Association Between Tumor Necrosis Factor-α and Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes: a Meta-Analysis

Tumor necrosis factor-α (TNF-α) is a cell signaling protein involved in systemic inflammation, and is also an important cytokine in the acute phase reaction. Several studies suggested a possible association between TNF-α and diabetic peripheral neuropathy (DPN) in type 2 diabetic patients, but no accurate conclusion was available. A systematic review and meta-analysis of observational studies was performed to comprehensively assess the association between serum TNF-α levels and DPN in type 2 diabetic patients. We searched Pubmed, Web of Science, Embase, and China Biology Medicine (CMB) databases for eligible studies. Study-specific data were combined using meta-analysis. Fourteen studies were finally included into the meta-analysis, which involved a total of 2650 participants. Meta-analysis showed that there were obviously increased serum TNF-α levels in DPN patients compared with type 2 diabetic patients without DPN (standard mean difference [SMD]?=?1.203, 95 % CI 0.795–1.611, P?<?0.001). There were also obviously increased levels of serum TNF-α in diabetic patients with DPN when compared with healthy controls (SMD?=?2.364, 95 % CI 1.333–3.394, P?<?0.001). In addition, there were increased serum TNF-α levels in painful DPN patients compared with painless DPN patients (SMD?=?0.964, 95 % CI 0.237–1.690, P?=?0.009). High level of serum TNF-α was significantly associated with increased risk of DPN in patients with type 2 diabetes (odds ratio [OR]?=?2.594, 95 % CI 1.182–5.500, P?=?0.017). Increased serum levels of TNF-α was not associated with increased risk of painful DPN in patients with type 2 diabetes (OR?=?2.486, 95 % CI 0.672–9.193, P?=?0.172). Sensitivity analysis showed that there was no obvious change in the pooled estimates when omitting single study by turns. Type 2 diabetic patients with peripheral neuropathy have obviously increased serum TNF-α levels than type 2 diabetic patients without peripheral neuropathy and healthy controls, and high level of serum TNF-α may be associated with increased risk of peripheral neuropathy independently. Further prospective cohort studies are needed to assess the association between TNF-α and DPN.     

Population-Based Study of Birth Prevalence and Factors Associated with Cleft Lip and/or Palate in Taiwan 2002–2009

Background

Facial cleft deformities, including cleft lip with or without cleft palate (CL/P) and cleft palate (CP), are common congenital birth anomalies, especially in Asia. This study aimed to analyze the prevalence of CL/P and CP and to identify associated factors in Taiwan.

Methods

This population-based epidemiological study retrospectively analyzed birth data obtained from the Department of Health in Taiwan for years 2002–2009. Frequency distribution, percentages and related predictors were investigated, and findings were presented by types of cleft deformities. Logistic regression analysis was performed to identify factors associated with cleft deformities.

Results

Overall prevalence of cleft deformities among 1,705,192 births was 0.1% for CL/P and 0.04% for CP over the 8-year study period. Higher prevalence of CL/P or CP was observed with multiple pregnancies, being male for CL/P, being female for CP, gestational age ≤37 weeks and lower birth weight (<1.5 kg). Both CL/P and CP were significantly associated with gestational age <37 weeks and birth weight<1.5 kg (all P <0.0001). CL/P was significantly associated with multiple parities (P = 0.0004–0.002). Male newborns and female newborns were significantly associated with CL/P and CP, respectively (both P<0.0001).

Conclusions

Overall prevalence for congenital cleft deformities in study subjects was 0.1%, in keeping with high rates in Asia. Results suggest the need for awareness and early identification of those at high risk for cleft deformities, including newborns with gestational age <37 weeks, weighing <1.5 kg at birth and women with multiple parities, as a potential strategy to counter long-term adverse effects on speech and language in this population.     

Prevalence of and Risk Factors for Asymptomatic In?ammatory (NIH-IV) Prostatitis in Chinese Men

Background

While many investigators have studied symptomatic prostatitis, little research has been done with regard to asymptomatic (NIH-IV) prostatitis.

Purpose

To describe the prevalence of and risk factors for NIH-IV prostatitis among a large male population.

