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The inflammatory potential of diet, assessed by Empirical Dietary Inflammatory Pattern (EDIP), may play a crucial role in the development of metabolic syndrome (MetS). However, limited research on this relationship is available. We hypothesized that EDIP is positively associated with MetS and its components. This longitudinal study included 1,177 participants (526 with type 1 diabetes mellitus (T1DM) and 651 without) from the Coronary Artery Calcification in Type 1 Diabetes study. Dietary assessment and anthropometric and biochemical measurements were assessed at baseline and 14-year follow-up. MetS status was defined using the Harmonization criteria. EDIP scores were computed based on a food frequency questionnaire. Generalized linear mixed models were applied and subgroup analyses were performed by diabetes status. Mean age of study participants was 38 years and 48% were male at baseline. EDIP was positively associated with MetS (β(T3 versus T1)=0.81, p

In type 2 diabetes, hyperuricemia is associated with cardiovascular disease (CVD) and the metabolic syndrome (MetS), but associations in type 1 diabetes (T1D) have not been well-defined. This study examined the relationships between serum urate (SU) concentrations, clinical and biochemical factors, and subsequent cardiovascular events in a well-characterized cohort of adults with T1D. In 973 participants with T1D in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC), associations were defined between SU, measured once in blood collected 1997–2000, and (a) concurrent MetS and (b) incident ‘any CVD’ and major adverse cardiovascular events (MACE) through 2013. SU was higher in men than women [mean (SD): 4.47 (0.99) vs. 3.39 (0.97) mg/dl, respectively, p Trial registration clinicaltrials.gov NCT00360815 and NCT00360893.

To examine the associations of dietary patterns and nutrients with coronary artery calcification (CAC) and pericardial adiposity (PAT) in adults with and without type 1 diabetes. We conducted a six-year longitudinal analysis of data from Coronary Artery Calcification in Type 1 Diabetes study [n = 1255; T1D: n = 563; non-DM: n = 692] collected at baseline, year 3 and year 6. Participants completed a validated food frequency questionnaire, a physical examination, and fasting (12 h overnight fast) biochemical analyses. CAC and PAT were measured using electron beam computed tomography. Dietary patterns were identified using factor analysis. Generalized estimating equations were used to examine associations of dietary patterns and nutrients with CAC and PAT in models adjusted for traditional cardiovascular risks. The ‘starchy veggies, meats and alcohol pattern’ was associated with significantly increased risk of CAC presence in all adjusted models; an increasing trend was observed with CAC progression. Increasing intake of dietary proteins and total fats were also associated with higher risk of the presence and/or progression of CAC in adjusted models (all p

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder with progressive systemic deposition of globotriaosylceramide, leading to life-threatening cardiac, central nervous system, and kidney disease. Current therapy involves symptomatic medical management, enzyme replacement therapy (ERT), dialysis, kidney transplantation, and, more recently, gene therapy. The aim of this systematic review was to assess outcomes of kidney transplantation among patients with FD. Methods: A comprehensive literature review was conducted utilizing MEDLINE, EMBASE, and Cochrane Database, from inception through to 28 February 2020, to identify studies that evaluate outcomes of kidney transplantation including patient and allograft survival among kidney transplant patients with FD. Effect estimates from each study were extracted and combined using the random-effects generic inverse variance method of DerSimonian and Laird. Results: In total, 11 studies, including 424 kidney transplant recipients with FD, were enrolled. The post-transplant median follow-up time ranged from 3 to 11.5 years. Overall, the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 32.5% (95%CI: 23.9%–42.5%), 14.5% (95%CI: 8.4%–23.7%), and 20.2% (95%CI: 15.4%–25.9%), respectively. In the sensitivity analysis, limited only to the recent studies (year 2001 or newer when ERT became available), the pooled estimated rates of all-cause graft failure, graft failure before death, and allograft rejection were 28.1% (95%CI: 20.5%–37.3%), 11.7% (95%CI: 8.4%–16.0%), and 20.2% (95%CI: 15.5%–26.0%), respectively. The pooled estimated rate of biopsy proven FD recurrence was 11.1% (95%CI: 3.6%–29.4%), respectively. There are no significant differences in the risks of all-cause graft failure (p = 0.10) or mortality (0.48) among recipients with vs. without FD. Conclusions: Despite possible FD recurrence after transplantation of 11.1%, allograft and patient survival are comparable among kidney transplant recipients with vs. without FD.

Dietary intakes play an important role in the development of metabolic complications during pregnancy. While reported observational studies reveal an inverse association of healthy diets with weight gain, gestational diabetes, and hypertensive complications during pregnancy, there is a paucity of studies conducted among women of specific ethnicities vulnerable to higher risks of pregnancy complications. This is a secondary cross sectional analysis using baseline data from a previously reported clinical trial. We aim to identify associations of maternal habitual dietary intakes with cardiometabolic risks and inflammatory profiles in primarily African American (AA) and Hispanic women in the first half of pregnancy. Fifty-two women met the study criteria and anthropometric, clinical, and dietary data were obtained at baseline. Linear regression analysis was used to determine associations after covariate adjustments. Among the maternal dietary nutrient intakes, total fats were positively associated with maternal body weight, BMI, and serum CRP (β ± SE: 0.25 ± 0.13, 0.28 ± 0.18, and 0.29 ± 0.14, respectively, all p &lt, 0.05), and saturated fats were positively associated with glycated hemoglobin (0.32 ± 0.12). Dietary fiber intake showed a consistent inverse association with body weight (−0.26 ± 0.13), BMI (−0.19 ± 0.15), glycated hemoglobin (−0.22 ± 0.16), as well as serum CRP (−0.19 ± 0.14). Among the maternal food group intakes, dairy intake was inversely associated with systolic blood pressure (−0.18 ± 0.15) and serum IL-6 (−0.22 ± 0.17), and vegetable intake showed an inverse association with serum CRP (−0.17 ± 0.12) all in adjusted analyses (all p &lt, 0.05). Thus, maternal diet modifications, especially decreasing fats and increasing fiber and dairy may help address obesity and inflammation leading to pregnancy complications in AA and Hispanic women.

Pregnancies affected by obesity are at high risk for developing metabolic complications with oxidative stress and adipocyte dysfunction contributing to the underlying pathologies. Few studies have examined the role of dietary interventions, especially those involving antioxidants including polyphenolic flavonoids found in fruits and vegetables on these pathologies in high-risk pregnant women. We conducted an 18 gestation-week randomized controlled trial to examine the effects of a dietary intervention comprising of whole blueberries and soluble fiber vs. control (standard prenatal care) on biomarkers of oxidative stress/antioxidant status and adipocyte and hormonal functions in pregnant women with obesity (n = 34). Serum samples were collected at baseline (&lt, 20 gestation weeks) and at the end of the study period (32–26 gestation weeks). Study findings showed maternal serum glutathione and antioxidant capacity to be significantly increased, and malondialdehyde to be decreased in the dietary intervention vs. control group (all p &lt, 0.05). Among the adipokine biomarkers, serum plasminogen activator inhibitor-1 and visfatin, as biomarkers of adipocyte dysfunction and insulin resistance, were also decreased following dietary intervention (all p &lt, 0.05). These findings support the need for supplementing maternal diets with berries and fiber to improve oxidative stress and risks of metabolic complications during pregnancy.

OBJECTIVES: Dietary berries, such as strawberries are rich in bioactive compounds and have been shown to lower cardiometabolic risks. We examined the dose-response effects of two dietary achievable doses of strawberries on glycemic control and lipid profiles in adults. METHODS: In this 14-week randomized controlled crossover study, adults with obesity and elevated serum LDL-cholesterol were assigned to one of the three arms for four weeks separated by a one-week washout period: control powder, one serving strawberries (low dose: 13 g powder/day), and 2.5 servings strawberries (high dose: 32 g powder/day). Participants were instructed to follow their usual diet and lifestyle while refraining from consuming other berries and related products throughout the study. Blood samples and anthropometric measures were collected at baseline and at the end of each four-week phase of intervention. RESULTS: Thirty-three participants completed all three phases of the trial [(mean ± SD): Age: 53 ± 13 y; BMI: 33 ± 3.0 kg/m(2)). Outcome measures were analyzed using a mixed model analysis of variance with statistical significance set at P

