onset 35-60 years (h (2) = 0.69). However, including patients with onset up to 75 years dropped the h (2) estimates to 0.31. Among quantitative traits, the highest h (2) estimates in all individuals and in non-diabetic individuals were seen for lean body mass (h (2) = 0.53-0.65), HDL-cholesterol (0.52-0.61) and suppression of NEFA during OGTT (0.63-0.76) followed by measures of insulin secretion (insulinogenic index [IG(30)] = 0.41-0.50) and insulin action (insulin sensitivity index [ISI] = 0.37-0.40). In contrast, physical activity showed rather low heritability (0.16-0.18), whereas smoking showed strong heritability (0.57-0.59). Family means of these traits differed two- to fivefold between families belonging to the lowest and highest quartile of the trait (p < 0.00001). CONCLUSIONS/INTERPRETATION: To detect stronger genetic effects in type 2 diabetes, it seems reasonable to restrict inclusion of patients to those with age at onset 35-60 years. Sequencing of families with extreme quantitative traits could be an important next step in the dissection of the genetics of type 2 diabetes.

Leisure-time physical activity and type 2 diabetes during a 28 year follow-up in twins.

AIMS/HYPOTHESIS: The study aimed to investigate whether baseline physical activity protects against the occurrence of type 2 diabetes during a 28 year follow-up, after controlling for childhood environment and genetic predisposition. METHODS: At baseline in 1975 same-sex twin pairs born in Finland before 1958 were sent a questionnaire including questions on physical activity. The participants (20,487 individuals, including 8,182 complete twin pairs) were divided into quintiles by leisure-time physical activity metabolic equivalent (MET) index (MET h/day). Type 2 diabetes was determined from nationwide registers for the follow-up period (1 January 1976-31 December 2004). Individual and pairwise Cox proportional hazard models were used. RESULTS: During follow-up, 1,082 type 2 diabetes cases were observed. Among all individuals, participants in MET quintiles (Q) III-V had significantly decreased risk for type 2 diabetes compared with sedentary individuals (QI). The pairwise analysis on pairs discordant for physical activity showed that participants in MET QII to V had significantly lower hazard ratios (0.61, 0.59, 0.61, 0.61) compared with sedentary participants. These findings from the pairwise analysis persisted after adjusting for BMI. In the pairwise analysis, the BMI-adjusted hazard ratio for type 2 diabetes was lower for physically active members of twin pairs (combined QII-V) than for inactive co-twins (HR 0.54; 95% CI 0.37-0.78). Similar results were obtained for both dizygotic and monozygotic pairs, as well as for the subgroup of twin pairs defined as free of co-morbidities in 1981 (HR 0.36; 95% CI 0.17-0.76). CONCLUSIONS/INTERPRETATION: Leisure-time physical activity protects from type 2 diabetes after taking familial and genetic effects into account.

Evidence that BMI and type 2 diabetes share only a minor fraction of genetic variance: a follow-up study of 23,585 monozygotic and dizygotic twins from the Finnish Twin Cohort Study.

AIMS/HYPOTHESIS: We investigated whether BMI predicts type 2 diabetes in twins and to what extent that is explained by common genetic factors. METHODS: This was a population-based twin cohort study. Monozygotic (n = 4,076) and dizygotic (n = 9,109) non-diabetic twin pairs born before 1958 answered a questionnaire in 1975, from which BMI was obtained. Information on incident cases of diabetes was obtained by linkage to nationwide registers until 2005. RESULTS: Altogether, 1,332 twins (6.3% of men, 5.1% of women) developed type 2 diabetes. The HR for type 2 diabetes increased monotonically with a mean of 1.22 (95% CI 1.20-1.24) per BMI unit and of 1.97 (95% CI 1.87-2.08) per SD of BMI. The HRs for lean, overweight, obese and morbidly obese participants were 0.59, 2.96, 6.80 and 13.64 as compared with normal weight participants. Model heritability estimates for bivariate variance due to an additive genetic component and non-shared environmental component were 75% (men) and 71% (women) for BMI, and 73% and 64%, respectively for type 2 diabetes. The correlations between genetic variance components (r (g)) indicated that one fifth of the covariance of BMI and type 2 diabetes was due to shared genetic influences. Although the mean monozygotic concordance for type 2 diabetes was approximately twice the dizygotic one, age of onset of diabetes within twin pair members varied greatly, irrespective of zygosity. CONCLUSIONS/INTERPRETATION: A 28-year follow-up of adult Finnish twins showed that despite high trait heritability estimates, only a fraction of covariation in BMI and incident type 2 diabetes was of genetic origin.

