Baseline Glucose Research Articles

P5469Isolated systolic hypertension and combined systolic-diastolic hypertension for prediction of new-onset diabetes mellitus: Data from a 8-year-follow-up study

Abstract Background/Introduction Isolated systolic hypertension (ISH) and combined systolic-diastolic hypertension (CH) are related with increased cardiovascular risk, while new-onset diabetes mellitus (NOD) is linked with atherosclerosis progression. Purpose The aim of the present study was to compare the predictive role of ISH and CH for the incidence of NOD in a cohort of essential hypertensive patients. Methods We followed up 1435 non-diabetic essential hypertensives with office systolic blood pressure (BP)≥140 mmHg [mean age 57 years, 730 males, office BP=153/92 mmHg] for a mean period of 8 years. All subjects had at least one annual visit and at baseline underwent echocardiographic study and blood sampling for estimation of metabolic profile. Patients with baseline ISH exhibited office systolic BP ≥140 mmHg and office diastolic BP <90 mmHg, while those with CH had office systolic BP ≥140 mmHg and office diastolic BP ≥90 mmHg. Moreover, NOD was defined if at one or more of the follow-up visits a previously non-diabetic patient reported being on insulin or an oral hypoglycemic drug or if casual plasma glucose concentration ≥200 mg/dl or fasting glucose concentration ≥126 mg/dl or 2-h post load glucose ≥200 mg/dl during an oral glucose tolerance test. Results The incidence of NOD over the follow-up period was 4.2% (n=60). Patients with ISH (n=460) compared to those with CH (n=975) were older (65±11 vs 54±10 years, p<0.0001), had at baseline lower waist circumference (94.5±11 vs 99±13 cm, p<0.0001), office systolic BP (149±12 vs 155±13 mmHg, p<0.0001), office diastolic BP (80±8 vs 98±6 mmHg, p<0.0001), while did not differ regarding left ventricular mass index, glucose and lipid levels (p=NS for all). Univariate Cox regression analysis revealed that baseline ISH (hazard ratio=2.143, p=0.016) and CH (hazard ratio=1.272, p=0.029) predicted NOD. However, in multivariate Cox regression model, age (hazard ratio=1.039, p<0.001), baseline glucose levels (hazard ratio 1.011, p=0.016), waist circumference (hazard ratio=1.067, p<0.001) and ISH (hazard ratio=1.651, p=0.029) but not CH turned out to be independent predictors of NOD. Conclusions In essential hypertensive patients, ISH but not CH exhibits independent prognostic value for NOD. These findings support that ISH constitutes a hypertensive phenotype of increased metabolic risk needing careful evaluation and treatment.

Glucose and insulin curve in pregnant mares and its relationship with clinical and biometric features of newborn foals

ABSTRACT: The aim of the present study was to describe the dynamics of glucose and insulin curves in pregnant mares, and to evaluate the curves according to body condition score, identifying the presence of insulin resistance and correlating these values with the weight, height and clinical changes of the neonates. For this, pregnant mares were evaluated and then grouped according to body condition score during the gestation length until lactation. GrM corresponds to mares with moderate body score (BCS 5-6); GrOv were mares with overweight body score (BCS 7) and GrOb were obese mares (BCS 8-9). A two-step oral sugar test (OST) was used to determine the data. Cortisol analysis was performed with 300-320 days of gestation, at foaling and after parturition. For evaluation of the neonate, a general clinical examination and, weight and height measurements were performed. The results showed hyperglycemia in response to OST with normal insulin values at foaling with a subsequent fall in both values at lactation disregarding group division. Baseline glucose was decreased in GrM compared to GrOv and GrOb with 70-100 days of gestation and with 130-160 days of gestation. With 270-300 days of gestation and post-partum GrOb had increased baseline glucose than GrM. After OST, glucose at foaling day in GrOb presented increased values than GrM. Baseline insulin values did not differ between groups. Post OST insulin levels were higher in GrOb than GrM and GrOv at parturition. No difference in cortisol between moments was identified. GrOb and GrOv maintained increased concentrations after foaling while GrM had a decrease. No correlation was found between maternal glucose and insulin values with foal weight and height, however, a lower ratio between neonatal weight and mare’s weight in GrOb and GrOv was identified in relation to the GrM. At foaling, mares presented glucose dysregulation, with obese and overweight mares presenting a greater response to OST.

