Development of a sustainable diet index in US adults.

BACKGROUND: A transformation towards healthy diets through a sustainable food system is essential to enhance both human and planet health. Development of a valid, multidimensional, quantitative index of a sustainable diet would allow monitoring progress in the US population. We evaluated the content and construct validity of a sustainable diet index for US adults (SDI-US) based on data collected at the individual level. METHODS: The SDI-US, adapted from the SDI validated in the French population, was developed using data on US adults aged 20 years and older from the National Health and Nutrition Examination Survey, 2007-2018 (n = 25,543). The index consisted of 4 sub-indices, made up of 12 indicators, corresponding to 4 dimensions of sustainable diets (nutritional quality, environmental impacts, affordability (economic), and ready-made product use behaviors (sociocultural)). A higher SDI-US score indicates greater alignment with sustainable diets (range: 4-20). Validation analyses were performed, including the assessment of the relevance of each indicator, correlations between individual indicators, sub-indices, and total SDI-US, differences in scores between sociodemographic subgroups, and associations with selected food groups in dietary guidelines, the alternative Mediterranean diet (aMed) score, and the EAT-Lancet diet score. RESULTS: Total SDI-US mean was 13.1 (standard error 0.04). The correlation between SDI-US and sub-indices ranged from 0.39 for the environmental sub-index to 0.61 for the economic sub-index (Pearson Correlation coefficient). The correlation between a modified SDI-US after removing each sub-index and the SDI-US ranged from 0.83 to 0.93. aMed scores and EAT-Lancet diet scores were significantly higher among adults in the highest SDI-US quintile compared to the lowest quintile (aMed: 4.6 vs. 3.2; EAT-Lancet diet score: 9.9 vs. 8.7 p < .0001 for both). CONCLUSIONS: Overall, content and construct validity of the SDI-US were acceptable. The SDI-US reflected the key features of sustainable diets by integrating four sub-indices, comparable to the SDI-France. The SDI-US can be used to assess alignment with sustainable diets in the US. Continued monitoring of US adults' diets using the SDI-US could help improve dietary sustainability.

Urinary symptoms and female sexual dysfunction in women with type 1 diabetes: the role of depression.

BACKGROUND: Some reports suggest that women with type 1 diabetes (T1D) have a greater burden of female sexual dysfunction (FSD) than women without T1D, but the etiology of this elevated risk is poorly understood. AIM: To examine the associations between FSD and urinary incontinence/lower urinary tract symptoms (UI/LUTS) in women with T1D and to evaluate how depression may mediate these relationships. METHODS: LUTS and UI symptoms were assessed in women with T1D who participated in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study. Multivariable logistic regression models estimated associations between FSD and UI/LUTS (overall and specific domains) and the impact of depression on these associations. OUTCOMES: FSD was measured with the Female Sexual Function Index-Reduced. RESULTS: In total, 499 self-reported sexually active women completed validated assessments of sexual and urinary function (mean ± SD age, 47.7 ± 7.6 years; T1D duration, 23.4 ± 5.15 years). FSD was reported in 232 (46%) responders. The frequency of UI and LUTS was 125 (25.1%) and 96 (19.2%), respectively. Neither UI nor its subcategories (urge, stress) were associated with FSD. Although LUTS (odds ratio [OR], 1.75; 95% CI, 1.09-2.77) and its symptoms of urgency (OR, 1.99; 95% CI, 1.09-3.61) and incomplete emptying (OR, 2.44; 95% CI, 1.23-4.85) were associated with FSD, these associations were attenuated following adjustment for depression and antidepressant medication use. Depression indicators were independently associated with FSD overall and across domains. CLINICAL IMPLICATIONS: The complex interplay of voiding dysfunction, mental health, and sexual function warrants further investigation to understand the potential implications for patient assessment, goal setting, treatment, and care planning. STRENGTHS AND LIMITATIONS: Data are from a prospective study of individuals with T1D. These results are unable to explore cause-and-effect relationships among LUTS, UI, depression, and FSD. The sample may not be representative of the general population of women with T1D. Because participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study are mostly White, generalizing the findings to other races and to type 2 diabetes may not be appropriate. While exclusion of sexually inactive women likely biases our findings toward the null, this design element permitted study of LUTS and UI in relation to aspects of FSD, the primary objective of this study. CONCLUSIONS: The significant associations between LUTS/UI and FSD among middle-aged women with T1D were greatly attenuated when depression was considered a mediating factor.

