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The Medical Clinics of North America May 2017Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are the most serious and life-threatening hyperglycemic emergencies in diabetes. DKA is more... (Review)
Review
Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are the most serious and life-threatening hyperglycemic emergencies in diabetes. DKA is more common in young people with type 1 diabetes and HHS in adult and elderly patients with type 2 diabetes. Features of the 2 disorders with ketoacidosis and hyperosmolality may coexist. Both are characterized by insulinopenia and severe hyperglycemia. Early diagnosis and management are paramount. Treatment is aggressive rehydration, insulin therapy, electrolyte replacement, and treatment of underlying precipitating events. This article reviews the epidemiology, pathogenesis, diagnosis, and management of hyperglycemic emergencies.
Topics: Bicarbonates; Diabetes Complications; Diabetic Ketoacidosis; Emergencies; Fluid Therapy; Hospital Mortality; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; Hypoglycemic Agents; Inflammation; Insulin; Oxidative Stress; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 28372715
DOI: 10.1016/j.mcna.2016.12.011 -
Current Diabetes Reports May 2017Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are diabetic emergencies that cause high morbidity and mortality. Their treatment differs in the... (Review)
Review
PURPOSE OF REVIEW
Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are diabetic emergencies that cause high morbidity and mortality. Their treatment differs in the UK and USA. This review delineates the differences in diagnosis and treatment between the two countries.
RECENT FINDINGS
Large-scale studies to determine optimal management of DKA and HHS are lacking. The diagnosis of DKA is based on disease severity in the USA, which differs from the UK. The diagnosis of HHS in the USA is based on total rather than effective osmolality. Unlike the USA, the UK has separate guidelines for DKA and HHS. Treatment of DKA and HHS also differs with respect to timing of fluid and insulin initiation. There is considerable overlap but important differences between the UK and USA guidelines for the management of DKA and HHS. Further research needs to be done to delineate a unifying diagnostic and treatment protocol.
Topics: Diabetic Ketoacidosis; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; United Kingdom; United States
PubMed: 28364357
DOI: 10.1007/s11892-017-0857-4 -
American Family Physician Dec 2017Hyperosmolar hyperglycemic state is a life-threatening emergency manifested by marked elevation of blood glucose and hyperosmolarity with little or no ketosis. Although...
Hyperosmolar hyperglycemic state is a life-threatening emergency manifested by marked elevation of blood glucose and hyperosmolarity with little or no ketosis. Although there are multiple precipitating causes, underlying infections are the most common. Other causes include certain medications, nonadherence to therapy, undiagnosed diabetes mellitus, substance abuse, and coexisting disease. In children and adolescents, hyperosmolar hyperglycemic state is often present when type 2 diabetes is diagnosed. Physical findings include profound dehydration and neurologic symptoms ranging from lethargy to coma. Treatment begins with intensive monitoring of the patient and laboratory values, especially glucose, sodium, and potassium levels. Vigorous correction of dehydration is critical, requiring an average of 9 L of 0.9% saline over 48 hours in adults. After urine output is established, potassium replacement should begin. Once dehydration is partially corrected, adults should receive an initial bolus of 0.1 units of intravenous insulin per kg of body weight, followed by a continuous infusion of 0.1 units per kg per hour (or a continuous infusion of 0.14 units per kg per hour without an initial bolus) until the blood glucose level decreases below 300 mg per dL. In children and adolescents, dehydration should be corrected at a rate of no more than 3 mOsm per hour to avoid cerebral edema. Identification and treatment of underlying and precipitating causes are necessary.
Topics: Adolescent; Adult; Blood Glucose; Child; Dehydration; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Fluid Therapy; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; Hypoglycemic Agents; Insulin; Potassium; Sodium
PubMed: 29431405
DOI: No ID Found -
Philosophical Transactions of the Royal... Jan 2018Best known as chaperones, heat shock proteins (HSPs) also have roles in cell signalling and regulation of metabolism. Rodent studies demonstrate that heat treatment,... (Review)
Review
Best known as chaperones, heat shock proteins (HSPs) also have roles in cell signalling and regulation of metabolism. Rodent studies demonstrate that heat treatment, transgenic overexpression and pharmacological induction of HSP72 prevent high-fat diet-induced glucose intolerance and skeletal muscle insulin resistance. Overexpression of skeletal muscle HSP72 in mice has been shown to increase endurance running capacity nearly twofold and increase mitochondrial content by 50%. A positive correlation between HSP72 mRNA expression and mitochondrial enzyme activity has been observed in human skeletal muscle, and HSP72 expression is markedly decreased in skeletal muscle of insulin resistant and type 2 diabetic patients. In addition, decreased levels of HSP72 correlate with insulin resistance and non-alcoholic fatty liver disease progression in livers from obese patients. These data suggest the targeted induction of HSPs could be a therapeutic approach for preventing metabolic disease by maintaining the body's natural stress response. Exercise elicits a number of metabolic adaptations and is a powerful tool in the prevention and treatment of insulin resistance. Exercise training is also a stimulus for increased HSP expression. Although the underlying mechanism(s) for exercise-induced HSP expression are currently unknown, the HSP response may be critical for the beneficial metabolic effects of exercise. Exercise-induced extracellular HSP release may also contribute to metabolic homeostasis by actively restoring HSP72 content in insulin resistant tissues containing low endogenous levels of HSPs.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.
