Use of confirmatory factor analysis for the identification of new components of the metabolic syndrome: the role of plasminogen activator inhibitor-1 and Haemoglobin A1c

BACKGROUND AND AIM: This study was aimed to identify additional components of metabolic syndrome from a set of cardiovascular risk markers. METHODS AND RESULTS: The homeostasis model assessment of insulin resistance (HOMA-IR), C-reactive protein, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor, homocysteine, Haemoglobin A1c (HbA1c), and lipoprotein(a) were assessed in a population-based sample of 902 nondiabetic adult subjects. Those biomarkers that were associated with metabolic syndrome were evaluated by multiple regression analysis, along with other traditional cardiovascular risk factors. Confirmatory factor analysis (CFA) was used to test the hypothesis that both the established components of metabolic syndrome and the novel variables identified by the regression analysis were associated with a single underlying factor. HOMA-IR, PAI-1 and HbA1c were the only biomarkers independently related to metabolic syndrome. CFA validated a one-factor model that included these variables. Moreover, the indices of goodness of fit were better for this expanded model than those obtained for a previously validated one-factor model that was restricted to the conventional elements of the syndrome. CONCLUSIONS: These findings show that PAI-1 and HbA1c are singularly linked to metabolic syndrome. Their elevation is presumably another manifestation of the same pathophysiological mechanism that underlies the recognized traits of the syndrome.     

Prevalence of and risk factors for pubic lipoma development in HIV-infected persons

BACKGROUND: The natural history of HIV-associated body habitus changes is unclear. In this report, we describe a novel manifestation of HIV-associated lipoaccumulation. METHODS: We noted the presence of suprapubic fat pads (pubic lipomas [PLs]) in several patients with preexisting HIV-associated body habitus abnormalities. Subsequently, we evaluated the prevalence of and associated risk factors for development of PLs by undertaking an observational cross-sectional study among patients with known lipodystrophy who attended a metabolic clinic in northern Italy. Inclusion criteria were a physician-confirmed diagnosis of lipodystrophy according to the Multicenter AIDS Cohort Study definition and, for those affected with PL, a readily noticeable PL on physical examination. RESULTS: We evaluated 582 patients with lipodystrophy: 214 female (36.7%) and 368 male (63.3%). The overall PL prevalence was 9.4% (95% confidence interval [CI]: 7.2% to 12.1%; P < 0.0001). PLs were more common among obese than nonobese individuals (34.5%, 95% CI: 17.9% to 5l.3% vs. 8%, 95% CI: 5.9% to 10.6%, respectively; P < 0.0001) and those with preexisting dorsocervical fat pads, commonly called "buffalo humps" (BHs) (18.5%, 95% CI: 12.7% to 25.4% vs. 6.1%, 95% CI: 4.03% to 8.83%, respectively, P < 0.0001; relative risk = 3.02, 95% CI: 1.84% to 4.96%, P < 0.0001). The PL prevalence in the nonobese HIV-infected population (body mass index [BMI] <30, n = 550) was 8.0% (95% CI: 5.9% to 10.6%; P < 0.0001). Logistic regression analyses identified the following factors as associated with a greater likelihood for PL: BMI >30 (beta = 0.18, SE = 0.04; P < 0.001), female gender (beta = 1.06, SE = 0.31; P < 0.001), and shorter duration of HIV infection (beta = -0.005, SE = 0.003; P = 0.04). We used a chain graph model to evaluate risk factors for BH and PL simultaneously. A nonnull interaction between these entities was evident, and this association seemed to be independent of factors positively associated with both (BMI and gender). CONCLUSIONS: PL is a newly recognized manifestation of HIV-associated lipoaccumulation that is more likely to occur among those with coexisting dorsocervical fat pads, suggesting the possibility of a common pathogenesis between the 2 entities. Likewise, PLs are more common among women, obese individuals, and those with a shorter duration of HIV infection. We suggest that PL should be considered part of the HIV-associated lipodystrophy syndrome.     

Hypoxanthine-guanine phosphoribosyltransferase. Genetic evidence for identical mutations in two partially deficient subjects.

