Hyperglycemia in the Hospital Setting Rajesh Garg, Margo Hudson
Page numbers followed by f refer to figure, t refer to table and b refer to box
18f-fluorodeoxyglucose 20
8-hydroxy-dehydroxyguanosine 15
Acidosis 79
Activator protein-1 (AP1) 16
Acute coronary syndrome (ACS) 17, 19
Acute myocardial
infarction (AMI) 3, 6, 19, 95
Acute renal failure 43, 76
Adipose tissue 81
Adrenergic agents 83
Advanced glycosylation end
products (AGE) 14
Alcohol intoxication 95
Alcoholic ketoacidosis 83
American association of clinical endocrinologists (AACE) 5
American Association of Diabetes
Educators (AADE) 111
American College of
Endocrinology (ACE) 72
American Diabetes
Association (ADA) 5, 32, 63, 66, 71, 73, 79, 87, 111, 120
American Hospital Association 65
American Quality Programs 65
American Society for Parenteral and
Enteral Nutrition (ASPEN) 77
Anion gap 81
Anion gap acidosis 83
differential diagnosis 84
Antihyperglycemic agents 71
Antioxidants 73
Anti-psychotic medications 83
Apoptosis 19
dimethylarginine (ADMA) 20
Atherosclerosis 18
Basal insulin 58, 60
Basal-bolus insulin therapy 46, 50, 96
B-cell lymphoma 2 15
Beta-hydoxybutyrate 80
Blood glucose (BG)
measuring methods 2939
validation 31, 32
specimens 29, 30
Cancer 95
Cardiac arrhythmias 96
Cardiac dysfunction 85
Cardiac dysrhythmias 22
Catecholamines 11, 22, 56
C-C motif ligand 5 18
Cerebral edema 85
Chemotaxis 21
Chronic renal failure 61
Clinical laboratory improvement
amendment (CLIA) 33
Coma, diabetic 4
Continuous glucose monitoring
systems (CGMS) 38, 39
Continuous intravenous (IV) insulin 102
Coronary artery bypass
grafting (CABG) 48
Coronary vasoconstriction 96
Correctional insulin scale 60
Cortisol 10, 11, 82
Dehydration 79, 81, 82
Dementia 83
Depression 83
Diabetes care plan 116t, 123t
Diabetes care, continuum of 118f
Diabetes education 109116
adult learning principles 113
educators 115
supportive resources 115
Diabetes visit
postdischarge 122
discharge summary reviewing 122
disease history reviewing 122
new onset 3, 4
pre-existing 3
Diabetic education
survival skill content 111
blood glucose monitoring 111
follow-up 113
hypoglycemia 112
medications 112
nutrition 111
obtaining supplies 113
sick day management 113
Diabetic gastroparesis 73
Diabetic ketoacidosis (DKA) 21, 79, 82, 85, 103
laboratory data 80
precipitating factors 83
Dialysis 76
DIGAMI 2 46, 49
DiNardo protocol 61
Duodenal homeobox-1 (PDX-1) 15
Eating disorders 83
Effective serum osmolality 81
Effective serum osms 81
Electrolyte abnormalities 92
magnesium 88
phosphate 88
potassium 88
Endocrine disorders 95
Endothelial dysfunction 96
Endotoxin (LPS) 21
Epinephrine 10, 82
E-selectin 20
Exogenous insulin 56, 61
Fatty acids
Free (FFA) 3, 15
N-6 polyunsaturated 76
polyunsaturated 73
monounsaturated (MUFAS) 73
saturated 73
Fructose-6-phosphate 11
GCMI program 65
Glomerular filtration
rate (GFR) 61, 62, 95
Glucagon 11, 82
Glucocorticoid 83
Gluconeogenesis 11, 81, 95
hepatic 10
renal 10
Glucose control mentored
implementation (GCMI) 62
Glucose control 63
glucometrics 63
measures of 64
target population 63
unit of analysis 63
Glucose dehydrogenase
quinone (GDH-PQQ) 31
Glucose dye oxidoreductase 31, 36
Glucose effect
on inflammation 15
on proinflammatory kinases 17
on protein-tyrosine phosphatase 1b 17
on toll-like receptors 17
Glucose infusions 56
Glucose infusion rate (GIR) 75
Glucose levels
in diabetes
