|Year : 2013 | Volume
| Issue : 3 | Page : 128-134
Challenging aspects of and solutions to diagnosis, prevention, and management of hypoglycemia in critically ill geriatric patients
Vishal Sehgal1, Sukhminder Jit Singh Bajwa2, Upinder Khaira3, Rinku Sehgal3, Anurag Bajaj3
1 Department of Medicine, Commonwealth Medical College, Scranton, PA, USA
2 Department of Anaesthesiology and Intensive Care Medicine, Gian Sagar Medical College, Banur, Patiala, Punjab, India
3 The Wright Center for Graduate Medical education, Scranton, PA, USA
|Date of Web Publication||19-Oct-2013|
Sukhminder Jit Singh Bajwa
Department of Anaesthesiology and Intensive Care, Gian Sagar Medical College and Hospital, Ram Nagar, Banur, Patiala, Punjab
Source of Support: None, Conflict of Interest: None
There is a worldwide pandemic of diabetes. Also there is a gradual and steady increase in the elderly population. Often clinicians are faced with managing dysglycemia in the elderly with underlying sepsis and multiple comorbidities. This predisposes the elderly to potentially increased chances of hypoglycemia in inpatient settings. This article reviews the altered renal physiology and its effects in the management of dysglycemia in the elderly population. It also emphasizes the role of renal insufficiency and sepsis as the main etiological factors for hypoglycemia in both diabetics and nondiabetics in the inpatient settings.
Keywords: Chronic kidney disease, diabetes, elderly, hyperglycemia, hypoglycemia
|How to cite this article:|
Sehgal V, Bajwa SS, Khaira U, Sehgal R, Bajaj A. Challenging aspects of and solutions to diagnosis, prevention, and management of hypoglycemia in critically ill geriatric patients. J Sci Soc 2013;40:128-34
|How to cite this URL:|
Sehgal V, Bajwa SS, Khaira U, Sehgal R, Bajaj A. Challenging aspects of and solutions to diagnosis, prevention, and management of hypoglycemia in critically ill geriatric patients. J Sci Soc [serial online] 2013 [cited 2020 Jan 19];40:128-34. Available from: http://www.jscisociety.com/text.asp?2013/40/3/128/120052
| Introduction|| |
The worldwide pandemic of diabetes has increased the healthcare costs exponentially even in the developing world. The twin problems of potentially preventable hyper- and hypoglycemia are a huge cost burden to the society. ,,
According to the American Diabetes Association (ADA), the total costs of diagnosed diabetes have risen to $245 billion in 2012 from $174 billion in 2007, when the cost was last examined. Majority of the cost is incurred in the inpatient care of diabetes [Figure 1]. The problem gets compounded by the increasing elderly population which is diabetic. In United States, more than 25% of the elderly are diabetic and the number is rapidly increasing. 
The elderly usually have multiple comorbidities which further compound the problem.  Also this set of population is frequently on polypharmacy and invariably has underlying chronic kidney disease (CKD) which presents a clinical conundrum for the clinician. Uncontrolled diabetes is related to increased readmissions to the hospital.  The risk of hyperglycemia has to be weighed against hypoglycemia which is potentially more devastating for this set of population.  Hypoglycemia is considered to be the main limiting factor in the treatment of hyperglycemia.  It increases cardiovascular and all-cause mortality in hospitalized diabetic patients.  Hypoglycemia is associated with increased morbidity, mortality, increased length of hospital stay (LOS) and increased healthcare costs. , Also the longer the LOS, the more the chances of hypoglycemia in inpatient settings.  As such less stringent glycemic control in the elderly and critical care patients is warranted. 
The present review is written with an aim to highlight the basic and essential clinical measures to prevent hypoglycemia in the critically ill geriatric population. The search strategies included extensive scrutiny of literary evidence from internet resources, journals and textbooks of endocrinology and anesthesiology, and intensive care among endocrinologists, anesthesiologists and intensivists of high academic caliber. The literature was explored for full text articles and abstracts from various search engines such as PubMed, Medscape, Scopus, Science Direct, Medline, Yahoo, Google Scholar, and many others, using key words like diabetes mellitus, geriatric, hyperglycaemia, hypoglycaemia, and insulin.
