Intrapair Differences Research Articles

Outcome of Twin Pregnancies According to Intrapair Birth Weight Differences

In Brief Objective To assess the clinical significance of twin intrapair birth weight differences. Methods This was a retrospective study of twin pregnancy outcomes. Intrapair birth weight differences were stratified into the following six groups: 14% or less, 15–20%, 21–25%, 26–30%, 31–40%, and 41% or more using the larger infant as the growth standard. Statistical analysis was done using the Mantel-Haenzel χ2 test. Results We studied 1370 consecutive women who delivered at Parkland Hospital, Dallas, Texas, between January 1, 1988, and December 31, 1996, and had twin gestations and live births or fetal deaths within 7 days of delivery. Greater birth weight discordance was significantly associated with preterm delivery due to intervention (P < .001). Noncephalic-cephalic presentations and cesarean delivery were also associated with greater discordance (P = .001 and .02, respectively). Neonatal morbidities, including low birth weight, intensive care admission, and respiratory distress, were all associated with higher birth weight discordance. Fetal abnormalities were more common with increased discordance (P < .001). Greater birth weight discordance was also associated with intrauterine fetal death. There were no differences in outcome for the smaller compared with the larger twin of the twin pair. Conclusion Twin birth weight discordance is problematic because severe divergent fetal growth increases the risk of fetal death and leads to obstetric intervention and consequent neonatal morbidity due to prematurity. Birth weight discordancy was associated with both antepartum fetal death and morbidity of prematurity in an analysis of 1370 consecutive twin gestations.

Outcome of twin pregnancies according to intrapair birth weight differences

Objective: To assess the clinical significance of twin intrapair birth weight differences. Methods: This was a retrospective study of twin pregnancy outcomes. Intrapair birth weight differences were stratified into the following six groups: 14% or less, 15–20%, 21–25%, 26–30%, 31–40%, and 41% or more using the larger infant as the growth standard. Statistical analysis was done using the Mantel-Haenzel χ 2 test. Results: We studied 1370 consecutive women who delivered at Parkland Hospital, Dallas, Texas, between January 1, 1988, and December 31, 1996, and had twin gestations and live births or fetal deaths within 7 days of delivery. Greater birth weight discordance was significantly associated with preterm delivery due to intervention ( P < .001). Noncephalic-cephalic presentations and cesarean delivery were also associated with greater discordance ( P = .001 and .02, respectively). Neonatal morbidities, including low birth weight, intensive care admission, and respiratory distress, were all associated with higher birth weight discordance. Fetal abnormalities were more common with increased discordance ( P < .001). Greater birth weight discordance was also associated with intrauterine fetal death. There were no differences in outcome for the smaller compared with the larger twin of the twin pair. Conclusion: Twin birth weight discordance is problematic because severe divergent fetal growth increases the risk of fetal death and leads to obstetric intervention and consequent neonatal morbidity due to prematurity.

Clustering of insulin resistance, total and central abdominal fat: same genes or same environment?

Obesity, insulin resistance and disturbed glucose metabolism cluster within the Insulin Resistance Syndrome (IRS). Whether this reflects shared genetic or environmental factors detectable in 'normal' populations (not selected for IRS features) is unknown. This study estimated (i) genetic influences on IRS traits and (ii) shared and specific genetic and environmental factors on the relationships between these traits in healthy female twins. Fasting insulin, glucose, total and central fat were measured in 59 monozygotic (MZ) and 51 dizygotic (DZ) female twin pairs aged (+/- SD) 52 +/- 13 years. Body fat was measured by dual-energy X-ray absorptiometry, insulin resistance and secretion by a modified homeostasis model assessment. Using intraclass correlation coefficients and univariate model-fitting analyses, genetic influences were found in total fat, central fat, insulin resistance, fasting glucose and insulin secretion, with genetic factors explaining 64, 57, 59, 75 and 68% of their variance, respectively, using the latter technique. In matched analysis intra-pair differences in total and central fat related to intra-pair differences in insulin resistance (r2 = 0.19, P < 0.001). Multivariate model-fitting showed a close genetic relationship between total and central fat (r = 0.88). The genetic correlation between IR and central fat (0.41) was significantly greater than that for total fat (0.24), suggesting that central fat is not only a predictor of, but shares considerable genetic influence with, insulin resistance. In Cholesky analysis, these genetic influences were separate from those shared between central and total fat. In conclusion, both shared and specific genetic factors regulate components of the IRS in healthy females. However, there were discrete genetic influences on beta-cell insulin secretion, not shared with other IRS components, suggesting that a separate genetic propensity exists for Type 2 diabetes. These findings suggest we may understand the genetic and environmental influences on IRS from the study of the normal population.