Topics: Animals; Exercise; Heat-Shock Proteins; Humans; Insulin Resistance; Mice; Physical Conditioning, Animal; Rats
PubMed: 29203714
DOI: 10.1098/rstb.2016.0529 -
Revue Medicale de Liege Feb 2014Hypoglycaemic episodes are rather common among diabetic patients, especially those treated with sulfonylureas or insulin (more in type 1 than in type 2 diabetes). The...
Hypoglycaemic episodes are rather common among diabetic patients, especially those treated with sulfonylureas or insulin (more in type 1 than in type 2 diabetes). The presentation of hypoglycaemia may considerably vary from patient-to-patient and from time-to-time in a given patient. With the illustration of a clinical case, we will describe the characteristics of the three main types of hypoglycaemia: severe hypoglycaemia (with or without coma), symptomatic hypoglycaemia (with or without confirmation) and asymptomatic hypoglycaemia ("hypoglycaemia unawareness") discovered as a low blood glucose measurement. We will also briefly analyse the reasons of such differences and the potential clinical consequences that these three main types of hypoglycaemia may exert in the real life of diabetic patients.
Topics: Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents
PubMed: 24683833
DOI: No ID Found -
Nature Communications Dec 2022A high-fat diet increases the risk of insulin resistance, type-2 diabetes, and non-alcoholic steato-hepatitis. Here we identified two heat-shock proteins,...
A high-fat diet increases the risk of insulin resistance, type-2 diabetes, and non-alcoholic steato-hepatitis. Here we identified two heat-shock proteins, Heat-Shock-Protein70 and Glucose-Regulated Protein78, which are increased in the jejunum of rats on a high-fat diet. We demonstrated a causal link between these proteins and hepatic and whole-body insulin-resistance, as well as the metabolic response to bariatric/metabolic surgery. Long-term continuous infusion of Heat-Shock-Protein70 and Glucose-Regulated Protein78 caused insulin-resistance, hyperglycemia, and non-alcoholic steato-hepatitis in rats on a chow diet, while in rats on a high-fat diet continuous infusion of monoclonal antibodies reversed these phenotypes, mimicking metabolic surgery. Infusion of these proteins or their antibodies was also associated with shifts in fecal microbiota composition. Serum levels of Heat-Shock-Protein70 and Glucose-Regulated Protein78were elevated in patients with non-alcoholic steato-hepatitis, but decreased following metabolic surgery. Understanding the intestinal regulation of metabolism may provide options to reverse metabolic diseases.
Topics: Rats; Animals; Insulin Resistance; Endoplasmic Reticulum Chaperone BiP; Heat-Shock Proteins; Insulin; Non-alcoholic Fatty Liver Disease; Diet, High-Fat; HSP70 Heat-Shock Proteins; Liver; Hyperglycemia; Glucose; Hepatitis
PubMed: 36513656
DOI: 10.1038/s41467-022-35310-5 -
Trends in Pharmacological Sciences Mar 2012Dysfunctional insulin and insulin-like growth factor-I (IGF-I) signaling contributes to the pathological progression of diabetes, diabetic peripheral neuropathy (DPN),... (Review)
Review
Dysfunctional insulin and insulin-like growth factor-I (IGF-I) signaling contributes to the pathological progression of diabetes, diabetic peripheral neuropathy (DPN), Alzheimer's (AD), Parkinson's (PD) and Huntington's diseases (HD). Despite their prevalence, there are limited therapeutic options available for the treatment of these neurodegenerative disorders. Therefore, establishing a link between insulin/IGF-I and the pathoetiology of these diseases may provide alternative approaches toward their management. Many of the heat shock proteins (Hsps) are well-known molecular chaperones that solubilize and clear damaged proteins and protein aggregates. Recent studies suggest that modulating Hsps may represent a promising therapeutic avenue for improving insulin and IGF-I signaling. Pharmacological induction of the heat shock response (HSR) may intersect with insulin/IGF-I signaling to improve aspects of neurodegenerative phenotypes. Herein, we review the intersection between Hsps and the insulin/IGF systems under normal and pathological conditions. The discussion will emphasize the potential of non-toxic HSR inducers as viable therapeutic agents.
