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The Lancet. Diabetes & Endocrinology Mar 2021Hyperglycaemia in people with and without diabetes admitted to the hospital is associated with a substantial increase in morbidity, mortality, and health-care costs.... (Review)
Review
Hyperglycaemia in people with and without diabetes admitted to the hospital is associated with a substantial increase in morbidity, mortality, and health-care costs. Professional societies have recommended insulin therapy as the cornerstone of inpatient pharmacological management. Intravenous insulin therapy is the treatment of choice in the critical care setting. In non-intensive care settings, several insulin protocols have been proposed to manage patients with hyperglycaemia; however, meta-analyses comparing different treatment regimens have not clearly endorsed the benefits of any particular strategy. Clinical guidelines recommend stopping oral antidiabetes drugs during hospitalisation; however, in some countries continuation of oral antidiabetes drugs is commonplace in some patients with type 2 diabetes admitted to hospital, and findings from clinical trials have suggested that non-insulin drugs, alone or in combination with basal insulin, can be used to achieve appropriate glycaemic control in selected populations. Advances in diabetes technology are revolutionising day-to-day diabetes care and work is ongoing to implement these technologies (ie, continuous glucose monitoring, automated insulin delivery) for inpatient care. Additionally, transformations in care have occurred during the COVID-19 pandemic, including the use of remote inpatient diabetes management-research is needed to assess the effects of such adaptations.
Topics: Blood Glucose; COVID-19; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Management; Hospitalization; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin
PubMed: 33515493
DOI: 10.1016/S2213-8587(20)30381-8 -
Cleveland Clinic Journal of Medicine Apr 2022Hyperglycemia is associated with poor clinical outcomes in critically ill patients. Initial clinical trials of intensive insulin therapy targeting blood glucose levels... (Review)
Review
Hyperglycemia is associated with poor clinical outcomes in critically ill patients. Initial clinical trials of intensive insulin therapy targeting blood glucose levels of 80 to 110 mg/dL showed improved outcomes, but subsequent trials found no benefits and even increased harm with this approach. Emerging literature has evaluated other glycemic indices including time-in-target blood glucose range, glycemic variability, and stress hyperglycemia ratio. These indices, while well described in observational studies, have not been addressed in the initial trials. Additionally, the patient's pre existing diabetes status and preadmission diabetic control may modulate the outcomes of stringent glycemic control, with worse outcomes of hyperglycemia being observed in patients without diabetes and in those with well-controlled diabetes. Most medical societies recommend less stringent glucose control in the range of 140 to 180 mg/dL for critically ill patients.
Topics: Blood Glucose; Critical Illness; Diabetes Mellitus; Glycemic Control; Humans; Hyperglycemia
PubMed: 35365557
DOI: 10.3949/ccjm.89a.20171 -
Diabetologia Sep 2023Diabetes is associated with excess morbidity and mortality due to both micro- and macrovascular complications, as well as a range of non-classical comorbidities.... (Review)
Review
Diabetes is associated with excess morbidity and mortality due to both micro- and macrovascular complications, as well as a range of non-classical comorbidities. Diabetes-associated microvascular complications are those considered most closely related to hyperglycaemia in a causal manner. However, some individuals with hyperglycaemia (even those with severe hyperglycaemia) do not develop microvascular diseases, which, together with evidence of co-occurrence of microvascular diseases in families, suggests a role for genetics. While genome-wide association studies (GWASs) produced firm evidence of multiple genetic variants underlying differential susceptibility to type 1 and type 2 diabetes, genetic determinants of microvascular complications are mostly suggestive. Identified susceptibility variants of diabetic kidney disease (DKD) in type 2 diabetes mirror variants underlying chronic kidney disease (CKD) in individuals without diabetes. As for retinopathy and neuropathy, reported risk variants currently lack large-scale replication. The reported associations between type 2 diabetes risk variants and microvascular complications may be explained by hyperglycaemia. More extensive phenotyping, along with adjustments for unmeasured confounding, including both early (fetal) and late-life (hyperglycaemia, hypertension, etc.) environmental factors, are urgently needed to understand the genetics of microvascular complications. Finally, genetic variants associated with reduced glycolysis, mitochondrial dysfunction and DNA damage and sustained cell regeneration may protect against microvascular complications, illustrating the utility of studies in individuals who have escaped these complications.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Genome-Wide Association Study; Diabetic Nephropathies; Hyperglycemia; Risk Factors
PubMed: 37452207
DOI: 10.1007/s00125-023-05964-x -
Journal of Food and Drug Analysis Mar 2021The major goals in the management of diabetes are to maintain optimum control of high blood glucose level or hyperglycemia. Dietary modification is one of the most... (Review)
Review
The major goals in the management of diabetes are to maintain optimum control of high blood glucose level or hyperglycemia. Dietary modification is one of the most recommended treatment modalities for diabetic patients. The use of foods sweetened with sugar alcohols (also known as polyols) such as xylitol, sorbitol, mannitol, maltitol, lactitol, isomalt and erythritol has brought an escalating interest in the recent years since some sugar alcohols do not rise plasma glucose, as they are partially digested and metabolised. Diet composition and adequacy may be altered by replacing carbohydrates with sugar alcohols. It has been established that these polyols are appropriate sugar substitutes for a healthy lifestyle and diabetic foods. The present review focuses on the evidence supporting the use of sugar alcohols in the management of diabetes, by evaluating their physical and chemical properties, metabolism, absorption, glycemic and insulinemic responses. Although documentation on the glycaemic and insulinemic response of polyols is evident that these compounds have beneficial effects on the better management of hyperglycemia, the possible side effects associated with their normal or higher dosages warned their use according to the relevant Food & Drug Administration guidelines. For the same reason, future studies should also focus on the possible toxicity and side effects associated with the consumption of sugar alcohols in order to define their safety.
