Drug-induced Hypoglycemia Research Articles

Anti-diabetic Effect of Myrtenal on Plasma and Tissue Glycoproteins Components in STZ Induced Experimental Diabetic Rats

The aim of present study was to evaluate the effect of myrtenal, a monoterpene on plasma and tissues glycoprotein components in streptozotocin-induced diabetic rats. Diabetes was induced in overnight fasted experimental rats by a single intraperitoneal injection of streptozotocin (STZ; 40 mg/kg body weight) dissolved in 0.1 M citrate buffer at pH 4.5. STZ-injected animals were given 20 % glucose solution for 24 h to prevent initial drug-induced hypoglycemia mortality. The levels of plasma glucose, plasma and tissues glycoproteins such as hexose, hexosamine, fucose and sialic acid were significantly increased whereas plasma insulin levels were significantly decreased in diabetic rats. On oral administration myrtenal (80 mg/kg b.w.) once daily to diabetic rats for the period of 28 days brought back the levels of plasma and tissues glycoprotein components. Based on the present study, we propose that myrtenal possesses significant protective effect on glycoprotein metabolism.

Higher risk of sulfonylurea-associated hypoglycemic symptoms in women with type 2 diabetes mellitus.

Although some evidence suggests that women may be at greater risk for hypoglycemia, no conclusion has been reached, and female sex has not been taken into account in antidiabetic drug-induced hypoglycemia. This study aimed to determine whether females are at a higher risk of sulfonylurea (SU)-associated hypoglycemia in daily clinical practice. The incidence of adverse reactions of SU was investigated in 2119 Japanese patients who participated in the Drug Event Monitoring project of the Japan Pharmaceutical Association, which was conducted in Kumamoto prefecture. A multiple logistic regression analysis was used to determine the association between the incidence of hypoglycemic symptoms and female sex, with adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). Female sex was found to be significantly associated with hypoglycemic symptoms (female vs. male; OR 2.04; 95% CI 1.22-3.41; p=0.007). The concomitant use of other antihyperglycemic agents (≥2 vs. 0 concomitant drug; OR 2.80; 95% CI 1.17-6.67; p=0.021), a shorter duration of diabetes medication (<3 vs. ≥24months; OR 4.14; 95% CI 1.06-16.14; p=0.041) and a longer follow-up period (OR 1.02; 95% CI 1.00-1.04; p=0.041) were identified as risk factors for hypoglycemia that were specific to females. To the best of our knowledge, this is the first report to focus on female sex as a potential risk factor for SU-associated hypoglycemia. Our results support the importance of individualized therapy, which may be effective not only for reducing the risk of hypoglycemia in females but also the risk of its consequences, such as cardiovascular disease, dementia and increased mortality.

The role of hormonal treatment in type 2 diabetes mellitus

The role of hormonal treatment in type 2 diabetes mellitus Syed Khalid ImamLiaquat National Hospital and Medical College, Karachi, Pakistan; Al-Mouwasat Hospital, Jubail Industrial City, Kingdom of Saudi ArabiaAbstract: Diabetes mellitus (DM) is a disorder of abnormal glucose metabolism resulting primarily from insulin resistance and relative insulin deficiency and characterized by hyperglycemia causing significant short- and long-term complications. Type 2 diabetes mellitus (T2DM) contributes to more than 90% of cases of diabetes. Obesity, sedentary lifestyles, and consumption of very high-caloric meals are thought to be the primary triggering factors causing T2DM in genetically predisposed individuals. Although treatment of hyperglycemia plays a key role in the management, therapies directed at other comorbid conditions, such as dyslipidemia, hypertension, hypercoagulability, obesity, and insulin resistance, have also been a major focus of research and therapy. DM is rising to an epidemic proportion globally, and it is, indeed, one of the most challenging public health problems in the 21st century. According to 2011 statistics, there were approximately 366 million diabetes cases worldwide, and this figure would probably increase to 552 million by 2030. Long-term complications from high blood sugar include coronary artery disease, cerebrovascular events, peripheral arterial diseases leading to amputation, retinopathy, nephropathy leading to end-stage renal disease requiring hemodialysis and transplantation, and neuropathy. The acute complication of T2DM includes drug-induced hypoglycemia, hyperosmolar hyperglycemic state, and although uncommon, ketoacidosis. Diabetes care requires a comprehensive and multidisciplinary approach to delay the progression to acute as well as chronic and debilitating long-term complications. This approach requires the thorough understanding of the pathophysiology of hyperglycemia and impact of various risk factors and comorbidities, careful selection of antihyperglycemic agents, active and frequent participation of diabetes educator, and involvement of multidisciplinary team. The objective of this review is to highlight recent trends in hormonal treatment and to explore new and innovative therapeutic modalities in the management of T2DM.Keywords: diabetes mellitus, hormonal treatment, early insulinization, glycosylated hemoglobin, ketoacidosis, hyperglycemia, hypoglycaemia