Environmental factors in the development of obesity in identical twins.

To study environmental factors promoting obesity when genetic factors are identical. Monozygotic (MZ) twins discordant for overweight were examined during a 3-day stay in an inpatient setting. The subjects were selected from the Finnish Twin Cohort. The study sample consisted of 23 healthy adult MZ twin pairs (14 female, nine male) with a difference of at least 3 kg/m2 in BMI. The mean BMI was 29.5 kg/m2 for the overweight twins and 22.9 kg/m2 for their lean co-twins. Interviews and standardized questionnaires were used to obtain information about energy and nutrient intake, eating behaviour, physical activity history, smoking and other background factors. The overweight co-twins had higher disinhibition scores (P = 0.007) and hunger scores (P = 0.005) in the 3-Factor Eating Questionnaire than their lean co-twins. Among women the mean daily energy intake was higher in the overweight twins than in their lean co-twins (8.8 vs 7.4 MJ; P = 0.045). In the twins discordant for smoking the mean BMI was higher in non-smokers than in smokers (BMI 29.7 +/- 4.4kg/m2 vs 23.8 +/- 3.1 kg/m2; P = 0.031). Difficulty in controlling eating in both sexes and high energy intake in women were related to overweight, independent of genetic background. Smoking explained the BMI difference among smoking discordant pairs. It is probable that individual twin pairs had different reasons behind the variation in weight gain resulting in non-significant intrapair differences in single obesity-promoting factors. Difference in living conditions (e.g. family-and work-related factors) may have promoted different living habits, especially eating behaviour, and may have led to different weight gain in identical twins.

Clustering of insulin resistance, total and central abdominal fat: same genes or same environment?

AbstractObesity, insulin resistance and disturbed glucose metabolism cluster within the Insulin Resistance Syndrome (IRS). Whether this reflects shared genetic or environmental factors detectable in ‘normal’ populations (not selected for IRS features) is unknown. This study estimated (i) genetic influences on IRS traits and (ii) shared and specific genetic and environmental factors on the relationships between these traits in healthy female twins. Fasting insulin, glucose, total and central fat were measured in 59 monozygotic (MZ) and 51 dizygotic (DZ) female twin pairs aged ( ± SD) 52 ± 13 years. Body fat was measured by dual-energy X-ray absorptiometry, insulin resistance and secretion by a modified homeostasis model assessment. Using intraclass correlation coefficients and univariate model-fitting analyses, genetic influences were found in total fat, central fat, insulin resistance, fasting glucose and insulin secretion, with genetic factors explaining 64, 57, 59, 75 and 68% of their variance, respectively, using the latter technique. In matched analysis intra-pair differences in total and central fat related to intra-pair differences in insulin resistance (r2 = 0.19, P &lt; 0.001). Multivariate model-fitting showed a close genetic relationship between total and central fat (r = 0.88). The genetic correlation between IR and central fat (0.41) was significantly greater than that for total fat (0.24), suggesting that central fat is not only a predictor of, but shares considerable genetic influence with, insulin resistance. In Cholesky analysis, these genetic influences were separate from those shared between central and total fat. In conclusion, both shared and specific genetic factors regulate components of the IRS in healthy females. However, there were discrete genetic influences on -cell insulin secretion, not shared with other IRS components, suggesting that a separate genetic propensity exists for Type2 diabetes. These findings suggest we may understand the genetic and environmental influences on IRS from the study of the normal population.

