bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual-Dimorphism in Exercise-Induced Beiging and Altered Mitochondrial Function in Inguinal White Adipose Tissue (iWAT) from the Mouse
Authors: NIGRO PASQUALE , MIDDELBEEK ROELAND , ALVES CHRISTIANO R. , ALBERTSON BRENT G. , ROWLAND LESLIE A. , WAGNER ANA B. , PRINCE NOAH B. , HIRSHMAN MICHAEL F. , GOODYEAR LAURIE J.
Published: June 2018

Regular physical exercise has numerous benefits on metabolic health, likely involving adaptations to many tissues, including adipose tissue. There are conflicting reports on the effects of exercise training on adaptations to iWAT and we hypothesized that these discrepancies may stem in part from sex-specific differences. Male and female 10 week old C57BL6/J mice were housed in cages with (trained) or without (sedentary) running wheels for 11 days (n=6-9/sex/experiment). Males performed less voluntary exercise vs. females (56±7 vs. 78±5 km; p<0.05). In males, training decreased iWAT fat pad weight (19.6%) and adipocyte size (19%) (both p<0.05), whereas training did not have these effects on iWAT in females, most likely due to increased food intake. Training did not alter perigonadal WAT weight or adipocyte size in either sex. In iWAT, training in males increased mRNA of the beiging genes Ucp1 (304%; p<0.01); Pgc1α (228%; p<0.05); Cidea (206%; p<0.05); and Dio2 (197%; p<0.01), as well as Ucp1 protein (124%; p<0.01), but none of these markers were increased in females. Exercise training also increased mitochondrial parameters in iWAT only from males, including basal respiration (170%; p<0.01), glycolytic capacity (227%; p<0.001) and the mitochondrial fission genes Opa1 (235%; p<0.05), Mfn1 (231%; p<0.001), and Mfn2 (229%; p<0.01). Since exercise may increase testosterone in male mice, we tested the effects of testosterone on iWAT beiging and mitochondria. iWAT of male and female mice were treated with testosterone (10μM) for 24 hours. Interestingly, testosterone increased Ucp1 protein (175%; p<0.05) and mRNA (386%; p<0.05) in iWAT from male, but not in females. We conclude that voluntary wheel running in mice results in beiging and mitochondrial adaptations to iWAT exclusively in males. Sex-specific differences in WAT function will be important to consider in all research investigating adipose tissue beiging and mitochondrial function.

Disclosure

P. Nigro: None. R. Middelbeek: None. C.R. Alves: None. B.G. Albertson: None. L.A. Rowland: None. A.B. Wagner: None. N.B. Prince: None. M.F. Hirshman: None. L.J. Goodyear: None.
Dietary Protein Intake Is Not Associated with Progression of Diabetic Nephropathy in Patients without Macroalbuminuria
Authors: KAJI AYUMI , HASHIMOTO YOSHITAKA , SAKAI RYOSUKE , OKAMURA TAKURO , YAMAZAKI MASAHIRO , FUKUI MICHIAKI
Published: June 2018

Background/Aims: Diabetic nephropathy is an important problem in patients with diabetes. However, little is known about the effect of dietary protein intake on albuminuria in patients with diabetes. Thus, the aim of this study was to clarify the association between dietary protein intake and change in urinary albumin excretion (UAE) or estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.

Methods: In this retrospective cohort study, we included 143 patients (71 men, average 64.0 (10.5) years, and median 14.5 (6.7-38.5) mg/gCr) without macroalbuminuria (UAE over 300 mg/gCr). Change in UAE or eGFR was defined as increase of UAE or GFR/follow-up duration (year). Habitual protein intake was estimated by a self-administered diet history questionnaire.

Results: Median follow-up duration was 5 years. Logistic regression analyses showed that baseline UAE was associated with change in UAE (β = 0.217, p = 0.012), but the protein intake was not (β = -0.064, p = 0.454) (Table). In addition, baseline Cr was associated with change in eGFR (β = 0.344, p = 0.001), but the protein intake was not (β = 0.001, p = 0.988).

Conclusions: Dietary protein intake was not associated with change in UAE or eGFR. This result suggests that protein restriction is not necessary in patients without macroalbuminuria.

Multiple regression analysis on δUAE or δeGFRδUAEstandardized regression coefficientp valueδeGFRstandardized regression coefficientp valueLog (UAE+1)0.2170.012Log (UAE+1)0.0490.560Protein intake (g/kg/day)-0.0640.454Protein intake (g/kg/day)-0.0330.698Usage of RAS inhibitor0.1140.193Usage of RAS inhibitor-0.2020.021Creatinine0.0470.646Creatinine0.398<0.001Age-0.0030.977Age0.0610.490BMI0.1190.184BMI-0.0420.634Men-0.1430.163Men0.1210.237

Disclosure

A. Kaji: None. Y. Hashimoto: Research Support; Self; Asahi Kasei Corporation, Fuji Foundation for Protein Research, Japan Society for the Promotion of Science, MSD K.K.. R. Sakai: None. T. Okamura: None. M. Yamazaki: None. M. Fukui: Research Support; Self; Grant-in-Aid for Scientific Research (C), Ono Pharmaceutical Co., Ltd., AstraZeneca, Astellas Pharma US, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kyowa Hakko Kirin Co., Ltd., Kissei Pharmaceutical Co., Ltd., MSD K.K., Novo Nordisk Foundation.
Clinical Study of Astaxanthin on Glucose Tolerance in Nondiabetic Subjects
Authors: URAKAZE MASAHARU , KOBASHI CHIKAAKI , SATOU YUKIHIRO , TAKAGI MASATOSHI , SHIGETA KOUICHI , TOSHIMA MASAHIRO , TAKAHASHI JIRO , NISHIDA MITSUNORI
Published: June 2018