Brain pathology in three subjects from the same pedigree with presenilin-1 (PSEN1) P264L mutation.

AIMS: Our goal was to assess pathological lesions with respect to type and distribution and to compare these results with the clinical presentation including symptoms and mode of progression in three members of the same pedigree with a P264L presenilin-1 gene mutation. METHODS: We used immunohistochemistry and a tissue microarray technique applied to post mortem brain tissue samples. RESULTS: All three subjects were demented, one subject displayed spastic paraparesis and two had Parkinsonism. All three cases displayed abundant cotton wool plaques composed of amyloid-beta42 but also containing other proteins, for example, hyperphosphorylated tau and in one case TAR DNA binding protein 43. The distribution of the pathology varied and seemed to some extent to be related to the clinical phenotype. An association was detected between neocortical/thalamic involvement and psychiatric symptoms, between striatal/amygdaloid involvement and Parkinsonism, and between brainstem involvement and spastic paraparesis. CONCLUSIONS: Subjects from the same pedigree carrying the same mutation display a clear variability in the type and distribution of pathology as well as in their clinical symptoms. These results emphasize that still unknown factors significantly alter the pathological and clinical phenotypes in genetically predetermined disease.

Long-term beneficial effects of glipizide treatment on glucose tolerance in subjects with impaired glucose tolerance.

AIMS: To assess the efficacy and long-term effects of glipizide treatment on glucose and insulin metabolism in individuals with impaired glucose tolerance (IGT). METHODS: Thirty-seven first-degree relatives of patients with type 2 diabetes fulfilling WHO criteria for IGT were randomized to treatment with either glipizide 2.5 mg once daily or matching placebo for 6 months. A 75 g, 2-h oral (OGTT) and 60 min intravenous glucose tolerance test (IVGTT) were performed at baseline and after 6 months. The subjects were followed up for another 12 months after discontinuation of treatment and a repeat OGTT was performed at 18 months. RESULTS: Thirty-three subjects fulfilled the study. Markers of insulin sensitivity - i.e. fasting insulin and HOMA(IR)-index - improved in the glipizide group (P = 0.04 and 0.02 respectively) as well as HDL cholesterol (P = 0.05) compared with placebo group after 6 months. At 18 months, both fasting and 2 h glucose concentrations were significantly lower in the glipizide group compared with the placebo group (P = 0.04 and 0.03 respectively). The prevalence of type 2 diabetes was 29.4% in the placebo group and 5.9% in the glipizide group at 18 months. This equals an 80% relative risk reduction in the active treatment group. CONCLUSIONS: Short-term treatment with glipizide improves glucose and insulin metabolism in subjects with IGT primarily by improving insulin sensitivity mediated by lowering glucose toxicity, thereby providing the beta cells rest. Larger studies are needed to establish whether these effects are sufficient to prevent progression to manifest type 2 diabetes and associated cardiovascular morbidity in subjects at increased risk of developing type 2 diabetes.

Heritability of model-derived parameters of beta cell secretion during intravenous and oral glucose tolerance tests: a study of twins.

AIMS/HYPOTHESIS: The genetic architecture of model-derived parameters of beta cell function has never been assessed. Therefore, we estimated heritability (h(2)) for model-derived phenotypes of insulin secretion in twins. METHODS: Thirty-three monozygotic (MZ) and 23 dizygotic (DZ) twin pairs from the Finnish Twin Cohort Study underwent an OGTT (plasma glucose/C-peptide at 0, 30, 60, 90 and 120 min). A subset of the twin pairs (21 MZ/20 DZ) also underwent an IVGTT (frequent sampling of plasma glucose/insulin from 0 to 60 min) followed by a 160-min euglycaemic-hyperinsulinaemic clamp (45 mU.min(-1).m(-2)). Mathematical modelling was applied to the IVGTT and the OGTT to assess first-phase (readily releasable insulin [RRI]) and second-phase (sigma) secretion (IVGTT), and a global index of beta cell performance (OGTT beta index). Intraclass correlation coefficients and genetic and non-genetic components for trait variances were computed to assess the h(2) of model-derived parameters. RESULTS: The intraclass correlation coefficients in MZ twins were 0.78 for RRI, 0.67 for sigma and 0.57 for OGTT beta index. In DZ twins the correlation coefficients were 0.23, 0.32 and 0.42, respectively. Using the most parsimonious model for each trait, the h(2)--the proportion of variance accounted for by genetic factors--was 76% (95% CI: 53-88%) for RRI, 28% (34-80%) for sigma and 53% (26-72%) for OGTT beta index. CONCLUSIONS/INTERPRETATION: Our findings demonstrate that model-derived parameters of insulin secretion have a substantial genetic component and may be used in the search for genetic determinants of beta cell function in humans.