Background: People with type 1 diabetes (T1D) have a greater risk of developing cardiovascular diseases than people without diabetes. Inflammation plays a key role in atherosclerosis and diet has been known to modify inflammation. However, little is known about this association in T1D. Methods: We conducted a six-year longitudinal analysis of data from Coronary Artery Calcification in Type 1 Diabetes study [n=1255; T1D: n=563; non-DM: n=692] collected at baseline, year 3 and year 6. Participants completed a validated food frequency questionnaire, a physical examination, and fasting (12h overnight fast) biochemical analyses. Biomarkers of inflammation and atherosclerosis [C-reactive protein (CRP), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), homocysteine (hcy) and adiponectin] were determined in serum samples at three time points. Dietary patterns were identified using factor analysis. Generalized estimating equations were used to examine associations of dietary patterns with inflammation in models adjusted for traditional cardiovascular risks. Results: In a multivariate model, increasing intake of carbohydrates and total fats were positively associated with CRP [β (95% CI): 0.013 (0.003, 0.023) and 0.025 (0.011, 0.039), respectively) and fibrinogen (0.007 (0.005, 0.010) and 0.010 (0.006, 0.014), respectively) when adjusted for age, sex, time, total calories, and diabetes status. Dietary fiber revealed an inverse association with CRP [-0.014 (-0.021, -0.007)], PAI-1 [-0.009 (-0.015, -0.003)], and hcy [-0.002 (-0.005, 0.000)], and a positive association with adiponectin [0.005 (0.000, 0.009)]. A dietary pattern characterized by ‘veggies, meats and alcohol’ was positively associated with adiponectin [0.022 (0.001, 0.043)]. Conclusions: Dietary carbohydrates and total fats were associated with biomarkers of inflammation and atherosclerosis, while fiber revealed protective associations in adults with and without T1D. Disclosure A. Basu: None. L. Chien: None. A. C. Alman: None. J. K. Snell-bergeon: Stock/Shareholder; Self; GlaxoSmithKline plc. Funding National Institutes of Health (R01HL61753)

Background: Limited access to adequate, affordable, and nutritious foods can drive adverse outcomes in patients with diabetes mellitus (DM). Understanding factors that impact food insecurity is vital in developing strategies to improve holistic health outcomes among patients with DM. Method: Seventy-one ambulatory patients with type 2 DM were recruited using an investigator-administered questionnaire and chart review. Variables on demographics, oral health, DM outcomes, and accessibility to healthy food were collected. Their oral health was inspected. Data were analyzed using multiple logistic regression. Results: Among study participants, 60.6% were female, 63.4% were non-white, mean age: 64.10±10.3 years, mean duration of diabetes: 15.80 ±9.1 years, and mean HbA1c: 7.80 ±1.5%. Vascular complications were present among 66.2% of participants. The logistic regression model was statistically significant (p < 0.0001) and explained 44.5% of food insecurity variance. Significant predictors of food insecurity include having less than high school education (OR 12.6, p = 0.04), living below the federal poverty threshold (OR 4.3, p = 0.04), and younger age (OR 0.91, p = 0.01). Race/ethnicity, gender, oral health indicators, and DM complications did not significantly predict food insecurity. Conclusions: In our study sample, younger patients with less than high school education and living below the federal poverty threshold were at higher risk of food insecurity. These findings underscore the need for targeted interventions among this high-risk group to reduce food insecurity and improve DM outcomes. Disclosure A. Alver: None. K. Izuora: None. A. Basu: None. A. Capurro: None. C. L. Gewelber: None. K. Baca: None. S. J. Williams: None. J. L. Ebersole: None. K. Batra: None. A. M. Patel: None.

The older adult population (65 years or older) with advanced or end-stage kidney disease is steadily growing, but rates of transplantation within this cohort have not increased in a similar fashion. Physical deconditioning, resulting in poor post-transplantation outcomes, is a primary concern among older renal patients. The assessment of physical function often holds more weight in the selection process for older candidates, despite evidence showing benefits of transplantation to this vulnerable population. Although several frailty assessment tools are being used increasingly to assess functional status, there is no standardized selection process for older candidates based on these assessment results. Also, it is unknown if timely targeted physical therapy interventions in older patients result in significant improvement of functioning capacity, translating to higher listing and transplantation rates, and improved post-transplantation outcomes. It is therefore of upmost importance not only to incorporate an effective objective functional status assessment process into selection and waitlist evaluation protocols, but also to have targeted interventions in place to maintain and improve physical conditioning among older renal patients. This paper reviews the commonly utilized assessment tools, and their applicability to older patients with renal disease. We also propose the need for definitive selection and waitlist management guidelines to formulate a streamlined assessment of functional capacity and transplant eligibility, as well as a process to maintain functional status, thereby increasing the access of older patients to renal transplantation. Keywords: elderly, physical assessment, transplant, transplant candidacy

Dietary berries are a rich source of several nutrients and phytochemicals and in recent years, accumulating evidence suggests they can reduce risks of several chronic diseases, including type 2 diabetes (T2D). The objective of this review is to summarize and discuss the role of dietary berries (taken as fresh, frozen, or other processed forms) on insulin resistance and biomarkers of T2D in human feeding studies. Reported feeding trials involve different berries taken in different forms, and consequently differences in nutritional or polyphenol composition must be considered in their interpretation. Commonly consumed berries, especially cranberries, blueberries, raspberries and strawberries, ameliorate postprandial hyperglycemia and hyperinsulinemia in overweight or obese adults with insulin resistance, and in adults with the metabolic syndrome (MetS). In non-acute long-term studies, these berries either alone, or in combination with other functional foods or dietary interventions, can improve glycemic and lipid profiles, blood pressure and surrogate markers of atherosclerosis. Studies specifically in people with T2D are few, and more knowledge is needed. Nevertheless, existing evidence, although sparse, suggests that berries have an emerging role in dietary strategies for the prevention of diabetes and its complications in adults. Despite the beneficial effects of berries on diabetes prevention and management, they must be consumed as part of a healthy and balanced diet.

Background and aims: Dietary berries, such as strawberries, are rich in bioactive compounds and have been shown to lower cardiometabolic risk. We examined the effects of two dietary achievable doses of strawberries on glycemic control and lipid profiles in obese adults with elevated serum LDL cholesterol (LDL-C). Methods: In this 14-week randomized controlled crossover study, participants were assigned to one of the three arms for four weeks separated by a one-week washout period: control powder, one serving (low dose: 13 g strawberry powder/day), or two-and-a -half servings (high dose: 32 g strawberry powder/day). Participants were instructed to follow their usual diet and lifestyle while refraining from consuming other berries and related products throughout the study interval. Blood samples, anthropometric measures, blood pressure, and dietary and physical activity data were collected at baseline and at the end of each four-week phase of intervention. Results: In total, 33 participants completed all three phases of the trial [(mean ± SD): Age: 53 ± 13 y, BMI: 33 ± 3.0 kg/m2). Findings revealed significant reductions in fasting insulin (p = 0.0002) and homeostatic model of assessment of insulin resistance (p = 0.0003) following the high dose strawberry phase when compared to the low dose strawberry and control phases. Glucose and conventional lipid profiles did not differ among the phases. Nuclear magnetic resonance-determined particle concentrations of total VLDL and chylomicrons, small VLDL, and total and small LDL were significantly decreased after the high dose strawberry phase, compared to control and low dose phases (all p &lt, 0.0001). Among the biomarkers of inflammation and adipokines measured, only serum PAI-1 showed a decrease after the high dose strawberry phase (p = 0.002). Conclusions: These data suggest that consuming strawberries at two-and-a-half servings for four weeks significantly improves insulin resistance, lipid particle profiles, and serum PAI-1 in obese adults with elevated serum LDL-C.

Lesion or disease of the somatosensory system leads to the development of neuropathic pain. Peripheral neuropathic pain encompasses damage or injury of the peripheral nervous system. On the other hand, 10–15% of individuals suffer from acute postoperative pain followed by persistent pain after undergoing surgeries. Antidepressants, anticonvulsants, baclofen, and clonidine are used to treat peripheral neuropathy, whereas opioids are used to treat postoperative pain. The negative effects associated with these drugs emphasize the search for alternative therapeutics with better efficacy and fewer side effects. Curcumin, a polyphenol isolated from the roots of Curcuma longa, possesses antibacterial, antioxidant, and anti-inflammatory properties. Furthermore, the low bioavailability and fast metabolism of curcumin have led to the advent of various curcumin formulations. The present review provides a comprehensive analysis on the effects of curcumin and its formulations in preclinical and clinical studies of neuropathic and postoperative pain. Based on the positive outcomes from both preclinical and clinical studies, curcumin holds the promise of mitigating or preventing neuropathic and postoperative pain conditions. However, more clinical studies with improved curcumin formulations are required to involve its use as adjuvant to neuropathic and postoperative drugs.

