Fasting Glucose Concentrations Research Articles

Empagliflozin Normalizes Fasting Hyperglycemia and Improves Postprandial Glucose Tolerance in Totally Pancreatectomized Patients: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.

Insulin remains the only glucose-lowering treatment modality recommended for totally pancreatectomized patients. We investigated the effects of the sodium-glucose cotransporter 2 inhibitor empagliflozin on fasting and postprandial glucose concentrations in pancreatectomized patients and matched healthy control participants. In a randomized, double-blind, placebo-controlled crossover study, 10 pancreatectomized patients and 10 matched control participants underwent two 3-h liquid mixed meal tests preceded by two doses of 25 mg empagliflozin (administered the night before and in the morning of the meal test) or placebo, respectively. Basal insulin was administered as usual, but bolus insulin was omitted before the meal test during experimental days. Compared with placebo, empagliflozin lowered fasting plasma glucose (5.0 ± 0.4 vs. 7.9 ± 0.9 mmol/L [mean ± SEM], P = 0.007) and postprandial plasma glucose excursions as assessed by baseline-subtracted area under the curve (1,080 [733; 1,231] vs. 1,169 [1,036; 1,417] pmol/L × min [median (25th and 75th percentiles)], P = 0.014) in the pancreatectomized patients. In the control participants, empagliflozin lowered fasting plasma glucose compared with placebo (5.1 ± 0.1 vs. 5.5 ± 0.1 mmol/L, P = 0.008) without affecting postprandial glucose excursions significantly. The pancreatomy group exhibited greater postprandial glucagon excursions compared with the control group on both experimental days (P ≤ 0.015); no within-group differences between days were observed. Empagliflozin administered the day before and immediately before a standardized liquid mixed meal test normalized fasting hyperglycemia and improved postprandial glucose tolerance in pancreatectomized patients.

Cardiometabolic risk factor clustering in persons with spinal cord injury: A principal component analysis approach

Context/Objective To identify cardiometabolic (CM) measurements that cluster to confer increased cardiovascular disease (CVD) risk using principal component analysis (PCA) in a cohort of chronic spinal cord injury (SCI) and healthy non-SCI individuals. Approach A cross-sectional study was performed in ninety-eight non-ambulatory men with chronic SCI and fifty-one healthy non-SCI individuals (ambulatory comparison group). Fasting blood samples were obtained for the following CM biomarkers: lipid, lipoprotein particle, fasting glucose and insulin concentrations, leptin, adiponectin, and markers of inflammation. Total and central adiposity [total body fat (TBF) percent and visceral adipose tissue (VAT) percent, respectively] were obtained by dual x-ray absorptiometry (DXA). A PCA was used to identify the CM outcome measurements that cluster to confer CVD risk in SCI and non-SCI cohorts. Results Using PCA, six factor-components (FC) were extracted, explaining 77% and 82% of the total variance in the SCI and non-SCI cohorts, respectively. In both groups, FC-1 was primarily composed of lipoprotein particle concentration variables. TBF and VAT were included in FC-2 in the SCI group, but not the non-SCI group. In the SCI cohort, logistic regression analysis results revealed that for every unit increase in the FC-1 standardized score generated from the statistical software during the PCA, there is a 216% increased risk of MetS (P = 0.001), a 209% increased risk of a 10-yr. FRS ≥ 10% (P = 0.001), and a 92% increase in the risk of HOMA2-IR ≥ 2.05 (P = 0.01). Conclusion Application of PCA identified 6-FC models for the SCI and non-SCI groups. The clustering of variables into the respective models varied considerably between the cohorts, indicating that CM outcomes may play a differential role on their conferring CVD-risk in individuals with chronic SCI.

Changes in Branched-Chain Amino Acids One Year after Sleeve Gastrectomy in Youth with Obesity and Their Association with Changes in Insulin Resistance.

Adults with obesity have a reduction in branched-chain amino acid (BCAA) levels following metabolic and bariatric surgery (MBS), which is hypothesized to contribute to the metabolic advantages of MBS. We examined this relationship in 62 youth 13-24 years old with severe obesity (47 female) over 12 months. Thirty had sleeve gastrectomy (SG) and 32 were non-surgical controls (NS). We measured fasting insulin, glucose, glycated hemoglobin (HbA1c), isoleucine, leucine, and valine concentrations, and post-prandial insulin and glucose, following a mixed meal tolerance test. Twenty-four-hour food recalls were collected. At baseline, groups did not differ in the intake or the serum levels of BCAAs, HbA1C, HOMA-IR, Matsuda index, insulinogenic index, or oral Disposition index (oDI). Over 12 months, SG vs. NS had greater reductions in serum BCAAs, and SG had significant reductions in BCAA intake. SG vs. NS had greater reductions in HbA1c and HOMA-IR, with increases in the Matsuda index and oDI. In SG, baseline leucine and total BCAA concentrations were negatively correlated with the baseline Matsuda index. Reductions in serum leucine were positively associated with the reductions in HOMA-IR over 12 months. These associations suggest a potential role of BCAA in regulating metabolic health. Reducing dietary intake and serum BCAA concentrations may reduce insulin resistance.

