Browsing by Subject "Hypoglycemic Agents"

Now showing 1 - 9 of 9
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    Combination of OHA Therapy in Type 2 Diabetes Mellitus
    (Association of Kenya Physicians, 2007) Shah, Siddharth; Association of Kenya Physicians Scientific Conference (11th : Mar. 2007 : Eldoret, Kenya)
    O.H.A. are the most common form of treatment of Type2 D.M. worldwide. When used judiciously they are important agents in the management of the most common form of diabetes. For economic, logistic and general effectiveness, oral agents are a dependable means of treating a large population of diabetics worldwide when used correctly.
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    Combination therapies prevent the neuropathic, proinflammatory characteristics of bone marrow in streptozotocin-induced diabetic rats
    (American Diabetes Association, 2015-02) Dominguez, James M.; Yorek, Mark A.; Grant, Maria B.; Department of Ophthalmology, IU School of Medicine
    We previously showed that peripheral neuropathy of the bone marrow was associated with loss of circadian rhythmicity of stem/progenitor cell release into the circulation. Bone marrow neuropathy results in dramatic changes in hematopoiesis that lead to microvascular complications, inflammation, and reduced endothelial repair. This series of events represents early pathogenesis before development of diabetic retinopathy. In this study we characterized early alterations within the bone marrow of streptozotocin (STZ)-induced diabetic rats following treatments that prevent experimental peripheral neuropathy. We asked whether bone marrow neuropathy and the associated bone marrow pathology were reversed with treatments that prevent peripheral neuropathy. Three strategies were tested: inhibition of neutral endopeptidase, inhibition of aldose reductase plus lipoic acid supplementation, and insulin therapy with antioxidants. All strategies prevented loss of nerve conduction velocity resulting from STZ-induced diabetes and corrected the STZ-induced diabetes-associated increase of immunoreactivity of neuropeptide Y, tyrosine hydroxylase, and somatostatin. The treatments also reduced concentrations of interleukin-1β, granulocyte colony-stimulating factor, and matrix metalloproteinase 2 in STZ-induced diabetic bone marrow supernatant and decreased the expression of NADPH oxidase 2, nitric oxide synthase 2, and nuclear factor-κB1 mRNA in bone marrow progenitor cells. These therapies represent novel approaches to attenuate the diabetic phenotype within the bone marrow and may constitute an important therapeutic strategy for diabetic microvascular complications.
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    Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer
    (American Diabetes Association, 2017-05) Andersen, Dana K.; Korc, Murray; Petersen, Gloria M.; Eibl, Guido; Li, Donghui; Rickels, Michael R.; Chari, Suresh T.; Abbruzzese, James L.; Medicine, School of Medicine
    The relationships between diabetes and pancreatic ductal adenocarcinoma (PDAC) are complex. Longstanding type 2 diabetes (T2DM) is a risk factor for pancreatic cancer, but increasing epidemiological data point to PDAC as also a cause of diabetes due to unknown mechanisms. New-onset diabetes is of particular interest to the oncology community as the differentiation of new-onset diabetes caused by PDAC as distinct from T2DM may allow for earlier diagnosis of PDAC. To address these relationships and raise awareness of the relationships between PDAC and diabetes, a symposium entitled Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer was held at the American Diabetes Association's 76th Scientific Sessions in June 2016. This article summarizes the data presented at that symposium, describing the current understanding of the interrelationships between diabetes, diabetes management, and pancreatic cancer, and identifies areas where additional research is needed.
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    Lack of the serum and glucocorticoid-inducible kinase SGK1 attenuates the volume retention after treatment with the PPARγ agonist pioglitazone
    (2008-05) Artunc, Ferruh; Sandulache, Diana; Nasir, Omaima; Boini, Krishna M.; Friedrich, Björn; Beier, Norbert; Dicks, Edith; Pötzsch, Sven; Klingel, Karin; Amann, Kerstin; Blazer-Yost, Bonnie; Scholz, Wolfgang; Risler, Teut; Kuhl, Dietmar; Lang, Florian
    PPARgamma-agonists enhance insulin sensitivity and improve glucose utilization in diabetic patients. Adverse effects of PPARgamma-agonists include volume retention and edema formation. Recent observations pointed to the ability of PPARgamma agonists to enhance transcription of the serum and glucocorticoid-inducible kinase SGK1, a kinase that is genomically upregulated by mineralocorticoids and stimulates various renal channels and transporters including the renal epithelial Na+ channel ENaC. SGK1 has been proposed to mediate the volume retention after treatment with PPARgamma agonists. To test this hypothesis, food containing the PPARgamma agonist pioglitazone (0.02%, i.e., approximately 25 mg/kg bw/day) was administered to gene-targeted mice lacking SGK1 (sgk1-/-, n=12) and their wild-type littermates (sgk1+/+), n=12). According to in situ hybridization, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence, treatment with pioglitazone significantly increased renal SGK1 mRNA and protein expression in sgk1+/+ mice. The treatment increased body weight significantly in both, sgk1+/+ mice (+2.2+/-0.3 g) and sgk-/- mice (+1.3+/-0.2 g), and decreased hematocrit significantly in sgk1+/+ mice (-6.5+/-1.0%) and sgk1-/- mice (-3.1+/-0.6%). Both effects were significantly (p<0.05) more pronounced in sgk1+/+ mice. According to Evans Blue distribution, pioglitazone increased plasma volume only in sgk1+/+ mice (from 50.9+/-3.9 to 63.7+/-2.5 microl/g bw) but not in sgk-/- mice (from 46.8+/-3.8 to 48.3+/-5.2 microl/g bw). Pioglitazone decreased aldosterone plasma levels and blood pressure and increased leptin plasma levels in both genotypes. We conclude that SGK1 contributes to but does not fully account for the volume retention during treatment with the PPARgamma agonist pioglitazone.