Background: Diet has been associated with poor glycemic control in diabetes. Few studies have examined this association in people with type 1 diabetes (T1D), who are at a higher risk for cardiovascular disease than people without diabetes. Methods: We report data from cross-sectional and longitudinal analyses from a coronary artery calcification in type 1 diabetes (CACTI) study (n = 1257, T1D: n = 568, non-diabetic controls: n = 689) collected between the years 2000 and 2002. Participants completed a validated food frequency questionnaire, a physical examination, and biochemical analyses. Dietary patterns based on variations in food group intake were created with principal components analysis. Linear regression was used to examine the associations of dietary patterns, macronutrients, and food groups with HbA1c in a model adjusted for relevant covariates and stratified by diabetes status. Results: Three dietary patterns were identified: “fruits, veggies, meats, cereal”, “baked desserts” and “convenience foods and alcohol” patterns. At baseline, a higher intake of the “baked dessert” pattern was significantly associated with higher HbA1c in T1D at baseline as well at year 6 of the study when adjusted for age, sex, BMI, total calories, and diabetes duration. No such associations were observed in the case of non-diabetic controls. Dietary saturated fats and animal fats were also positively associated with HbA1c in adults with T1D at baseline and/or at year 6. Conclusions: The habitual intake of a dietary pattern that is characterized by an increased intake of added sugar and saturated fats, such as in baked desserts, may increase risks of poor glycemic control in T1D.

Background: C3 glomerulopathy (C3G), a rare glomerular disease mediated by alternative complement pathway dysregulation, is associated with a high rate of recurrence and graft loss after kidney transplantation (KTx). We aimed to assess the efficacy of different treatments for C3G recurrence after KTx. Methods: Databases (MEDLINE, EMBASE, and Cochrane Database) were searched from inception through 3 May, 2019. Studies were included that reported outcomes of adult KTx recipients with C3G. Effect estimates from individual studies were combined using the random-effects, generic inverse variance method of DerSimonian and Laird., The protocol for this meta-analysis is registered with PROSPERO (no. CRD42019125718). Results: Twelve studies (7 cohort studies and 5 case series) consisting of 122 KTx patients with C3G (73 C3 glomerulonephritis (C3GN) and 49 dense deposit disease (DDD)) were included. The pooled estimated rates of allograft loss among KTx patients with C3G were 33% (95% CI: 12&ndash, 57%) after eculizumab, 42% (95% CI: 2&ndash, 89%) after therapeutic plasma exchange (TPE), and 81% (95% CI: 50&ndash, 100%) after rituximab. Subgroup analysis based on type of C3G was performed. Pooled estimated rates of allograft loss in C3GN KTx patients were 22% (95% CI: 5&ndash, 46%) after eculizumab, 56% (95% CI: 6&ndash, 100%) after TPE, and 70% (95% CI: 24&ndash, 100%) after rituximab. Pooled estimated rates of allograft loss in DDD KTx patients were 53% (95% CI: 0&ndash, 100%) after eculizumab. Data on allograft loss in DDD after TPE (1 case series, 0/2 (0%) allograft loss at 6 months) and rituximab (1 cohort, 3/3 (100%) allograft loss) were limited. Among 66 patients (38 C3GN, 28 DDD) who received no treatment (due to stable allograft function at presentation and/or clinical judgment of physicians), pooled estimated rates of allograft loss were 32% (95% CI: 7&ndash, 64%) and 53% (95% CI: 28&ndash, 77%) for C3GN and DDD, respectively. Among treated C3G patients, data on soluble membrane attack complex of complement (sMAC) were limited to patients treated with eculizumab (N = 7). 80% of patients with elevated sMAC before eculizumab responded to treatment. In addition, all patients who responded to eculizumab had normal sMAC levels after post-eculizumab. Conclusions: Our study suggests that the lowest incidence of allograft loss (33%) among KTX patients with C3G are those treated with eculizumab. Among those who received no treatment for C3G due to stable allograft function, there is a high incidence of allograft loss of 32% in C3GN and 53% in DDD. sMAC level may help to select good responders to eculizumab.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy that adversely affects maternal and offspring health. Maternal obesity, oxidative stress, and inflammation have been implicated in GDM. In non-pregnant adults, intakes of dietary bioactive compounds inversely associate with insulin resistance and inflammation. However, associations of dietary bioactive compounds with biomarkers of adiposity, antioxidant vitamin and mineral status, oxidative stress, and inflammation in GDM have not been fully elucidated. We addressed this gap by conducting a semi-quantitative review of observational studies and randomized controlled trials published between 2010 and 2020 and retrieved from Google Scholar, Medline, and PubMed. Our analysis revealed that women with GDM are more likely to consume a pro-inflammatory diet before pregnancy and tend to consume fewer antioxidant vitamins and minerals during pregnancy than healthy pregnant women. Women with GDM also have lower blood levels of vitamins A, C, and D and certain adipokines. Several dietary bioactive compounds were noted to improve antioxidant status and biomarkers of inflammation. The Dietary Approaches to Stop Hypertension (DASH) diet and soybean oligosaccharides increased antioxidant enzyme levels. Supplementing n-3 fatty acids, probiotics, synbiotics, and trace elements increased antioxidant enzymes and reduced hs-CRP and MDA. Improvements in inflammation by vitamin D may be contingent upon co-supplementation with other dietary bioactive compounds.

BACKGROUND Gestational diabetes mellitus (GDM) is a growing public health concern and maternal obesity and poor dietary intakes could be implicated. Dietary polyphenols and fiber mitigate the risk of diabetes and its complications, but little is known about their efficacy in preventing GDM. OBJECTIVES We examined the effects of whole blueberry and soluble fiber supplementation on primary outcomes of cardiometabolic profiles in women at high risk of developing GDM. METHODS Women (n = 34; mean ± SD age: 27 ± 5 y; BMI: 35.5 ± 4.0 kg/m2; previous history of GDM ∼56%; Hispanic ∼79%) were recruited in early pregnancy (

Dyslipidemia and inflammation exacerbate postprandial metabolic stress in people with diabetes. Acute dietary supplementation with polyphenols shows promise in improving postprandial metabolic stress in type 2 diabetes (T2D). Cocoa is a rich source of dietary polyphenols with demonstrated cardioprotective effects in adults without diabetes. To date, the acute effects of cocoa on postprandial lipids and inflammation have received little attention in the presence of T2D. This report expands on our earlier observation that polyphenol-rich cocoa, given as a beverage with a fast-food-style, high-fat breakfast, increased postprandial high-density lipoprotein-cholesterol (HDL-C) in adults with T2D. We now test whether polyphenol-rich cocoa modulated postprandial apolipoproteins (Apo-A1, B), non-esterified fatty acids, nuclear magnetic resonance (NMR)-derived lipoprotein subclass profiles, and select biomarkers of inflammation following the same dietary challenge. We found that cocoa decreased NMR-derived concentrations of total very low-density lipoprotein and chylomicron particles and increased the concentration of total HDL particles over the 6-hour postprandial phase. Serum interleukin-18 was decreased by cocoa vs. placebo. Thus, polyphenol-rich cocoa may alleviate postprandial dyslipidemia and inflammation following a high-fat dietary challenge in adults with T2D. The study was registered at clinicaltrials.gov as NCT01886989.

Background: Among the modifiable risk factors, diet plays an important role in the risks and progression of poor glycemic control in diabetes. However, few studies have examined this association in people who have type 1 diabetes (T1D), who are at a greater risk of developing cardiovascular diseases than people without diabetes. Methods: We conducted cross-sectional and longitudinal analyses of data from CACTI study [n=1257; T1D: n=568; nondiabetic controls: n=689] collected between March 2000 and April 2002. Participants completed a validated food frequency questionnaire, a physical examination and fasting biochemical analyses (12h fast). At baseline, dietary patterns based on variations in food group intake were created with principal components analysis (PCA). Linear regression was used to examine associations of dietary patterns with HbA1c in a model adjusted for age and sex and stratified by diabetes status. Results: Three dietary patterns were identified using PCA as follows: ’fruits, veggies, meats, cereal’, ’baked desserts’ and ’convenience foods and alcohol’ patterns. At baseline, higher intake of ’baked dessert’ pattern was significantly associated with higher HbA1c in T1D (β±SE: 0.10±0.05, p=0.03), but not in nondiabetic controls (0.06±0.04, p=0.21) when adjusted for age, sex and baseline total calories, as well as diabetes duration for T1D. At year-6, baseline higher intake of ’baked dessert’ pattern tended to be associated with increasing HbA1c in T1D (β±SE: 0.11±0.06, p=0.06), but not in nondiabetic controls (0.01±0.04, p=0.68) when adjusted for the same covariates. Conclusions: Habitual intake of a dietary pattern that is characterized by an increased intake of added sugar and saturated fats, such as in baked desserts may increase risks of poor glycemic control in T1D. Disclosure A. Basu: None. A.C. Alman: None. J.K. Snell-Bergeon: Stock/Shareholder; Self; GlaxoSmithKline plc. Funding American Diabetes Association (7-13-CD-10 to J.K.S-B.)