Astaxanthin (ASTX) is a xanthophyll carotenoid produced by Haemococcus pluvialis, and is found in microalgae, plankton, krill and other seafood. ASTX has strong antioxidant activity, which is an attractive nutraceutical for further investigation in diabetes, lipid profile, and atherosclerotic cardiovascular disease where antioxidant cellular protection may be of clinical benefit. We already reported the effects of astaxanthin (randomized, double-blind, placebo-controlled study) on glucose metabolism and lipid profile in 44 healthy volunteers in the 10th Asia Pacific Conference on Clinical Nutrition 2017. Here we report the effects of ASTX on glucose metabolism in 29 subjects whose HbA1c was from 5.6 % to 6.4 % at baseline. Data of 75g OGTT and HbA1c in 29 subjects (16 in ASTX group and 13 in Placebo group) were analyzed. After ASTX (12mg/day) supplementation for 12 weeks, the glucose level at 30 min by 75g OGTT was significantly decreased compared to before. The level of HbA1c was also significantly decreased compared to before. Furthermore, we assessed indices of insulin resistance derived from OGTT. Both Matsuda index and hepatic insulin resistance were improved after ASTX (12mg/day) supplementation, although muscle insulin sensitivity index was unchanged. Our results suggest that ASTX might have beneficial effects on the prevention of diabetes in subjects whose HbA1c was from 5.6 % to 6.4 %, including subjects with prediabetes.

Disclosure

M. Urakaze: Research Support; Self; Fuji Chemical Industry Co., Ltd.. C. Kobashi: None. Y. Satou: None. M. Takagi: None. K. Shigeta: None. M. Toshima: Research Support; Self; Fuji Chemical Industry Co., Ltd. J. Takahashi: Employee; Self; Fuji Chemical Industry Co., Ltd. M. Nishida: Other Relationship; Self; Fuji Chemical Industry Co., Ltd..
Saccharin Does Not Affect Insulin Resistance in 14 Overweight Adults without Diabetes
Authors: RADHOLM KARIN , KALIN KENNY , WENNBERG MARIA , WOODWARD MARK , ESQ.  , BÄCKHED FREDRIK , ROLANDSSON OLOV
Published: June 2018

Background: Most non-caloric artificial sweeteners (NAS) are not digested, but come in contact with the gut microbiota, an interaction that has been associated with impaired glucose control. We aimed to further investigate whether NAS affect insulin sensitivity.

Methods: The study was an open label study where participants acted as their own controls before and after exposure of 240 mg saccharin/day for three months. Participants were 55-65 years old, with a body mass index of 26-29 kg/m2 without diabetes. Insulin sensitivity was assessed by use of hyperinsulinemic-euglycemic clamps and ’M value’ was calculated by dividing the glucose infusion rate during the last 60 minutes of the clamp by body weight (mg/kg/min).

Results: Of the 14 included participants, one did not complete the study. There was no change in insulin resistance after exposure to saccharin. The mean M value difference (∆M) for all participants was 0.0 (SD 1.6). ∆M was not related to age (p value 0.162) or sex (p value 0.578). Individual M values from the first and second insulin clamp are shown in the Figure and indicate some individual responses.

Conclusions: In contrast to the larger epidemiologic studies, we did not observe a strong effect of NAS on insulin sensitivity. Some individuals exhibited impaired insulin sensitivity and we are currently investigating whether individualized responses are dependent on shifts in the gut microbiota.

Disclosure

K. Radholm: None. K. Kalin: None. M. Wennberg: None. M. Woodward: None. F. Bäckhed: Board Member; Self; Metabogen AB. Stock/Shareholder; Self; Metabogen AB. Advisory Panel; Self; Ferring Pharmaceuticals. O. Rolandsson: None.
Effect of High ß-Glucan Barley on Postprandial Plasma Glucose Levels in Subjects with Normal Glucose Tolerance and Patients with Type 2 Diabetes
Authors: HIGA MARIKO , HASHIMOTO AYANA , HAYASAKA MOE , HIJIKATA MAI , UEDA AYAMI , ODA KENZABURO , KATO DAISUKE , YAMASHITA KAORU , ICHIJO TAKAMASA
Published: June 2018

Increasing evidence supports a more prominent role for postprandial glucose (PPG) regulation in the management of type 2 diabetes. Viscous dietary fibers including oat and barley β-glucan are one of the most effective classes of functional food ingredients for reducing PPG. We investigated the effect of high β-glucan barley on postprandial plasma glucose and C-peptide levels using a meal tolerance test and continuous glucose monitoring (CGM) in 15 subjects with normal glucose tolerance (NGT) and 29 type 2 diabetic patients. A 500-kcal meal tolerance test, using white rice alone (white rice) or white rice mixed with 50% of barley (Kirari-mochi®) containing 1.5-times β-glucan higher than usual barley (barley), was performed, and plasma glucose and C-peptide levels were measured every 30 minutes for 180 minutes. Daily glucose variability was measured using CGM over two days, while subjects consumed 1600-kcal or 1800-kcal test meals consisting of white rice or barley. Subsequently, a meal tolerance test with identical carbohydrate quantity (52g carbohydrate) with or without 1.8g of β-glucan, was performed in 7 diabetic patients. In NGT subjects and diabetic patients, the incremental area under the curve (AUC) of plasma glucose and C-peptide levels for 180 minutes after the meal tolerance test were significantly decreased following the consumption of barley compared to the consumption of white rice alone. The studies using CGM have demonstrated that the consumption of barley lead to a significant decrease in the 24-h standard deviation of blood glucose (24-h SDBG) and mean amplitude of glycemic excursion (MAGE) in diabetic patients. Similar results were obtained in subsequent tests with identical carbohydrate quantity but with β-glucan.

In conclusion, these results suggest that high-β-glucan barley may contribute to decreased PPG levels and endogenous insulin secretion in both patients with type 2 diabetes and the subjects with NGT.

