Reduction of exercise-induced albuminuria by aspirin-dipyridamole in patients with diabetes mellitus

The exercise-induced increase in albumin excretion was measured in six patients with insulin-dependent diabetes mellitus, in whom there was no evidence of established diabetic renal disease. Urinary albumin excretion was measured on urine samples taken at rest and immediately after a 20 minute period of exercise on a bicycle ergometer at 600 kpm/min. Following a three week course of aspirin (330 mg)--dipyridamole (75 mg) taken three times daily there was significant reduction in exercise-induced albuminuria (expressed as the ratio of albumin excretion rate during exercise to that at rest before exercise) when compared to administration of placebo (P less than 0.05). These results suggest that aspirin-dipyridamole might modify the development of persistent proteinuria in patients with insulin-dependent diabetes mellitus.     

Increased intramyocellular lipid accumulation in HIV-infected women with fat redistribution.

The human immunodeficiency virus (HIV)-lipodystrophy syndrome is associated with fat redistribution and metabolic abnormalities, including insulin resistance. Increased intramyocellular lipid (IMCL) concentrations are thought to contribute to insulin resistance, being linked to metabolic and body composition variables. We examined 46 women: HIV infected with fat redistribution (n = 25), and age- and body mass index-matched HIV-negative controls (n = 21). IMCL was measured by 1H-magnetic resonance spectroscopy, and body composition was assessed with computed tomography, dual-energy X-ray absorptiometry (DEXA), and magnetic resonance imaging. Plasma lipid profile and markers of glucose homeostasis were obtained. IMCL was significantly increased in tibialis anterior [135.0 +/- 11.5 vs. 85.1 +/- 13.2 institutional units (IU); P = 0.007] and soleus [643.7 +/- 61.0 vs. 443.6 +/- 47.2 IU, P = 0.017] of HIV-infected subjects compared with controls. Among HIV-infected subjects, calf subcutaneous fat area (17.8 +/- 2.3 vs. 35.0 +/- 2.5 cm2, P < 0.0001) and extremity fat by DEXA (11.8 +/- 1.1 vs. 15.6 +/- 1.2 kg, P = 0.024) were reduced, whereas visceral abdominal fat (125.2 +/- 11.3 vs. 74.4 +/- 12.3 cm2, P = 0.004), triglycerides (131.1 +/- 11.0 vs. 66.3 +/- 12.3 mg/dl, P = 0.0003), and fasting insulin (10.8 +/- 0.9 vs. 7.0 +/- 0.9 microIU/ml, P = 0.004) were increased compared with control subjects. Triglycerides (r = 0.39, P = 0.05) and extremity fat as percentage of whole body fat by DEXA (r = -0.51, P = 0.01) correlated significantly with IMCL in the HIV but not the control group. Extremity fat (beta = -633.53, P = 0.03) remained significantly associated with IMCL among HIV-infected patients, controlling for visceral abdominal fat, abdominal subcutaneous fat, and antiretroviral medications in a regression model. These data demonstrate increased IMCL in HIV-infected women with a mixed lipodystrophy pattern, being most significantly associated with reduced extremity fat. Further studies are necessary to determine the relationship between extremity fat loss and increased IMCL in HIV-infected women.     

Increased adrenal androgen secretion with inhibition of 11beta-hydroxylase in HIV-infected women

Adrenal androgen production is reduced in association with disease severity in HIV-infected women. This response may be maladaptive in terms of maintenance of lean body mass, functional status, and immune function. The aim of this study was to assess whether the use of an adrenal enzyme inhibitor of 11beta-hydroxylase might increase androgen production in this population. We conducted a randomized, double-blind, placebo-controlled study of metyrapone (500 mg p.o. qid) or placebo for 2 wk in 10 HIV-infected women with AIDS wasting [weight <90% ideal body weight (IBW) or weight loss >10%] and reduced androgen levels. Basal and ACTH-stimulated androgen, mineralocorticoid, and glucocorticoid levels were measured at baseline and after 14 days of treatment. Subjects were similar in age (40.9 +/- 0.9 yr), weight (91.7 +/- 3.5% IBW) and hormone concentrations at study entry. Total testosterone (84 +/- 54 vs. -0.4 +/- 2 ng/dl, P = 0.024), free testosterone (6.5 +/- 2.8 vs. 0.1 +/- 0.1 pg/ml, P = 0.024), DHEA (5.0 +/- 3.2 vs. -0.6 +/- 0.5 microg/l, P = 0.024), and 11-deoxycortisol (2,145 +/- 820 vs. -14 +/- 22 ng/dl, P = 0.024) levels increased in response to metyrapone compared with placebo treatment. In response to ACTH, significant increases in the DHEA/cortisol ratio (174 +/- 48 vs. 3 +/- 3, P = 0.008) were seen in the metyrapone group compared with placebo. Blood pressure and electrolytes did not change, and signs of adrenal insufficiency were not apparent. These data demonstrate that inhibition of 11beta-hydroxylase with metyrapone increases adrenal androgen secretion in HIV-infected women. Further studies are needed to assess the physiological effects of this strategy to increase anabolic hormone levels in severe stress, including detailed testing to rule out the potential risk of concomitant adrenal insufficiency.     

