Moderate Hyperglycemia Research Articles

Effects of Stress Hyperglycemia on Short-Term Prognosis of Patients Without Diabetes Mellitus in Coronary Care Unit.

Background: Diabetes mellitus (DM) has a high morbidity and mortality worldwide, and it is a risk factor for cardiovascular diseases. Non-diabetic stress hyperglycemia is common in severely ill patients, and it could affect prognosis. This study aimed to analyze the influence of different blood glucose levels on prognosis from the perspective of stress hyperglycemia by comparing them with normal blood glucose levels and those of patients with DM.Methods: A retrospective study of 1,401 patients in coronary care unit (CCU) from the critical care database called Medical Information Mart for Intensive Care IV was performed. Patients were assigned to the following groups 1–4 based on their history of DM, random blood glucose, and HbA1c levels: normal blood glucose group, moderate stress hyperglycemia group, severe stress hyperglycemia group and DM group. The main outcome of this study was 30- and 90-day mortality rates. The associations between groups and outcomes were analyzed using Kaplan–Meier survival analysis, Cox proportional hazard regression model and competing risk regression model.Results: A total of 1,401 patients in CCU were enrolled in this study. The Kaplan–Meier survival curve showed that group 1 had a higher survival probability than groups 3 and 4 in terms of 30- and 90-day mortalities. After controlling the potential confounders in Cox regression, groups 3 and 4 had a statistically significant higher risk of both mortalities than group 1, while no difference in mortality risk was found between groups 2 and 1. The hazard ratios [95% confidence interval (CI)] of 30- and 90-day mortality rates for group 3 were 2.77(1.39,5.54) and 2.59(1.31,5.12), respectively, while those for group 4 were 1.92(1.08,3.40) and 1.94(1.11,3.37), respectively.Conclusions: Severe stress hyperglycemia (≥200 mg/dL) in patients without DM in CCU may increase the risk of short-term death, which is greater than the prognostic effect in patients with diabetes. Patients with normal blood glucose levels and moderate stress hyperglycemia (140 mg/dL ≤ RBG <200 mg/dL) had no effect on short-term outcomes in patients with CCU.

Admission blood glucose level and outcome in patients requiring venoarterial extracorporeal membrane oxygenation

BackgroundPatients with cardiogenic shock or cardiac arrest undergoing venoarterial extracorporeal membrane oxygenation (V-A ECMO) frequently present with blood glucose levels out of normal range. The clinical relevance of such findings in the context of V-A ECMO is unknown. We therefore investigated the prognostic relevance of blood glucose at time of cannulation for V-A ECMO.MethodsWe conducted a single-center retrospective registry study. All patients receiving V-A ECMO from October 2010 to January 2020 were included if blood glucose level at time of cannulation were documented. Patients were divided in five groups according to the initial blood glucose level ranging from hypoglycemic (< 80 mg/dl), normoglycemic (80–140 mg/dl), to mild (141-240 mg/dl), moderate (241–400 mg/dl), and severe (> 400 mg/dl) hyperglycemia, respectively. Clinical presentation, arterial blood gas analysis, and survival were compared between the groups.Results392 patients met inclusion criteria. Median age was 62 years (51.5–70.0), SAPS II at admission was 54 (43.5–63.0), and 108/392 (27.6%) were female. 131/392 were discharged alive (hospital survival 33.4%). At time of cannulation, survivors had higher pH, hemoglobin, calcium, bicarbonate but lower potassium and lactate levels compared to non-survivors (all p < 0.01). Outcome of patients diagnosed with particularly high (> 400 mg/dl) and low (< 80 mg/dl) blood glucose at time of V-A ECMO cannulation, respectively, was worse compared to patients with normoglycemic, mildly or moderately elevated values (p = 0.02). Glucose was independently associated with poor outcome after adjustment for other predictors of survival and persisted in all investigated subgroups.ConclusionArterial blood glucose at time of V-A ECMO cannulation predicts in-hospital survival of patients with cardiac shock or after ECPR. Whether dysglycemia represents a potential therapeutic target requires further evaluation in prospective studies.Graphical

