Tessa Rue

Temporal trends in the prevalence of diabetic kidney disease in the United States

CONTEXT Diabetes is the leading cause of kidney disease in the developed world. Over time, the prevalence of diabetic kidney disease (DKD) may increase due to the expanding size of the diabetes population or decrease due to the implementation of diabetes therapies. OBJECTIVE To define temporal changes in DKD prevalence in the United States. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analyses of the Third National Health and Nutrition Examination Survey (NHANES III) from 1988-1994 (N = 15,073), NHANES 1999-2004 (N = 13,045), and NHANES 2005-2008 (N = 9588). Participants with diabetes were defined by levels of hemoglobin A(1c) of 6.5% or greater, use of glucose-lowering medications, or both (n = 1431 in NHANES III; n = 1443 in NHANES 1999-2004; n = 1280 in NHANES 2005-2008). MAIN OUTCOME MEASURES Diabetic kidney disease was defined as diabetes with albuminuria (ratio of urine albumin to creatinine ≥30 mg/g), impaired glomerular filtration rate (<60 mL/min/1.73 m(2) estimated using the Chronic Kidney Disease Epidemiology Collaboration formula), or both. Prevalence of albuminuria was adjusted to estimate persistent albuminuria. RESULTS The prevalence of DKD in the US population was 2.2% (95% confidence interval [CI], 1.8%-2.6%) in NHANES III, 2.8% (95% CI, 2.4%-3.1%) in NHANES 1999-2004, and 3.3% (95% CI, 2.8%-3.7%) in NHANES 2005-2008 (P <.001 for trend). The prevalence of DKD increased in direct proportion to the prevalence of diabetes, without a change in the prevalence of DKD among those with diabetes. Among persons with diabetes, use of glucose-lowering medications increased from 56.2% (95% CI, 52.1%-60.4%) in NHANES III to 74.2% (95% CI, 70.4%-78.0%) in NHANES 2005-2008 (P <.001); use of renin-angiotensin-aldosterone system inhibitors increased from 11.2% (95% CI, 9.0%-13.4%) to 40.6% (95% CI, 37.2%-43.9%), respectively (P <.001); the prevalence of impaired glomerular filtration rate increased from 14.9% (95% CI, 12.1%-17.8%) to 17.7% (95% CI, 15.2%-20.2%), respectively (P = .03); and the prevalence of albuminuria decreased from 27.3% (95% CI, 22.0%-32.7%) to 23.7% (95% CI, 19.3%-28.0%), respectively, but this was not statistically significant (P = .07). CONCLUSIONS Prevalence of DKD in the United States increased from 1988 to 2008 in proportion to the prevalence of diabetes. Among persons with diabetes, prevalence of DKD was stable despite increased use of glucose-lowering medications and renin-angiotensin-aldosterone system inhibitors.

Long-term Renal Outcomes of Patients With Type 1 Diabetes Mellitus and Microalbuminuria: An Analysis of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Cohort

BACKGROUND Microalbuminuria is a common diagnosis in the clinical care of patients with type 1 diabetes mellitus. Long-term outcomes after the development of microalbuminuria are variable. METHODS We quantified the incidence of and risk factors for long-term renal outcomes after the development of microalbuminuria in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. The DCCT randomly assigned 1441 persons with type 1 diabetes to intensive or conventional diabetes therapy, and participants were subsequently followed up during the observational EDIC study. During the DCCT/EDIC study, 325 participants developed incident persistent microalbuminuria (albumin excretion rate, ≥30 mg/24 h at 2 consecutive study visits). We assessed their subsequent renal outcomes, including progression to macroalbuminuria (albumin excretion rate, ≥300 mg/24 h at 2 consecutive visits), impaired glomerular filtration rate (estimated glomerular filtration rate, <60 mL/min/1.73 m(2) at 2 consecutive study visits), end-stage renal disease, and regression to normoalbuminuria (albumin excretion rate, <30 mg/24 h at 2 consecutive visits). RESULTS The median follow-up period after persistent microalbuminuria diagnosis was 13 years (maximum, 23 years). Ten-year cumulative incidences of progression to macroalbuminuria, impaired glomerular filtration rate, end-stage renal disease, and regression to normoalbuminuria were 28%, 15%, 4%, and 40%, respectively. Albuminuria outcomes were more favorable with intensive diabetes therapy, lower glycated hemoglobin level, absence of retinopathy, female sex, lower blood pressure, and lower concentrations of low-density lipoprotein cholesterol and triglycerides. Lower glycated hemoglobin level, absence of retinopathy, and lower blood pressure were also associated with decreased risk of impaired glomerular filtration rate. CONCLUSIONS After the development of persistent microalbuminuria, progression and regression of kidney disease each commonly occur. Intensive glycemic control, lower blood pressure, and a more favorable lipid profile are associated with improved outcomes.

