Type 1 Diabetes Adults Research Articles

Insulin resistance and type 2 diabetes in children

Type 2 diabetes (T2D) is an emerging health risk in obese children and adolescents. Both environmental (lack of physical activity, excess nutritional intake, sedentary lifestyle) and genetic factors contribute to this global epidemic. The growing prevalence of T2D in youth is also associated with a consistently increased incidence of metabolic and cardiovascular complications. Insulin resistance (IR), i.e., whole-body decreased glucose uptake in response to physiological insulin levels, determines impaired glucose homeostasis and it is recognized as cardinal trigger of T2D and cardiovascular disease in both adults and children. In particular, IR and beta-cell dysfunction lead to the persistent hyperglycemia which characterizes T2D. Indeed, both pathological states influence each other and presumably play a crucial, synergistic role in the pathogenesis of T2D, although the precise mechanisms are not completely understood. However, beta-cell dysfunction and IR induce impaired glucose metabolism, thus leading to the progression to T2D. Therefore, understanding the mechanisms correlated with the decline of beta-cell function and IR is crucial in order to control, prevent, and treat T2D in youth. This review focuses on the current knowledge regarding IR and T2D in children and adolescents and showcases interesting opportunities and stimulating challenges for the development of new preventative approaches and therapeutic strategies for young patients with T2D.

Impact of Real-Time CGM Data Sharing on Quality of Life in the Caregivers of Adults and Children With Type 1 Diabetes.

To examine caregivers' experiences with real-time continuous glucose monitoring (RT-CGM) data sharing and its impact on quality of life (QoL) and health outcomes. Parents of children with type 1 diabetes (T1D) (N = 303) and spouses/partners of T1D adults (N = 212) using the Dexcom G5 Mobile or G6 RT-CGM system and who were actively following their T1Ds' RT-CGM data completed a survey examining their perceived value of data sharing, the impact of sharing on their own QoL and their child/partner's health, and how they used RT-CGM data to support their T1Ds' diabetes management. Regression analyses examined whether their actions were linked to reported changes in QoL and health outcomes. Respondents were predominantly non-Hispanic White (91.1% parents; 88.7% partners), female (78.2% parents; 54.7% partners), and college-educated (65.3% parents; 61.8% partners). The majority reported that data sharing had enhanced hypoglycemic confidence (97.7% parents; 98.1% partners), overall well-being (60.4% parents; 63.2% partners), and sleep quality (78.0% parents; 61.3% partners). Of note, three positive caregiver actions were broadly consistent and significant predictors of QoL and health benefits for both parents and partners: celebrating success related to glycemic control, providing encouragement when glycemic control is challenging, and teamwork discussions about how the caregiver should respond to out-of-range values. RT-CGM data sharing was associated with a range of QoL and health benefits for caregivers. Degree of benefits was influenced by the collaborative actions taken by caregivers to support their child's or partner's diabetes management. To determine the most effective strategies for collaborative data sharing, longitudinal trials are needed.

Neural Signatures of Handgrip Fatigue in Type 1 Diabetic Men and Women.

Type 1 diabetes (T1D) is associated with reduced muscular strength and greater muscle fatigability. Along with changes in muscular mechanisms, T1D is also linked to structural changes in the brain. How the neurophysiological mechanisms underlying muscle fatigue is altered with T1D and sex related differences of these mechanisms are still not well investigated. The aim of this study was to determine the impact of T1D on the neural correlates of handgrip fatigue and examine sex and T1D related differences in neuromuscular performance parameters, neural activation and functional connectivity patterns between the motor regions of the brain. Forty-two adults, balanced by condition (healthy vs T1D) and sex (male vs female), and performed submaximal isometric handgrip contractions until voluntary exhaustion. Initial strength, endurance time, strength loss, force variability, and complexity measures were collected. Additionally, hemodynamic responses from motor-function related cortical regions, using functional near-infrared spectroscopy (fNIRS), were obtained. Overall, females exhibited lower initial strength (p < 0.0001), and greater strength loss (p = 0.023) than males. While initial strength was significantly lower in the T1D group (p = 0.012) compared to the healthy group, endurance times and strength loss were comparable between the two groups. Force complexity, measured as approximate entropy, was found to be lower throughout the experiment for the T1D group (p = 0.0378), indicating lower online motor adaptability. Although, T1D and healthy groups fatigued similarly, only the T1D group exhibited increased neural activation in the left (p = 0.095) and right (p = 0.072) supplementary motor areas (SMA) over time. A sex × condition × fatigue interaction effect (p = 0.044) showed that while increased activation was observed in both T1D females and healthy males from the Early to Middle phase, this was not observed in healthy females or T1D males. These findings demonstrate that T1D adults had lower adaptability to fatigue which they compensated for by increasing neural effort. This study highlights the importance of examining both neural and motor performance signatures when investigating the impact of chronic conditions on neuromuscular fatigue. Additionally, the findings have implications for developing intervention strategies for training, rehabilitation, and ergonomics considerations for individuals with chronic conditions.