Longitudinal patterns of urinary incontinence and associated predictors in women with type 1 diabetes.

AIMS: Urinary incontinence (UI) in women is a dynamic condition with numerous risk factors yet most studies have focused on examining its prevalence at a single time. The objective of this study was to describe the long-term time course of UI in women with type 1 diabetes (T1D). METHODS: Longitudinal data in women with T1D were collected from 568 women in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow-up of the Diabetes Control and Complications Trial (DCCT) cohort. Over a 12-year period, participants annually responded to whether they had experienced UI in the past year. RESULTS: We identified four categories of UI in this population over time: 205 (36.1%) women never reported UI (no UI), 70 (12.3%) reported it one or two consecutive years only (isolated UI), 247 (43.5%) periodically changed status between UI and no UI (intermittent UI), and 46 (8.1%) reported UI continuously after the first report (persistent UI). Compared to women reporting no/isolated UI, women displaying the intermittent phenotype were significantly more likely to be obese (OR: 1.86, 95% CI 1.15, 3.00) and report prior hysterectomy (OR: 2.57, 95% CI: 1.39, 4.77); whereas women with persistent UI were significantly more likely to have abnormal autonomic function (OR: 2.36, 95% CI: 1.16-4.80). CONCLUSIONS: UI is a dynamic condition in women with T1D. Varying risk factors observed for the different phenotypes of UI suggest distinctive pathophysiological mechanisms. These findings have the potential to be used to guide individualized interventions for UI in women with diabetes.

Models to Assess the Association of a Semiquantitative Exposure With Outcomes.

A semiquantitative risk factor has 2 components: any exposure (yes/no) and the quantitative amount of exposure (if exposed). We describe the statistical properties of alternative analyses with such a risk factor using linear, logistic, or Cox proportional hazards models. Often analyses employ the amount exposed as a single quantitative covariate, including the nonexposed with value zero. However, this analysis provides a biased estimate of the exposure coefficient (slope) and we describe the magnitude of the bias. This bias can be eliminated by adding a binary covariate for exposed versus not to the model. This 2-factor analysis captures the full risk-factor effect on the outcome. However, the coefficient for any exposure versus not does not have a meaningful interpretation. Alternatively, when exposure values among those exposed are centered (by subtracting the mean), the estimate of this coefficient represents the difference in the outcome between those exposed versus not in aggregate. We also show that the biased model provides biased estimates of the coefficients for other covariates added to the model. Proper analysis of a semiquantitative risk factor should start with a 2-factor model, with centering, to assess the joint contributions of the 2 components of the risk-factor exposure. Properties of models were illustrated using data from a multisite study in North America (1983-2019).

The minimum intensity of a mixed exposure that increases the risk of an outcome.

Semi-quantitative exposures, such as smoking and alcohol consumption, are common in clinical studies. Their association with outcomes is captured using either a single quantitative variable that includes nonexposed with a value of zero, or using two variables by adding an additional binary variable exposed versus not exposed. Herein, we propose two approaches to determine a lower bound on the amount of such an exposure (eg, number of cigarettes smoked per day) that significantly increases the risk of outcomes. Using smoking as illustration, the first approach consists of sequentially testing the effect of 1, 2, and so on, cigarettes per day, which requires an adjustment for multiplicity to protect the overall type-I error. An alternative gatekeeping approach is also described. The proposed methods are illustrated for the association of smoking with clinically confirmed neuropathy in a logistic regression model, and for the association of smoking with the risk of CVD in a Cox PH regression model.