Increased prevalence of metabolic syndrome in patients with acne inversa

Background

Acne inversa (AI; also designated as Hidradenitis suppurativa) is a common chronic inflammatory skin disease, localized in the axillary, inguinal and perianal skin areas that causes painful, fistulating sinuses with malodorous purulence and scars. Several chronic inflammatory diseases are associated with the metabolic syndrome and its consequences including arteriosclerosis, coronary heart disease, myocardial infraction, and stroke. So far, the association of AI with systemic metabolic alterations is largely unexplored.

Methods and Findings

A hospital-based case-control study in 80 AI patients and 100 age- and sex-matched control participants was carried out. The prevalence of central obesity (odds ratio 5.88), hypertriglyceridemia (odds ratio 2.24), hypo-HDL-cholesterolemia (odds ratio 4.56), and hyperglycemia (odds ratio 4.09) in AI patients was significantly higher than in controls. Furthermore, the metabolic syndrome, previously defined as the presence of at least three of the five alterations listed above, was more common in those patients compared to controls (40.0% versus 13.0%; odds ratio 4.46, 95% confidence interval 2.02 to 9.96; P<0.001). AI patients with metabolic syndrome also had more pronounced metabolic alterations than controls with metabolic syndrome. Interestingly, there was no correlation between the severity or duration of the disease and the levels of respective parameters or the number of criteria defining the metabolic syndrome. Rather, the metabolic syndrome was observed in a disproportionately high percentage of young AI patients.

Conclusions

This study shows for the first time that AI patients have a high prevalence of the metabolic syndrome and all of its criteria. It further suggests that the inflammation present in AI patients does not have a major impact on the development of metabolic alterations. Instead, evidence is given for a role of metabolic alterations in the development of AI. We recommend monitoring of AI patients in order to correct their modifiable cardiovascular risk factors.     

Association of low level viremia with inflammation and mortality in HIV-infected adults

Background

Whether HIV viremia, particularly at low levels is associated with inflammation, increased coagulation, and all-cause mortality is unclear.

Methods

The associations of HIV RNA level with C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and mortality were evaluated in 1116 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV infection. HIV RNA level was categorized as undetectable (i.e., “target not detected”), 1–19, 20–399, 400–9999, and ≥10,000 copies/ml. Covariates included demographics, lifestyle, adipose tissue, and HIV-related factors.

Results

HIV RNA level had little association with CRP. Categories of HIV RNA below 10,000 copies/ml had similar levels of IL-6 compared with an undetectable HIV RNA level, while HIV RNA ≥10,000 copies/ml was associated with 89% higher IL-6 (p<0.001). This association was attenuated by ∼50% after adjustment for CD4+ cell count. Higher HIV RNA was associated with higher fibrinogen. Compared to an undetectable HIV RNA level, fibrinogen was 0.6%, 1.9%, 4.5%, 4.6%, and 9.4% higher across HIV RNA categories, respectively, and statistically significant at the highest level (p = 0.0002 for HIV RNA ≥10,000 copies/ml). Higher HIV RNA was associated with mortality during follow-up in unadjusted analysis, but showed little association after adjustment for CD4+ cell count and inflammation.

Conclusion

HIV RNA ≥10,000 copies/ml was associated with higher IL-6 and fibrinogen, but lower levels of viremia appeared similar, and there was little association with CRP. The relationship of HIV RNA with IL-6 was strongly affected by CD4 cell depletion. After adjustment for CD4+ cell count and inflammation, viremia did not appear to be substantially associated with mortality risk over 5 years.     

Increased prevalence of mitral valve prolapse in patients with migraine.