EFFECT OF TETRAHYDROCURCUMIN IN STREPTOZOTOCIN - NICOTINAMIDE INDUCED DIABETES

Diabetes is a major health problem affecting major populations worldwide. It is characterized by absolute or relative deficiencies in insulin secretion and/or insulin action associated with chronic hyperglycemia and disturbances of carbohydrate, lipid and protein metabolism. As a consequence of the metabolic derangements in diabetes, various complications develop including both macro and micro-vascular dysfunctions. Pancreatic cell dysfunction and insulin resistance are the two hallmarks of type 2 diabetes mellitus. Treatment of diabetes without any side effects is still a challenge to the medical system. There is an increasing demand by patients to use the natural products with antidiabetic activity, because insulin and oral hypoglycemic drugs are having so many side effects. Streptozotocin (STZ)-nicotinamide type 2 model shares a number of features with human type 2 diabetes and is characterized by moderate stable hyperglycemia, glucose intolerance, altered but significant glucose-stimulated insulin secretion, in vivo and in vitro. Tetrahydrocurcumin (THC) is one of the major colorless metabolite of curcumin. THC has been reported to exhibit the same physiological and pharmacological properties of curcumin. Curcumin is rapidly metabolized during absorption from the intestine, yielding THC, which has shown the strongest antioxidant activity among all curcuminoids. THC one of the active metabolites in curcumin on blood glucose and plasma insulin in streptozotocin induced diabetic rats. Different doses of THC (20, 40 and 80 mg\kg body weight) were orally administered to diabetic rats for 45 days, after which activities 6-weeks treatment with various doses of THC and curcumin on glucose levels were assayed

Standaryzowana kompozycja polifenoli z bergamoty – kompleksowy suplement diety o właściwościach plejotropowych na tle innych dostępnych na rynku wybranych naturalnych substancji hipolipemizujących

Bergamot juice has a particularly high content and a unique composition of flavonoids. It is particularly rich in flavanones and flavones. Standardized bergamot polyphenolic fraction has the same polyphenol profile as in the juice, but flavonoids are over 200 times more concentrated. Many data show its brilliant performance in hyperlipidaemia and moderate hyperglycemia. In addition, compared to other dietary supplements available on the market, it has beneficial pleiotropic properties.

The investigation of the efficacy ratio of cress seeds supplementation to moderate hyperglycemia and hepatotoxicity in streptozotocin-induced diabetic rats.

Oxidative stress resulting from chronic hyperglycemia induced many complications in diabetes and led to disorders and dysfunctions in different organs. This study aimed to evaluate the hepatoprotective rate of cress seeds (CS) or Lepidium sativum seeds in the diet on lowering hyperglycemia and oxidative stress damaging. Diabetes was induced by a single intraperitoneal injection of 60mg/kg of streptozotocin (STZ). Forty-eight male rats were randomly divided into six groups : (D-0) and (ND-0) diabetic, and non-diabetic groups were fed with a normal diet, (ND-CS2) and (ND-CS5) non-diabetic groups were fed with diet containing 2 % and 5 % of cress seeds respectively, (D-CS2) and (D-CS5) diabetic groups were fed with diet containing 2 % and 5 % of cress seeds respectively. After 28 days of treatment, biochemical, histological, and oxidative parameters were determined. Hepatic and pancreatic histological sections were developed. STZ-injection caused hyperglycemia accompanied by a disturbance in biochemical parameters and intensified oxidative stress status compared to the (ND-0) group. Hepatic and pancreatic histological sections of diabetic rats showed a disrupted architecture. However, the cress seeds-diet revealed a significant decrease of hyperglycemia and a reduction of the intensity of oxidative stress induced by diabetes compared to the (D-0) group, remarked by a decreased level of Malondialdehyde (MDA) and high levels of glutathione (GSH) and the antioxidant enzymes, led to the decrease of the majority of parameters principally hepatic and lipid profile with histological regeneration. Cress seeds supplementation confirmed their potential anti-diabetic and antioxidant activities with higher efficacy of 5 % dose than the lower dose of 2 %. Therefore, 5 % of cress seeds administration seems to be the excellent rate recommended in controlling diabetes and its complications.