Glycemic variability and hypoglycemia before and after Roux-en-Y Gastric Bypass and Sleeve Gastrectomy – A cohort study of females without diabetes

BackgroundRoux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) lead to lower fasting glucose concentrations, but might cause higher glycemic variability (GV) and increased risk of hypoglycemia. However, it has been sparsely studied in patients without preoperative diabetes under normal living conditions. ObjectivesTo study 24-hour interstitial glucose (IG) concentrations, GV, the occurrence of hypoglycemia and dietary intake before and after laparoscopic RYGB and SG in females without diabetes. SettingOutpatient bariatric units at a community and a university hospital. MethodsContinuous glucose monitoring and open-ended food recording over 4 days in 4 study periods: at baseline, during the preoperative low-energy diet (LED) regimen, and at 6 and 12 months postoperatively. ResultsOf 47 patients included at baseline, 83%, 81%, and 79% completed the remaining 3 study periods. The mean 24-hour IG concentration was similar during the preoperative LED regimen and after surgery and significantly lower compared to baseline in both surgical groups. GV was significantly increased 6 and 12 months after surgery compared to baseline. The self-reported carbohydrate intake was positively associated with GV after surgery. IG concentrations below 3.9 mmol/L were observed in 14/25 (56%) of RYGB- and 9/12 (75%) of SG-treated patients 12 months after surgery. About 70% of patients with low IG concentrations also reported hypoglycemic symptoms. ConclusionsThe lower IG concentration in combination with the higher GV after surgery, might create a lower margin to hypoglycemia. This could help explain the increased occurrence of hypoglycemic episodes after RYGB and SG.

Micronutrients in High-Fat Diet Modify Insulin Resistance and Its Regulatory Genes in Adult Male Mice.

Obesity and insulin resistance (IR) are associated with epigenetic changes of gene expression. However, the relationship between micronutrients, epigenetic regulation of gene expression, and IR during development of diet-induced obesity has yet to be defined. Our objective is to describe the effect of micronutrient addition to diets on IR and its related genes during obesity development. Male C57BL/6J mice are fed a high-fat (HFD) or low-fat (LFD) diets with or without a multi-vitamin mineral mix (MVM) addition containing vitamins A, B1, B6, B12, and Zn, and Se for 9 weeks. Compared to LFD mice, HFD mice have higher body weight, IR, fasting glucose, insulin, C-peptide, leptin, and hepatic triglyceride concentrations, and dysregulated gene expression in liver, muscle, pancreas, and fat tissues (p < 0.05). The addition of MVM reduces these HFD-induced effects. HFD downregulates 27 genes associated with insulin regulation and adipose tissue function across all tissues by an average of 47% and upregulates five genes by 230% (p < 0.001). Adding MVM downregulates five genes and upregulates one in HFD-fed mice. Both HFD and MVM alter one-carbon metabolites. Addition of micronutrients to the HFD decreases IR and modifies associated gene expression in obese and lean mice.

Diet and physical activity and metabolic disorders in patients with schizophrenia and bipolar affective disorder in the Polish population.

There are numerous reports of a higher prevalence of metabolic disorders in patients with schizophrenia and bipolar disorder (BD), yet its connections to diet and physical activity remain not fully explained. This article aimed to evaluate diet, physical activity and selected biochemical and anthropometric parameters associated with metabolism in patients with schizophrenia and BD and to analyse the relationships between these variables in the subjects. A total of 126 adults participated in the study: 47 patients with schizophrenia, 54 patients with BD and 25 patients in mental illness remission (reference group). Data were collected on the underlying illness and concomitant illnesses, and the severity of symptoms of the current episode was assessed using the following scales: PANSS, MADRS and YMRS. An assessment of the subjects' diet (KomPAN questionnaire) and their physical activity (International Physical Activity Questionnaire) was carried out. Anthropometric and blood pressure measurements were taken and BMI and WHR were calculated. Serum concentrations of fasting glucose, TSH, total cholesterol, LDL and HDL fractions, triglycerides and leptin, ghrelin and resistin were determined. For statistical analysis, the significance level was set at 0.05. For multiple comparisons one way ANOVA or Kruskal Wallis were used with post hoc Tukey and Dunn tests, respectively. To determine correlation of variables, Pearson's linear correlation coefficient or Spearman's rank correlation coefficient were used. A total of 50.8% of the subjects had at least one metabolic disorder-most commonly excessive body weight (66.7%) and abdominal obesity (64.3%). Patients did not differ significantly in terms of physical activity, but they did differ in mean time spent sitting-with this being significantly longer for all groups than in the general population. The subjects differed in diet: patients with BD consumed less unhealthy foods than patients with schizophrenia. The highest correlations between physical activity, diet and variables defining metabolic disorders were found in patients with BD. Only in patients with schizophrenia were there significant correlations between the course of the disease and physical activity. The results suggest the existence of associations between diet, physical activity, and metabolic disorders in both BD and schizophrenia patients. They also suggest a tendency among those patients to spend long periods of time sitting.