Incretin as a Pathophysiological Component and Target for Treatment in Youth Type 2 Diabetes (T2D)

Incretin hormones have recently been considered an important pathophysiological factor for T2D in adults and youth due to their role in augmenting insulin secretion (Michaliszyn et al., 2014). It is recognized that glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are glucose-dependent hormones released from the gut that stimulate insulin release from pancreatic β-cells (Muscelli et al., 2006). Thus, the insulin response to oral glucose is significantly greater than the intravenous (IV) glucose administration response; this is known as the incretin effect (Michaliszyn et al., 2014). To date, adults with T2D demonstrate a remarkable decrease in the incretin effect (Nauck et al., 1986), whereas there is lack of evidence in pediatric populations. The incretin effect is also associated with β-cell glucose sensitivity (βCGS), attesting incretins as a high-promising target for T2D treatment (Michaliszyn et al., 2014). Utilizing GLP-1 receptor agonists can be advantageous as a therapeutic option for both adults and youth (Tamborlane et al., 2019; Vanderheiden et al., 2016; Yeow et al., 2017). While metformin and insulin were the sole treatment options for Y-T2D prior to FDA approval (in 2019) for the use of GLP-1 agonists, a recent RISE (Restoring Insulin Secretion) clinical trial reported disappointing results that both metformin alone and insulin glargine for three months followed by metformin for nine months were not effective in restoring/preserving β-cell function in youth with prediabetes and T2D (RISE Consortium &amp; RISE Consortium Investigators, 2019). On the contrary, the role of GLP-1 and the efficacy of the GLP-1 receptors in T2D signifies a strong target for potential treatment. Additional clinical trials are warranted to see if monotherapy of GLP-1 agonist vs. combined (metformin + liraglutide) therapy is effective to reserve Y-T2D to prediabetes and/or normal state. More importantly, future research should focus on disease prevention rather than treatment to avoid aggressive complications and metabolic degradations of Y-T2D (RISE Consortium &amp; RISE Consortium Investigators, 2019). Altogether, it would be germane to investigate whether lifestyle changes (diet, physical activity, exercise medicine) can improve the incretin effect in conjunction with glycemic control in youth.

The influence of time in range on daily mood in adults with type 1 diabetes

To investigate the impact of time in range (TIR) on mood in adults with type 1 diabetes (T1D). We followed a cohort of 219 T1D adults, all currently employing a real-time continuous glucose monitoring system (RT-CGM), to investigate how daily changes in CGM metrics were associated with nightly reports of positive and negative mood over a two-week period. Greater daily %TIR (70-180 mg/dL) and less time in "severe" hyperglycemia (% time above range (TAR) > 300 mg/dL) were both significantly associated with higher ratings on all positive mood elements and lower ratings on most negative mood elements (all ps < 0.05). When entered together as predictors, %TIR but not %TAR >300 emerged as an independent predictor of many of the positive and negative mood variables. Neither daily changes in time spent in hypoglycemia (< 70 mg/dL) nor glycemic variability (represented by the coefficient of variation) were significantly related to reported mood. This study provides the first evidence that time in range (%TIR) is associated with, and likely enhances, daily mood. Consistent with previous studies, we also found that more time spent in "severe" hyperglycemia is linked to more negative mood.

Quantifying Accelerometer-Based Tremor Features of Neuromuscular Fatigue in Healthy and Diabetic Adults

Neuromuscular fatigue affects workers' productivity and health, which is further deteriorated with chronic conditions such as type 1 diabetes (T1D). Enhanced physiological tremor, a key indicator of neuromuscular fatigue, shows great potential in detecting the onset of neuromuscular fatigue. This study aims to determine the feasibility of using a cost-effective wearable accelerometer-based microelectromechanical sensor to convey neuromuscular fatigue-related tremor information in healthy and T1D adults. 42 adults (22 healthy, 20 T1D), equipped with a finger and a wrist accelerometer, performed intermittent submaximal isometric handgrip fatigue exercises using a grip dynamometer. Motor variability feature, namely, Coefficient of Variation (CV), and motor complexity feature, namely approximate entropy (ApEn), were extracted from the force signal of dynamometer and from the finger and wrist tremor accelerometry signals and subjected to statistical analysis. First, significant positive correlations were found between tremor accelerometry and force signal in terms of motor variability and complexity features. Second, a three-way (fatigue phase: early, middle, late; gender: male, female; condition: healthy, T1D) analysis of variance resulted in a significant fatigue effect on both accelerometry and force measurements in terms of motor variability and complexity features. Apart from finger CV, no other features showed any gender or condition effects. These findings indicate that finger and wrist tremors measured by accelerometer-based sensors can retain the robustness of fatigue-related motor variability and complexity. Wrist tremor features were found to capture fatigue development across both healthy and diabetic males and females, thereby offering comparable fatigue detection and management in adults with chronic conditions.

