iMed

Comparison of prognosis for men with type 2 diabetes mellitus and men with cardiovascular disease.

admin — Wed, 07 Jan 2009 13:19:37 +0000

CMAJ. 2009 Jan 6; 180(1): 40-7
Dagenais GR, St-Pierre A, Gilbert P, Lamarche B, Després JP, Bernard PM, Bogaty P

BACKGROUND: People with type 2 diabetes mellitus are at high risk for cardiovascular disease. In some studies, the mortality rate among people with this condition has been equivalent to that among people with cardiovascular disease. We compared cardiovascular mortality between incident cases of diabetes and cardiovascular disease. METHODS: The study population was part of a random sample of 4376 men from Quebec, Canada, aged 35 to 64 years, who did not have cardiovascular disease in 1974 and who were followed until 1998. Three groups of incident cases were identified: diabetes without cardiovascular disease, first cardiovascular event (myocardial infarction, unstable angina or stroke) without diabetes, and both cardiovascular disease and diabetes. These cases were age-matched to a control group without diabetes or cardiovascular disease. RESULTS: During the 24-year follow-up period, new diabetes without cardiovascular disease was documented in 137 men. A first cardiovascular event without diabetes was documented in 527 men. Relative to the 627 controls, men with 1 of the 2 diseases of interest had higher cardiovascular mortality (age-adjusted relative risk [RR] 3.11, 95% confidence interval [CI] 1.96-4.92) for those with diabetes and 4.46 (95% CI 3.15-6.30) for those with cardiovascular disease). However, within the first 5 years after diagnosis, men with cardiovascular disease had higher cardiovascular mortality than men with diabetes (age-adjusted RR 2.03, 95% CI 1.01-4.08). INTERPRETATION: Men with isolated type 2 diabetes and men with isolated cardiovascular disease had similar cardiovascular mortality rates several years after initial diagnosis of either condition. These findings reinforce the need to prevent and optimally manage diabetes and cardiovascular disease.

Use of medical care for chronic conditions.

admin — Wed, 07 Jan 2009 13:19:34 +0000

Health Aff (Millwood). 2009 Jan-Feb; 28(1): 26-35
Decker SL, Schappert SM, Sisk JE

We used nationally representative data from the National Center for Health Statistics to compare 1995-96 and 2005-06 ambulatory care visit and 1996 and 2006 hospital discharge rates for adults for eight major chronic conditions. For the eight conditions combined, ambulatory care visit rates rose 21 percent, while hospital discharge rates fell 9 percent. Discharge rates fell for heart disease, cancer, and cerebrovascular disease. Ambulatory care visit rates rose at least 30 percent for arthritis, hypertension, diabetes, and depression. Medicaid recipients and black adults obtain more of their ambulatory care in hospital emergency and outpatient departments and less in physician offices than others do.

Preventing chronic disease: an important investment, but don’t count on cost savings.

admin — Wed, 07 Jan 2009 13:19:31 +0000

Health Aff (Millwood). 2009 Jan-Feb; 28(1): 42-5
Russell LB

Over the four decades since cost-effectiveness analysis was first applied to health and medicine, hundreds of studies have shown that prevention usually adds to medical costs instead of reducing them. Medications for hypertension and elevated cholesterol, diet and exercise to prevent diabetes, and screening and early treatment for cancer all add more to medical costs than they save. Careful choices about frequency, groups to target, and component costs can increase the likelihood that interventions will be highly cost-effective or even cost-saving.

The Diabetes Prevention Program: how the participants did it.

admin — Wed, 07 Jan 2009 13:19:28 +0000

Health Aff (Millwood). 2009 Jan-Feb; 28(1): 57-62
Brink S

Selected environmental risk factors and congenital heart defects.

admin — Wed, 07 Jan 2009 13:19:25 +0000

Medicina (Kaunas). 2008; 44(11): 827-32
Kuciene R, Dulskiene V

The aim of the article is to review the published scientific literature and epidemiological studies about the effect of selected environmental risk factors on congenital heart defects in infants. According to recent reports, the prevalence of congenital heart defects is around 1% of live births. Congenital heart malformations are the leading cause of infant mortality. Unfortunately, the majority of the causes of heart defects remain unknown. These malformations are caused by interaction of genetic and environmental factors. The article reviews selected environmental risk factors: maternal illnesses and conditions associated with metabolic disorder (maternal diabetes, obesity, phenylketonuria), maternal lifestyle factors (alcohol use, smoking), which may increase the risk of congenital heart defects.

