• Title, Summary, Keyword: normoglycemia

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Higher dextrose delivety via TPN related to the development of hyperglycemia in non-diabetic critically ill patients

  • Lee, Ho-Sun;Koh, Shin-Ok;Park, Moo-Suk
    • Nutrition Research and Practice
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    • v.5 no.5
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    • pp.450-454
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    • 2011
  • The beneficial effects of total parenteral nutrition (TPN) in improving the nutritional status of malnourished patients during hospital stays have been well established. However, recent randomized trials and meta-analyses have reported an increased rate of TPN-associated complications and mortality in critically ill patients. The increased risk of complications during TPN therapy has been linked to the development of hyperglycemia, especially during the first few days of TPN therapy. This retrospective study was conducted to determine whether the amount of dextrose from TPN in the 1st week in the intensive care unit (ICU) was related to the development of hyperglycemia and the clinical outcome. We included 88 non-diabetic critically ill patients who stayed in the medical ICU for more than two days. The subjects were 65 ${\pm}$ 16 years old, and the mean APACHE (Acute Physiology and Chronic Health Evaluation) II score upon admission was 20.9${\pm}$7.1. The subjects received 2.3${\pm}$1.4 g/kg/day of dextrose intravenously. We divided the subjects into two groups according to the mean blood glucose (BG) level during the 1st week of ICU stay: <140 mg/dl vs ${\geq}$ 140 mg/dl. Baseline BG and the amount of dextrose delivered via TPN were significantly higher in the hyperglycemia group than those in the normoglycemia group. Mortality was higher in the hyperglycemia group than in the normoglycemia group (42.4% vs 12.8%, P=0.008). The amount of dextrose from TPN was the only significant variable in the multiple linear regression analysis, which included age, APACHE II score, baseline blood glucose concentration and dextrose delivery via TPN as independent variables. We concluded that the amount of dextrose delivered via TPN might be associated with the development of hyperglycemia in critically ill patients without a history of diabetes mellitus. The amount of dextrose in TPN should be decided and adapted carefully to maintain blood glucose within the target range.

New anti-diabetic agents (새로운 당뇨병 치료제)

  • Kim, Doo-Man
    • Journal of the Korean Medical Association
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    • v.60 no.12
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    • pp.992-997
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    • 2017
  • Diabetes mellitus is characterized by hyperglycemia due to insulin deficiency and/or insulin resistance. Cardiovascular disease (CVD) is a major comorbidity of type 2 diabetes mellitus, and is the most common cause of death in people with diabetes mellitus. Several clinical trials have addressed the long-term effects of near-normoglycemia on CVD, but did not find evidence of an effect. However, some recent clinical trials of sodium glucose cotransporter 2 inhibitors (EMPA-REG [Empagliflozin Cardiovascular Outcomes and Mortality in Type 2 Diabetes Trial], CANVAS [Canagliflozin Cardiovascular Assessment Study]) or glucagon-like peptide-1 agonists (LEADER [Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation], SUSTAIN-6 [Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes]) showed very promising results regarding the prevention of CVD. In this review, I discuss some of these new anti-diabetic agents and present clinical information regarding these drugs.

Depressing and Blood Glucose Testing in Women Type2 Diabetic Patients (여성 당뇨병환자의 우울과 자가 혈당측정 회수)

  • Kim, Hee-Seung;Park, Chai-Soon
    • Korean Journal of Women Health Nursing
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    • v.9 no.4
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    • pp.432-438
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    • 2003
  • Purpose: The purpose of this study was to investigate the depression and, the frequency of blood glucose testing in women type2 diabetic patients. Method: 114 Participants were recruited from the endocrinology outpatient department of a tertiary care hospital in an urban city. Depression was measured by visual analogue scale. Blood glucose testing was measured the frequency during past 1 week. Result: Depression was higher in hyperglycemia patient (fasting blood glucose$\geq$110mg/dl) than in normoglycemia patient(fasting blood glucose <110mg/dl). The blood glucose testing frequency as lower in 50-59 years old than in less than 39 years old. And it was lower in middle school graduate than in college graduate. The blood glucose testing was negatively correlated with patient's age. Conclusion: The depression program should be developed for hyperglycemia diabetic patients. And the blood glucose testing education program should be developed for aged and low educational level patients.