Hypoglycemia has traditionally been defined as low blood sugars with symptoms of hypoglycemia.  The cut-off value for hypoglycemia remains debatable with most favoring a value of <63 mg/dl. , But the exact definition needs to be individualized. In our opinion, any self-monitored blood glucose value <70 mg/dl should alert the patient or clinician regarding harmful effects of hypoglycemia.
The ADA working group on hypoglycemia  has classified hypoglycemia into the following categories:
Incidence of hypoglycemia
- Severe hypoglycemia: hypoglycemia requiring assistance and use of carbohydrates or glucagon.
- Documented symptomatic hypoglycemia: symptoms of hypoglycemia with BGM < 70 mg/dl.
- Asymptomatic hypoglycemia: no symptoms but BGM < 70 mg/dl.
- Probably symptomatic hypoglycemia: symptoms but no documented BGM.
- Relative hypoglycemia: symptomatic but BGM > 70 mg/dl.
Type 1 diabetes has much more incidents of hypoglycemia as compared to type 2 diabetes. This is because recurrent hypoglycemia impairs the counter regulatory mechanisms to subsequent hypoglycemia. There are countless episodes of asymptomatic hypoglycemia, two episodes of symptomatic hypoglycemia and one episode of severe hypoglycemia per year.
Type 2 diabetes is much more frequent and clinically we see many more cases of hypoglycemia in type 2 diabetics. In 50% of the cases, insulin is responsible, and in 20% cases, it is long-acting sulphonylureas  which are considered to cause hypoglycemia.
Consequences in the elderly
It is a known fact that the incidence of neuroglycopenic manifestations in the elderly is higher as compared to autonomic manifestations. This includes dizziness, delirium, subsequent falls, and increased risk of dementia. In a diabetes control and complications trial, the patients on more intensive control had a higher level of hypoglycemia.  In addition, the ACCORD trial recommended an HBA1C target of less than 8% in people with life expectancy of less than 10 years.
Risk factors for hypoglycemia in the elderly
Numerous mechanisms are responsible for a higher incidence of hypoglycemia the elderly population as compared to the younger population. These include, but are not limited to, the following:
Causes of hypoglycemia in inpatient settings
- Impaired counter regulatory mechanisms: These may be due to many reasons. The most common cause is a prior history of severe hypoglycemia which may be the result of intensive glycemic control.
- Insulin excess is also an important cause. This may be due increased exogenous insulin per se or secondary to long-acting secretagogues especially sulphonylureas. In general, in non-critically ill patients, using insulin less than 0.6 U/kg has been associated with lesser episodes of hypoglycemia.  Another important cause in hospital settings may be the decreased metabolism of insulin in AKI. This would be discussed in detail here.
The cause of hypoglycemia in the elderly diabetic population is a complex interplay between multiple factors and is seldom attributable to one single cause [Figure 2]. In the inpatient settings, failure to adjust the diabetic medications with the diminished oral intake is the most common correctable cause of hypoglycemia in the hospitalized elderly diabetics. ,
Also, the elderly are at risk of severe hypoglycemia which can be secondary to higher possibility of hypoglycemic unawareness due to autonomic neuropathy. , Elderly have multiple co-morbidities and are on polypharmacy which compounds the problem. Insulin and long-acting insulin secretagogue may cause profound hypoglycemia in the elderly leading to increased cardiovascular adverse events in inpatient settings. , Besides some medications such as quinolones, which are frequently used in the hospital settings, could potentiate hypoglycemia in hospitalized patients.  In the critical care settings when patients have multiorgan dysfunction, this gets magnified due to the changed metabolism of hypoglycemic agents. This is especially true for elderly patients with congestive heart failure (CHF) or sepsis in whom low flow states cause an altered metabolism of drugs in the kidney and liver.  Adrenal insufficiency in such settings could also potentially cause hypoglycemia.