Vitamin D Toxicosis in a Blue-Tongued Skink (Tiliqua scincoides) Presented with Epistaxis and Tongue Discoloration

A 10-yr-old intact blue-tongued skink (Tiliqua scincoides) of unknown sex presented for epistaxis and dyspnea. On physical examination, dysecdysis, necrosis of the tip of the tail, and a pink discoloration of the proximal third of the tongue were noted in addition to epistaxis, dyspnea, and tachypnea. Clinical pathology findings included marked polychromatophilia, moderate heterophilia with signs of toxicity, a regenerative left shift, and moderate hyperglycemia. Because of the suspicion of an infectious etiology, antibiotics were prescribed. Meloxicam was also administered without clinical improvement. Swelling of the pharyngeal area was noted on whole-body computed tomographic and magnetic resonance imaging. Oro-pharyngeal endoscopic-guided biopsies were performed under general anesthesia. Histology was consistent with moderate erosion and goblet cell hyperplasia. Plasma 25-hydroxyvitamin D3 concentration was 768 nmol/L and was interpreted as possible vitamin D toxicosis. Prednisolone was prescribed to enhance calciuresis and treat potential vasculitis, but the skink was ultimately euthanized. Histopathologic examination was consistent with vitamin D toxicosis. The diet of this skink mostly consisted of greens dusted with a supplement containing calcium and vitamin D3. This case report describes the challenges associated with antemortem diagnosis of a vitamin D toxicosis, even with current imaging techniques. It highlights that specific reference intervals should be established for 25-hydroxyvitamin D3 and ionized calcium concentrations in various reptile species. Clinicians presented with a blue-tongued skink displaying a pink tongue or tail necrosis should consider vitamin D toxicosis in their differential diagnosis.

Prognostic value of packed cell volume and blood glucose concentration in 954 client-owned chelonians.

To evaluate the prognostic value of PCV and blood glucose concentration in chelonians presented for veterinary care and to develop risk categories on the basis of the interaction of these analytes. 954 client-owned chelonians (34 genera). Medical records of 1,059 client-owned chelonians presented to 2 veterinary institutions between 2014 and 2018 were reviewed. Logistic regression models were developed to evaluate factors associated with death, including PCV and blood glucose concentrations. There were 954 chelonians (34 genera) for which the data required to be included in the analysis were available. Both PCV and blood glucose concentration were significant prognostic indicators of death. Odds of death for chelonians with severe anemia (PCV, < 10%) and moderate anemia (PCV, 11% to 20%) were 6.8 times (adjusted odds ratio [aOR], 6.8; 95% CI, 3.8 to 12.3) and 1.6 times (aOR, 1.6; 95% CI, 1.01 to 2.7), respectively, the odds of death for chelonians with PCV within reference range. Odds of death for chelonians with severe hypoglycemia (< 30 mg/dL), moderate hyperglycemia (91 to 150 mg/dL), and severe hyperglycemia (> 181 mg/dL) were 5.3 times (aOR, 5.3; 95% CI; 2.4 to 11.4), 3 times (aOR, 3.0;95% CI, 1.4 to 6.3), and 4.3 times (aOR, 4.3; 95% CI, 2.4 to 7.6), respectively, the odds of death for chelonians with blood glucose concentration within reference range. Five risk categories were identified on the basis of PCV and blood glucose concentration. Derangements in PCV and blood glucose concentration in client-owned chelonians were associated with increased odds of death. On the basis of these results, more aggressive diagnostic testing and treatments may be indicated in chelonians with similar alterations.

Challenges and Strategies for Inpatient Diabetes Management in Older Adults.

Adults older than 65 years of age are the fastest growing segment of the U.S. population. Aging is also one of the most important risk factors for diabetes, and about one-third of all individuals with diabetes are in this age-group. Older people with diabetes are more likely to have comorbidities such as hypertension, ischemic heart disease, chronic kidney disease, and cognitive impairment, which lead to higher rates of hospital admissions compared with individuals without diabetes. Professional organizations have recommended patient-centric individualized glycemic reduction approaches, with an emphasis on potential harms of intensive glycemic control and overtreatment in older adults. Insulin therapy remains a mainstay of diabetes management in the inpatient setting regardless of patients' age; however, there is uncertainty about optimal glycemic targets during the hospital stay. Increasing evidence supports selective use of dipeptidyl peptidase-4 inhibitors, alone or in combination with low-dose basal insulin, in older noncritically ill patients with mild to moderate hyperglycemia. This article reviews the prevalence, diagnosis, and monitoring of, and the available treatment strategies for, diabetes among elderly patients in the inpatient setting.

Oral antidiabetes agents for the management of inpatient hyperglycaemia: so far, yet so close.