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Critical Care Medicine (호흡기내과 의사를 위한 Respiratory Review of 2010)

  • Park, Jie-Hae;Chae, Jin-Nyeong;Choi, Won-Il
    • Tuberculosis and Respiratory Diseases
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    • v.69 no.2
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    • pp.75-80
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    • 2010
  • The year of 2009~2010 brought a number of concepts and new ideas were evaluated with promising results. However, some studies that challenged many beliefs. In acute respiratory distress syndrome (ARDS), recent clinical studies took into consideration of pathophysiologic changes of respiratory system compliance. Meta-analysis of positive end-expiratory pressure trials showed survival benefit of high positive end-expiratory pressure in ARDS. Until now, prone positioning did not show survival benefit in patients with ARDS. Extracorporeal membrane oxygenation (ECMO) based management improved survival in patients with severe ARDS. ECMO can be a management option in severe ARDS. Sedation is a standard practice in critically ill patients needing mechanical ventilation. However, Danish group reported less sedation of critically ill patients receiving mechanical ventilation was associated with an increase in days without ventilation. Although this single center study has some limitations, the overall results are promising. Use of maximal sterile barrier precautions (mask, sterile gown, sterile gloves, and large sterile drapes) with chlorhexidine-impregnated dressing reduced central venous catheter related infection. Selective oropharyngeal decontamination (application of topical antibiotics in the oropharynx) reduced the mortality rate of an intensive care unit (ICU) population. Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial reported intensive glucose control increased mortality among adults in the ICU. Some of the results of above papers are promising. However, some ideas may need for more frequent individual assessment and increase the workload of ICU staffs. Before implementation of new practice in ICU, we should take into consideration of individual hospital situation including human and material resources.

Lack of Metformin Effects on Different Molecular Subtypes of Breast Cancer under Normoglycemic Conditions: An in vitro Study

  • Sadighi, Sanambar;Amanpour, Saeid;Behrouzi, Bita;Khorgami, Zhinoos;Muhammadnejad, Samad
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2287-2290
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    • 2014
  • Background: In the past few years, a considerable number of preclinical studies have been proposed metformin as a potential anticancer agent, but some of these studies suffer from a number of methodological limitations such as assessment of cytotoxicity in the presence of supraphysiological glucose concentrations or applying suprapharmacological levels of the drug. These objections have limited the translation of published preclinical data to the clinical setting. The present study aimed to investigate direct anticancer effects of metformin on different molecular subtypes of breast cancer with pharmacological concentrations and under normoglycemic conditions in vitro. Materials and Methods: Breast cancer cell lines from luminal A, luminal B, ErbB2 and triple-negative molecular subtypes were treated with a pharmacological concentration of metformin (2mM) at a glucose concentration of 5.5mM. Time-dependant cell viability was assessed by dye exclusion assay. MTTbased cytotoxicity assays were also performed with metformin alone or in combination with paclitaxel. Results: Metformin did not show any growth inhibitory effects or time-dependant cytotoxicity on breast cancer cell lines in the presence of normal glucose concentrations at the therapeutic plasma level. No augmentation of the antineoplastic properties of paclitaxel was apparent under the tested conditions. Conclusions: Metformin is probably unable to exert cytotoxic or cytostatic effects on breast cancer subtypes at pharmacological concentrations and normal plasma glucose levels. These results highlight the importance of establishing a higher steady-state plasma concentration of metformin in the clinical setting for assessment of anticancer effects in normoglycemic patients.

Treatment of Autoimmune Diabetes by Inhibiting the Initial Event

  • Lee, Myung-Shik
    • IMMUNE NETWORK
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    • v.13 no.5
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    • pp.194-198
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    • 2013
  • Recent papers have shown that the initial event in the pathogenesis of autoimmune type 1 diabetes (T1D) comprises sensing of molecular patterns released from apoptotic ${\beta}$-cells by innate immune receptors such as toll-like receptor (TLR). We have reported that apoptotic ${\beta}$-cells undergoing secondary necrosis called 'late apoptotic' ${\beta}$-cells stimulate dendritic cells (DCs) and induce diabetogenic T cell priming through TLR2. The role of other innate immune receptors such as TLR7 or TLR9 in the initiation of T1D has also been suggested. We hypothesized that TLR2 blockade could inhibit T1D at the initial step of T1D. Indeed, when a TLR2 agonist, $Pam3CSK_4$ was administered chronically, the development of T1D in nonobese diabetic (NOD) mice was inhibited. Diabetogenic T cell priming by DCs was attenuated by chronic treatment with $Pam3CSK_4$, indicating DC tolerance. For the treatment of established T1D, immune tolerance alone is not enough because ${\beta}$-cell mass is critically reduced. We employed TLR2 tolerance in conjunction with islet transplantation, which led to reversal of newly established T1D. Dipeptidyl peptidase 4 (DPP4) inhibitors are a new class of anti-diabetic agents that have beneficial effects on ${\beta}$-cells. We investigated whether a combination of DPP4 inhibition and TLR2 tolerization could reverse newly established T1D without islet transplantation. We could achieve normoglycemia by TLR2 tolerization in combination with DPP4 inhibition but not by TLR2 tolerization or DPP4 inhibition alone. ${\beta}$-cell mass was significantly increased by combined treatment with TLR2 tolerization and DPP4 inhibition. These results suggest the possibility that a novel strategy of TLR tolerization will be available for the inhibition or treatment of established T1D when combined with measures increasing critically reduced ${\beta}$-cell mass of T1D patients such as DPP4 inhibition or stem cell technology.