Bone marrow-derived cells and epithelial tumours: more than just an inflammatory relationship.

admin — Wed, 07 Jan 2009 13:19:22 +0000

Curr Opin Oncol. 2009 Jan; 21(1): 77-82
Alison MR, Lim S, Houghton JM

PURPOSE OF REVIEW: Cancer-associated fibroblasts/myofibroblasts and inflammatory cells produce a vast array of growth factors, chemokines and extracellular matrix (ECM) components that facilitate cancer progression, invasion/metastasis and neovascularization. This review highlights some surprisingly novel mechanisms of this paracrine relationship. RECENT FINDINGS: Mesenchymal stem/stromal cells (MSCs) are known for their tropism towards certain tumours, but now we find that cross-talk between tumours and MSCs leads to greater tumour motility and metastasis. Two closely related populations of immature myeloid cells, so-called 'cap cells' and myeloid-derived suppressor cells (MDSCs) also cross-talk with tumour cells, promoting invasion and metastasis through matrix metalloproteinase (MMP) secretion, as well as contributing to neovascularization and T-cell tolerance. The contribution of bone marrow-derived cells (BMDCs) to tumour neovascularization is controversial, but BMD--endothelial progenitor cells (EPCs)--are strongly implicated in the angiogenic switch in a mouse model. BMDCs are also credited with the creation of premetastatic niches to which metastatic cells adhere via integrins. SUMMARY: There is no doubt that BMDCs are not simply bystanders in the tumour battleground. The mechanisms through which they aid tumour progression are numerous; effective treatments that combat BMDC-tumour cross-talk are surely on the way.

Correlation between audiovestibular function tests and hearing outcomes in severe to profound sudden sensorineural hearing loss.

admin — Wed, 07 Jan 2009 13:19:19 +0000

Ear Hear. 2009 Feb; 30(1): 110-4
Wang CT, Huang TW, Kuo SW, Cheng PW

OBJECTIVE: This study investigated whether audiovestibular function tests, namely auditory brain stem response (ABR) and vestibular-evoked myogenic potential (VEMP) tests were correlated to hearing outcomes after controlling the effects of other potential confounding factors in severe to profound sudden sensorineural hearing loss (SSHL). DESIGN: Eighty-eight patients with severe to profound SSHL were enrolled in this study. Pretreatment hearing levels, results of audiovestibular function tests, and final hearing outcomes were recorded from retrospective chart reviews. Other factors, including age, gender, delay of treatment, vertigo, diabetes mellitus, and hypertension, were collected as well. Comparative analysis between multiple variables and hearing outcomes was conducted using the cumulative logits model in overall subjects. Further, multivariate analysis of prognostic factors was conducted in the stratified groups of severe (70 dB HL <hearing level 90 dB HL) SSHL. RESULTS: Multivariate analysis showed that pretreatment hearing levels, presence of vertigo, and results of ABR and VEMP testing were significant outcome predictors in the overall subjects. Stratification analysis demonstrated that both the presence of ABR and VEMP waveforms were significantly correlated with better hearing outcomes in the group of severe SSHL [ABR: adjusted odds ratio (aOR) = 14.7, 95% confidence interval (CI) = 1.78 to 122, p = 0.01; VEMP: aOR = 5.91, 95% CI = 1.18 to 29.5, p = 0.03], whereas the presence of vertigo was the only significant negative prognostic factor in the group of profound SSHL (aOR = 0.24, 95% CI = 0.06 to 0.95, p = 0.04). Other variables, including age, gender, diabetes mellitus, hypertension, and delay of treatment, were not significantly related to hearing outcomes in both groups (p > 0.05). A predictive hearing recovery table with the combined ABR and VEMP results was proposed for the group of severe SSHL. CONCLUSIONS: ABR and VEMP tests should be included in the battery of neurootological examinations in patients with severe SSHL because the presence of both waveforms might indicate favorable hearing outcomes. The presence of vertigo might portend a worse prognosis in patients with profound SSHL. A presumed table in predicting hearing outcomes was suggested for patients with severe SSHL.