Hyperglycaemia is an ongoing challenge in hospital settings and is associated with poor outcomes. Current recommendations for the management of inpatient hyperglycaemia suggest insulin as the main glucose-lowering treatment choice and limit the administration of oral antidiabetes agents to a small proportion of cases because of safety concerns. To present and critically appraise the available evidence on the use of oral antidiabetes agents in the hospital setting and the risk-benefit balance of such an approach in the era of cardiovascular outcomes trials. PubMed, Embase and Google Scholar databases were searched to identify relevant published work. Available evidence on the efficacy and the safety profile of oral agents in the context of their use in hospitalized individuals are summarized and discussed in this narrative review. There is no robust evidence to suggest the use of metformin,thiazolidinediones, sulfonylureas and sodium-glucose co-transporter-2 inhibitors in the hospital setting, although some of their effects on acute outcomes deserve further evaluation in future studies. However, the use of dipeptidyl peptidase-4 inhibitors in inpatients with type 2 diabetes is supported by a few, well-designed, randomized controlled trials.These trials have demonstrated good safety and tolerability profiles, comparable to insulin glucose-lowering efficacy, and a reduction in insulin dose when dipeptidyl peptidase-4 inhibitors are co-administered with insulin, in individualswith mild to moderate hyperglycaemia and a stable clinical condition. The administration of dipeptidyl peptidase-4 inhibitors to specific groups of inpatients might be a safe and effective alternative to insulin.

315-OR: Hyperglycemia Increases Central Aortic Stiffness in Response to Insulin in Healthy Humans

Introduction: Insulin exerts several opposing hemodynamic vascular actions, including stimulation of both nitric oxide-mediated vasodilation and endothelin-1-mediated vasoconstriction. Notably, hyperglycemia switches the vascular response to insulin from dilation to constriction in pre-clinical studies. To our knowledge, hyperglycemia’s effect on insulin’s action on vascular stiffness in humans is unknown. The American Heart Association recently recommended that vascular stiffness be determined noninvasively by carotid-femoral pulse wave velocity (cfPWV) and/or using wave separation analyses (WSA) instead of aortic augmentation index (AIx). Methods: Thirteen lean, healthy subjects twice received a 1 mU/kg/min 2-hour insulin clamp. In one study, subjects were euglycemic and in the second, hyperglycemic (∼200 mg/dL) for 2 hours before and throughout the clamp. In each study, octreotide was infused to block endogenous insulin secretion. We assessed vascular stiffness with cfPWV, AIx, and WSA at baseline and after the 2-hour insulin clamp. Linear mixed model was used for statistical analysis, with Bonferroni correction for between-study comparisons. Spearman correlation was used to evaluate the relationship between PWV and WSA components. Results: Compared to baseline, insulin increased cfPWV (p=0.03) during hyperglycemia without affecting AIx or components of WSA. No changes were observed during euglycemia, and insulin levels did not differ between groups. Neither AIx nor WSA components (i.e., backward and forward wave amplitude and reflection magnitude) correlated with cfPWV. Discussion: We provide the first evidence that 4 hours of moderate hyperglycemia unmasks an action of physiologic hyperinsulinemia to increase central aortic stiffness (as measured by cfPWV) in healthy humans. Second, our results suggest that neither AIx nor WSA components correlate with cfPWV as measures of vascular stiffness. Disclosure W.B. Horton: None. L. Jahn: None. L. Hartline: None. J.T. Patrie: None. E. Barrett: None.