Influence of current and past hormone replacement therapy on bone mineral density: a study of discordant postmenopausal twins.

There is controversy about the ideal timing of hormone replacement therapy (HRT) and duration of treatment. In this study we have examined intrapair differences in bone mineral density (BMD) in twins who were discordant for HRT use. Twin pairs in which only one co-twin had been exposed to HRT for more than 12 months continuously were selected from 365 postmenopausal monozygotic (MZ) and dizygotic (DZ) pairs recruited as part of the St Thomas' Adult UK Twin Registry of normal volunteers. BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck. Intrapair differences in BMD between HRT users and non-users were compared. A total of 65 HRT-discordant pairs were identified, of which 36 were discordant for current HRT use (mean age: 55.3 years, median duration of HRT use: 36 months) and 29 were discordant for past HRT use (mean age: 60.4 years, median HRT duration: 30 months). Among current users BMD was consistently and significantly higher than in non-users at both sites (lumbar spine mean intrapair difference (IPD%): 12.3%, 95% confidence interval (CI): 7.1%, 17.5%; femoral neck IPD%: 8.6%, 95% CI: 3.4%, 13.7%). The intrapair differences were substantially smaller when past users and non-users were compared (lumbar spine IPD%: 2.4%, 95% CI: -3.7%, 8.6%; femoral neck IPD%: 0.4%, 95% CI: -5.3%, 6.0%). These differences remained little changed after adjusting for the potential confounding effects of the duration of HRT use, and intrapair differences in alcohol and tobacco consumption and physical exercise. The results confirm, in a closely matched design, the findings of other observational research that current use of HRT has a major effect on BMD at the lumbar spine and femoral neck. Past users of HRT do not, however, show the same benefits. The clinical implications of these findings are that HRT needs to be used continuously to influence BMD and that alternative treatments need to be considered in those who discontinue HRT.

Changes of voice parameters and melody patterns during the first year of life in human twins

The study analyzed changes of cry characteristics of twins using spectrograms, fundamental frequency contours (melody), and several indicators of microvariability of the fundamental frequency (F0) calculated with the aid of a KAY Elemetrics CSL Model 4305. Subjects were 15 identical and 15 fraternal healthy twin pairs, whose spontaneous utterances were recorded every 6 weeks over the first year of life. Developmental changes of F0, jitter, perturbation quotient, degree of voiceless, degree of subharmonic components as well as the evolution of complex melody patterns were analyzed. Correlations of the voice data with anthropometric data (weight, length, head circumference) and obstetrical factors (time of gestation, presentation, birth modus) were calculated to consider influences by growth discordance or different birth histories. As identical twins have a much greater congenital synchronization of development, universals of prespeech evolution are more convincingly expressed in these pairs (lower intrapair differences). A statistically significant higher intrapair concordance in identical twins was found for the mean F0 within the first week of life, for the mean F0 and jitter in the period within 5–8 months of life, and for certain melody patterns. For other parameters, significant intrapair differences between identical and fraternal twins were not found.