new onset 5
pre-existing 4
in hyperglycemia nondiabetic 5
Glucose management team (GMT) 120
Glucose management 100107
clinical management team 105b
steering committee 101b
Glucose oxidase enzyme 31
Glucose targets 51, 52t
medical 52
surgical 52
Glucose transporters (GLUT) 11
Glucose-6-phosphate 11, 30
Glycemic control mentored
implementation (GCMI) 66
Glycemic control 4, 5, 94, 95, 54, 119
improvement programs 66
Glycemic targets 72
Glycemic variability 50
Glyceraldehyde-3-phosphate 11
Glycogenolysis 11, 81
Glycolysis 11, 30
hemoglobin (HbA1c orA1c) 119
Glycosylated hemoglobin (HbA1c) 5
Growth hormone 11
Heat stroke 83
Hemofiltration 76
Hemoglobin A1c 37
Hepatic glucose output 81
Hepatic steatosis 76
Hepatocytes 12
HHS 82, 85
High performance liquid
chromatography (HPLC) 37
High-mobility group protein B1
(HMG-B1) 21
Homeostasis model assessment 17
Human regular insulin 56
Hyperbilirubinemia 36
Hyperchloremic non-anion
gap acidosis 90
acute 10
nondiabetic 3, 5
postoperative 4, 6
stress 5
Hyperglycemic crises 7992
complications 90
diagnostic laboratory criteria 79
epidemiology 79
etiology 82
history 84
laboratory findings 84
pathophysiology 81
physical findings 84
precipitating factors 82
prevention 91
fluids 85, 86t
insulin 87
sodium bicarbonate 86
use of protocols 88
electrolyte repletion 89t
initial fluid and insulin therapy 89t
laboratory testing 89t
Hyperkalemia 88
Hyperosmolar hyperglycemic
syndrome (HHS) 79, 103
laboratory data 80
Hyperthyroidism 83
Hypocalcemia 88
Hypocortisolism 95
Hypoglycemia management 65
Hypoglycemia 21, 90, 9497
effect on mortality and morbidity 95
etiology 94
mortality and morbidity 97
prevention 96, 97b
treatment 96, 97b
Hypokalemia 86, 90
Hypotension 84
Hypothermia 36
ICAM-1 20
Icodextrin 36
Ikkβ 17
Il-1 18
Il-1b 16
Il-2 18
Il-4 18
Il-6 16, 18, 21
Il-8 16
Impaired vascular function 19
Inducible no synthase (INOS) 20
Inhibitor kappa kinase β 13
Inpatient diabetes certification
program 66
Insulin infusion 56, 64, 96
Insulin intravenous, disadvantages 56
Insulin order sets
in the intensive care unit 54
in the noncritical care 58
Insulin receptor substrate-1 (IRS-1) 12
Insulin resistance 10, 11, 12, 13, 18, 19, 61, 76, 82
correctional 74
intravenous 54
dosing schedule 58
neutral protamine
hagedorn (NPH) 74
nutritional 57, 60
rapid acting 58
supplemental 74
total daily dose (TDD) of 60
Interleukin-6 (IL-6) 12, 96
International organization for
standardization (ISO) guideline 33
Intralipid infusion 76
Intravenous glucose monitoring
systems 39
Intravenous glucose
tolerance (FSIGT) 17
IRS-1 13
Ischemia 96
JNK-1 17
Joint commission program 66
Jun N terminal kinase-1 (JNK-1) 13
Kawasaki disease 36
Ketoacidosis 82
Ketone bodies 79, 80f, 81
Ketonemia 87
Ketosis 81
Kussmaul breathing 84
Lactic acidosis 84
Leuven trials 72
Lipase 85
Lipolysis 81
Lipopeptides 13
Lipopolysaccharide 13
Liver failure 95
Macronutrients 73
MafA gene 15
Malnutrition 70
Maltose 36
Matrix metalloproteinase-2 (MMP-2) 16
MCP-1 18
Mean glucose 58, 64
Metabolic acidosis 83
Micronutrients 73
MR spectroscopy 20
Myocardial infarction (MI) 43, 49, 84
Nephrotoxic drugs 61
Nicotinamide adenine dinucleotide
phosphate (NADP) 30
N-methyl-d-aspartate (NMDA)
receptor 20
Norepinephrine 10
Normoglycemia in intensive care
evaluation 57
enteral 70, 72
parenteral 70, 75
Oral hypoglycemic
agents (OHAS) 59, 103
Order sets
special situation 60