Patients with classic migraine (69 women and 31 men) selected randomly from a practice list of over 1000 were matched for age, sex and neighbourhood with 100 people who did not have headache problems, and both groups underwent M-mode and two-dimensional echocardiography and clinical examination by cardiologists blinded to the subjects'' clinical status. The mean ages were 34.9 +/- 11.3 years for the migraine group and 33.1 +/- 9.9 years for the control group. Definite and possible mitral valve prolapse (MVP), diagnosed according to predefined echocardiographic criteria, were found about twice as often in the migraine group as in the control group (in 15 v. 7 and 16 v. 8 patients respectively); the echocardiograms were definitely normal in 69 migraine patients and 85 controls (chi 2 = 8.39, p less than 0.025). Altogether 25% of the migraine group and 11% of the control group had evidence of MVP from a combination of the echocardiographic and auscultatory findings (chi 2 = 5.72, p less than 0.025). The odds ratio was 2.7, with 95% confidence limits of 1.17 and 6.29. The association between migraine and MVP has implications for the understanding of platelet abnormalities and episodes of cerebral ischemia occurring in both these conditions.     

Soluble RAGE but not endogenous secretory RAGE is associated with albuminuria in patients with type 2 diabetes

Aims

Type 2 diabetes is characterised by increased plasma concentrations of pro-inflammatory cytokines [such as tumour necrosis factor – alpha; TNF-α] and soluble forms of adhesion molecules involved in leukocyte – endothelial interactions. These molecules are synthesised as transmembrane proteins and the plasma soluble forms are generated by ectodomain cleavage from the cell surface by members of the ADAM [a disintegrin and metalloproteinase] proteinase family. We hypothesised that plasma low density lipoprotein [LDL] from subjects with Type 2 diabetes would influence in vitro monocytic ADAM and matrix metalloproteinase [MMP] gene expression differently compared to control LDL.

Methods

We examined relative mRNA expression by real time PCR in a monocytic cell line [THP-1] cultured for 4, 8 and 24 hrs with human plasma LDL derived from subjects with [n = 5] or without [n = 4] Type 2 diabetes. Gene expression for MMP-1 and 9, and ADAM – 8, 15, 17 and 28 was studied.

Results

Type 2 diabetes LDL significantly increased gene expression of MMP – 1 [p < 0.01] MMP – 9 [p < 0.001], and ADAM 17 [p < 0.05], – 28 [p < 0.01] and – 15 [p < 0.01] compared to control LDL. Type 2 diabetes LDL had disparate effects on inhibitors of MMP.

Conclusion

These data suggest that Type 2 diabetes LDL could lead to increased adhesion molecule and TNF alpha cell surface shedding, and vascular plaque instability, by promoting increased expression of ADAM and MMP genes.     

Increased risk of severe acute pancreatitis in patients with diabetes

Aims We prospectively assessed the age- and sex-specific incidence rates and relative risks of overall and severe acute pancreatitis in Taiwanese with diabetes. Methods The study cohort included age- and-sex-matched groups of patients with (n?=?547?554) and without (n?=?584?373) diabetes. Incidence rate was estimated under Poisson assumption and relative risks of acute pancreatitis and severe acute pancreatitis, based on modified Atlanta criteria, were indicated by hazard ratios estimated from Cox proportional hazard regression models. Results Over an 8-year follow-up period, the incidence of acute pancreatitis was 2.98 and 1.68 per 1000 person-years for patients with and without diabetes, respectively, representing a covariate adjusted hazard ratio of 1.53 (95% confidence interval 1.49-1.58). Diabetes was associated with a significantly elevated risk of acute pancreatitis in all sex and age stratifications, with the highest hazard ratio noted for study subjects aged 相似文献   

Increased genetic variance of BMI with a higher prevalence of obesity

Background and objectives

There is no doubt that the dramatic worldwide increase in obesity prevalence is due to changes in environmental factors. However, twin studies suggest that genetic differences are responsible for the major part of the variation in body mass index (BMI) and other measures of body fatness within populations. Several recent studies suggest that the genetic effects on adiposity may be stronger when combined with presumed risk factors for obesity. We tested the hypothesis that a higher prevalence of obesity and overweight and a higher BMI mean is associated with a larger genetic variation in BMI.

Methods

The data consisted of self-reported height and weight from two Danish twin surveys in 1994 and 2002. A total of 15,017 monozygotic and dizygotic twin pairs were divided into subgroups by year of birth (from 1931 through 1982) and sex. The genetic and environmental variance components of BMI were calculated for each subgroup using the classical twin design. Likewise, the prevalence of obesity, prevalence of overweight and the mean of the BMI distribution was calculated for each subgroup and tested as explanatory variables in a random effects meta-regression model with the square root of the additive genetic variance (equal to the standard deviation) as the dependent variable.