Valoración de la grasa hepática y pancreática como biomarcadores de imagen en el síndrome metabólico

ObjectiveTo objectively evaluate hepatic and pancreatic involvement in metabolic syndrome through magnetic resonance imaging (MRI) biomarkers. Material and methodsFrom an initial retrospective sample of 407 patients diagnosed with metabolic syndrome studied by MRI in a single center during a 2-year period, 154 were excluded because of a lack of clinical and/or laboratory data, pancreatic abnormalities, or inadequate quality of MRI studies. To measure hepatic and pancreatic fat, we used chemical shift imaging (in-phase and out-of-phase), measuring the fat fraction (%) in regions of interest in the pancreas and liver. Associations between the fat fraction and selected clinical and laboratory variables were assessed with beta regression models. ResultsIn the end, 253 patients were included. The hepatic fat fraction was 4.9% and the pancreatic fat fraction was 7.9%. We found no significant associations between the hepatic fat fraction and any of the clinical or laboratory variables. However, the pancreatic fat fraction was positively associated with age (OR=1.025, p<0.001) and baseline glucose (OR=1.005, p<0.001). Patients with diabetes had higher values of pancreatic fat fraction (OR=2.64, p=0.038). Pancreatic fat fraction and hepatic fat fraction were positively associated (OR=69.44, p<0.001). ConclusionsPancreatic steatosis can be considered a marker of metabolic syndrome and diabetes. Quantitative MRI enables the diagnosis and grading of fatty pancreas through simple chemical shift techniques.

Plasma Metabolomics to Identify and Stratify Patients With Impaired Glucose Tolerance.

Impaired glucose tolerance (IGT) is one of the presymptomatic states of type 2 diabetes mellitus and requires an oral glucose tolerance test (OGTT) for diagnosis. Our aims were twofold: (i) characterize signatures of small molecules predicting the OGTT response and (ii) identify metabolic subgroups of participants with IGT. Plasma samples from 827 participants of the Study of Health in Pomerania free of diabetes were measured using mass spectrometry and proton-nuclear magnetic resonance spectroscopy. Linear regression analyses were used to screen for metabolites significantly associated with the OGTT response after 2 hours, adjusting for baseline glucose and insulin levels as well as important confounders. A signature predictive for IGT was established using regularized logistic regression. All cases with IGT (N = 159) were selected and subjected to unsupervised clustering using a k-means approach. In total, 99 metabolites and 22 lipoprotein measures were significantly associated with either 2-hour glucose or 2-hour insulin levels. Those comprised variations in baseline concentrations of branched-chain amino ketoacids, acylcarnitines, lysophospholipids, or phosphatidylcholines, largely confirming previous studies. By the use of these metabolites, subjects with IGT segregated into two distinct groups. Our IGT prediction model combining both clinical and metabolomics traits achieved an area under the curve of 0.84, slightly improving the prediction based on established clinical measures. The present metabolomics approach revealed molecular signatures associated directly to the response of the OGTT and to IGT in line with previous studies. However, clustering of subjects with IGT revealed distinct metabolic signatures of otherwise similar individuals, pointing toward the possibility of metabolomics for patient stratification.

Metabolic syndrome and trajectory of knee pain in older adults

To examine the association of metabolic syndrome (MetS) and its components with knee pain severity trajectories. Data from a population-based cohort study were utilised. Baseline blood pressure, glucose, triglycerides and high-density lipoprotein (HDL) cholesterol were measured. MetS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III criteria. Radiographic knee osteoarthritis (ROA) was assessed by X-ray. Pain severity was measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain questionnaire at each time-point. Group-based trajectory modelling was used to identify pain trajectories and multi-nominal logistic regression was used for analysis. Mediation analysis was performed to assess whether body mass index (BMI)/central obesity mediated the association between MetS, its components and pain trajectories. Among 985 participants (Mean±SD age: 62.9±7.4, 50% female), 32% had MetS and 60% had ROA. Three pain trajectories were identified: 'Minimal pain' (52%), 'Mild pain' (33%) and 'Moderate pain' (15%). After adjustment for potential confounders, central obesity increased risk of belonging to both 'Mild pain' and 'Moderate pain' trajectories as compared to the 'Minimal pain' trajectory group, but MetS [relative risk ratio (RRR): 2.26, 95%CI 1.50-3.39], hypertriglyceridemia (RRR: 1.75, 95%CI 1.16-2.62) and low HDL (RRR: 1.67, 95%CI 1.10-2.52) were only associated with 'Moderate pain' trajectory. BMI/central obesity explained 37-70% of these associations. Results were similar in those with ROA. MetS and its components are predominantly associated with worse pain trajectories through central obesity, suggesting that the development and maintenance of worse pain trajectories may be caused by MetS.