Modeling Carbohydrate Counting Error in Type 1 Diabetes Management.

Background: The error in estimating meal carbohydrates (CHO) amount is a critical mistake committed by type 1 diabetes (T1D) subjects. The aim of this study is both to investigate which factors, related to meals and subjects, affect the CHO counting error most and to develop a mathematical model of CHO counting error embeddable in T1D patient decision simulators to conduct in silico clinical trials.Methods: A published dataset of 50 T1D adults is used, which includes a patient's CHO count of 692 meals, dietitian's estimates of meal composition (used as reference), and several potential explanatory factors. The CHO counting error is modeled by multiple linear regression, with stepwise variable selection starting from 10 candidate predictors, that is, education level, insulin treatment duration, age, body weight, meal type, CHO, lipid, energy, protein, and fiber content. Inclusion of quadratic and interaction terms is also evaluated.Results: Larger errors correspond to larger meals, and most of the large meals are underestimated. The linear model selects CHO (P < 0.00001), meal type (P < 0.00001), and body weight (P = 0.047), whereas its extended version embeds a quadratic term of CHO (P < 0.00001) and interaction terms of meal type with CHO (P = 0.0001) and fiber amount (P = 0.001). The extended model explains 34.9% of the CHO counting error variance. Comparison with the CHO counting error description previously used in the T1D patient decision simulator shows that the proposed models return more credible realizations.Conclusions: The most important predictors of CHO counting errors are CHO and meal type. The mathematical models proposed improve the description of patients' behavior in the T1D patient decision simulator.

Relationships of adipocyte-fatty acid binding protein and lipocalin 2 with risk factors and chronic complications in type 2 diabetes and effects of fenofibrate: A fenofibrate Intervention and event lowering in diabetes sub-study

AimsTo investigate determinants of circulating levels of adipocyte-fatty acid binding protein (A-FABP) and lipocalin-2 (LCN2), their relationships with cardiovascular disease (CVD) and microvascular events, and effects of fenofibrate in type 2 diabetes (T2D). MethodsA-FABP and LCN2 were quantified in baseline plasma from 2000 T2D adults in a Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial sub-study and correlates thereof determined. In a subset (n = 200) adipokines were also measured on-trial. ResultsFemale sex, older age, higher body mass index (BMI), HbA1c, insulin resistance index, triglycerides, plasma creatinine and homocysteine, shorter diabetes duration, and use of oral hypoglycaemic agents alone were independent determinants of higher A-FABP. Higher BMI, fibrinogen and homocysteine, Caucasian race, and lower fasting glucose, HDL-cholesterol, apolipoprotein A-II and estimated glomerular filtration rate were independent predictors of higher LCN2 levels. Baseline A-FABP and LCN2 levels were associated with multiple new CVD and microvascular events over 5-years, though significance was lost after risk factor adjustment. Fenofibrate increased A-FABP but did not change LCN2 levels. ConclusionsBaseline plasma A-FABP and LCN2 levels were associated with concurrent CVD risk factors, and on-trial chronic complications, likely mediated via traditional risk factors. Fenofibrate increased A-FABP modestly but did not affect LCN2 levels.Clinical Trial Registration: ISRCTN 64783481.

Contributions of Fat and Carbohydrate Metabolism to Glucose Homeostasis in Childhood Change With Age and Puberty: A 12-Years Cohort Study (EARLYBIRD 77)

Puberty—a period when susceptibility to the onset of Type 2 diabetes (T2D) increases—is marked with profound physiological and metabolic changes. In the EarlyBird cohort, children who developed impaired fasting glycemia in adolescence already exhibited higher fasting blood glucose at 5 years of age, independent of their body mass index (BMI), suggesting that pubertal factors may modify existing predisposition. Understanding how the physiological changes during childhood influence glucose homeostasis and how the central energy metabolism may help deciphering the mechanisms that underlie the risk of developing T2D in children and adults. We investigated these associations by analyzing glycemic variations with molecular markers of central energy metabolism, substrate oxidation status and pubertal stages in the EarlyBird cohort. The EarlyBird study is a non-interventional, prospective cohort study, that recruited 307 healthy UK children at age 5, and followed them annually throughout childhood for 12 years. Longitudinal data on blood biochemistry, respiratory exchange ratio, and anthropometry, available from 150 children were integrated with fasting glycemia. The gradual rise in blood glucose during childhood associates with age-dependent changes in molecular processes and substrate oxidation status, namely (i) greater pre-pubertal fat utilization, ketogenesis, and fatty acid oxidation, and (ii) greater pubertal carbohydrate oxidation and glycolytic metabolism (Cori and Cahill Cycles) associated with different amino acid exchanges between muscle and other tissues (proline, glutamine, alanine). Since children's metabolic and nutritional requirements evolve during childhood, this study has potential clinical implications for the development of nutritional strategies for disease prevention in children.