Hypoglycemia may also be seen in elderly nondiabetic patients in inpatient settings. A retrospective study by Mendoza et al. concluded that CKD was the most common cause of hypoglycemia in the elderly nondiabetics [Figure 3]. This was followed by alcohol intoxication, liver failure, sepsis, cancer, and endocrine disorders. 
Insulin metabolism and renal insufficiency
Renal function should be assessed diligently for preventing hyper- and hypoglycemia. Insulin has a molecular weight of about 6000. About 60% of insulin is excreted through the kidneys by glomerular filtration and about 40% is excreted by extraction from peritubular vessels. In the proximal tubular cells, it is transported to lysosomes which break it down to amino acids. About 1% of insulin is excreted unchanged in the urine. With the decreasing glomerular filtration rate (GFR) in CKD, insulin metabolism remains constant. This is because even though GFR decreases, there is a concomitant increase in the extraction of insulin from peritubular vessels. But when GFR falls below 15, there is a decrease in the metabolism of insulin and a patient gets predisposed to hypoglycemia.
In general, when GFR drops below 60, there is an increased incidence of hypoglycemia in both diabetics and nondiabetics.  This is due to decreased renal gluconeogenesis and decreased antiinsulin hormones due to autonomic neuropathy.
Uremia impairs the tissue sensitivity to insulin which gets better when the patient is dialyzed. Anemia also contributes to insulin resistance which tends to improve when erythropoietin is started. The clinician needs to be aware of these conundrums while caring for the elderly with CKD. Most elderly patients have underlying CKD and the drugs need to be dosed based on their changing renal profile.  This is especially true for oral hypoglycemic and long-acting insulin. Insulin dosing as per the decreased creatinine clearance has been shown to decrease the incidence of inpatient hypoglycemia. , Even after using short-acting insulin in patients with hyperkalemia with underlying renal insufficiency, they remain at risk of hypoglycemia secondary to decreased insulin metabolism. 
Clinical manifestations of hypoglycemia could be myriad. Though easily recognized in the young and middle-aged people, it may be obscure in elderly patients who could have masking of hypoglycemia awareness secondary to dementia, polypharmacy, comorbidities, and adverse drug reactions.
Elderly especially those with a compromised renal function are at a heightened risk of hypoglycemia when treated with long-acting sulphonylureas in the hospital settings.  The elderly often have dementia and cognitive impairment which are independently associated with an increased risk for hypoglycemia.  Postsurgical patients are at a heightened risk for hypoglycemic complications. This is more so when they have poor preoperative glycemic control. 
Classically, symptoms may be subclassified as autonomic or neuroglycopenic [Figure 4]. An autonomic response may manifest as sweating, weakness, tachycardia, palpitations, tremor, or paresthesia which may result in falls in the elderly and subsequent hospitalization.  Neuroglycopenia may manifest as confusion, seizure, focal deficits, and loss of consciousness.
Severe hypoglycemia (BG < 40) impairs the hormonal and autonomic response to subsequent hypoglycemia.  This may contribute directly to increased morbidity and mortality associated with diabetes. This negates the survival benefits associated with a tight control of hyperglycemia. , Hypoglycemia is a prognostic marker for mortality in the hospitalized elderly nondiabetics. 
It is mandatory during the management of hypoglycaemia to hold off all the hypoglycemic medications. If the patient is able to swallow safely, rapidly absorbed carbohydrate should be given. If the patient has an altered mental status and is unable to swallow, he should be managed by giving an intravenous (IV) bolus of 50 ml of 50% dextrose.
Dextrose infusion should ensure the delivery of 6-9 mg/kg per minute of glucose to maintain BGM above 80. Amounts needed vary depending upon the cause and severity of hypoglycemia.
Blood glucose is measured 10-15 min after the initial IV bolus and monitored every 30-60 min thereafter until stability is reached.