One case of type 1 diabetes caused by PD-1 inhibitor and literature review

This article reported a case of type 1 diabetes caused by a programmed death-1 (PD-1) inhibitor. The patient was a 52-year-old man with metastatic renal cell carcinoma who received the combined therapy of PD-1 inhibitor Nivolumab and vascular endothelial growth factor (VEGF) inhibitor Bevacizumab. He presented with thirst, polydipsia, polyuria, repeated vomiting, and fatigue 9 weeks after initiation of the therapy and developed into diabetic ketoacidosis about 2 weeks later, with blood glucose 50.9 mmol/L, HbA1C8.4%, serum fasted and glucose-loaded C peptide <0.01 ng/ml, arginine test negative, and autoantibodies negative. The patient was diagnosed as type 1 diabetes caused by the PD-1 inhibitor and was given intensive glucose lowering treatment with insulin, his water and electrolyte disorders were also corrected. His symptoms improved but he had to continue insulin treatment. It is recommended to check baseline glucose level prior to the initiation of treatment with PD-1 inhibitor, and should carefully monitor the clinical symptoms and glucose levels during the treatment. Timely detection, correct diagnosis and treatment are important to ensure patients′ safety and to improve their prognosis. Key words: PD-1 inhibitor; Diabetes mellitus, type 1

Association between person and disease related factors and the planned diabetes care in people who receive person-centered type 2 diabetes care: An implementation study.

AimsTo assess the planned diabetes care for the coming year and its associated factors in patients with Type 2 diabetes who have a person-centered annual consultation.MethodsImplementation study of a new consultation model in 47 general practices (primary care) and 6 outpatient clinics (secondary care); 1200 patients from primary and 166 from secondary care participated. Data collection took place between November 2015 and February 2017. Outcomes: preferred monitoring frequency; referral to other health care provider(s); medication change. One measurement at the end of the consultation. We performed logistic regression analyses. Differences between primary and secondary care were analyzed.ResultsMany patients arranged a monitoring frequency <4 times per year (general practices 19.5%, outpatient clinics 40%, p < .001). Type of provider (physician/nurse, OR 3.83, p < .001), baseline HbA1c (OR 1.02, p = .017), glucose lowering medication; and setting treatment goals (OR .65, p = .048) were associated with the chosen frequency. Independently associated with a referral were age (OR .99, p = .039), baseline glucose lowering medication and patients’ goal setting (OR 1.52, p = .016). Medication change was associated with type of provider, baseline HbA1c, blood glucose lowering medication, quality of life (OR .80, p = .037) and setting treatment goals (OR 2.64, p = .001).ConclusionsNot only disease but also person related factors, especially setting treatment goals, are independently associated with planned care use in person-centered diabetes care.

Neither Hormonal Factors Nor AGEs Explain Lower Prostate Cancer Risk in Older Men With Diabetes Mellitus.

Diabetes mellitus is conventionally associated with an increased risk of cancer; however, inverse associations of diabetes with prostate cancer are well described. Mechanisms are unclear, although hormonal factors, including alterations in sex hormone and IGF1 concentrations due to metabolic disturbances, have been hypothesized to play a role. To assess sex hormones, IGF1, glucose, and advanced glycation end products (AGEs) as potential mediators of the association between diabetes mellitus and prostate cancer. Longitudinal cohort study. The association of baseline diabetes with prostate cancer incidence was assessed using proportional hazards competing risks analysis in 3149 men followed for 12 years. Baseline hormone, glucose, and carboxymethyllysine (CML) levels were examined as potential mediators of this association. Diabetes was associated with a lower prostate cancer risk (fully adjusted subhazard ratio, 0.63; 95% CI, 0.43 to 0.92; P = 0.017). This association was unchanged after accounting for testosterone, DHT, estradiol, or SHBG. Similarly, the addition of IGF1 or its binding proteins 1 and 3, or glucose, did not alter this association. CML was not associated with the risk of prostate cancer, and additional correction for CML in the fully adjusted model did not alter the inverse association of diabetes and prostate cancer risk. In this study, alterations in sex hormone, IGF1, glucose, and CML levels did not account for the inverse association of diabetes and prostate cancer risk. Further studies are required to provide more insight into underlying causes of this association.