341-OR: Association between Age at Diagnosis of Type 2 Diabetes and Subsequent Risk of Dementia and Its Major Subtypes

Objectives: Type 2 diabetes mellitus (T2DM) is recognized as a major contributor to cognitive decline and dementia in older adults but its importance for its contribution according to age at diagnosis of T2DM remains uncertain. We aimed to investigate the association between dementia and its subtypes in relation to the age at diagnosis of T2DM. Research design and methods: In a population cohort study with the Korean National Health Insurance Service data (2012-2014), a total of 612,201 patients with newly diagnosed T2DM were included. Controls were randomly selected from the general population and matched with a 1:2 ratio based on the propensity score. Participants were followed for until December, 2019. Outcomes of interest were all-cause dementia, Alzheimer’s disease (AD) and vascular dementia (VD). The association of T2DM with dementia was stratified by baseline fasting glucose concentration in patients with T2DM. Cox regression was used to study the excess risk of outcomes. Results: During 6.25 years follow-up, dementia developed in 66,186 patients with T2DM compared with 85,358 control subjects. Patients with T2DM diagnosed at ≤50 years had the highest excess risk for most outcomes relative to control with hazard ratio (HR) (95% CI) of 3.30 (3.11-3.50) for all-cause dementia, 4.08 (3.17-5.23) for AD, and 5.86 (3.87-8.88) for VD. All risks attenuated progressively with each increasing decade at diagnostic age but remained significant; for T2DM diagnosed at ≥80 years, the HR (95% CI) was 1.38 (1.34-1.41) for all-cause dementia, 1.36 (1.32-1.40) for AD, and 1.99 (1.71-2.31) for VD. When the analyses were stratified by fasting glucose concentration, a dose-response association was observed. Conclusion: In this population-based cohort study, younger age at diagnosis of T2DM was associated with a higher risk of risk of both AD and VD. Physicians should closely monitor cognitive function in diabetic patients especially in those with young onset T2DM. Disclosure Y.Kim: None. D.Seo: None. M.Kim: None. Y.Cho: None. S.Ahn: None. S.Hong: None. S.Kim: None.

235-LB: Incretin-Linked Adipose Tissue Microvascular Blood Flow in Healthy People With and Without a Family History of Type 2 Diabetes

Adipose tissue microvascular blood flow (ATMBF) increases in response to a mixed meal challenge (MMC) to promote nutrient storage. This vascular action is impaired in apparently healthy people with a parent with type 2 diabetes (FH+). The mechanisms for this vascular impairment in FH+ are unknow. We aimed to investigate whether incretins [glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)] are associated with ATMBF responses to a MMC. Thirteen healthy (FH-, no parents or grandparents with type 2 diabetes) and fourteen FH+ underwent a 2-hr MMC after an overnight fast. Age, BMI, fasting and peak postprandial blood glucose and plasma insulin concentrations were similar between FH- and FH+ (Table 1). Baseline ATMBF, assessed by contrast ultrasound, was similar between groups, but was impaired in FH+ in response to the MMC (Table 1). Peak plasma GLP-1 and GIP concentrations, but not their ratio (GLP-1:GIP), were higher in FH+ in response to the MMC (Table 1). GLP-1 and GIP concentrations were not associated with ATMBF, however, GLP-1:GIP was significantly associated with postprandial ATMBF at 1-hr (p=0.025, r=0.46). We conclude that impaired postprandial ATMBF in FH+ is not exclusively linked to incretin levels. However, lower GLP-1:GIP ratios may be linked to impaired ATMBF responses in the postprandial state. Disclosure K. Roberts-thomson: None. L. Parker: None. M. Keske: None.

1547-P: The Differential Effect of Glucagon-Like Peptide-1 Receptor Blockade on Glucose Metabolism in People With and Without Type 2 Diabetes

