Dataset Information

Lipoprotein insulin resistance score and risk of incident diabetes during extended follow-up of 20 years: The Women's Health Study.

ABSTRACT: Type II diabetes (T2D) is preceded by prolonged insulin resistance and relative insulin deficiency incompletely captured by glucose metabolism parameters, high-density lipoprotein (HDL) cholesterol and triglycerides.Whether lipoprotein insulin resistance (LPIR) score, a metabolomic marker, is associated with incident diabetes and improves risk reclassification over traditional markers on extended follow-up.Among 25,925 nondiabetic women aged 45 years or older, LPIR was measured by nuclear magnetic resonance spectroscopy as a weighted score of very low density lipoprotein, low-density lipoprotein, and HDL particle sizes, and their subsets concentrations. We run adjusted cox regression models for LPIR with incident T2D (20.4 years median follow-up).Adjusting for demographics, body mass index, life style factors, blood pressure, and T2D family history, the LPIR hazard ratio for T2D (hazard ratio [HR] per standard deviation, 95% confidence interval) was 1.95 (1.85, 2.06). Further adjusting for HbA1c, C-reactive protein, triglycerides, HDL and low-density lipoprotein cholesterol, LPIR HR was attenuated to 1.41 (1.31, 1.53) and had the strongest association with T2D after HbA1C in mutually adjusted models. The association persisted even in those with optimal clinical profiles, adjusted HR per standard deviation 1.91 (1.17, 3.13). In participants deemed at intermediate T2D risk by the Framingham Offspring T2D score, LPIR led to a net reclassification of 0.145 (0.117, 0.175).In middle-aged or older healthy women followed prospectively for over 20 years, LPIR was robustly associated with incident T2D, including among those with an optimal clinical metabolic profile. LPIR improved T2D risk classification and may guide early and targeted prevention strategies.

SUBMITTER: Harada PHN

PROVIDER: S-EPMC5644504 | biostudies-literature | 2017 Sep - Oct

REPOSITORIES: biostudies-literature

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Lipoprotein insulin resistance score and risk of incident diabetes during extended follow-up of 20 years: The Women's Health Study.

Harada Paulo H N PHN Demler Olga V OV Dugani Sagar B SB Akinkuolie Akintunde O AO Moorthy Manickavasagar V MV Ridker Paul M PM Cook Nancy R NR Pradhan Aruna D AD Mora Samia S

Journal of clinical lipidology 20170621 5

<h4>Background</h4>Type II diabetes (T2D) is preceded by prolonged insulin resistance and relative insulin deficiency incompletely captured by glucose metabolism parameters, high-density lipoprotein (HDL) cholesterol and triglycerides.<h4>Objective</h4>Whether lipoprotein insulin resistance (LPIR) score, a metabolomic marker, is associated with incident diabetes and improves risk reclassification over traditional markers on extended follow-up.<h4>Methods</h4>Among 25,925 nondiabetic women aged 4 ...[more]

PMID: 28733174

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Project description:BACKGROUND:Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant genetic disorder with a wide variety of clinical manifestations due to the presence of multiple arteriovenous malformations in various tissues and organs. OBJECTIVE:To study the need for hospital admittance in a group of HHT patients and matched controls during a 20 years follow-up period commencing in 1995. METHODS:All HHT patients in the County of Funen, Denmark, were included. For each patient, three age and sex matched controls were identified at the time of enrolment. Data on all hospitalisations were extracted from the national health registers and compared with clinical records. The hospitalisations were grouped as HHT relevant or not HHT relevant based on the discharge diagnosis (International Classification of Diseases, ICD10) and with particular focus on infections, bleedings and thromboembolic events. Patients with HHT were compared with controls concerning the first time incidence of each discharge diagnosis. RESULTS:We included 73 HHT patients and 219 controls of which one control was lost to follow-up. HHT-patients had significantly more hospitalisations per person caused by infections in joints and bones, but not caused by infections in general. Bleeding episodes were, as expected, more frequent among the HHT-patients. The study revealed a similar incidence of abscesses and thromboembolisms, including in the central nervous system, among the HHT patients and controls. CONCLUSIONS:Based on this study Danish HHT patients had an increased comorbidity of infections in joints and bones and of bleeding episodes. However, the incidence of thromboembolisms, cerebral abscesses and other conditions commonly considered related to HHT was comparable between the patients and the controls. The patients included in this study were closely monitored at a highly specialised HHT Centre where they received relevant diagnostic evaluation, treatment and counselling. Since this is assumed to benefit the overall health of the patients, it may explain why these patients were less prone to comorbidity than other studies have suggested.

Project description:Plasma estrogen and androgen levels are positively associated with postmenopausal breast cancer risk, but how long a single blood measurement can predict risk and whether the associations vary by tumor hormone receptor status remain unclear. We conducted nested case-control analyses within the Nurses' Health Study. Blood samples were collected in 1989-1990 and again in 2000-2002. Among postmenopausal women not using postmenopausal hormones at blood collection, 707 cases were diagnosed through June 2010, with two matched controls per case. We used unconditional logistic regression analyses to estimate the relative risks controlling for other breast cancer risk factors. The intra-class correlation coefficients for two blood measurements collected 10 years apart ranged from 0.54 (dehydroepiandrosterone sulfate, DHEAS) to 0.74 (sex hormone-binding globulin, SHBG). Overall, women in the top (vs. bottom) 25 % of levels of estradiol, free estradiol, testosterone, free testosterone, and DHEAS were at a 50-110 % higher risk of breast cancer (p (trend) < 0.001). SHBG was inversely associated with risk (p (trend) = 0.004). RRs were similar when comparing cases diagnosed 1-10 versus 11-20 years (or 16-20 years) after blood collection (p (interaction) > 0.2). Except for DHEAS, the associations varied significantly by hormone receptor status (p (heterogeneity) ? 0.02). For example, the RRs (95 % CIs) comparing the highest versus lowest quartile were 2.8 (2.0-4.0; p (trend) < 0.001) for ER +/PR + tumors versus 1.1 (0.6-2.1; p (trend) = 0.98) for ER-/PR- tumors for estradiol, and 1.8 (1.3-2.5; p (trend) < 0.001) versus 0.6 (0.3-1.2; p (trend) = 0.35) for testosterone. One measure of circulating sex hormones in postmenopausal women can predict risk of hormone receptor positive breast cancer for up to 16-20 years.

Dataset Information

Lipoprotein insulin resistance score and risk of incident diabetes during extended follow-up of 20 years: The Women's Health Study.

Publications

Lipoprotein insulin resistance score and risk of incident diabetes during extended follow-up of 20 years: The Women's Health Study.

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