Methods

The study population was comprised of 1,868 men at the second phase recruitment of a population-based cohort in China. Asymptomatic and symptomatic men were defined by the National Institutes of Health Chronic Prostatitis (CP) Symptom Index. Meanwhile, EPS specimens and their leukocyte count were collected. Lifestyle and demographic characteristics were obtained through a questionnaire.

Results

Prevalence of NIH-IV prostatitis was 21.1% among 1,868 asymptomatic men aged 19–78 years and increased with age. After adjusteing for potential confounding variables (age, smoking habits, alcohol drinking habits, education, physical activity, hypertension, dyslipidemia, obesity and diabetes), age remained a significant factor for NIH-IV prostatitis (OR = 1.35; 95% CI = 1.06–1.71; P = 0.01) and the risk of NIH-IV prostatitis was significantly higher in smokers≧15 pack/years than non-smokers (OR = 1.33; 95% CI = 1.01–1.75; P = 0.03). In addition, compared with non-drinkers, the OR of NIH-IV prostatitis in drinkers ≧1 drinks/week was 1.35 (95% CI = 1.03, 1.77, p = 0.02) after adjusting for the other variables above. In addition, having less than a college education may be a risk factor for NIH-IV prostatitis, although a statistically significant difference did not exist in our data (OR = 1.22; 95% CI = 0.97–1.52; P = 0.08).

Conclusions

Our findings suggest that NIH-IV prostatitis is prevalent in China. Age, smoking, drinking and lower education levels were associated with an increased risk of NIH-IV prostatitis. The prevalence of NIH-IV prostatitis should be taken into account when estimating the total prevalence of CP in future studies.     

Socio-Demographic and Clinical Differences in Subjects with Tuberculosis with and without Diabetes Mellitus in Brazil – A Multivariate Analysis

Background

Several studies have evaluated the relationship between diabetes mellitus (DM) and tuberculosis (TB), but the nature of this relationship is not fully understood. TB incidence may be influenced by immunosuppression from DM, but this association may be confounded by other clinical and socioeconomic factors. We aimed to assess socio-demographic and clinical differences in TB patients with and without DM.

Methods

Using the Brazilian national surveillance system (SINAN), we compared 1,797 subjects with TB and DM with 29,275 subjects diagnosed with TB only in 2009. We performed multivariate analysis to identify factors associated with the presence of DM among TB patients.

Results

Subjects with TB – DM were older; have initial positive sputum smear test (OR = 1.42, 95% CI 1.26–1.60), and were more likely to die from TB (OR = 1.44, 95% CI 1.03–2.01). They were less likely to have been institutionalized [in prison, shelter, orphanage, psychiatric hospital (OR = 0.74, 95% CI 0.60–0.93)]; developed extra pulmonary TB (OR = 0.62, 95% CI 0.51–0.75) and to return to TB treatment after abandonment (OR = 0.66, 95% CI 0.51–0.86).

Conclusions

Prevalence of NCD continues to rise in developing countries, especially with the rise of elderly population, the prevention and treatment of infectious diseases will be urgent. DM and TB represent a critical intersection between communicable and non-communicable diseases in these countries and the effect of DM on TB incidence and outcomes provide numerous opportunities for collaboration and management of these complex diseases in the national public health programs.     

Prevalence of and Factors Associated with Lens Opacities in a Korean Adult Population with and without Diabetes: The 2008–2009 Korea National Health and Nutrition Examination Survey

Objective

We examined the prevalence of and factors associated with lens opacities in a Korean adult population with and without diabetes.

Research Design and Methods

Among the 11,163 adults (≥19 years old) from the fourth Korea National Health and Nutrition Examination Survey in 2008–2009, the data from laboratory tests, nutritional surveys, and slit-lamp examinations of 10,248 persons (4,397 men, 5,851 women) were examined. Cataract was defined as the presence of any nuclear, cortical, subcapsular, or mixed cataract in at least one eye, using the Lens Opacities Classification System III.