Topics: Animals; Heat-Shock Proteins; Heat-Shock Response; Humans; Insulin; Insulin-Like Growth Factor I; Neurodegenerative Diseases
PubMed: 22172248
DOI: 10.1016/j.tips.2011.11.001 -
Cell Stress & Chaperones Jan 2023Excess nutrient flux into the cellular energy system results in a scenario of cellular metabolic stress in diseases involving insulin resistance, such as type 2... (Review)
Review
Excess nutrient flux into the cellular energy system results in a scenario of cellular metabolic stress in diseases involving insulin resistance, such as type 2 diabetes, referred to as nutri-stress and results in cellular bioenergetic imbalance, which leads to insulin resistance and disease. Under nutri-stress, the heat shock response system is compromised due to metabolic abnormalities that disturb energy homeostasis. Heat shock proteins (HSPs) are the chief protectors of intracellular homeostasis during stress. Heat shock response (HSR) impairment contributes to several metabolic pathways that aggravate chronic hyperglycaemia and insulin resistance, highlighting a central role in disease pathogenesis. This article discusses the role of nutri-stress-related molecular events in causing insulin resistance and the nature of the roles played by heat shock proteins in some of the crucial checkpoints of the molecular networks involved in insulin resistance. Ample evidence suggests that the heat shock machinery regulates critical pathways in mitochondrial function and energy metabolism and that cellular energy status highly influences it. Weakening of HSPs, therefore, leads to loss of their vital cytoprotective functions, propagating nutri-stress in the system. Further research into the mechanistic roles of HSPs in metabolic homeostasis will help widen our understanding of lifestyle diseases, their onset, and complications. These inducible proteins may be crucial to attenuating lifestyle risk factors and disease management.
Topics: Humans; Heat-Shock Proteins; Insulin Resistance; Diabetes Mellitus, Type 2; Heat-Shock Response; Mitochondria
PubMed: 36441381
DOI: 10.1007/s12192-022-01314-9 -
Diabetes Care Feb 2020Many patients with hyperglycemic crises present with combined features of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). The implications of... (Observational Study)
Observational Study
OBJECTIVE
Many patients with hyperglycemic crises present with combined features of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). The implications of concomitant acidosis and hyperosmolality are not well known. We investigated hospital outcomes in patients with isolated or combined hyperglycemic crises.
RESEARCH DESIGN AND METHODS
We analyzed admissions data listing DKA or HHS at two academic hospitals. We determined ) the frequency distributions of HHS, DKA, and combined DKA-HHS (DKA criteria plus elevated effective osmolality); ) the relationship of markers of severity of illness and clinical comorbidities with 30-day all-cause mortality; and ) the relationship of hospital complications associated with insulin therapy (hypoglycemia and hypokalemia) with mortality.
RESULTS
There were 1,211 patients who had a first admission with confirmed hyperglycemic crises criteria, 465 (38%) who had isolated DKA, 421 (35%) who had isolated HHS, and 325 (27%) who had combined features of DKA-HHS. After adjustment for age, sex, BMI, race, and Charlson Comorbidity Index score, subjects with combined DKA-HHS had higher in-hospital mortality compared with subjects with isolated hyperglycemic crises (adjusted odds ratio [aOR] 2.7; 95% CI 1.4, 4.9; = 0.0019). In all groups, hypoglycemia (<40 mg/dL) during treatment was associated with a 4.8-fold increase in mortality (aOR 4.8; 95% CI 1.4, 16.8). Hypokalemia ≤3.5 mEq/L was frequent (55%). Severe hypokalemia (≤2.5 mEq/L) was associated with increased inpatient mortality (aOR 4.9; 95% CI 1.3, 18.8; = 0.02).
CONCLUSIONS
Combined DKA-HHS is associated with higher mortality compared with isolated DKA or HHS. Severe hypokalemia and severe hypoglycemia are associated with higher hospital mortality in patients with hyperglycemic crises.
Topics: Adult; Aged; Cohort Studies; Comorbidity; Diabetic Ketoacidosis; Female; Hospital Mortality; Hospitalization; Hospitals; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; Insulin; Insulin, Regular, Human; Male; Middle Aged; Prognosis; Retrospective Studies; United States; Young Adult
PubMed: 31704689
DOI: 10.2337/dc19-1168