Causative anti-diabetic drugs and the underlying clinical factors for hypoglycemia in patients with diabetes.

Recent clinical trials indicated that the intensive glycemic control do not reduce cardiovascular disease mortality among diabetic patients, challenging a significance of the strict glycemic control in diabetes management. Furthermore, retrospective analysis of the Action to Control Cardiovascular Risk in Diabetes study demonstrated a significant association between hypoglycemia and mortality. Here, we systematically reviewed the drug-induced hypoglycemia, and also the underlying clinical factors for hypoglycemia in patients with diabetes. The sulfonylurea use is significantly associated with severe hypoglycemia in patients with type 2 diabetes. The use of biguanide (approximately 45%-76%) and thiazolidinediones (approximately 15%-34%) are also highly associated with the development of severe hypoglycemia. In patients treated with insulin, the intensified insulin therapy is more frequently associated with severe hypoglycemia than the conventional insulin therapy and continuous subcutaneous insulin infusion. Among the underlying clinical factors for development of severe hypoglycemia, low socioeconomic status, aging, longer duration of diabetes, high HbA1c and low body mass index, comorbidities are precipitating factors for severe hypoglycemia. Poor cognitive and mental functions are also associated with severe hypoglycemia.

English

Hypoglycemia is a common, potentially fatal, yet preventable problem. Drug-induced hypoglycemia remains the commonest cause of hypoglycemia. A 63 year old non-diabetic male, a known case of chronic liver disease, on regular medications, presented with unconsciousness, unresponsiveness since two hours. Immediate random blood sugar was 11 mg/dl. On proper history and clinical examination, diagnosis of oral hypoglycemic agent induced hypoglycemic coma was made and immediately intravenous dextrose resuscitation was started. Patient regained consciousness after four hours and became fully oriented after 24 hours. Throughout his hospital course, strict and frequent glucose monitoring was done and dextrose infused accordingly. Patient remained hemodynamically stable throughout the hospital course. He was discharged from the hospital after 72 hours in an otherwise healthy condition. Drug induced hypoglycemia is now so relatively common that virtually every unconscious patient should be considered hypoglycemic until immediate estimation of the blood sugar level rules the condition in or out.

Molecular mechanism of sulphonylurea block of K(ATP) channels carrying mutations that impair ATP inhibition and cause neonatal diabetes.

Sulphonylurea drugs are the therapy of choice for treating neonatal diabetes (ND) caused by mutations in the ATP-sensitive K+ channel (KATP channel). We investigated the interactions between MgATP, MgADP, and the sulphonylurea gliclazide with KATP channels expressed in Xenopus oocytes. In the absence of MgATP, gliclazide block was similar for wild-type channels and those carrying the Kir6.2 ND mutations R210C, G334D, I296L, and V59M. Gliclazide abolished the stimulatory effect of MgATP on all channels. Conversely, high MgATP concentrations reduced the gliclazide concentration, producing a half-maximal block of G334D and R201C channels and suggesting a mutual antagonism between nucleotide and gliclazide binding. The maximal extent of high-affinity gliclazide block of wild-type channels was increased by MgATP, but this effect was smaller for ND channels; channels that were least sensitive to ATP inhibition showed the smallest increase in sulphonylurea block. Consequently, G334D and I296L channels were not fully blocked, even at physiological MgATP concentrations (1 mmol/L). Glibenclamide block was also reduced in β-cells expressing Kir6.2-V59M channels. These data help to explain why patients with some mutations (e.g., G334D, I296L) are insensitive to sulphonylurea therapy, why higher drug concentrations are needed to treat ND than type 2 diabetes, and why patients with severe ND mutations are less prone to drug-induced hypoglycemia.