perioperative period 60
renal insufficiency 61
self-management 60
Organ perfusion 96
Organ system failure 96
Osmolal gap 81, 84
Osmotic diuresis 81, 84
Oxidative stress 19, 76
effect on
cellular damage 13
insulin secretion 15
vascular function 14
glucose effect on 15
Pancreatic β-cell deficiency 82
Pancreatitis 85
Pathogen-associated molecular
patterns (PAMPS) 13
hexosamine 11, 14
pentose phosphate 11
phosphatidylinositol 3-kinase (PI3-K) 12
polyol 11
protein kinase C (PKC) 11
PDSA method 104
Pentamidine 83
Peptidoglycans 13
Percutaneous coronary
intervention (PCI) 19
Peripheral blood 56
Phagocytosis 21
Phosphoinositide-3-kinase (PI-3-K) 12
PI3-K 13
PI-3-K 19
PI-3-K pathway 12
PKC 15
PKC-β2 17
Pneumonia 43, 83
Point of care (POC) glucose
testing 29, 39, 55, 56, 59, 63, 87
benefits of 32, 33t
devices 31, 39
accuracy 35, 36
limitations of 32
Polydipsia 84
Polyneuropathy 76
Polyol flux 14
Polyuria 84
Positron emission tomography (PET) 20
Postdischarge follow-up, barriers 121
Potassium 3, 85, 87
Potassium infusion 19
Potassium phosphate 88
Proinflammatory cytokines 12
Proinflammatory kinases 12
Protein kinase C 14
Protein tyrosine phosphatae-1B
(PTP-1B) 12, 13, 17, 19
Pulmonary embolism 4
QT prolongation 96
Recommended dietary
allowance (RDA) 71
Renal failure 62, 83, 84
Renal insufficiency 95
SC insulin pump 103
Secondary hyperparathyroidism 61
Sepsis 43
Septic shock 95
Serum bicarbonate 84
Serum osmolality 81, 85
Serum osms 81
Severe lipemia 36
Sliding scale insulin 59, 96
Society of hospital medicine (SHM) 60
SOCS-3 17, 18
Soy protein 73
Splenectomy 38
Starvation ketosis 84
Steroids 56
Subcutaneous (SC)
insulin 57, 88, 96, 102
Suppressor of cytokine
signaling (SOCS-3) 12
Surgical care improvement
project (SCIP) 65
Survival using glucose algorithm
regulation (Nice-Sugar) 57
Survival using glucose algorithm
regulation (Nice-Sugar) trial 72
Tachycardia 84
The diabetes control and
complication trial (DCCT) 37
The glycemic control team 106
Thiazide 83
TLR-1 18
TLR-2 17, 18
TLR-4 17, 18
TLR-7 18
TLR-9 18
TNFα 14, 16, 18, 21
Toll-like receptors (TLRS) 12, 13
Triglyceride 85
Troponin 19
Tumor necrosis factor-alpha (TNFα) 12
Uncomplicated DKA 87
Urinary tract infection (UTI) 83
Use of protocol, subsequent fluid and
insulin therapy 91t
Vascular endothelial growth
factor (VEGF) 18
Vascular surgery 48
Ventricular arrhythmias 96
Weight loss 84
Chapter Notes

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Editors Rajesh Garg MD Assistant Professor Department of Medicine Division of Endocrinology, Diabetes and Hypertension Brigham and Women's Hospital Harvard Medical School Boston, MA, USA Margo Hudson MD Instructor Department of Medicine Division of Endocrinology, Diabetes and Hypertension Brigham and Women's Hospital Harvard Medical School Boston, MA, USA Foreword Deborah J Wexler MD MSc
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Hyperglycemia in the Hospital Setting
First Edition: 2014
Printed at
5Dedicated to
Our teachers who imparted to us
the gift of knowledge and
our patients who keep challenging us over time
7Contributors Foreword
Once the exclusive concern of endocrinologists and disregarded by many others, management of Hyperglycemia in the Hospital Setting has become the standard of care. Three major developments since the start of this century have come together to support this advance.