692-P: Hyperglycemia Impairs Aerobic Adaptation to Exercise

Improved aerobic exercise capacity (VO2max) has emerged as one of the most important health benefits of aerobic exercise training. However, hyperglycemia is associated with low VO2max in humans, even when physical activity levels are matched. To determine how glycemia influences aerobic adaptations with exercise training, we induced moderate hyperglycemia (+50-70 mg/dL vs. control) in mouse models that mimic the pathologies of type 1 or type 2 diabetes: 1) Low-dose Streptozotocin treatment (STZ), or 2) Western diet (WD) feeding. Normoglycemic mice acted as controls (CON). All mice completed ∼500 km of voluntary wheel running over an 8-wk aerobic training period, and achieved the expected metabolic benefits from exercise training. However, metabolic improvements were uncoupled from aerobic adaptation in hyperglycemic WD and STZ mice, who failed to improve VO2max beyond the level of sedentary controls. In contrast, CON mice had a 2-fold increase in VO2max in response to the same training intervention. In hyperglycemic models, blunted improvements in VO2max were associated with structural changes to muscle, including glucose-induced modifications to the extracellular matrix (e.g., glycation and collagen accretion), and reduced exercise-induced angiogenesis and oxidative fiber-type shifts. Thus, our data provide evidence that aerobic muscle remodeling, which is critical for augmenting VO2max, is impaired by hyperglycemia. In addition, we show that chronic hyperglycemia causes hyper-activation of a JNK/SMAD2 signaling network in muscle with acute aerobic exercise, which is a known molecular mechanism that inhibits aerobic adaptation. Accordingly, in human subjects, we show that impaired glucose tolerance strongly predicts hyper-activation of this inhibitory signaling network in conjunction with low VO2max. Taken together, we demonstrate that hyperglycemia, regardless of etiology, may interfere with fundamental adaptations to aerobic exercise training and negatively regulate improvements in VO2max. Disclosure T. MacDonald: None. P. Pathak: None. N.M. Fernandez: None. E.C. Freitas: None. S. Hafida: None. J. Mitri: Consultant; Spouse/Partner; Janssen Pharmaceuticals, Inc., kymera. Consultant; Self; national dairy council/local dairy council. Research Support; Spouse/Partner; AbbVie Inc., beigene, Janssen Pharmaceuticals, Inc. Research Support; Self; Kowa Pharmaceuticals America, Inc., national dairy council. Research Support; Spouse/Partner; pharma cyclic, TG therapeutics. S.J. Lessard: None. Funding American Heart Association (19POST34381036)

1041-P: Randomized Controlled Trial on the Efficacy of Supplemental Rapid-Acting Insulin during Basal-Bolus Regimen in Non-ICU Patients with Type 2 Diabetes

The administration of rapid-acting insulin per sliding scale (SSI) for correction of hyperglycemia in non-ICU patients with type 2 diabetes (T2D) is used with most basal-bolus insulin (BBI) regimens; however, the safety and efficacy of using SSI has not been tested in RCTs. In this non-inferiority RCT, we tested whether correction of hyperglycemia before meals and bedtime improves glycemic control in patients treated with BBI regimens. Patients with T2D with a blood glucose (BG) &amp;gt; 140 mg/dl treated with BBI were randomized to SSI for BG &amp;gt;140 mg/dl (intensive supplement) or to SSI for BG &amp;gt;260 mg/dl (non-intensive supplement). Primary outcome was difference in mean BG levels between the groups during hospital stay. There were no differences in baseline characteristics between the intensive and non-intensive supplement groups. There were no differences between groups in mean daily BG, length of stay (LOS), hypoglycemia (BG &amp;lt; 70 or &amp;lt; 54 mg/dl), severe hyperglycemia (BG &amp;gt; 350 mg/dl), and total, basal, prandial or supplemental daily insulin doses (U/day). In patients with any BG 140-260 mg/dl and without BG &amp;gt; 260 mg/dl, mean BG did not differ but non-intensive group needed more prandial insulin. Conclusion: Adding correction/supplement SSI in non-ICU T2D patients with mild to moderate hyperglycemia (&amp;lt;260 mg/dl) on basal bolus regimen does not improve glycemic control. Disclosure P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. S. Cardona: None. M.A. Urrutia: None. R.J. Galindo: Advisory Panel; Self; Lilly Diabetes. Consultant; Self; Valeritas, Inc. Research Support; Self; Novo Nordisk Inc. Other Relationship; Self; UpToDate. G. Davis: None. J. Haw: None. M. Fayfman: None. A. Migdal: None. Y. Guo: None. F.J. Pasquel: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp. Research Support; Self; Dexcom, Inc., Merck Sharp &amp; Dohme Corp., National Institutes of Health. G.E. Umpierrez: None. Funding National Institutes of Health

Hopf bifurcation and chaos in time-delay model of glucose-insulin regulatory system

Abstract Mathematical modeling is very helpful for non-invasive investigation of glucose-insulin interaction. In this paper a new time delay mathematical model for glucose-insulin endocrine metabolic regulatory feedback system incorporating the β-cell dynamic and function for regulating and maintaining bloodstream insulin level, has been proposed. The proposed model includes the mathematical representation of an important biological fact that the moderate hyperglycemia leads to the growth of the β-cell number (negative feedback) while extreme hyperglycemia leads to the reduction of the β-cell number (positive feedback). The dynamical behavior of the model is analyzed analytically using Hopf bifurcation theorem and numerically such as two dimensional bifurcation diagrams with respect to two essential parameters of the model are obtained. The results show that the time delay in insulin secretion in response to blood glucose level, and the delay in glucose drop due to increased insulin concentration can give rise to complex dynamics, such as periodic oscillation consistent with the biological findings and periodic doubling cascade and chaotic state which represent metabolic disorder that may lead to diabetes mellitus.