Polymorphisms in neprilysin gene affect the risk of Alzheimer's disease in Finnish patients.

OBJECTIVES: Neprilysin (NEP) is an amyloid beta-peptide (Abeta) degrading enzyme expressed in the brain, and accumulation of Abeta is the neuropathological hallmark in Alzheimer's disease (AD). In this study we investigated whether polymorphisms in the NEP gene have an effect on the risk for AD. METHODS: The frequencies of seven single nucleotide polymorphisms (SNPs) and apolipoprotein E (APOE) were assessed in 390 AD patients and 468 cognitively healthy controls. Genotypes of the study groups were compared using binary logistic regression analysis. Haplotype frequencies of the SNPs were estimated from genotype data. RESULTS: Two SNPs, rs989692 and rs3736187, had significantly different allelic and genotypic frequencies (uncorrected p = 0.01) between the AD and the control subjects and haplotype analysis showed significant association between AD and NEP polymorphisms. CONCLUSION: Taken together, these findings suggest that polymorphisms in the NEP gene increase risk for AD and support a potential role for NEP in AD.

Possible association of nicastrin polymorphisms and Alzheimer disease in the Finnish population.

The authors previously reported that genetic variation in the gene coding for nicastrin (NCSTN) modified risk for familial early-onset Alzheimer disease (AD) in a Dutch population-based sample. Risk was highest in patients without an APOE epsilon4 allele. Here, they evaluated if NCSTN polymorphisms increased risk of AD in the eastern Finnish population. A significant difference in one haplotype was observed in AD patients without the APOE epsilon4 allele.

Polymorphisms in the CYP19 gene confer increased risk for Alzheimer disease.

BACKGROUND: Brain aromatase may be neuroprotective by increasing the local estrogen levels in injured neurons. Aromatase is encoded by the CYP19 gene located at 15q21.1, a chromosomal region in linkage disequilibrium (LD) with Alzheimer disease (AD) in this sample. OBJECTIVE: To investigate whether nine single-nucleotide polymorphisms (SNP) spanning the CYP19 gene were associated with AD. METHODS: Three hundred ninety-four patients were compared with 469 nondemented control subjects using single-locus and haplotype approaches. Haplotypes were identified using the expectation/maximization algorithm and latent class analysis, which included additional information on age, sex, and APOE polymorphism. RESULTS: Allelic and genotypic frequencies for three adjacent SNP differed between AD and control groups. Both haplotype approaches identified an approximately 60% increase (p = 0.02) in the risk of AD for one haplotype and similar levels of excess risk irrespective of APOE polymorphism and gender. CONCLUSION: Genetic variation in the brain aromatase gene may modify the risk for AD.

Auditory adaptation is differentially impaired in familial and sporadic Alzheimer's disease.

Neurophysiologic measures are particularly sensitive to alterations in attention and arousal. The purpose of this study was to evaluate the auditory adaptation of normal and mildly demented elderly people. We compared the automatic behavior of an auditory evoked potential (N100) in three age-matched groups of elderly subjects, one with familial Alzheimer's disease (AD), one with sporadic AD and one healthy group. All AD subjects corresponded clinically and neuropsychologically with the early stage of dementia. The dynamic range of auditory adaptation is known to be related to age, and normal auditory adaptation for the age was observed in our healthy aged and sporadic AD subjects, whereas the familial AD subjects lacked normal adaptation. The familial AD subjects also showed statistically significantly smaller peak amplitudes and shorter latencies of the N100 throughout the habituation test. This persistent difference in automatic habituation of sensory responses supports the view that different subtypes of AD are differentially affected. The observed differences give an objective measure of the impaired involuntary adaptive functions of neuronal networks involved in auditory processing in subtypes of AD. Since habituation reflects the most primitive stage of learning and short-term memory, altered habituation may predict faster deterioration of clinical status in the familial group of AD subjects.