Results

The size of additive genetic variation was positively and significantly associated with obesity prevalence (p = 0.001) and the mean of the BMI distribution (p = 0.015). The association with prevalence of overweight was positive but not statistically significant (p = 0.177).

Conclusion

The results suggest that the genetic variation in BMI increases as the prevalence of obesity, prevalence of overweight and the BMI mean increases. The findings suggest that the genes related to body fatness are expressed more aggressively under the influence of an obesity-promoting environment.     

Increased prevalence of Brucella suis and pseudorabies virus antibodies in adults of an isolated feral swine population in coastal South Carolina

Two hundred twenty seven adult (> 8 mo) feral swine (Sus scrofa) trapped from April through July 1999 at three locations on a coastal South Carolina (USA) peninsula with restricted ingress and egress were tested for Brucella suis and pseudorabies virus (PRV) antibodies. Approximately 44% of the animals tested positive for B. suis antibodies and 61% tested positive for antibodies to PRV. Previous surveys (1976 and 1992) of feral swine at the same location with similar methods indicated lower seroprevalences (28% and 18% for B. suis and 0% and 19% for PRV). We also found 39% of feral swine seropositive (n = 179) for Trichinella spiralis and 49% seropositive (n = 181) for Toxoplasma gondii. Results of repeated sampling demonstrated that seroprevalence to pathogens can increase with time in an isolated, unhunted population of feral swine suggesting an increased risk to local domestic livestock and potentially to human health.     

The prevalence of obesity in ethnic admixture adults

Objective: To determine whether the prevalence of obesity in ethnic admixture adults varies systematically from the average of the prevalence estimates for the ethnic groups with whom they share a common ethnicity. Methods and Procedures: The sample included 215,000 adults who reported one or more ethnicities, height, weight, and other characteristics through a mailed survey. Results: The highest age‐adjusted prevalence of overweight (BMI ≥ 25) was in Hawaiian/Latino men (88%; n = 41) and black/Latina women (74.5%; n = 79), and highest obesity (BMI ≥ 30) rates were in Hawaiian/Latino men (53.7%; n = 41) and Hawaiian women (39.2%, n = 1,247). The prevalence estimates for most admixed groups were similar to or higher than the average of the prevalences for the ethnic groups with whom they shared common ethnicities. For instance, the prevalence of overweight/obesity in five ethnic admixtures—Asian/white, Hawaiian/white, Hawaiian/Asian, Latina/white, and Hawaiian/Asian/white ethnic admixtures—was significantly higher (P < 0.0001) than the average of the prevalence estimates for their component ethnic groups. Discussion: The identification of individuals who have a high‐risk ethnic admixture is important not only to the personal health and well‐being of such individuals, but could also be important to future efforts in order to control the epidemic of obesity in the United States.     

LADA--latent autoimmune diabetes in adults

Latent Autoimmune Diabetes In Adults (LADA) is a form of autoimmune-mediated diabetes in adults. The progression of beta-cell failure is slower than in childhood type 1 diabetes. Patients with LADA present with more preserved beta-cell function than those with classic type 1 diabetes. The diagnosis of LADA according to Immunology of Diabetes Society is based on three features: age over 35 years, the presence at least one of four circulating autoantibodies to pancreatic islet cell antigens and lack of requirement for insulin at least 6 month after diagnosis. The level of C-peptide secretion after stimulation with intravenous glucagon helped to diagnosis. There are different opinions in relation to treatment of LADA. Some studies suggest, that insulin treatment is indicated at the time of diagnosis LADA, some of them--when patients upon failure of oral hypoglycemic treatment.     

The prevalence of regulatory T cells in lymphoid tissue is correlated with viral load in HIV-infected patients

Inadequate local cell-mediated immunity appears crucial for the establishment of chronic HIV infection. Accumulation of regulatory T cells (Treg) at the site of HIV replication, the lymphoid organs, may influence the outcome of HIV infection. Our data provide the first evidence that chronic HIV infection changes Treg tissue distribution. Several molecules characteristics of Treg (FoxP3, CTLA-4, glucocorticoid-induced TNFR family-related receptor, and CD25) were expressed more in tonsils of untreated patients compared with antiretroviral-treated patients. Importantly, most FoxP3+ cells expressed CTLA-4, but not CD69. Furthermore, a direct correlation between FoxP3 levels and viral load was evident. In contrast, FoxP3 expression was decreased in circulating T cells from untreated patients, but normalized after initiation of treatment. Functional markers of Treg activity (indoleamine 2,3-dioxygenase, TGF-beta, and CD80) were markedly increased in the tonsils of untreated patients. Our data could provide a new basis for immune-based therapies that counteract in vivo Treg and thereby reinforce appropriate antiviral immunity.     