Comparative corneal topography and refractive variables in monozygotic and dizygotic twins

PURPOSE: To investigate the role of heredity in determining corneal shape, axial length, and overall refractive error.METHODS: Twenty monozygotic and 19 dizygotic twin pairs, age 12 to 73 years, were enrolled in the study. Zygosity was determined by physical similarity and by responses to questions adapted from surveys. Two twin pairs were excluded because of undetermined zygosity and one pair because of keratoconus (both siblings). Refractive error was determined by an automated refractor. Manifest refraction was also recorded, as well as cycloplegic refraction in subjects under age 18 years. Corneal topography data and manual keratometer readings were also obtained. Axial lengths were determined by A-scan ultrasound. Data were analyzed by Student t tests only in the right eye. Left-eye data were comparable for all variables.RESULTS: Mean intrapair difference in refractive error (spherical equivalent) was less for monozygotic than for dizygotic twins (RE: 0.41 vs 1.53; P = .001). Mean intrapair difference in axial length was less for monozygotic twins (RE: 0.39 vs 0.76 mm; P = .031). Corneal topography data (power and meridian) in all zones (3, 5, and 7 mm) also showed smaller mean differences among monozygotic pairs than dizygotic, but the difference was statistically significant only for the 5-mm zone. In addition, most Holladay Diagnostic Summary variables that were studied did not show any statistically significant differences.CONCLUSIONS: Axial length and overall refractive error have a significant genetic basis. Corneal topography data appear to have other overriding determining factors for several of the variables studied.

Genes versus environment. The relationship between dietary fat and total and central abdominal fat.

The influence of diet on body fat has not been quantified independently of genetic influences, although both are held to contribute to regulation of body fat stores. This study examined 1) the relationship between recent diet and total body and central abdominal fat in middle-aged female twins independent of genetic and important environmental factors and 2) evidence of interaction between diet and genetic predisposition. Measurements in 436 healthy female twins (aged 58 +/- 10 years) included dietary intake by food frequency questionnaire (validated against a 7-day food diary, n = 162), BMI, total body and central abdominal fat by dual-energy X-ray absorptiometry, and environmental covariates (smoking habit, hormone replacement, and physical activity) by standardized questionnaire. Dietary energy underreporters were excluded. Intake of dietary fat (total and subtype) and carbohydrates was not related to BMI or to total or central fat, confirmed in quintile analysis. With genetic and environmental factors controlled in 90 monozygotic pairs, differences in the intake of energy, fat, or protein were not related to intrapair differences in total and central body fat. However, a minor inverse relationship between carbohydrate intake and total adiposity was confirmed (r = -0.25, P = 0.02). In paired analyses, the twin with the higher intake of total sugars had significantly lower total body and central abdominal adiposity. There was no evidence of a gene-environment interaction between intake of fat or carbohydrates contributing to greater body fat mass in subjects genetically predisposed to obesity. Using validated dietary measures and direct measures of body fat and excluding underreporters, no relationship between dietary fat and body fat was found in middle-aged women, particularly after controlling for genetic and some environmental factors. The role of dietary factors in determining total body and central abdominal fat appears to have been overestimated in past cross-sectional studies.

Serum lipids, lipoproteins, and lipid metabolizing enzymes in identical twins discordant for obesity.

Obesity is associated with adverse changes in plasma lipoprotein metabolism, but it is not known completely how this association is modified by genetic factors. We assessed the contribution of obesity to serum lipid and lipoprotein levels and lipid metabolizing enzyme activities by examining 23 identical twin pairs (9 male, 14 female) who had, on the average, an 18-kg intrapair difference in BW. Compared with lean co-twins, obese co-twins had approximately 20% higher low-density lipoprotein (LDL) cholesterol (P < 0.01), 20% lower high-density lipoprotein2 cholesterol (P = 0.010), and 90% (men) or 35% (women) higher (P < or = 0.06) total, very-low-density lipoprotein and LDL triglycerides. The pairs were divided into subgroups by the gender-specific median value of abdominal visceral fat (AVF) area in the obese co-twin and by apolipoprotein E 4 phenotype. The intrapair differences in serum cholesterol fractions were similar in twin pairs with high or low AVF, whereas only high AVF pairs showed significant differences in triglyceride fractions. The greatest intrapair differences in total, very-low-density lipoprotein and LDL triglycerides were observed in apolipoprotein E 4-positive pairs expressing high AVF. Compared with lean co-twins, lecithin cholesterol acyltransferase activity was 18% higher (P < 0.001) and hepatic lipase activity was 38% higher (P = 0.016) in obese co-twins with high AVF. When genetic factors are identical, obesity is associated with an atherogenic lipid profile, especially in subjects with high visceral fat accumulation.