Glucagon-Like Peptide-1 (GLP-1) is present within the islet but the effects of GLP-1 Receptor (GLP1R) blockade on islet function in humans remains unknown. To address this, we studied 12 nondiabetic individuals (54 ± 2 years, 33 ± 1 kg/m2) and 11 people with type 2 diabetes (DM2 - 58 ± 2 years, 34 ± 2 kg/m2) on 2 occasions in random order. On each occasion, after an overnight fast, [3-3H] glucose was used to measure glucose turnover during fasting and a hyperglycemic clamp (~9 mmol/l) using the tracer dilution technique. On one occasion exendin-9,39 (300pmol/kg/min) was infused to block GLP1R, while on the other saline was infused. Exendin-9,39 increased fasting glucose concentrations in those without (4.6 ± 0.4 vs. 5.5 ± 0.1 mmol/l, saline vs. exendin-9,39 respectively, p = 0.04) and in those with DM2 (7.3 ± 0.5 vs. 8.3 ± 0.6 mmol/l, p = 0.03). Fasting islet hormone concentrations were unchanged, but inappropriate for the higher fasting glucose observed during exendin-9,39 infusion. The same pattern was seen in people with DM2 except that fasting glucagon concentrations increased (8.3 ± 0.5 vs. 10.2 ± 0.6 pmol/l, p &amp;lt; 0.01) and remained elevated throughout hyperglycemia (4.7 ± 0.4 vs. 7.7 ± 0.6 pmol/l, p &amp;lt; 0.02). Insulin secretion rate calculated by deconvolution of C-peptide concentrations was also decreased in DM2 (0.54 ± 0.08 vs. 0.51 ± 0.08 nmol/min, p = 0.02). Consequently, suppression of endogenous glucose production by hyperglycemia was impaired in people with DM2 (2.9 ± 0.4 vs. 5.7 ± 0.3 μmol/kg/min, p &amp;lt; 0.01). Intriguingly, 1st phase response to hyperglycemia was decreased in those without DM2 (3.5 ± 0.6 vs. 2.5 ± 0.5 nmol per 10 min, p = 0.04). These data show that in humans, GLP1R blockade impairs fasting α- and β-cell function resulting in fasting hyperglycemia. Subtle effects are also present in response to hyperglycemia. This implies that intra-islet GLP1R activation sustains islet responses to glucose and it does so to a greater degree in people with DM2. Disclosure A.A. Welch: None. R.A. Farahani: None. M. Zeini: None. A.M. Egan: None. M.C. Laurenti: None. C. Cobelli: None. C. Dalla Man: Research Support; Sanofi-Aventis Deutschland GmbH, Becton, Dickinson and Company. A. Vella: Other Relationship; Novo Nordisk. Advisory Panel; Rezolute, Inc. Consultant; Crinetics Pharmaceuticals, Inc., Hanmi Pharm. Co., Ltd., Zealand Pharma A/S. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK126206)

1646-P: The Effect of Glucagon-Like Peptide-1 Receptor Blockade and Acute Insulin Resistance on Islet Function and Glucose Metabolism in People without Diabetes

Intra-islet Glucagon-Like Peptide-1 (GLP-1) is increased by islet inflammation and diabetes. GLP-1 Receptor (GLP1R) blockade with exendin-9,39 impairs fasting islet function in people with and without type 2 diabetes (DM2). In addition, it decreases insulin secretion and glucagon suppression in response to hyperglycemia in people with DM2. We sought to examine if free fatty acid (FFA) elevation to induce acute insulin resistance in people without DM2 replicated the effects of GLP1R blockade seen in DM2. We studied 6 nondiabetic individuals (54 ± 4 years, 33 ± 1 kg/m2) on 4 occasions in random order. Glucose metabolism was measured after an overnight fast and during a hyperglycemic clamp (~9 mmol/l) using [3-3H] glucose. On two occasions Intralipid® and heparin were infused to raise FFA. Exendin-9,39 (300pmol/kg/min) was infused to block GLP1R in the presence or absence of FFA elevation, while on the other days saline was infused. In the absence of FFA elevation, exendin-9,39 infusion increased fasting glucose concentrations (5.0 ± 0.1 vs. 5.4 ± 0.1 mmol/l, saline vs. exendin-9,39 respectively, p = 0.01). This pattern was also observed when FFA were elevated (5.3 ± 0.1 vs. 5.7 ± 0.2 mmol/l, p = 0.02). Fasting insulin, C-peptide (without FFA: 0.9 ± 0.1 vs. 0.8 ± 0.1 nmol/l, p = 0.17; with FFA: 1.1 ± 0.1 vs. 1.0 ± 0.1 nmol/l, p = 0.08) and glucagon concentrations were unchanged, but inappropriate for the higher fasting glucose observed during exendin-9,39 infusion. Exendin-9,39 infusion did not alter islet hormone secretion during the clamp in the presence or absence of FFA elevation. The magnitude of changes induced by exendin-9,39 did not differ in the presence or absence of FFA elevation (p &amp;gt; 0.10). These experiments confirm the effects of GLP1R blockade on fasting α- and β-cell function in people without DM2. However, FFA elevation does not replicate the abnormalities of islet function observed in people with DM2 when exendin-9,39 is infused. Disclosure M. Zeini: None. R.A. Farahani: None. A.A. Welch: None. M.C. Laurenti: None. C. Cobelli: None. C. Dalla Man: Research Support; Sanofi-Aventis Deutschland GmbH, Becton, Dickinson and Company. A.M. Egan: None. A. Vella: Other Relationship; Novo Nordisk. Advisory Panel; Rezolute, Inc. Consultant; Crinetics Pharmaceuticals, Inc., Hanmi Pharm. Co., Ltd., Zealand Pharma A/S. Funding National Institutes of Health (DK126206)

Physiology of sedentary behavior.