First, the publication of a seminal study of intensive insulin treatment in Belgian surgical intensive care unit (ICU) patients in 2001 focused enormous attention on the appropriate treatment of hyperglycemia in critically ill patients. The pendulum has swung several times since that publication between various approaches and treatment targets in intensive care settings. Nonetheless, it is fair to say that seminal paper, which showed a significant mortality benefit, gave rise to randomized trials outside the intensive care setting. The safety and efficacy of basal-bolus insulin regimens in general medical and surgical care settings in the improving outcomes has launched widespread efforts to manage hyperglycemia.
Second, the quality and safety movement, which has grown exponentially over the past decade, necessarily took up insulin, one of the top five medications associated with medical error, as a priority area. Approaches to improve quality and safety of insulin use have included educational efforts, standardized order sets, and team-based care to manage complex insulin regimens in the hospital setting. These efforts have been led by hospitalists, pharmacists, and nurses in addition to endocrinologists.
Finally, and most recently, the recognition of the importance of transitions of care between hospital and home, and the role of the acute inpatient admission as one point on the continuum of care within an accountable care organization context, has promoted attention to the need to extend the lessons of the quality and safety interventions beyond the acute setting.
Hyperglycemia in the Hospital Setting spans the progress in all of these areas to provide a comprehensive guide to this ever-challenging, and now widely accepted, goal in the care of all of our patients.
Deborah J Wexler md msc
Assistant Professor
Department of Medicine Harvard Medical School
Co-Clinical Director Massachusetts General Hospital Diabetes Center
Boston, MA, USA
Over many years working together on a team dedicated to diabetes management, we have learned a great deal about glucose management in hospitalized patients. While we have seen the field evolving over time, we also have noticed a dearth of books devoted to this topic. Hyperglycemia in the Hospital Setting, we believe will be a comprehensive and practical source of information on management of glucose in the inpatient setting. We hope to fill the void by addressing the major commonly encountered situations with straightforward information on physiology and treatment plans that we know are effective, while reviewing current literature on these topics and some of the remaining controversies.
The book is evidence-based with expert opinion provided where necessary. We begin with a discussion of the epidemiology of hyperglycemia in hospitalized patients and then proceed to a discussion of the current evidence for harm caused by hyperglycemia. We follow with a discussion of glucose monitoring and situations which may interfere with it. We next tackle the controversial topic of glucose goals for hospitalized patients followed by management strategies to achieve these goals. The next three chapters focus on the specific situations of patients on nutritional support, hyperglycemic emergencies and hypoglycemia. Finally, we end with discussions of the team approach to inpatient glucose management, using hospitalization as a time to improve patient education and to improve outpatient care by improving discharge planning. Improving patient outcomes is at the core of the book.
We hope that physicians, pharmacists, physician assistants, and nurses at all levels of training will find the book useful.
Rajesh Garg
Margo Hudson
We wish to acknowledge the team members of Diabetes Management Service at the Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, who have contributed to Hyperglycemia in the Hospital Setting either directly by writing chapters or indirectly by sharing their experiences with us. Through a shared team work, we gained the experience and knowledge that have formed the core of the book. Rita Marie McCarthy, Nurse Practitioner and Samira Sheth, Nurse Practitioner helped us to manage the heavy load of patient care while we worked on the book. We also acknowledge the professional support and advice of our colleagues, Merri Pendergrass Carolyn Becker, Graham T McMahon, and Alexander Turchin, who were always available to give a fresh viewpoint on a wide range of topics. Finally, we acknowledge our spouses Neeta Garg, and Jim Hudson, who offered many suggestions throughout the process to make this a better book.