If glucose cannot be given by parenteral or oral routes, glucagon, 1 mg intramuscular (IM) or subcutaneous (SC),
Critical care setting
Severe hypoglycemia may be seen in sepsis especially in the elderly.  Hypoglycemia in patients with sepsis is associated with an increased risk of mortality.  Other comorbidities which increase the potential for hypoglycemia in critical care settings include renal insufficiency, hepatic insufficiency, septic shock, mechanical ventilation, and intensive insulin control. , In critical care settings, hypoglycemia could be a biomarker of adverse outcomes rather than cause as patients with acute hypoglycemic episodes are sick and frail with multiple comorbidities.  Evidence supports the use of less stringent criteria for glycemic control in critical care settings with the target glucose level of 140-180 mg/dl. ,,,,,,, In selected patients, a target level of of 110-140 mg/dl may be appropriate. The aim should be to avoid extremes of glucose rather than euglycemia.  A large absolute decrease in blood glucose levels, especially if <100, should alert the clinician about impending hypoglycemia and should trigger a preventive step. , ADA strongly recommends using IV insulin in critical care settings and switching to SC insulin with basal bolus insulin (BBI) when stable.  IV insulin should be restricted to critical care settings only as the incidence of hyper- and hypoglycemia significantly increases if the patient is allowed to eat.  BBI is superior to sliding scale insulin (SSI) in the inpatient management of hyperglycemia although risk of mild hypoglycemia is more with BBI. ,,,,, Poorly controlled glucose in critical care settings is highly detrimental as glycemic control in an ICU is a measure of quality of care, safety, and cost. 
Assessment, prevention, and patient self-recognition is the key to successfully prevent postoperative hypoglycemia.  Poor preoperative glycemic control is associated with poor postoperative outcomes.  Perioperative glycemic control should be based on outpatient treatment regimens and underlying comorbidities to minimize hypo- and hyperglycemia.  In the inpatient settings, there is a tendency for intensive glycemic control to minimize the risk of infection, but that should be weighed against the risk of hypoglycemia. , The Society for Ambulatory Anesthesia does not issue any guidelines for glycemic control in perioperative settings during ambulatory surgery due to lack of any good quality evidence. 
Metformin may be used as an adjunct to insulin in the postoperative period if there is no renal insufficiency or any other contraindication. 
Use of sulfonylureas (especially glyburide) in the elderly may be associated with an increased risk of hypoglycemia both in outpatient and inpatient settings.  These should preferably be withheld during hospitalization to minimize the risk of hypoglycemia.  Glipizide is acceptable if sulfonylureas have to be used due to their short life and minimal renal clearance. Insulin analogs, both, short and long acting, are proven to be more effective if renal insufficiency is taken into account while prescribing the same. 
| Conclusion|| |
In the elderly population, sepsis and CKD are the main pathologies that should alert the clinician about the possibility of hypoglycemia in both diabetics and nondiabetics. The hallmark of the glycemic control in hospitalized patients is to avoid hypoglycemia while optimizing glycemic control. , Continuous glucose monitoring is an upcoming tool which could be used in the coming years to minimize hypoglycemia in hospitalized settings. , An institution-wide glucose management program with a multidisciplinary approach is the best way to decrease inpatient hypoglycemic episodes while ensuring optimum glycemic control. ,,,,,,,,, Meticulous attention should be paid in transition from IV to SC and also from outpatient to inpatient to minimize hypoglycemia.  Universal education of all medical personnel in the management of dysglycemia could potentially minimize hypo- and hyperglycemia. ,,,, This would improve patient outcomes and decrease morbidity, mortality, and cost associated with dysglycemia management.