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    Lifestyle and metformin interventions have a durable effect to lower CRP and tPA levels in the diabetes prevention program except in those who develop diabetes
    (American Diabetes Association, 2014-08) Goldberg, Ronald B.; Temprosa, Marinella G.; Mather, Kieren J.; Orchard, Trevor J.; Kitabchi, Abbas E.; Watson, Karol E.; Diabetes Prevention Program Research Group; Department of Medicine, IU School of Medicine
    OBJECTIVE: We evaluate whether lifestyle and metformin interventions used to prevent diabetes have durable effects on markers of inflammation and coagulation and whether the effects are influenced by the development of diabetes. RESEARCH DESIGN AND METHODS: The Diabetes Prevention Program was a controlled clinical trial of 3,234 subjects at high risk for diabetes who were randomized to lifestyle, metformin, or placebo interventions for 3.4 years. Diabetes was diagnosed semiannually by fasting glucose and annually by oral glucose tolerance testing. In addition to baseline testing, anthropometry was performed every 6 months; fasting insulin yearly; and hs-CRP, tissue plasminogen activator (tPA), and fibrinogen at 1 year and end of study (EOS). RESULTS: CRP and tPA levels were unchanged in the placebo group but fell in the lifestyle and metformin groups at 1 year and remained lower at EOS. These reductions were not seen in those who developed diabetes over the course of the study despite intervention. Fibrinogen was lower at 1 year in the lifestyle group. Differences in weight and weight change explained most of the influence of diabetes on the CRP response in the lifestyle group, but only partly in the placebo and metformin groups. Weight, insulin sensitivity, and hyperglycemia differences each accounted for the influence of diabetes on the tPA response. CONCLUSIONS: Lifestyle and metformin interventions have durable effects to lower hs-CRP and tPA. Incident diabetes prevented these improvements, and this was accounted for by differences in weight, insulin resistance, and glucose levels.
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    Metabolic syndrome components and their response to lifestyle and metformin interventions are associated with differences in diabetes risk in persons with impaired glucose tolerance
    (Wiley Blackwell (Blackwell Publishing), 2014-04) Florez, Hermes; Temprosa, Marinella G.; Orchard, Trevor J.; Mather, Kieren J.; Marcovina, Santica M.; Barrett-Connor, Elizabeth; Horton, Edward; Saudek, Christopher; Pi-Sunyer, Xavier F.; Ratner, Robert E.; Goldberg, Ronald B.; Department of Medicine, IU School of Medicine
    AIMS: To determine the association of metabolic syndrome (MetS) and its components with diabetes risk in participants with impaired glucose tolerance (IGT), and whether intervention-related changes in MetS lead to differences in diabetes incidence. METHODS: We used the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) revised MetS definition at baseline and intervention-related changes of its components to predict incident diabetes using Cox models in 3234 Diabetes Prevention Program (DPP) participants with IGT over an average follow-up of 3.2 years. RESULTS: In an intention-to-treat analysis, the demographic-adjusted hazard ratios (95% confidence interval) for diabetes in those with MetS (vs. no MetS) at baseline were 1.7 (1.3-2.3), 1.7 (1.2-2.3) and 2.0 (1.3-3.0) for placebo, metformin and lifestyle groups, respectively. Higher levels of fasting plasma glucose and triglycerides at baseline were independently associated with increased risk of diabetes. Greater waist circumference (WC) was associated with higher risk in placebo and lifestyle groups, but not in the metformin group. In a multivariate model, favourable changes in WC (placebo and lifestyle) and high-density lipoprotein cholesterol (placebo and metformin) contributed to reduced diabetes risk. CONCLUSIONS: MetS and some of its components are associated with increased diabetes incidence in persons with IGT in a manner that differed according to DPP intervention. After hyperglycaemia, the most predictive factors for diabetes were baseline hypertriglyceridaemia and both baseline and lifestyle-associated changes in WC. Targeting these cardiometabolic risk factors may help to assess the benefits of interventions that reduce diabetes incidence.
