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Binsaleh AY, El-Haggar SM, Hegazy SK, Maher MM, Bahgat MM, Elmasry TA, Alrubia S, Alsegiani AS, Eldesoqui M, Bahaa MM. The adjunctive role of metformin in patients with mild to moderate ulcerative colitis: a randomized controlled study. Front Pharmacol 2025; 16:1507009. [PMID: 40191419 PMCID: PMC11969268 DOI: 10.3389/fphar.2025.1507009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Accepted: 02/14/2025] [Indexed: 04/09/2025] Open
Abstract
Background Metformin, hypoglycemic medication, is recognized for its diverse properties and its capacity to influence the inflammatory pathways. Medications with anti-inflammatory and anti-oxidative characteristics have been demonstrated to be able to elicit and sustain remission in ulcerative colitis (UC), chronic inflammatory disorder of the bowel. Studies in both preclinical and clinical settings have looked into the several metabolic pathways via which metformin protects against UC. Aim To assess efficacy of metformin as adjunctive therapy in patients with mild to moderate UC. Methods This clinical research was double-blinded, randomized, controlled, and involved 60 patients with mild to moderate UC. The participants were randomly assigned to one of two groups (n = 30). The control group was given 1 g of mesalamine three times a day (t.i.d.) for a period of 6 months (mesalamine group). The metformin group was given 500 mg of metformin twice daily and 1 g of mesalamine t. i.d. For a period of 6 months. Patients with UC were assessed by a gastroenterologist using the disease activity index (DAI) both at the beginning of treatment and 6 months thereafter. To evaluate the drug's biological efficacy, measurements of fecal calprotectin, serum C-reactive protein (CRP), interleukin 10 (IL-10), and nitric oxide (NO) were taken both before and after treatment. Study outcomes Decrease in DAI and change in the level of measured serum and fecal markers. Results The metformin group displayed a statistical reduction in DAI (p = 0.0001), serum CRP (p = 0.019), NO (p = 0.04), and fecal calprotectin (p = 0.027), as well as a significant increase in IL-10 (p = 0.04) when compared to the mesalamine group. There was a significant direct correlation between DAI and calprotectin (p < 0.0001, r = 0.551), and between DAI and CRP (p < 0.0001, r = 0.794). There was a significant negative correlation between DAI and IL-10 (p = 0.0003, r = 0.371). Conclusion Metformin may be an effective adjunct drug in management of patients with mild to moderate UC by decreasing DAI and other inflammatory markers that were involved in the pathogenesis of UC. Clinical Trial Registration identifier NCT05553704.
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Affiliation(s)
- Ammena Y. Binsaleh
- Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Sahar M. El-Haggar
- Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, El-Gharbia Government, Tanta, Egypt
| | - Sahar K. Hegazy
- Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, El-Gharbia Government, Tanta, Egypt
- Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, Egypt
| | - Maha M. Maher
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
- Internal Medicine Department, Faculty of Medicine, Horus University, New Damietta, Egypt
| | - Monir M. Bahgat
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Thanaa A. Elmasry
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Tanta University, Tanta, Al-Gharbia, Egypt
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Sinai University, Arish campus, Egypt
| | - Sarah Alrubia
- Pharmaceutical Chemistry Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Amsha S. Alsegiani
- Pharmaceutical Chemistry Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Mamdouh Eldesoqui
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia
| | - Mostafa M. Bahaa
- Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, Egypt
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Lopez-Candales A, Monte S, Sawalha K, Norgard NB. Time to revisit the true role of metformin in type 2 diabetes mellitus. Postgrad Med 2023; 135:539-542. [PMID: 37294638 DOI: 10.1080/00325481.2023.2224036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 06/06/2023] [Indexed: 06/11/2023]
Affiliation(s)
- Angel Lopez-Candales
- Cardiovascular Medicine Division, University Health Truman Medical Center, University of Missouri-Kansas City, Missouri-Kansas, MO, USA
| | - Scott Monte
- School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, NY, USA
| | - Khalid Sawalha
- Nutrition and Metabolism, Department of Medicine, University of Missouri-Kansas City, Kansas, MO, USA
| | - Nicholas B Norgard
- Department of Medicine, University Health Truman Medical Center, University of Missouri-Kansas City, Kansas, MO, USA
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Kinard JL, Collie J, Turner C, Chapleau RR. Using a pilot-centric, qualitative drug risk assessment model to identify opportunities for implementing pharmacogenetics. FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES 2022. [DOI: 10.1186/s43094-022-00427-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Risk assessment models are at the core of flight medicine, weighing both the impact of the flight environment on an aviator and the potential impact of medical events in aviators on flight operations. Pharmacogenetics is the application of a patient’s genetic information to reduce medication risk. Here, we use three medical conditions commonly encountered by the U.S. Air Force’s flight medicine community (asthma, diabetes, and hypertension) to demonstrate a framework for implementing occupationally relevant pharmacogenetics. We identified medications approved by the U.S. Food & Drug Administration for each condition, obtained adverse effects and frequencies, scored each adverse effect’s impact on work duties from 0 to 4 in increasing severity, and used control theory to stratify the medications by occupational risk. For those medications within 10% of the control limits, pharmacogenetic information was collected from PharmGKb.
Results
We observed a correlation of 0.557 between our risk scores and previous reports for 20 medications, demonstrating robustness of our scoring. Using average risks for those 20 medications, we set control theory acceptable and tolerable thresholds at 601,109.5 and 2,097,721, respectively. The majority of medications for the three conditions were below the thresholds (66 and 26, respectively). Three medications have pharmacogenetic guidance provided by regulatory bodies.
Conclusions
By focusing first on risk to performing occupational tasks and then on genetic implementation, our work presents a framework by which pharmacogenetics can be selectively applied by considering specific occupational and environmental risks, thereby saving costs and reducing possible psychological burdens on patients.
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Muradoğlu S, Yeşiltepe Mutlu G, Gökçe T, Can E, Hatun Ş. An Evaluation of Glucagon Injection Anxiety and Its Association with the Fear of Hypoglycemia among the Parents of Children with Type 1 Diabetes. J Clin Res Pediatr Endocrinol 2021; 13:285-292. [PMID: 33491925 DOI: 10.1007/978-3-030-67455-7_3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2025] Open
Abstract
OBJECTIVE Hypoglycemia is a common acute complication of type 1 diabetes (T1D), which may cause seizure, loss of consciousness, and temporary motor or sensory impairment. Glucagon administration is an effective way of treating severe hypoglycemia, especially in a free-living setting. Nonetheless, families have difficulties in managing severe hypoglycemia due to their anxiety and challenges with current glucagon administration techniques. The aim of the current study was to explore the associations between parental fear of hypoglycemia (FoH) and their general anxiety level, and in particular, their attitudes towards and thoughts on glucagon administration. METHODS Parents of children with T1D completed questionnaires assessing background and clinical information, FoH, generalized anxiety disorder (GAD) and parental anxiety for glucagon administration (PAGA). RESULTS Sixty-eight parents participated. Positive correlations were found between parental GAD-7 score and both FoH and the number of night-time blood glucose measurements and there was a negative correlation with the child’s age. Parents mean self-evaluation score of their competence in glucagon administration was 6 (standard deviation±2.9) on a scale of 0 to 10. Unsurprisingly, this score was negatively correlated with the PAGA scores. There was no significant difference between children using continuous glucose monitoring system and self-monitoring of blood glucose in terms of parental FoH, anxiety and misconceptions about glucagon administration. CONCLUSION The results showed that parents of children with T1D had anxiety and fear connected with hypoglycemia and glucagon administration. Structured and practical training should be implemented to increase parents’ self-confidence including annual refresher training for home glucagon administration.
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Affiliation(s)
- Serra Muradoğlu
- Koç University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, İstanbul, Turkey
| | - Gül Yeşiltepe Mutlu
- Koç University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, İstanbul, Turkey
| | - Tuğba Gökçe
- Koç University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, İstanbul, Turkey
| | - Ecem Can
- Koç University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, İstanbul, Turkey
| | - Şükrü Hatun
- Koç University Faculty of Medicine, Department of Pediatric Endocrinology and Diabetes, İstanbul, Turkey
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Akhmetova VR, Akhmadiev NS, Zainullin RA, Khayrullina VR, Mescheryakova ES, Glushkova NA. Synthesis, in vitro and in silico studies of inhibitory activity towards α-amylase of bis-azole scaffolds linked by an alkylsulfanyl chain. CAN J CHEM 2020. [DOI: 10.1139/cjc-2019-0186] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Twelve new α,ω-bis[(3,5-dimethylpyrazol-4-yl)methylsulfanyl]alkanes linked by alkyl, diethyl sulfide, and triethyl dioxide spacers were prepared by the multicomponent reaction of acetylacetone, formaldehyde, α,ω-dithiols, and monosubstituted hydrazines. Testing of these products for inhibition of α-amylase enzyme in vitro showed that bis(N-methylpyrazolylmethylsulfanyl)ethane 4a inhibits the enzyme by the competitive mechanism. Meanwhile, the water-soluble adduct of bis(isoxazolylmethylsulfanyl)ethane 2 with HCl (2·HCl) is a noncompetitive inhibitor. The molecular docking results attest to high complementarity between the test molecules and the enzymes such as α-amylases from Aspergillus niger and human pancreas. Bis-pyrazole compounds 1, 1·HCl, and 4a and bis-isoxazole compounds 2 and 2·HCl positioned in the active site of both α-amylases form two closely spaced clusters. For all cases, the bioactive conformations of the modeled ligands were identified, demonstrating high affinity of the bis-azoles (1, 1·HCl, 2, 2·HCl, 4a) to the enzymes. Hydrogen bonds stabilizing their position in both α-amylases active sites were identified.