Genetic and environmental contributions to the association between quantitative ultrasound and bone mineral density measurements: a twin study.

This study was designed to assess the relative contributions of genetic and environmental factors to the variation and covariation of quantitative ultrasound (QUS) measurements and their relationships to bone mineral density (BMD). Forty-nine monozygotic (MZ) and 44 dizygotic (DZ) female twins between 20 and 83 years of age (53 +/- 13 years, mean +/- SD) were studied. Digital (phalangeal) QUS (speed of sound [SOS]) and calcaneal QUS (broadband ultrasound attenuation [BUA] and velocity of sound [VOS]) were measured using a DBM Sonic 1200 ultrasound densitometer and a CUBA ultrasound densitometer, respectively. Femoral neck (FN), lumbar spine (LS), and total body (TB) BMD were measured using dual-energy X-ray absorptiometry. Familial resemblance and hence heritability (proportion of variance of a trait attributable to genetic factors) were assessed by analysis of variance, univariate, and multivariate model-fitting genetic analyses. In both QUS and BMD parameters, MZ twins were more alike than DZ pairs. Estimates of heritability for age- and weight-adjusted BUA, VOS, and SOS were 0.74, 0.55, and 0.82, respectively. Corresponding indices of heritability for LS, FN, and TB BMD were 0.79, 0.77, and 0.82, respectively. In cross-sectional analysis, both BUA and SOS, but not VOS, were independently associated with BMD measurements. However, analysis based on intrapair differences suggested that only BUA was related to BMD. Bivariate genetic analysis indicated that the genetic correlations between BUA and BMD ranged between 0.43 and 0.51 (p < 0.001), whereas the environmental correlations ranged between 0.20 and 0.28 (p < 0.01). While the genetic correlations within QUS and BMD measurements were significant, factor analysis indicates that common genes affect BMD at different sites. Also, individual QUS measurements appear to be influenced by some common sets of genes rather than by environmental factors. Significant environmental correlations were only found for BMD measurements and ranged between 0.50 and 0.65 (p < 0.001). These data suggest that QUS and BMD measurements are highly heritable traits. While it appears that there is a common set of genes influencing both QUS and BMD measurements, specific genes yet to be identified appear to have greater effects than that of shared genes in each trait.

Genetic and Environmental Correlations Between Bone Formation and Bone Mineral Density: A Twin Study

Bone mineral density (BMD) and bone turnover are both heritable. Although bone turnover affects bone mass, it is not clear whether these parameters are under common genetic or environmental control. The relative contribution of genetic and environmental factors to the determination of an index of bone turnover, bone specific alkaline phosphatase (BSAP), and the extent of common genetic regulation with BMD, were examined in 97 female twin pairs, aged 50 ± 15 years (mean ± SD), consisting of 48 monozygotic (MZ) and 49 dizygotic (DZ) pairs. BSAP was analyzed by radioimmunometric assay. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) was measured by dual-energy X-ray absorptiometry. Twin resemblance for variable traits was assessed by intraclass correlation coefficients. Estimates of genetic and environmental components of variance were based on univariate and multivariate genetic models. As expected, BSAP in premenopausal women (9.8 ± 4.3 μg/L) was significantly lower than in postmenopausal women (13.3 ± 6.6 μg/L, p < 0.001), but similar to the subgroup of postmenopausal women on hormone replacement therapy (10.8 ± 2.6 μg/L, p = 0.15). Although BSAP and BMD were correlated in a cross-sectional analysis ( r = −0.35, p < 0.001 for LS-BMD; r = −0.16, p = 0.03 for FN-BMD), the intrapair difference in BSAP was not significantly correlated with the intrapair difference in BMD for MZ twin pairs. After adjustment for menopausal status, the intraclass correlation for BSAP was significantly higher in MZ than DZ twins (0.60 ± 0.09 vs. 0.27 ± 0.13, p = 0.03). Univariate model-fitting analyses indicated a heritability of 63% for BSAP, and 77% and 72% for lumbar spine and femoral neck BMD, respectively. By multivariate analyses, genes specifically influencing BSAP accounted for 16% of the total genetic variance in LS-BMD and 4% of the total genetic variance in FN-BMD. There was no evidence for shared environmental factors affecting BSAP and BMD. These findings indicate that BSAP and BMD are heritable and negatively correlated. However, the genetic loci influencing BSAP and BMD appear to be largely independent as are any environmental factors.