Variations in tryptophan hydroxylase 2 linked to decreased serotonergic activity are associated with elevated risk for metabolic syndrome in depression.

admin — Wed, 07 Jan 2009 13:19:16 +0000

Mol Psychiatry. 2009 Jan 6;
Kloiber S, Kohli MA, Brueckl T, Ripke S, Ising M, Uhr M, Menke A, Unschuld PG, Horstmann S, Salyakina D, Muller-Myhsok B, Binder EB, Holsboer F, Lucae S

Major depression and the metabolic syndrome (MetS) are interacting clinical conditions influenced by genetic susceptibility. For both disorders, impaired serotonergic neurotransmission in specific brain areas has been suggested. This led us to investigate whether variants in the gene coding for tryptophan hydroxylase 2 (TPH2), the brain-specific and rate-limiting enzyme for serotonin biosynthesis, might be predictive for an increased liability for the development of MetS in depressed patients. In a case-control study consisting of 988 patients with recurrent unipolar depression (RUD) and 1023 psychiatric healthy controls, MetS components were ascertained according to the International Diabetes Foundation criteria. A total of 41 single nucleotide polymorphisms fully covering the TPH2 gene region were genotyped in stage 1 (300 patients/300 controls), resulting in significant genetic associations of polymorphisms located in exon 7 and intron 8 of TPH2 and the occurrence of MetS in depressed patients after correction for age, gender and multiple testing (51 RUD-MetS/179 RUD-non-MetS). We were able to confirm the significant association of rs17110690 in stage 2 (688 patients/723 controls; 110 RUD-MetS/549 RUD-non-MetS) and to link risk-genotypes and risk-haplotypes for MetS to lower TPH2 mRNA expression and to lower 5-hydroxyindoleacetic acid levels in cerebrospinal fluid previously reported in functional studies. Our findings suggest that TPH2 polymorphisms characterize a subgroup of depressed patients who are especially prone to develop metabolic disorders induced by a genotype-dependent impairment of serotonergic neurotransmission. Identifying depressed patients at high risk for MetS using genetic variants could have direct clinical impact on individualized disease management and prevention strategies.Molecular Psychiatry advance online publication, 6 January 2009; doi:10.1038/mp.2008.142.

Peripheral mononuclear cell resistin mRNA expression is increased in type 2 diabetic women.

admin — Wed, 07 Jan 2009 13:19:13 +0000

Mediators Inflamm. 2008; 2008: 892864
Tsiotra PC, Tsigos C, Anastasiou E, Yfanti E, Boutati E, Souvatzoglou E, Kyrou I, Raptis SA

Resistin has been shown to cause insulin resistance and to impair glucose tolerance in rodents, but in humans its physiological role still remains elusive. The aim of this study was to examine whether resistin mRNA expression in human peripheral mononuclear cells (PBMCs) and its corresponding plasma levels are altered in type 2 diabetes. Resistin mRNA levels were easily detectable in human PBMC, and found to be higher in DM2 compared to healthy women (P = .05). Similarly, mononuclear mRNA levels of the proinflammatory cytokines IL-1beta, TNF-alpha, and IL-6 were all significantly higher in DM2 compared to control women (P < .001). The corresponding plasma resistin levels were slightly, but not significantly, increased in DM2 women (P = .051), and overall, they correlated significantly with BMI (r = 0.406, P = .010) and waist circumference (r = 0.516, P = .003), but not with fasting insulin levels or HOMA-IR. Resistin mRNA expression is increased in PBMC from DM2 women, together with increased expression of the inflammatory cytokines IL-1beta, TNF-alpha, and IL-6, independent of obesity. These results suggest that resistin and cytokines might contribute to the low-grade inflammation and the increased atherogenic risk observed in these patients.

IL2RA/CD25 gene polymorphisms: uneven association with multiple sclerosis (MS) and type 1 diabetes (T1D).

admin — Wed, 07 Jan 2009 13:19:10 +0000

PLoS ONE. 2009; 4(1): e4137
Alcina A, Fedetz M, Ndagire D, Fernández O, Leyva L, Guerrero M, Abad-Grau MM, Arnal C, Delgado C, Lucas M, Izquierdo G, Matesanz F

BACKGROUND: IL-2 receptor (IL2R) alpha is the specific component of the high affinity IL2R system involved in the immune response and in the control of autoimmunity. METHODS AND RESULTS: Here we perform a replication and fine mapping of the IL2RA gene region analyzing 3 SNPs previously associated with multiple sclerosis (MS) and 5 SNPs associated with type 1 diabetes (T1D) in a collection of 798 MS patients and 927 matched Caucasian controls from the south of Spain. We observed association with MS in 6 of 8 SNPs. The rs1570538, at the 3'- UTR extreme of the gene, previously reported to have a weak association with MS, is replicated here (P = 0.032). The most associated T1D SNP (rs41295061) was not associated with MS in the present study. However, the rs35285258, belonging to another independent group of SNPs associated with T1D, showed the maximal association in this study but different risk allele. We replicated the association of only one (rs2104286) of the two IL2RA SNPs identified in the recently performed genome-wide association study of MS. CONCLUSIONS: These findings confirm and extend the association of this gene with MS and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between MS and T1D suggesting different immunopathological roles of IL2RA in these two diseases.