The A54T polymorphism at the intestinal fatty acid binding protein 2 is associated with insulin resistance in glucose tolerant Caucasians

BACKGROUND: An A54T polymorphism at the fatty acid binding protein 2 (FABP2) locus was found to be associated with insulin resistance in non-diabetic Pima Indians. To see whether this association is present in other populations, we performed a cross sectional study to examine the role of this polymorphism on insulin resistance in 55 healthy and normotensive Caucasian subjects with normal glucose tolerance. Insulin sensitivity (%S) and beta cell function (%B) were assessed using the Homeostasis Model Assessment (HOMA). Their genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism assay. The relationship between the genotypes and the phenotypes was examined. RESULTS: After genotyping, we identified 24 AA, 27 AT and 4 TT subjects. The TT subjects were combined with the AT subjects during the analysis due to its small sample size. No differences were noted in gender distribution, clinical features, and fasting lipid profile between the two genotypic groups (AA vs. AT/TT). The AT/TT group had a higher fasting plasma insulin concentration and a lower %S than the AA group (p = 0.0444 and p = 0.0461, respectively). However, no differences were noted in plasma glucose concentrations and %B. Univariate analysis revealed that this polymorphism explained 7.3% of the variation in %S. Multivariate analysis revealed that the polymorphism was an independent determinant for %S (p = 0.0434) and with body mass index accounted for 28.7% of the variation in %S. In contrast, this polymorphism had no impact on %B. CONCLUSIONS: The A54T polymorphism at the FABP2 locus is a risk factor for insulin resistance in a Caucasian population

Hepatic glucokinase promoter polymorphism is associated with hepatic insulin resistance in Asian Indians.

BACKGROUND: The role of glucokinase (GCK) in the pathogenesis of maturity-onset diabetes of the young is well established. However, its role in the common form of type 2 diabetes is far from convincing. We investigated the role of the G-to-A polymorphism in the hepatic GCK promoter on insulin sensitivity and beta cell function in 63 normotensive Asian Indians with normal glucose tolerance. As proposed by Matsuda and DeFronzo, hepatic insulin sensitivity (ISI(H)) and total body insulin sensitivity (ISI(M)) were estimated from the oral glucose tolerance test. Beta cell function was estimated using %B from the Homeostasis Model Assessment and insulingenic index (dI/dG). RESULT: We identified 38 GG, 24 GA, and one AA subjects. The AA subject was pooled with the GA subjects during the analysis. No difference was noted in the demographic features between the two genotypic groups (GG vs. GA/AA). Compared to the GG group, the GA/AA group had a lower ISI(H) (p=0.002), a lower ISI(M) (p=0.009), a higher %B (p=0.014), and a higher dI/dG (p=0.030). Multivariate analysis revealed that this polymorphism is an independent determinant for ISI(H) (p=0.019) and along with age, waist-hip ratio, gender, and diastolic blood pressure accounted for 51.5% of the variation of ISI(H). However, this polymorphism was a weak, but independent determinant for ISI(M) (p=0.089) and %B (p=0.083). Furthermore, it had no independent effect on dI/dG (p=0.135). CONCLUSIONS: These data suggest that the G-to-A polymorphism in the hepatic GCK promoter is associated with hepatic insulin resistance in Asian Indians

Burden of Adverse Metabolic Factors Is Associated With Increased Left Ventricular Concentricity in Adults With Normal-Range Body Mass Index: The Framingham Heart Study

Introduction: Persons with normal-range body mass index (BMI) but adverse metabolic characteristics associated with obesity have been described as metabolically-obese normal weight (MONW). We sought to determine whether adverse metabolic profile is associated with alterations in left ventricular (LV) structure or function among adults with normal BMI. Methods: From the 1794 Framingham Heart Study Offspring cohort adults who underwent cardiac magnetic resonance imaging (CMRI) , we identified 446 free of non-skin cancer and prevalent clinical cardiovascular disease (CVD) who had 18.5≤BMI\u3c25.0 kg/m2 and complete covariates. We calculated a metabolic score (MS) where 1 point was assigned for each of: a) fasting glucose≥100 mg/dL or diabetes; b) SBP≥140 or DBP≥90 mmHg or antihypertensive treatment; c) TG≥150 or HDL_C \u3c40(M)/\u3c50(W) mg/dL or lipid treatment; d) HOMA-IR≥2.5; e) waist circumference ≥102/88cm for M/W. Participants were classified as MS0 (no points), MS1 (exactly 1 point), or MS2+ (≥2 points). LV mass (LVM), end-diastolic volume (EDV), ejection fraction (EF), and concentricity (LVM/EDV) were measured from breathhold cine SSFP CMR scans; we calculated LVM/BSA. Analysis of covariance (ANCOVA) was used to compare MS1 and MS2+ groups to the MS0 group. CMRI variables were adjusted for sex, age, heart rate (HR) and body size (BSA); LVM/BSA was adjusted for sex, age, HR only. We also tested for linear trend across metabolic groups. Results: LV concentricity increased with worsening metabolic status. This was driven by lower LV EDV, not increased LVM. LVM did not differ across (trend) or between MS-groups. LVEDV decreased across groups but only MS2 differed significantly from MS0. LVEF increased slightly but significantly across MS-groups. Conclusions: In a community-dwelling cohort, among participants who were free of cancer and clinical CVD and had normal BMI, worsening metabolic profile was associated with adverse remodeling of the left ventricle, reflected by greater LV concentricity