Effect of disparities in birth weight on differences in postnatal growth of monozygotic and dizygotic twins

SummaryInfluence of intrapair differences in birth weight (IDBW) on the patterns of postnatal growth of MZ and DZ twins from middle/late childhood to adolescence were studied in 49 MZ, 40 DZ male and 40 MZ, 35 DZ female pairs coming from the Wrocław Longitudinal Twins Study. Intrapair differences in the patterns in postnatal growth were expressed in several indices: average differences in standardized values (ASD Height, ASD Weight); absolute average differences in standardized values (ABSD Height, ABSD Weight); average Euclidean distances coefficient (EUCD Height, EUCD Weight); coefficient of shape differences (SHC Height, SHC Weight); measure of deviation (MD Height, MD Weight) and correlation coefficient for the standardized attained values (CORC Height, CORC Weight). Relationships between IDBW and indices were based on the means of Spearman Rank Order Correlation. Additionally for 40 MZ, 35 DZ male and 25 MZ, 18 DZ female pairs, the relationships between IDBW and intrapair differences in biological parameters derived from Preece Baines model 1, describing differences in time (DT1), height (DH1), velocity (DV1) at the beginning of the adolescent growth spurt, differences in time (DT2), height (DH2), velocity (DV2) at peak height velocity and differences in adult height (DAH) were examined. The results showed that only in MZ girls did dissimilarity in birth weights significantly impair the subsequent growth in stature. Furthermore, the results revealed that birth weight influences the parameter describing adult stature in MZ girls. It is concluded that the lack of relationship in DZ twins is due to their unique genotype, which strongly determines the postnatal growth. Three possible interpretations are given as explanations of the results obtained in this study: male excess neonates mortality, ‘third factor’ and programmed of growth in utero.

The effects of perinatal hypoxic risk on developmental outcome in early and middle childhood: A twin study.

The goal of this study of 66 twins was to determine whether motor and cognitive functions assessed in early and middle childhood are vulnerable to perinatal hypoxic risk. In an earlier study of 76 infant and toddler twins (S. Raz, F. Shah, & C. Sander, 1996), the authors found that intrapair discrepancy on the Mental Developmental Index, but not on the Psychomotor Developmental Index, of the Bayley Scales of Infant Development was associated with discordance for perinatal hypoxic risk. The twins at lower risk outperformed their higher risk co-twins. In the present study the authors sought to establish in a new sample of preschool and school-age twins whether gaps in performance persist into early and middle childhood. Although the disparity in hypoxic risk between the co-twins was typically moderate, significant intrapair differences were observed on the measure of motor performance. Among the motor abilities examined, skills involving visually guided ballistic arm movements appeared to be the most vulnerable to perinatal risk.

Associations between insulin-like growth factor-I (IGF-I), IGF-binding protein-1, insulin and other metabolic measures after controlling for genetic influences: results from middle-aged and elderly monozygotic twins.