Results

The weighted prevalence of cataracts were 23.5% [95% confidence interval (CI), 21.7–25.4] in a Korean adult population (19–39 years old, 1.8% [1.3–2.5], 40–64 years old, 25.2% [22.5–28.1],≥65 years old, 87.8% [85.4–89.9])and 54.7% [50.1–59.2] in a diabetic population(19–39 years old, 11.6% [4.5–26.5], 40–64 years old, 41.1% [35.4–47.0], ≥65 years old, 88.3% [83.5–91.8]). In a logistic regression analysis, age, myopia, and the presence of diabetes were independent risk factors. For young (age 19–39 years) and middle aged (age 40–65 years) adults with diabetes, the OR of having a lens opacity is 5.04 [1.41–17.98] and 1.47 [1.11–1.94], respectively, as those without diabetes, whereas for adults aged 65 and older, there was no difference in the prevalence of cataract.

Conclusions

According to these national survey data, ∼ 24% of Korean adults and ∼ 55% of people with diabetes have cataracts. The presence of diabetes was independently associated with cataracts in young and middle aged adults.     

Prevalence of Comorbidities and Baseline Characteristics of LAP-BAND AP? Subjects in the Helping Evaluate Reduction in Obesity (HERO) Study

Objective

To describe the baseline characteristics in patients who chose placement of a LAP-BAND AP® System (LBAP) and participated in the Helping Evaluate Reduction in Obesity (HERO) Study across regions.

Patients and Methods

HERO is a five- year, prospective, multicenter, international study of patients with LBAP placement between July 22, 2009 and January 31, 2011. In addition to baseline and peri-surgery clinical data, seven follow up visits are scheduled at 3, 6 and 12 months, and annually through year five. Data collection included family and medical history, clinical outcomes, laboratory data, health-related quality of life (HRQoL), productivity, healthcare resource utilization, and adverse events.

Results

LBAP were placed in 1106 enrolled patients; 56.6% from the US, 26.3% from Europe, 7.1% from Canada, and 10.0% from Australia. The majority were female (n = 877 (79.3%)) with a mean age of 43 years (s.d. = 11.4) and mean body mass index of 45.1 kg/m² (s.d. = 6.9). The most common comorbidities were hypertension (HTN) (overall  = 42.9%) and diabetes (overall 22.2%, with 27% from the US and 14% from Europe). Overall, less than 5% had a history of cardiovascular disease. The prevalence rates of HTN, diabetes and cardiovascular disease were significantly (p<0.001) higher in men than in women across all regions. Overall HRQoL also worsened with increasing BMI.

Conclusions

The HERO study is the first large, multinational and long-term registry with the LBAP. This study will provide real-world outcomes data on LAGB that will help inform patient choice, clinician treatment strategies, and payer reimbursement decisions.     

A Five-Year Prospective Study of Diabetic Retinopathy Progression in Chinese Type 2 Diabetes Patients with “Well-Controlled” Blood Glucose

Purpose

To determine the progression rate and risk factors for diabetic retinopathy (DR) in Chinese type 2 diabetic patients who have reached the target hemoglobin A1c (HbA1c) level recommended by the American Diabetes Association.

Methods

This was a 5-year community-based prospective study. The study population consisted of patients with type 2 diabetes with HbA1c less than 7.0%. Demographic information, systemic examination results and ophthalmological test results for each participant were collected. The outcome of this study was the progression of DR, which was defined as an increase in DR grade in one or both eyes at the final visit in comparison to the baseline status. The association between each potential risk factor and DR progression was studied.

Results

A total of 453 patients with HbA1c less than 7.0% were included in the study group. In 146 patients (32.22%), DR developed or progressed during the five-year follow-up. Baseline HbA1c level was the only independent risk factor for DR progression (p<0.01, OR = 2.84, 95%CI: 2.11~3.82). The logistic regression function suggested that the possibility of DR progression increased fastest when baseline HbA1c increased from 5.2% to 6.4%. The 5-year DR progression rate in patients with baseline HbA1c less than 5.2%, between 5.2% and 6.4%, and over 6.4% were 19.62%, 24.41%, and 76.83%, respectively.

Conclusions

To slow the progression of DR in Chinese patients with type 2 diabetes, more intensive glucose control is recommended.     