Circulating adhesion molecules and associations with HbA1c, hypertension, nephropathy, and retinopathy in the Treatment Options for type 2 Diabetes in Adolescent and Youth study.

BACKGROUND: The Treatment Options for type 2 Diabetes in Adolescent and Youth study, a randomized clinical trial of three treatments for type 2 diabetes (T2DM) in youth, demonstrated treatment failure (defined as sustained HbA1c ≥8%, or inability to wean insulin after 3 months after acute metabolic decomposition) in over half of the participants. Given that binding of mononuclear cells to vascular endothelium, initiated by cellular adhesion molecules and chemokines, is an early step in vascular injury, we sought to evaluate (a) changes in cellular adhesion molecule levels during the trial; (b) effect of diabetes treatment; and (c) association of markers with HbA1c, hypertension, hypercholesterolemia, nephropathy, and retinopathy. METHODS: Participants (n = 515 of 699) that had baseline assessment of adhesion molecules (monocyte chemoattractant protein-1 [MCP-1], vascular cell adhesion marker [VCAM], intercellular adhesion marker [ICAM], and E-Selectin) and at least one other assessment, measured at month 12, 24, or 36, were included. RESULTS: Over 1 to 3 years, significant increases in MCP-1 and decreases in VCAM (both P < .0001) concentrations were found; however, no significant interactions were identified with treatment group for any molecule. For every 1% increase in HbA1c, ICAM increased by 1.8%, VCAM by 1.5%, and E-selectin by 6.8% (all P < .0001). E-selectin increased by 3.7% and 4.2% for every 10 mm Hg increase in systolic and diastolic blood pressure, respectively (both P < .0001). ICAM was 10.2% higher and E-selectin was 15.5% higher in participants with microalbuminuria (both P < .01). There was no significant association of adhesion molecule levels with retinopathy. CONCLUSION: Concentrations of cellular adhesion molecules rise with increasing HbA1c in youth with T2DM, and are associated with blood pressure and microalbuminuria, markers of vascular injury.

RISK FACTORS FOR HEARING IMPAIRMENT IN TYPE 1 DIABETES.

Objective: Studies have demonstrated that glycated hemoglobin (HbA1c) is a significant predictor of hearing impairment in type 1 diabetes. We identified additional factors associated with hearing impairment in participants with type 1 diabetes from the Diabetes Control and Complications Trial and its observational follow-up, the Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Methods: A total of 1,150 DCCT/EDIC participants were recruited for the Hearing Study. A medical history, physical measurements, and a self-administered hearing questionnaire were obtained. Audiometry was performed by study-certified personnel and assessed centrally. Logistic regression models assessed the association of risk factors and comorbidities with speech- and high-frequency hearing impairment. Results: Mean age was 55 ± 7 years, duration of diabetes 34 ± 5 years, and DCCT/EDIC HbA1c 7.9 ± 0.9% (63 mmol/mol). In multivariable models, higher odds of speech-frequency impairment were significantly associated with older age, higher HbA1c, history of noise exposure, male sex, and higher triglycerides. Higher odds of high-frequency impairment were associated with older age, male sex, history of noise exposure, higher skin intrinsic florescence (SIF) as a marker of tissue glycation, higher HbA1c, nonprofessional/nontechnical occupations, sedentary activity, and lower low-density-lipoprotein cholesterol. Among participants who previously completed computed tomography and carotid ultrasonography, coronary artery calcification (CAC) >0 and carotid intima-medial thickness were significantly associated with high-but not speech-frequency impairment. Conclusion: Consistent with previous reports, male sex, age, several metabolic factors, and noise exposure are independently associated with hearing impairment. The association with SIF further emphasizes the importance of glycemia-as a modifiable risk factor-over time. In addition, the macrovascular contribution of CAC is novel and important. Abbreviations: AER = albumin excretion rate; CAC = coronary artery calcification; CVD = cardiovascular disease; DCCT/EDIC = Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications; eGFR = estimated glomerular filtration rate; ETDRS = Early Treatment Diabetic Retinopathy Study; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; IMT = intima-media thickness; LDL = low-density lipoprotein; NHANES = National Health and Nutrition Examination Survey; OR = odds ratio; SIF = skin intrinsic fluorescence; T1D = type 1 diabetes.

Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC type 1 diabetes cohort.

We examined whether persistence of epigenetic DNA methylation (DNA-me) alterations at specific loci over two different time points in people with diabetes are associated with metabolic memory, the prolonged beneficial effects of intensive vs. conventional therapy during the Diabetes Control and Complications Trial (DCCT) on the progression of microvascular outcomes in the long-term follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We compared DNA-me profiles in genomic DNA of whole blood (WB) isolated at EDIC Study baseline from 32 cases (DCCT conventional therapy group subjects showing retinopathy or albuminuria progression by EDIC Study year 10) vs. 31 controls (DCCT intensive therapy group subjects without complication progression by EDIC year 10). DNA-me was also profiled in blood monocytes (Monos) of the same patients obtained during EDIC Study years 16-17. In WB, 153 loci depicted hypomethylation, and 225 depicted hypermethylation, whereas in Monos, 155 hypomethylated loci and 247 hypermethylated loci were found (fold change ≥1.3; P < 0.005; cases vs. controls). Twelve annotated differentially methylated loci were common in both WB and Monos, including thioredoxin-interacting protein (TXNIP), known to be associated with hyperglycemia and related complications. A set of differentially methylated loci depicted similar trends of associations with prior HbA1c in both WB and Monos. In vitro, high glucose induced similar persistent hypomethylation at TXNIP in cultured THP1 Monos. These results show that DNA-me differences during the DCCT persist at certain loci associated with glycemia for several years during the EDIC Study and support an epigenetic explanation for metabolic memory.

The relationship of blood glucose with cardiovascular disease is mediated over time by traditional risk factors in type 1 diabetes: the DCCT/EDIC study.

AIMS/HYPOTHESIS: Chronic hyperglycaemia, as measured by HbA1c levels, is a major risk factor for atherosclerosis and cardiovascular disease (CVD) in type 1 diabetes. Our aim was to describe the degree to which the effect of HbA1c on the risk of CVD is mediated by its effect on traditional risk factors over time, and how these mediation pathways change over time. METHODS: The DCCT and its observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC), followed 1441 participants for a mean of 27 years, with periodic measurement of HbA1c and risk factors over time. We assessed the proportion of the HbA1c effect on risk of CVD that was mediated through its effects on systolic BP (SBP), pulse rate, triacylglycerols and LDL-cholesterol (LDLc) levels, and how the proportion mediated changed over time. RESULTS: The association of HbA1c with CVD outcomes was stable over time, while that of traditional risk factors (SBP, pulse rate, triacylglycerols and LDLc) increased. At 10 years of follow-up, the effect of HbA1c on 10 year CVD risk was minimally mediated by SBP (2.7%), increasing to 26% at 20 years. Likewise, from 10 year follow-up to 20 year follow-up, the proportion of HbA1c effect mediated through pulse rate increased from 6.3% to 29.3%, through triacylglycerols from 2.2% to 22.4%, and through LDLc from 9.2% to 30.7%. CONCLUSIONS/INTERPRETATION: As participants age, the predictive association of mean HbA1c on subsequent CVD events is increasingly mediated by its effect on standard risk factors. Thus, management of traditional non-glycaemic CVD risk factors may have increasing benefits in an ageing type 1 diabetes population with longstanding hyperglycaemia. TRIAL REGISTRATION: ClinicalTrials.gov NCT00360893 and NCT00360815.

Longitudinal Patterns of Occurrence and Remission of Erectile Dysfunction in Men With Type 1 Diabetes.