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Affiliation(s)
- Vnira R. Akhmetova
- Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russia
| | - Nail S. Akhmadiev
- Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russia
| | - Radik A. Zainullin
- Ufa State Petroleum Technological University, 1 Kosmonavtov Str., Ufa 450062, Russia
| | | | - Ekaterina S. Mescheryakova
- Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russia
| | - Natalia A. Glushkova
- Ufa State Petroleum Technological University, 1 Kosmonavtov Str., Ufa 450062, Russia
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Augestad IL, Pintana H, Larsson M, Krizhanovskii C, Nyström T, Klein T, Darsalia V, Patrone C. Regulation of Glycemia in the Recovery Phase After Stroke Counteracts the Detrimental Effect of Obesity-Induced Type 2 Diabetes on Neurological Recovery. Diabetes 2020; 69:1961-1973. [PMID: 32540876 DOI: 10.2337/db20-0095] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Accepted: 06/09/2020] [Indexed: 11/13/2022]
Abstract
The interplay between obesity and type 2 diabetes (T2D) in poststroke recovery is unclear. Moreover, the impact of glucose control during the chronic phase after stroke is undetermined. We investigated whether obesity-induced T2D impairs neurological recovery after stroke by using a clinically relevant experimental design. We also investigated the potential efficacy of two clinically used T2D drugs: the dipeptidyl peptidase 4 inhibitor linagliptin and the sulfonylurea glimepiride. We induced transient middle cerebral artery occlusion (tMCAO) in T2D/obese mice (after 7 months of high-fat diet [HFD]) and age-matched controls. After stroke, we replaced HFD with standard diet for 8 weeks to mimic the poststroke clinical situation. Linagliptin or glimepiride were administered daily from 3 days after tMCAO for 8 weeks. We assessed neurological recovery weekly by upper-limb grip strength. Brain damage, neuroinflammation, stroke-induced neurogenesis, and atrophy of parvalbumin-positive (PV+) interneurons were quantified by immunohistochemistry. T2D/obesity impaired poststroke neurological recovery in association with hyperglycemia, neuroinflammation, and atrophy of PV+ interneurons. Both drugs counteracted these effects. In nondiabetic mice, only linagliptin accelerated recovery. These findings shed light on the interplay between obesity and T2D in stroke recovery. Moreover, they promote the use of rehabilitative strategies that are based on efficacious glycemia regulation, even if initiated days after stroke.
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Affiliation(s)
- Ingrid Lovise Augestad
- Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Hiranya Pintana
- Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Martin Larsson
- Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Camilla Krizhanovskii
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Department of Research, Södertälje Hospital, Karolinska Institutet, Södertälje, Sweden
| | - Thomas Nyström
- Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Thomas Klein
- Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany
| | - Vladimer Darsalia
- Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Cesare Patrone
- Department of Clinical Science and Education, Södersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden
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7
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Jitschin A, Schleser-Mohr S, Stierling A, Meier JJ, Nauck MA. Risk of hypoglycaemia associated with professional, recreational, and traffic-related activities in patients with type 2 diabetes: a cross-sectional study by questionnaire. Acta Diabetol 2020; 57:965-972. [PMID: 32166401 DOI: 10.1007/s00592-020-01502-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 02/11/2020] [Indexed: 11/30/2022]
Abstract
AIMS We aimed to quantify the exposure to physical exercise associated with professional, recreational, or traffic-related activities in patients with type 2 diabetes, which may provoke or aggravate hypoglycaemic episodes, and to assess whether such risks determine the choice of medications minimizing the risk of hypoglycaemia. METHODS In total, 203 patients with type 2 diabetes (98 women, 105 men, age 65 [56;72; median, inter-quartile range] years, diabetes duration 10 [5;15] years) were recruited from a German diabetes practice. A questionnaire assessed their engagement in professional, recreational, or traffic-related activities. The prescription insulin or sulphonylureas was quantified in relation to the number of such activities. RESULTS 63.5% of the patients were treated with insulin, 7.4% with sulphonylureas, and 70.9% with either. Sixty-six patients (22.7%) were professionally active: 36 (54.4%) of those were professionally exposed to risky behaviour (14 [31.8%] patients with exposure to multiple risks and 20 (30.3%) who experienced hypoglycaemic episodes in the past year). In total, 194 (95.6%) patients were exposed to risky behaviour during recreational activities, 129 (63.6%) to multiple ones. All patients were exposed to traffic-related activities, 144 (70.9%) were exposed to more than being pedestrian, and 24 (11.8%) experienced hypoglycaemic episodes while in traffic. CONCLUSIONS Patients with type 2 diabetes are exposed to risks associated with professional, recreational, and traffic-related activities. We recommend a careful assessment of such risks before glucose-lowering medications with a potential for provoking hypoglycaemic episodes are prescribed.
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Affiliation(s)
- Anne Jitschin
- Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany
| | | | - Almut Stierling
- Diabetes-Schwerpunktpraxis am Gauss-Wall, Göttingen, Germany
| | - Juris J Meier
- Diabetes Division, Katholisches Klinikum Bochum, St. Josef-Hospital (Ruhr-University Bochum), Gudrunstr. 56, 44791, Bochum, Germany
| | - Michael A Nauck
- Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany.
- Diabetes Division, Katholisches Klinikum Bochum, St. Josef-Hospital (Ruhr-University Bochum), Gudrunstr. 56, 44791, Bochum, Germany.
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8
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Sivitz WI, Phillips LS, Wexler DJ, Fortmann SP, Camp AW, Tiktin M, Perez M, Craig J, Hollander PA, Cherrington A, Aroda VR, Tan MH, Krakoff J, Rasouli N, Butera NM, Younes N. Optimization of Metformin in the GRADE Cohort: Effect on Glycemia and Body Weight. Diabetes Care 2020; 43:940-947. [PMID: 32139384 PMCID: PMC7171946 DOI: 10.2337/dc19-1769] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Accepted: 01/19/2020] [Indexed: 02/03/2023]
Abstract
OBJECTIVE We evaluated the effect of optimizing metformin dosing on glycemia and body weight in type 2 diabetes. RESEARCH DESIGN AND METHODS This was a prespecified analysis of 6,823 participants in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) taking metformin as the sole glucose-lowering drug who completed a 4- to 14-week (mean ± SD 7.9 ± 2.4) run-in in which metformin was adjusted to 2,000 mg/day or a maximally tolerated lower dose. Participants had type 2 diabetes for <10 years and an HbA1c ≥6.8% (51 mmol/mol) while taking ≥500 mg of metformin/day. Participants also received diet and exercise counseling. The primary outcome was the change in HbA1c during run-in. RESULTS Adjusted for duration of run-in, the mean ± SD change in HbA1c was -0.65 ± 0.02% (-7.1 ± 0.2 mmol/mol) when the dose was increased by ≥1,000 mg/day, -0.48 ± 0.02% (-5.2 ± 0.2 mmol/mol) when the dose was unchanged, and -0.23 ± 0.07% (-2.5 ± 0.8 mmol/mol) when the dose was decreased (n = 2,169, 3,548, and 192, respectively). Higher HbA1c at entry predicted greater reduction in HbA1c (P < 0.001) in univariate and multivariate analyses. Weight loss adjusted for duration of run-in averaged 0.91 ± 0.05 kg in participants who increased metformin by ≥1,000 mg/day (n = 1,894). CONCLUSIONS Optimizing metformin to 2,000 mg/day or a maximally tolerated lower dose combined with emphasis on medication adherence and lifestyle can improve glycemia in type 2 diabetes and HbA1c values ≥6.8% (51 mmol/mol). These findings may help guide efforts to optimize metformin therapy among persons with type 2 diabetes and suboptimal glycemic control.
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Affiliation(s)
| | - Lawrence S Phillips
- Atlanta VA Medical Center, Decatur, GA
- Emory University School of Medicine, Atlanta, GA
| | - Deborah J Wexler
- Diabetes Clinical Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | | | - Anne W Camp
- Fair Haven Community Health Care, New Haven, CT
| | | | | | | | | | | | | | | | | | | | - Nicole M Butera
- Department of Biostatistics and Bioinformatics, The Biostatistics Center, Milken Institute School of Public Health, The George Washington University, Rockville, MD
| | - Naji Younes
- Department of Biostatistics and Bioinformatics, The Biostatistics Center, Milken Institute School of Public Health, The George Washington University, Rockville, MD
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9
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Sharma R, Arora M, Garg R, Bansal P. A closer look at the 2019 Beers criteria. DRUGS & THERAPY PERSPECTIVES 2020. [DOI: 10.1007/s40267-019-00704-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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10
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Saraswati K, Sichanh C, Newton PN, Caillet C. Quality of medical products for diabetes management: a systematic review. BMJ Glob Health 2019; 4:e001636. [PMID: 31637025 PMCID: PMC6768360 DOI: 10.1136/bmjgh-2019-001636] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 07/18/2019] [Accepted: 07/20/2019] [Indexed: 11/04/2022] Open
Abstract
Background The global prevalence of diabetes mellitus is increasing alarmingly. However, the quality of vital medicines and medical products used to treat and monitor diabetes remains uncertain but of potential great public health significance. Here, we review the available evidence on the quality of antidiabetic medicines and supplies for self-monitoring of blood glucose (SMBG) and discuss their potential impact for the patients and society. Methods Searches were conducted in PubMed, Embase, Google Scholar, Google and relevant websites in English and French. The Medicine Quality Assessment Reporting Guideline (MEDQUARG) was used to assess the quality of medicine quality surveys. Results 52 publications on the quality of antidiabetic medicines, including 5 medicine quality prevalence surveys and 20 equivalence studies, were analysed. The prevalence surveys and equivalence studies included 674 samples of which 73 (10.8%) were of poor quality. The median (Q1-Q3) concordance with MEDQUARG items was 30.8% (19.2%-42.3%). No prevalence surveys on SMBG supplies' quality were found, but 29 publications, including falsified products and incorrect results due to strip degradation or contamination, were identified. Conclusion There is little accessible evidence on the quality of antidiabetic medicines and SMBG supplies. Surveys were poorly designed and reported, making data aggregation and interpretation problematic. Despite these caveats, these results suggest that there are important issues with the quality of medical products for diabetes that need focused monitoring. There is an urgent need to achieve consensus protocols for designing, conducting and reporting medical product quality surveys. PROSPERO registration number CRD42016039841.