AGL gene mutation and clinical features in Korean patients with glycogen storage disease type III (한국인 제3형 당원병 환자의 임상상 및 AGL 유전자형)

  • Ko, Jung Min;Lee, Jung Hyun;Kim, Gu-Hwan;Yoo, Han-Wook
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.6 no.1
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    • pp.15-23
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    • 2006
  • Purpose: Glycogen storage disease type III (GSD-III), is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme is amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), which is responsible for the debranching of the glycogen molecule during catabolism. The disease has been demonstrated to show clinical and biochemical heterogeneity, reflecting the genotype-phenotype heterogeneity among different patients. In this study, we analyzed mutations of the AGL gene in three unrelated Korean GSD-III patients and discussed their clinical and laboratory implications. Methods: We studied three GSD-III patients and the clinical features were characterized. Sequence analysis of 35exons and part exon-intron boundaries of the AGLgene in patients were carried out by direct DNA sequencing method using genomic DNA isolated from patients' peripheral leukocytes. Results: The clinical features included hepatomegaly (in all patients), seizures (in patient 2), growth failure (in patients 1), hyperlipidemia (in patients 1 and 3), raised transaminases and creatinine kinase concentrations (in all patients) and mild EKG abnormalities (in patients 2). Liver transplantation was performed in patient 2due to progressive hepatic fibrosis. Administration of raw-corn-starch could maintain normoglycemia and improve the condition. DNA sequence analysis revealed mutations in 5 out of 6 alleles. Patient 1 was a compound heterozygote of c.1282 G>A (p.R428K) and c.1306delA (p.S603PfsX6), patient 2 with c.1510_1511insT (p.Y504LfsX10), and patient 3 with c.3416 T>C (p.L1139P) and c.l735+1 G>T (Y538_R578delfsX4) mutations. Except R428K mutation, 4 other mutations identified in3 patients were novel. Conclusion: GSD-III patients have variable phenotypic characteristics resembling GSD-Ia. The molecular defects in the AGL gene of Korean GSD-III patients were genetically heterogeneous.

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Ultrastructural Change and Insulin Distribution of the Cultured Pancreatic Islet $\beta$-cell (배양된 이자섬 $\beta$세포의 미세구조적 변화와 인슐린 분포 양상)

  • Min, Byoung-Hoon;Kim, Soo-Jin
    • Applied Microscopy
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    • v.37 no.4
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    • pp.249-258
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    • 2007
  • The Pancreatic islet are the clusters of endocrine cells scattered through out the exocrine pancreas. Transplantation of a sufficient pancreatic islets can normalize blood glucose level so that may prevent devastating complications of type I diabetes(IDDM) and other side effects of the IDDM. Recently, there are several approaches to transplant sufficient pancreatic islet, and it was comprised in increase or regeneration of the endogenous $\beta$-cell mass from donor's pancreas, but relatively few studies have been devoted to the morphological characters of the isolated and 3 day cultured pancreatic islets. We investigated morphological pattern of intracellular structure of isolated and 3 day cultured pancreatic islets. The morphological characters of the pancreatic islets were observed by scanning electron microscope and transmission electron microscope, and insulin distribution of the each islets were observed by transmission electron microscope, and were labeled with insulin antibody. Intracellular structures including nuclei, mitochondria, RER, Golgi complex and many secretory granules were normally appeared in the isolated pancreatic islets which was extracted immediately dornor's pancreas, however, There is a significant morphological changes between the 3 day cultured pancreatic islets and isolated islets. 3 day cultured pancreatic islet's $\beta$-cells had normal nuclei but increased cytoplasm mass and RER and developed Golgi complex. Insulin secretory granules were decreased in numbers rather than isolated pancreatic islet. In this study, the pattern of intracellular structure variation was examined during pancreatic islet culture. Most distinct features are variation of the insulin secretory granules, and developed RER, and dilated golgi complex. Therefore, we suggested that the various change of the morphological characters on cultured pancreatic islets were responsible for the function(biosynthesis and secretion of insulin) and growth. These results were also cultured islets have greater ability to recover and maintain normoglycemia than isolated islet transplantation.