Sedentary behaviors (SB) are characterized by low energy expenditure while in a sitting or reclining posture. Evidence relevant to understanding the physiology of SB can be derived from studies employing several experimental models: bed rest, immobilization, reduced step count, and reducing/interrupting prolonged SB. We examine the relevant physiological evidence relating to body weight and energy balance, intermediary metabolism, cardiovascular and respiratory systems, the musculoskeletal system, the central nervous system, and immunity and inflammatory responses. Excessive and prolonged SB can lead to insulin resistance, vascular dysfunction, shift in substrate use toward carbohydrate oxidation, shift in muscle fiber from oxidative to glycolytic type, reduced cardiorespiratory fitness, loss of muscle mass and strength and bone mass, and increased total body fat mass and visceral fat depot, blood lipid concentrations, and inflammation. Despite marked differences across individual studies, longer term interventions aimed at reducing/interrupting SB have resulted in small, albeit marginally clinically meaningful, benefits on body weight, waist circumference, percent body fat, fasting glucose, insulin, HbA1c and HDL concentrations, systolic blood pressure, and vascular function in adults and older adults. There is more limited evidence for other health-related outcomes and physiological systems and for children and adolescents. Future research should focus on the investigation of molecular and cellular mechanisms underpinning adaptations to increasing and reducing/interrupting SB and the necessary changes in SB and physical activity to impact physiological systems and overall health in diverse population groups.

Effects of dietary quality, physical activity and weight loss on glucose homeostasis in persons with and without prediabetes in the PREMIER trial.

We examined the contribution of changes in diet quality, physical activity and weight loss to improvements in insulin resistance (HOMA-IR index) and fasting glucose concentrations in a long-term behavioural trial. Furthermore, we compared the effects of lifestyle changes on glycaemic markers for individuals with and without prediabetes. The PREMIER trial was an 18-month parallel randomized trial of the impact of behavioural lifestyle interventions implementing lifestyle recommendations (dietary changes, physical activity, moderate weight loss) in adults with prehypertension or stage 1 hypertension. We analysed data on 685 men and women without diabetes. Data on body weight, fitness (treadmill test), dietary intake (24-h recalls) and glycaemic outcomes were collected at baseline and at 6 and 18 months. We used general linear models to assess the association between the exposure variables and glycaemic markers. The mean (SD) age was 49.9 (8.8) years, the mean (SD) body mass index was 32.9 (5.7) kg/m2 , and 35% had prediabetes at baseline. Weight loss and improvements in fitness and diet quality were each significantly associated with lower HOMA-IR and fasting glucose concentrations at 6 and 18 months. Mediation analysis indicated that the effects of fitness and diet quality were partly mediated by weight loss, but significant direct effects of diet and fitness (independent of weight changes) were also observed. Furthermore, insulin sensitivity and fasting glucose improved significantly in participants with and without prediabetes. Our findings indicate that behavioural lifestyle interventions can substantially improve glucose metabolism in persons with and without prediabetes and that the effects of diet quality and physical activity are partly independent of weight loss.

Short-chain fatty acids and insulin sensitivity: a systematic review and meta-analysis.

There is substantial evidence that reduced short-chain fatty acids (SCFAs) in the gut are associated with obesity and type 2 diabetes, although findings from clinical interventions that can increase SCFAs are inconsistent. This systematic review and meta-analysis aimed to assess the effect of SCFA interventions on fasting glucose, fasting insulin, and homeostatic model assessment of insulin resistance (HOMA-IR). Relevant articles published up to July 28, 2022, were extracted from PubMed and Embase using the MeSH (Medical Subject Headings) terms of the defined keywords [(short-chain fatty acids) AND (obesity OR diabetes OR insulin sensitivity)] and their synonyms. Data analyses were performed independently by two researchers who used the Cochrane meta-analysis checklist and the PRISMA guidelines. Clinical studies and trials that measured SCFAs and reported glucose homeostasis parameters were included in the analysis. Standardized mean differences (SMDs) with 95%CIs were calculated using a random-effects model in the data extraction tool Review Manager version 5.4 (RevMan 5.4). The risk-of-bias assessment was performed following the Cochrane checklist for randomized and crossover studies. In total, 6040 nonduplicate studies were identified, 23 of which met the defined criteria, reported fasting insulin, fasting glucose, or HOMA-IR values, and reported change in SCFA concentrations post intervention. Meta-analyses of these studies indicated that fasting insulin concentrations were significantly reduced (overall effect: SMD = -0.15; 95%CI = -0.29 to -0.01, P = 0.04) in treatment groups, relative to placebo groups, at the end of the intervention. Studies with a confirmed increase in SCFAs at the end of intervention also had a significant effect on lowering fasting insulin (P = 0.008). Elevated levels of SCFAs, compared with baseline levels, were associated with beneficial effects on HOMA-IR (P < 0.00001). There was no significant change in fasting glucose concentrations. Increased postintervention levels of SCFAs are associated with lower fasting insulin concentrations, offering a beneficial effect on insulin sensitivity. PROSPERO registration number CRD42021257248.