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Affiliation(s)
- Kartika Saraswati
- Lao-Oxford-Mahosot-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People's Democratic Republic.,Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.,Infectious Diseases Data Observatory/WorldWide Antimalarial Resistance Network, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK
| | - Chanvilay Sichanh
- Lao-Oxford-Mahosot-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People's Democratic Republic
| | - Paul N Newton
- Lao-Oxford-Mahosot-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People's Democratic Republic.,Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.,Infectious Diseases Data Observatory/WorldWide Antimalarial Resistance Network, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK
| | - Céline Caillet
- Lao-Oxford-Mahosot-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People's Democratic Republic.,Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.,Infectious Diseases Data Observatory/WorldWide Antimalarial Resistance Network, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK
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11
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Su PF, Zhong J, Ou HT. Semiparametric additive rates model for recurrent events data with intermittent gaps. Stat Med 2018; 38:1343-1356. [DOI: 10.1002/sim.8042] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Revised: 10/11/2018] [Accepted: 10/27/2018] [Indexed: 01/28/2023]
Affiliation(s)
- Pei-Fang Su
- Department of Statistics; National Cheng Kung University; Tainan Taiwan
| | - Junjiang Zhong
- School of Applied Mathematics; Xiamen University of Technology; Xiamen China
| | - Huang-Tz Ou
- Institute of Clinical Pharmacy and Pharmaceutical Sciences, Department of Pharmacy, College of Medicine; National Cheng Kung University; Tainan Taiwan
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12
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Ebadi SA, Darvish P, Fard AJ, Lima BS, Ahangar OG. Hypoglycemia and cognitive function in diabetic patients. Diabetes Metab Syndr 2018; 12:893-896. [PMID: 29887517 DOI: 10.1016/j.dsx.2018.05.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Accepted: 05/14/2018] [Indexed: 01/02/2023]
Abstract
AIMS Hypoglycemia can be considered the most common complication of Diabetes Mellitus treatment. So far, controversial studies have been carried out to examine the impacts of hypoglycemia on the cognitive function. METHODS This study was conducted as case-control. The case group was 35 patients with Diabetes Mellitus Types I or II hospitalized in Imam Hussein Hospital, Tehran, Iran, who have experienced hypoglycemic attacks (glucose level below 70 mg/dl). The control group consisted of diabetic patients hospitalized in hospital, but they had no history of hypoglycemia. As the blood glucose level became in normal range and the patients' Mental status became stable, the brain cognitive function was examined using Mini-Mental State test. RESULTS The mean age of the subjects in the case and control groups was 56.77, 53.73 years old, respectively. The mean cognitive score in the control and hypoglycemic groups was 29.09 and 25.29, respectively. The mean MMSE cognitive score was significantly diminished in the hypoglycemic group (p < 0.001). CONCLUSIONS This study indicated that incidence of hypoglycemia in diabetic patients is associated with cognitive disorders. Further, there is a linear association between cognitive disorders and hypoglycemia, age and diabetes mellitus complication.
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Affiliation(s)
- Seyed Alireza Ebadi
- Department of Internal Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parichehr Darvish
- Department of Internal Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Ali Jamshidi Fard
- Department of Internal Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behnam Safarpour Lima
- Department of Neurology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Omid Gharoei Ahangar
- Department of Internal Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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13
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Uppal S, Italiya KS, Chitkara D, Mittal A. Nanoparticulate-based drug delivery systems for small molecule anti-diabetic drugs: An emerging paradigm for effective therapy. Acta Biomater 2018; 81:20-42. [PMID: 30268916 DOI: 10.1016/j.actbio.2018.09.049] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 09/14/2018] [Accepted: 09/26/2018] [Indexed: 12/11/2022]
Abstract
Emergence of nanoparticulate drug delivery systems in diabetes has facilitated improved delivery of small molecule drugs which could dramatically improve the quality of life for diabetics. Conventional dosage forms of the anti-diabetic drugs exhibit variable/less bioavailability and short half-life, demanding frequent dosing and causing increased side-effects resulting in ineffectiveness of therapy and non-compliance with the patients. Considering the chronic nature of diabetes, nanotechnology-based approaches are more promising in terms of providing site-specific delivery of drugs with higher bioavailability and reduced dosage regimen. Nanomedicines act at the cellular and molecular levels to enhance the uptake of the drug into the cells or block the efflux mechanisms thus retaining the drug inside the cell for a longer duration of time. Many studies have hinted at the possibility of administering peptide drugs like glucagon like peptides orally by encapsulation into nanoparticles. Nanoparticles also allow further modifications including their encapsulation into microparticles, polyethylene glycol (PEG)-PEGylation- or functionalization with ligands for active targeting. Nevertheless, such remarkable benefits are fraught with their long-term safety concerns, regulatory hurdles, limitations of scale-up and ineffective patent protection which have hindered their commercialization. This review summarizes the latest advances in the area of nanoformulations as applied to the delivery of anti-diabetics. STATEMENT OF SIGNIFICANCE: The present work describes the latest advancements in the area of nanoformulations for anti-diabetic therapy along with highlighting the advantages that these nanoformulations offer at molecular level for diabetes. Although several potent orally active anti-hyperglycemic agents are available, the current challenges in efficient management of diabetes include optimization of the present therapies to ensure an optimum and stable level of glucose, and also to reduce the occurrence of long term complications associated with diabetes. Nanoformulations because of their high surface area to volume ratio provide improved efficacy, targeting their delivery to the desired site of action tends to minimize adverse effects and administration of peptide drugs by oral route is also possible by encapsulating them in nanoparticles. As we reflect on the success and failures of latest research on nanoformulations for the treatment of diabetes, it is important not to dwell on lack of FDA approvals but rather define future directions that guarantee more effective anti-diabetic treatment. In proposed review we have explored the latest advancement in anti-diabetic nanotechnology based formulations.
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Affiliation(s)
- Siddharth Uppal
- Department of Pharmacy, Birla Institute of Technology and Science (BITS-PILANI), Pilani, Rajasthan 333031, India
| | - Kishan S Italiya
- Department of Pharmacy, Birla Institute of Technology and Science (BITS-PILANI), Pilani, Rajasthan 333031, India
| | - Deepak Chitkara
- Department of Pharmacy, Birla Institute of Technology and Science (BITS-PILANI), Pilani, Rajasthan 333031, India
| | - Anupama Mittal
- Department of Pharmacy, Birla Institute of Technology and Science (BITS-PILANI), Pilani, Rajasthan 333031, India.
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Raji A, Long J, Lam RLH, O'Neill EA, Engel SS. Efficacy and Safety of Sitagliptin in Hispanic/Latino Patients with Type 2 Diabetes: A Pooled Analysis from Ten Randomized, Placebo-Controlled Phase 3 Clinical Trials. Diabetes Ther 2018; 9:1581-1589. [PMID: 29936573 PMCID: PMC6064579 DOI: 10.1007/s13300-018-0461-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Indexed: 10/31/2022] Open
Abstract
INTRODUCTION To assess the efficacy and safety profile of the dipeptidyl-peptidase-4 inhibitor sitagliptin in a population of self-identified Hispanic/Latino patients with type 2 diabetes. METHODS Data were pooled from ten randomized, double-blind studies in which subjects were treated with sitagliptin 100 mg/day (as mono- or combination therapy) or placebo, and used to evaluate the glycemic efficacy, safety, and tolerability of sitagliptin compared with placebo after 24 weeks of treatment. RESULTS A total of 804 Hispanic/Latino patients were included in the analysis. Baseline characteristics in the treatment groups were similar (mean baseline HbA1c of approximately 8.5%). The LS mean HbA1c changes from baseline were - 0.94% with sitagliptin and - 0.32% with placebo, and the between-group difference was - 0.62%, p < 0.001. After 24 weeks of treatment, 35% and 18% of subjects were at the HbA1c goal of < 7% in the sitagliptin and placebo groups, respectively. Body weight increased slightly in both treatment groups. Incidences of adverse events of hypoglycemia were similar and low (1.9% and 1.4% for sitagliptin and placebo, respectively) in both groups in studies in which insulin or sulfonylurea were not used and were similar (9% and 11% for sitagliptin and placebo, respectively) when all studies were included. Overall safety and tolerability of treatment with sitagliptin and placebo were similar. No clinically meaningful differences between the safety profile of sitagliptin in the Hispanic/Latino population analyzed here and broader populations previously evaluated were observed. CONCLUSION In this pooled analysis of sitagliptin therapy vs placebo in Hispanic/Latino patients, sitagliptin provided significant improvement in glycemic control and was generally well tolerated. FUNDING Merck & Co., Inc., Kenilworth, NJ, USA.
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Soltani G, Hatefi Z, Salehi AR, Khosravi S, Ghiasi MR, Teke K, Aminorroaya A, Salehi R. Pharmacogenomics of Sulfonylureas Response in Relation to rs7754840 Polymorphisms in Cyclin-Dependent Kinase 5 Regulatory Subunit-associated Protein 1-like (CDKAL1) Gene in Iranian Type 2 Diabetes Patients. Adv Biomed Res 2018; 7:96. [PMID: 30050884 PMCID: PMC6036778 DOI: 10.4103/abr.abr_144_17] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background: Sulfonylureas are important drugs of choice for treatment of type 2 diabetes mellitus (T2DM). It is suggested that differential response to sulfonylureas from T2DM patients is under influence of single nucleotide polymorphisms in some of the target genes. In spite of favorable therapeutic effects, sulfonylureas are associated with some adverse side effects such as microvascular complications and stroke, especially in older patients. Therefore, for T2DM patients who are getting less benefit, sulfonylureas should be avoided. Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like (CDKAL1) gene variation is reported to be associated with sulfonylureas effectiveness. Due to the inconsistency of available data regarding association of rs7754840 in CDKAL1 gene with sulfonylureas response in T2DM patients, the present study is conducted. Materials and Methods: Fifty-one diabetic patients sensitive to sulfonylureas and 51 patients resistant to sulfonylureas treatment were recruited to this study. After extraction of DNA from patients' peripheral blood samples, rs7754840 single-nucleotide polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism assay using MaeII (Tail) restriction enzyme. Results: Frequency of G allele in resistant group was more than sensitive group (71, 6% vs. 57, 8%). Regression analysis was shown significant association between GG genotype and higher risk of resistance to sulfonylureas treatment (odds ratio = 2.250 [95% confidential intervals: 1.010–5.012]; P = 0.046). Conclusion: Our data confirmed that genotypes of rs7754840 are significantly associated with sulfonylureas treatment response. rs7754840 in CDKAL1 gene in combination with other clinicopathological findings would help to move towards personalized therapy of T2DM patients.