Seasonal variations on endothelium-dependent flow-mediated vasodilation in adults with type 2 diabetes and nondiabetic adults with hypertension and/or dyslipidaemia who perform regular exercise.

IntroductionEndothelium‐dependent flow‐mediated dilation (FMD) of the brachial artery often changes seasonally. We aimed to examine the association between the seasonal variation on FMD and regular exercise in adults with type 2 diabetes (T2D) and nondiabetic adults with hypertension and/or dyslipidaemia (non‐T2D).MethodsThis retrospective study included 14 T2D and 17 non‐T2D adults, who started to perform moderate‐intensity aerobic exercise for 30‐40 min/d at a hospital gym in 2006‐2010 and maintained exercise performance at least 2 d/wk until the end of the observation period. We observed and analysed the data for 5 years (from March 2011 to February 2016). FMD, cardio‐ankle vascular index (CAVI) and metabolic outcomes were compared among seasons in the T2D and non‐T2D groups.ResultsThe FMD values were lower in winter than in other seasons in both groups (all P < .01). The annual range of FMD was larger by 31% in the T2D group than in the non‐T2D group (P < .05). The systolic blood pressure (BP) values were higher in winter than in other seasons in both groups (all P < .01), and the diastolic BP values were higher in winter than in summer in both groups (T2D: P < .05; non‐T2D: P < .01). CAVI and other outcomes did not change seasonally.ConclusionsFlow‐mediated vasodilation showed seasonal variation in T2D adults, even if they performed exercise regularly for a long period of time. Additionally, we found that the annual range of FMD might increase with the presence of T2D.

98-OR: Placental DNA Methylation Changes Associated with Birthweight and Overlaps with Adult Type 2 Diabetes

Background: There is cumulating evidence for associations between birthweight-lowering genetic factors and increased risk of type 2 diabetes (T2D). Given the crucial role of the placenta in supporting fetal growth, epigenetic mechanisms in placenta may lend insights into prevention of T2D in early life. We investigated epigenetic changes in placenta associated with birthweight and those that overlap with T2D risk. Methods: DNA methylation was measured using Illumina’s Infinium Human Methylation450 Beadchip in placenta samples obtained from race/ethnic-diverse pregnant women who participated in the NICHD Fetal Growth Studies (n=301). Associations between DNA methylation and birthweight were tested using linear regression models. Next, we examined whether DNA methylation at loci previously implicated in adult T2D were associated with birthweight in placenta. The relationship between DNA methylation and gene expression was tested in 75 placenta samples profiled for both DNA methylation and gene expression. Statistical tests were considered significant at a false discovery rate &amp;lt; 0.05. Results: Placenta methylation at 15 cytosine-phosphate-guanine (CpG) sites was significantly associated with birthweight, of which methylation at UBXN11, LBX2, CNIH2, and PDE9A was significantly associated with expression of nearby genes. At six CpG sites (MGRN1, AMIGO2, CHD3 and three intergenic regions) known in previous studies to be associated with adult T2D, we found significant associations between DNA methylation in placenta and birthweight. For all the six CpG sites, the methylation changes related to increased risk of T2D were associated with lower birthweight. Conclusions: We found novel placental DNA methylation signatures associated with lower birthweight and higher risk of adult T2D. Our findings provide the first evidence to suggest that epigenetic changes in the placenta may be one potential mechanism that explains the link between early growth and later life T2D. Disclosure F. Tekola-Ayele: None. T. Workalemahu: None. X. Zeng: None. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development

151-OR: Radiologic Evidence that Hypothalamic Tissue Is Abnormal in Adults with Obesity and Type 2 Diabetes or Impaired Glucose Homeostasis