It has previously been shown that the serum levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin are influenced by genetic effects to various degrees. From a clinical and preventive point of view, however, it is important to identify potentially modifiable non-genetic factors influencing the levels of these measures. Because monozygotic twin pairs share the same genetic background, differences in phenotypic levels within monozygotic twin paris are believed to be due to non-genetic influences. Accordingly, the associations between intrapair differences in one phenotype and intrapair differences in another phenotype are also due to non-genetic influences. The present sample of 97 pairs of monozygotic twins from the population-based Swedish Adoption/Twin Study of Aging (SATSA) provided the opportunity to assess non-genetic influences on the levels of IGF-I, IGFBP-1, and insulin. Several metabolic measures were found to account for the variation of IGF-I, IGFBP-1, and insulin after controlling for the genetic influences. IGFBP-1 and glucose were significant predictors for the levels of IGF-I. IGFBP-1 and glucose together explained about one quarter of the non-genetic variation of IGF-I. However, when IGFBP-1 was dropped from the regression model, insulin was the only independent predictor of IGF-I, and explained about 19% of the non-genetic variation for IGF-I. For IGFBP-1, insulin and IGF-I, were the significant non-genetic predictors. Insulin and IGF-I explained about 28 and 8% respectively of the non-genetic variation for IGFBP-1, while for insulin, IGF-I, triglycerides, body height, glucose, and body mass index (BMI) explained approximately 20, 12, 6, 5 and 5% respectively of the non-genetic variation.

Long term influence of insulin dependent diabetes mellitus on refraction and its components: a population based twin study

AIMTo study whether refraction of the eye, or some of its components is influenced by duration of insulin dependent diabetes mellitus.METHODSFrom the young cohort of the population based Danish Twin...

Sonographic examination does not predict twin growth discordance accurately

To assess the accuracy of estimating birth weight among twins with discordancy (intra-pair difference in actual birth weight of more than 25%) and to determine the relative accuracy of an intra-pair difference in abdominal circumference (delta AC) of 20 mm or more or in estimated fetal weight (delta EFW) of 25% or more for the identification of discordant growth in twins. Over a 6-year period, we identified all non-anomalous twin pairs with gestational ages greater than 23 weeks and sonographic examinations within 3 weeks of birth. Ultrasonographic biometry of both twins included AC, head circumference, and femur length; these indices were used to estimate fetal weight by Hadlock's formula. Likelihood ratios, receiver-operating characteristic curves, and prediction limits were applied to assess the accuracy of the two diagnostic methods to predict an abnormal outcome. A total of 242 twin pairs were studied. The mean gestational age among the 21 twins with abnormal growth (30.6 +/- 4.6 weeks) was significantly less than among the 221 twins with normal growth (33.2 +/- 4.0 weeks) (P < .005). The biometric measurements of fetal parts, sonographic estimate of fetal weight, and actual birth weight for both fetuses were significantly less for discordant twin pairs (P < .05). The accuracy of predicting birth weight, as determined by mean error and percentage of the estimate within 10% of the actual weight, was similar between the groups. Receiver-operating characteristic curves showed that both diagnostic tests yielded areas under the two curves not significantly different from the area under the nondiagnostic line (P > .05). Most important, prediction limit calculations indicated that a 90% certainty that the actual birth weight discordance was at least 25% was achievable only if delta AC was 172 mm or greater or delta EFW was 112% or more. The most popular current methods (difference in AC or EFW) for predicting discordant growth in twin gestations have limited accuracy when held to a standard for discordance that requires a birth weight difference of at least 25%.

Heritability for Alzheimer's disease: the study of dementia in Swedish twins.