Awareness is the key to preventing and/or minimizing drug-induced hypoglycaemia

Awareness is the key to preventing and/or minimizing drug-induced hypoglycaemia

Clinical Analysis of 135 Type 2 Diabetes Patients with Severe Drug-Induced Hypoglycemia

Clinical Analysis of 135 Type 2 Diabetes Patients with Severe Drug-Induced Hypoglycemia

Drug-Induced Glucose Alterations Part 1: Drug-Induced Hypoglycemia

Many pharmacological agents commonly used in clinical practice affect glucose homeostasis, interfering with the body's balance between insulin, glucagon, catecholamines, growth hormone, and cortisol. Drug-induced serum glucose alterations manifested as hyperglycemia or hypoglycemia and ranging from mild to moderate to severe symptoms either appearing acutely or chronically, have perpetual effects on the body, particularly in patients with diabetes. This article and a second one that will appear in the next issue of this journal review drug-induced serum glucose alterations in a two-part series. In this article, we review pertinent clinical information on the incidence of drug-induced hypoglycemia and discuss the underlying pathophysiological mechanisms involved. Hypoglycemia is clinically defined as a serum glucose concentration low enough to cause the signs and symptoms differentiated in Table 1.1–4 Depending on the severity, hypoglycemic symptoms include irritability, impaired concentration, neurological deficits, seizures, coma, and even neuronal death.5 However, clinical manifestations vary from individual to individual, and some report hypoglycemic symptoms even when serum glucose levels do not reflect hypoglycemia or vice versa. Although definitions of hypoglycemia differ in the literature, many trials will differentiate between hypoglycemia (asymptomatic and symptomatic low serum glucose levels) and severe hypoglycemia. This article will cover and report both when applicable. The American Diabetes Association (ADA) Workgroup on Hypoglycemia has defined and classified hypoglycemia based on the severity of symptoms in patients diagnosed with diabetes as outlined in Table 2.2 In general, severe hypoglycemia develops when a reduction in blood glucose is enough to require assistance from another person to actively administer carbohydrate, glucagon, or other corrective actions.2 Severe hypoglycemia is a serious clinical syndrome that continues to be the most common endocrine emergency faced by health care providers and remains the limiting factor in effective diabetes management for many patients.6 …

Adverse drug reactions in Germany: direct costs of internal medicine hospitalizations

German hospital reimbursement modalities changed as a result of the introduction of Diagnosis Related Groups (DRG) in 2004. Therefore, no data on the direct costs of adverse drug reactions (ADRs) resulting in admissions to departments of internal medicine are available. The objective was to quantify the ADR-related economic burden (direct costs) of hospitalizations in internal medicine wards in Germany. Record-based study analyzing the patient records of about 57,000 hospitalizations between 2006 and 2007 of the Net of Regional Pharmacovigilance Centers (Germany). All ADRs were evaluated by a team of experts in pharmacovigilance for severity, causality, and preventability. The calculation of accurate person-related costs for ADRs relied on the German DRG system (G-DRG 2009). Descriptive and bootstrap statistical methods were applied for data analysis. The incidence of hospitalization due to at least 'possible' serious outpatient ADRs was estimated to be approximately 3.25%. Mean age of the 1834 patients was 71.0 years (SD 14.7). Most frequent ADRs were gastrointestinal hemorrhage (n = 336) and drug-induced hypoglycemia (n = 270). Average inpatient length-of-stay was 9.3 days (SD 7.1). Average treatment costs of a single ADR were estimated to be approximately €2250. The total costs sum to €434 million per year for Germany. Considering the proportion of preventable cases (20.1%), this equals a saving potential of €87 million per year. Preventing ADRs is advisable in order to realize significant nationwide savings potential. Our cost estimates provide a reliable benchmark as they were calculated based on an intensified ADR surveillance and an accurate person-related cost application.