Disclosure

M. Higa: None. A. Hashimoto: None. M. Hayasaka: None. M. Hijikata: None. A. Ueda: None. K. Oda: None. D. Kato: None. K. Yamashita: None. T. Ichijo: None.
Carnosine Supplementation Reduces Plasma Soluble Transferrin Receptor in Healthy Overweight or Obese Individuals—A Pilot Randomised Trial
Authors: DE COURTEN BARBORA , UKROPEC JOZEF , ALDINI GIANCARLO , UKROPCOVA BARBARA , BAYE ESTIFANOS
Published: June 2018

Abnormalities of iron homeostasis has been shown to cause insulin resistance, type 2 diabetes and cardiovascular disease. Treatment with iron chelators has shown to reverse several chronic diseases including type 2 diabetes. Carnosine, an over-the-counter food supplement with chelating properties, has been shown to lower serum iron and glucose concentrations in diabetic rodents. We have previously shown that carnosine supplementation prevented worsening of glucose metabolism in healthy overweight and obese adults. Yet, the role of carnosine on markers of iron metabolism in humans has not been investigated. We aimed to determine whether carnosine supplementation has an effect on iron parameters in overweight and obese, otherwise healthy adults. We included twenty-six participants, which were randomly allocated to receive 1g carnosine (n=14) or identical placebo (n=12) twice daily for 12 weeks. Iron parameters including iron, ferritin, transferrin, soluble transferrin receptor, total iron binding capacity and iron saturation were measured in serum or plasma by standard commercial assays (Beckman Coulter Diagnostics, New South Wales, Australia). Carnosine supplementation decreased plasma soluble transferrin receptor compared to placebo (mean change difference: -0.07 ± 0.0mg/l, p = 0.04). None of the other iron parameters were different between carnosine and placebo groups. Soluble transferrin receptor was inversely associated with urinary carnosine concentrations after adjusting for age, sex and body mass index (β coefficient: -0.01; 95% confidence interval: -0.02 to -0.003). Neither carnosinase-1 activity nor content correlated with soluble transferrin receptor. Our findings suggest that carnosine may regulate iron metabolism in high risk groups that may contribute to the prevention of insulin resistance and type 2 diabetes. Larger human clinical trials are required to confirm our results.

Disclosure

B. de Courten: None. J. Ukropec: None. G. Aldini: None. B. Ukropcova: None. E. Baye: None.
Increase in Galectin-3 Contributes to Glucose Intolerance and Insulin Resistance following Exposure to the Common Food Additive Carrageenan
Authors: TOBACMAN JOANNE K. , BHATTACHARYYA SUMIT , FEFERMAN LEONID
Published: June 2018

Exposure to low concentration of the common food additive carrageenan (CGN) leads to impaired glucose tolerance and insulin resistance in C57BL/6J mice, due to CGN’s pro-inflammatory effects and changes in phospho-IRS1 phosphorylation. CGN is a sulfated polysaccharide with α-1,3 and β-1,4 galactosidic bonds. Other studies showed: 1) CGN reduced activity of arylsulfatase B, which removes sulfate groups from N-acetylgalactosamine 4-sulfate residues of chondroitin 4-sulfate (C4S) and dermatan sulfate; and 2) galectin-3 binds less with C4S when ARSB is reduced. Increase in galectin-3, which binds to β-galactosides, was reported to inhibit insulin signaling (Li P et al) by effects on the insulin receptor. This background led to the current assessment of effects of the no-CGN diet on galectin-3 levels in serum and galectin-3 mRNA in circulating mononuclear cells. Blood samples were obtained from adults with prediabetes before and after dietary intervention. Baseline serum galectin-3 values averaged 8.94 ng/ml (range 4.06-12.64). In 7 patients on a no-CGN diet for 12 weeks, the mean level declined to 7.25 ng/ml (p=0.006, paired t-test). In contrast, serum galectin-3 was unchanged in participants on the CGN-containing control diet and increased by over 2 ng/ml in subjects on their regular diet. mRNA expression of galectin-3 (NGALS3) in circulating mononuclear cells of patients on the no-CGN diet declined by 69%, and increased by 36% in the CGN-containing diet group and by 98% in the regular diet group (p=0.0002, 1-way ANOVA). Also, serum galectin-3 levels increased to 1.72 times baseline in C57BL/6J mice given CGN in their water supply for 12 weeks. In HepG2 cells, exogenous galectin-3 (25 µg/ml) inhibited insulin-induced glucose uptake by 39%, and was highly correlated with decline in tyrosine phosphorylation of IRS-1. These findings suggest that CGN contributes to glucose intolerance and insulin resistance, in part, by effects on galectin-3.

Disclosure

J.K. Tobacman: None. S. Bhattacharyya: None. L. Feferman: None.
Dietary Energy Density (DED) Is Significantly Associated with Obesity in Japanese Patients with Type 2 Diabetes Mellitus (T2DM)
Authors: TAKEDA YASUNAGA , FUJIHARA KAZUYA , MORIKAWA SAKIKO Y. , HORIKAWA CHIKA , HATTA MARIKO , ISHII DAI , HIRASAWA REIKO , YACHI YOKO , SONE HIROHITO
Published: June 2018

DED, defined as the ratio of energy intake (EI) to food weight, is receiving increased attention reflecting recent reports of its associations with elevated risks for obesity and T2DM in general populations. However, only a few studies have investigated the associations between DED and metabolic variables in patients with established diabetes, which led us to analyze the association between DED and obesity in Japanese patients with T2DM. Cross-sectionally investigated were 1,576 outpatients with T2DM (men 60.8%) who attended 26 clinics having diabetes specialists. Dietary habits were obtained by the Food Frequency Questionnaire based on food groups (FFQg). DED (kcal/g) was calculated by dividing EI (kcal) from foods (excluding beverages) by these food weights (g) and was categorized into tertiles (low (L), <1.36; medium (M), 1.36-1.53; high (H), ≥1.54). We compared nutritional intake between groups by ANCOVA. Multivariate logistic regression model was used to estimate adjusted odds ratios for obesity (BMI≥25) in each tertile and per 1 kcal/g of DED, together with tests of combined tertiles of DED and EI. Both EI (kcal) (L, 1692; M, 1787; H, 1862, p for trend< 0.001) and the fat-energy ratio (%) (L, 28.5; M, 29.5; H, 30.7, p for trend< 0.001) were positively associated according to tertiles of DED. Adjusted odds ratios for obesity were also significantly increased according to tertiles of DED (L, ref; M, 1.33(95% CI:1.01-1.75); H, 1.76(1.32-2.36), p for trend< 0.001) and 4.29(2.38-7.73) per 1 kcal/g of DED. Possibility of obesity was significantly higher for patients in the top tertile of DED regardless of EI but was not significant for those in the bottom tertile regardless of EI.