Gliosis, a cellular response to injury in neural tissue, is linked to diet-induced obesity in rodent models. Growing evidence also implicates reactive gliosis and inflammation of the mediobasal hypothalamus (MBH) as a potential mechanism connecting obesity to insulin resistance. We tested for radiologic evidence of MBH gliosis in humans in relation to impaired glucose homeostasis and type 2 diabetes (T2D), independent of obesity. Adults with obesity and 1) T2D not on insulin (N=17), 2) impaired glucose tolerance (IGT; N=21), or 3) normal glucose tolerance (NGT; N=29) by OGTT underwent magnetic resonance imaging to measure mean bilateral T2 relaxation time (ms) in the MBH and 3 control regions. Longer T2 relaxation time is a marker of gliosis. Groups were matched for race, sex, BMI and % body fat (P=0.99), but age differed (T2D 54 ± 8 y, IGT 46 ± 11 y, NGT 45 ± 12 y; P=0.02). Group differences in T2 relaxation time varied by brain region (interaction: chi2(6) = 65, P&amp;lt;0.0001, adjusted for sex and age). Bonferroni-corrected post-tests confirmed that MBH, but not control region, T2 relaxation times were longer in T2D (180 ± 26 ms) than IGT (160 ± 26 ms, P&amp;lt;0.0001) or NGT (152 ± 17 ms, P&amp;lt;0.0001) groups. Among all 67 subjects, fasting glucose, 2-hr post-glucose, and hemoglobin A1c values were each positively associated with MBH, but not control region, T2 relaxation times (interactions by region all P&amp;lt; 0.0001, MBH all P&amp;lt; 0.0001, control regions all NS). Among the 50 subjects without T2D, interactions remained significant (all P&amp;lt;0.0001), and greater 2-hr post-glucose and hemoglobin A1c were associated with longer MBH T2 relaxation times (β = 0.22 ms, P&amp;lt;0.0001 and β = 14.8 ms, P=0.002, respectively) whereas a trend was present for fasting glucose concentrations (β = 0.38 ms, P=0.06). These data provide novel evidence that the degree of inflammation and gliosis in glucose-regulating areas of the brain is related to impaired glucose homeostasis and T2D in adults with obesity. Disclosure J.L. Rosenbaum: None. L.E. Sewaybricker: None. S. Chandrasekaran: None. M. De Leon: None. M. Webb: None. S.J. Melhorn: None. E. Schur: None. Funding American Diabetes Association (1-17-ICTS-085 to E.S.)

400-P: High Levels of Glycemic Coefficient of Variation Are Associated with Higher Hypoglycemia Episodes in T1D Adults in a Brazilian Tertiary Hospital

People with type 1 diabetes (T1D) have a higher risk of hypoglycemia (H), especially in the presence of high glycemic excursion, increasing cardiovascular mortality. The coefficient of variation (CV) allows current assessment of glycemic control and therapeutic adequacy. This cross-sectional study investigated the associations among H episodes, CV, glycemic variability (GV), and T1D clinical and laboratory parameters. Sixty T1D patients aged ≥18 years and followed for at least six months in a Brazilian Public Tertiary Hospital were included. Three seven-point glycemic profiles were performed in consecutive days, totalizing 21 blood glucose tests. The indicators GV, standard deviation (SD)/glycemic mean (mg/dL) and CV, SD/glycemic mean were calculated from data record in the monitor. H was classified as H1:&amp;lt;70 and ≥54mg/dL and H2:&amp;lt;54mg/dL. Statistical analysis was performed with Spearman correlation and Mann-Whitney (p&amp;lt;0.05 was considered significant). Of all, 73.3% were women, aged 34.7 ± 2.3 years, T1D duration: 22.5 ± 9.7 years, HbA1c 8.8 ± 1.8%, GV 70.9 ± 25.9mg/dL (goal&amp;lt;50) and CV 42.8 ± 9.6% (goal&amp;lt;36%). H occurred in 76.7%, and H2 in 50% of T1D patients. H1 was positively correlated with CV (p&amp;lt;0.0001) and T1D duration (p&amp;lt;0.0271); negatively with mean of glycemia (p&amp;lt;0.0001), and glycemia above target (&amp;gt;180mg/dL) (p&amp;lt;0.0004). H2 was positively correlated with CV (p&amp;lt;0.0005); blood glucose below target (&amp;lt;70mg/dL) (p&amp;lt;0.0001), and reported weekly frequency of hypoglycemia (p&amp;lt;0.0470). T1D patients presented high VC and GV. Only CV had a significant correlation with H1 and H2 episodes. Education about quickly hypoglycemia treatment is highly required, mainly in the presence of asymptomatic episodes. Systematic glycemic monitoring and continuing education in diabetes, targeting insulin dose adjustments, glycemic goals, healthy food orientation, and physical activity may reduce life risks of this population. Disclosure T.B. Brasil: None. A.C. Sposito: None. B. Adachi: None. W.M. Volpini: None. E.J. Pavin: None.