Drug-Induced Hypoglycaemia

Drugs are the most frequent cause of hypoglycaemia in adults. Although hypoglycaemia is a well known adverse effect of antidiabetic agents, it may occasionally develop in the course of treatment with drugs used in everyday clinical practice, including NSAIDs, analgesics, antibacterials, antimalarials, antiarrhythmics, antidepressants and other miscellaneous agents. They induce hypoglycaemia by stimulating insulin release, reducing insulin clearance or interfering with glucose metabolism. Several drugs may also potentiate the hypoglycaemic effect of antidiabetic agents. Administration of these agents to individuals with diabetes mellitus is of most concern. Many of these drugs, and depending on clinical setting, may also induce hyperglycaemia. Drug-induced hepatotoxicity and nephrotoxicity may lead in certain circumstances to hypoglycaemia. Some drugs may also induce hypoglycaemia by causing pancreatitis. Drug-induced hypoglycaemia is usually mild but may be severe. Effective clinical management can be handled through awareness of this drug-induced adverse effect on blood glucose levels. Herein, we review pertinent clinical information on the incidence of drug-induced hypoglycaemia and discuss the underlying pathophysiological mechanisms, and prevention and management.

Blood glucose test strips: options to reduce usage.

Recent evidence suggests that, despite widespread use, self-monitoring of blood glucose levels has little clinical benefit in many patients with diabetes. The impact of more focused public-payer policies for the use of blood glucose test strips may be substantial. We conducted a cross-sectional analysis of annual prescription claims for test strips between 1997 and 2008 for patients in Ontario aged 65 and older with diabetes. Patients were stratified into 1 of 4 hierarchical groups according to the most intensive glucose-lowering treatment received during each calendar year. Test strip use was calculated annually for each group over the study period, and the effects of 5 hypothetical policy scenarios of more selective test strip use were assessed. Test strip use increased by almost 250% from 1997 to 2008, with 52.6% (n = 263,513) of included patients receiving a prescription during 2008. Almost half of these patients were at low risk for drug-induced hypoglycemia. In 2008, over 117 million test strips were dispensed in Ontario; however, more focused policy scenarios could have reduced this number by between 9.5 million and 74.5 million test strips. Many people who self-monitor their blood glucose are at relatively low risk for drug-induced hypoglycemia. The economic benefits associated with more selective testing could be redirected to more effective interventions for patients with diabetes.

An Unusual Outbreak of Hypoglycemia — A Correction

To the Editor: In our letter to the Editor (Feb. 12 issue),1 we reported on 150 nondiabetic patients with drug-induced hypoglycemia due to four brands of sexual-enhancement drugs that were contaminated with glyburide. Two recent articles by some of the authors of our letter have appeared elsewhere. One article described the neuroglycopenic and adrenergic symptoms of severe hypoglycemia in 15 of these patients,2 and the other described findings indicative of hypoglycemia on brain magnetic resonance imaging in 7 of these patients3; there were overlaps between these two groups of patients. The cases of hypoglycemia reported in both articles pertained . . .

Hyperinsulinisme de l'enfant et de l'adolescent: quand la détermination de la concentration en insuline n'est pas toujours suffisante (version française)

Hypoglycemia in infants and children can lead to seizures, developmental delay, and permanent brain damage. Hyperinsulinism (HI) is the most common cause of both transient and permanent disorders of hypoglycemia. HI is characterized by dysregulated insulin secretion, which results in persistent mild to severe hypoglycemia. The various forms of HI represent a group of clinically, genetically, and morphologically heterogeneous disorders. Congenital hyperinsulinism is associated with mutations of SUR-1 and Kir6.2, glucokinase, glutamate dehydrogenase, short-chain 3-hydroxyacyl-CoA dehydrogenase, and ectopic expression on beta-cell plasma membrane of SLC16A1. Hyperinsulinism can be associated with perinatal stress such as birth asphyxia, maternal toxemia, prematurity, or intrauterine growth retardation, resulting in prolonged neonatal hypoglycemia. Mimickers of hyperinsulinism include neonatal panhypopituitarism, drug-induced hypoglycemia, insulinoma, antiinsulin and insulin-receptor stimulating antibodies, Beckwith-Wiedemann Syndrome, and congenital disorders of glycosylation. Laboratory testing for hyperinsulinism may include quantification of blood glucose, plasma insulin, plasma beta-hydroxybutyrate, plasma fatty acids, plasma ammonia, plasma acylcarnitine profile, and urine organic acids. Genetic testing is available through commercial laboratories for genes known to be associated with hyperinsulinism. Acute insulin response (AIR) tests are useful in phenotypic characterization. Imaging and histologic tools are also available for diagnosing and classifying hyperinsulinism. The goal of treatment in infants with hyperinsulinism is to prevent brain damage from hypoglycemia by maintaining plasma glucose levels above 700 mg/L (70 mg/dL) through pharmacologic or surgical therapy. The management of hyperinsulinism requires a multidisciplinary approach that includes pediatric endocrinologists, radiologists, surgeons, and pathologists who are trained in diagnosing, identifying, and treating hyperinsulinism.

