Incidence of type 2 diabetes in familial combined hyperlipidemia

Abstract

ObjectiveFamilial combined hyperlipidemia (FCHL) is common among survivors of a premature myocardial infarction. FCHL patients are characterized by visceral obesity, fatty liver, and insulin resistance. The aim of the present study was to determine the incidence and determinants of type 2 diabetes (T2D) in a longitudinal cohort of FCHL pedigrees.Research design and methodsFCHL patients, their unaffected relatives and spouses included in our baseline cohort in 1998–2005 (n=596) were re-invited to determine the incidence of self-reported T2D (that was confirmed by medical records), used as the primary outcome measure. The Fatty Liver Index (FLI) and Homeostasis Model Assessment Insulin Resistance (HOMA2-IR) were used as markers of fatty liver and insulin resistance, respectively. A subset of the original cohort underwent ultrasound of the liver, and subcutaneous and visceral fat in 2002–2005 (n=275; ‘ultrasound subcohort’).ResultsFollow-up data (median: 15 years) was acquired for 76%. The incidence rate of T2D was significantly higher in FCHL patients compared with spouses (19.2 per 1000 person-years vs 2.8 per 1000 person-years; HR : 6.3, 95% CI: 2.4 to 16.8), whereas no differences were observed between unaffected relatives and spouses (HR: 0.9, 95% CI: 0.3 to 2.6). Cox’s proportional hazard regression analyses showed that baseline HOMA2-IR and FLI≥60, but not waist circumference, BMI, or the FCHL affected state, were independently associated with incident T2D. Similar results were obtained in the ultrasound subcohort (median follow-up: 11 years), in which baseline HOMA2-IR and fatty liver (assessed by ultrasound) were independently associated with incident T2D.ConclusionThis study further corroborates the suggestion that the liver plays a central role in the pathogenesis of cardiometabolic complications in FCHL. It supports periodical screening for T2D in this high-risk population.

Combined hyperlipidemia is genetically similar to isolated hypertriglyceridemia

“…1,2 CHL is often associated with other comorbidities, such as obesity and type 2 diabetes, and patients are at increased risk of atherosclerotic cardiovascular disease (ASCVD). [3][4][5] Over the last five decades, efforts to identify a genetic basis have frequently started with the premise that CHL is a single gene or monogenic disorder. 6 In early studies of extended families, a monogenic inheritance pattern was inferred, similar to familial hypercholesterolemia (FH).…”

Association of familial combined hyperlipidemia with acute coronary syndrome

“…With timely diagnosis and application of adequate treatment, it is possible to improve the quality of life and prevent the life-threatening complications of familial combined hyperipidemia. [14]. Kardiometabolički faktori rizika kao što su hipertenzija i metabolički sindrom su nezavisni prediktori velikih kardiovaskularnih događaja kod pacijenata sa FCHL [15].…”

Einfluss erhöhter Lipoprotein-konzentrationen auf die Prognose von Patienten mit Diabetes mellitus

“…Hierbei handelt es sich um eine genetisch bedingte Fettstoffwechselstörung, deren Phänotyp ähnlich der Dyslipid ämie bei Typ-2-Diabetes und beim metabolisch-vaskulären Syndrom ist [1]. VLDL, VLDL-Remnants und LDL, deren Hauptprotein Apolipoprotein B ist, sind in wechselnder Ausprägung als Folge einer VLDL-Überproduktion und verminderten Clearance der Lipoproteine erhöht [6]. Die Diagnose wird anhand der Konzentrationen von Apolipoprotein B (> 1,2 g/l [120 mg/dl] und der nTG (> 1,5 mmol/l [132 mg/dl]) gestellt.…”

“…Die Diagnose wird anhand der Konzentrationen von Apolipoprotein B (> 1,2 g/l [120 mg/dl] und der nTG (> 1,5 mmol/l [132 mg/dl]) gestellt. Die Inzidenz eines Typ-2-Diabetes war im Vergleich zu von der Krankheit nicht betroffenen Verwandten und zu Partnern ebenso wie die KVE-Rate erhöht [6,7].…”