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Affiliation(s)
- Goljahan Soltani
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Tehran, Iran
| | - Zahra Hatefi
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Tehran, Iran
| | - Ahmad Reza Salehi
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Tehran, Iran
| | - Sharifeh Khosravi
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Tehran, Iran
| | - Moosa Rahimi Ghiasi
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Tehran, Iran
| | - Keimer Teke
- Iranian Blood Transfusion Organization Research Centre, Tehran, Iran
| | - Ashraf Aminorroaya
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Rasoul Salehi
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Tehran, Iran
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Dissanayake HA, Keerthisena GSP, Gamage KKK, Liyanage JH, Ihalagama IRHS, Wijetunga WMUA, Tillekaratne TAD, Katulanda GW, Katulanda P. Hypoglycaemia in diabetes: do we think enough of the cause? An observational study on prevalence and causes of hypoglycaemia among patients with type 2 diabetes in an out-patient setting in Sri Lanka. BMC Endocr Disord 2018; 18:35. [PMID: 29884151 PMCID: PMC5994038 DOI: 10.1186/s12902-018-0264-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Accepted: 06/01/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Hypoglycaemia is a feared experience for people with diabetes. We aimed to study the prevalence and causes of hypoglycaemia among Sri Lankans with diabetes. METHODS One thousand patients with diabetes attending a private sector diabetic clinic were interviewed using a structured questionnaire. Hypoglycaemic episodes within the preceding month were inquired and severity was graded according to clinical features and/or capillary blood glucose levels. RESULTS Mean age 55.0 years (± 12.5), 58.6% were males, mean diabetes duration 10.6 years (± 8.1), mean FPG 7.48 mmol/l (± 2.79) and mean HbA1c 7.82% (± 1.71) (62 mmol/mol). Of them, 26.1%. (mild 20.7%, moderate 3.9%, and severe 1.5%) experienced symptomatic hypoglycaemia. Sudden change diet (46.7%), unaccustomed exercise (15.7%) and increase in antihyperglycaemic therapy dosage (14.9%) were the recognized causes. Cause was not recognized by 16.3%. Non-prescribed native food items accounted for hypoglycaemia in 16.9% of patients (Momordica charantia 54.5%, Costus speciosus 52.3%, Salacia prinoides 11.4%, Coccinia grandis 6.8%, Adenanthera pavonina 4.5%). Severity of hypoglycaemia was positively correlated to age and duration of diabetes but not to HbA1C. CONCLUSION Hypoglycaemia is common among patients with diabetes. Patients need advice on regular diet and exercise. Consumption of non-prescribed native foods should be considered as a possible cause.
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Affiliation(s)
- H. A. Dissanayake
- Diabetes Research Unit, Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
- University Medical Unit, National Hospital of Sri Lanka, Colombo 10, Sri Lanka
| | - G. S. P. Keerthisena
- Diabetes Research Unit, Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | - K. K. K. Gamage
- Diabetes Research Unit, Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | - J. H. Liyanage
- Diabetes Research Unit, Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | - I. R. H. S. Ihalagama
- Diabetes Research Unit, Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | - W. M. U. A. Wijetunga
- Diabetes Research Unit, Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | - T. A. D. Tillekaratne
- Diabetes Research Unit, Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | | | - P. Katulanda
- Diabetes Research Unit, Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
- Cruddas Link Fellow, Harris Manchester University, University of Oxford, Oxford, UK
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Gosho M. Risk of Hypoglycemia After Concomitant Use of Antidiabetic, Antihypertensive, and Antihyperlipidemic Medications: A Database Study. J Clin Pharmacol 2018; 58:1324-1331. [DOI: 10.1002/jcph.1147] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Accepted: 04/02/2018] [Indexed: 11/08/2022]
Affiliation(s)
- Masahiko Gosho
- Department of Biostatistics; Faculty of Medicine; University of Tsukuba; Tsukuba Ibaraki Japan
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Duncan EAS, Fitzpatrick D, Ikegwuonu T, Evans J, Maxwell M. Role and prevalence of impaired awareness of hypoglycaemia in ambulance service attendances to people who have had a severe hypoglycaemic emergency: a mixed-methods study. BMJ Open 2018; 8:e019522. [PMID: 29691243 PMCID: PMC5922484 DOI: 10.1136/bmjopen-2017-019522] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
OBJECTIVES (1) To compare the experiences of people who are affected by diabetes-related hypoglycaemia and either do or do not require an emergency attendance and (2) to measure the prevalence of impaired awareness of hypoglycaemia in patients who are attended by an ambulance service due to a severe hypoglycaemic event. DESIGN A sequential mixed-methods study. SETTING A qualitative interview study was undertaken with 31 people with diabetes (types 1 and 2) resident in the central belt of Scotland. A national prevalence survey of 590 Scottish Ambulance Service patients who had recently experienced a severe hypoglycaemic emergency requiring ambulance clinicians attendance. Impaired awareness of hypoglycaemia was measured using two standardised measures. RESULTS Considerable differences in impaired awareness of hypoglycaemia were found in the experiences of participants who did or did not require the ambulance service to treat their severe hypoglycaemic events. Those who required an ambulance reported fewer warning signs and symptoms. The prevalence of impaired awareness of hypoglycaemia in ambulance service call-outs as assessed by two standardised measures was 53% and 60%, respectively. CONCLUSIONS The prevalence of impaired awareness of hypoglycaemia among those who require an ambulance following a hypoglycaemic event is more than twice that found in the general population of people with diabetes. This may be because the experiences of impaired awareness in people who require an ambulance following a severe hypoglycaemic event differ to those who do not. This study provides important information to guide future prehospital clinical practice, and to develop and evaluate theoretically informed interventions. Improvements in prehospital care for this patient population could lead to global improvements in health outcomes and decreased service costs.
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Affiliation(s)
- Edward A S Duncan
- Nursing, Midwifery and Allied Health Professions Research Unit (NMAHP RU), Faculty of Health Sciences and Sport, The University of Stirling, Stirling, UK
| | - David Fitzpatrick
- Faculty of Health Science and Sport, University of Stirling, Stirling, UK
| | - Theresa Ikegwuonu
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Josie Evans
- Faculty of Health Sciences and Sport, University of Stirling, Stirling, UK
| | - Margaret Maxwell
- Nursing, Midwifery and Allied Health Professions Research Unit, University of Stirling, Stirling, UK
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Leonard CE, Han X, Bilker WB, Flory JH, Brensinger CM, Flockhart DA, Gagne JJ, Cardillo S, Hennessy S. Comparative risk of severe hypoglycemia among concomitant users of thiazolidinedione antidiabetic agents and antihyperlipidemics. Diabetes Res Clin Pract 2016; 115:60-7. [PMID: 27242124 PMCID: PMC4890073 DOI: 10.1016/j.diabres.2016.03.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Revised: 02/08/2016] [Accepted: 03/04/2016] [Indexed: 10/22/2022]
Abstract
We conducted high-dimensional propensity score-adjusted cohort studies to examine whether thiazolidinedione use with a statin or fibrate was associated with an increased risk of severe hypoglycemia. We found that concomitant therapy with a thiazolidinedione+fibrate was associated with a generally delayed increased risk of severe hypoglycemia.
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Affiliation(s)
- Charles E Leonard
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, United States; Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, United States.
| | - Xu Han
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, United States; Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, United States
| | - Warren B Bilker
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, United States; Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, United States; Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, 3535 Market Street, Philadelphia, PA 19104, United States
| | - James H Flory
- Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, United States; Department of Healthcare Policy and Research, Division of Comparative Effectiveness, Weill Cornell Medical College, 402 East 67th Street, New York, NY 10065, United States
| | - Colleen M Brensinger
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, United States
| | - David A Flockhart
- Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, United States; Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, 950 West Walnut Street, Indianapolis, IN 46202, United States
| | - Joshua J Gagne
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Boston, MA 02120, United States
| | - Serena Cardillo
- Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, United States; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA 19104, United States
| | - Sean Hennessy
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, United States; Center for Pharmacoepidemiology Research and Training, Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, United States; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine at the University of Pennsylvania, 34th Street & Civic Center Boulevard, Philadelphia, PA 19104, United States
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Jafari B, Britton ME. Hypoglycaemia in elderly patients with type 2 diabetes mellitus: a review of risk factors, consequences and prevention. JOURNAL OF PHARMACY PRACTICE AND RESEARCH 2015. [DOI: 10.1002/jppr.1163] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Affiliation(s)
- Badieh Jafari
- Department of General Medicine and Aged Care; Hervey Bay Hospital; Queensland Australia
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21
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Pimentel AL, Bauer AC, Camargo JL. Renal posttransplantation diabetes mellitus: An overview. Clin Chim Acta 2015; 450:327-32. [DOI: 10.1016/j.cca.2015.09.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Revised: 09/05/2015] [Accepted: 09/10/2015] [Indexed: 12/25/2022]
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Zhou J, Zheng F, Guo X, Yang H, Zhang M, Tian H, Guo L, Li Q, Mo Y, Jia W. Glargine insulin/gliclazide MR combination therapy is more effective than premixed insulin monotherapy in Chinese patients with type 2 diabetes inadequately controlled on oral antidiabetic drugs. Diabetes Metab Res Rev 2015; 31:725-33. [PMID: 25952634 DOI: 10.1002/dmrr.2661] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2014] [Accepted: 04/28/2015] [Indexed: 02/05/2023]
Abstract
BACKGROUND The aim of this study is to compare the efficacy and safety of once-daily insulin glargine plus gliclazide modified release combination therapy versus twice-daily premixed insulin monotherapy in Chinese type 2 diabetic patients insufficiently controlled by oral antidiabetic agents. METHODS In a 12-week, multicenter, randomized, parallel-group clinical trial, patients with poor glycaemic control (fasting plasma glucose ≥ 7.0 mmol/L and 7.5% < haemoglobin A1c ≤ 10%) on oral antidiabetic drugs were randomized to the treatment groups for combination therapy (n = 52) or monotherapy (n = 53). Continuous glucose monitoring was carried out over two 72-h periods, at the beginning and the end of the study, and the data were used to calculate the 24-h mean blood glucose, mean amplitude of glycaemic excursions, standard deviation of blood glucose, and the mean of daily differences. RESULTS The mean haemoglobin A1c decrease from baseline to study end was significant for both treatment groups (combination therapy: -1.23 ± 0.92%; insulin monotherapy: -1.02 ± 1.04%); moreover, the combination therapy group showed a significantly more robust haemoglobin A1c decrease (p = 0.0308). Both therapies significantly reduced the 24-h mean blood glucose (both, p < 0.001), but neither produced a significant effect on glycaemic variability, calculated as mean amplitude of glycaemic excursions, standard deviation of blood glucose, and mean of daily differences. In addition, the effects on rates of hypoglycaemic episodes were similar between the two therapies. CONCLUSIONS Chinese patients with type 2 diabetes inadequately controlled with oral antidiabetic agents attained greater benefit from once-daily insulin glargine plus gliclazide modified release regimen than from a twice-daily premixed insulin regimen.