Effects of β3-Adrenergic Receptor Polymorphism on the Hyperglycemia in Korean Subjects (베타 3-아드레날린 수용체의 유전자형이 고혈당증 유발에 미치는 영향)

  • 오현희;최선미;양현성;김길수;윤유식
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.1
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    • pp.83-90
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    • 2004
  • This study was conducted to examine the effects of $\beta$3-adrenergic receptor polymorphism on the blood glucose level and obesity in 530 volunteers, who attended a weight loss program in a local obesity clinic. The age differences in total subjects and the distribution of male and female were 26.55$\pm$0.31 yr, 9.1% (n=48), 90.9% (n=492). The genotype distribution of $\beta$3-AR gene polymorphism were WW type 75%, WR type 22% and RR type 3%. Among many parameters, fasting blood glucose was significantly higher in WR+RR type (p=0.001) compared with WW type. When the subjects were divided into two groups by 6.105 mmol/L of the fasting blood glucose level, the frequency of hyperglycemia was 23.3% in WW type subjects, while there was a increase to 35.6% in WR+RR type subjects (p=0.011, $\chi$$^2$-analysis). When hyperglycemia group was compared with normoglycemia group, obesity index (p=0.044), %body fat (p=0.046) and TG (p=0.000) were significantly higher, and HDL (p=0.006) was significantly lower in the hyperglycemia. When all of the above factors were included in stepwise logistic regression analysis to find risk factors of hyperglycemia, the results were that the odds ratio for hyperglycemia were 2.015 (p=0.011) for WR+RR type of $\beta$3-AR gene, 2.165 (p=0.000) for TG and 0.419 (p=0.059) for HDL cholesterol. There was a significantly positive correlation between the blood glucose vs BMI, WHR, body fat in the WW type (r=0.099, 0.119, 0.082) However, in the WR and RR type there were no significance between the blood glucose vs BMI, WHR, body fat. These data suggest that the WR+RR genotype of $\beta$3-AR has a very strong association with increased blood glucose level and might be a significant risk factor for hyperglycemia among Korean subjects.

AGL gene mutation and clinical features in Korean patients with glycogen storage disease type III

  • Ko, Jung-Min;Kim, Gu-Hwan;Yoo, Han-Wook
    • Journal of Genetic Medicine
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    • v.4 no.1
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    • pp.72-79
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    • 2007
  • Purpose : Glycogen storage disease type III (GSD-III) is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme, amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), is responsible for the debranching of the glycogen molecule during catabolism. The disease shows clinical and biochemical heterogeneity, reflecting genotype-phenotype heterogeneity among different patients. In this study, we aim at analyzing mutations of the AGL gene in three unrelated Korean GSD-III patients, and characterizing their clinical and laboratory findings. Methods : We characterized the clinical features of three unrelated Korean GSD-III patients by biochemical, histological and imaging studies. The 35 exons and part of exon-intron boundaries of AGL were analyzed by direct sequencing using genomic DNA extracted from the peripheral leukocytes of patients. Results : Diverse clinical features were observed in these patients including hepatomegaly (all patients), seizures (patient 2), grow th failure (patients 1 and 2), hyperlipidemia (patients 1 and 3), raised transaminase and creatine kinase concentrations (all patients), and mild cardiomyopathy (patient 2). Liver transplantation w as performed in patient 2 due to progressive hepatic fibrosis. A dministration of uncooked corn starch maintained normoglycemia and improved biochemical and growth profiles. DNA sequence analysis revealed mutations in 5 out of 6 alleles. Patient 1 was a compound heterozygote of c.1282 G>A (p.R428K) and c.1306delA (p.S603PfsX6), patient 2 had c.1510_1511insT (p.Y 504L fsX 10), and patient 3 had c.3416 T >C (p.L 1139P) and c.1735+1 G>T (p.Y 538_R578delfsX 4) mutations. A part from the p.R428K mutation, the 4 other substitutions identified w ere nov el. Conclusion : GSD-III patients display variable phenotypic characteristics resembling those of GSD-Ia. Molecular defects in the AGL gene of Korean GSD-III patients are genetically heterogeneous.

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