| References|| |
|1.||Shrestha SS, Zhang P, Barker L, Imperatore G. Medical expenditures associated with diabetes acute complications in privately insured U.S. youth. Diabetes Care 2010;33:2617-22. |
|2.||Wexler DJ, Meigs JB, Cagliero E, Nathan DM, Grant RW. Prevalence of hyper- and hypoglycemia among inpatients with diabetes: A national survey of 44 U.S. hospitals. Diabetes Care 2007;30:367-9. |
|3.||Bajwa SS, Kalra S. Diabeto-anaesthesia: A subspecialty needing endocrine introspection. Indian J Anaesth 2012;56:513-7 |
|4.||Soe K, Sacerdote A, Karam J, Bahtiyar G. Management of type 2 diabetes mellitus in the elderly. Maturitas 2011;70:151-9. |
|5.||Abbatecola AM, Paolisso G. Diabetes care targets in older persons. Diabetes Res Clin Pract 2009;86(Suppl 1):S35-40. |
|6.||Dungan KM, Osei K, Nagaraja HN, Schuster DP, Binkley P. Relationship between glycemic control and readmission rates in patients hospitalized with congestive heart failure during implementation of hospital-wide initiatives. Endocr Pract 2010;16:945-51. |
|7.||Ha WC, Oh SJ, Kim JH, Lee JM, Chang SA, Sohn TS, et al. Severe hypoglycemia is a serious complication and becoming an economic burden in diabetes. Diabetes Metab J 2012;36:280-4. |
|8.||Brunton SA. Hypoglycemic potential of current and emerging pharmacotherapies in type 2 diabetes mellitus. Postgrad Med 2012;124:74-83. |
|9.||Hsu PF, Sung SH, Cheng HM, Yeh JS, Liu WL, Chan WL, et al. Association of clinical Symptomatic Hypoglycemia with cardiovascular events and total mortality in type 2 diabetes Mellitus: A nationwide population-based study. Diabetes Care 2012;36:894-900. |
|10.||Brodovicz KG, Mehta V, Zhang Q, Zhao C, Davies MJ, Chen J, et al. Association between hypoglycemia and inpatient mortality and length of hospital stay in hospitalized, insulin-treated patients. Curr Med Res Opin 2013;29:101-7. |
|11.||Bailon RM, Cook CB, Hovan MJ, Hull BP, Seifert KM, Miller-Cage V, et al. Temporal and geographic patterns of hypoglycemia among hospitalized patients with diabetes mellitus. J Diabetes Sci Technol 2009;3:261-8. |
|12.||Pichardo-Lowden A, Gabbay RA. Management of hyperglycemia during the perioperative period. Curr Diab Rep 2012;12:108-18. |
|13.||Workgroup on Hypoglycemia AeDA. Defining and reporting hypoglycemia in diabetes: A report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care 2005;28:1245-9. |
|14.||Frier BM. Defining hypoglycaemia: What level has clinical relevance? Diabetologia 2009;52:31-4. |
|15.||Swinnen SG, Mullins P, Miller M, Hoekstra JB, Holleman F. Changing the glucose cut-off values that define hypoglycaemia has a major effect on reported frequencies of hypoglycaemia. Diabetologia 2009;52:38-41. |
|16.||Zammitt NN, Frier BM. Hypoglycemia in type 2 diabetes: Pathophysiology, frequency, and effects of different treatment modalities. Diabetes Care 2005;28:2948-61. |
|17.||Hypoglycemia in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group. Diabetes 1997;46:271-86. |
|18.||Rubin DJ, Rybin D, Doros G, McDonnell ME. Weight-based, insulin dose-related hypoglycemia in hospitalized patients with diabetes. Diabetes Care 2011;34:1723-8. |
|19.||Smith WD, Winterstein AG, Johns T, Rosenberg E, Sauer BC. Causes of hyperglycemia and hypoglycemia in adult inpatients. Am J Health Syst Pharm 2005;62:714-9. |
|20.||Bajwa SS, Kalra S. Glycaemic control in ICU. In: Bajaj S, editor, et al. Endocrine Society of India Manual of Clinical Endocrinology. Vol. 1. 2012. p. 115-23. |
|21.||Berlin I, Sachon CI, Grimaldi A. Identification of factors associated with impaired hypoglycaemia awareness in patients with type 1 and type 2 diabetes mellitus. Diabetes Metab 2005;31:246-51. |
