The role of body mass index, insulin, and adiponectin in the relation between fat distribution and bone mineral density.

Despite the positive association between body mass index (BMI) and bone mineral density (BMD) and content (BMC), the role of fat distribution in BMD/BMC remains unclear. We examined relationships between BMD/BMC and various measurements of fat distribution and studied the role of BMI, insulin, and adiponectin in these relations. Using a cross-sectional investigation of 2631 participants from the Erasmus Rucphen Family study, we studied associations between BMD (using dual-energy X-ray absorptiometry (DXA]) at the hip, lumbar spine, total body (BMD and BMC), and fat distribution by the waist-to-hip ratio (WHR), waist-to-thigh ratio (WTR), and DXA-based trunk-to-leg fat ratio and android-to-gynoid fat ratio. Analyses were stratified by gender and median age (48.0 years in women and 49.2 years in men) and were performed with and without adjustment for BMI, fasting insulin, and adiponectin. Using linear regression (adjusting for age, height, smoking, and use of alcohol), most relationships between fat distribution and BMD and BMC were positive, except for WTR. After BMI adjustment, most correlations were negative except for trunk-to-leg fat ratio in both genders. No consistent influence of age or menopausal status was found. Insulin and adiponectin levels did not explain either positive or negative associations. In conclusion, positive associations between android fat distribution and BMD/BMC are explained by higher BMI but not by higher insulin and/or lower adiponectin levels. Inverse associations after adjustment for BMI suggest that android fat deposition as measured by the WHR, WTR, and DXA-based android-to-gynoid fat ratio is not beneficial and possibly even deleterious for bone.

Familial aggregation of preeclampsia and intrauterine growth restriction in a genetically isolated population in The Netherlands.

Preeclampsia and intrauterine growth restriction are related, pregnancy-specific disorders with a substantial genetic influence, which may have a joint genetic aetiology. We investigated familial aggregation, consanguinity and parent-of-origin effects for preeclampsia and IUGR. Fifty women with previous preeclampsia and 56 with previous pregnancies complicated by intrauterine growth restriction were recruited from a recent genetically isolated population in the Netherlands. Their relationships were estimated by means of a large genealogy database that contains information on more than 110 000 individuals from the isolate over 23 generations. Relationships were quantified using kinship and inbreeding coefficients. Parent-of-origin effects were evaluated by comparing parental kinships. Eighty-six women (39 preeclampsia and 47 intrauterine growth restriction) could be linked to one common ancestor within 14 generations. The proportion of related women with previous preeclampsia (95.6%) or pregnancies complicated by intrauterine growth restriction (95.1%) was significantly greater than expected by chance (P<0.001). Combined analysis of both disorders did not change the magnitude of familial aggregation. The proportion of women born from consanguineous marriages was increased in women with previous preeclampsia (81.8%) and those with intrauterine growth restriction (78%) compared to a random sample (P<0.001). Maternal and paternal kinships were not significantly different in both disorders. We demonstrate cosegregation of preeclampsia and intrauterine growth restriction, supporting a common genetic aetiology. The high proportion of parental consanguineous marriages suggests the possibility of an underlying recessive mutation. No evidence was found for a parent-of-origin effect either in preeclampsia or in intrauterine growth restriction.

Severe, very early onset preeclampsia: subsequent pregnancies and future parental cardiovascular health.

OBJECTIVE: To study subsequent pregnancy outcome in women with severe, very early onset preeclampsia (onset before 24 weeks' gestation) and to analyze cardiovascular risk profiles of these women and their partners. STUDY DESIGN: Twenty women with preeclampsia with an onset before 24 weeks' gestation, admitted between 1 January 1993 and 31 December 2002 at a tertiary university referral center, were enrolled in the study. Data on subsequent pregnancies were obtained from medical records. Their cardiovascular risk profiles and those of their partners (n=15) were compared with those of 20 control women after uncomplicated pregnancies only, matched for age and parity, and those of their partners (n=13). Body weight, height, waist and hip circumference, blood pressure and intima media thickness (IMT) of the common carotid artery were measured. Fasted blood samples were drawn for detection of metabolic cardiovascular risk factors. RESULTS: Of the 20 case women 17 women had 24 subsequent pregnancies, of which 12 (50%) were complicated by preeclampsia. Severe preeclampsia developed in five (21%) pregnancies. No perinatal deaths occurred. Case women had significantly more often chronic hypertension as compared to controls (55% vs. 10%, P=0.002). IMT of the common carotid artery was increased in a subset of case women using antihypertensive medication (P=0.03). Case women showed increased microalbuminuria (P<0.05). No differences were found in cardiovascular risk profiles between partners of cases and controls. CONCLUSIONS: Women with severe, very early onset preeclampsia have an increased risk of preeclampsia in future pregnancies, yet neonatal outcome is, in general, favourable. Regarding cardiovascular health, women after severe, very early onset preeclampsia exhibit more risk factors compared to controls whereas men who fathered these pregnancies do not.

Shared constitutional risks for maternal vascular-related pregnancy complications and future cardiovascular disease.

Maternal predisposition to vascular and metabolic disease may underlie both vascular-related pregnancy complications, such as preeclampsia and intrauterine growth restriction, as well as future maternal cardiovascular disease. We aimed to substantiate this hypothesis with biochemical and anthropometric evidence by conducting an intergenerational case-control study in a Dutch isolated population including 106 women after preeclampsia or intrauterine growth restriction (median follow-up: 7.1 years) and their fathers (n=43) and mothers (n=64), as well as 106 control subjects after uncomplicated pregnancies with their fathers (n=51) and mothers (n=68). Cardiovascular risk profiles were assessed, including fasting glucose, lipids, anthropometrics, blood pressure, intima-media thickness, and metabolic syndrome. We found significantly higher fasting glucose levels, larger waist circumferences, and a 5-fold increased prevalence of hypertension in women with a history of preeclampsia as compared with control subjects (P<0.001). Likewise, their parents had higher glucose levels than control parents (P<0.05). Their mothers had larger waist circumferences and higher blood pressures (P<0.05). Also, women after pregnancies complicated by intrauterine growth restriction had higher glucose levels and increased prevalence of hypertension (P<0.01). Their fathers showed higher glucose levels as well (P<0.05). Mean carotid intima-media thickness was increased in a subset of women after preeclampsia diagnosed with chronic hypertension as compared with those without hypertension (P<0.01). Metabolic syndrome was more prevalent both in women with a history of preeclampsia and their mothers (P<0.05). We demonstrated intergenerational similarities in cardiovascular risk profiles between women after preeclampsia or intrauterine growth restriction and their parents. These findings suggest shared constitutional risks for vascular-related pregnancy complications and future cardiovascular disease.