Preparation of enzyme based polymeric biomimetic nanoparticle for the controlled release of insulin

This study aims to assess the faster responsiveness of the insulin release which is a self-regulated insulin delivery system constructed by encapsulating insulin and enzyme glucose oxidase into hyaluronic acid and 2-nitroimidazole which works mainly for stabilizing the hyperglycemia state based on the blood glucose level. Enzyme based nanoparticles were prepared by simple ionic gelation method. Insulin loaded nanoparticles kept for stability studies estimated by using human insulin enzyme linked immunosorbent assay (ELISA Kit) showing stability upto 30 days at 4 °C. The average diameter of the nanoparticles were having around 193 nm and achieved high insulin entrapment efficiencies (approximately 85%). In vitro studies showed the release of insulin from enzyme based nanoparticles which was effectively correlated by creating an external blood glucose different glycemic environment where different concentrations of glucose were taken estimated by human insulin ELISA assay. The equilibrium was achieved for high glucose concentration at 400 mg/dL (hyperglycemia state) was cumulative increase upto 53% of insulin release with immediate stabilization observed within 0.5 h and glucose concentration (moderate hyperglycemia) at 250 mg/dL showed release of insulin upto 43.5% with stable decline. Normal glucose level at 100 mg/dL (normoglycemia) showed normal release upto 25.3% whereas with less glucose concentration at 50 mg/dL (hypoglycemia state) only 15% release was found. Overall, this preliminary study showed excellent rapid responsiveness towards hyperglycemia condition which might act as a potential biomimetic system in triggering the release of insulin in sustained manner.

Effects of Acute SGLT2 Blockade and Dietary NaCl on Glomerular Hemodynamics in Diabetic Rats

Inhibitors of the main proximal tubular Na‐glucose cotransporter (SGLT2) mitigate diabetic glomerular hyperfiltration and are approved by FDA for slowing the progression of diabetic kidney disease. It has been proposed that SGLT2 inhibitors improve hard renal outcomes by reducing the glomerular capillary pressure gradient (ΔP) through TGF signaling, which begins with a decrease in fluid reabsorption by the proximal tubule (Jprox). However, the effect of SGLT2 inhibition on ΔP has not been measured up to now.We studied effects of acute SGLT2 blockade (ertugliflozin) on Jprox and glomerular hemodynamics by 2‐period micropuncture in STZ‐diabetic rats fed high or low NaCl diets (HS/LS). ΔP was measured by direct capillary puncture in Wistar Froemter rats (MWF), which have surface glomeruli suitable for this purpose. ΔP was computed from tubular stop‐flow pressure in Wistar rats (Wis), which lack surface glomeruli. Hence, TGF was allowed to operate normally while measuring ΔP in MWF but rendered inoperative while measuring ΔP in Wis. SGLT2 blockade was confirmed to reduce Jprox by collecting fluid from late proximal tubules for volume and inulin clearance.Summary and Conclusions about the diabetic kidney under conditions of moderate hyperglycemia: SGLT2 blockade acutely reduces Jprox, which leads to a decrease in glomerular capillary pressure, but only when TGF is permitted to operate normally. Baseline glomerular capillary pressure varies inversely with dietary NaCl and the impact of SGLT2 blockade applies across a wide range of dietary NaCl.Support or Funding InformationNIDDK RO1 DK112042 Merck Group (n) Glucose (mg/dl) GFR(ml/min) ΔP (mmHg) Jprox' (nl/min) control SGLT2 blocked control SGLT2 blocked control SGLT2 blocked MWF LS (6) 344±41 4.2±0.5 3.5±0.5 * 41.2±1.5 33.0±1.9 * MWF HS (8) 408±35 4.1±0.3 3.3±0.4 * 36.6±1.3 ** 32.4±1.6 * Wis LS (6) 355±41 4.8±0.4 3.8±0.5 * 43.6±1.9 43.7±2.4 18.9±1.3 10.2±1.1 * Wis HS (9) 400±52 4.5±0.5 3.8±0.6 * 32.6±2.3 ** 35.7±3.0 18.1±1.3 12.6±1.1 * *P&lt;0.01 vs control period. **P&lt;0.01 vs LS. Jprox’ is Jprox adjusted for single nephron GFR by ANCOVA to obtain the "primary" effect of SGLT2 blockade on the tubule.