Background: Measurement of biomarkers associated with cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM) should improve our understanding of the pathogenesis of CVD and enhance disease prediction. Innovative approaches like the use of dried blood samples in assessing these biomarkers could simplify population-based studies. Method: In this ongoing cross-sectional study, we enrolled 44 patients with T2DM (41% male, mean age 63.7 years). Following a fingerstick, five drops of blood were collected using a device containing absorbent paper and a desiccant (HemaSpot-HF®). Levels of C-reactive protein (CRP) and fibrinogen were measured using a Luminex assay. The presence of vascular complications (retinopathy, nephropathy, neuropathy, heart disease or stroke) was determined through an interview of each participant and a detailed chart review. Nonparametric M-W tests with exact p-values were used to compare groups using SPSS and R software. Results: Patients with nephropathy had significantly higher levels of fibrinogen recovered from the devices (147.55 ± 163.27 mg/dl) compared to those without nephropathy (22.64 ± 10.27 mg/dl), (p=0.043). There was no significant relationship between fibrinogen and other vascular complications or CRP with any of the vascular complications associated with T2DM (p>0.05 for all). Conclusion: Higher plasma fibrinogen was found among patients with T2DM and nephropathy compared to those without nephropathy. This may reflect a higher state of systemic inflammation related to tissue damage. The use of a dried blood sample method for biomarker assays can be applied to larger population studies and towards simplifying translational biologic research. Disclosure K. Izuora: None. A. Basu: None. A. Alver: None. A. Salazar: None. A. Capurro: None. C.L. Gewelber: None. C.L. Cross: None. S.J. Williams: None. J.L. Ebersole: None.

OBJECTIVES: Dietary berries have been shown to lower cardio-metabolic risks in clinical trials. We examined the dose-response effects of two dietary achievable doses of strawberries on low-density lipoprotein cholesterol (LDL-C) and insulin resistance in adults with metabolic syndrome. METHODS: In this 14-week randomized controlled crossover study, adults with metabolic syndrome were assigned to one of the three arms for 4 weeks separated by a one-week washout period: control powder, one serving strawberries (13 g powder/day), and 2.5 servings strawberries (32 g powder/day). The freeze-dried powders were blended in water, and participants consumed half the daily dose in the morning and half in the evening. Participants were instructed to follow their usual diet and lifestyle while refraining from consuming other berries and related products throughout the study. RESULTS: Thirty participants completed all three phases of the trial (baseline profiles: weight: 90.8 ± 22.4 kg, BMI: 33.1 ± 4.2 kg/m(2), waist circumference: 109 ± 12.5 cm, HbA(1c) : 5.8 ± 0.2%). Outcome measures were analyzed using a multivariate analysis of variance with statistical significance set at P

OBJECTIVES: Gestational diabetes mellitus (GDM) is one of the most common health complications during pregnancy. Medical nutrition therapy is the mainstay of treatment for GDM, however, there is no current consensus on the optimal dietary approaches for prevention and management of hyperglycemia during pregnancy. Our objective is to assess the relationship of plant-based diets, foods, and dietary supplements with GDM and maternal glycemic biomarkers in observational and clinical studies. METHODS: A systematic review was performed using PubMed to identify original articles from 1999–2019 following the PRISMA checklist statement. Articles were excluded if they were review articles, conference abstracts, not in English or did not meet the pre-defined PICOS (Population, Intervention/exposure, Comparison, Outcome, Study design) criteria. Articles were screened for relevance, extracted and summarized, and assessed for risk of bias and quality. RESULTS: A total of 431 articles were screened, 33 observational studies (prospective cohort: n = 26, case-control: n = 3, cross-sectional: n = 4) involving 147,576 women and 11 randomized clinical trials involving 3940 women were included. Among the observational studies, Mediterranean diet (MedDiet), fiber, and vegetable rich diets were associated with a significant decrease in GDM risk. Among the clinical trials, Dietary Approaches to Stop Hypertension (DASH) diet, MedDiet, soy, phytosterol spread, evening primrose, chili powder and a traditional Chinese herb, Artemisia scoparia Waldst. & Kit. (Asteraceae) (n = 1) exhibited improved maternal hyperglycemia, insulin resistance or sensitivity, and hypoadiponectinemia. CONCLUSIONS: These findings suggest that plant-based diets may be effective in preventing and managing hyperglycemia during pregnancy. Particularly, adherence to a MedDiet may improve maternal glycemic biomarker and decrease risk of GDM. FUNDING SOURCES: UNLV Faculty research start up award.

Approximately 22% of U.S. adults and 25% of adults globally have metabolic syndrome (MetS). Key features, such as dysglycemia and dyslipidemia, predict type 2 diabetes, cardiovascular disease, premature disability, and death. Acute supplementation of dietary polyphenols and post-meal physical activity hold promise in improving postprandial dysmetabolism. To our knowledge, no published review has described the effects of either intervention on postprandial glucose, insulin, lipids, and markers of oxidative damage and inflammation in adults with features of MetS. Thus, we conducted this review of controlled clinical trials that provided dietary polyphenols from oils, fruits, teas, and legumes during a dietary challenge, or implemented walking, cycling, and stair climbing and descending after a dietary challenge. Clinical trials were identified using ClinicalTrials.gov, PubMed, and Google Scholar and were published between 2000 and 2019. Dietary polyphenols from extra virgin olive oil, grapes, blackcurrants, strawberries, black tea, and black beans improved postprandial glucose, insulin, and markers of oxidative damage and inflammation, but results were not consistent among clinical trials. Freeze-dried strawberry powder distinctly improved postprandial insulin and markers of oxidative damage and inflammation. Post-meal physical activity attenuated postprandial glucose, but effects on postprandial lipids and markers of oxidative damage and inflammation were inconclusive. Consuming dietary polyphenols with a meal and completing physical activity after a meal may mitigate postprandial dysmetabolism in adults with features of MetS.

Preeclampsia (PE), a pregnancy-specific hypertensive disorder, is a significant cause of maternal and perinatal mortality worldwide. While the underlying causes of this maternal syndrome are not clearly understood, oxidative stress, especially in the placenta, is considered a biologically plausible contributor. Oxidative stress is enhanced in pregnancies complicated by type 1 diabetes mellitus (T1DM), and diabetes is associated with a fourfold higher prevalence of PE. In human pregnancies complicated by diabetes, observational studies correlate multivitamin use with decreased risk of birth defects. In contrast, the largest clinical trial of antioxidant vitamin supplementation (vitamin C and E) in pregnancy in women with T1DM found no effect on the incidence of PE. Several emerging studies show benefits of probiotics, omega-3 fatty acids and green tea phytochemicals in improving oxidative stress and metabolic profiles in gestational diabetes, and these compounds deserve further investigation for efficacy against PE in pregnant T1DM women.

Circulating apolipoprotein-defined lipoprotein subclasses (ADLS) and apolipoproteins predict vascular events in the general and type 2 diabetes populations, but data in T1D are limited. We examined associations of ADLS, serum apolipoproteins, and conventional lipids with carotid intima-media thickness (IMT) measured contemporaneously and 6 years later in 417 T1D participants [men: n = 269, age 42 ± 6 y (mean ± SD); women: n = 148, age 39 ± 8 y] in the Epidemiology of Diabetes Interventions and Complications study, the follow-up of the Diabetes Control and Complications Trial (DCCT). Date were analyzed by multiple linear regression stratified by sex, and adjusted for time-averaged hemoglobin A1C, diabetes duration, hypertension, BMI, albuminuria, DCCT randomization, smoking, statin treatment, and ultrasound devices. In cross-sectional analyses, lipoprotein B (Lp-B), Lp-B:C, Lp-B:E+Lp-B:C:E, Apo-A-II, Apo-B, Apo-C-III-HP (heparin precipitate; i.e., Apo-C-III in Apo-B-containing lipoproteins), and Apo-E were positively associated with common and/or internal carotid IMT in men, but only Apo-C-III (total) was (positively) associated with internal carotid IMT in women. In prospective analyses, Lp-B, Apo-B, and Apo-C-III-HP were positively associated with common and/or internal carotid IMT in men, while Lp-A1:AII and Apo-A1 were inversely associated with internal carotid IMT in women. The only significant prospective association between conventional lipids and IMT was between triacylglycerols and internal carotid IMT in men. ADLS and apolipoprotein concentrations may provide sex-specific biomarkers and suggest mechanisms for IMT in people with T1D.