Genome-wide linkage disequilibrium mapping of late-onset Alzheimer's disease in Finland.

BACKGROUND: AD is a complex neurodegenerative disorder comprising several disease-associated chromosome loci. To find novel susceptibility genes for late-onset AD, a population-based genome-wide search using linkage disequilibrium (LD) mapping approach has been performed. METHOD: Forty-seven patients with late-onset AD and 51 age-matched control subjects were carefully chosen from the same geographic area in eastern Finland, where the population is descended mainly from a small group of original founders. These subjects were initially genotyped with 366 polymorphic microsatellite markers, and a follow-up analysis was performed with additional microsatellite markers for those chromosome loci found to be associated with AD. RESULTS: Initial genome-wide screening revealed 21 chromosomal loci significantly associated with AD in addition to the 13q12 locus described previously. Subsequent comparison of single-allele frequencies of the microsatellite markers in the AD and control groups indicated the presence both of possible risk alleles (odds ratio [OR] > 1) and of possible protective alleles (OR < 1). Screening of the LD regions with additional microsatellite markers revealed seven chromosomal loci where more than one microsatellite marker was associated with AD (1p36.12, 2p22.2, 3q28, 4p13, 10p13, 18q12.1, and 19p13.3) in addition to the 13q12 locus. CONCLUSIONS: These genome-wide LD screening data suggest that several AD-associated chromosomal loci exist, which may encompass novel susceptibility genes for late-onset AD. Therefore, extensive screening of the genes located in the vicinity of these LD regions is necessary to elucidate their role in AD.

CLN3 protein is targeted to neuronal synapses but excluded from synaptic vesicles: new clues to Batten disease.

Batten disease (juvenile neuronal ceroid lipofuscinosis, JNCL), the most common neurodegenerative disease of childhood, is caused by mutations in the CLN3 gene encoding a putative transmembrane protein. The function of CLN3 is currently unknown but it has been shown to localize in the endosomal/lysosomal compartments of non-neuronal cells. In addition, several other intracellular localizations have been proposed and the controversy of the reports suggests that CLN3 may have different intracellular localization in different cell types. Batten disease severely affects neuronal cells but leaves other organs clinically unaffected, and thus it is of utmost importance to approach the disease mechanism by studying the expression and localization of CLN3 in the brain and neuronal cells. We have analysed here CLN3 in the mouse brain using in situ hybridization, immunohistochemical staining and western blot analysis of subcellular fractions. As visual deterioration is the hallmark of Batten disease we have set up primary retinal cultures from the mouse and analysed both endogenous mouse CLN3 and Semliki Forest virus-mediated human CLN3 localization using immunofluorescence staining and confocal microscopy. We demonstrate that CLN3 is abundantly expressed in neuronal cells, especially in the cortex, hippocampus and cerebellum of the adult mouse brain. Furthermore, our results indicate that in neurons CLN3 is not solely a lysosomal protein. It is localized in the synaptosomes but, interestingly, is not targeted to the synaptic vesicles. The novel localization of CLN3 directs attention towards molecular alterations at the synapses. This should yield important clues about the mechanisms of neurodegeneration in Batten disease.

Metabolic impact of a family history of Type 2 diabetes. Results from a European multicentre study (EGIR).