Effects of acute changes in fasting glucose and free fatty acid concentrations on indices of β-cell function and glucose metabolism in subjects without diabetes.

Elevated fasting free fatty acids (FFAs) and fasting glucose are additively associated with impaired glucose tolerance (IGT) and decreased β-cell function [quantified as disposition index (DI)]. We sought to examine how changes in fasting FFA and glucose alter islet function. We studied 10 subjects with normal fasting glucose (NFG) and normal glucose tolerance (NGT) on two occasions. On one occasion, Intralipid and glucose were infused overnight to mimic conditions present in IFG/IGT. In addition, we studied seven subjects with IFG/IGT on two occasions. On one occasion, insulin was infused to lower overnight FFA and glucose concentrations to those observed in people with NFG/NGT. The following morning, a labeled mixed meal was used to measure postprandial glucose metabolism and β-cell function. Elevation of overnight fasting FFA and glucose in NFG/NGT did not alter peak or integrated glucose concentrations (2.0 ± 0.1 vs. 2.0 ± 0.1 Mol per 5 h, Saline vs. Intralipid/glucose, P = 0.55). Although overall β-cell function quantified by the Disposition Index was unchanged, the dynamic component of β-cell responsivity (ϕd) was decreased by Intralipid and glucose infusion (9 ± 1 vs. 16 ± 3 10-9, P = 0.02). In people with IFG/IGT, insulin did not alter postprandial glucose concentrations or indices of β-cell function. Endogenous glucose production and glucose disappearance were also unchanged in both groups. We conclude that acute, overnight changes in FFA, and glucose concentrations do not alter islet function or glucose metabolism in prediabetes.NEW & NOTEWORTHY This experiment studied the effect of changes in overnight concentrations of free fatty acids (FFAs) and glucose on β-cell function and glucose metabolism. In response to elevation of these metabolites, the dynamic component of the β-cell response to glucose was impaired. This suggests that in health overnight hyperglycemia and FFA elevation can deplete preformed insulin granules in the β-cell.

EFFECTIVENESS AND SAFETY OF CHONDROGUARD THERAPY IN PATIENTS WITH ENDOCRINE PHENOTYPE OF OSTEOARTHRITIS

Objective. To evaluate the efficiency and safety of therapy with parenteral chondroitin sulfate (CS) Chondroguard®, CS-Bioactive© (Bioiberica S.A.U., Spain); ZAO “Sotex” PharmFirm, Russia) in patients with Stage II knee osteoarthritis (KOA), grade 1 knee functional insufficiency (FI), and type 2 diabetes mellitus (T2DM). Subjects and methods. A 50-day comparative pilot study involved 80 patients with Kellgren-Lawrence Stage II KOA, grade 1 FI, and T2DM, who were divided into 2 groups; Group 1 (a study group; n=40) received CS (Chondroguard®, 100 mg/ml, intramuscularly, every other day; the first three injections of 1 ml each; if they were well tolerated; starting from injection 4 of ml each; the treatment cycle was 25 injections for 50 days) and therapy for T2DM and its complications; Group 2 (a comparison group; n=40) took oral symptomatic slow acting drugs for osteoarthritis (SYSADOA) agents containing CS, glucosamine, unsaponifiable compounds of avocado and soybean, and therapy for T2DM and its complications. On study days 0 and 50, the investigators calculated in the patients the scores of the visual analogue scale (VAS), WOMAC index, the Lequesne index, those of the WHO and the Narango Therapy Safety Scales, assessed the parameters of the blood hormonal and metabolic profile, free radical oxidation (FRO), antioxidant system (AOS), and the levels of blood proinflammatory factors. Results. In Group 1, therapy with CS was well tolerated and was accompanied by a reduction in pain intensity on VAS at rest and in motion, in functional restrictions on the WOMAS index and the Lequesne index, as well аs by a decrease in blood proinflammatory markers (С-reactive protein, interleukin 6 and 1β, leptin, lipocalin-2), in the concentration of fasting and postprandial glucose, HbA1c, С-peptide, insulin-like growth factor-1, and in FRO-AOS activity (malondialdehyde, protein oxidative modification, superoxide dismutase) as compared with the indicators in Group 2. Conclusion. Chondroguard® was shown to be effective and safe in the combination therapy in patients with Stage II endocrine KOA phenotype, grade 1 FI, and T2DM.

Insulin Sensitivity and β-Cell Function During Early and Late Pregnancy in Women With and Without Gestational Diabetes Mellitus.