Drug-Induced Hypoglycemia: A Systematic Review

Drug-induced hypoglycemia is a significant adverse effect that may cause important morbidity. The aim of the study was to systematically review the literature for drugs reported to cause hypoglycemia and assess the quality of evidence and strength of association supporting this causal link. We searched electronic databases (MEDLINE, EMBASE, Web of Science, and SCOPUS) and the drug information system Micromedex through November 2007 and sought additional references from experts. Studies were eligible if they reported hypoglycemia as a side effect of a drug not used to treat hyperglycemia, regardless of their design, language, size, or follow-up duration. We excluded hypoglycemia caused by industrial exposures, nonpharmacological chemical exposures, alcohol, herbs, nutritional supplements, and in vitro and animal studies. Reviewers extracted study characteristics and methodological quality and, when possible, data to estimate the odds of developing hypoglycemia when exposed to the offending agent. We found 448 eligible studies that described 2696 cases of hypoglycemia associated with 164 different drugs. The quality of evidence supporting associations between drugs and hypoglycemia was mostly very low due to methodological limitations and imprecision. The most commonly reported offending drugs were quinolones, pentamidine, quinine, beta blockers, angiotensin-converting enzyme agents, and IGF. Very low quality evidence substantiates the association between hypoglycemia and the use of numerous nondiabetic drugs.

Hiperinsulinismo na infância: quando apenas uma dosagem de insulina não é suficiente

INTRODUCAO: A hipoglicemia em bebes e criancas pode causar convulsoes, atraso de desenvolvimento e dano cerebral permanente. O hiperinsulinismo (HI) e a causa mais comum de hipoglicemia, seja transitoria ou permanente. A HI e caracterizada pela secrecao inadequada de insulina, o que resulta em hipoglicemia persistente, de leve a grave. As diferentes formas de HI representam um grupo de doencas clinica, genetica e morfologicamente heterogeneo. CONTEUDO: Hiperinsulinismo congenito esta associado as mutacoes de SUR-1 e Kir6.2, glucoquinase, glutamato desidrogenase, 3-hidroxiacil-CoA desidrogenase de cadeia curta e expressao ectopica de SLC16A1 na membrana plasmatica das celulas beta. O HI pode estar associado ao estresse perinatal, como asfixia do nascimento, toxemia materna, prematuridade ou retardo do crescimento intra-uterino, resultando em hipoglicemia neonatal prolongada. Mimetismo de HI neonatal inclui pan-hipopituitarismo, hipoglicemia induzida por farmaco, insulinoma, anticorpos antiinsulina e estimuladores do receptor de insulina, sindrome de Beckwith-Wiedemann e disturbios congenitos de glicosilacao. Exames laboratoriais para HI podem incluir quantificacao de glicose, insulina, β-hidroxibutirato, acidos graxos, amonia e perfil de acilcarnitinas plasmaticos, alem de acidos orgânicos urinarios. Os exames geneticos estao disponiveis em laboratorios comerciais para os genes sabidamente associados a hiperinsulinemia. Testes de resposta insulinica aguda (RIA) sao uteis na caracterizacao fenotipica. Exames de imagem e histologicos tambem estao disponiveis para diagnosticar e classificar o HI. O objetivo do tratamento de criancas com HI e prevenir os danos cerebrais da hipoglicemia, mantendo niveis de glicose plasmatica acima de 70mg/dl por terapia farmacologica ou cirurgica. CONCLUSAO:A terapeutica do HI requer abordagem multidisciplinar que inclui endocrinologistas pediatricos, radiologistas, cirurgioes e patologistas, os quais sao treinados para diagnosticar, identificar e tratar o hiperinsulinismo.