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Affiliation(s)
- Jian Zhou
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China
| | - Fenping Zheng
- Department of Endocrinology and Metabolism, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Xiaohui Guo
- Department of Endocrinology and Metabolism, Peking University First Hospital, Beijing, China
| | - Huazhang Yang
- Department of Endocrinology and Metabolism, Guangdong General Hospital, Guangzhou, Guangdong, China
| | - Muxun Zhang
- Department of Endocrinology and Metabolism, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Haoming Tian
- Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China
| | - Lixin Guo
- Department of Endocrinology and Metabolism, Beijing Hospital of Ministry of Public Health, Beijing, China
| | - Qiang Li
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yifei Mo
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China
| | - Weiping Jia
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China
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Abstract
Hypoglycemia caused by treatment with a sulfonylurea, a glinide, or insulin coupled with compromised defenses against the resulting falling plasma glucose concentrations is a problem for many people with diabetes. It is often recurrent, causes significant morbidity and occasional mortality, limits maintenance of euglycemia, and impairs physiological and behavioral defenses against subsequent hypoglycemia. Minimizing hypoglycemia includes acknowledging the problem; considering each risk factor; and applying the principles of intensive glycemic therapy, including drug selection and selective application of diabetes treatment technologies. For diabetes health-care providers treating most people with diabetes who are at risk for or are suffering from iatrogenic hypoglycemia, these principles include selecting appropriate individualized glycemic goals and providing structured patient education to reduce the incidence of hypoglycemia. This is typically combined with short-term scrupulous avoidance of hypoglycemia, which often will reverse impaired awareness of hypoglycemia. Clearly, the risk of hypoglycemia is modifiable.
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Martín-Timón I, del Cañizo-Gómez FJ. Mechanisms of hypoglycemia unawareness and implications in diabetic patients. World J Diabetes 2015; 6:912-926. [PMID: 26185599 PMCID: PMC4499525 DOI: 10.4239/wjd.v6.i7.912] [Citation(s) in RCA: 131] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2014] [Revised: 12/30/2014] [Accepted: 04/02/2015] [Indexed: 02/05/2023] Open
Abstract
Hypoglycemia unawareness (HU) is defined at the onset of neuroglycopenia before the appearance of autonomic warning symptoms. It is a major limitation to achieving tight diabetes and reduced quality of life. HU occurs in approximately 40% of people with type 1 diabetes mellitus (T1DM) and with less frequency in T2DM. Though the aetiology of HU is multifactorial, possible mechanisms include chronic exposure to low blood glucose, antecedent hypoglycaemia, recurrent severe hypoglycaemia and the failure of counter-regulatory hormones. Clinically it manifests as the inability to recognise impeding hypoglycaemia by symptoms, but the mechanisms and mediators remain largely unknown. Prevention and management of HU is complex, and can only be achieved by a multifactorial intervention of clinical care and structured patient education by the diabetes team. Less know regarding the impact of medications on the development or recognition of this condition in patients with diabetes. Several medications are thought to worsen or promote HU, whereas others may have an attenuating effect on the problem. This article reviews recent advances in how the brain senses and responds to hypoglycaemia, novel mechanisms by which people with insulin-treated diabetes develop HU and impaired counter-regulatory responses. The consequences that HU has on the person with diabetes and their family are also described. Finally, it examines the evidence for prevention and treatment of HU, and summarizes the effects of medications that may influence it.
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Shankar RR, Xu L, Golm GT, O'Neill EA, Goldstein BJ, Kaufman KD, Engel SS. A comparison of glycaemic effects of sitagliptin and sulfonylureas in elderly patients with type 2 diabetes mellitus. Int J Clin Pract 2015; 69:626-31. [PMID: 25652751 DOI: 10.1111/ijcp.12607] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
INTRODUCTION In the USA, 45% of patients with type 2 diabetes mellitus (T2DM) are elderly (≥ 65 years old). In general, use of sulfonylurea increases with patient age as does the associated risk for hypoglycaemia, and the consequences of hypoglycaemia can be more pronounced in elderly patients. Sitagliptin, a DPP-4 inhibitor, improves glycaemic control in adult patients of all ages with T2DM, with a low risk of hypoglycaemia when used alone or in combination with other antidiabetic agents that are not generally associated with hypoglycaemia when used independently. METHODS In a post hoc analysis, pooled data from elderly patients who participated in one of three double-blind studies comparing the effects of therapy with sitagliptin (100 mg/day) vs. sulfonylurea (in titrated doses) were analysed for changes from baseline in HbA1c, fasting plasma glucose (FPG), and body weight and for the incidence of reported symptomatic hypoglycaemia. In these studies, patients on diet alone or metformin were randomised to sitagliptin or glipizide for 104 weeks (studies 1 and 2) or glimepiride for 30 weeks (study 3). The analysis included 372 elderly patients who completed a trial through 25 or 30 weeks. RESULTS Both HbA1c and FPG decreased from baseline with each treatment, with no statistically significant differences between treatments. A significantly lower incidence of reported hypoglycaemia was observed with sitagliptin compared with sulfonylurea (6.2% vs. 27.8%; p < 0.001). Body weight decreased significantly with sitagliptin but not with sulfonylurea. Significantly more patients on sitagliptin than on sulfonylureas achieved a composite end-point of >0.5% HbA1c reduction with no reported hypoglycaemia or increase in body weight (44.1% vs. 16.0%; p < 0.001). CONCLUSION In this analysis of elderly patients with T2DM, compared with sulfonylurea, sitagliptin provided similar glycaemic efficacy with less hypoglycaemia and with body weight loss.
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Affiliation(s)
- R R Shankar
- Merck & Co., Inc., Whitehouse Station, NJ, USA
| | - L Xu
- Merck & Co., Inc., Whitehouse Station, NJ, USA
| | - G T Golm
- Merck & Co., Inc., Whitehouse Station, NJ, USA
| | - E A O'Neill
- Merck & Co., Inc., Whitehouse Station, NJ, USA
| | | | - K D Kaufman
- Merck & Co., Inc., Whitehouse Station, NJ, USA
| | - S S Engel
- Merck & Co., Inc., Whitehouse Station, NJ, USA
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Brunmair B, Lehner Z, Stadlbauer K, Adorjan I, Frobel K, Scherer T, Luger A, Bauer L, Fürnsinn C. 55P0110, a Novel Synthetic Compound Developed from a Plant Derived Backbone Structure, Shows Promising Anti-Hyperglycaemic Activity in Mice. PLoS One 2015; 10:e0126847. [PMID: 25973898 PMCID: PMC4431753 DOI: 10.1371/journal.pone.0126847] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Accepted: 04/08/2015] [Indexed: 11/18/2022] Open
Abstract
Starting off with a structure derived from the natural compound multiflorine, a derivatisation program aimed at the discovery and initial characterisation of novel compounds with antidiabetic potential. Design and discovery of the structures was guided by oral bioactivities obtained in oral glucose tolerance tests in mice. 55P0110, one among several new compounds with distinct anti-hyperglycaemic activity, was further examined to characterise its pharmacology and mode of action. Whereas a single oral dose of 55P0110 did not affect basal glycaemia, it markedly improved the glucose tolerance of healthy and diabetic mice (peak blood glucose in glucose tolerance test, mmol/l: healthy mice with 90 mg/kg 55P0110, 17.0 ± 1.2 vs. 10.1 ± 1.1; diabetic mice with 180 mg/kg 55P0110, 23.1 ± 0.9 vs. 11.1 ± 1.4; p<0.001 each). Closer examination argued against retarded glucose resorption from the gut, increased glucose excretion in urine, acute insulin-like or insulin sensitising properties, and direct inhibition of dipeptidyl peptidase-4 as the cause of glucose lowering. Hence, 55P0110 seems to act via a target not exploited by any drug presently approved for the treatment of diabetes mellitus. Whereas the insulinotropic sulfonylurea gliclazide (16 mg/kg) distinctly increased the circulating insulin-per-glucose ratio under basal conditions, 55P0110 (90 mg/kg) lacked such an effect (30 min. after dosing, nmol/mol: vehicle, 2.49 ± 0.27; 55P0110, 2.99 ± 0.35; gliclazide, 8.97 ± 0.49; p<0.001 each vs. gliclazide). Under an exogenous glucose challenge, however, 55P0110 increased this ratio to the same extent as gliclazide (20 min. after glucose feeding: vehicle, 2.53 ± 0.41; 55P0110, 3.80 ± 0.46; gliclazide, 3.99 ± 0.26; p<0.05 each vs. vehicle). By augmenting the glucose stimulated increase in plasma insulin, 55P0110 thus shows distinct anti-hyperglycaemic action in combination with low risk for fasting hypoglycaemia in mice. In summary, we have discovered a novel class of fully synthetic substituted quinazolidines with an attractive pharmacological profile that recommends the structures for further evaluation as candidates for the treatment of diabetes mellitus.