BACKGROUND: Men with diabetes are at greater risk of erectile dysfunction (ED). AIM: To describe the natural history of ED in men with type 1 diabetes. METHODS: We examined up to 30 years of prospectively collected annual ED status and demographic and clinical variables from 600 male participants in the Diabetes Control and Complications Trial (DCCT; 1983-1993) and its follow-up study, the Epidemiology of Diabetes Interventions and Complications (1994-present; data in this study are through 2012). OUTCOMES: Yes vs no response to whether the participant had experienced impotence in the past year and whether he had used ED medication. RESULTS: Sixty-one percent of men reported ED at least once during the study. For some men, the initial report of ED was permanent. For others, potency returned and was lost multiple times. Visual display of the data showed four longitudinal ED phenotypes: never (38.7%), isolated (6.7%), intermittent (41.8%), and persistent (12.8%). Men who never reported ED or in only 1 isolated year were younger, had lower body mass index, and better glycemic control than men in the intermittent and persistent groups at DCCT baseline. In a multivariable logistic model comparing men at their first year reporting ED, men who were older had lower odds of remission and men who were in the conventional DCCT treatment group had higher odds of remission. CLINICAL TRANSLATION: If validated in other cohorts, such findings could be used to guide individualized interventions for patients with ED. STRENGTHS AND LIMITATIONS: This is the first examination of ED with repeated measures at an annual resolution, with up to 30 years of responses for each participant. However, the yes vs no response is a limitation because the real phenotype is not binary and the question can be interpreted differently depending on the participant. CONCLUSIONS: Age, glycemic control, and BMI were important longitudinal predictors of ED. We have described a more complex ED phenotype, with variation in remission patterns, which could offer insight into different mechanisms or opportunities for intervention. If validated in other cohorts, such findings could be used to establish more accurate prognostication of outcomes for patients with ED to guide individualized interventions. Palmer MR, Holt SK, Sarma AV, et al. Longitudinal Patterns of Occurrence and Remission of Erectile Dysfunction in Men With Type 1 Diabetes. J Sex Med 2017;14:1187-1194.

Glycemic Control and Urinary Tract Infections in Women with Type 1 Diabetes: Results from the DCCT/EDIC.

PURPOSE: We examined the relationship between glycemic control and urinary tract infections in women with type 1 diabetes mellitus. MATERIALS AND METHODS: Women enrolled in the Epidemiology of Diabetes Interventions and Complications study, the observational followup of the Diabetes Control and Complications Trial, were surveyed to assess the rate of physician diagnosed urinary tract infections in the preceding 12 months. The relationship between glycated hemoglobin levels and number of urinary tract infections in the previous 12 months was assessed using a multivariable Poisson regression model. RESULTS: A total of 572 women were evaluated at year 17. Mean age was 50.7 ± 7.2 years, mean body mass index was 28.6 ± 5.9 kg/m(2), mean type 1 diabetes duration was 29.8 ± 5.0 years and mean glycated hemoglobin was 8.0% ± 0.9%. Of these women 86 (15.0%) reported at least 1 physician diagnosed urinary tract infection during the last 12 months. Higher glycated hemoglobin levels were significantly associated with number of urinary tract infections such that for every unit increase (1%) in recent glycated hemoglobin level, there was a 21% (p=0.02) increase in urinary tract infection frequency in the previous 12 months after adjusting for race, hysterectomy status, urinary incontinence, sexual activity in the last 12 months, peripheral and autonomic neuropathy, and nephropathy. CONCLUSIONS: The frequency of urinary tract infections increases with poor glycemic control in women with type 1 diabetes. This relationship is independent of other well described predictors of urinary tract infections and suggests that factors directly related to glycemic control may influence the risk of lower urinary tract infections.

Testosterone and cardiac mass and function in men with type 1 diabetes in the Epidemiology of Diabetes Interventions and Complications Study (EDIC).