In past reports of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency a marked degree of molecular heterogeneity has been noted. We have previously described two apparently unrelated subjects with partial HPRT deficiency, G.S. and D.B., who have a mutant form of HPRT with remarkably similar alterations in physical and kinetic properties. The mutation in G.S. is a serine to leucine substitution at amino acid 110 as determined by amino acid sequence analysis. This mutant enzyme has been designated HPRTLondon. We have examined HPRT cDNA from D.B. using two different methods to determine if the similar properties of mutant HPRT from these two subjects are the result of a common mutation. HPRT cDNA clones were obtained by routine cloning techniques and by polymerase chain reaction amplification of single-stranded cDNA reverse transcribed from mRNA derived from subject D.B. Dideoxynucleotide sequencing revealed a single mutation, a C to T transition at bp 329 in clones generated by both methods. This mutation in D.B. predicts the identical amino acid substitution described in HPRTLondon. A C to T nucleotide transition at 329 in D.B. creates an Hpa I site in exon 4 of the HPRT gene. Southern blot analysis of genomic DNA isolated from lymphoblasts derived from G.S. and D.B. revealed that both have this additional Hpa I site, indicating that the similarly altered protein sequence is due to the identical transition in the HPRT gene.     

Glycaemic,blood pressure and cholesterol control in 25 629 diabetics

Objective

To examine and compare the extent to which people with type 2 diabetes (T2DM) are achieving haemoglobin A_1c (HbA_1c), blood pressure (BP) and LDL cholesterol (LDL-C) treatment targets.

Methods

A review of databases (MEDLINE Ovid, Pubmed and Sabinet) was performed and limited to the following terms: type 2 diabetes mellitus AND guideline AND goal achievement for the years 2009 to 2014 (five years).

Results

A total of 14 studies (25 629 patients) were selected across 19 different countries. An HbA_1c level of 7.0% (or less) was achieved by 44.5% of subjects (range 19.2–70.5%), while 35.2% (range 7.4–66.3%) achieved BP of 130/80 mmHg (or less), and 51.4% (range 20.0–82.9%) had an LDL-C level of either 2.5 or 2.6 mmol/l (100 mg/dl or less).

Conclusion

Despite guideline recommendations that lowering of HbA_1c, BP and lipids to target levels in T2DM will lead to a reduction in morbidity and mortality rates, we found that control of these risk factors remains suboptimal, even across different settings.     

Stimulating spectrum of human recombinant multi-CSF (IL-3) on human marrow precursors: importance of accessory cells

Recently, human multi-CSF was obtained by molecular cloning. In the present study, the effects of multi-CSF in vitro were investigated by comparative culture of whole bone marrow or progenitor cells obtained by sorting the cell fraction that binds the monoclonal antibody (MoAb) B13C5 (CD 34). Multi-CSF stimulated erythroid (BFU-E), multipotential (CFU-GEMM) and eosinophil (CFU-Eo) colonies in cultures of the progenitor cell enriched fraction, whereas (besides BFU-E, CFU-GEMM, and CFU-Eo) granulocyte (CFU-G), granulocyte-macrophage (CFU-GM), and macrophage (CFU-M) colony-forming cells also were stimulated by multi- CSF when unfractionated bone marrow was cultured. Reconstitution of the progenitor cell fraction (B13C5 positive) with the B13C5-negative population restored the broad spectrum of progenitor cell stimulation. This suggested that accessory cells are required for expression of the full spectrum of progenitor cell stimulation by multi-CSF. Subsequently, specific marrow cell populations, including T lymphocytes, granulocytic cells, and monocytes, were prepared by using selected MoAbs in complement-mediated lysis or cell sorting, added to cultures of hematopoietic progenitors and tested for accessory cell function. The results demonstrate that small numbers of monocytes permit the stimulation of CFU-G, CFU-GM, and CFU-M by multi-CSF. These monocyte-dependent stimulating effects on CFU-G, CFU-GM, and CFU-M could also be achieved by adding recombinant GM-CSF as a substitute for monocytes to the cultures. Therefore, multi-CSF most likely has direct stimulative effects on BFU-E, CFU-GEMM, and CFU-Eo and indirect effects on CFU-G, CFU-GM, and CFU-M in the presence of monocytes.     

Nutritional status of Palestinian preschoolers in the Gaza Strip: a cross-sectional study

Background  

The authors examined factors associated with nutritional resilience/vulnerability among preschoolers in the Gaza Strip in 2007, where political violence and deprivation are widespread.     

Factors related to and consequences of adherence to antiretroviral therapy in an ambulatory HIV-infected patient cohort

In a confidential medication adherence questionnaire completed by 255 participants in the HIV Outpatient Study (HOPS) between March and November 1999, 33% reported skipping antiretroviral doses within the previous 3 days. The respondents, with a median age of 41, were predominantly male (86%), white (62%), and highly educated (33% had some post-high school training but no college degree and 39% had a college degree; only 11% had less than a high school diploma). Twenty-one percent had a history of injection drug use, 12% were unemployed, and 18% had Medicaid insurance. Questions about difficulty taking antiretroviral medications or drug holidays identified an additional 16% of patients experiencing adherence problems and explained significantly more of the failure to achieve undetectable viral loads than simply querying about skipped doses.