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Affiliation(s)
- Barbara Brunmair
- Division of Endocrinology & Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Zsuzsanna Lehner
- Division of Endocrinology & Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Karin Stadlbauer
- Division of Endocrinology & Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | | | - Klaus Frobel
- 55pharma Drug Discovery & Development AG, Vienna, Austria
| | - Thomas Scherer
- Division of Endocrinology & Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Anton Luger
- Division of Endocrinology & Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | | | - Clemens Fürnsinn
- Division of Endocrinology & Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria
- * E-mail:
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Martorella AJ. Iatrogenic Hypoglycemia in Patients with Type 2 Diabetes: Comparison of Insulin Analog Premixes and Human Insulin Premixes. Postgrad Med 2015; 123:7-16. [DOI: 10.3810/pgm.2011.07.2299] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Naidoo P, Rambiritch V, Butkow N, Saman S. Optimal utilisation of sulphonylureas in resource-constrained settings. Cardiovasc J Afr 2015; 25:83-5. [PMID: 24844554 PMCID: PMC4026768 DOI: 10.5830/cvja-2014-007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Accepted: 02/04/2014] [Indexed: 01/21/2023] Open
Abstract
Abstract Sulphonylureas (SUs) are oral anti-diabetic drugs (OADs) that were introduced more than 60 years ago. Clinicians are familiar with their use and they remain extensively used. However, the SU class is associated with adverse effects of weight gain and hypoglycaemia. In addition, their effects on cardiovascular events remain contentious. Newer classes of anti-diabetic agents have been developed and these agents are weight neutral (di-peptidyl peptidase IV inhibitors), while others reduce weight (glucagon-like peptide analogues and sodium glucose co-transporter inhibitors). Furthermore, the newer agents are less likely to cause hypoglycaemia and have a potentially better cardiovascular safety profile. However, the newer agents are more costly than SUs and their long-term safety is unknown. It is therefore likely that SUs will continue to be used, and more so in resource-limited settings. One may mitigate the adverse effects of weight gain and hypoglycaemia associated with the SU class by using members within this class that are less probable to cause these adverse effects. Furthermore, the specific SU must be used at the lowest effective therapeutic dose. In patients at high risk of SU-induced hypoglycaemic episodes (frail, clinically significant renal impairment), or patients in whom hypoglycaemic episodes may have devastating effects (bus drivers), newer anti-diabetic agents may be a justifiable alternative option.
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Affiliation(s)
| | | | - Neil Butkow
- Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
| | - Selvarajah Saman
- Port Shepstone Regional Hospital and University of Kwa-Zulu Natal, Durban, South Africa
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Gallwitz B, Kusterer K, Hildemann S, Fresenius K. Type II diabetes and its therapy in clinical practice - results from the standardised non-interventional registry SIRTA. Int J Clin Pract 2014; 68:1442-53. [PMID: 25298194 DOI: 10.1111/ijcp.12497] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND AND METHODS Modern antidiabetic therapies should achieve low HbA1c values and avoid hypoglycaemic complications. The registry SIRTA included 1522 patients with type II diabetes mellitus (T2DM) from 306 German medical practices. Patients had an HbA1c > 6.5% under the maximum tolerated metformin dose. If required, they received combination therapy with other antidiabetics according to the guideline of the German Diabetes Society [Deutsche Diabetes Gesellschaft (DDG)] or usual medical practice. Patients were followed up for 6 months. The target criteria included the achievement of HbA1c target values and the emergence of severe hypoglycaemic episodes. RESULTS Most patients (64.0%) were planned to achieve an HbA1c target < 6.5%, the standard target recommended by the 2009 DDG guideline valid throughout the registry. Primarily to reduce the individual risk for hypoglycaemia, 32.4% of patients had a less strict HbA1c-target of 6.5-7.0%. These targets were achieved by 31.3% and 44.3% of patients, respectively. Combination therapies increased from 45% to 56% over the 6 months registry. Four patients had severe hypoglycaemias (0.26%). CONCLUSIONS The registry confirms results from other epidemiologic studies on the therapy of T2DM in everyday practice. The treatment strategies applied effectively reduced blood glucose and avoided severe hypoglycaemias. An early therapy of insufficiently controlled patients with T2DM is important, as lower baseline values facilitated achieving HbA1c targets.
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Affiliation(s)
- B Gallwitz
- Department of Medicine IV, Eberhard-Karls University Tübingen, Tübingen, Germany
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The 2012 SEMDSA Guideline for the Management of Type 2 Diabetes (Revised). JOURNAL OF ENDOCRINOLOGY, METABOLISM AND DIABETES OF SOUTH AFRICA 2014. [DOI: 10.1080/22201009.2012.10872287] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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31
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The 2012 SEMDSA Guideline for the Management of type 2 Diabetes. JOURNAL OF ENDOCRINOLOGY METABOLISM AND DIABETES OF SOUTH AFRICA 2014. [DOI: 10.1080/22201009.2012.10872277] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
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Dardano A, Bianchi C, Del Prato S, Miccoli R. Insulin degludec/insulin aspart combination for the treatment of type 1 and type 2 diabetes. Vasc Health Risk Manag 2014; 10:465-75. [PMID: 25143741 PMCID: PMC4132254 DOI: 10.2147/vhrm.s40097] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Glycemic control remains the major therapeutic objective to prevent or delay the onset and progression of complications related to diabetes mellitus. Insulin therapy represents a cornerstone in the treatment of diabetes and has been used widely for achieving glycemic goals. Nevertheless, a large portion of the population with diabetes does not meet the internationally agreed glycemic targets. Moreover, insulin treatment, especially if intensive, may be associated with emergency room visits and hospitalization due to hypoglycemic events. Therefore, fear of hypoglycemia or hypoglycemic events represents the main barriers to the attainment of glycemic targets. The burden associated with multiple daily injections also remains a significant obstacle to initiating and maintaining insulin therapy. The most attractive insulin treatment approach should meet the patients’ preference, rather than demanding patients to change or adapt their lifestyle. Insulin degludec/insulin aspart (IDegAsp) is a new combination, formulated with ultra-long-acting insulin degludec and rapid-acting insulin aspart, with peculiar pharmacological features, clinical efficacy, safety, and tolerability. IDegAsp provides similar, noninferior glycemic control to a standard basal–bolus regimen in patients with type 1 diabetes mellitus, with additional benefits of significantly lower episodes of hypoglycemia (particularly nocturnal) and fewer daily insulin injections. Moreover, although treatment strategy and patients’ viewpoint are different in type 1 and type 2 diabetes, trial results suggest that IDegAsp may be an appropriate and reasonable option for initiating insulin therapy in patients with type 2 diabetes inadequately controlled on maximal doses of conventional oral agents. This paper will discuss the role of IDegAsp combination as a novel treatment option in diabetic patients.
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Affiliation(s)
- Angela Dardano
- Department of Clinical and Experimental Medicine, Section of Diabetes and Metabolic Diseases, University of Pisa, Pisa, Italy
| | - Cristina Bianchi
- Department of Clinical and Experimental Medicine, Section of Diabetes and Metabolic Diseases, University of Pisa, Pisa, Italy
| | - Stefano Del Prato
- Department of Clinical and Experimental Medicine, Section of Diabetes and Metabolic Diseases, University of Pisa, Pisa, Italy
| | - Roberto Miccoli
- Department of Clinical and Experimental Medicine, Section of Diabetes and Metabolic Diseases, University of Pisa, Pisa, Italy
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Abstract
The selection of a glycemic goal in a person with diabetes is a compromise between the documented upside of glycemic control-the partial prevention or delay of microvascular complications-and the documented downside of glycemic control-the recurrent morbidity and potential mortality of iatrogenic hypoglycemia. The latter is not an issue if glycemic control is accomplished with drugs that do not cause hypoglycemia or with substantial weight loss. However, hypoglycemia becomes an issue if glycemic control is accomplished with a sulfonylurea, a glinide, or insulin, particularly in the setting of absolute endogenous insulin deficiency with loss of the normal decrease in circulating insulin and increase in glucagon secretion and attenuation of the sympathoadrenal response as plasma glucose concentrations fall. Then the selection of a glycemic goal should be linked to the risk of hypoglycemia. A reasonable individualized glycemic goal is the lowest A1C that does not cause severe hypoglycemia and preserves awareness of hypoglycemia, preferably with little or no symptomatic or even asymptomatic hypoglycemia, at a given stage in the evolution of the individual's diabetes.
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Abstract
OBJECTIVE To review and discuss the risks and impact of hypoglycemia and provide guidance for the prevention of hypoglycemia in type 2 diabetes (T2DM). METHODS We review and discuss the risks and impact of hypoglycemia, providing specific guidance regarding the prevention of hypoglycemia and judicial selection of glucose-lowering agents in individuals with T2DM. RESULTS Hypoglycemia in T2DM is underrecognized and underreported. Emerging evidence from large clinical trials suggest that hypoglycemia may be an important risk factor for morbidity and mortality in T2DM. In addition, hypoglycemia is associated with reduced quality of life, greater healthcare utilization costs, and poor adherence to medical regiments. CONCLUSION These findings have led professional organizations to emphasize the prevention of hypoglycemia as an important consideration when initiating or intensifying treatment regimens. In clinical settings, particular attention should be paid to a patient's risk for hypoglycemia when initiating or intensifying the pharmacological treatment regimen. The endocrinologist can play an important role in educating not only the patient, but also other members of the diabetes-management team regarding the need for individualized therapy.
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Affiliation(s)
- Etie Moghissi
- Department of Medicine, University of California, Marina Del Rey, California 90292, USA.