|22.||Holstein A, Plaschke A, Egberts EH. Clinical characterisation of severe hypoglycaemia-a prospective population-based study. Exp Clin Endocrinol Diabetes 2003;111:364-9. |
|23.||Panicker GK, Karnad DR, Salvi V, Kothari S. Cardiovascular risk of oral antidiabetic drugs: Current evidence and regulatory requirements for new drugs. J Assoc Physicians India 2012;60:56-61. |
|24.||Mishra A, Dave N. Norfloxacin-induced hypoglycemia and urticaria. Indian J Pharmacol 2012;44:415-6. |
|25.||Arinzon Z, Fidelman Z, Berner YN, Adunsky A. Infection-related hypoglycemia in institutionalized demented patients: A comparative study of diabetic and nondiabetic patients. Arch Gerontol Geriatr 2007;45:191-200. |
|26.||Mendoza A, Kim YN, Chernoff A. Hypoglycemia in hospitalized adult patients without diabetes. Endocr Pract 2005;11:91-6. |
|27.||Moen MF, Zhan M, Hsu VD, Walker LD, Einhorn LM, Seliger SL, et al. Frequency of hypoglycemia and its significance in chronic kidney disease. Clin J Am Soc Nephrol 2009;4:1121-7. |
|28.||Pratley RE, Gilbert M. Clinical management of elderly patients with type 2 diabetes mellitus. Postgrad Med 2012;124:133-43. |
|29.||Baldwin D, Zander J, Munoz C, Raghu P, DeLange-Hudec S, Lee H, et al. A randomized trial of two weight-based doses of insulin glargine and glulisine in hospitalized subjects with type 2 diabetes and renal insufficiency. Diabetes Care 2012;35:1970-4. |
|30.||Winterstein AG, Hatton RC, Gonzalez-Rothi R, Johns TE, Segal R. Identifying clinically significant preventable adverse drug events through a hospital's database of adverse drug reaction reports. Am J Health Syst Pharm 2002;59:1742-9. |
|31.||Schafers S, Naunheim R, Vijayan A, Tobin G. Incidence of hypoglycemia following insulin-based acute stabilization of hyperkalemia treatment. J Hosp Med 2012;7:239-42. |
|32.||Deusenberry CM, Coley KC, Korytkowski MT, Donihi AC. Hypoglycemia in hospitalized patients treated with sulfonylureas. Pharmacotherapy 2012;32:613-7. |
|33.||Feil DG, Rajan M, Soroka O, Tseng CL, Miller DR, Pogach LM. Risk of hypoglycemia in older veterans with dementia and cognitive impairment: Implications for practice and policy. J Am Geriatr Soc 2011;59:2263-72. |
|34.||Dhatariya K, Levy N, Kilvert A, Watson B, Cousins D, Flanagan D, et al. NHS Diabetes guideline for the perioperative management of the adult patient with diabetes. Diabet Med 2012;29:420-33. |
|35.||Tsur A, Segal Z. Falls in stroke patients:risk factors and risk management. Isr Med Assoc J 2010;12:216-9. |
|36.||Adler GK, Bonyhay I, Failing H, Waring E, Dotson S, Freeman R. Antecedent hypoglycemia impairs autonomic cardiovascular function: Implications for rigorous glycemic control. Diabetes 2009;58:360-6. |
|37.||Krinsley JS, Grover A. Severe hypoglycemia in critically ill patients: Risk factors and outcomes. Crit Care Med 2007;35:2262-7. |
|38.||Alam T, Weintraub N, Weinreb J. What is the proper use of hemoglobin A1c monitoring in the elderly? J Am Med Dir Assoc 2006;7(3 Suppl):S60-4,59. |
|39.||Mannucci E, Monami M, Mannucci M, Chiasserini V, Nicoletti P, Gabbani L, et al. Incidence and prognostic significance of hypoglycemia in hospitalized non-diabetic elderly patients. Aging Clin Exp Res 2006;18:446-51. |
|40.||Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER, et al. Evaluation and management of adult hypoglycemic disorders: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2009;94:709-28. |