OBJECTIVE: Low testosterone concentrations have been reported to be associated with increased risk of congestive heart failure, but the mechanisms are unclear. Our objective was to examine the relationship between endogenous testosterone and measures of cardiac mass and function among men with type 1 diabetes. DESIGN: Secondary analysis of a prospective observational study. PARTICIPANTS: Men (n = 508) in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow-up of the Diabetes Control and Complications Trial (DCCT). MEASUREMENTS: Testosterone assessed by liquid chromatography mass spectrometry at EDIC year 10 and cardiac magnetic resonance imaging (CMR) measures at EDIC years 14/15. Linear regression models were used to assess the relationship between testosterone, sex hormone binding globulin (SHBG) and left ventricular (LV) mass, volume, ejection fraction and cardiac index before and after adjustment for age, randomization arm, alcohol and cigarette use, macroalbuminuria, haemoglobin A1c, insulin dose, body mass index, lipids, blood pressure, use of antihypertensive medications and microvascular complications. RESULTS: In fully adjusted models, total testosterone concentrations were significantly associated with LV mass (P = 0·014), end-diastolic volume (P = 0·002), end-systolic volume (P = 0·012) and stroke volume (P = 0·022), but not measures of LV function after adjustment for cardiac risk factors. Bioavailable testosterone was associated with LV mass, but not volume or function, while SHBG was associated with volume, but not mass or function. CONCLUSIONS: Among men with type 1 diabetes, higher total testosterone was associated with higher LV mass and volume, but not with function. The clinical significance of this association remains to be established.

Urogenital Autonomic Dysfunction in Diabetes.

This review details the epidemiology, possible mechanisms, and risk factors associated with urogenital autonomic dysfunction in diabetes. Autonomic neuropathy in diabetes is associated with various urological complications including bladder and sexual dysfunction. Several studies have reported the high prevalence of bladder and sexual dysfunction in both men and women. The DCCT/EDIC UroEDIC study examined the association between cardiovascular autonomic neuropathy and bladder and sexual dysfunction in a large cohort of participants with type 1 diabetes and was the first to report significant associations. Future studies are needed to further evaluate the association of urogenital complications and autonomic dysfunction in diabetes.

Cardiovascular autonomic neuropathy, erectile dysfunction and lower urinary tract symptoms in men with type 1 diabetes: findings from the DCCT/EDIC.

PURPOSE: We evaluated the association between cardiovascular autonomic neuropathy, and erectile dysfunction and lower urinary tract symptoms in men with type 1 diabetes. MATERIALS AND METHODS: Male type 1 diabetes participants (635) in the DCCT/EDIC were studied. Cardiovascular autonomic neuropathy was assessed by standardized cardiovascular reflex tests including changes in respiratory rate variation with deep breathing, Valsalva maneuver (Valsalva ratio) and changes in supine to standing diastolic blood pressure. Erectile dysfunction was assessed by a proxy item from the International Index of Erectile Function, and lower urinary tract symptoms were assessed with the AUASI (American Urological Association Symptom Index). Multivariable logistic regression models estimated the association between cardiovascular autonomic neuropathy and erectile dysfunction and/or lower urinary tract symptoms, adjusting for time weighted glycemic control, blood pressure, age and other covariates. RESULTS: Men in whom erectile dysfunction and/or lower urinary tract symptoms developed during EDIC had a significantly lower respiratory rate variation and Valsalva ratio at DCCT closeout and EDIC year 16/17 compared to those without erectile dysfunction or lower urinary tract symptoms. In adjusted analysis, participants with cardiovascular autonomic neuropathy had 2.65 greater odds of erectile dysfunction and lower urinary tract symptoms (95% CI 1.47-4.79). CONCLUSIONS: These data suggest that cardiovascular autonomic neuropathy predicts the development of urological complications in men with long-standing type 1 diabetes. Studies evaluating the mechanisms contributing to these interactions are warranted for targeting effective prevention or treatment.

Poor glycemic control is associated with reduced prostate specific antigen concentrations in men with type 1 diabetes.