Arthritis is a global health concern affecting a significant proportion of the population and associated with reduced quality of life. Among the different forms of arthritis, osteoarthritis (OA) and rheumatoid arthritis (RA) are the most common and lacking a definite cure in the affected individuals. Fruits, such as berries and pomegranates are rich sources of a variety of dietary bioactive compounds, especially the polyphenolic flavonoids that have been associated with antioxidant, anti-inflammatory and analgesic effects. Emerging research demonstrates a protective role of fruits and their polyphenols in pre-clinical, clinical and epidemiological studies of OA and RA. In this context, commonly available fruits, such as blueberries, raspberries and strawberries, and pomegranates have shown promising results in reducing pain and inflammation in experimental models and in human clinical studies of arthritis. There is also some evidence on the role of specific fruit polyphenols, such as quercetin and citrus flavonoids in alleviating RA symptoms. These emerging data deserve further investigation in rigorous scientific studies to determine the mechanisms, dosing and selection of fruits and fruit extracts in arthritis management.

Objective: Knee osteoarthritis (OA) is increasingly prevalent in obese people, who often have high cardio-metabolic risk factors. Among the few available non-surgical approaches, nutraceuticals have gained popularity, and dietary berries have mitigated arthritis symptoms in observational and animal studies. Clinical studies in OA are sparse, but recently we reported that strawberry supplementation can mitigate pain and reduce inflammatory markers in adults with knee OA. This study extends those observations. Methods: We conducted a randomized cross-over double-blind placebo-controlled trial on the effects of dietary freeze-dried strawberries on obesity-related hormones, biomarkers of inflammation and lipid peroxidation. Seventeen subjects (4 men, 13 women; age 57 ± 3 year) were randomized to strawberry supplements (50 g day−1 for 12 weeks) vs. placebo (50 g day−1, matched for calories and fiber), for two 12-week intervention periods, separated by 2-week washout phase. Results: Among 24 biomarkers of inflammation examined (Bioplex-Pro human inflammation panel), 12 were detectable in all samples. Among these, high-sensitivity TNF-α (hs-TNF-α) and the soluble tumor necrosis factor receptor (sTNF-R2) were significantly decreased after strawberry consumption (p < 0.05). There were no changes in other biomarkers of the TNF super family, such as APRIL and BAFF. Among serum biomarkers of oxidative stress, 4-hydroxy-2-nonenal (4-HNE) and conjugated dienes were also reduced (p < 0.05). No changes were observed in body weight, serum obesity-related hormones, or osteocalcin. Conclusion: Strawberries lowered TNF-α, and lipid peroxidation products in obese adults with knee OA. Since, they also mitigate pain, these findings merit further investigation in larger trials.

Strawberries, a popularly consumed berry fruit, are rich in bioactive compounds with antioxidant effects. In this study, we examined the effects of two dietary achievable doses of strawberries on the antioxidant status and biomarkers of endothelial function in adults with features of metabolic syndrome and a confirmed low baseline of fruit and vegetable intake. In a 14-week randomized controlled crossover study, participants were assigned to one of three groups for four weeks separated by a one-week washout period: control powder, one serving (low dose: 13 g strawberry powder/day), or 2.5 servings (high dose: 32 g strawberry powder/day). Blood samples and health data were collected at baseline and at the end of each four-week phase of intervention. Thirty-three participants completed all three phases of the trial. Significant increases were observed in serum antioxidant capacity and superoxide dismutase activity as well as decreases in lipid peroxidation after both low and high dose strawberry phases when compared with the control phase. Significant decreases were also observed in soluble vascular cell adhesion molecule-1 and tumor necrosis factor-α with the high dose strawberry phase. These data confirm that consuming strawberries for four weeks significantly improves antioxidant status, endothelial function, and inflammation in adults with cardiometabolic risks.

Recent research supports a favorable role of cranberries on cardiometabolic health. Postprandial metabolism, especially hyperglycemia, has been shown to be an independent cardiovascular risk and few clinical studies have reported the role of berries in improving postprandial dysmetabolism. We investigated the postprandial effects of dried cranberries following a high-fat breakfast challenge in obese participants with type 2 diabetes (T2DM), in a randomized crossover trial. Blood draw and vascular measurements were conducted at fasting, 1, 2 and 4 hours (h), following the consumption of a fast-food style high-fat breakfast (70 g fat, 974 kcal) with or without cranberries (40 g). Analyses of our data (n = 25; BMI (kg m(−2)) (mean ± s.d.) = 39.5 ± 6.5; age (years) = 56 ± 6) revealed that postprandial increases in glucose were significantly lower in the cranberry vs. control at 2 & 4 h (p < 0.05). No significant differences were noted in insulin, insulin resistance evaluated by homeostasis model assessment, lipid profiles and blood pressure between the cranberry and control groups. Among the biomarkers of inflammation and oxidation, postprandial serum interleukin-18 and malondialdehyde were significantly lower at 4 h, and serum total nitrite was higher at 2 h in the cranberry vs. control group (all p < 0.05). No effects were noted on C-reactive protein or interlukin-6. Overall, dietary cranberries had notable effects in improving high-fat breakfast induced postprandial glucose and selected biomarkers of inflammation and oxidation in participants with T2DM. These findings provide evidence that adding whole cranberries to a high-fat meal may improve postprandial blood glucose management and warrant further investigation.

Background: Among the modifiable risk factors, diet plays an important role in the risks and progression of atherosclerotic cardiovascular disease (ASCVD). However, few studies have examined this association in people with type 1 diabetes (T1D) who are at a greater risk of developing ASCVD than nondiabetic (non-DM) controls. Methods: We conducted cross-sectional and longitudinal analyses of data from CACTI study [n=1257; T1D: n=568; non-DM: n=689] collected between March 2000 and April 2002. Participants completed a validated food frequency questionnaire, a physical examination and fasting biochemical analyses (12h fast), and coronary artery calcification (CAC) was measured using electron beam computed tomography. At baseline, dietary patterns based on variations in food group intake were created with principal components analysis (PCA). Logistic regression was used to examine associations of dietary patterns with the CAC prevalence in a model adjusted for age and sex and stratified by diabetes status. Results: Three dietary patterns were identified using PCA as follows: ‘fruits, veggies, meats, cereal’, ‘baked desserts’ and ‘convenience foods and alcohol’ patterns. At baseline, no significant associations of dietary patterns with CAC prevalence were observed. At year-6, ‘baked dessert’ pattern was significantly associated with increased risk of CAC ( Conclusions: Habitual intake of a dietary pattern that is characterized by an increased intake of added sugar and fats, such as in baked desserts may increase risks of atherosclerosis in T1D. Thus, dietary adjustments to improve this pattern may be atheroprotective. Disclosure A. Basu: None. A.C. Alman: None. J.K. Snell-Bergeon: None. Funding American Diabetes Association (7-13-CD-10 to J.K.S-B.)

Periodontal disease damages tissues as a result of dysregulated host responses against the chronic bacterial biofilm insult and approximately 50% of US adults &gt, 30 years old exhibit periodontitis. The association of five blood nutrients and periodontitis were evaluated due to our previous findings regarding a potential protective effect for these nutrients in periodontal disease derived from the US population sampled as part of the National Health and Nutrition Examination Survey (1999&ndash, 2004). Data from over 15,000 subjects was analyzed for blood levels of cis-&beta, carotene, &beta, cryptoxanthin, folate, vitamin D, and vitamin E, linked with analysis of the presence and severity of periodontitis. Moderate/severe disease patients had lower cis-&beta, carotene levels across all racial/ethnic groups and these decreased levels in moderate/severe periodontitis were exacerbated with age. &beta, cryptoxanthin demonstrated lower levels in severe disease patients across the entire age range in all racial/ethnic groups. Folate differences were evident across the various age groups with consistently lower levels in periodontitis patients &gt, 30 years and most pronounced in females. Lower levels of vitamin D were consistently noted across the entire age range of patients with a greater difference seen in females with periodontitis. Finally, an analytical approach to identify interactions among these nutrients related to age and periodontitis showed interactions of vitamin D in females, and folate with race in the population. These findings suggest that improving specific nutrient intake leading to elevated blood levels of a combination of these protective factors may provide a novel strategy to affect the significant increase in periodontitis that occurs with aging.