11-LB: A Phase 2 Study of Liquid Stable Glucagon to Treat Hypoglycemia-Associated Autonomic Failure

Objective: To evaluate a novel, ready-to-use, liquid stable, continuous subcutaneous (SC) glucagon infusion (CSGI; Xeris Pharmaceuticals) for the treatment of Hypoglycemia Associated Autonomic Failure (HAAF) in adults with type 1 diabetes (T1D). Method: This was a Phase 2 double-blind, randomized, placebo-controlled parallel trial in T1D adults with HAAF (Gold Score ≥4). Subjects were randomized to receive 1 month of high-rate CSGI (HCSGI, 80 μg/hour), low-rate CSGI (LCSGI, 20 μg/hour), or placebo. Epinephrine hormone response to hypoglycemia (assessed during stepwise hypoglycemia clamp procedure) and Gold Scores were measured at baseline, end of treatment, and both 3- and 6-months post-treatment. Results: Forty-nine subjects were randomized to receive treatment (HCSGI n=15; LCSGI n=18; placebo n=16). No statistically significant differences in mean epinephrine hormone response or Gold Scores were observed across treatment arms at end of treatment. Long-term follow-up of the subjects was stopped early. For completed follow-up clamps (31 subjects, 3 months; 22 subjects, 6 months), LCSGI did not exhibit differences to placebo. However, HCSGI 3 and 6 month mean epinephrine hormone responses were greater (p=NS) and Gold Scores improved [(-1.1±1.5 vs. 0.5±1.5; 3 months, p=NS) and (-1.2±1.5 vs. -0.6±0.9; 6 months, p=NS)]. The administration of CSGI was associated with mild to moderate nausea (5.9% for LCSGI and, 20% for HCSGI,) and vomiting (11.8% for LCSGI and 13.3% for HCSGI,). CSGI was not associated with pain, injection site reactions, or necrolytic migratory erythema. No related SAEs were reported. Conclusion: Compared to placebo in a small group of T1D adults with HAAF, HCSGI may exhibit improvements in Gold Score at both 3 and 6 months. Mean serum epinephrine may be a suboptimal biomarker of HAAF. CSGI was safely used with concomitant insulin, and there were no related SAEs. Disclosure J. Pettus: Consultant; Self; Diasome Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., MannKind Corporation, Novo Nordisk Inc., Sanofi. S. Nakhle: None. F. Ovalle: Research Support; Self; Gan &amp; Lee Pharmaceuticals, Gilead Sciences, Inc., Lilly Diabetes, Novo Nordisk A/S, Sanofi, Xeris Pharmaceuticals, Inc. M.K. Junaidi: Employee; Self; Xeris Pharmaceuticals, Inc. N.C. Close: Employee; Self; EmpiriStat, Inc. V. Conoscenti: None. A. Nguyen: None.

677-P: Use of a Hybrid Closed-Loop System Lowers CHO Requirements during Prolonged Exercise

Some individuals with type 1 diabetes (T1D) use the DIY Kit RileyLink Loop System (Loop) during exercise to avoid hypoglycemia and maintain optimal glucose levels; however, the system has no regulatory approval. This exploratory retrospective analysis assessed carbohydrate (CHO) requirements for maintaining glucose in target range (70-180 mg/dL) during and after 2 days of prolonged cycling, comparing the Loop with rtCGM plus insulin pump (rtCGM+P). Seven T1D adults (2 female/5 male, age 41±11 years, 6.1±0.8% A1C) were enrolled. Cycling was divided into two parts each day (Part 1, 28 miles; Part 2, 17 miles) with an hour lunch between parts. CHO intake was lower in the Loop group vs. rtCGM+P on Day1. (Table 1) More CHOs were required on Day2 than Day1 with Loop use (rtCGM+P users did not cycle on Day2). Prandial insulin doses were notably lower at the Day2 lunch meal vs. Day1 44 g CHO/IU vs. 6 g CHO/IU. Loop users vs. rtCGM+P users spent notably less time &amp;lt;70 mg/dL on Day 1 (5.4 ± 4.4% vs. 12 ± 17%, respectively) and Post Exercise Day (3.8 ± 2.8% vs. 0.5 ± 0.7%, respectively). Time spent within 70 - 180 mg/dL were comparable on Day1 (84 ± 16% vs. 82 ± 17%, respectively) and Post Exercise Day (88 ± 10% vs. 91 ± 11%, respectively. Use of the Loop was associated with lower CHO requirements during prolonged exercise. Loop settings must be adjusted before and after exercise to maintain glucose levels &amp;lt;220 mg/dL. Disclosure M. Mueller-Korbsch: Research Support; Self; Dexcom, Inc., Menarini Group, Novo Nordisk A/S. L. Fruehwald: None. M. Heer: None. M. Fangmeyer-Binder: None. D. Reinhart-Mikocki: None. P. Fasching: None.