In conclusion, higher DED, which is related to higher fat intake, was strongly associated with a greater chance of having obesity in T2DM patients regardless of EI. Therefore, DED is critical in assessing diet quality and has clinical relevance in obesity management of patients with T2DM.

Disclosure

Y. Takeda: None. K. Fujihara: None. S.Y. Morikawa: None. C. Horikawa: None. M. Hatta: None. D. Ishii: None. R. Hirasawa: None. Y. Yachi: None. H. Sone: Research Support; Self; Novo Nordisk Inc., Eli Lilly and Company, MSD K.K., Chugai Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Daiichi Sankyo Company, Limited, Ono Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Sanofi, Kowa Pharmaceuticals America, Inc., Eisai Inc..
Changes of the Bone Metabolism Markers and Body Composition in Nonalcoholic Fatty Liver Disease by the SGLT2 inhibitor
Authors: WATANABE CHIZURU , AKUTA NORIO , SUZUKI YOSHIYUKI , KOBAYASHI MASAHIRO , MORI YASUMICHI , KUMADA HIROMITSU
Published: June 2018

We reported that histological improvement was confirmed after 24 weeks of Canagliflozin (CANA) therapy in nonalcoholic fatty liver disease (NAFLD). While increase of the fracture according to the CANVAS Program was reported. In type 2 diabetes patients with NAFLD (T2ND) who showed histological improvement by using CANA (100 mg/ day), we investigated the bone metabolism markers and the body composition (measured using an INBODY770) after at least 1 year of same treatment. The changes of the parameters (Liver enzymes, serum bone specific alkaline phosphatase (BAP: nMBCE/mMCr) and urinary N-telopeptide of collagen type-I (uNTx: U/L)) were investigated before starting treatment (Pre), after 24 weeks (24W), and at the end of follow-up (Post). Six patients (4 men and 2 women, aged 55.3±7.2 years, HbA1c8.4±2.0%, BMI: 28.6±2.2 and the duration 8.0±7.7 years) were able to evaluate bone metabolism, and the follow-up period was 1.3±0.2 years. HbA1c, Liver enzymes and Ferritin levels showed further improvement after more than 24 weeks. The Post-Pre difference of bone minerals (BMi) showed a significant positive correlation with the change of skeletal muscle mass and a significant negative correlation with HbA1c at 24W. In 2 cases that the rate of skeletal muscle mass loss for total body weight loss at 24W was ≥ 30%, the Post BMi decreased more than 5%. There was no correlation with the improvement of the NAFLD activity score by the liver biopsy. BAP levels didn’t change during CANA treatment, while uNTx levels increased in all patients at 24W, but almost returned to Pre levels at Post. (uNTx: Pre 31.3(8.2)/ 24W 425.9(344.5)/ Post 38.1(3.9)). The uNTx levels showed a pronounced increase from Pre (24.0) to 24W (2143.3) in 1 patient with a history of fracture. During long-term CANA therapy, there was ongoing improvement of the liver inflammation markers in T2ND, while these findings suggest that early changes of bone resorption by CANA therapy predict the subsequent state of bone metabolism.

Disclosure

C. Watanabe: None. N. Akuta: None. Y. Suzuki: None. M. Kobayashi: None. Y. Mori: None. H. Kumada: None.
Baseline Vitamin D as a Surrogate Marker for Type 2 Diabetes Remission and Weight Loss following Sleeve Gastrectomy
Authors: ALADEL ALANOUD , PIYA MILAN K. , AZHARIAN SAHAR , CHRISTIAN MARK , MENON VINOD , MCTERNAN PHILIP G.
Published: June 2018

Background: Vitamin D deficiency is associated with obesity and type 2 diabetes mellitus (T2DM), although the use of circulating Vitamin D levels as a predictor of weight loss induced T2DM remission is unclear. Therefore, the aim of this study was to analyze whether pre-bariatric surgery vitamin D levels may predict T2DM outcomes 12 months post-SG.

Method: A cohort of 220 obese participants (74.5% female) with T2DM (Age: 50±9.5yr, BMI: 51.4±7Kg/m2; n=103) and without T2DM (Age: 46±9yr, BMI: 53.5±6.5Kg/m2; n=117) undergoing SG participated in an ethics approved study in a single bariatric centre in the UK. Patient anthropometric and biochemical data including vitamin D were collected at baseline and 12 months post-SG; no vitamin D supplementation at baseline was given.

Results: Baseline vitamin D levels inversely correlated with baseline BMI (P<0.001, r=-0.35). Age, pre-op weight loss and vitamin D levels were correlated with HbA1c 12 months post-SG (P<0.001, r=0.28, P<0.001, r=-0.25 and P<0.05, r=-0.19). Furthermore, baseline vitamin D levels predicted levels of HbA1c post-surgery following adjustment for pre-op weight loss and age. Within the T2DM group, those that achieved T2DM remission 12 months post-SG (49.5%; n=51) had a higher baseline vitamin D compared to those not in remission (43.5±23.8 vs. 33±19nmol/L; P<0.05), with no significant differences between the two groups in baseline BMI, hypertension, pre-op weight loss or excess weight loss (EWL). Interestingly, patients with higher pre-surgical Vitamin D levels also had significantly lower BMI (P<0.005) and higher % EWL (P<0.05) 12 months post-surgery.