Evaluation of the gestational diabetes mellitus diagnostic criteria recommended by the international association of diabetes and pregnancy study group for long-term maternal postpartum outcomes in mainland China.

The gestational diabetes mellitus (GDM) diagnostic criteria recommended by the International Association of Diabetes and Pregnancy Study Group (IADPSG) were established based on the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study and have been the most commonly used criteria for determining GDM worldwide. Although individuals from mainland China were not included in the HAPO study, the IADPSG criteria have been used in China since 2011. However, the appropriateness of the criteria for evaluating maternal postpartum outcomes in mainland China are unknown. We conducted this study to determine whether the IADPSG criteria are appropriate for Chinese patients for evaluating long-term maternal postpartum outcomes.Eighty-four patients who were diagnosed with hyperglycemia during pregnancy and had delivery in Peking University First Hospital from February 2007 to December 2009 were enrolled in the study. For patients in Group A, GDM was diagnosed using both the National Diabetes Data Group (NDDG) and the IADPSG criteria, while patients in Group B, gestational impaired glucose tolerance (GIGT) was diagnosed using the NDDG criteria while GDM was diagnosed based on the IADPSG criteria. Anthropometric data, glucose metabolism, lipid profiles, β cell function, and insulin resistance index were evaluated and compared to baseline after 5- to 6-year postpartum period.Patients in group A had significantly higher oral glucose tolerance test (OGTT) fasting, 2-hour and 3-hour plasma glucose levels compared to patients in group B at 24 to 28 weeks of gestation (P < .05). No significant differences were observed between the groups for anthropometric data, postpartum abnormal glucose metabolism (50.91% vs 44.83%, P = .596), type 2 diabetes mellitus (T2DM) (16.36% vs 3.45%, P = .167), lipid profiles, β cell function (homeostasis model assessment β-cell function index (HOMA-β) 1.04 vs 0.99, P = .935) and insulin resistance (homeostasis model assessment insulin resistance index (HOMA-IR) 2.01 vs 1.69, P = .583).Patients diagnosed with GDM using either the NDDG or IADPSG criteria had abnormal glucose levels and lipid metabolism after delivery. Patients with mild hyperglycemia had similar postpartum β-cell functional impairment and insulin resistance to those with moderate hyperglycemia during pregnancy. Hence, with respect to maternal long-term postpartum outcomes, the IADPSG diagnostic criteria for GDM could be appropriate for patients in mainland China.

Peculiarities of Metabolism of Rats with Fructose-induced Insulin Resistance Against the Background of Congenital and Acquired Iodine Deficiency

Animals following a high-fructose diet during eight weeks, have experienced changes in metabolism and the signs of insulin resistance have developed. Under such conditions, moderate hyperglycemia, hyperinsulinemia, hyperuricemia, an increase of the level of glycosylated hemoglobin in whole blood were observed. The significant role of the HOMA-IR index, as an early marker of carbohydrate metabolism disorders at the stage of pre-diabetes, has been confirmed. In experimental animals against the background of the high-fructose diet, the changes in the lipid spectrum of the blood were revealed: an increase of the total cholesterol level, low-density lipoproteins, triglycerides against the background of a high-density lipoproteins decrease. These disorders and a significant increase of the atherogenicity reflect the development of secondary dyslipidemia. In this case, the disorders of carbohydrate metabolism were combined with the degree of dyslipidemia. Males were found to have at increased risk of development the insulin resistance and comorbid pathology. Iodine deficiency, especially of congenital nature, is an aggravating factor of metabolic disorders. The obtained data can serve as a basis for extend of preventive measures and identification of the priority treatment schemes for type 2 diabetes mellitus in residents of endemic regions.

Neuroprotective Dipeptide Noopept Prevents DNA Damage in Mice with Modeled Prediabetes.

In experiments on BALB/c mice, prediabetes was modeled by administration of streptozotocin in a dose of 130 mg/kg. DNA damage was assessed by the method of DNA comets. Noopept (0.5 mg/kg intraperitoneally) was administered for 14 days before and for 6, 13, or 14 days after streptozotocin administration. Despite moderate hyperglycemia and increased malondialdehyde level, the intensity of DNA damage in cells of the pancreas, liver, and kidneys significantly surpassed the control values. Noopept normalized these parameters due to its pronounced antigenotoxic effect. For both the damaging effect of streptozotocin and the normalizing effect of Noopept, DNA changes manifested mainly in terms of atypical DNA comets. Our findings confirm the role of DNA damage in the pathogenesis of diabetes. They indicate the possibility of pharmacological protection of pancreatic β cells with the neuroprotective drug and provide an important argument in favor of the hypothesis about the similarity of the mechanisms of formation of the resistance of neurons and β cells to the cytotoxic influences.