Preprocedural Neutrophil to Albumin Ratio Predicts In-Stent Restenosis Following Carotid Angioplasty and Stenting

Background and purposeIn-stent restenosis (ISR) is unfavorable to the long-term efficacy of carotid angioplasty and stenting (CAS). Inflammation plays a critical role in the development of ISR. The aim of the study was to investigate whether neutrophil to albumin ratio (NAR) is a predictor of ISR in patients undergoing CAS. MethodsWe retrospectively recruited patients who underwent CAS. These patients were divided into restenosis group and nonrestenosis group. NAR was examined prior to the CAS procedure. Clinical and radiographic assessments were performed at 6 months and annually after the procedure. ISR was defined as greater than or equal to 50% stenosis in the treated lesion. Cox regression was used to identify predictors of ISR following CAS. ResultsDuring a mean follow-up period of 14.6 months, a total of 459 treated arteries (in 427 participants) were enrolled, among which 72 (15.7%) developed ISR. On multivariate analysis, baseline NAR greater than or equal to13.4, residual stenosis, lesion length, and baseline glucose level were associated with ISR (hazard ratio 1.94[95% confidence interval (CI), 1.08-3.49], 1.09[95% CI, 1.07-1.12], 1.04[95% CI, 1.01-1.06], and 1.01[95% CI, 1.00-1.02], respectively). ConclusionElevated preprocedural NAR may be a predictor of ISR in patients undergoing CAS.

Physiological condition of nestling great tits (Parus major) declines with the date of brood initiation: a long term study of first clutches

In seasonal environments, a temporal decline in breeding performance (e.g. clutch size, nestling condition, and fledging success) of altricial bird species is a well-known phenomenon. In this study, we present the effect of laying phenology on the physiological condition of nestling great tits (Parus major) in 14 consecutive breeding seasons. We used blood haemoglobin and baseline glucose concentrations as indicators of nestling physiological condition. Nestling blood haemoglobin reflects food base quality and availability during the breeding period. Blood glucose concentration can be used as a supplementary reverse index of condition, since it is negatively related to environmental quality. It might be indicative of the stress caused by unfavourable extrinsic factors, though, due to potential confounding factors such as adverse weather conditions, low food quality, or feeding interruptions, glucose levels should be used in this ecological context with caution. Great tit nestlings from earlier broods were characterised by higher mean haemoglobin concentrations, indicating a seasonal decline in food quality and availability. The blood glucose concentration displayed an opposite pattern, with nestlings from earlier broods being characterised by lower mean concentrations than those from later broods. However, very little of the variation in blood glucose concentration can be explained by the variation in laying date, which suggests that blood glucose concentration is of little importance in the context of breeding phenology. Our results show that the physiological condition of nestlings of this species decreases as the breeding season progresses, most probably due to environmental factors.

EPA and DHA elicit distinct transcriptional responses to high-fat feeding in skeletal muscle and liver.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert numerous beneficial biological effects and attenuate diet-induced insulin resistance in rodent models. In the present study, the independent, tissue-specific effects of two nutritionally relevant n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were characterized in the context of a high-fat diet (HFD). EPA and DHA supplementation (3.2% of total fat) in 6-mo-old male C57BL/6 mice fed an HFD (60% fat) partially mitigated reductions in insulin sensitivity. At 5 wk, the area above the curve below baseline glucose following an intraperitoneal insulin tolerance test was 54.5% lower in HFD than control, whereas HFD + EPA and HFD + DHA showed 27.6% and 17.1% reductions, respectively. At 10 wk, HFD increased mitochondrial oxidative capacity supported by lipid and carbohydrate-based substrates in both liver and skeletal muscle (P < 0.05), with little effect of EPA or DHA supplementation. Whole genome transcriptomic analyses revealed HFD-induced transcriptional changes indicative of inflammation and fibrosis in both liver and muscle. Gene set enrichment analyses indicated a downregulation of transcripts associated with extracellular matrix in muscle (family-wise error rate P < 0.01) and liver (P = 0.04) and in transcripts associated with inflammation in muscle (P = 0.03) in HFD + DHA compared with HFD alone. In contrast, EPA appeared to potentiate some proinflammatory effects of the HFD. In the skeletal muscle, DHA increased the expression of stress-responsive genes, whereas EPA upregulated the expression of transcripts related to cell cycle. Therefore, although both EPA and DHA supplementation during HFD partially preserve insulin signaling, they modulate distinct processes, highlighting their unique biological effects in the context of obesity.