1862-P: Remission of Type 2 Diabetes and Metabolic Parameters Changes with a High-Protein Diet

The purpose of this study was to determine if remission of type 2 diabetes(T2D) can be achieved by macronutrients dietary changes without diabetes medications. High Protein (HP)(30% protein, 30% fat, 40% carbohydrates) or High Carbohydrate (HC)(15% protein, 30% fat, 55% carbohydrates) diets were used to study remission of type 2 diabetes(T2D) to Normal Glucose Tolerance(NGT), weight loss, body composition, and metabolic parameters in this randomized controlled clinical trial feeding study for 6 month(mo) in obese T2D adults. T2D adults age 20-65 years were randomized to a HP or HC diet for 6 mo with all food provided. Caloric need for weight loss was determined by Resting Metabolic Rate(RMR) -500 calories/day. Oral Glucose Tolerance Tests (OGTT) were performed at Baseline (BL) and 6 mo to determine T2D/NGT status. A BL ≥126 mg/dl and HbA1c ≥6.5% and 2 hr glucose &amp;gt;199mg/dl was considered T2D and remission was BL&amp;lt;126 mg/ml and HbA1c&amp;lt;6.5% and 2 hr glucose &amp;lt;140 mg/dl. DXA was done at BL and 6 mo. Food pick up and weight checks were weekly.The T2D subjects on HP diet had 100% remission to NGT while the HC diet subjects had 33% remission. Both diet groups had significant weight loss (HP =15.4±5 lb, HC=19.9±5 lb), improvement in insulin sensitivity determined by HOMA IR [HP(BL 5.3±0.29; 6 mo 2.1±0.13)], [HC(BL 5.2±0.27; 6 mo 4.4±0.26)] and decrease in HbA1c [HP(BL 7.7±.05; 6 mo 5.6±.02)], [HC(BL 7.8±.04; 6 mo 6.6±.06)] and blood pressure improvement S/D [HP (BL 129/85, 6 mo 117/78)], [HC(BL 130/85; 6 mo 117/78)]. HP group had a 2.7%± 0.4% increase in lean body mass and 2.9± 0.4% decrease in fat mass while the HC group had a 1.9%±0.3 and 3.3±0.9 % decrease in lean and fat mass respectively. Both diets resulted in weight loss, improvement in glucose tolerance and insulin sensitivity but only the HP diet produced 100% remission of T2D to NGT. Disclosure F.B. Stentz: None. A. Ammons: None. Funding AD Baskin (R073316012)

894-P: Intermittent Use of Flash Glucose Monitoring (FGM) and Education Improves Glycemia in Type 2 Diabetes (T2D) in Singapore: Pilot Data from Glimpse Project

Limited evidence exists on the use of FGM in people with type 2 diabetes (T2D) on non-prandial insulin therapies. Aim: To study the feasibility of intermittent FGM and education among sub-optimally controlled T2D. Adult T2Ds on any treatment but prandial insulin, HbA1c 7.5-10%, received Freestyle Libre sensor and structured education. Sensor use was continuous for 6 weeks (w), then 2 weekly up to 24w. A blinded sensor was worn at -2w and 24w. n=28, 11 men, mean age 55± 12 y, BMI 27.2 ± 4 kg/m2, 6/28 on basal insulin. Mean HbA1c fell from baseline of 8.5 ± 0.5% to 7.9 ± 0.9% (69 to 63 mmol/mol, p=0.001) and was sustained to 24w (fig 1). SD and TAR (&amp;gt;13.9 mmol/L) showed a trend to improvement (Table 1). Intermittent FGM use with education in T2D showed a sustained improvement in glycemia up to 24 weeks. Disclosure S. Rama Chandran: None. M. Gandhi: None. K. Adaikan: None. N. Tan: None. I.K.Y. Phoon: None. D. Gardner: None. Funding Singapore Ministry of Health (MH34:31/2)

MON-LB110 A Phase 2 Evaluation of a Ready-To-Use Liquid Stable Continuous Subcutaneous Glucagon Infusion for the Treatment of Hypoglycemia Associated Autonomic Failure