|41.||Gamble JM, Eurich DT, Marrie TJ, Majumdar SR. Admission hypoglycemia and increased mortality in patients hospitalized with pneumonia. Am J Med 2010;123:556.e11-6. |
|42.||Lleva RR, Inzucchi SE. Hospital management of hyperglycemia. Curr Opin Endocrinol Diabetes Obes 2011;18:110-8. |
|43.||Carey M, Boucai L, Zonszein J. Impact of hypoglycemia in hospitalized patients. Curr Diab Rep 2013;13:107-13. |
|44.||Buchleitner AM, Martínez-Alonso M, Hernández M, Solà I, Mauricio D. Perioperative glycaemic control for diabetic patients undergoing surgery. Cochrane Database Syst Rev 2012;9:CD007315. |
|45.||Baker L, Juneja R, Bruno A. Management of hyperglycemia in acute ischemic stroke. Curr Treat Options Neurol 2011;13:616-28. |
|46.||Farrokhi F, Smiley D, Umpierrez GE. Glycemic control in non-diabetic critically ill patients. Best Pract Res Clin Endocrinol Metab 2011;25:813-24. |
|47.||Moghissi ES. Addressing hyperglycemia from hospital admission to discharge. Curr Med Res Opin 2010;26:589-98. |
|48.||Moghissi ES. Reexamining the evidence for inpatient glucose control: New recommendations for glycemic targets. Am J Health Syst Pharm 2010;67(16 Suppl 8):S3-8. |
|49.||Bajwa SS. Intensive care management of critically sick diabetic patients. Indian J Endocr Metab 2011;15:349-50. |
|50.||Sawin G, Shaughnessy AF. Glucose control in hospitalized patients. Am Fam Physician 2010;81:1121-4. |
|51.||NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY, Blair D, Foster D, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009;360:1283-97. |
|52.||Godoy DA, Di Napoli M, Biestro A, Lenhardt R. Perioperative glucose control in neurosurgical patients. Anesthesiol Res Pract 2012;2012:690362. |
|53.||Cook CB, Potter DJ, Kongable GL. Characterizing glucose changes antecedent to hypoglycemic events in the intensive care unit. Endocr Pract 2012;18:317-24. |
|54.||Shogbon AO, Levy SB. Intensive glucose control in the management of diabetes mellitus and inpatient hyperglycemia. Am J Health Syst Pharm 2010;67:798-805. |
|55.||Smiley D, Rhee M, Peng L, Roediger L, Mulligan P, Satterwhite L, et al. Safety and efficacy of continuous insulin infusion in noncritical care settings. J Hosp Med 2010;5:212-7. |
|56.||Roberts GW, Aguilar-Loza N, Esterman A, Burt MG, Stranks SN. Basal-bolus insulin versus sliding-scale insulin for inpatient glycaemic control: A clinical practice comparison. Med J Aust 2012;196:266-9. |
|57.||Chen HJ, Steinke DT, Karounos DG, Lane MT, Matson AW. Intensive insulin protocol implementation and outcomes in the medical and surgical wards at a Veterans Affairs Medical Center. Ann Pharmacother 2010;44:249-56. |
|58.||Juneja R, Foster SA, Whiteman D, Fahrbach JL. The nuts and bolts of subcutaneous insulin therapy in non-critical care hospital settings. Postgrad Med 2010;122:153-62. |
|59.||Pollom RD. Optimizing inpatient glycemic control with basal-bolus insulin therapy. Hosp Pract 2010;38:98-107. |
|60.||Nau KC, Lorenzetti RC, Cucuzzella M, Devine T, Kline J. Glycemic control in hospitalized patients not in intensive care: Beyond sliding-scale insulin. Am Fam Physician 2010;81:1130-5. |
|61.||Wallace CR. Postoperative management of hypoglycemia. Orthop Nurs 2012;31:328-33;quiz 334-25. |
|62.||Rizvi AA, Chillag SA, Chillag KJ. Perioperative management of diabetes and hyperglycemia in patients undergoing orthopaedic surgery. J Am Acad Orthop Surg 2010;18:426-35. |
|63.||Murad MH, Coburn JA, Coto-Yglesias F, Dzyubak S, Hazem A, Lane MA, et al. Glycemic control in non-critically ill hospitalized patients: A systematic review and meta-analysis. J Clin Endocrinol Metab 2012;97:49-58. |