974-P: Beyond Carbohydrate Counting (CC)

CC is central to diabetes self-management in patients on insulin. Measuring devices, reference materials, and time are required. Continuous glucose monitoring (CGM) is increasingly available to insulin requiring diabetics: a rich data set that can be used to assess glucose appearance (Ra), disposal (Rd), and insulin need beyond CC. Fat and protein also contribute the height and duration of the glucose concentration curve. This is not accounted for with CC. Most patient's base insulin doses on previous meal experience and CGM directional arrows and not CC. CGM provides a means for individualizing insulin management quantitatively beyond premeal CC. Calculations: Data: CGM meal related glucose concentration vs. time curve, Kg body weight to calculate Volume of distribution (Vd). Glucose clearance [CL = (1/time)*Vd)]. (a)=Vd*Pkglucose*e*conversion factor. Conversion factor (CF = 1.12) converts blood glucose to plasma or interstitial fluid glucose (ISF glucose). Meal/insulin taken can be expressed as glucose appearance (a)/insulin or glucose clearance/insulin taken. (a) and CL make it possible to calculate a true area under the curve which differs with the timing and amount of insulin before the meal. Example: Weight 80.1 kg; Vd = 135 dL, time 340 minutes. Baseline glucose (BL) = 71.5 mg/dL. Glucose Peak (Pk) = 159 mg/dL. Insulin taken: 13 units. CL = 43mL/min. Depending on the time insulin is taken before the studied meal: (a) = 159 mg/dL*e*Vd or (a) = (159 mg/dL*e-BL/e) or (a) = ((159 mg/dL*e) - BL)*Vd. CL/insulin and (a)/insulin. In this case: CL = 43 mL/min/13 units; (a) = 48.7 g/13 units. Meal by references: 46.0 g CHO. Conclusion: This methodology marries pharmacokinetics with diet/insulin responses and goes beyond problematic CC in quantitating glucose appearance and disposal. The calculations determine post-hepatic glucose appearance and disposal. If available meal glucose is known, hepatic glycogen storage can be estimated also. Calculations can be performed using a ruler, cell phone calculator, and CGM glucose curves. Disclosure J.S. Melish: None.

241-OR: Restenosis after Percutaneous Transluminal Coronary Angioplasty in Patients with Different Categories of Glucose Tolerance: A 2-Year Follow-Up Study

Patients with diabetes (DM) are at high risk for restenosis after coronary stenting. Information relating the outcome of percutaneous transluminal coronary angioplasty (PTCA) to prediabetes is, however, limited. The study objective was to investigate the relationship between restenosis after PTCA and baseline glucose categories. We retrospectively analyzed data of 1003 patients (mean age 58.5±4.2 years, 61.5% of men, mean history of coronary heart disease 9.5±1.1 years) who undertook PTCA at Emergency Department between Jan 2008 and Dec 2011. Baseline measures included blood pressure (BP), fasting plasma glucose, lipid profile, HbA1c, C-reactive protein (C-RP), and 2-hour capillary glucose. All patients had follow-up coronary angiography 2 year after PTCA. Restenosis was defined as ≧ 50% stenosis in stent or within 5 mm adjacent to stent. The rate of restenosis was compared among patients with normal glucose tolerance (NGT, n=436), impaired glucose regulation (IGR, n=275), and DM (n=292) according to their baseline glucose levels or prior history of DM. Patients with DM had highest levels of body mass index (BMI), BP, triglycerides (TG), and C-RP, followed by those with IGR and NGT (P&amp;lt;0.01).The number of lesion was 1.6, 1.8, and 2.5 in patients with NGT, IGR, and DM, respectively (p&amp;lt;0.05). At year 2, the rate of restenosis were 4.2%, 5.3%, and 12.0% in patients with NGT, IGT, and DM, respectively (P&amp;lt;0.05). Among DM subgroup, compared with patients with A1c&amp;lt;8%, those with A1c&amp;gt;8% had increased rate of restenosis (14.6% vs. 11.2%, P&amp;lt;0.05). In the logistic regression model, the odd ratio (OR) of having restenosis was 1.46 (95% CI: 1.05-1.87) for DM and 1.10 (95% CI: 1.01-1.25) for IGR, after adjusting for age, history of coronary heart disease, BMI, BP, LDL-C, TG, and C-RP. Restenosis is more frequent in patients with compared those without DM. Prediabetes is associated with increased risk of restenosis after PTCA. Disclosure L. Zhang: None. Y. Gu: None. X. Yin: None. J. Wang: None. N. Wang: None. Y. Yang: None. Y. Dong: None.