“Someone’s got to do it” – Primary care providers (PCPs) describe caring for rural women with mental health problems

Objective: Little is known about how primary care providers (PCPs) approach mental health care for low-income rural women. We developed a qualitative research study to explore the attitudes and practices of PCPs regarding the care of mood and anxiety disorders in rural women. Method: We conducted semi-structured interviews with 19 family physicians, internists, and obstetrician-gynecologists (OBGYNs) in office-based practices in rural central Pennsylvania. Using thematic analysis, investigators developed a coding scheme. Questions focused on 1) screening and diagnosis of mental health conditions, 2) barriers to treatment among rural women, 3) management of mental illnesses in rural women, and 4) ideas to improve care for this population. Results: PCP responses reflected these themes: 1) PCPs identify mental illnesses through several mechanisms including routine screening, indicator-based assessment, and self-identification by the patient; 2) Rural culture and social ecology are significant barriers to women in need of mental healthcare; 3) Mental healthcare resource limitations in rural communities lead PCPs to seek creative solutions to care for rural women with mental illnesses; 4) To improve mental healthcare in rural communities, both social norms and resource limitations must be addressed. Conclusion: Our findings can inform future interventions to improve women\u27s mental healthcare in rural communities. Ideas include promoting generalist education in mental healthcare, and expanding access to consultative networks. In addition, community programs to reduce the stigma of mental illnesses in rural communities may promote healthcare seeking and receptiveness to treatment

Pericardial Fat Thickness Increases with Greater Burden of Adverse Metabolic Factors Among Adults with Normal-Range Body Mass Index: The Framingham Heart Study

Introduction: Greater burden of pericardial fat is associated with increased body mass index (BMI). Obesity is associated with unfavorable metabolic characteristics such as hypertension, dyslipidemia, and glucose intolerance. We sought to determine whether unfavorable metabolic profile alone, in the absence of excess BMI, was itself associated with increased pericardial fat thickness (PFT). Methods:From the 1,794 Framingham Offspring cohort adults who underwent cardiac magnetic resonance (CMR), we identified 446 free of non-skin cancer and prevalent clinical cardiovascular disease (CVD) who had 18.5≤BMI2and complete covariates. We calculated a metabolic score (MS) based on ATPIII criteria where 1 point was assigned for each of: a) fasting glucose≥100 mg/dL or diabetes; b) SBP≥130 or DBP≥85 mmHg or antihypertensive treatment; c) triglycerides≥150 mg/dL; d) HDL cholesterol \u3c40(M)/ Results: PFT increased with worsening metabolic score at the fixed locations of the apical and mid-level RV, as well as at maximal PFT. On pairwise comparisons, only the MS3+ group had PFT that was consistently significantly greater than that of MS0. Conclusions: In a community-dwelling cohort, among participants who were free of cancer and clinical CVD and had normal-range or BMI, worsening metabolic profile was associated with increased pericardial fat thickness

A new Holocene record of geomagnetic secular variation from Windermere, UK

Paleomagnetic secular variation (PSV) records serve as valuable independent stratigraphic correlation and dating tools for marine and terrestrial sediment sequences, and enhance knowledge of geomagnetic field dynamics. We present a new radiocarbon-dated record (WINPSV-12K) of Holocene geomagnetic secular variation from Windermere, updating the existing 1981 UK master PSV curve. Our analyses used continuous U-channel samples taken from the center of four sediment cores retrieved from Windermere in 2012. The natural remanent magnetization (NRM) of each U-channel was measured before and after stepwise alternating field (AF) demagnetization on a superconducting rock magnetometer at intervals of 0.5-cm or 1-cm. The NRM data reveal a stable and well-defined primary magnetization. Component declinations and inclinations estimated using Principal Component Analysis (PCA) of NRM data from the four Windermere cores correlate well on their independent radiocarbon age models. The four records were stacked using a sliding window bootstrap method, resulting in a composite Holocene PSV record (WINPSV-12K). On millennial timescales WINPSV-12K correlates well with other records from Western Europe and the northern North Atlantic to a resolution of ∼ 1 kyr, given age uncertainties and spatial variability between records. WINPSV-12K also compares well to the CALS10k.2 and pfm9k.1a model predictions for Windermere. Key regionally-significant PSV inclination features of WINPSV-12K which correlate with other North Atlantic records include peaks at 5–6, 8.5, and 10 cal ka BP, and a trough at 7calkaBP. Key PSV declination features include the eastward swing from 5.5–2.3 cal ka BP followed by a major westward excursion at 2.3 cal ka BP, peaks at 1.1 and 7calkaBP, and troughs at 5.4 and 8.2 cal ka BP, with the caveat that an estimated magnetic lock-in delay of at least 100–200 yr is present. PSV variations on 1–3 kyr timescales are interpreted to represent strengthening and weakening of the North American versus the Siberian and European–Mediterranean high-latitude flux lobes, based on the close similarities between the North Atlantic regional records and the antiphase existing in the East Asian Stack record and the North East Pacific inclination stack. WINPSV-12K provides a regionally-important new PSV reference curve whose prominent features may serve as stratigraphic markers for North Atlantic paleo-records