PURPOSE: Previous studies have revealed lower prostate specific antigen concentrations in men with type 2 diabetes, paralleling the reported lower prevalence of prostate cancer in diabetic men. Data are lacking on prostate specific antigen in men with type 1 diabetes whose insulin and obesity profiles differ from those with type 2 diabetes mellitus. In this study we examined the relationship between long-term glycemic control and prostate specific antigen in men with type 1 diabetes mellitus. MATERIALS AND METHODS: Total prostate specific antigen was measured at one time in 639 men in the EDIC, the observational followup of participants in the DCCT. The relationship between DCCT/EDIC weighted mean hemoglobin A1c and log prostate specific antigen was assessed using linear regression modeling after adjusting for age, body mass index, total testosterone, statin and thiazide medication use, diabetes duration, and DCCT randomization arm and cohort. RESULTS: Median subject age was 52 years, body mass index was 28.4 kg/m(2) and DCCT/EDIC time-weighted hemoglobin A1c was 7.9%. Median prostate specific antigen was 0.64 ng/ml (IQR 0.43, 1.05). Prostate specific antigen increased significantly with age (p <0.0001) and with lower time-weighted hemoglobin A1c (p <0.0001). Each 10% increase in hemoglobin A1c was accompanied by an 11% reduction in prostate specific antigen (p=0.0001). CONCLUSIONS: Prostate specific antigen decreases as hemoglobin A1c increases in men with type 1 diabetes mellitus. This relationship is independent of age, body mass index, androgen levels, medication use and measures of diabetes severity, which suggests that factors related to glycemia may directly affect prostate specific antigen levels.

Testosterone Concentrations and Cardiovascular Autonomic Neuropathy in Men with Type 1 Diabetes in the Epidemiology of Diabetes Interventions and Complications Study (EDIC).

INTRODUCTION: Previous studies have reported that lower testosterone concentrations are associated with cardiovascular autonomic neuropathy (CAN), a risk factor for cardiovascular events. However, no studies have examined this relationship in men with type 1 diabetes, who are at high risk for CAN. AIM: The aim of this study was to examine the associations between testosterone concentrations and measures of CAN in a large, well-characterized cohort of men with type 1 diabetes. METHODS: We conducted an analysis of men in the Diabetes Control and Complications Trial (DCCT), a randomized trial of intensive glucose control, and its observational follow-up the Epidemiology of Diabetes Intervention and Complications (EDIC) Study. Testosterone was measured by liquid chromatography mass spectrometry in stored samples from EDIC follow-up years 10 and 17. Regression models were used to assess the cross-sectional relationships between testosterone and CAN measures. MAIN OUTCOME MEASURES: The main CAN measure from EDIC follow-up year 17 was a standardized composite of R-R variation with paced breathing < 15, or R-R variation 15-20 combined with either a Valsalva ratio ≤ 1.5 or a decrease in diastolic blood pressure > 10 mm Hg upon standing. Continuous R-R variation and Valsalva ratio were secondary outcomes. RESULTS: Lower total and bioavailable testosterone concentrations at follow-up years 10 and 17 were not associated with the presence of CAN at year 17. In analyses using Valsalva ratio as a continuous measure, higher total (P = 0.01) and bioavailable testosterone concentrations (P = 0.005) were associated with a higher (more favorable) Valsalva ratio after adjustment for covariates including age, body mass index, smoking status, hypertension, and glycemia. CONCLUSIONS: Testosterone levels are not associated with CAN among men with type 1 diabetes. Although testosterone is associated with a higher Valsalva ratio, a more favorable indicator, the clinical significance of this association is not known.

Conventional Versus Video Laryngoscopy for Tracheal Tube Exchange: Glottic Visualization, Success Rates, Complications, and Rescue Alternatives in the High-Risk Difficult Airway Patient.