1719-P: Plasma Glucose Response to Oral Dexamethasone Predicts Incident Prediabetes in Normoglycemic Offspring of Parents with Type 2 Diabetes

Background: Dexamethasone (dex) challenge was used historically to diagnose chemical diabetes. Here we determined its utility in predicting prediabetes in a biracial cohort. Methods: We studied 190 euglycemic subjects with parental type 2 diabetes. After a baseline 75-gram OGTT, subjects ingested 2 mg dex at 10 PM and returned at 8AM for measurement of plasma cortisol and glucose. Subjects were followed quarterly for incident prediabetes for 5 years. Serial assessments included OGTT, insulin secretion (IVGTT), and insulin sensitivity (euglycemic clamp). Results: Table 1 shows baseline characteristics and response to dex. Progressors to prediabetes had a higher glycemic response to dex than nonprogressors (&amp;lt;0.0001). In a regression model, post-dex fasting glucose level remained a significant predictor of Incident prediabetes after controlling for age, weight, waist, and baseline glucose (P&amp;lt;0.001). From ROC analysis, fasting plasma glucose ≥110 mg/dL after dex predicted incident prediabetes with 80% sensitivity and 60% specificity. Conclusion: Glycemic response to 2mg dex predicts incident prediabetes and could be useful for stratification and selection of high-risk subjects for lifestyle intervention. Table 1: Baseline demographic and glucoregulatory characteristics of subjects who developed prediabetes compared to those who remained normoglycemic. Disclosure E. Nyenwe: None. N.A. Umekwe: None. D.J. James: None. F. Ariganjoye: None. J.Y. Wan: None. S. Dagogo-Jack: Board Member; Self; Jana Care Inc. Consultant; Self; Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Sanofi-Aventis. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Stock/Shareholder; Self; Dance Biopharm Holdings Inc. Funding American Diabetes Association (7-07-MN-13 to S.D-J.); National Institutes of Health

Preliminary Results on the Effectiveness of a Nutrition Intervention in Lowering Diabetes Risk in Prediabetic People Living with HIV (PLWH) in MASH Cohort (OR36-06-19)

ObjectivesThe objective of this study is to assess the effectiveness of a 6-month nutrition intervention to improve glycemic parameters and inflammation in prediabetic PLWH on stable ART with undetectable HIV viral load. MethodsA 6-month randomized, controlled nutrition intervention was conducted in prediabetic PLWH. The study participants for the intervention were recruited from the Miami Adult Studies for HIV (MASH) cohort at the FIU-Borinquen Research Clinic. Upon their consent, the participants were randomized into the intervention group or the control group. Participants randomized in the intervention group met once a month for approximately 1 hour where they received medical nutrition therapy, nutrition counseling and nutrition education; participants randomized into the control group received educational material at baseline. Blood was drawn at baseline and at 6-month to measure fasting blood glucose (FBG) and high sensitivity C-reactive protein (hs-CRP). ResultsA total of 38 participants were recruited and randomized into either the intervention group (n = 20) or the control group (n = 18). We found that the FBG for the 6-month follow-up for the intervention group was significantly lower than the baseline FBG values of the same study group (paired t-test; P = 0.031). No significant difference was found in the control group between the baseline and 6-month fasting blood glucose values (P = 0.068). Moreover, no significant difference was found in pre/post C-reactive protein (CRP) levels in the intervention or control group (paired t-test; P = 0.404 and P = 0.117 respectively). There was a significant difference in CRP levels at baseline (P = 0.028) between the study groups but no difference at the 6-month follow up (Mann Whitney U test: P = 0.430). ConclusionsThe results from this intervention support the notion that a nutrition intervention is effective in prediabetic PLWH to lower diabetes risk by significantly lowering fasting blood glucose and may be implemented into larger scale interventions; however, no significant changes was seen in hs-CRP values between the 2 groups. Funding SourcesNational Institute of General Medical Sciences (NIGMS): Research Initiative for Scientific Enhancement (RISE), Biomedical Research Initiative (BRI) Grant, National Institute on Drug Abuse 5U01DA040381-03 and FIU-Dissertation Funding.