Serum phosphorus concentrations in the third National Health and Nutrition Examination Survey (NHANES III).

BACKGROUND Higher serum phosphorus concentrations within the normal laboratory range have been associated with cardiovascular events and mortality in large prospective cohort studies of individuals with and without kidney disease. Reasons for interindividual variation in steady-state serum phosphorus concentrations are largely unknown. STUDY DESIGN Cross-sectional study. SETTING & PARTICIPANTS 15,513 participants in the Third National Health and Nutrition Examination Survey. PREDICTORS Demographic data, dietary intake measured by means of 24-hour dietary recall and food-frequency questionnaire, and established cardiovascular risk factors. OUTCOME & MEASUREMENTS Serum phosphorus concentration. RESULTS Mean serum phosphorus concentrations were significantly greater in women (+0.16 mg/dL versus men; P < 0.001) and people of non-Hispanic black and Hispanic race/ethnicity (+0.06 and +0.07 mg/dL versus non-Hispanic white, respectively; P < 0.001). Dietary intakes of phosphorus and phosphorus-rich foods were associated only weakly with circulating serum phosphorus concentrations, if at all. Higher serum phosphorus levels were associated with lower calculated Framingham coronary heart disease risk scores, which are based on traditional atherosclerosis risk factors. In aggregate, demographic, nutritional, cardiovascular, and kidney function variables explained only 12% of the variation in circulating serum phosphorus concentrations. LIMITATIONS Results may differ with advanced kidney disease. CONCLUSIONS Serum phosphorus concentration is weakly related to dietary phosphorus and not related to a diverse array of phosphorus-rich foods in the general population. Factors determining serum phosphorus concentration are largely unknown. Previously observed associations of serum phosphorus concentrations with cardiovascular events are unlikely to be a result of differences in dietary intake or traditional cardiovascular risk factors.

Insulin Therapy, Hyperglycemia, and Hypertension in Type 1 Diabetes Mellitus

BACKGROUND Diabetes mellitus and hypertension are closely linked, but the long-term blood pressure effects of glucose-lowering therapy and hyperglycemia are not clear. METHODS We examined the effects of intensive insulin therapy and hyperglycemia on the development of hypertension in the Diabetes Control and Complications Trial (DCCT) and its observational follow-up, the Epidemiology of Diabetes Intervention and Complications (EDIC) study. Incident hypertension was defined as 2 consecutive study visits with a systolic blood pressure of 140 mm Hg or higher, a diastolic blood pressure of 90 mm Hg or higher, or use of antihypertensive medications to treat high blood pressure. RESULTS Participants were enrolled from August 23, 1983, through June 30, 1989. During a 15.8-year median follow-up, 630 of 1441 participants developed hypertension. During the DCCT, the incidence of hypertension was similar comparing participants assigned to intensive vs conventional therapy. However, intensive therapy during the DCCT reduced the risk of incident hypertension by 24% during EDIC study follow-up (hazard ratio, 0.76; 95% confidence interval [CI], 0.64-0.92). A higher hemoglobin A(1c) level, measured at baseline or throughout follow-up, was associated with increased risk for incident hypertension (adjusted hazard ratios, 1.11 [95% CI, 1.06-1.17] and 1.25 [95% CI, 1.14-1.37], respectively, for each 1% higher hemoglobin A(1c) level), and glycemic control appeared to mediate the antihypertensive benefit of intensive therapy. Older age, male sex, family history of hypertension, greater baseline body mass index, weight gain, and greater albumin excretion rate were independently associated with increased risk of hypertension. CONCLUSIONS Hyperglycemia is a risk factor for incident hypertension in type 1 diabetes, and intensive insulin therapy reduces the long-term risk of developing hypertension.