Alzheimer's disease has been thought to have familial and sporadic forms, and several genetic defects have been identified that chiefly explain early-onset familial cases. In this study, our purpose was to detect all cases of dementia in an established twin registry and to estimate total extent of genetic contribution to liability to Alzheimer's disease. At the first stage, members of the registry were screened for dementia, using in-person or telephone mental status testing. At the second stage, those who screened positively and their partners were referred for clinical work-ups, including neuropsychological assessment, physician examination, laboratory tests, and neuroimaging. Clinical diagnoses were assigned at a multidisciplinary consensus conference. Probandwise concordance rates were examined by zygosity, and structural modeling was applied to the data to estimate genetic and environmental influences, using both single- and multiple-threshold models. Sixty-five pairs were identified in which one or both was demented. The probandwise concordance rate for Alzheimer's disease among monozygotic pairs was 67%; the corresponding figure for dizygotic pairs was 22%. Heritability of liability to Alzheimer's disease was estimated to be .74; to any dementia, .43. The other variance is attributable to environmental influences. Findings indicate a substantial genetic effect for these predominantly late-onset Alzheimer's disease cases. At the same time, structural modeling results and large intra-pair differences in age of onset suggest that environmental factors are also important in determining whether and when an individual may develop dementia.

Glucose metabolism in identical twins discordant for obesity. The critical role of visceral fat.

Obesity, especially intraabdominally deposited fatness, is associated with reduced insulin sensitivity. However, it is not well established whether this association is confounded by genetic factors. We studied 23 monozygous twin pairs (14 female, 9 male), 33-59 yr old, who had, on the average, 18 kg intrapair difference in body weight. A 75-g oral glucose tolerance test with glucose and insulin measurements at 30-min intervals was performed, and fat distribution was determined with magnetic resonance imaging. The pairs were divided into two groups by the gender-specific median of the abdominal visceral fat area (AVF) in the obese co-twins. In the high-AVF pairs, the mean area under curve (AUC) for glucose (mmol x min/L) was 758 vs. 968 (P = 0.001), AUC for insulin (mU x min/L) was 4320 vs. 8741 (P = 0.001), and insulin sensitivity index (mg x L x L/mmol x mU x min) was 71.5 vs. 45.9 (P < 0.001) in the lean and obese co-twins, respectively. In the low AVF pairs, the mean AUC for glucose was 669 vs. 706 (not significant), AUC for insulin was 3323 vs. 4241 (not significant), and the sensitivity index was 85.2 vs. 73.7 (P = 0.04) in the lean and obese co-twins, respectively. In subjects who are genetically identical but who are discordant for body mass, only those who differ most in visceral fat level are characterized by major alterations in insulin sensitivity and glucose tolerance.

Relation between plasma leptin levels and measures of body fat in identical twins discordant for obesity.

Plasma levels of leptin, the recently discovered satiety hormone, are associated with adiposity in humans. To determine whether genetic factors or body fat distribution affect the association between leptin levels and obesity. 23 healthy identical twin pairs (9 male pairs and 14 female pairs, 33 to 59 years of age) who were discordant for obesity (average weight difference, 18 kg). Fasting plasma leptin levels were measured by radioimmunoassay. Distribution of abdominal fat into visceral and subcutaneous compartments was estimated by use of magnetic resonance imaging. Plasma leptin levels were threefold higher in obese twins than in lean twins (mean +/- SD, 18.7 +/- 12.5 micrograms/L compared with 6.4 +/- 4.8 micrograms/L; P < 0.001); a similar difference was seen when the entire study group was divided according to sex. Compared with lean twins, plasma leptin levels were 3.7-fold higher in the obese twins who had visceral fat accumulation greater than the median and 2.1-fold higher in the obese twins who had visceral fat accumulation less than the median. The intrapair differences in leptin levels correlated with the corresponding differences in percentage of body fat in women (r = 0.73; P = 0.003) but not in men and correlated with differences in visceral fat area in men (r = 0.79; P = 0.019) and women (r = 0.73; P = 0.007). In multiple regression analyses that included intrapair differences in visceral fat area and total body fat, the association between differences in visceral fat area and leptin levels was significant in men (P = 0.029) but not in women. Plasma leptin levels are increased in obese persons, independent of genetic background. Visceral fat may be of special importance in the regulation of leptin levels, but it is probably less important in women than in men.