BACKGROUND: Insulin resistance was found in some but not in all previous studies of non-diabetic first degree relatives of Type 2 diabetic patients. Small study groups, ethnic differences and/or non-optimal techniques may explain the conflicting results. AIM: To study the impact of a family history of Type 2 diabetes on insulin action in a large group of non-diabetic Europeans using the 'gold standard' euglycaemic hyperinsulinaemic clamp technique. METHODS: Non-diabetic subjects (n = 235) with a positive family history of Type 2 diabetes (FH+) and 564 subjects with no family history of diabetes (FH-) were recruited from The European Group of Insulin Resistance (EGIR) database. This database includes measurements of insulin action using the insulin clamp technique (1 mU/kg per min) in normal glucose-tolerant individuals from 20 different European centres. In a subset of subjects the measurements were performed in combination with indirect calorimetry (n = 80 vs. 213 with and without family history of Type 2 diabetes). RESULTS: The body mass index (BMI) was slightly higher in FH+ compared with FH- (26.7 +/- 4.6 vs. 25.1 +/- 4.7 kg/m(2); P < 0.02). After correction for covariates according to differences between investigators and subject characteristics including BMI (multiple regression analysis), insulin-stimulated glucose disposal was lower in FH+ compared with FH- (P < 0.00001). Insulin-stimulated glucose oxidation was slightly increased in FH+ compared with FH-, and insulin-stimulated non-oxidative glucose metabolism was consequently markedly reduced in FH+ compared with FH- (P < 0.0005). CONCLUSION: Insulin resistance is present in European non-diabetic relatives of Type 2 diabetic patients. The insulin resistance is independent of degree of obesity and is restricted solely to the pathway of non-oxidative glucose metabolism. Diabet. Med. 18, 533-540 (2001)

Metabolic effects of metformin in patients with impaired glucose tolerance.

AIMS: To assess the effect of metformin on insulin sensitivity, glucose tolerance and components of the metabolic syndrome in patients with impaired glucose tolerance (IGT). METHODS: Forty first-degree relatives of patients with Type 2 diabetes fulfilling WHO criteria for IGT and participating in the Botnia study in Finland were randomized to treatment with either metformin 500 mg b.i.d. or placebo for 6 months. An oral glucose tolerance test (OGTT) and a euglycaemic hyperinsulinaemic clamp in combination with indirect calorimetry was performed at 0 and 6 months. The patients were followed after stopping treatment for another 6 months in an open trial and a repeat OGTT was performed at 12 months. RESULTS: Metformin treatment resulted in a 20% improvement in insulin-stimulated glucose metabolism (from 28.7 +/- 13 to 34.4 +/- 10.7 micromol/kg fat-free mass (FFM)/min) compared with placebo (P = 0.01), which was primarily due to an increase in glucose oxidation (from 16.6 +/- 3.6 to 19.1 +/- 4.4 micromol/kg FFM; P = 0.03) These changes were associated with a minimal improvement in glucose tolerance, which was maintained after 12 months. CONCLUSIONS: Metformin improves insulin sensitivity in subjects with IGT primarily by reversal of the glucose fatty acid cycle. Obviously large multicentre studies are needed to establish whether these effects are sufficient to prevent progression to manifest Type 2 diabetes and associated cardiovascular morbidity and mortality. Diabet. Med. 18, 578-583 (2001)

Assessment of beta-cell function during the oral glucose tolerance test by a minimal model of insulin secretion.

OBJECTIVE: To characterise the performance of beta-cell during a standard oral glucose tolerance test (OGTT). DESIGN: Fifty-six subjects were studied. A minimal analogic model of beta-cell secretion during the OGTT was applied to all OGTTs (see below). The amount of insulin secreted over 120' in response to oral glucose (OGTT-ISR; Insulin Units 120'-1 m-2 BSA) and an index of beta-cell secretory 'force' (beta-Index; pmol.min-2.m-2 BSA) were computed with the aid of the model. In protocol A, 10 healthy subjects underwent two repeat 75 g OGTT with frequent (every 10'-15') blood sampling for glucose and C-peptide to test the reproducibility of OGTT-ISR and beta-Index with a complete or a reduced data set. In protocol B, 7 healthy subjects underwent three OGTTs (50, 100 or 150 g), to test the stability of the beta-Index under different glucose loads. In protocol C, 29 subjects (15 with normal glucose tolerance, 7 with impaired glucose tolerance and 7 with newly diagnosed type 2 diabetes) underwent two repeat 75 g OGTT with reduced (every 30' for 120') blood sampling to compare the reproducibility and the discriminant ratio (DR) of OGTT-ISR and beta-index with the insulinogenic index (IG-Index: Delta Insulin 30' - Basal/Delta Glucose 30' - Basal). In protocol D, 20 subjects (14 with normal glucose tolerance, 5 with impaired glucose tolerance and 1 with newly-diagnosed type 2 diabetes) underwent a 75 g OGTT and an intravenous glucose tolerance test (IVGTT) on separate days to explore the relationships between acute (0'-10') insulin response (AIR) during the IVGTT and beta-index and OGTT-ISR during the OGTT. RESULTS: In all protocols, the minimal analogic model of C-peptide secretion achieved a reasonable fit of the experimental data. In protocol A, a good reproducibility of both beta-index and OGTT-ISR was observed with both complete and reduced (every 30') data sets. In protocol B, increasing the oral glucose load caused progressive increases in OGTT-ISR (from 2.63 +/- 0.70 to 5.11 +/- 0.91 Units.120'-1.m-2 BSA; P < 0.01), but the beta-index stayed the same (4.14 +/- 0.35 vs. 4.29 +/- 0.30 vs. 4.30 +/- 0.33 pmol.min-2.m-2 BSA). In protocol C, both OGTT-ISR and beta-index had lower day-to-day CVs (17.6 +/- 2.2 and 12.4 +/- 2.4%, respectively) and higher DRs (2.57 and 1.74, respectively) than the IG-index (CV: 35.5 +/- 6.3%; DR: 0.934). OGTT-ISR was positively correlated to BMI (P < 0.03), whereas beta-index was inversely related to both fasting and 2 h plasma glucose (P < 0.01 for both). In protocol D, beta-index, but not OGTT-ISR, was significantly correlated to AIR (r = 0.542, P < 0.02). CONCLUSIONS: Analogically modelling beta-cell function during the OGTT provides a simple, useful tool for the physiological assessment of beta-cell function.