BACKGROUND: Tracheal tube exchange is a simple concept but not a simple procedure because hypoxemia, esophageal intubation, and loss of airway may occur with life-threatening ramifications. Combining laryngoscopy with an airway exchange catheter (AEC) may lessen the exchange risk. Laryngoscopy is useful for a pre-exchange examination and to open a pathway for endotracheal tube (ETT) passage. Direct laryngoscopy (DL) is hampered by a restricted "line of sight"; thus, airway assessment and exchange may proceed blindly and contribute to difficulty and complications. We hypothesized that video laryngoscopy (VL), when compared with DL, will improve glottic viewing for airway assessment, and the VL-AEC method of ETT exchange will result in a reduction in airway and hemodynamic complications in high-risk patients when compared with a historical group of patients who underwent DL + AEC-assisted exchange. METHODS: Critically ill patients requiring an ETT exchange underwent DL-assisted pre-exchange airway assessment. If the DL-assisted pre-exchange assessment rendered a "poor view," these patients underwent a VL-based airway assessment followed by a VL-assisted ETT exchange procedure. The DL and VL pre-exchange assessments were compared. The attempts, complications, and rescue devices required for ETT exchange were analyzed. These exchange results were then compared with a historical control group of patients who (1) were classified as a poor view on DL-assisted pre-exchange airway assessment; and (2) underwent a DL + AEC-assisted exchange. The airway assessment and ETT exchange were performed by a board-certified anesthesiologist from the Department of Anesthesiology alone or with anesthesia resident assistance. RESULTS: Three hundred twenty-eight patients with a poor view on initial DL examination underwent a subsequent VL with comparison of views with the 337 patients in the historical control group (DL + AEC). A majority (88%) had a "full or near-full view" on VL examination. The first-pass success rate for ETT exchange was greater in the VL group (91.5% vs 67.7% with DL; P = 0.0001) and the number of patients requiring 3+ attempts was lower (1.2% vs 6.8% with DL; P = 0.0003). A commensurate difference in the incidence of mild and severe hypoxemia, esophageal intubation, bradycardia, and the need for rescue airway device intervention was also observed with VL exchange procedures when compared with the historical DL + AEC group. CONCLUSIONS: These findings support the hypothesis that VL may result in better glottic viewing for airway assessment and may permit the ETT exchange procedure to be performed with fewer airway and hemodynamic complications. Execution of the ETT exchange over an AEC was augmented by improved glottic visualization to allow more efficient and timely ETT passage. Multiple attempts to resecure the airway increased the number of exchange complications. VL + AEC exchange led to fewer attempts and is consistent with the recommendation of the American Society of Anesthesiologists Difficult Airway Task Force to limit laryngoscopic attempts and, as a consequence, decrease complications. A VL-based pre-exchange airway assessment may be a valuable procedure for both planning the exchange and uncovering unrecognized airway maladies, for example, partial or complete self-extubation.

GWAS identifies an NAT2 acetylator status tag single nucleotide polymorphism to be a major locus for skin fluorescence.

AIMS/HYPOTHESIS: Skin fluorescence (SF) is a non-invasive marker of AGEs and is associated with the long-term complications of diabetes. SF increases with age and is also greater among individuals with diabetes. A familial correlation of SF suggests that genetics may play a role. We therefore performed parallel genome-wide association studies of SF in two cohorts. METHODS: Cohort 1 included 1,082 participants, 35-67 years of age with type 1 diabetes. Cohort 2 included 8,721 participants without diabetes, aged 18-90 years. RESULTS: rs1495741 was significantly associated with SF in Cohort 1 (p < 6 × 10(-10)), which is known to tag the NAT2 acetylator phenotype. The fast acetylator genotype was associated with lower SF, explaining up to 15% of the variance. In Cohort 2, the top signal associated with SF (p = 8.3 × 10(-42)) was rs4921914, also in NAT2, 440 bases upstream of rs1495741 (linkage disequilibrium r (2) = 1.0 for rs4921914 with rs1495741). We replicated these results in two additional cohorts, one with and one without type 1 diabetes. Finally, to understand which compounds are contributing to the NAT2-SF signal, we examined 11 compounds assayed from skin biopsies (n = 198): the fast acetylator genotype was associated with lower levels of the AGEs hydroimidazolones of glyoxal (p = 0.017). CONCLUSIONS/INTERPRETATION: We identified a robust association between NAT2 and SF in people with and without diabetes. Our findings provide proof of principle that genetic variation contributes to interindividual SF and that NAT2 acetylation status plays a major role.