Topics: Blood Glucose; Diabetes Mellitus; Humans; Hyperglycemia; Hypoglycemic Agents; Sugar Alcohols
PubMed: 35696228
DOI: 10.38212/2224-6614.3107 -
Cardiovascular Diabetology Sep 2023Diabetes mellitus is a metabolic disease characterized by long-term hyperglycaemia, which leads to microangiopathy and macroangiopathy and ultimately increases the... (Review)
Review
Diabetes mellitus is a metabolic disease characterized by long-term hyperglycaemia, which leads to microangiopathy and macroangiopathy and ultimately increases the mortality of diabetic patients. Endothelial dysfunction, which has been recognized as a key factor in the pathogenesis of diabetic microangiopathy and macroangiopathy, is characterized by a reduction in NO bioavailability. Oxidative stress, which is the main pathogenic factor in diabetes, is one of the major triggers of endothelial dysfunction through the reduction in NO. In this review, we summarize the four sources of ROS in the diabetic vasculature and the underlying molecular mechanisms by which the pathogenic factors hyperglycaemia, hyperlipidaemia, adipokines and insulin resistance induce oxidative stress in endothelial cells in the context of diabetes. In addition, we discuss oxidative stress-targeted interventions, including hypoglycaemic drugs, antioxidants and lifestyle interventions, and their effects on diabetes-induced endothelial dysfunction. In summary, our review provides comprehensive insight into the roles of oxidative stress in diabetes-induced endothelial dysfunction.
Topics: Humans; Endothelial Cells; Vascular Diseases; Diabetes Mellitus; Hyperglycemia; Oxidative Stress
PubMed: 37660030
DOI: 10.1186/s12933-023-01965-7 -
Physiological Research Dec 2020Heterozygous inactivating mutations of the glucokinase (GCK) gene are causing GCK-MODY, one of the most common forms of the Maturity Onset Diabetes of the Young (MODY).... (Review)
Review
Heterozygous inactivating mutations of the glucokinase (GCK) gene are causing GCK-MODY, one of the most common forms of the Maturity Onset Diabetes of the Young (MODY). GCK-MODY is characterized by fasting hyperglycemia without apparent worsening with aging and low risk for chronic vascular complications. Despite the mild clinical course, GCK-MODY could be misdiagnosed as type 1 or type 2 diabetes. In the diagnostic process, the clinical suspicion is often based on the clinical diagnostic criteria for GCK-MODY and should be confirmed by DNA analysis. However, there are several issues in the clinical and also in genetic part that could complicate the diagnostic process. Most of the people with GCK-MODY do not require any pharmacotherapy. The exception are pregnant women with a fetus which did not inherit GCK mutation from the mother. Such a child has accelerated growth, and has increased risk for diabetic foetopathy. In this situation the mother should be treated with substitutional doses of insulin. Therefore, distinguishing GCK-MODY from gestational diabetes in pregnancy is very important. For this purpose, special clinical diagnostic criteria for clinical identification of GCK-MODY in pregnancy are used. This review updates information on GCK-MODY and discusses several currently not solved problems in the clinical diagnostic process, genetics, and treatment of this type of monogenic diabetes.