|64.||Storey S, Von Ah D. Impact of malglycemia on clinical outcomes in hospitalized patients with cancer: A review of the literature. Oncol Nurs Forum 2012;39:458-65. |
|65.||Joshi GP, Chung F, Vann MA, Ahmad S, Gan TJ, Goulson DT, et al. Society for Ambulatory Anesthesia consensus statement on perioperative blood glucose management in diabetic patients undergoing ambulatory surgery. Anesth Analg 2010;111:1378-87. |
|66.||Baradari AG, Zeydi AE, Aarabi M, Ghafari R. Metformin as an adjunct to insulin for glycemic control in patients with type 2 diabetes after CABG surgery: A randomized double blind clinical trial. Pak J Biol Sci 2011;14:1047-54. |
|67.||Franchin A, Corradin ML, Giantin V, Rossi F, Zanatta F, Attanasio F, et al. Diabetes in a geriatric ward: Efficacy and safety of new insulin analogs in very old inpatients. Aging Clin Exp Res 2012;24(3 Suppl):17-9. |
|68.||Beck RW, Calhoun P, Kollman C. Use of continuous glucose monitoring as an outcome measure in clinical trials. Diabetes Technol Ther 2012;14:877-82. |
|69.||Tansey MJ, Beck RW, Buckingham BA, Mauras N, Fiallo-Scharer R, Xing D, et al. Accuracy of the modified Continuous Glucose Monitoring System (CGMS) sensor in an outpatient setting: Results from a diabetes research in children network (DirecNet) study. Diabetes Technol Ther 2005;7:109-14. |
|70.||Munoz M, Pronovost P, Dintzis J, Kemmerer T, Wang NY, Chang YT, et al. Implementing and evaluating a multicomponent inpatient diabetes management program: Putting research into practice. Jt Comm J Qual Patient Saf 2012;38:195-206. |
|71.||Alexanian SM, McDonnell ME, Akhtar S. Creating a perioperative glycemic control program. Anesthesiol Res Pract 2011;2011:465974. |
|72.||Bernard JB, Munoz C, Harper J, Muriello M, Rico E, Baldwin D. Treatment of inpatient hyperglycemia beginning in the emergency department: A randomized trial using insulins aspart and detemir compared with usual care. J Hosp Med 2011;6:279-84. |
|73.||Donihi AC, Gibson JM, Noschese ML, DiNardo MM, Koerbel GL, Curll M, et al. Effect of a targeted glycemic management program on provider response to inpatient hyperglycemia. Endocr Pract 2011;17:552-7. |
|74.||Cook CB, Elias B, Kongable GL, Potter DJ, Shepherd KM, McMahon D. Diabetes and hyperglycemia quality improvement efforts in hospitals in the United States: Current status, practice variation, and barriers to implementation. Endocr Pract 2010;16:219-230. |
|75.||Moghissi ES, Hirsch IB. Hospital management of diabetes. Endocrinol Metab Clin North Am 2005;34:99-116. |
|76.||Qureshi A, Deakins DA, Reynolds LR. Obstacles to optimal management of inpatient hyperglycemia in noncritically ill patients. Hosp Pract (Minneap) 2012;40:36-43. |
|77.||Tamler R, Green DE, Skamagas M, Breen TL, Lu K, Looker HC, et al. Durability of the effect of online diabetes training for medical residents on knowledge, confidence, and inpatient glycemia. J Diabetes 2012;4:281-90. |
|78.||Latta S, Alhosaini MN, Al-Solaiman Y, Zena M, Khasawneh F, Eranki V, et al. Management of inpatient hyperglycemia: Assessing knowledge and barriers to better care among residents. Am J Ther 2011;18:355-65. |
|79.||Tamler R, Green DE, Skamagas M, Breen TL, Looker HC, LeRoith D. Effect of case-based training for medical residents on confidence, knowledge, and management of inpatient glycemia. Postgrad Med 2011;123:99-106. |
|80.||Selig PM, Popek V, Peebles KM. Minimizing hypoglycemia in the wake of a tight glycemic control protocol in hospitalized patients. J Nurs Care Qual 2010;25:255-60. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]