Hyperinsulinism in Infancy and Childhood: When an Insulin Level Is Not Always Enough

Hypoglycemia in infants and children can lead to seizures, developmental delay, and permanent brain damage. Hyperinsulinism (HI) is the most common cause of both transient and permanent disorders of hypoglycemia. HI is characterized by dysregulated insulin secretion, which results in persistent mild to severe hypoglycemia. The various forms of HI represent a group of clinically, genetically, and morphologically heterogeneous disorders. Congenital hyperinsulinism is associated with mutations of SUR-1 and Kir6.2, glucokinase, glutamate dehydrogenase, short-chain 3-hydroxyacyl-CoA dehydrogenase, and ectopic expression on beta-cell plasma membrane of SLC16A1. Hyperinsulinism can be associated with perinatal stress such as birth asphyxia, maternal toxemia, prematurity, or intrauterine growth retardation, resulting in prolonged neonatal hypoglycemia. Mimickers of hyperinsulinism include neonatal panhypopituitarism, drug-induced hypoglycemia, insulinoma, antiinsulin and insulin-receptor stimulating antibodies, Beckwith-Wiedemann Syndrome, and congenital disorders of glycosylation. Laboratory testing for hyperinsulinism may include quantification of blood glucose, plasma insulin, plasma beta-hydroxybutyrate, plasma fatty acids, plasma ammonia, plasma acylcarnitine profile, and urine organic acids. Genetic testing is available through commercial laboratories for genes known to be associated with hyperinsulinism. Acute insulin response (AIR) tests are useful in phenotypic characterization. Imaging and histologic tools are also available for diagnosing and classifying hyperinsulinism. The goal of treatment in infants with hyperinsulinism is to prevent brain damage from hypoglycemia by maintaining plasma glucose levels above 700 mg/L (70 mg/dL) through pharmacologic or surgical therapy. The management of hyperinsulinism requires a multidisciplinary approach that includes pediatric endocrinologists, radiologists, surgeons, and pathologists who are trained in diagnosing, identifying, and treating hyperinsulinism.

Drug-Induced Hypoglycemia in 50 Patients with Type 2 Diabetes Mellitus Necessitating Emergency Treatment

Drug-Induced Hypoglycemia in 50 Patients with Type 2 Diabetes Mellitus Necessitating Emergency Treatment

A Novel Solution to a Case of Occult Drug-Induced Hypoglycemia

A Novel Solution to a Case of Occult Drug-Induced Hypoglycemia

Automated Surveillance for Adverse Drug Events at a Community Hospital and an Academic Medical Center

To compare the rates and nature of ADEs at an academic medical center and a community hospital using a single computerized ADE surveillance system. Prospective cohort study of patients admitted to two tertiary care hospitals. Outcome Measure Adverse drug events identified by automated surveillance and voluntary reporting. We implemented an automated surveillance system across an academic medical center and a community hospital. Potential events identified by the computer were reviewed in detail by medication safety pharmacists and scored for causality and severity. Findings were compared between the two hospitals, and with voluntary reports from nurses and pharmacists. Over the 8 month study period, 25,177 patients were admitted to the university hospital and 8,029 to the community hospital. There were 1,116 ADEs in 900 patients at the university hospital for an overall rate of 4.4 ADEs per 100 admissions. At the community hospital, 399 patients experienced 501 ADEs for a rate of 6.2 events per 100 admissions. Rates of antibiotic-associated colitis, drug-induced hypoglycemia, and anticoagulation-related ADEs were significantly higher at the community hospital compared with the university hospital. Computerized surveillance detected ADEs at a rate 3.6 times that of voluntary reporting at the university hospital and 12.3 times that at the community hospital. Operation of a common automated ADE surveillance system across hospitals permits meaningful comparison of ADE rates in different inpatient settings. Automated surveillance detects ADEs at rates far higher than voluntary reporting, and the difference may be greater in the community hospital setting. Community hospitals may experience higher rates of certain types of ADEs compared with academic medical centers.