Association of atrial fibrillation with hemorrhagic transformation after intravenous thrombolysis in patients with ischemic stroke

To investigate the association of atrial fibrillation (AF) with hemorrhagic transformation (HT) in patients with ischemic stroke treated by intravenous thrombolysis. Clinical data of 3272 patients treated by intravenous thrombolysis from 71 hospitals in Zhejiang Province during June 2017 and December 2018 were retrospectively reviewed. Intracranial HT was defined as intracranial hemorrhage suggested by imaging examination 24 hours after intravenous thrombolysis. Patients were dichotomized into HT group (n=533) and non-HT group (n=2739). The association of AF and HT was analyzed by univariate analysis and binary logistic regression. Compared with the non-HT group, the HT group were older, had longer onset to needle time (ONT), higher baseline National Institute of Health Stroke Scale (NIHSS) score, higher baseline glucose level, and higher AF rate (P<0.05 or P<0.01). Binary logistic regression analysis revealed that AF was independently associated with HT (OR=2.527, 95%CI:2.030-3.146, P<0.01). AF is independently associated with the occurrence of HT in ischemic stroke patients treated with intravenous thrombolysis.

Predictable early onset high-dose-glucocorticoid-associated-irAE and its predictive role in anti-PD-1 monotherapy treated advanced melanoma patients.

9544 Background: Though uncommon, a subgroup of patients with melanoma develop early-onset severe immune-related adverse effects (irAEs) that require immunosuppressive treatment with high-dose glucocorticoids (HD-GCCs). We aimed to examine the impact of early onset HD-GCC-associated-irAE (EO-HGA-irAE) in the setting of anti-PD-1 monotherapy initiation on prognosis and to develop a predictive scoring system. Methods: Clinical data was collected retrospectively from advanced melanoma patients treated with anti-PD-1 monotherapy at Massachusetts General Hospital from Sept 2009 to Dec 2017. The relationship between EO-HGA-irAE and PFS (defined as time from anti-PD-1 monotherapy initiation to PD) was assessed using 8-week conditional landmark analysis (Kaplan-Meier curves, log-rank test) and time-dependent COX regression model (multivariate analysis). Demographic characteristics and baseline routine laboratory variables were collected and correlated with occurrence of EO-HGA-irAE using logistic regression modeling. Best cutoff values were identified using ROC curve (Youden index) to dichotomize continuous variables. Results: Among 146 patients, 13 (8.9%) developed EO-HGA-irAE. In 8-week landmark analysis, median PFS was 2.9 (95% CI, 2.8-3.0) and 17.5 (95% CI, 10.8-24.2) months (P = .001) for patients with and without EO-HGA-irAE, respectively. Multivariate analysis revealed that EO-HGA-irAE was independently correlated with significantly higher risk of disease progression with hazard ratio of 2.4 (95% CI 1.4-4.0) (P = .001). Potential predictive variables (P &lt; .25 for continuous variables, P &lt; .1 for dichotomous variables) in favor of the occurrence of EO-HGA-irAE included age, baseline glucose, and neutrophil, eosinophil, and WBC count. After dichotomization and further validation using a logistic regression model, a scoring system (score range 0-3) composed of 3 dichotomized predictors, including age, baseline glucose, and baseline neutrophil count was developed with odds ratio of 3.4 (95% CI, 1.6-8.8) (P = .001). The probabilities of patients scoring 0,1,2,3 of developing EO-HGA-irAE were 1.1%, 3.5%, 11.1%, and 29.9%, respectively. Conclusions: Development of EO-HGA-irAE is correlated with shorter PFS in advanced melanoma patients treated with anti-PD-1 monotherapy. A scoring system based on age and simple, easily accessible, routinely tested biomarkers can be used to help predict the risk of EO-HGA-irAE occurrence. Validation with a larger sample size is required.

The Effect of Wolffia globosa Mankai, a Green Aquatic Plant, on Postprandial Glycemic Response: A Randomized Crossover Controlled Trial.