Conclusion: Baseline Vitamin D levels appear to be an independent indicator for successful T2DM remission and weight loss, 12 months following SG. The use of baseline Vitamin D levels may help us predict those more likely to do well and prioritize post-surgery support to achieve success for all participant groups.

Disclosure

A. Aladel: None. M.K. Piya: None. S. Azharian: None. M. Christian: None. V. Menon: None. P.G. McTernan: None.
Ascorbic Acid Supplementation Improves Postprandial Glucose and Blood Pressure in People with Type 2 Diabetes
Authors: MASON SHAUN , RASMUSSEN BODIL , WADLEY GLENN D.
Published: June 2018

The aim of the study was to investigate whether ascorbic acid (AA) supplementation improves postprandial glucose responses under free living conditions in people with type 2 diabetes (T2D). Thirty-one people with T2D (26 male, 5 female; aged 61.8 ± 6.8y; duration of diabetes 5.6 ± 4.6y [mean ± SD]) and stable glucose control (HbA1c 7.6 ± 0.7%) and blood pressure (SBP 139 ± 10; DBP 85 ± 9 mmHg) completed a randomized cross-over study involving 4 months of oral AA (2 x 500 mg/day) supplementation and 4 months of placebo supplementation (# ACTRN12616000276459). A minimum wash-out of 4 weeks separated treatments. Participants were affixed with continuous glucose monitors for 48h and consumed standardized meals pre and post supplementation. Intention to treat analyses were used to analyse data. Postprandial glucose area under the curve for 3.5h post meals (10.5h total) and the percent of day spent in hyperglycaemia (>10 mmol/l) were significantly lower by 31% and 11% (∼2.5h) after AA supplementation when compared to placebo, respectively (p<0.05). Significantly lower systolic (-6 mmHg) and diastolic (-4 mmHg) blood pressures were also found after AA supplementation compared to placebo. There were no effects of AA supplementation on percent of day spent in hypoglycaemia (<4 mmol/l), average 24h glucose or HbA1c. Treatments were well tolerated by participants, with no adverse effects reported. Capsule compliance was high for both treatments (AA: 93 ± 11%; placebo: 95 ± 7%).

In summary, AA supplementation attenuated the daily post-prandial glucose response and the proportion of day spent in hyperglycaemia in people with T2D. AA also improved blood pressure in this group. This evidence collected under free-living conditions strengthens the argument for AA as a beneficial adjunct therapy to improve glycaemic control and cardio-metabolic health for people with T2D.

Disclosure

S. Mason: None. B. Rasmussen: None. G.D. Wadley: None.
Social Support or Diabetes Distress—What Relates More Closely to Diabetes Self-Management in Hispanics?
Authors: CLARK TAYLOR , EUYOQUE JOHANNA A. , PHILIS-TSIMIKAS ATHENA , GALLO LINDA , FORTMANN ADDIE L.
Published: June 2018

Adherence to recommended self-management behaviors is particularly poor among Hispanics with type 2 diabetes (T2D), which increases risk for developing serious complications. In addition to minority status, research has also shown diabetes distress to predict poorer diabetes self-management. In contrast, social-environmental support for disease management has emerged as a potential protective factor, given associations of greater support with better diabetes self-care. This study aimed to compare the relative associations of support [Chronic Illness Resource Survey] and diabetes distress [Diabetes Distress Scale] with diabetes self-management [Summary of Diabetes Self-Care Activities]. A cross-sectional baseline analysis of N=126 Hispanic adults with poorly controlled T2D (HbA1c ≥ 7.5%) at federally-qualified health centers in Southern California was performed. When examined separately, lower diabetes distress (rs = -.26 and -.18) and higher support (rs = .49 and .22) were both significantly associated with better diet and exercise, respectively (ps < .05). However, when entered in joint linear regression models, only support remained a statistically significant predictor of diet (β = 0.46) and exercise (β = 0.18), ps < .05. The associations of diabetes distress with self-management behaviors decreased in magnitude by 30-58% after control for support, and were no longer statistically significant. While diabetes distress certainly impacts self-management behaviors, these findings indicate that support may be a relatively stronger correlate in this population - perhaps due to the emphasis the Hispanic culture places on interpersonal relationships. Findings point to social-environmental support for disease management (not just distress) as an important target for diabetes self-management interventions. However, further longitudinal research is needed to fully disentangle the associations among distress, support, and self-management behaviors.

Disclosure

T. Clark: None. J.A. Euyoque: None. A. Philis-Tsimikas: Research Support; Self; Dexcom, Inc.. Advisory Panel; Self; Dexcom, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Novo Nordisk A/S, Sanofi, Mylan. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc.. Stock/Shareholder; Spouse/Partner; Esperion Therapeutics, Ionis Pharmaceuticals, Inc.. Advisory Panel; Self; AstraZeneca. L. Gallo: None. A.L. Fortmann: None.
Establishing a Clinical Cut-Point for the PAID-Peds (Problem Areas in Diabetes-Pediatric) Survey
Authors: COMMISSARIAT PERSIS V. , TINSLEY LIANE J. , VOLKENING LISA , BUTLER DEBORAH A. , ANDERSON BARBARA , LAFFEL LORI M.
Published: June 2018

Limited access to pediatric diabetes mental health care suggests a need to readily identify youth requiring referral. The current study aimed to establish a clinically meaningful cut-point on the PAID-Peds, a previously validated measure of diabetes distress in youth with type 1 diabetes (T1D).

The 20-item PAID-Peds has shown construct validity with measures of depressive symptoms, diabetes-specific family conflict (DSFC), and general quality of life (QoL). Higher scores (range 0-100) indicate more distress. ROC analyses in youth 8-17 years old compared PAID-Peds scores against established clinical cutoffs for depressive symptoms on the Center for Epidemiological Studies - Depression Scale (CES-D) and Depression Scale for Children (CES-DC) to identify a meaningful clinical cutoff for the PAID-Peds. Confirmation of the cutoff score included assessment of convergent validity with glycemic control and teen-reported measures of treatment adherence, diabetes specific family conflict, and QoL.