OBJECTIVE:A novel, ready-to-use, liquid stable, continuous subcutaneous glucagon infusion (CSGI; Xeris Pharmaceuticals) was evaluated for the treatment of adults with type 1 diabetes (T1D) with documented Hypoglycemia Associated Autonomic Failure (HAAF). METHOD:This was a Phase 2 prospective, multi-center, randomized, placebo-controlled, double-blind, parallel trial in T1D adults with documented HAAF, defined as Gold Scale Score ≥4. Subjects were randomized in a 1:1:1 ratio to receive 4 weeks of continuous treatment (via Omnipod pump) with high rate CSGI (80mcg/hour), low rate CSGI, (20mcg/hour) or placebo (matched infusion rates for low and high rate CSGI). The primary endpoint evaluated at 4 weeks was the percent change of the epinephrine hormone response after 30 minutes of induced hypoglycemia. Epinephrine levels and hypoglycemia symptoms were recorded following a stepwise hypoglycemia clamp, and results compared between study treatment arms. Following the first four weeks, subjects continued for an additional 24 weeks to assess their epinephrine hormone response to hypoglycemia measured at 3 months post-treatment (16 weeks), and 6 months post-treatment (28 weeks). RESULTS:Forty-nine subjects were randomized to receive treatment with high rate CSGI (n=15), low rate CSGI (n=18), or matching placebo (n=16). At the end of study treatment, there were no statistically significant differences between the treatment arms for percent change of epinephrine hormone response during a stepwise hypoglycemia clamp (CSGI vs. placebo; p=0.160). As a result, long-term follow-up of the subjects was stopped early. The long-term follow-up data collected to date will be reported separately. The administration of low and high rate CSGI was associated with mild to moderate nausea (5.9%, 20%, respectively) and vomiting (11.8%, 13.3%, respectively) that was self-limited and required no additional intervention. In this 4-week assessment, CSGI was not associated with pain nor significant injection site reactions, and no SAEs related to CSGI were reported. CONCLUSION:In this proof-of-concept study, CSGI did not demonstrate statistically significant improvements in plasma epinephrine concentration when compared to placebo at 4 weeks. While there were positive epinephrine and improved hypoglycemia awareness responses observed in some subjects, the equivocal efficacy results observed may be explained by the unanticipated and incomplete elimination of hypoglycemia on CSGI therapy, and those on placebo therapy experienced hypoglycemia improvement. CSGI can be safely used with concomitant diabetes medications, and there were no SAEs related to CSGI. The 4-week administration of both low and high rate CSGI was safe and well tolerated.

Association between exposure to ambient fine particulate matter and prevalence of type 2 diabetes in Iran: an ecological study.

Epidemiological evidence for the link between long-term exposure to air particulate matter (PM2.5) and occurrence of type 2 diabetes (T2D) is limited such that little is known about the effect of PM2.5 exposure and adult T2D prevalence. Thus, the aim of this ecological study is to evaluate the contribution of ambient PM2.5 exposure to the adult T2D prevalence in the large population of Iran. The study was conducted based on Iran's large-scale cross-sectional surveilling non-communicable diseases (NCDs) risk factors (Timpka et al. 2015b). A total of 31,050 participants were enrolled in three sequential processes of study using cluster random sampling. PM2.5 data in the urban area of 31 provinces of Iran were acquired from Tehran Air Quality Control Company (AQCC) and the Department of Environment (DoE) of Iran during 2012-2016. Moreover, major and minor diabetes risk factors were considered; the Pearson correlation and a stepwise regression model were performed to estimate associations between risk factors and diabetes and prediabetes prevalence. The results showed T2D prevalence was more frequent among women (10.61%) than men (9.35%). A weak positive correlation was observed between PM2.5 level and diabetes prevalence with a correlation coefficient of 0.275, although there was no significant association between PM2.5 value and prediabetes prevalence. Moreover, none of the variables included in the regression model could predict the prevalence of diabetes and prediabetes. According to our study results, it can be suggested that investigating the association between PM2.5 exposure and T2D prevalence at individual level may provide a better understanding of PM2.5 exposure and the risk of T2D prevalence.

Impact of Self-Reported Sitting Time and Transtheoretical Model Based on Exercise Behavior Change on Glycemic and Weight Control in Japanese Adults with Type 1 Diabetes: A Cross-Sectional Study.

This cross-sectional study aimed to examine the associations among self-reported sitting time (ST), transtheoretical model (TTM) based on exercise behavior change, and glycemic and weight control in Japanese adults with type 1 diabetes (T1D). Forty-two adults (age, 44.0 (33.3–56.8) years) with uncomplicated T1D answered questions regarding their lifestyles, including ST per day, and TTM using self-administered questionnaires. The glycated hemoglobin (HbA1c) level correlated with age and ST (p < 0.05, p < 0.01, respectively), whereas body mass index correlated with duration of T1D and TTM (p < 0.05, p < 0.01, respectively). Logistic regression analysis showed that poor glycemic control (HbA1c, >7%) was associated with ST (odds ratio, 3.53 (95% confidence interval, 1.54–8.11), p < 0.01). In addition, the cut-off points for quartiles of ST were 4.6, 6.0, and 8.0 h/day, and the HbA1c level in the lowest quartile was 15% lower than that in the highest quartile (p < 0.01). Although further studies with larger samples are needed, these results implied that expanded self-reported ST might be related to poor glycemic control in Japanese T1D adults, most of whom were lean, young and middle-aged, regardless of TTM based on exercise behavior change.