Technical-Induced Hemolysis in Patients with Respiratory Failure Supported with Veno-Venous ECMO – Prevalence and Risk Factors

The aim of the study was to explore the prevalence and risk factors for technical-induced hemolysis in adults supported with veno-venous extracorporeal membrane oxygenation (vvECMO) and to analyze the effect of hemolytic episodes on outcome. This was a retrospective, single-center study that included 318 adult patients (Regensburg ECMO Registry, 2009–2014) with acute respiratory failure treated with different modern miniaturized ECMO systems. Free plasma hemoglobin (fHb) was used as indicator for hemolysis. Throughout a cumulative support duration of 4,142 days on ECMO only 1.7% of the fHb levels were above a critical value of 500 mg/l. A grave rise in fHb indicated pumphead thrombosis (n = 8), while acute oxygenator thrombosis (n = 15) did not affect fHb. Replacement of the pumphead normalized fHb within two days. Neither pump or cannula type nor duration on the first system was associated with hemolysis. Multiple trauma, need for kidney replacement therapy, increased daily red blood cell transfusion requirements, and high blood flow (3.0–4.5 L/min) through small-sized cannulas significantly resulted in augmented blood cell trauma. Survivors were characterized by lower peak levels of fHb [90 (60, 142) mg/l] in comparison to non-survivors [148 (91, 256) mg/l, p≤0.001]. In conclusion, marked hemolysis is not common in vvECMO with modern devices. Clinically obvious hemolysis often is caused by pumphead thrombosis. High flow velocity through small cannulas may also cause technical-induced hemolysis. In patients who developed lung failure due to trauma, fHb was elevated independantly of ECMO. In our cohort, the occurance of hemolysis was associated with increased mortality.     

Incidence of and Risk Factors Associated with Pulmonary and Extra-Pulmonary Tuberculosis in Saudi Arabia (2010–2011)

Setting

National Tuberculosis Program, Department of Public Health, Ministry of Health, Kingdom of Saudi Arabia (KSA).

Objective

To summarize data on the incidence of tuberculosis and associated risk factors for cases reported during 2010–2011.

Design

Retrospective analysis of routinely collected data through an established national disease notification system of the Ministry of Health in KSA.

Results

The estimated incidence of all forms of tuberculosis fell from 15.8/100000 (95% CI: 15.3/100,000–16.3/100,000) in 2010 to 13.8/100,000 (95% CI: 13.4/100,000–14.2/100,000) in 2011. Saudis experienced a decrease from 11.8/100,000 (95% CI: 11.3/100,000 to 12.3/100,000) in 2010 to 9.9/100,000 (95% CI: 9.5/100,000–10.4/100,000) in 2011 while the incidence in non-Saudis declined from 24.7/100,000 (95% CI: 23.6/100,000 to 25.7/100,000) in 2010 to 22.5/100,000 (95% CI: 21.5/100,000 to 23.4/100,000) in 2011. The proportion of Extra Pulmonary TB (EPTB) which increased minimally from 30% in 2010 to 32% in 2011 was higher than global figures and strongly associated with age, sex, nationality and occupation.

Conclusion

The current estimated incidence of about 14/100,000 in 2011 is less than half its estimated value of 44/100000 in 1990. Without prejudice to any under-reporting, the KSA appeared to be on the course for TB elimination by 2050 having reached the first milestone set by WHO. The proportion of EPTB remains higher than global figure and age, sex, nationality and occupation were significant independent predictors of EPTB.     

Sex-Specific Prevalence of Diabetes and Cardiovascular Risk Factors in the Middle-Aged Population of China: A Subgroup Analysis of the 2007–2008 China National Diabetes and Metabolic Disorders Study