Chronic type 2 but not type 1 diabetes impairs myocardial ischaemic tolerance and preconditioning in C57Bl/6 mice

• What is the central question of this study? What is the impact of chronic adult-onset diabetes on cardiac ischaemic outcomes and preconditioning? • What is the main finding and its importance? Chronic adult-onset type 2 but not type 1 diabetes significantly impairs myocardial ischaemic tolerance and ischaemic preconditioning. Preconditioning may be detrimental in type 2 diabetes, exaggerating nitrosative stress and apoptotic protein expression. Effects of diabetes on myocardial responses to ischaemia-reperfusion (I-R) and cardioprotective stimuli remain contentious, potentially reflecting influences of disease duration and time of onset. Chronic adult-onset type 1 diabetes (T1D) and type 2 diabetes (T2D) were modelled non-genetically in male C57Bl/6 mice via 5×50mgkg-1 daily streptozotocin (STZ) injections + 12weeks' standard chow or 1×75mgkg-1 STZ injection + 12weeks' obesogenic diet (32% calories as fat, 57% carbohydrate, 11% protein), respectively. Systemic outcomes were assessed and myocardial responses to I-R ± ischaemic preconditioning (IPC; 3×5min I-R) determined in Langendorff perfused hearts. Uncontrolled T1D was characterised by pronounced hyperglycaemia (25mm fasting glucose), glucose intolerance and ∼10% body weight loss, whereas T2D mice exhibited moderate hyperglycaemia (15mm), hyperinsulinaemia, glucose intolerance and 17% weight gain. Circulating ghrelin, resistin and noradrenaline were unchanged with T1D, while leptin increased and noradrenaline declined in T2D mice. Ischaemic tolerance and IPC were preserved in T1D hearts. In contrast, T2D worsened post-ischaemic function (∼40% greater diastolic and contractile dysfunction) and cell death (100% higher troponin efflux), and abolished IPC protection. Whereas IPC reduced post-ischaemic nitrotyrosine and pro-apoptotic Bak and Bax levels in non-diabetic hearts, these effects were reduced in T1D and IPC augmented Bax and nitrosylation in T2D hearts. The data demonstrate chronic T1D does not inhibit myocardial I-R tolerance or IPC, whereas metabolic and endocrine disruption in T2D is associated with ischaemic intolerance and inhibition of IPC. Indeed, normally protective IPC may exaggerate damage mechanisms in T2D hearts.

Volume-Based Feeding Enhances Enteral Delivery by Maximizing the Optimal Rate of Enteral Feeding (FEED MORE).

The importance of enteral nutrition (EN) in critically ill patients is well documented. However, actual administration of EN frequently does not amount to prescribed nutrition goals. Persistent underfeeding may lead to impaired immune response, increased mortality, and higher costs. Traditionally, EN uses a rate-based approach, utilizing slow titration to goal and a final fixed hourly rate, regardless of interruptions in feeding. Volume-based feeding (VBF) establishes a 24-hour EN goal volume, and the rate varies to achieve this daily goal when interruptions occur. This was a retrospective, single-center, quasi-experimental study comparing traditional rate-based feeding (RBF) to VBF in adult patients admitted to the medical and neurosurgical intensive care units (ICUs). The primary outcome was mean percentage of total goal energy received after EN initiation until 7 days, transfer from ICU, removal of feeding tube, or oral diet order placed. Secondary outcomes included mean percentage of total goal protein received, percentage of patients meeting 80% of nutrition goals, incidence of gastric residual volumes >400mL, and incidence of moderate hyperglycemia (>250mg/dL). The study enrolled 189 patients. Mean percentage of goal energy delivered (75% RBF, 102% VBF; P < .001) and goal protein delivered (68% RBF, 87% VBF; P < .001) was significantly higher with VBF compared with RBF. VBF demonstrated a significant increase in energy and protein delivery with no major safety or tolerability issues. VBF should be considered for use in ICU patients to optimize nutrition delivery.