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36
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Glucose control: Non-insulin therapies. S Afr Fam Pract (2004) 2014. [DOI: 10.1080/20786204.2014.10844579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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Vora J, Caputo S, Damci T, Orozco-Beltran D, Pan C, Svendsen AL, Sølje KS, Khunti K. Effect of once-daily insulin detemir on oral antidiabetic drug (OAD) use in patients with type 2 diabetes. J Clin Pharm Ther 2013; 39:136-43. [PMID: 24329524 DOI: 10.1111/jcpt.12116] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2013] [Accepted: 11/05/2013] [Indexed: 11/30/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE There are acknowledged benefits to continuing metformin when initiating insulin, but there appears to be growing concern over the role of sulphonylureas and thiazolidinediones when used in combination with insulin. This analysis investigates the effects of continuing or discontinuing oral antidiabetic drugs (OADs) following the initiation of once-daily insulin detemir. METHODS SOLVE is a 24-week, multinational observational study of insulin detemir initiation in patients with type 2 diabetes mellitus treated with one or more OADs. RESULTS In the total cohort (n = 17 374), there were significant improvements in HbA1c (-1·3%, 95% CI -1·34; -1·27%) and weight (-0·6 kg, 95% CI -0·65; -0·47 kg), with an increase in the incidence rate of minor hypoglycaemia (+0·256 events ppy, P < 0·001), but not severe hypoglycaemia (-0·038 events ppy, P < 0·001). Study participants had information on OAD use either prior to (n = 17 086) or during insulin initiation (n = 16 346). HbA1c reductions were significantly greater in patients continuing treatment with metformin (-1·3% vs. -1·1%, P < 0·01), thiazolidinediones (-1·3% vs. -1·0%, P < 0·01) and DPP-IV inhibitors (-1·3% vs. -0·9%, P < 0·001). Final insulin doses were significantly greater in patients discontinuing treatment with sulphonylureas (0·29 vs. 0·26 IU/kg, P < 0·001), glinides (0·28 vs. 0·26 IU/kg, P < 0·01), thiazolidinediones (0·31 vs. 0·26 IU/kg, P < 0·001) and DPP-IV inhibitors (0·35 vs. 0·29 IU/kg, P < 0·001) compared with patients continuing these respective agents. All patient subgroups had a mean weight loss irrespective of OAD continuation, apart from those continuing thiazolidinediones (+0·2 kg). The largest improvements in weight were seen following the withdrawal of sulphonylureas and thiazolidinediones (-1·1 and -1·1 kg, respectively). WHAT IS NEW AND CONCLUSION Discontinuation (or switching) of OADs at the time of insulin initiation appears to be governed principally by concerns about hypoglycaemia and weight. HbA1c improvements were smaller in patients discontinuing OADs at the time of insulin initiation and may be associated with insufficient insulin titration.
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Affiliation(s)
- J Vora
- Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, Liverpool, UK
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Moghissi E. Management of type 2 diabetes mellitus in older patients: current and emerging treatment options. Diabetes Ther 2013; 4:239-56. [PMID: 24096685 PMCID: PMC3889320 DOI: 10.1007/s13300-013-0039-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2013] [Indexed: 12/19/2022] Open
Abstract
Elderly patients with type 2 diabetes mellitus (T2DM) are a rapidly emerging population that presents unique clinical challenges. This diverse patient group can differ widely in terms of physical and mental status, which can increase their risk of complications including hypoglycemia, falls, and depression. These factors can negatively impact their glycemic control, safety, and quality of life. The risk of hypoglycemic events is elevated among elderly patients with diabetes. In many cases, these events are related to antidiabetic therapy and the pursuit of strict glycemic control. Fear of a hypoglycemic episode, on the part of the patient and/or healthcare provider, is another major barrier to achieving glycemic control. Hypoglycemic events, even in the absence of awareness of the event (asymptomatic), can have negative consequences. To help manage these risks, several national and international organizations have proposed guidelines to address individualized treatment goals for older adults with diabetes. This article reviews current treatment guidelines for setting glycemic targets in elderly patients with T2DM, and discusses the role of emerging treatment options in this patient population.
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Affiliation(s)
- Etie Moghissi
- UCLA David Geffen School of Medicine, University of California, 4644 Lincoln Blvd., Suite 409, Marina del Rey, Los Angeles, CA, 90292, USA,
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Holstein A, Beil W, Kovacs P. CYP2C metabolism of oral antidiabetic drugs--impact on pharmacokinetics, drug interactions and pharmacogenetic aspects. Expert Opin Drug Metab Toxicol 2013; 8:1549-63. [PMID: 23153186 DOI: 10.1517/17425255.2012.722619] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The cytochrome P4502C enzymes account for the metabolism of approximately 20% of therapeutic drugs including certain oral antidiabetic drugs (OADs). AREAS COVERED This review focuses on the effect of CYP2C enzymes on metabolism of sulphonylureas (SUs), meglitinides, and thiazolidinediones (TZDs) discussing their impact on pharmacokinetics, drug interactions and toxicological profiles. Pharmacogenetic aspects reflecting individual gene variants and variable drug effects are also considered. EXPERT OPINION Genetic polymorphisms of CYP2C9 enzymes (*2/*2, *2/*3, *3/*3) influence the glycaemic response to SUs and impair their substrate metabolism. Restricted data from small-sized studies with heterogenous definitions of hypoglycaemia revealed no clear association between CYP2C9 genotypes and the risk of hypoglycaemia. Functional polymorphisms of CYP2C8- and CYP2C9 drug metabolizing genes affect markedly pharmacokinetics of meglitinides. Compared to wild-type carriers, patients treated with TZDs and carrying the common CYP2C8*3 and *4 variants showed a reduced glycaemic control. The strong CYP2C8 and OATP1B1 inhibitor gemfibrozil increases substantially the plasma concentrations of repaglinide and TZDs. Numerous metabolic drug interactions exist between SUs and commonly prescribed drugs, especially anti-infectives. The complex pharmacokinetic and pharmacogenetic properties and the unfavourable short and long term risk profile of glibenclamide and glimepiride raise the question whether their use can be justified any longer.
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Affiliation(s)
- Andreas Holstein
- Lippe-Detmold Hospital, First Department of Medicine, Röntgenstr. 18, Detmold, 32756, Germany.
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Zhang W, Kim D, Philip E, Miyan Z, Barykina I, Schmidt B, Stein H. A Multinational, Observational Study to Investigate the Efficacy, Safety and Tolerability of Acarbose as Add-On or Monotherapy in a Range of Patients: The GlucoVIP Study. Clin Drug Investig 2013; 33:263-74. [DOI: 10.1007/s40261-013-0063-3] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Abstract
The concept of hypoglycemia-associated autonomic failure (HAAF) in diabetes posits that recent antecedent hypoglycemia, as well as sleep or prior exercise, causes both defective glucose counterregulation (by attenuating the adrenomedullary epinephrine response, in the setting of absent insulin and glucagon responses) and hypoglycemia unawareness (by attenuating the sympathoadrenal, largely the sympathetic neural, response) and thus a vicious cycle of recurrent hypoglycemia. Albeit with different time courses, the pathophysiology of defense against hypoglycemia - no decrease in therapeutic insulin, no increase in glucagon and an attenuated increase in sympathoadrenal activity - is the same in type 1 diabetes and advanced type 2 diabetes. Hypoglycemia unawareness is reversible by 2-3 weeks of scrupulous avoidance of hypoglycemia in most affected patients. The pathophysiology of HAAF in diabetes explains why the incidence of hypoglycemia increases as patients approach the absolute endogenous insulin deficient end of the disease, provides a comprehensive set of risk factors including those indicative of HAAF, and leads logically to the practice of hypoglycemia risk factor reduction. Because of the risk of hypoglycemic mortality, presumably from cardiac arrhythmias, glycemic goals in diabetes should be individualized, based in part on the risk of hypoglycemia. By practicing hypoglycemia risk reduction - addressing the issue, applying the principles of aggressive glycemic therapy and considering both the conventional risk factors and those indicative of HAAF - it is possible to both improve glycemic control and reduce the risk of hypoglycemia in many patients with diabetes.
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Affiliation(s)
- Philip E Cryer
- Department of Medicine, Washington University in St. Louis and Barnes-Jewish Hospital, St. Louis, Missouri, USA.
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Viswanathan M, Joshi SR, Bhansali A. Hypoglycemia in type 2 diabetes: Standpoint of an experts' committee (India hypoglycemia study group). Indian J Endocrinol Metab 2012; 16:894-898. [PMID: 23226632 PMCID: PMC3510957 DOI: 10.4103/2230-8210.102986] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The epidemic of type 2 diabetes and the recognition that achieving specific glycemic goals can substantially reduce morbidity have made the effective treatment of hyperglycemia a top priority. Despite compelling evidence that tight glycemic control is crucial for delaying disease progression, increased risk of hypoglycemia associated with such control underscore the complexity of diabetes management. In most cases, hypoglycemia results from an excess of insulin, either absolute or relative to the available glucose substrate and the factors perhaps exacerbating the risk are pharmacokinetic imperfections, behavioral, co-morbidities etc. Additionally, many patients remain undiagnosed, and many diagnosed patients are not treated appropriately. In this article, the challenges of hypoglycemia, confronting health care providers and their patients with diabetes, are discussed for making treatment decisions that will help minimize risk of hypoglycemia and eventually overcome formidable barriers to optimal diabetes management. Strategies to treat and minimize the frequency and severity of hypoglycemia without compromising on glycemic goals are also presented.
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Affiliation(s)
- Mohan Viswanathan
- Department of Diabetology, Dr. Mohan's Diabetes Specialties Centre and Madras Diabetes Research Foundation, WHO Collaborating Centre for Non Communicable Diseases Prevention and Control, Gopalapuram, Chennai, India
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Shafiee G, Mohajeri-Tehrani M, Pajouhi M, Larijani B. The importance of hypoglycemia in diabetic patients. J Diabetes Metab Disord 2012; 11:17. [PMID: 23497433 PMCID: PMC3598174 DOI: 10.1186/2251-6581-11-17] [Citation(s) in RCA: 100] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2012] [Accepted: 07/18/2012] [Indexed: 02/07/2023]
Abstract
Hypoglycemia is one of the most important complications of diabetes treatment. The risk of severe hypoglycemia is higher in elderly patients, those having comorbidities such as vascular disease or renal failure, pregnant women and in children with type 1diabetes. Moreover, in type 2 diabetes, progressive insulin deficiency, longer duration of diabetes, and tight glycemic control increase the risk of hypoglycemia as much as type 1 diabetes.Episodes hypoglycemia may lead to impairment of counter-regulatory system, with the potential of development of hypoglycemia unawareness. So, hypoglycemia may increase the vascular events even death in addition to other possible detrimental effects. Glycemic control should be individualized based on patient characteristics with some degree of safety. Recognition of hypoglycemia risk factors, blood glucose monitoring, selection of appropriate regimens and educational programs for healthcare professionals and patients with diabetes are the major issues to maintain good glycemic control, minimize the risk of hypoglycemia, and prevent long- term complications.