Topics: Diabetes Mellitus, Type 2; Female; Glucokinase; Heterozygote; Humans; Hyperglycemia; Mutation; Pregnancy
PubMed: 33129248
DOI: 10.33549/physiolres.934487 -
The Journal of Clinical Endocrinology... Mar 2023Graves orbitopathy (GO) or thyroid eye disease is a potentially sight-threatening and disfiguring autoimmune disease. Teprotumumab is a monoclonal antibody against the... (Observational Study)
Observational Study
CONTEXT
Graves orbitopathy (GO) or thyroid eye disease is a potentially sight-threatening and disfiguring autoimmune disease. Teprotumumab is a monoclonal antibody against the insulin-like growth factor-I receptor that was recently approved for GO treatment. Hyperglycemia is a recognized adverse event of teprotumumab, occurring in 10% of patients in 2 recent randomized controlled trials.
OBJECTIVE
Our study aimed to report the incidence, severity, management, and longitudinal glycemic changes in patients treated with teprotumumab in an academic practice cohort.
METHODS
This longitudinal, observational study included all consecutive patients treated with teprotumumab between March 2020 and May 2022 at 1 institution. Hemoglobin A1c (HbA1c) was measured every 3 months.
RESULTS
Forty-two patients with baseline normoglycemia (n = 22), prediabetes (n = 10), and diabetes (n = 10) were followed for a mean of 47.5 weeks. Overall, HbA1c increased by 0.5% at 3 months. Least-squares mean changes in HbA1c at 3 months were 1.3 (P < .001), 0.7 (P = .01), and 0.1 (P = .41) in patients with diabetes, prediabetes, and normoglycemia, respectively. Twenty-two patients (52%) had hyperglycemia, which was graded as mild, moderate, and life-threatening in 55% (12/22), 41% (9/22), and 5% (1/22) of cases, respectively. Age, pre-existing diabetes, and Hispanic and Asian race/ethnicity were significant risk factors for hyperglycemia. Among patients with hyperglycemia, 36.4% (8/22) returned to baseline glycemic status at last follow-up.
CONCLUSION
While effective, teprotumumab carries a significant risk of hyperglycemia, especially in patients with diabetes. Hyperglycemia may persist after stopping teprotumumab. These findings underscore the importance of guidelines for screening and management of teprotumumab-related hyperglycemia.
Topics: Humans; Graves Ophthalmopathy; Glycated Hemoglobin; Prediabetic State; Hyperglycemia
PubMed: 36300333
DOI: 10.1210/clinem/dgac627 -
Science Immunology Apr 2023The relationship between diabetes and coronavirus disease 2019 (COVID-19) is bidirectional: Although individuals with diabetes and high blood glucose (hyperglycemia) are...
The relationship between diabetes and coronavirus disease 2019 (COVID-19) is bidirectional: Although individuals with diabetes and high blood glucose (hyperglycemia) are predisposed to severe COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can also cause hyperglycemia and exacerbate underlying metabolic syndrome. Therefore, interventions capable of breaking the network of SARS-CoV-2 infection, hyperglycemia, and hyperinflammation, all factors that drive COVID-19 pathophysiology, are urgently needed. Here, we show that genetic ablation or pharmacological inhibition of mitochondrial pyruvate carrier (MPC) attenuates severe disease after influenza or SARS-CoV-2 pneumonia. MPC inhibition using a second-generation insulin sensitizer, MSDC-0602K (MSDC), dampened pulmonary inflammation and promoted lung recovery while concurrently reducing blood glucose levels and hyperlipidemia after viral pneumonia in obese mice. Mechanistically, MPC inhibition enhanced mitochondrial fitness and destabilized hypoxia-inducible factor-1α, leading to dampened virus-induced inflammatory responses in both murine and human lung macrophages. We further showed that MSDC enhanced responses to nirmatrelvir (the antiviral component of Paxlovid) to provide high levels of protection against severe host disease development after SARS-CoV-2 infection and suppressed cellular inflammation in human COVID-19 lung autopsies, demonstrating its translational potential for treating severe COVID-19. Collectively, we uncover a metabolic pathway that simultaneously modulates pulmonary inflammation, tissue recovery, and host metabolic health, presenting a synergistic therapeutic strategy to treat severe COVID-19, particularly in patients with underlying metabolic disease.
Topics: Humans; Animals; Mice; COVID-19; Monocarboxylic Acid Transporters; SARS-CoV-2; Blood Glucose; Hyperglycemia; Diabetes Mellitus
PubMed: 36821695
DOI: 10.1126/sciimmunol.adf0348 -
Diabetes & Vascular Disease Research 2022The goal of this study was to analyze the effect of COVID-19 drugs and biologicals on hyperglycemia. A literature search with key terms, such as "COVID-19 drugs and...