The sex difference in the prevalence rates of diabetes and cardiovascular diseases (CVDs) among the middle-aged population in China remain largely unknown. Therefore, we analyzed differences in the prevalence of diabetes, self-reported CVDs, and some CVD risk factors among men and women in the middle-aged population (30–49 years) and in individuals aged 50 years and older using data from the China National Diabetes and Metabolic Disorders Study of 2007–2008. Middle-aged men appeared to have significantly a higher prevalence of diabetes and self-reported CVDs than middle-aged women (8.07% vs 5.06% for diabetes, P < 0.001; 0.64% vs 0.22% for CVDs, P < 0.001). Men also showed higher rates of central obesity, hypertension, and dyslipidemia than women (all P < 0.01). Compared with women, men were more likely to drink alcohol and smoke cigarettes but less likely to be under diet control. The sex-specific differences in prediabetes, CVD, and CVD risk factors between men and women were diminished or even reversed in the population aged 50 years and older. No sex-specific differences were found in the prevalences of a family history of diabetes, coronary heart disease, and hypertension (P > 0.05) in middle-aged population. Specific strategies to reduce modifiable risk factors for the prevention and control of diabetes and CVD may be warranted in this population.     

Prevalence of Depression in a Large Urban South Indian Population — The Chennai Urban Rural Epidemiology Study (Cures – 70)

Background

In India there are very few population based data on prevalence of depression. The aim of the study was to determine the prevalence of depression in an urban south Indian population.

Methods and Findings

Subjects were recruited from the Chennai Urban Rural Epidemiology Study (CURES), involving 26,001 subjects randomly recruited from 46 of the 155 corporation wards of Chennai (formerly Madras) city in South India. 25,455 subjects participated in this study (response rate 97.9%). Depression was assessed using a self-reported and previously validated instrument, the Patient Health Questionnaire (PHQ) – 12. Age adjustment was made according to the 2001 census of India. The overall prevalence of depression was 15.1% (age-adjusted, 15.9%) and was higher in females (females 16.3% vs. males 13.9%, p<0.0001). The odds ratio (OR) for depression in female subjects was 1.20 [Confidence Intervals (CI): 1.12–1.28, p<0.001] compared to male subjects. Depressed mood was the most common symptom (30.8%), followed by tiredness (30.0%) while more severe symptoms such as suicidal thoughts (12.4%) and speech and motor retardation (12.4%) were less common. There was an increasing trend in the prevalence of depression with age among both female (p<0.001) and male subjects (p<0.001). The prevalence of depression was higher in the low income group (19.3%) compared to the higher income group (5.9%, p<0.001). Prevalence of depression was also higher among divorced (26.5%) and widowed (20%) compared to currently married subjects (15.4%, p<0.001).

Conclusions

This is the largest population-based study from India to report on prevalence of depression and shows that among urban south Indians, the prevalence of depression was 15.1%. Age, female gender and lower socio-economic status are some of the factors associated with depression in this population.     

Older Age Is Associated with Peripheral Blood Expansion of Na?ve B Cells in HIV-Infected Subjects on Antiretroviral Therapy

Older HIV infected subjects were previously found to have significant B cell expansion during initial antiretroviral therapy in a prospective age-differentiated cohort of older and younger (≥45 vs. ≤30 years) HIV-infected subjects initiating antiretroviral therapy (ART) through the AIDS Clinical Trials Group. Here to further describe this expansion, using a subset of subjects from the same cohort, we characterized B cell phenotypes at baseline and after 192 weeks of ART in both older and younger HIV-infected groups and compared them to uninfected age-matched controls. We also examined whether phenotypes at baseline associated with response to tetanus and hepatitis A vaccine at 12 weeks. Forty six subjects were analyzed in the HIV infected group (21 older, 25 younger) and 30 in the control group (15 per age group). We observed naïve B cells to normalize in younger subjects after 192 weeks of ART, while in older subjects naïve B cells increased to greater levels than those of controls (p = 0.045). Absolute resting memory (RM) cell count was significantly lower in the older HIV infected group at baseline compared to controls and numbers normalized after 192 weeks of ART (p<0.001). Baseline RM cell count positively correlated with week 12 increase in antibody to tetanus vaccine among both younger and older HIV-infected subjects combined (p = 0.01), but not in controls. The age-associated naïve B cell expansion is a novel finding and we discuss several possible explanations for this observation. Relationship between RM cells at baseline and tetanus responses may lead to insights about the effects of HIV infection on B cell memory function and vaccine responses.     