The sample included 427 youth ((M±SD) age 14.3±2.1 years, T1D duration 6.4±3.7 years, and A1c 8.4±1.1%); 49% were male, 83% white, 83% from 2-parent families, and 69% pump-treated. ROC analyses identified a cut-point of 41, with sensitivity of 79%, specificity of 69%, and negative predictive value (NPV) of 94%. Youth with PAID-Peds scores ≥41 (n=168) vs. <41 were more likely to be female (59 vs. 45%), perform less frequent BG monitoring (4.8 vs. 5.5x/day), and have higher A1c (8.6 vs. 8.2%) (p <.01 for all). Youth endorsing more distress (≥41 vs. <41) also reported lower adherence and QoL, and more DSFC (p <.001 for all).

The cutoff score of 41 on the PAID-Peds has acceptable sensitivity, specificity, and NPV, and warrants future assessment in clinical research and practice. Establishing a cut-point for clinically meaningful diabetes distress may help clinicians to identify youth at risk for poorer biomedical and psychosocial outcomes, thereby prompting timelier referral for mental health support.

Disclosure

P.V. Commissariat: None. L.J. Tinsley: None. L. Volkening: None. D.A. Butler: None. B. Anderson: Advisory Panel; Self; Sanofi-Aventis. L.M. Laffel: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US, MannKind Corporation, Roche Diagnostics Corporation, Dexcom, Inc., Insulet Corporation, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Johnson & Johnson Diabetes Institute, LLC..
Diabetes Distress and All-Cause Mortality in Patients with Type 2 Diabetes—A Prospective Cohort Study
Authors: HAYASHINO YASUAKI , OKAMURA SHINTARO , TSUJII SATORU , ISHII HITOSHI
Published: June 2018

We studied a cohort of 3,3Japanese patients with type 2 diabetes to determine the prospective association between diabetes distress measured by problem areas in diabetes (PAID) survey at baseline and subsequent risk of all-cause mortality. Longitudinal data were obtained from this cohort who completed the PAID survey at baseline. We excluded patients with a past history of any cancer. We categorized PAID total score into quintiles and assessed the independent correlation with all-cause mortality using the Cox proportional hazards model adjusted for potential confounders [age, gender, BMI, HbA1c, diabetes therapy, urine albumin/creatinine ratio, retinopathy, diabetic neuropathy, and past medical history]. Mean patient age, BMI, and HbA1c level were 64.9 years, 24.6 kg/m2, and 7.5% (57.6 mmol/mol), respectively. Median total PAID score was 29 overall, and 21, 25, 30, 39, and 55 for the1st to 5th quintiles, respectively. We observed 251 of any death cases during median follow-up of 6.1 years. Compared with the 1st quintile of PAID score, the multi-variable adjusted hazard ratios of all-cause mortality were 1.11 (95% CI, 0.78-1.60; p = 0.56), 0.87 (95% CI, 0.56-1.35; p = 0.524), 0.95 (95% CI, 0.62-1.44; p = 0.802), and 1.60 (95% CI, 1.09-2.35; p = 0.016).

In conclusion, diabetes distress measured by the PAID survey was associated with a subsequent risk of all-cause mortality in patients with type 2 diabetes.

Disclosure

Y. Hayashino: None. S. Okamura: None. S. Tsujii: None. H. Ishii: None.
Behavior Change of Participants in Group vs. Individual DPP Weight Loss Interventions—The SHINE Study
Authors: TRIEF PAULA M. , DELAHANTY LINDA M. , CIBULA DONALD A. , WEINSTOCK RUTH S.
Published: June 2018

Objective: To compare change in physical activity (PA) and dietary fat intake (DFI) in the SHINE (Support, Health Information, Nutrition and Exercise) Study. SHINE was a randomized, controlled weight loss trial (n=257) of 2 telephone (to increase reach) translations of the Diabetes Prevention Program (DPP) lifestyle change intervention, delivered at 5 diverse healthcare sites.

Methods: Participants (metabolic syndrome, no diabetes) were randomized to the DPP lifestyle change program, participating individually (solo; n=129) or in a group conference call (group; n=128). The 16-session DPP curriculum was delivered in year-1 by trained primary care staff and coaches, with continued contact in year-2. Participants: mean age= 51.8 years, 74.3% female, 85.6% white, 44.1% employed, 36.9% annual income <$30K, mean BMI= 39.3 kg/m2, mean PA = 2428.0 mets/week, mean DFI = 33.5% of total calories. We previously reported that both group and solo arms lost significant weight, but solo participants regained. Here we look at change in PA (International Physical Activity Quest.) and DFI (NCI Fat Screener). Mixed linear models compared mean change from baseline in PA and DFI, within and between arms, at 6, 12 and 24 mos. for this longitudinal dataset.

Results: Compared to baseline, the group arm increased PA at 6, 12 and 24 mos. (71.0, 139.5, 255.0 mets/week), the solo arm only improved at 24 mos. (102.0 mets/week). Compared to baseline, the group arm showed decreased DFI at 6, 12 and 24 mos. (1.4%, 1.4%, 1.4%); the solo arm improved at 6 and 12 mos. (2.6%, 2.9%) but not at 24 mos. There were no differences between arms in means for PA or DFI.

Conclusions: Primary care staff can be trained to deliver a telephonic DPP translation that is effective to achieve significant PA and DFI behavior change. Despite anecdotal concerns that group contact may be less tailored to individuals and thus less effective, we found that group may be more effective than solo contact in achieving activity and diet changes associated with weight loss.