To compare the postprandial and overnight glycemic response using a novel green aquatic plant thought to provide a dietary source for high-quality protein, with an iso-carbohydrate/protein/caloric dairy shake. This is a randomized controlled crossover trial among 20 abdominally obese participants (age 51.4 years; fasting plasma glucose 110.9 mg/dL), who were allocated to replace dinner with either, first, a green shake containing Wolffia globosa duckweed (Mankai: specific-strain) or an iso-carbohydrate/protein/calorie yogurt shake. A 2-week flash glucose-monitoring system was used to assess postmeal glucose dynamics (6 net administration days; 97 observation days in total). We further obtained from each participant dietary/daily activity/satiety scale/sleep logs. Participants were recruited from the green-Mediterranean diet arm of the 18-month Dietary Intervention Randomized Controlled Trial-Polyphenols Unprocessed (DIRECT-PLUS) study. Wolffia globosa Mankai elicited a lower postprandial glucose peak compared with yogurt (∆peak = 13.4 ± 9.2 vs. 19.3 ± 15.1 mg/dL; P = 0.044), which occurred later (77.5 ± 29.2 vs. 59.2 ± 28.4 min; P = 0.037) and returned faster to baseline glucose levels (135.8 ± 53.1 vs. 197.5 ± 70.2 min; P = 0.012). The mean post-net incremental area under the curve (netAUC) was lower with Wolffia globosa up to 60 and 180 min (netAUC 60 min: 185.1 ± 340.1 vs. 441.4 ± 336.5 mg/dL/min, P = 0.005; netAUC 180 min: 707.9 ± 1,428.5 vs. 1,576.6 ± 1,810.1 mg/dL/min, P = 0.037). A Wolffia globosa-based shake replacing dinner resulted in lower next-morning fasting glucose levels (83.2 ± 0.8 vs. 86.6 ± 13 mg/dL; P = 0.041). Overall, postprandial glucose levels from the shake administration until the next morning were lower in the Wolffia globosa Mankai green shake compared with the yogurt shake (P < 0.001). Overnight sleep duration was similar (378.2 ± 22.4 vs. 375.9 ± 28.4 min; P = 0.72), and satiety rank was slightly higher for the Wolffia globosa shake compared with the yogurt shake (7.5 vs. 6.5; P = 0.035). Wolffia globosa Mankai duckweed may serve as an emerging alternative plant protein source with potential beneficial postprandial glycemic effects.

Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes.

The response to metformin, the most commonly used drug for the treatment of type 2 diabetes (T2D), is highly variable. The common variant rs7903146 C>T within the transcription factor 7-like 2 gene (TCF7L2) is the strongest genetic risk factor associated with T2D to date. In this study, we explored the effects of the TCF7L2 rs7903146 genotype on metformin response in T2D. The study included 86 newly diagnosed patients with T2D, incident users of metformin. Levels of fasting glucose, insulin, HbA1c, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and anthropometric parameters were measured prior to metformin therapy, and 6 and 12 months after the treatment. Genotyping of the TCF7L2 rs7903146 was performed by the Sequenom MassARRAY® iPLEX® platform. At baseline, the diabetes risk allele (T) showed an association with lower triglyceride levels (p = 0.037). After 12 months of metformin treatment, the T allele was associated with 25.9% lower fasting insulin levels (95% CI 10.9-38.3%, p = 0.002) and 29.1% lower HOMA-IR index (95% CI 10.1-44.1%, p = 0.005), after adjustment for baseline values. Moreover, the T allele was associated with 6.7% lower fasting glucose levels (95% CI 1.1-12.0%, p = 0.021), adjusted for baseline glucose and baseline HOMA-%B levels, after 6 months of metformin treatment. This effect was more pronounced in the TT carriers who had 16.8% lower fasting glucose levels (95% CI 7.0-25.6%, p = 0.002) compared to the patients with CC genotype. Our results suggest that the TCF7L2 rs7903146 variant affects markers of insulin resistance and glycemic response to metformin in newly diagnosed patients with T2D within the first year of metformin treatment.

Homeostatic Model Assessment in Kidney Transplantation

IntroductionLong-term kidney transplantation survival has been limited to cardiovascular-disease-associated death, which may be related to insulin resistance. The aim of this study is to evaluate the association between homeostatic model assessment (HOMA) and renal graft function. Materials and methodsFrom January 2013 to March 2015, 55 nondiabetic kidney recipients were reviewed retrospectively with their baseline fasting serum insulin and glucose levels as the basis the following indexes: 1. HOMA insulin resistance (HOMA-IR), 2. HOMA-β, and 3. insulin-glucose ratio (IGR). These patients were divided into 2 groups according to their HOMA indexes, and the serum creatinine (Cr) and estimated glomerular filtration rate (eGFR) were analyzed on the basis of every 6 months up to 3 years after kidney transplantation. Finally, we evaluate whether these HOMA indexes are a determinant factor of eGFR at post-transplant 1 year, 2 year, and 3 year. ResultsThere was no persisting difference in Cr and eGFR between high- and low-HOMA indexes except that the Cr and eGFR difference by HOMA-β stratification increased with time and became nearly significant at 3 years after transplantation. Further univariate and multivariate linear regression models showed no factor affected the 1-year eGFR independently, while weight affected the 2-year eGFR and only HOMA-β affected the 3-year eGFR independently. ConclusionIn non-diabetic kidney recipients, the eGFR difference between high- and low-HOMA-β patients increases over time. In multivariate linear regression, HOMA-β, but not HOMA-IR nor IGR, has independent significant association with eGFR at 3 years after transplantation.