To evaluate the metabolic alterations associated with gestational diabetes mellitus (GDM) in women with overweight or obesity. We compared fasting and postprandial plasma glucose and free fatty acid (FFA) concentrations, insulin sensitivity (IS; Matsuda index), and β-cell function (i.e., β-cell responsiveness to glucose) by using a frequently sampled oral glucose tolerance test (OGTT) at 15 and 35 weeks' gestation in women with overweight or obesity who had GDM (n = 29) or did not have GDM (No-GDM; n = 164) at 35 weeks. At 15 weeks, IS and β-cell function were lower, and fasting, 1-h, and total area-under-the-curve plasma glucose concentrations during the OGTT were higher (all P < 0.05) in the GDM than in the No-GDM group. At 35 weeks compared with 15 weeks, IS decreased, β-cell function increased, and postprandial suppression of plasma FFA was blunted in both the GDM and No-GDM groups, but the decrease in IS and the increase in postprandial FFA concentration were greater and the increase in β-cell function was less (all P ≤ 0.05) in the GDM than in the No-GDM group. A receiver operating characteristic curve analysis showed that both fasting plasma glucose and 1-h OGTT glucose concentration at 15 weeks are predictors of GDM, but the predictive power was <30%. Women with overweight or obesity and GDM, compared with those without GDM, have worse IS and β-cell function early during pregnancy and a greater subsequent decline in IS and blunted increase in β-cell function. Increased fasting and 1-h OGTT plasma glucose concentration early during pregnancy are markers of increased GDM risk, albeit with weak predictive power.

0145 Associations Among Childhood Stress, Actigraphy-Measured Sleep Efficiency, and Fasting Glucose Concentrations in Young Adults

Abstract Introduction Psychosocial stress exposure during the first 18 years of life promotes adverse sleep and cardiometabolic health effects. The purpose of the study was to investigate the relationships between childhood stress (CS), sleep efficiency (SE), and fasting glucose levels (FG) in young adulthood. Methods In 24 adults between the ages of 18 and 35 years (83% Female; mean±SD, age = 24±5 y), CS was assessed using a retrospective childhood stress assessment and averaged across reference ages of 5, 10, and 15 years old. FG concentrations were obtained from whole blood samples and SE was assessed using an actigraphy device (ActTrust2) worn on the wrist for 7 days, yielding ≥6 days of sleep data. Zero-order correlations were used to investigate the relationships among CS, SE, and FG. Multiple linear regression analyses were used to examine the effect of CS and SE on FG controlling for sex. To explore preliminary indications of a mechanistic effect of SE on the link between CS and FG, ANCOVA analysis was used. Participants were grouped as either low CS (CS-low) or high CS (CS-high), and analyses were completed with sex as the only covariate and sex and SE as covariates, with FG as the outcome. Results CS was associated with FG (r=0.50, p=0.01) and SE (r=-0.41, p=0.47), and SE with FG (r=-0.45, p=0.03). The association of CS with FG (β=0.51, p=0.016) and SE (β=-0.43, p=0.046) remained with adjustment for sex. ANCOVA analyses confirmed the effect of CS on FG, where FG was higher in CS-high than CS-low with adjustment for sex (92.4±4.8 vs. 83.6±5.4 mg/dL; p=0.008). Additional adjustment for SE reduced the difference between CS-high and CS-low, but this difference remained significant (91.6±5.0 vs. 84.5±5.5 mg/dL; p=0.044). Conclusion CS is linked with elevated FG and low SE in young adults. Our preliminary data suggest that SE warrants further examination as a potential mechanism by which CS relates to FG, but larger sample sizes will be necessary to draw definitive conclusions. Support (if any) Research reported in this publication was supported in part by the NCATS of the NIH (UL1TR002537) and by the Injury Prevention Research Center through the CDC (R49 CE003095).

The influence of 17β-estradiol plus norethisterone acetate treatment on markers of glucose and insulin metabolism in women: a systematic review and meta-analysis of randomized controlled trials.

Despite the fact that some evidence suggests that the administration of 17β-estradiol plus norethisterone acetate influences glucose and insulin metabolism in women, these findings are still contradictory. Thus, we aimed to examine the impact of the co-administration of 17β-estradiol and norethisterone acetate on glycated haemoglobin (HbA1c), fasting glucose, insulin and C-peptide concentrations in females by means of a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched four databases (PubMed/MEDLINE, Scopus, Embase, and Web of Science) using specific keywords and word combinations. The random-effects model (DerSimonian and Laird model) was employed to compute the weighted mean difference (WMD) and 95% confidence intervals (CIs) for the variations from baseline of HbA1c, fasting glucose, insulin, and C-peptide concentrations. In total, 14 RCTs were entered into the quantitative synthesis. The combined administration of 17β-estradiol and norethisterone acetate decreased HbA1c (WMD: -0.65%, 95% CI: -1.15 to -0.15; P=0.011), fasting glucose (WMD: -11.05 mg/dL, 95% CI: -16.6 to -5.5; P<0.001) and insulin (WMD: -1.35 mIU/L, 95% CI: -2.20 to -0.50; P=0.001) levels. C-peptide concentrations' declined only in females diagnosed with overweight/obesity or diabetes. Evidence to date points out that the administration of 17β-estradiol and norethisterone acetate has a positive impact on glucose metabolism in women by reducing fasting glucose, HbA1c, and insulin values. Future studies need to confirm the potential benefits of this drug combination in the prevention and/or management of cardiometabolic disorders.