Our objective is to define differences in circulating lipoprotein subclasses between intensive versus conventional management of type 1 diabetes during the randomization phase of the Diabetes Control and Complications Trial (DCCT). NMR-determined lipoprotein subclass profiles (NMR-LSPs), which estimate molar subclass concentrations and mean particle diameters, were determined in 1,294 DCCT subjects after a median of 5 years (interquartile range: 4–6 years) of randomization to intensive or conventional diabetes management. In cross-sectional analyses, we compared standard lipids and NMR-LSPs between treatment groups. Standard total, LDL, and HDL cholesterol levels were similar between randomization groups, while triglyceride levels were lower in the intensively treated group. NMR-LSPs showed that intensive therapy was associated with larger LDL diameter (20.7 vs. 20.6 nm, P = 0.01) and lower levels of small LDL (median: 465 vs. 552 nmol/l, P = 0.007), total IDL/LDL (mean: 1,000 vs. 1,053 nmol/l, P = 0.01), and small HDL (mean: 17.3 vs. 18.6 ¼mol/l, P < 0.0001), the latter accounting for reduced total HDL (mean: 33.8 vs. 34.8 ¼mol/l, P = 0.01). In conclusion, intensive diabetes therapy was associated with potentially favorable changes in LDL and HDL subclasses in sera. Further research will determine whether these changes contribute to the beneficial effects of intensive diabetes management on vascular complications.

Dyslipidemia has been linked to vascular complications of Type 1 diabetes (T1DM). We investigated the prospective associations of nuclear magnetic resonance-determined lipoprotein subclass profiles (NMR-LSP) and conventional lipid profiles with carotid intima-media thickness (IMT) in T1DM.NMR-LSP and conventional lipids were measured in a subset of Diabetes Control and Complications Trial (DCCT) participants (n = 455) at study entry ('baseline', 1983-89), and were related to carotid IMT determined by ultrasonography during the observational follow-up of the DCCT, the Epidemiology of Diabetes Interventions and Complications (EDIC) study, at EDIC Year 12 (2004-2006). Associations were defined using multiple linear regression stratified by gender, and following adjustment for HbA1c, diabetes duration, body mass index, albuminuria, DCCT randomization group, smoking status, statin use, and ultrasound devices.In men, significant positive associations were observed between some baseline NMR-subclasses of LDL (total IDL/LDL and large LDL) and common and/or internal carotid IMT, and between conventional total- and LDL-cholesterol and non-HDL-cholesterol and common carotid IMT, at EDIC Year 12; these persisted in adjusted analyses (p0.05). Large LDL particles and conventional triglycerides were positively associated with common carotid IMT changes over 12 years (p0.05). Inverse associations of mean HDL diameter and large HDL concentrations, and positive associations of small LDL with common and/or internal carotid IMT (all p0.05) were found, but did not persist in adjusted analyses. No significant associations were observed in women.NMR-LSP-derived LDL particles, in addition to conventional lipid profiles, may help in identifying men with T1DM at highest risk for vascular disease.

APOB, APOC3, and APOE and apolipoprotein-defined lipoprotein subclasses (ADLSs; based on qualitative apolipoprotein complement) have been associated with dyslipidemia and CVD. Our main objective was to define associations of serum apolipoproteins and ADLSs with "any CVD" and "major atherosclerotic cardiovascular events" (MACEs) in a prospective study of T1D. Serum apolipoproteins and ADLSs (14 biomarkers in total) were measured in sera (obtained between 1997 and 2000) from a subset (n = 465) of the Epidemiology of Diabetes Interventions and Complications cohort. Prospective associations of "any CVD" (myocardial infarction, stroke, confirmed angina, silent myocardial infarction, revascularization, or congestive heart failure) and MACEs (fatal or nonfatal myocardial infarction or stroke), over 5,943 and 6,180 patient-years follow-up, respectively, were investigated using Cox proportional hazards models that were unadjusted and adjusted for risk factors. During 15 years of follow-up, 50 "any CVD" events and 24 MACEs occurred. Nominally significant positive univariate associations with "any CVD" were APOB, APOC3 and its subfractions [heparin precipitate, heparin-soluble (HS)], and ADLS-defined Lp-B. In adjusted analyses, APOC3-HS remained nominally significant. Nominally significant positive univariate associations with MACEs were APOC3 and its subfractions and Lp-B:C; those with total APOC3 and APOC3-HS persisted in adjusted analyses. However, these associations did not reach significance after adjusting for multiple testing. There were no significant associations of APOA1, APOA2, APOE, or other ADLSs with either "any CVD" or MACEs. These hypothesis-generating data suggest that total serum APOC3 and APOC3 in HDL are potentially important predictive biomarkers for any CVD and MACEs in adults with T1D.

Background: Serum uric acid (UA) is associated with the pathogenesis of diabetes complications, including cardiovascular disease (CVD) and kidney injury. Current epidemiological evidence is limited regarding the association between UA and the development of CVD in type 1 diabetes mellitus (T1DM). Objective: To examine associations of serum UA with CVD and major atherosclerotic cardiovascular events (MACE) in T1DM. Methods: UA was measured in sera (1997-2000) from a subset of participants (n=973; males=540, females=433) in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Subsequent CVD events were adjudicated by a review committee masked to DCCT assignment and HbA1c levels, and defined as the time to the first of any of the following: non-fatal myocardial infarction (MI) or stroke, CVD death, silent MI on annual ECG, angina confirmed by ischemic changes with exercise tolerance testing, congestive heart failure, or revascularization; MACE were defined as a composite of CVD death, nonfatal MI, or stroke. Cox proportional hazards models were used to evaluate prospectively the effect of UA as a fixed covariate on CVD and MACE, separately by gender, and adjusted for age and HbA1c. Results: Over 15 years follow-up, there were 201 adjudicated CVD events among 110 participants (HR=1.10 per 1 mg/dl change in UA, 95% CI 0.93-1.30); 61 males experienced 96 events (HR=1.15, 95% CI 0.90-1.46) and 49 females, 105 events (HR=1.17, 95% CI 0.88-1.56). There were 62 adjudicated MACE among 53 participants (HR=1.18, 95% CI 0.93-1.49); 29 males experienced 31 events (HR=1.10, 95% CI 0.77-1.58) and 24 females, 31 events (HR=1.47, 95% CI 1.01-2.14). No significant associations between quartiles of UA and either CVD or MACE were observed in either sex. Conclusions: Our results show UA may not serve as a predictive biomarker for CVD events in T1DM adults. Sex-specific associations with MACE deserve further investigation. Disclosure A. Basu: None. B. Braffett: None. A. Jenkins: Research Support; Self; Medtronic, Mylan, Sanofi-Aventis. I. Bebu: None. R.L. Klein: None. M.F. Lopes-Virella: None. S. Dagogo-Jack: None. T.J. Orchard: None. A. Wallia: Research Support; Self; UnitedHealth Group. Consultant; Self; Glytec Systems, Lexicon Pharmaceuticals, Inc.. Research Support; Self; Eli Lilly and Company. J. Lachin: Board Member; Self; AbbVie Inc., Celgene Corporation. W. Garvey: Advisory Panel; Self; Novo Nordisk Inc., Merck & Co., Inc.. Research Support; Self; Sanofi, Pfizer Inc., Novo Nordisk Inc., AstraZeneca, Merck & Co., Inc., Elcelyx Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Eisai Inc.. T. Lyons: None.

Background: Apolipoproteins Apo-B, Apo-C-III, and Apo-E are atherogenic and are associated with diabetic dyslipidemia and cardiovascular disease (CVD). Apolipoprotein-defined lipoprotein subclasses (ADLS) also show associations with CVD, but prospective associations of these detailed metrics with CVD in people with type 1 diabetes (T1DM) have not been explored. Objective: Prospective associations of serum apolipoproteins and ADLS with CVD and major atherosclerotic cardiovascular events (MACE: composite of CVD death, nonfatal myocardial infraction or nonfatal stroke) in T1DM. Methods: Serum apolipoproteins and ADLS (14 biomarkers in total) measured in sera (1997-2000) in a subset (n=465) of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications cohort. Prospective associations of CVD and MACE over 5942 and 6180 patient-years follow-up, respectively, were investigated using Cox proportional hazards models unadjusted and adjusted for risk factors. Results: During 15 years follow-up, 50 CVD and 24 MACE events occurred. Significant positive univariate associations for CVD were: Lp-B, Apo-B, Apo-C-III (total, heparin precipitate (HP), i.e., Apo-C-III in VLDL, and heparin soluble (HS), i.e., Apo-C-III in HDL) and Lp-B:C; for MACE: Apo-C-III sub fractions (total, Apo-C-III-HP, and Apo-C-III-HS). Adjusting for sex, age, HbA1c, systolic blood pressure, pulse rate, LDL-cholesterol, and triglycerides: for CVD, Apo-C-III-HS remained significant (HR (95% CI): 1.18 (1.03, 1.35); P=0.01). For MACE, total Apo-C-III and Apo-C-III-HS persisted when adjusted for age, HbA1c and LDL [1.11 (1.01, 1.22); P=0.02, and 1.22 (1.02, 1.45); P=0.02, respectively], but not for age, HbA1c and (log) triglycerides. No significant associations of other ADLS, Apo-A-I, A-II and Apo-E with CVD/MACE were observed. Conclusions: Total serum Apo-C-III and Apo-C-III in HDL and Apo-B-containing lipoproteins may serve as predictive biomarkers for CVD events in T1DM adults. Disclosure A. Basu: None. I. Bebu: None. A. Jenkins: Research Support; Self; Medtronic, Mylan, Sanofi-Aventis. J. Stoner: None. Y. Zhang: None. R.L. Klein: None. M.F. Lopes-Virella: None. W. Garvey: Advisory Panel; Self; Novo Nordisk Inc., Merck & Co., Inc.. Research Support; Self; Sanofi, Pfizer Inc., Novo Nordisk Inc., AstraZeneca, Merck & Co., Inc., Elcelyx Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Eisai Inc. M. Budoff: Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Amarin Corporation. T. Lyons: None.