Rhombencephalosynapsis: a hindbrain malformation associated with incomplete separation of midbrain and forebrain, hydrocephalus and a broad spectrum of severity

Rhombencephalosynapsis is a midline brain malformation characterized by missing cerebellar vermis with apparent fusion of the cerebellar hemispheres. Rhombencephalosynapsis can be seen in isolation or together with other central nervous system and extra-central nervous system malformations. Gómez-López-Hernández syndrome combines rhombencephalosynapsis with parietal/temporal alopecia and sometimes trigeminal anaesthesia, towering skull shape and dysmorphic features. Rhombencephalosynapsis can also be seen in patients with features of vertebral anomalies, anal atresia, cardiovascular anomalies, trachea-oesophageal fistula, renal anomalies, limb defects (VACTERL) association. Based on a comprehensive evaluation of neuroimaging findings in 42 patients with rhombencephalosynapsis, we propose a spectrum of severity, ranging from mild (the partial absence of nodulus, anterior and posterior vermis), to moderate (the absence of posterior vermis with some anterior vermis and nodulus present), to severe (the absence of posterior and anterior vermis with some nodulus present), to complete (the absence of the entire vermis including nodulus). We demonstrate that the severity of rhombencephalosynapsis correlates with fusion of the tonsils, as well as midbrain abnormalities including aqueductal stenosis and midline fusion of the tectum. Rhombencephalosynapsis is also associated with multiple forebrain abnormalities including absent olfactory bulbs, dysgenesis of the corpus callosum, absent septum pellucidum and, in rare patients, atypical forms of holoprosencephaly. The frequent association between rhombencephalosynapsis and aqueductal stenosis prompted us to evaluate brain magnetic resonance images in other patients with aqueductal stenosis at our institution, and remarkably, we identified rhombencephalosynapsis in 9%. Strikingly, subjects with more severe rhombencephalosynapsis have more severely abnormal neurodevelopmental outcome, as do subjects with holoprosencephaly and patients with VACTERL features. In summary, our data provide improved diagnostic and prognostic information, and support disruption of dorsal-ventral patterning as a mechanism underlying rhombencephalosynapsis.

Racial/ethnic differences in the association between obesity and major depressive disorder: findings from the Comprehensive Psychiatric Epidemiology Surveys

Objectives. This study examined whether the association between obesity and 12-month prevalence of major depressive disorder (MDD) varied according to racial/ethnic status and nativity in representative national samples of black, Latino, Asian, and non-Hispanic white people. Methods. We used data from the Comprehensive Psychiatric Epidemiology Surveys. Results. In analyses by gender, obesity was associated with an elevated risk of MDD among non-Hispanic white women (adjusted odds ratio [AOR] =1.73; 95% confidence interval [CI] 1.27, 2.35; p=0.001). Formal test for interaction revealed significant variation by race present between non- Hispanic white women and black, Latin, and Asian women. No significant differences were evident among men. In analyses by nativity, the association between obesity and MDD was significant among U.S.-born non-Hispanic white women (AOR=1.62; 95% CI 1.16, 2.27; p=0.001) and U.S.-born black women (AOR=1.29; 95% CI 1.01, 1.66; p=0.041). Significant interactions were present among U.S.-born white and black women, Latin women, and Asian women. No significant interactions were evident among foreign-born women. Similarly, no significant differences were present among native-born or foreign-born men. Conclusions. The findings suggest that the association between obesity and MDD varies according to racial/ethnic status and nativity. Understanding the link between obesity and depression may be imperative to designing interventions to address body weight maintenance and reduction strategies among women.

Association of Combinations of Lipid Parameters With Carotid Intima-Media Thickness and Coronary Artery Calcium in the MESA (Multi-Ethnic Study of Atherosclerosis)

OBJECTIVES The purpose of this study was to determine the association of combinations of lipid parameters with subclinical atherosclerosis. BACKGROUND Carotid intima-media thickness (CIMT) and coronary artery calcium (CAC) are significantly associated with incident cardiovascular disease (CVD). The association between common dyslipidemias (combined hyperlipidemia, [simple] hypercholesterolemia, dyslipidemia of metabolic syndrome, isolated low high-density lipoprotein cholesterol, and isolated hypertriglyceridemia) compared with normolipemia, and CIMT and CAC has not been previously examined. METHODS The MESA (Multi-Ethnic Study of Atherosclerosis) participants were White, Chinese, African-American, or Hispanic adults without clinical CVD. Subjects with diabetes mellitus or who were receiving lipid-lowering therapy were excluded. Every participant was classified into only 1 of 6 groups defined by specific low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride cut points. Multivariate linear and relative risk regressions evaluated the cross-sectional associations with CIMT and CAC after adjusting for CVD risk factors. Interactions with race, sex, and high-sensitivity C-reactive protein were evaluated for CIMT and CAC outcomes. RESULTS Among 4,792 participants, only those with combined hyperlipidemia and hypercholesterolemia demonstrated both increased common CIMT (combined hyperlipidemia 0.048 mm thicker, 95% confidence interval [CI]: 0.016 to 0.080 mm; hypercholesterolemia 0.048 mm thicker, 95% CI: 0.029 to 0.067 mm) and internal CIMT (combined hyperlipidemia 0.120 mm thicker, 95% CI: 0.032 to 0.208 mm; and hypercholesterolemia 0.161 mm thicker, 95% CI: 0.098 to 0.223 mm) as well as increased risk for prevalent CAC (combined hyperlipidemia relative risk: 1.22, 95% CI: 1.08 to 1.38; hypercholesterolemia relative risk: 1.22, 95% CI: 1.11 to 1.34) compared with normolipemia. The interactions between lipid parameters and race, sex, or high-sensitivity C-reactive protein were not significant for any outcomes. CONCLUSIONS Combined hyperlipidemia and simple hypercholesterolemia were associated with increased CIMT and prevalent CAC in a relatively healthy multiethnic population.