Decreased Cystathionine-γ-lyase (CSE) Activity in Livers of Type 1 Diabetic Rats and Peripheral Blood Mononuclear Cells (PBMC) of Type 1 Diabetic Patients

The liver plays a major role in the formation of H₂S, a novel signaling molecule. Diabetes is associated with lower blood levels of H₂S. This study investigated the activities of cystathionine-γ-lyase (CSE, the enzyme that catalyzes H₂S formation) in livers of type 1 diabetic (T1D) animals and in peripheral blood mononuclear cells (PBMC) isolated from T1D patients. T1D is associated with both hyperketonemia (acetoacetate and β-hydroxybutyrate) and hyperglycemia. This study also examined the role of hyperglycemia and hyperketonemia per se in decreased CSE activity using U937 monocytes and PBMC isolated from healthy subjects. Livers from streptozotocin-treated T1D rats demonstrated a significantly higher reactive oxygen species production, lower CSE protein expression and activity, and lower H₂S formation compared with those of controls. Studies with T1D patients showed a decrease in CSE protein expression and activity in PBMC compared with those of age-matched normal subjects. Cell culture studies demonstrated that high glucose (25 mm) and/or acetoacetate (4 mm) increased reactive oxygen species, decreased CSE mRNA expression, protein expression, and enzymatic activity, and reduced H₂S levels; however, β-hydroxybutyrate treatment had no effect. A similar effect, which was also observed in PBMC treated with high glucose alone or along with acetoacetate, was prevented by vitamin D supplementation. Studies with CSE siRNA provide evidence for a relationship between impaired CSE expression and reduced H₂S levels. This study demonstrates for the first time that both hyperglycemia and hyperketonemia mediate a reduction in CSE expression and activity, which can contribute to the impaired H₂S signaling associated with diabetes.     

Molecular Characterization of the Fecal Microbiota in Patients with Nonalcoholic Steatohepatitis – A Longitudinal Study

Background

The human gut microbiota has profound influence on host metabolism and immunity. This study characterized the fecal microbiota in patients with nonalcoholic steatohepatitis (NASH). The relationship between microbiota changes and changes in hepatic steatosis was also studied.

Methods

Fecal microbiota of histology-proven NASH patients and healthy controls was analyzed by 16S ribosomal RNA pyrosequencing. NASH patients were from a previously reported randomized trial on probiotic treatment. Proton-magnetic resonance spectroscopy was performed to monitor changes in intrahepatic triglyceride content (IHTG).

Results

A total of 420,344 16S sequences with acceptable quality were obtained from 16 NASH patients and 22 controls. NASH patients had lower fecal abundance of Faecalibacterium and Anaerosporobacter but higher abundance of Parabacteroides and Allisonella. Partial least-square discriminant analysis yielded a model of 10 genera that discriminated NASH patients from controls. At month 6, 6 of 7 patients in the probiotic group and 4 of 9 patients in the usual care group had improvement in IHTG (P = 0.15). Improvement in IHTG was associated with a reduction in the abundance of Firmicutes (R² = 0.4820, P = 0.0028) and increase in Bacteroidetes (R² = 0.4366, P = 0.0053). This was accompanied by corresponding changes at the class, order and genus levels. In contrast, bacterial biodiversity did not differ between NASH patients and controls, and did not change with probiotic treatment.

Conclusions

NASH patients have fecal dysbiosis, and changes in microbiota correlate with improvement in hepatic steatosis. Further studies are required to investigate the mechanism underlying the interaction between gut microbes and the liver.     

Secular Trends in Prevalence and Risk Factors of Obesity in Infants and Preschool Children in 9 Chinese Cities, 1986–2006

Introduction

No prevalence/trends were reported in Chinese infants and preschool children at the national level in this historical period of 1980s–2000s. The objectives of this paper were to present the 20-year trends in prevalence and risk factors of obesity in children below 7 years.

Methods

Data obtained from a series of three sequential national surveys performed using the same design in the same 9 cities in 1986, 1996 and 2006. Weight and height (length <3 years) were measured using unified procedures at each period. Obesity was defined as a weight-for-height ≥120% of median of the NCHS/WHO international reference. A population-based paired matching case-control study was employed for screening risk factors.

