Germline and somatic mosaicism in a family with multiple endocrine neoplasia type 1 (MEN1) syndrome.

Context Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease caused by mutations in the tumor suppressor gene MEN1 and can be diagnosed based on clinical, familial and/or genetic criteria. We present a family in which we found both germline and somatic mosaicism for MEN1. Family description In our proband, we diagnosed MEN1.

Rare NOX3 Variants Confer Susceptibility to Agranulocytosis During Thyrostatic Treatment of Graves' Disease.

Agranulocytosis is a rare and serious adverse effect of antithyroid drugs, with unknown etiology. The present study aimed to uncover genetic susceptibility and underlying mechanisms of antithyroid drug-induced agranulocytosis (ATDAC). We studied two independent families with familial Graves' disease, of which several members developed ATDAC.

MEN1-Dependent Breast Cancer: Indication for Early Screening? Results From the Dutch MEN1 Study Group.

Objective: Multiple endocrine neoplasia type 1 (MEN1) is associated with an early-onset elevated breast cancer risk. This finding potentially has implications for breast cancer screening for women with MEN1, and therefore it is necessary to assess whether other risk factors are involved to identify those at greatest risk.

Design: A cross-sectional case control study was performed using the Dutch MEN1 cohort, including >90% of the adult Dutch MEN1 population.

Higher central fat mass and lower peripheral lean mass are independent determinants of endothelial dysfunction in the elderly: the Hoorn study.

Objective: To investigate whether an adverse body composition is associated with endothelial dysfunction (ED) and the extent to which any such association could be explained by low-grade inflammation (LGI) and/or insulin resistance (HOMA2-IR).

Methods: We studied 475 individuals from the Hoorn Study [mean (range) age, 68.9 (60-87) years, 245 women).

Clustering of metabolic syndrome traits is associated with maladaptive carotid remodeling and stiffening: a 6-year longitudinal study.

Maladaptive arterial remodeling may constitute a mechanism underlying the risk of stroke in individuals with the metabolic syndrome (MetS), but evidence supporting this contention derives from cross-sectional studies only. We, therefore, investigated, in apparently healthy adults, whether changes in MetS status between the ages of 36 and 42 years (never [n=207, reference group], incident [n=31], recovery [n=23], and persistent [n=32]) were associated with changes in carotid interadventitial diameter, lumen diameter, intima-media thickness, circumferential wall tension and stress, and Young's elastic modulus. All data analyses were adjusted for sex, height, and (changes in) age, lifestyle variables, low-density lipoprotein cholesterol, and use of antihypertensive medication.

Impaired glucose metabolism and type 2 diabetes are associated with hypercoagulability: potential role of central adiposity and low-grade inflammation--the Hoorn Study.

Introduction: Type 2 diabetes (DM2) is associated with greater risk for cardiovascular disease (CVD), which may, at least partially, be explained by prothrombotic alterations. We therefore investigated; first, the extent to which individuals with impaired glucose metabolism (IGM) and/or DM2 had greater levels of thrombin generation than those with normal glucose metabolism (NGM); and second, whether any differences were independent of other cardiovascular risk factors, such as smoking, hypertension, dyslipidaemia, (micro)albuminuria, glycemic control and (central) adiposity, and/or were potentially 'mediated' by low-grade inflammation (high-sensitivity C-reactive protein (hsCRP)).

Materials And Methods: We studied 744 individuals from the Hoorn Study (275 NGM, 176 IGM and 293 DM2, mean age 68.

Metabolic syndrome in nondiabetic individuals associated with maladaptive carotid remodeling: the Hoorn Study.

Background: The metabolic syndrome (MetS) is associated with an increased risk of stroke. Arterial remodeling could play an important role herein as maladaptive remodeling is a risk factor for stroke. The purpose of this study was to investigate whether MetS was associated with maladaptive remodeling of the carotid artery and if any such association was independent of hemodynamic variables.

High prevalence of diabetes mellitus in patients with liver cirrhosis.

Aims: The reported prevalence of Type 2 diabetes mellitus in patients with liver cirrhosis is five times higher than in the general population. However, these data were never adjusted for classical risk factors for Type 2 diabetes. We therefore investigated the association between cirrhosis and Type 2 diabetes and adjusted for known risk factors for Type 2 diabetes.

Body composition as determinant of thrombin generation in plasma: the Hoorn study.

Objective: The association between obesity and cardiovascular disease and venous thromboembolism might, at least partially, be explained by a hypercoagulable state. The extent to which body fat mass and its distribution contribute to a hypercoagulable state is unknown. In this study, we investigated the association between body composition and thrombin generation and evaluated the potential mediating role of low-grade inflammation.

Hepatocyte nuclear factor (HNF)1A and HNF4A substitution occurring simultaneously in a family with maturity-onset diabetes of the young.

Introduction: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by an early age at onset, autosomal dominant inheritance and a primary defect in the function of the B-cells of the pancreas. We report a family with two members carrying a substitution in both the hepatocyte nuclear factor (HNF)1A and HNF4A gene simultaneously.

Case Report: A 39-year-old man was referred because of mild diabetic retinopathy.

Microalbuminuria and cardiovascular autonomic dysfunction are independently associated with cardiovascular mortality: evidence for distinct pathways: the Hoorn Study.

Objective: Microalbuminuria is associated with cardiovascular mortality, particularly among individuals with type 2 diabetes, but the mechanisms underlying this association are not completely understood. Microalbuminuria is known to be associated with cardiovascular autonomic dysfunction (C-AD), and C-AD in turn is associated with cardiovascular mortality. The purpose of this study, therefore, was to investigate whether C-AD can explain the relationship between microalbuminuria and cardiovascular mortality.