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    PPAR-γ/IL-10 axis inhibits MyD88 expression and ameliorates murine polymicrobial sepsis
    (The American Association of Immunologists, 2014-03-01) Ferreira, Ana Elisa; Sisti, Flavia; Sônego, Fabiane; Wang, Suojang; Filgueiras, Luciano; Brandt, Stephanie; Serezani, Ana Paula Moreira; Cunha, Fernando Q.; Alves-Filho, Jose Carlos; Serezani, Carlos Henrique; Department of Microbiology and Immunology, IU School of Medicine
    Polymicrobial sepsis induces organ failure and is accompanied by overwhelming inflammatory response and impairment of microbial killing. Peroxisome proliferator-activated receptor (PPAR)-γ is a nuclear receptor with pleiotropic effects on lipid metabolism, inflammation, and cell proliferation. The insulin-sensitizing drugs thiazolidinediones (TZDs) are specific PPAR-γ agonists. TZDs exert anti-inflammatory actions in different disease models, including polymicrobial sepsis. The TZD pioglitazone, which has been approved by the U.S. Food and Drug Administration, improves sepsis outcome; however, the molecular programs that mediate its effect have not been determined. In a murine model of sepsis, we now show that pioglitazone treatment improves microbial clearance and enhances neutrophil recruitment to the site of infection. We also observed reduced proinflammatory cytokine production and high IL-10 levels in pioglitazone-treated mice. These effects were associated with a decrease in STAT-1-dependent expression of MyD88 in vivo and in vitro. IL-10R blockage abolished PPAR-γ-mediated inhibition of MyD88 expression. These data demonstrate that the primary mechanism by which pioglitazone protects against polymicrobial sepsis is through the impairment of MyD88 responses. This appears to represent a novel regulatory program. In this regard, pioglitazone provides advantages as a therapeutic tool, because it improves different aspects of host defense during sepsis, ultimately enhancing survival.
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    The Stroke Hyperglycemia Insulin Network Effort (SHINE) trial protocol: a randomized, blinded, efficacy trial of standard vs. intensive hyperglycemia management in acute stroke
    (Wiley Blackwell (Blackwell Publishing), 2014-02) Bruno, Askiel; Durkalski, Valerie L.; Hall, Christiana E.; Juneja, Rattan; Barsan, William G.; Janis, Scott; Meurer, William J.; Fansler, Amy; Johnston, Karen C.; SHINE investigators; Department of Medicine, IU School of Medicine
    RATIONALE: Patients with acute ischemic stroke and hyperglycemia have worse outcomes than those without hyperglycemia. Intensive glucose control during acute stroke is feasible and can be accomplished safely but has not been fully assessed for efficacy. AIMS: The Stroke Hyperglycemia Insulin Network Effort trial aims to determine the safety and efficacy of standard vs. intensive glucose control with insulin in hyperglycemic acute ischemic stroke patients. DESIGN: This is a randomized, blinded, multicenter, phase III trial of approximately 1400 hyperglycemic patients who receive either standard sliding scale subcutaneous insulin (blood glucose range 80-179 mg/dL, 4·44-9·93 mmol/L) or continuous intravenous insulin (target blood glucose 80-130 mg/dL, 4·44-7·21 mmol/L) for up to 72 h, starting within 12 h of stroke symptom onset. The acute treatment phase is single blind (for the patients), but the final outcome assessment is double blind. The study is powered to detect a 7% absolute difference in favorable outcome at 90 days. STUDY OUTCOMES: The primary outcome is a baseline severity adjusted 90-day modified Rankin Scale score, defined as 0, 0-1, or 0-2, if the baseline National Institutes of Health Stroke Scale score is 3-7, 8-14, or 15-22, respectively. The primary safety outcome is the rate of severe hypoglycemia (<40 mg/dL, <2·22 mmol/L). DISCUSSION: This trial will provide important novel information about preferred management of acute ischemic stroke patients with hyperglycemia. It will determine the potential benefits and risks of intensive glucose control during acute stroke.
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    Type 1 diabetes
    (Elsevier, 2018-06-16) DiMeglio, Linda A.; Evans-Molina, Carmella; Oram, Richard A.; Pediatrics, IU School of Medicine
    Type 1 diabetes is a chronic autoimmune disease characterised by insulin deficiency and resultant hyperglycaemia. Knowledge of type 1 diabetes has rapidly increased over the past 25 years, resulting in a broad understanding about many aspects of the disease, including its genetics, epidemiology, immune and β-cell phenotypes, and disease burden. Interventions to preserve β cells have been tested, and several methods to improve clinical disease management have been assessed. However, wide gaps still exist in our understanding of type 1 diabetes and our ability to standardise clinical care and decrease disease-associated complications and burden. This Seminar gives an overview of the current understanding of the disease and potential future directions for research and care.