Relationship between continuous glucose monitor (CGM)-assessed glycemic health and biological markers of cardiovascular health in adults

BackgroundAdults with overweight or obesity have a higher risk of the development of impaired glycemic health and cardiometabolic disorders. Glycemic variability acts as a more sensitive assessment of glycemic health compared to other clinical measures. Oxidative stress and diminished vascular health play a key role in the development of cardiometabolic disorders.ObjectiveTo examine the relationship between glucose concentrations and glycemic variability with biological markers of vascular health and oxidative stress.MethodsAdults (n = 28; body mass index = 32.3 ± 6.3 kg/m2) completed 7-day continuous glucose monitoring. Percentage of time each day glucose concentrations were < 70 mg/dL, 70–180 mg/dL, and > 180 mg/dL was evaluated. Means of 24-h, waking and night sleep hours, maximum, minimum, and difference between maximum and minimum (Max–Min) glucose concentrations were determined. Measurements of intra- and inter-day glycemic variability were calculated. Fasting concentrations of glucose, vascular health marker nitric oxide (NO), and oxidative stress marker myeloperoxidase (MPO) were measured, and the ratio of NO concentration to MPO concentration (NO:MPO) was calculated (propensity to vasodilate).ResultsMPO concentration negatively correlated with glycemic variability measured as the mean amplitude of glycemic excursion (r2 = 0.23, β = − 0.62, p = 0.03), while the NO:MPO ratio positively correlated with fasting glucose concentration (r2 = 0.22, β = 3.79, p = 0.01).ConclusionsOur findings suggest that an increased propensity to vasodilate relates to increased fasting glucose concentration, while increased oxidative stress relates to decreased glycemic variability. These findings were unexpected and necessitates further research into the potential mechanisms of these findings for cardiometabolic health in adults having overweight or obesity.

76 Digestibility of a diet with or without reed sedge peat in exercised horses

An experiment was conducted to determine the effect of a concentrate diet containing Reed Sedge Peat (RSP) on nutrient digestibility, and serum glucose and insulin concentrations in mature exercised horses. The addition of RSP to the diet may effect nutrient digestibility and glucose metabolism in exercising horses. Six stock-type geldings (μ 546 kg), ranging from 8 to 19 yr of age, were fed a diet consisting of coastal Bermudagrass hay and a concentrate with or without RSP in a duplicated 3 × 3 Latin-square design. Three dietary treatments consisted of: control, no RSP (C); 10 lb/ton RSP (RSP10; Kent Nutrition Group, Muscatine, IA); and 20 lb/ton RSP added (RSP20). The 12-wk study consisted of 3 21-d adjustment periods followed by a 3-d fecal collection period. Total feces voided was collected every 4 h. Blood was collected 30 min pre-feeding, 30 min post-feeding, 8 h post-feeding, 30 min pre- Standard Exercise Test (SET); then 30 s, and 10, 30, 60, and 120 min post-SET. Horses were fed hay at a minimum 2% body weight per day and 2.2 kg/d of each dietary treatment. Feed and feces were analyzed for dry matter (DM), crude protein (CP), ether extract (EE), acid detergent fiber (ADF), neutral detergent fiber (NDF), ash, Ca, and P concentrations. Blood serum was analyzed for fasting insulin and glucose concentrations. Data for nutrient digestibilities, and serum glucose and insulin concentrations were analyzed using theProc Mixed Procedure of SAS v. 9.4. Significant differences between means were declared at P < 0.05. There was an effect of period on apparent DM (P = 0.02), NDF (P = 0.04), ADF (P = 0.01), Ca (P = 0.03), and P (P = 0.01) digestibility. There was an effect of treatment (P = 0.03) on pre- and post-prandial serum glucose concentrations. Horses consuming RSP20 (95.5 mg/dL) had greater overall mean serum glucose concentrations compared with horses consuming RSP10 (87.2 mg/dL) and C (86.6 mg/dL). Overall post-prandial serum insulin concentrations (17.81 uIU/mL) were greater (P < 0.01) compared with pre-prandial (7.1 uIU/mL) and 8 h post-prandial (6.52 uIU/mL). Immediately following exercise, mean serum glucose concentrations decreased (P < 0.01) from 86.43 mg/mL pre-SET to 80.13 mg/dL. Serum insulin concentrations decreased (P < 0.01) from 5.56 ulU/mL pre-SET to 3.05 ulU/mL post-SET. The data suggests no benefits were observed in nutrient digestibility when RSP was added to horses’ diets. However, greater glucose concentrations with the RSP20 diet may provide more energy for performance of the horse. Therefore, further research may be warranted to investigate effects of RSP on glucose and insulin dynamics in exercising horses.