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Affiliation(s)
- Gita Shafiee
- Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Shariati Hospital, North Kargar Street, 14114, Tehran, Iran.
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Ha WC, Oh SJ, Kim JH, Lee JM, Chang SA, Sohn TS, Son HS. Severe hypoglycemia is a serious complication and becoming an economic burden in diabetes. Diabetes Metab J 2012; 36:280-4. [PMID: 22950059 PMCID: PMC3428416 DOI: 10.4093/dmj.2012.36.4.280] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2012] [Accepted: 06/22/2012] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND The prevalence of hypoglycemia is increasing due to the growing incidence of diabetes and the latest strict guidelines for glycated hemoglobin (HbA1c) levels under 7%. This study examined the clinical characteristics, causal factors, and medical costs of severely hypoglycemic patients in an emergency room (ER) of Uijeongbu St. Mary's Hospital. METHODS The study consisted of a retrospective analysis of the characteristics, risk factors, and medical costs of 320 severely hypoglycemic patients with diabetes who presented to an ER of Uijeongbu St. Mary's Hospital from January 1, 2006 to December 31, 2009. RESULTS Most hypoglycemic patients (87.5%, 280/320) were over 60 years old with a mean age of 69.5±10.9 years and a mean HbA1c level of 6.95±1.46%. Mean serum glucose as noted in the ER was 37.9±34.5 mg/dL. Renal function was decreased, serum creatinine was 2.0±2.1 mg/dL and estimated glomerular filtration rate (eGFR) was 48.0±33.6 mL/min/1.73 m(2). In addition, hypoglycemic patients typically were taking sulfonylureas or insulin and a variety of other medications, and had a long history of diabetes. CONCLUSION Severe hypoglycemia is frequent in older diabetic patients, subjects with low HbA1c levels, and nephropathic patients. Therefore, personalized attention is warranted, especially in long-term diabetics with multiple comorbidities who may not have been properly educated or may need re-education for hypoglycemia.
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Affiliation(s)
- Won Chul Ha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, Uijeongbu, Korea
| | - Su Jin Oh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, Uijeongbu, Korea
| | - Ji Hyun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jung Min Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Sang Ah Chang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Paul's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Tae Seo Sohn
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, Uijeongbu, Korea
| | - Hyun Shik Son
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, Uijeongbu, Korea
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Hanefeld M. Acarbose revisited for efficacy, safety and cardiovascular benefits: a key role for controlling glycemic variability. Expert Rev Endocrinol Metab 2012; 7:395-405. [PMID: 30754166 DOI: 10.1586/eem.12.35] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
There is a growing body of evidence to illustrate the effect of postprandial hyperglycemia (PPHG) in cardiovascular disease development and as a key component of diurnal hyperglycemia. Agents such as acarbose, which has been shown to reduce 24-h glycemia and glycated hemoglobin (mainly via its effects on PPHG), may have the potential to reduce the risk of adverse cardiovascular outcomes as indicated in secondary analyses of the STOP-NIDDM trial. Although the results of the NAVIGATOR trial showed no effect of PPHG reduction on cardiovascular outcomes, acarbose has a different mode of action to nateglinide. This could lead to marked cardiovascular differences, and it is important to fully investigate this. The ongoing ACE trial will determine the effect of acarbose on a composite primary end point of cardiovascular outcomes.
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Affiliation(s)
- Markolf Hanefeld
- a Center for Clinical Studies, GWT - Technical University Dresden, Fiedlerstrasse 34, 01307 Dresden, Germany.
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Holstein JD, Kovacs P, Patzer O, Stumvoll M, Holstein A. The Ser1369Ala variant of ABCC8 and the risk for severe sulfonylurea-induced hypoglycemia in German patients with Type 2 diabetes. Pharmacogenomics 2012; 13:5-7; author reply 9-10. [PMID: 22176616 DOI: 10.2217/pgs.11.150] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
A letter in response to: Sato R, Watanabe H, Genma R et al. ABCC8 polymorphism (Ser1369Ala): influence on severe hypoglycemia due to sulfonylureas. Pharmacogenomics 11(12), 1743–1750 (2010).
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Gökalp O, Gunes A, Cam H, Cure E, Aydın O, Tamer MN, Scordo MG, Dahl ML. Mild hypoglycaemic attacks induced by sulphonylureas related to CYP2C9, CYP2C19 and CYP2C8 polymorphisms in routine clinical setting. Eur J Clin Pharmacol 2011; 67:1223-1229. [PMID: 21691805 DOI: 10.1007/s00228-011-1078-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2011] [Accepted: 05/31/2011] [Indexed: 02/07/2023]
Abstract
AIM To evaluate the impact of polymorphisms in the cytochrome P450 (CYP) 2C9, 2C19 and 2C8 genes on the risk of mild hypoglycaemic attacks in patients treated with sulphonylureas. METHODS One hundred and eight type 2 diabetic patients (50 men, 58 women), treated with oral antidiabetics, including at least one from the sulphonylurea group (glimepiride n = 50, gliclazide n = 46, or glipizide n = 12) for 3 months or longer, were included in the study. Symptoms of hypoglycaemia (sweating, tremor, anxiety and palpitations) during a 3 month period were recorded and confirmed by home glucose measurements. Gender, age, body mass index, creatinine clearance, HbA1c, oral antidiabetic dose and concomitant medication were assessed together with functional CYP2C9, CYP2C19 and CYP2C8 polymorphisms, analysed by real-time PCR methods. RESULTS Fifteen patients (eight men, seven women) reported hypoglycaemia symptoms which were validated by their home glucose measurements (< 70 mg/dl). Heterozygosity and homozygosity for CYP2C9 variant alleles (*2 or *3) tended to be more frequent among patients who reported hypoglycaemic attacks (60 and 7%) than those who did not (39 and 3%). Similarly, the CYP2C8*1/*3 genotype tended to be more frequent in patients with (47%) than without (27%) hypoglycaemia, while no such trend was observed for CYP2C19 variants. However, only in the gliclazide group a significant association between CYP2C9 genotype and hypoglycaemic attacks was observed (P = 0.035). None of the other covariates showed any significant association with the risk of hypoglycaemic attacks. CONCLUSIONS CYP2C9 polymorphisms leading to decreased enzyme activity show a modest impact on the risk of mild hypoglycaemia attacks during oral antidiabetic treatment, with a significant association in patients treated with gliclazide.
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Affiliation(s)
- Osman Gökalp
- Medical Faculty, Department of Pharmacology, Dicle University, Diyarbakir, Turkey
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Manolopoulos VG, Ragia G, Tavridou A. Pharmacogenomics of oral antidiabetic medications: current data and pharmacoepigenomic perspective. Pharmacogenomics 2011; 12:1161-91. [PMID: 21843065 DOI: 10.2217/pgs.11.65] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) is an increasingly prevalent disease. Several classes of drugs are currently available to treat T2DM patients; however, clinical response to these drugs often exhibits significant variation among individuals. For the oral antidiabetic drug classes of sulfonylureas, nonsulfonylurea insulin secretagogs, biguanides and thiazolidinediones, pharmacogenomic evidence has accumulated demonstrating an association between specific gene polymorphisms and interindividual variability in their therapeutic and adverse reaction effects. These polymorphisms are in genes of molecules involved in metabolism, transport and therapeutic mechanisms of the aforementioned drugs. Overall, it appears that pharmacogenomics has the potential to improve the management of T2DM and help clinicians in the effective prescribing of oral antidiabetic medications. Although pharmacogenomics can explain some of the heterogeneity in dose requirements, response and incidence of adverse effects of drugs between individuals, it is now clearly understood that much of the diversity in drug effects cannot be solely explained by studying the genomic diversity. Epigenomics, the field that focuses on nongenomic modifications that influence gene expression, may expand the scope of pharmacogenomics towards optimization of drug therapy. Therefore, pharmacoepigenomics, the combined analysis of genetic variations and epigenetic modifications, holds promise for the realization of personalized medicine. Although pharmacoepigenomics has so far been evaluated mainly in cancer pharmacotherapy, studies on epigenomic modifications during T2DM development provide useful data on the potential of pharmacoepigenomics to elucidate the mechanisms underlying interindividual response to oral antidiabetic treatment. In summary, the present article focuses on available data from pharmacogenomic studies of oral antidiabetic drugs and also provides an overview of T2DM epigenomic research, which has the potential to boost the development of pharmacoepigenomics in antidiabetic treatment.
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Affiliation(s)
- Vangelis G Manolopoulos
- Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100 Alexandroupolis, Greece.
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Abstract
Hypoglycemia is a common finding in both daily clinical practice and acute care settings. The causes of severe hypoglycemia (SH) are multi-factorial and the major etiologies are iatrogenic, infectious diseases with sepsis and tumor or autoimmune diseases. With the advent of aggressive lowering of HbA1c values to achieve optimal glycemic control, patients are at increased risk of hypoglycemic episodes. Iatrogenic hypoglycemia can cause recurrent morbidity, sometime irreversible neurologic complications and even death, and further preclude maintenance of euglycemia over a lifetime of diabetes. Recent studies have shown that hypoglycemia is associated with adverse outcomes in many acute illnesses. In addition, hypoglycemia is associated with increased mortality among elderly and non-diabetic hospitalized patients. Clinicians should have high clinical suspicion of subtle symptoms of hypoglycemia and provide prompt treatment. Clinicians should know that hypoglycemia is associated with considerable adverse outcomes in many acute critical illnesses. In order to reduce hypoglycemia-associated morbidity and mortality, timely health education programs and close monitoring should be applied to those diabetic patients presenting to the Emergency Department with SH. ED disposition strategies should be further validated and justified to achieve balance between the benefits of euglycemia and the risks of SH. We discuss relevant issues regarding hypoglycemia in emergency and critical care settings.
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Affiliation(s)
- Shih-Hung Tsai
- Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Yen-Yue Lin
- Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chin-Wang Hsu
- Department of Critical & Emergency Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan
| | - Chien-Sheng Cheng
- Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Der-Ming Chu
- Peng-Hu Branch, Tri-Service General Hospital, National Defense Medical Center, Peng-Hu, Taiwan
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