Results

In 1986, there was no substantial obesity epidemic, but the overall obesity prevalence reached 3.4% (boys 4.1% and girls 2.7%) in 2006, rising by 2.8 times between 1986 and 2006. Reversed gender difference, relatively higher prevalence in preschool age and more rapid increase in the second 10-year were three very obvious characteristics in China, e.g. prevalence of boys 9.9% and girls 4.9% in 2006 and increasing rate of boys 0.45 percentage points per year (pp/y) and girls 0.21 pp/y at 6–7 years groups, 0.17 pp/y of the second 10-year higher 1-fold than previous.

Conclusions

China has been moving into the alarming epidemic of childhood obesity. Effort should be immediately made to prevent further deterioration. High birth weight, high parental BMI and several behavioral and family-related factors were identified and had important practical value for obesity intervention.     

Prevalence and Clinical Significance of HIV Drug Resistance Mutations by Ultra-Deep Sequencing in Antiretroviral-Na?ve Subjects in the CASTLE Study

Background

CASTLE compared the efficacy of atazanavir/ritonavir with lopinavir/ritonavir, each in combination with tenofovir-emtricitabine in ARV-naïve subjects from 5 continents.

Objectives

Determine the baseline rate and clinical significance of TDR mutations using ultra-deep sequencing (UDS) in ARV-naïve subjects in CASTLE.

Methods

A case control study was performed on baseline samples for all 53 subjects with virologic failures (VF) at Week 48 and 95 subjects with virologic successes (VS) randomly selected and matched by CD4 count and viral load. UDS was performed using 454 Life Sciences/Roche technology.

Results

Of 148 samples, 141 had successful UDS (86 subtype B, 55 non-B subtypes). Overall, 30.5% of subjects had a TDR mutation at baseline; 15.6% only had TDR(s) at <20% of the viral population. There was no difference in the rate of TDRs by B (30.2%) or non-B subtypes (30.9%). VF (51) and VS (90) had similar rates of any TDRs (25.5% vs. 33.3%), NNRTI TDRs (11.1% vs.11.8%) and NRTI TDRs (24.4% vs. 25.5%). Of 9 (6.4%) subjects with M184V/I (7 at <20% levels), 6 experienced VF. 16 (11.3%) subjects had multiple TAMs, and 7 experienced VF. 3 (2.1%) subjects had both multiple TAMs+M184V, and all experienced VF. Of 14 (9.9%) subjects with PI TDRs (11 at <20% levels): only 1 experienced virologic failure. The majority of PI TDRs were found in isolation (e.g. 46I) at <20% levels, and had low resistance algorithm scores.

Conclusion

Among a representative sample of ARV-naïve subjects in CASTLE, TDR mutations were common (30.5%); B and non-B subtypes had similar rates of TDRs. Subjects with multiple PI TDRs were infrequent. Overall, TDRs did not affect virologic response for subjects on a boosted PI by week 48; however, a small subset of subjects with extensive NRTI backbone TDR patterns experienced virologic failure.     

Iron-Related Factors in Early Pregnancy and Subsequent Risk of Gestational Diabetes Mellitus: the Ma’anshan Birth Cohort (MABC) Study

Serum magnesium (Mg) is reported to be reduced in individuals with obesity, hypertension, and diabetes mellitus and has been suggested as a marker for metabolic syndrome. We have studied changes in serum Mg concentrations in a group of obese patients (n = 92) with and without diabetes mellitus after weight loss induced by dieting and bariatric surgery. At inclusion, 11% (10/92) of the population had severe Mg deficiency (< 0.75 mmol/L) and median serum Mg was lower in diabetic (n = 20) compared to non-diabetic (n = 72) patients (p = 0.002). A weight loss of 10 kg after 8 weeks of lifestyle interventions was accompanied by increased serum Mg of about 5% in both diabetic and non-diabetic patients. Serum Mg remained stable thereafter in the non-diabetic patients, while it continued to increase in the diabetic patients after bariatric surgery. Six months after bariatric surgery, there was no significant difference in serum Mg concentration between the groups (p = 0.08). The optimal range of circulating Mg concentration is not known, but as even small increments in serum Mg are reported to lower the risk of cardiovascular and ischemic heart disease, our results are interesting in a public health perspective.