Disclosure

P.M. Trief: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. L.M. Delahanty: Consultant; Self; Janssen Pharmaceuticals, Inc., Akcea Therapeutics, Nutrisystem, Inc.. Advisory Panel; Self; Jana Care Inc., Omada Health, Inc.. D.A. Cibula: None. R.S. Weinstock: Research Support; Self; Medtronic MiniMed, Inc., Mylan, Kowa Pharmaceuticals America, Inc., Diasome Pharmaceuticals, Inc., Calibra Medical, Dexcom, Inc., Ultradian Diagnostics LLC., JAEB Center For Health Research, JDRF, National Institute of Diabetes and Digestive and Kidney Diseases.
Psychosocial Benefits of Structured Support for Self-Care in Teens with Type 1 Diabetes (T1D)—Results of an RCT
Authors: COMMISSARIAT PERSIS V. , VOLKENING LISA , BUTLER DEBORAH A. , ANDERSON BARBARA , LAFFEL LORI M.
Published: June 2018

There are salient outcomes beyond A1c, including patient-reported outcomes, in the current era of diabetes interventions. The current study assessed psychosocial effects over 1 year in the Teenwork Study, an RCT utilizing text-messaging (TM) and problem solving (PS) interventions in a 2x2 factorial design, in teens with T1D.

Teens ages 13-17 from 2 U.S. clinical sites were randomized to 4 groups: PS, TM, PS+TM, or usual care. The PS and PS+TM groups had quarterly intervention sessions with study staff targeting barriers and strategies to improve self-care related to BG monitoring and insulin administration. The TM and PS+TM groups received reminders to check BG levels at self-selected times from 1-4 times/day. All teens completed measures of affect around BG monitoring, depressive symptoms, self-efficacy, parent involvement in diabetes care, diabetes-specific family conflict, diabetes distress, and general quality of life at baseline and 1 year. Changes in survey scores from 0 to 12 months were analyzed by group assignment, controlling for baseline scores.

The sample included 281 teens ([M±SD] age 15.0±1.3 years, T1D duration 6.6±3.8 years, 4.6±1.9 BG checks/day, A1c 8.5±1.1%). Teens were 51% male, 78% white, and 80% from 2-parent families; 64% used pump therapy. At entry, groups had similar demographic and diabetes characteristics. After 1 year, all 4 groups had a significant increase in independent care behaviors (less parent involvement) (p<.001). Teens in the PS+TM group had decreases in diabetes family conflict (p=.009) and diabetes distress (p=.01). There were no changes in other psychosocial measures.

Increased independent self-care across groups was likely developmentally driven. Combined PS+TM reduced teen-reported diabetes family conflict and diabetes distress. Providing problem-solving skills at quarterly visits with text reminders between visits together may serve to encourage and empower teens with T1D, thus improving their psychosocial outcomes.

Disclosure

P.V. Commissariat: None. L. Volkening: None. D.A. Butler: None. B. Anderson: Advisory Panel; Self; Sanofi-Aventis. L.M. Laffel: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US, MannKind Corporation, Roche Diagnostics Corporation, Dexcom, Inc., Insulet Corporation, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Johnson & Johnson Diabetes Institute, LLC..
Sleep Quality and Heart Rate Variability in Adolescents with Type 1 or Type 2 Diabetes
Authors: FAULKNER MELISSA S. , HELVIG ASHLEY
Published: June 2018

Regardless of the type of diabetes, there is twice the risk of experiencing cardiovascular (CV) disease complications in comparison to not having the disease. Although these complications and associated symptoms are rarely noted in adolescents with diabetes, early identification of biobehavioral markers for CV risks are essential for targeted approaches for prevention of later disease sequelae. Decreased sleep quality and heart rate variability (HRV) have both independently been associated with diabetes or the presence of obesity and risk for developing diabetes, as well as with CV disease. Studies exploring both sleep quality and HRV in adolescents with diabetes are not available. Thus, we conducted a secondary analysis of data from an existing study to examine differences in sleep quality and HRV in adolescents with type 1 (T1D) vs. type 2 diabetes (T2D); and to determine if there were associations between HRV and sleep quality. Adolescents with T1D (n = 101; 56 males) or T2D (n= 37; 16 males) completed 24-hour HRV Holter monitoring and measurement using Burdick Vision Premier™ ECG Analysis and Editing software system (Waukesha, WI), hemoglobin A1c (HbA1c) using the Abbott IMx® assay method, and a self-report global measure of the impact of diabetes on their sleep quality using a 5-point Likert scale. Duration of diabetes was greater (P \ .001) and measures of HRV were higher in T1D (P \ .01); BMI and BMI z-scores (P \ .001) and systolic and diastolic BP (P ≤ .05) were higher in T2D. No differences in recent or average HbA1c, Tanner staging or sleep quality were found. Both spectral and time domain measures of HRV were associated with sleep quality in T2D (r = - .51 to -.38, P \ .02); only time domain measures were associated with sleep quality in T1D (r = -. 21 to -.19, P ≤ .05). Poorer sleep quality was evident in those with lower HRV; these linkages were stronger in those with T2D. Further study is warranted to elucidate risks and improve sleep quality and CV outcomes in youth with diabetes.

Disclosure

M.S. Faulkner: None. A. Helvig: None.
Glycemic Variability from CGM Correlates with Indices of Glucose Metabolism in Healthy Obesity but Not in Type 2 Diabetes
Authors: ELSHAFIE AHMED , LAM WAI , PARIKH LISA , RANGEL ELIZABETH SANCHEZ , SCHMIDT CHRISTIAN P. , HWANG JANICE , YECKEL CATHERINE W. , SHERWIN ROBERT , BELFORT-DEAGUIAR RENATA
Published: June 2018