The goal of this study was to analyze the effect of COVID-19 drugs and biologicals on hyperglycemia. A literature search with key terms, such as "COVID-19 drugs and hyperglycemia" and "COVID-19 vaccines and hyperglycemia," was conducted using PubMed through September 2021. The CDC data were referenced for current COVID-19 profile and statistics. The NIH COVID-19 guidelines were referenced for updated treatment recommendations. Micromedex and UpToDate were used for drug and disease information. Current results suggested that corticosteroids (dexamethasone), remdesivir and antivirals (lopinavir and ritonavir) all have the potential to significantly raise blood glucose levels putting patients at elevated risk for severe complications. In contrary, hydroxychloroquine is associated with hypoglycemia, and tocilizumab decreases inflammation which is associated with improving glucose levels. Other anti-cytokine bioactive molecules are correlated with lower blood glucose in patients with and without diabetes mellitus. Ivermectin, used for mild COVID-19 disease, possesses the potential for lowering blood glucose. Covishield, Pfizer-BioNTech, and Moderna have all been associated with hyperglycemia after the first dose. Individualized /personalized patient care is required for diabetic mellitus patients with COVID-19 infection. Improper drug therapy aggravates hyperglycemic conditions and other comorbid conditions, leading to increased morbidity and mortality.
Topics: Blood Glucose; COVID-19; COVID-19 Vaccines; ChAdOx1 nCoV-19; Diabetes Mellitus; Humans; Hyperglycemia; SARS-CoV-2
PubMed: 35695412
DOI: 10.1177/14791641221095091 -
The Lancet. Child & Adolescent Health Apr 2021Hyperglycaemia and hypoglycaemia are common in preterm infants and have been associated with increased risk of mortality and morbidity. Interventions to reduce risk... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Hyperglycaemia and hypoglycaemia are common in preterm infants and have been associated with increased risk of mortality and morbidity. Interventions to reduce risk associated with these exposures are particularly challenging due to the infrequent measurement of blood glucose concentrations, with the potential of causing more harm instead of improving outcomes for these infants. Continuous glucose monitoring (CGM) is widely used in adults and children with diabetes to improve glucose control, but has not been approved for use in neonates. The REACT trial aimed to evaluate the efficacy and safety of CGM in preterm infants requiring intensive care.
METHODS
This international, open-label, randomised controlled trial was done in 13 neonatal intensive care units in the UK, Spain, and the Netherlands. Infants were included if they were within 24 h of birth, had a birthweight of 1200 g or less, had a gestational age up to 33 weeks plus 6 days, and had parental written informed consent. Infants were randomly assigned (1:1) to real-time CGM or standard care (with masked CGM for comparison) using a central web randomisation system, stratified by recruiting centre and gestational age (<26 or ≥26 weeks). The primary efficacy outcome was the proportion of time sensor glucose concentration was 2·6-10 mmol/L for the first week of life. Safety outcomes related to hypoglycaemia (glucose concentrations <2·6 mmol/L) in the first 7 days of life. All outcomes were assessed on the basis of intention to treat in the full analysis set with available data. The study is registered with the International Standard Randomised Control Trials Registry, ISRCTN12793535.
FINDINGS
Between July 4, 2016, and Jan 27, 2019, 182 infants were enrolled, 180 of whom were randomly assigned (85 to real-time CGM, 95 to standard care). 70 infants in the real-time CGM intervention group and 85 in the standard care group had CGM data and were included in the primary analysis. Compared with infants in the standard care group, infants managed using CGM had more time in the 2·6-10 mmol/L glucose concentration target range (mean proportion of time 84% [SD 22] vs 94% [11]; adjusted mean difference 8·9% [95% CI 3·4-14·4]), equivalent to 13 h (95% CI 5-21). More infants in the standard care group were exposed to at least one episode of sensor glucose concentration of less than 2·6 mmol/L for more than 1 h than those in the intervention group (13 [15%] of 85 vs four [6%] of 70). There were no serious adverse events related to the use of the device or episodes of infection.
INTERPRETATION
Real-time CGM can reduce exposure to prolonged or severe hyperglycaemia and hypoglycaemia. Further studies using CGM are required to determine optimal glucose targets, strategies to obtain them, and the potential effect on long-term health outcomes.
FUNDING
National Institute for Health Research Efficacy and Mechanisms Evaluation Programme.
Topics: Blood Glucose; Female; Glucose; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Infant, Extremely Premature; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Insulin; Intensive Care Units, Neonatal; Male; Monitoring, Physiologic; Netherlands; Spain; Time Factors; United Kingdom
PubMed: 33577770
DOI: 10.1016/S2352-4642(20)30367-9