Background: Intake of sufficient dietary fiber has been recommended for glucose control, and typically low fiber intake is observed in the general population. The role of fiber in glycemic control in reported literature is inconsistent and few reports are available in populations with type 1 diabetes (T1D). Methods: We conducted a cross-sectional analysis of data from the CACTI study [n=1257; T1D: n=568; nondiabetic controls: n=689] collected between March 2000 and April 2002. Participants completed a validated food frequency questionnaire, a physical examination and fasting biochemical analyses (12h fast) at screening visit. We used linear regression models to examine associations of total dietary fiber with HbA1c as a continuous variable. Models were stratified by diabetes status, and adjusted for age, sex and total calories, and diabetes duration in the T1D group. We also examined correlations of fiber with HbA1c. Results: Baseline dietary fiber intake and HbA1c in the T1D group were 16g [median (IQ): 11-22g) and 7.9±1.3% mean (SD), respectively, and in the nondiabetic controls were 15g [median (IQ): 11-21g) and 5.4±0.4%, respectively. Pearson partial correlation coefficients revealed a significant but weak inverse association of total dietary fiber with HbA1c when adjusted for age, sex, diabetes status and total calories (r= -0.07, p=0.01). In adjusted linear regression models, total dietary fiber was significantly and inversely associated with HbA1c in the T1D group [estimate (beta±SE)= -0.32±0.15, p=0.034], as well as in the nondiabetic controls [-0.10±0.04, p=0.009]. Thus, at observed levels of intake, total dietary fiber reveals a protective association against poor glycemic control in T1D adults and in nondiabetic controls. Disclosure A. Basu: None. A.C. Alman: None. J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation.

Background: Postprandial metabolic impairments in diabetes have been shown to play an important role in vascular complications. Dietary polyphenols and other bioactive compounds in berries have been shown to improve postprandial hyperglycemia and related metabolic impairments, but few clinical studies have been reported in diabetes. Objective: To examine the effects of daily dietary raspberries on postprandial and 4-week fasting glucose, lipids and biomarkers of inflammation in obese adults with type 2 diabetes. Design: This was a randomized crossover study with 2 different phases: a “postprandial phase” of acute raspberry supplementation (2 separate days at least 1 week apart), followed by a 1-week washout phase and then a 10-week “diet supplement phase”, with and without raspberry supplementation periods of 4 weeks each, separated by 2-week washout phase. Results: The postprandial phase revealed significantly lower levels of serum glucose at 2 and 4 h postprandial after raspberry versus control phase. In addition, among the serum biomarkers of inflammation, interleukin (IL)-6 and high-sensitivity tumor necrosis factor alpha (hsTNF-α) were also lower at 4 h postprandial following raspberry versus control meal (all p < 0.05). Finally, postprandial serum triglycerides showed a decreasing trend at 4 h in the raspberry versus control phase. Four-week daily raspberry supplementation continued to show a significant lowering effects on IL-6 and hsTNF-α versus control phase (all p < 0.05); systolic blood pressure revealed a decreasing trend after 4-week of raspberry supplementation. No effects were noted on fasting glucose and lipids, C-reactive protein and arterial elasticity. Conclusions: Thus, dietary raspberries, which are low in calories and high in polyphenols and other nutrients may lower postprandial hyperglycemia and inflammation, and in general exert selected anti-inflammatory effects in adults with diabetes. These findings deserve further investigation.

Biosynthesis of gold nanoparticles of distinct geometric shapes with highly functional protein coats without additional capping steps is rarely reported. This study describes green synthesis of protein-coated gold nanoparticles for the first time from the edible, mycorrhizal fungus Tricholoma crassum (Berk.) Sacc. The nanoparticles were of the size range 5–25 nm and of different shapes. Spectroscopic analysis showed red shift of the absorption maxima with longer reaction period during production and blue shift with increase in pH. These were characterized with spectroscopy, SEM, TEM, AFM, XRD, and DLS. The particle size could be altered by changing synthesis parameters. These had potent antimicrobial activity against bacteria, fungi, and multi-drug-resistant pathogenic bacteria. These also had inhibitory effect on the growth kinetics of bacteria and germination of fungal spores. These showed apoptotic properties on eukaryotic cells when tested with comet assays. Moreover, the particles are capped with a natural 40 kDa protein which was utilized as attachment sites for genes to be delivered into sarcoma cancer cells. The present work also attempted at optimizing safe dosage of these nanoparticles using hemolysis assays, for application in therapy. Large-scale production of the nanoparticles in fermentors and other possible applications of the particles have been discussed. Electronic supplementary material The online version of this article (10.1186/s11671-018-2561-y) contains supplementary material, which is available to authorized users.

Background: Dietary cocoa is an important source of flavonoids and is associated with favorable cardiovascular disease effects, such as improvements in vascular function and lipid profiles, in nondiabetic adults. Type 2 diabetes (T2D) is associated with adverse effects on postprandial serum glucose, lipids, inflammation, and vascular function. Objective: We examined the hypothesis that cocoa reduces metabolic stress in obese T2D adults after a high-fat fast-food–style meal. Methods: Adults with T2D [n = 18; age (mean ± SE): 56 ± 3 y; BMI (in kg/m2): 35.3 ± 2.0; 14 women; 4 men] were randomly assigned to receive cocoa beverage (960 mg total polyphenols; 480 mg flavanols) or flavanol-free placebo (110 mg total polyphenols

Plasma total homocysteine (tHcy) has been positively associated with carotid intima-media thickness (IMT) in non-diabetic populations and in a few cross-sectional studies of diabetic patients. We investigated cross-sectional and prospective associations of a single measure of tHcy with common and internal carotid IMT over a 6-year period in type 1 diabetes.tHcy levels were measured once, in plasma obtained in 1997-1999 from patients (n = 599) in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow-up of the Diabetes Control and Complications Trial (DCCT). Common and internal carotid IMT were determined twice, in EDIC "Year 6" (1998-2000) and "Year 12" (2004-2006), using B-mode ultra-sonography.After adjustment, plasma tHcy [median (interquartile range): 6.2 (5.1, 7.5) μmol/L] was significantly correlated with age, diastolic blood pressure, renal dysfunction, and smoking (all p 0.05). In an unadjusted model only, increasing quartiles of tHcy correlated with common and internal carotid IMT, again at both EDIC time-points (p 0.01). However, multivariate logistic regression revealed no significant associations between increasing quartiles of tHcy and the 6-year change in common and internal carotid IMT (highest vs. lowest quintile) when adjusted for conventional risk factors.In a type 1 diabetes cohort from the EDIC study, plasma tHcy measured in samples drawn in 1997-1999 was associated with measures of common and internal carotid IMT measured both one and seven years later, but not with IMT progression between the two time-points. The data do not support routine measurement of tHcy in people with Type 1 diabetes.