Racial differences in the prevalence of antenatal depression

OBJECTIVE This study examined whether there were racial/ethnic differences in the prevalence of antenatal depression based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnostic criteria in a community-based sample of pregnant women. METHOD Data were drawn from an ongoing registry of pregnant women receiving prenatal care at a university obstetric clinic from January 2004 through March 2010 (N =1997). Logistic regression models adjusting for sociodemographic, psychiatric, behavioral and clinical characteristics were used to examine racial/ethnic differences in antenatal depression as measured by the Patient Health Questionnaire. RESULTS Overall, 5.1% of the sample reported antenatal depression. Blacks and Asian/Pacific Islanders were at increased risk for antenatal depression compared to non-Hispanic White women. This increased risk of antenatal depression among Blacks and Asian/Pacific Islanders remained after adjustment for a variety of risk factors. CONCLUSION Results suggest the importance of race/ethnicity as a risk factor for antenatal depression. Prevention and treatment strategies geared toward the mental health needs of Black and Asian/Pacific Islander women are needed to reduce the racial/ethnic disparities in antenatal depression.

A Genetic Expression Profile Associated with Oral Cancer Identifies a Group of Patients at High Risk of Poor Survival

Purpose: To determine if gene expression signature of invasive oral squamous cell carcinoma (OSCC) can subclassify OSCC based on survival. Experimental Design: We analyzed the expression of 131 genes in 119 OSCC, 35 normal, and 17 dysplastic mucosa to identify cluster-defined subgroups. Multivariate Cox regression was used to estimate the association between gene expression and survival. By stepwise Cox regression, the top predictive models of OSCC-specific survival were determined and compared by receiver operating characteristic analysis. Results: The 3-year overall mean ± SE survival for a cluster of 45 OSCC patients was 38.7 ± 0.09% compared with 69.1 ± 0.08% for the remaining patients. Multivariate analysis adjusted for age, sex, and stage showed that the 45 OSCC patient cluster had worse overall and OSCC-specific survival (hazard ratio, 3.31; 95% confidence interval, 1.66-6.58 and hazard ratio, 5.43; 95% confidence interval, 2.32-12.73, respectively). Stepwise Cox regression on the 131 probe sets revealed that a model with a term for LAMC2 (laminin γ2) gene expression best identified patients with worst OSCC-specific survival. We fit a Cox model with a term for a principal component analysis-derived risk score marker and two other models that combined stage with either LAMC2 or PCA. The area under the curve for models combining stage with either LAMC2 or PCA was 0.80 or 0.82, respectively, compared with 0.70 for stage alone (P = 0.013 and 0.008, respectively). Conclusions: Gene expression and stage combined predict survival of OSCC patients better than stage alone.

Mindful awareness in body-oriented therapy as an adjunct to women's substance use disorder treatment: A pilot feasibility study

This study examined mindful awareness in body-oriented therapy (MABT) feasibility as a novel adjunct to womens substance use disorder (SUD) treatment. As an individual therapy, MABT combines manual and mind-body approaches to develop interoception and self-care tools for emotion regulation. A 2-group randomized controlled trial repeated-measures design was used, comparing MABT to treatment as usual (TAU) on relapse to substance use and related health outcomes. Sixty-one women were screened for eligibility, and 46 enrolled. Participants randomized to MABT received 8 weekly MABT sessions. Results showed moderate to large effects, including significantly fewer days on substance use, the primary outcome, for MABT compared with TAU at posttest. Secondary outcomes showed improved eating disorder symptoms, depression, anxiety, dissociation, perceived stress, physical symptom frequency, and bodily dissociation for MABT compared with TAU at the 9-month follow-up. In conclusion, it is feasible to implement MABT in womens SUD treatment, and results suggest that MABT is worthy of further efficacy testing.