A gene conferring susceptibility to type 2 diabetes in conjunction with obesity is located on chromosome 18p11.

Genome-wide nonparametric linkage analysis of 480 sib-pairs affected with type 2 diabetes revealed linkage to a previously unreported susceptibility locus on chromosome 18p11. This result improved with stringent subphenotyping using age- and sex-adjusted BMI, ultimately reaching a logarithm of odds of 3.82 (allele sharing 0.6654) at a point between markers D18S976 and D18S391 when the most obese 20% of the sample was analyzed. Several genes on chromosome 18 have been suggested as metabolic disease candidates, but none of these colocalize with our linkage result. We conclude that our results provide support for the presence of a currently uncharacterized gene on chromosome 18p, certain alleles of which confer increased susceptibility to type 2 diabetes in conjunction with obesity. We additionally observed moderate evidence for linkage to chromosome 1, near marker D1S3462; chromosome 4, near marker D4S2361; chromosome 5, near marker D5S1505; and chromosome 17, near marker D17S1301.

Heritability of leptin levels and the shared genetic effects on body mass index and leptin in adult Finnish twins.

OBJECTIVES: Leptin is involved in the regulation of body weight, but the relative role of genetic and environmental influences on inter-individual variation in leptin levels is unknown. DESIGN AND SUBJECTS: To investigate the genetic and environmental contributions to the association of body mass index (BMI) with serum leptin levels, 58 monozygotic (MZ, 27M, 31F), and 74 like-sexed dizygotic (DZ, 32M, 42F) Finnish twin pairs aged 50--76 y were studied. MEASUREMENTS: Serum leptin levels, weight, height, hip and waist measurements. RESULTS: Women had higher mean leptin levels (16.8+/-9.5 ng/ml), and more overall variability in leptin levels than men (6.4+/-3.5 ng/ml; P<0.0001). Leptin levels correlated highly with BMI in men and women. Among women, the MZ and DZ pairwise correlations for leptin were 0.41 (P=0.009) and 0.07 (P=0.32), respectively. Among men the MZ and DZ pairwise correlations for leptin were 0.47 (P=0.006) and 0.23 (P=0.10). Univariate twin analysis indicated that, among women, 34% and, among men, 45% of the variance in leptin can be attributed to additive genetic effects, and the remainder to unique environmental effects. Significant non-additive genetic or shared familial effects could not be demonstrated. A bivariate twin analysis of leptin and BMI indicated that the correlation between additive genetic effects on leptin and BMI was 0.79 (95% CI 0.68--0.86) in women, and 0.68 (0.51--0.80) in men. The correlation between environmental effects on leptin and BMI was 0.77 (95% CI 0.66--0.85) in women, and 0.48 (0.26--0.66) in men. CONCLUSION: Leptin levels are moderately heritable in older adults, and a substantial proportion of genetic effects are in common on leptin levels and obesity in both women and men. International Journal of Obesity (2001) 25, 132-137