Dietary flavonoid intake, especially berry flavonoids, has been associated with reduced risks of cardiovascular disease (CVD) in large prospective cohorts. Few clinical studies have examined the effects of dietary berries on CVD risk factors. We examined the hypothesis that freeze-dried strawberries (FDS) improve lipid and lipoprotein profiles and lower biomarkers of inflammation and lipid oxidation in adults with abdominal adiposity and elevated serum lipids. In a randomized dose-response controlled trial, 60 volunteers [5 men and 55 women; aged 49 ± 10 y; BMI: 36 ± 5 kg/m(2) (means ± SDs)] were assigned to consume 1 of the following 4 beverages for 12 wk: 1) low-dose FDS (LD-FDS; 25 g/d); 2) low-dose control (LD-C); 3) high-dose FDS (HD-FDS; 50 g/d); and 4) high-dose control (HD-C). Control beverages were matched for calories and total fiber. Blood draws, anthropometrics, blood pressure, and dietary data were collected at screening (0 wk) and after 12-wk intervention. Dose-response analyses revealed significantly greater decreases in serum total and LDL cholesterol and nuclear magnetic resonance (NMR)-derived small LDL particle concentration in HD-FDS [33 ± 6 mg/dL, 28 ± 7 mg/dL, and 301 ± 78 nmol/L, respectively (means ± SEMs)] vs. LD-FDS (-3 ± 11 mg/dL, -3 ± 9 mg/dL, and -28 ± 124 nmol/L, respectively) over 12 wk (0-12 wk; all P < 0.05). Compared with controls, only the decreases in total and LDL cholesterol in HD-FDS remained significant vs. HD-C (0.7 ± 12 and 1.4 ± 9 mg/dL, respectively) over 12 wk (0-12 wk; all P < 0.05). Both doses of strawberries showed a similar decrease in serum malondialdehyde at 12 wk (LD-FDS: 1.3 ± 0.2 μmol/L; HD-FDS: 1.2 ± 0.1 μmol/L) vs. controls (LD-C: 2.1 ± 0.2 μmol/L; HD-C: 2.3 ± 0.2 μmol/L) (P < 0.05). In general, strawberry intervention did not affect any measures of adiposity, blood pressure, glycemia, and serum concentrations of HDL cholesterol and triglycerides, C-reactive protein, and adhesion molecules. Thus, HD-FDS exerted greater effects in lowering serum total and LDL cholesterol and NMR-derived small LDL particles vs. LD-FDS in the 12-wk study. These findings warrant additional investigation in larger trials. This trial was registered at clinicaltrials.gov as NCT01883401.

Blood lipids are an important biomarker of cardiovascular health and disease. Among the lipid biomarkers that have been widely used to monitor and predict cardiovascular diseases (CVD), elevated LDL and low HDL cholesterol (C), as well as elevated triglyceride-rich lipoproteins, deserve special attention in their predictive abilities, and thus have been the targets of several therapeutic and dietary approaches to improving lipid profiles. Among natural foods and nutraceuticals, dietary berries are a rich source of nutrients, fiber, and various types of phytochemicals. Berries as whole fruits, juices, and purified extracts have been shown to lower total and LDL-C, and increase HDL-C in clinical studies in participants with elevated blood lipids, type 2 diabetes or metabolic syndrome. This short review aimed to further discuss the mechanisms and magnitude of the lipid-lowering effects of dietary berries, with emphasis on reported clinical studies. Based on the emerging evidence, colorful berry fruits may thus be included in a healthy diet for the prevention and management of CVD.

Emerging research provides substantial evidence to classify strawberries as a functional food with several preventive and therapeutic health benefits. Strawberries, a rich source of phytochemicals (ellagic acid, anthocyanins, quercetin, and catechin) and vitamins (ascorbic acid and folic acid), have been highly ranked among dietary sources of polyphenols and antioxidant capacity. It should however be noted that these bioactive factors can be significantly affected by differences in strawberry cultivars, agricultural practices, storage, and processing methods: freezing versus dry heat has been associated with maximum retention of strawberry bioactives in several studies. Nutritional epidemiology shows inverse association between strawberry consumption and incidence of hypertension or serum C-reactive protein; controlled feeding studies have identified the ability of strawberries to attenuate high-fat diet induced postprandial oxidative stress and inflammation, or postprandial hyperglycemia, or hyperlipidemia in subjects with cardiovascular risk factors. Mechanistic studies have elucidated specific biochemical pathways that might confer these protective effects of strawberries: upregulation of endothelial nitric oxide synthase (eNOS) activity, downregulation of NF-kB activity and subsequent inflammation, or inhibitions of carbohydrate digestive enzymes. These health effects may be attributed to the synergistic effects of nutrients and phytochemicals in strawberries. Further studies are needed to define the optimal dose and duration of strawberry intake in affecting levels of biomarkers or pathways related to chronic diseases.

Aims Dyslipoproteinemia has been associated with nephropathy in diabetes, with stronger correlations in men than in women. We aimed to characterize and compare plasma lipoprotein profiles associated with normal and increased albuminuria in men and women using apolipoprotein-defined lipoprotein subclasses and simple apolipoprotein measures. Methods This is a cross-sectional study in a subset (154 women and 282 men) of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort, using samples obtained in 1997–9. Immunochemical methods were used to quantify plasma apolipoprotein-based lipoprotein subclasses and individual apolipoprotein levels. Results In adjusted analyses, elevated Lipoprotein-B (Lp-B) was significantly associated with macroalbuminuria in men [odds ratios (OR) and 95% confidence interval (CI): 2.13 (1.15–3.97)] and women [3.01 (1.11–8.12)], while association with Lp-B:C was observed only in men [1.84 (1.19–2.86)]. For individual apolipoproteins the following significant associations with macroalbuminuria were observed in men only: Apolipoprotein B (ApoB) [1.97 (1.20–3.25)], Apo-AII [0.52 (0.29–0.93)], ApoC-III [1.95 (1.16–3.30)], “ApoC-III in VLDL” (heparin–manganese precipitate) [1.88 (1.16–3.04)], and “ApoCIII in HDL” (heparin–manganese supernatant) [2.03 (1.27–3.26)], all P Conclusions Atherogenic apolipoprotein-based profiles are associated with nephropathy in Type 1 diabetic men and to a lesser extent in women. The difference could result from the greater prevalence and severity of dyslipoproteinemia, and from the greater prevalence of renal dysfunction, in men vs women.

OBJECTIVE Inflammation and endothelial dysfunction have been associated with the immunobiology of preeclampsia (PE), a significant cause of adverse pregnancy outcomes. The prevalence of PE is elevated several fold in the presence of maternal type 1 diabetes mellitus (T1DM). Although cross-sectional studies of pregnancies among women without diabetes have shown altered inflammatory markers in the presence of PE, longitudinal studies of diabetic women are lacking. In maternal serum samples, we examined the temporal associations of markers of inflammation with the subsequent development of PE in women with T1DM. RESEARCH DESIGN AND METHODS We conducted longitudinal analyses of serum C-reactive protein (CRP), adhesion molecules, and cytokines during the first (mean ± SD, 12.2 ± 1.9 weeks), second (21.6 ± 1.5 weeks), and third (31.5 ± 1.7 weeks) trimesters of pregnancy (visits 1–3, respectively). All study visits took place before the onset of PE. Covariates were BMI, HbA1c, age of onset, duration of diabetes, and mean arterial pressure. RESULTS In women with T1DM who developed PE versus those who remained normotensive, CRP tended to be higher at visits 1 (P = 0.07) and 2 (P = 0.06) and was significantly higher at visit 3 (P < 0.05); soluble E-selectin and interferon-γ–inducible protein-10 (IP-10) were significantly higher at visit 3; interleukin-1 receptor antagonist (IL-1ra) and eotaxin were higher and lower, respectively, at visit 2 (all P < 0.05). These conclusions persisted following adjustment for covariates. CONCLUSIONS In pregnant women with T1DM, elevated CRP, soluble E-selectin, IL-1ra, and IP-10 and lower eotaxin were associated with subsequent PE. The role of inflammatory factors as markers and potential mechanisms of the high prevalence of PE in T1DM merits further investigation.

Aims/hypothesis We aimed to determine whether plasma lipoproteins, after leakage into the retina and modification by glycation and oxidation, contribute to the development of diabetic retinopathy in a mouse model of type 1 diabetes. Methods To simulate permeation of plasma lipoproteins into retinal tissues, streptozotocin-induced mouse models of diabetes and non-diabetic mice were challenged with intravitreal injection of human ‘highly-oxidised glycated’ low-density lipoprotein (HOG-LDL), native- (N-) LDL, or the vehicle PBS. Retinal histology, electroretinography (ERG) and biochemical markers were assessed over the subsequent 14 days. Results Intravitreal administration of N-LDL and PBS had no effect on retinal structure or function in either diabetic or non-diabetic animals. In non-diabetic mice, HOG-LDL elicited a transient inflammatory response without altering retinal function, but in diabetic mice it caused severe, progressive retinal injury, with abnormal morphology, ERG changes, vascular leakage, vascular endothelial growth factor overexpression, gliosis, endoplasmic reticulum stress, and propensity to apoptosis. Conclusions/interpretation Diabetes confers susceptibility to retinal injury imposed by intravitreal injection of modified LDL. The data add to the existing evidence that extravasated, modified plasma lipoproteins contribute to the propagation of diabetic retinopathy. Intravitreal delivery of HOG-LDL simulates a stress known to be present, in addition to hyperglycaemia, in human diabetic retinopathy once blood-retinal barriers are compromised. Electronic supplementary material The online version of this article (doi:10.1007/s00125-016-4012-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.