Increased urinary angiotensin-converting enzyme 2 in renal transplant patients with diabetes

Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a renoprotective enzyme, since it converts angiotensin (Ang) II to Ang-(1-7). ACE2 has been detected in urine from patients with chronic kidney disease. We measured urinary ACE2 activity and protein levels in renal transplant patients (age 54 yrs, 65% male, 38% diabetes, n?=?100) and healthy controls (age 45 yrs, 26% male, n?=?50), and determined factors associated with elevated urinary ACE2 in the patients. Urine from transplant subjects was also assayed for ACE mRNA and protein. No subjects were taking inhibitors of the renin-angiotensin system. Urinary ACE2 levels were significantly higher in transplant patients compared to controls (p?=?0.003 for ACE2 activity, and p≤0.001 for ACE2 protein by ELISA or western analysis). Transplant patients with diabetes mellitus had significantly increased urinary ACE2 activity and protein levels compared to non-diabetics (p<0.001), while ACE2 mRNA levels did not differ. Urinary ACE activity and protein were significantly increased in diabetic transplant subjects, while ACE mRNA levels did not differ from non-diabetic subjects. After adjusting for confounding variables, diabetes was significantly associated with urinary ACE2 activity (p?=?0.003) and protein levels (p<0.001), while female gender was associated with urinary mRNA levels for both ACE2 and ACE. These data indicate that urinary ACE2 is increased in renal transplant recipients with diabetes, possibly due to increased shedding from tubular cells. Urinary ACE2 could be a marker of renal renin-angiotensin system activation in these patients.     

Increased carotid thickness in subjects with recently-diagnosed diabetes from rural cameroon

Background

We have recently shown a high prevalence of diabetes and obesity in rural Cameroon, despite an improved lifestyle. Diabetes in rural Africa remains underdiagnosed and its role in increasing risk of atherosclerosis in these populations is unknown. We investigated the prevalence of carotid atherosclerosis and cardiovascular risk factors in a population of subjects with recently-diagnosed diabetes from rural Cameroon.

Methodology/Principal Findings

In a case-control study, carotid intima-media thickness (IMT) was measured in 74 subjects with diabetes (diagnosed <2 years), aged 47–85 and 109 controls comparable for age and sex. Subjects were recruited during a health campaign conducted in April 2009. Blood glucose control (HbA1c, fasting blood glucose) and major cardiovascular risk factors (complete lipid panel, blood pressure) were also measured. Mean carotid IMT was higher in subjects with diabetes than healthy controls at each scanned segment (common, internal carotid and bulb) (P<0.05), except the near wall of the left bulb. Vascular stiffness tended to be higher and pressure-strain elastic modulus of the left carotid was increased in subjects with diabetes than controls (P<0.05), but distensibility was similar between the two groups. At least one plaque >0.9 mm was found in 4%, 45.9% and 20% of diabetic subjects at the common, bulb or internal carotid, respectively. Only 25% of patients had an HbA1c<7%, while over 41.6% presented with marked hyperglycemia (HbA1c>9%). The prevalence of diabetic subjects with abnormal levels of LDL-cholesterol, triglycerides, HDL-cholesterol or blood pressure was 45%, 16.6%, 15% and 65.7%, respectively.

Conclusions

Carotid thickness is increased in subjects with diabetes from a rural area of Cameroon, despite the relatively recent diagnosis. These findings and the high rate of uncontrolled diabetes in this population support the increasing concern of diabetes and cardiovascular diseases in African countries and indicate the need for multifaceted health interventions in urban and rural settings.     

Cost-effectiveness of early versus standard antiretroviral therapy in HIV-infected adults in Haiti

Background

In a randomized clinical trial of early versus standard antiretroviral therapy (ART) in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial.

Methods and Findings

Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS), including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART) and US$979 (standard ART). Early ART patients had higher mean costs for ART (US$398 versus US$81) but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384). The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS–US$9,979/YLS) including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS–US$5,537/YLS).

Conclusions

Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm³ in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita) after a maximum of 3 years, after excluding research-related laboratory tests.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00120510","term_id":"NCT00120510"}}NCT00120510 Please see later in the article for the Editors'' Summary