We evaluated the relationship between measurements of beta cell function and insulin resistance assessed from OGTT and 2-step glucose clamp data with indices of glucose variability (GV) obtained with a continuous glucose monitor (CGM) in obese subjects with and without type 2 diabetes (T2D). 17 healthy obese (OB) (FPG 91 ± 4.9mg/dl and A1c 5.2 ± 0.4%) and 8 age- and weight-matched participants with T2D treated with diet and/or metformin (FPG 131.5 ± 42.8 mg/dl and A1c 6.8 ± 0.8%) wore CGM (Dexcom®) for up to 5 days. EasyGV® software was used to calculate indices of GV: standard deviation (SD), mean amplitude of glycemic excursions (MAGE), J-Index, continuous overlapping net glycemic action (CONGA), and Glycemic Risk Assessment in Diabetes Equation (GRADE). Indices of glucose metabolism were determined with a 2 hour OGTT and a two-step hyperglycemic-euglycemic clamp. Insulin levels during the hyperglycemic-step of clamp (116 ± 126 vs. 40 ± 23 mU/mL) were equal in both groups, while glucose infusion rate (GIR) (7.7 ± 3.1 vs. 3.9 ± 2.4 mg/kg/minutes) during euglycemia was as expected significantly lower in the T2D subjects compared to OB subjects. GV indices (SD, CONGA, J-Index, GRADE) were statistically lower in OB vs. T2D (P<0.05). Insulin Sensitivity Index (ISI0-120) and the insulin secretion-sensitivity index-2 (ISSI-2) were also lower in obese than in T2D subjects (P<0.001). CGM indices (mean, CONGA, J-index, and GRADE) correlated with incremental AUC of insulin during the OGTT, but not for glucose; as well as insulin levels during the hyperglycemic-step (r=0.740, P<0.01), and GIR during the euglycemic step of the clamp (r= -0.733, P<0.01). CGM measures of GV (CONGA, J-Index, and GRADE) were lower in obese compared to T2D subjects. These results suggest that GV indices are surrogate measurements of beta cell function and insulin action in obese subjects, and may help determine progression to T2D.

Disclosure

A. Elshafie: None. W. Lam: None. L. Parikh: None. E. Sanchez Rangel: None. C.P. Schmidt: None. J. Hwang: None. C.W. Yeckel: None. R. Sherwin: Other Relationship; Self; QuintilesIMS, MannKind Corporation. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Other Relationship; Self; ICON plc. R. Belfort-DeAguiar: Research Support; Self; GlaxoSmithKline plc..
Diabetic Complications Associated with Poor Sleep Quality in Type 2 Diabetes
Authors: CHOI DUGHYUN , KIM BO-YEON , JUNG CHAN-HEE , KIM CHUL-HEE , KANG SUNG-KOO , MOK JI-OH
Published: June 2018

Purpose: Metabolic disorders are known to cause poor sleep quality. However, there is not much research about the association of diabetic complications and poor sleep quality. Our aim was to find out which diabetic complications are associated with poor sleep quality in type 2 diabetes (T2D).

Methods: In this cross-section study, sleep quality of 151 T2D patients were assessed by using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. PSQI score was interpreted as good sleep quality for ≤ 5 and poor sleep quality for > 5. Microvascular complications were assessed with the presence of diabetic retinopathy, diabetic polyneuropathy (DPN) and microalbuminuria. Macrovascular complications were assessed with ankle-brachial index, pulse wave velocity, and carotid intima-media thickness.

Results: Fasting c-peptide, insulin, triglyceride (TG) and waist-hip ratio (WHR) were higher in the poor sleep quality group. Among the complications, the proportion of DPN was higher in the poor sleep quality group (31.7% vs. 15.2%, p=0.020). Other diabetic complications did not show a significant difference between both groups (Table). After adjustment for sex, age, usage of insulin, TG, WHR and DPN, fasting c-peptide was the only significant marker for poor sleep quality in T2D (OR = 2.207, p = 0.048).

Conclusion: DPN was higher in the poor sleep quality group. Other diabetic complications showed no significant difference in both groups.

Disclosure

D. Choi: None. B. Kim: None. C. Jung: None. C. Kim: None. S. Kang: None. J. Mok: None.
Cognitive Function Is Impaired in Recently Diagnosed Type 2 Diabetes, but Not in Type 1 Diabetes
Authors: VAN GEMERT THERESA , WÖLWER WOLFGANG , WEBER KATHARINA S. , HOYER ANNIKA , STRASSBURGER KLAUS , BOHNAU NORA T. , BRÜGGEN MARIE , OVELGOENNE KATHARINA , GÖSSMANN EVA-MARIA , BURKART VOLKER , SZENDROEDI JULIA , RODEN MICHAEL , MÜSSIG KARSTEN
Published: June 2018

Diabetes associates with higher risk of dementia. We hypothesized that cognitive function is already impaired during the early course of diabetes. Thus, we performed a cross-sectional analysis within the German Diabetes Study including patients within the first year after diagnosis of type 1 (n=82) or type 2 (n=119) diabetes, patients with type 1 (n=45) or type 2 (n=65) diabetes five years after study inclusion and metabolically healthy humans (n=42). Participants underwent comprehensive metabolic phenotyping and testing of different domains of cognitive function. Cognition test outcomes were compared using linear regression models with age, sex, and crystallized intelligence as independent variables. Furthermore, within the groups, associations between cognitive function and age, sex, body mass index (BMI), insulin sensitivity, high-sensitivity C-reactive protein, hemoglobin A1c, and crystallized intelligence were studied using linear regression analysis. In participants with recently diagnosed diabetes, verbal memory was poorer in patients with type 2 diabetes (P=0.029), but not in type 1 diabetes (P=0.154) when compared to healthy individuals. Five years after diagnosis, type 2 diabetes patients also showed decreased verbal memory than those with type 1 diabetes (P=0.013). In addition to crystallized intelligence, a higher BMI among individuals with recently diagnosed type 2 and male sex among individuals with recently diagnosed type 1 diabetes were associated with impaired verbal memory (all P<0.05).

In conclusion, verbal memory is impaired in individuals with recently diagnosed type 2 diabetes and likely associated with higher body mass.

Disclosure

T. van Gemert: None. W. Wölwer: None. K.S. Weber: None. A. Hoyer: None. K. Strassburger: None. N.T. Bohnau: None. M. Brüggen: None. K. Ovelgoenne: None. E. Gössmann: None. V. Burkart: None. J. Szendroedi: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi. K. Müssig: None.