Management of InpatientHyperglycemia and Diabetesin Older AdultsDiabetes Care 2017;40:509–517 | DOI: 10.2337/dc16-0989

Adults aged 65 years and older are the fastest growing segment of the U.S.population, and their number is expected to double to 89 million between2010 and 2050. The prevalence of diabetes in hospitalized adults aged 65–75 yearsand over 80 years of age has been estimated to be 20% and 40%, respectively.Similar to general populations, the presence of hyperglycemia and diabetes inelderly patients is associated with increased risk of hospital complications,longer length of stay, and increased mortality compared with subjects withnormoglycemia. Clinical guidelines recommend target blood glucose between140 and 180 mg/dL (7.8 and 10 mmol/L) for most patients in the intensive careunit (ICU). A similar blood glucose target is recommended for patients in non-ICU settings; however, glycemic targets should be individualized in older adultson the basis of a patient’s clinical status, risk of hypoglycemia, and presence ofdiabetes complications. Insulin is the preferred agent to manage hyperglycemiaand diabetes in the hospital. Continuous insulin infusion in the ICU and rationaluse of basal-bolus or basal plus supplement regimens in non-ICU settings areeffective in achieving glycemic goals. Noninsulin regimens with the use ofdipeptidyl peptidase 4 inhibitors alone or in combination with basal insulinhave been shown to be safe and effective and may represent an alternativeto basal-bolus regimens in elderly patients. Smooth transition of care to theoutpatient setting is facilitated by providing oral and written instructions re-garding timing and dosing of insulin as well as education in basic skills for homemanagement.

The global burden of diabetes has increased significantly during the past twodecades and is expected to affect more than 642 million adults by 2040, withthe majority of patients having type 2 diabetes (1). In the U.S., the Centers forDisease Control and Prevention has estimated that 9.3% of the total populationhas diabetes (2) and forecasted that the incidence will double by 2050 (3). Di-abetes disproportionally affects the elderly, as more than 25% of the U.S. popu-lation older than 65 years of age has diabetes (4). For those aged 65–74 years, therates doubled from 10.1 to 21.5% between 1993 and 2014, and for those aged75 years or older, the rate increased from 8.0 to 19.2% between 1990 to 2014 (5).Patients with diabetes are more likely to require hospital admissions comparedwith individuals without diabetes. Results from the National Hospital DischargeSurvey (NHDS) estimated that ;250,000 hospitalized patients had diabetes as afirst-listed diagnosis in 2010, with a more than three times higher rate for indi-viduals aged 65 years and older (48.9 per 10,000 population) compared withpatients younger than 45 years (13.3 per 10,000 population) (6).

Division of Endocrinology, Metabolism and Lip-ids, Department of Medicine, Emory UniversitySchool of Medicine, Atlanta, GA

Corresponding author: Guillermo E. Umpierrez,geumpie@emory.edu.

Received 5 May 2016 and accepted 2 November2016.

© 2017 by the American Diabetes Association.Readers may use this article as long as the workis properly cited, the use is educational and notfor profit, and the work is not altered. More infor-mation is available at http://www.diabetesjournals.org/content/license.

See accompanying articles, pp. 440,444, 453, 461, 468, 476, 485, 494,502, 518, and 526.

Guillermo E. Umpierrez and

Francisco J. Pasquel

Diabetes Care Volume 40, April 2017 509

DIABETES

ANDAGING

Several observational and prospec-tive randomized trials have reported astrong association between inpatienthyperglycemia and poor clinical out-come with regard to mortality, morbid-ity, length of stay, infections, and overallcomplications (7,8). In addition, substan-tial evidence indicates that correction ofhyperglycemia reduces infections, hospi-tal complications, and mortality (9–11).Few prospective studies, however, havefocused on the management of elderlypatients in the inpatient setting. This re-view will examine the prevalence, diag-nosis and monitoring, and availablerecommendations on the hospital man-agement of hyperglycemia and diabetesin the elderly population.

PREVALENCE

The overall prevalence of inpatient hy-perglycemia and diabetes in elderly pa-tients is not known. Cross-sectionalstudies have reported an estimatedprevalence of diabetes in older adultsaged 65–75 and .80 years of 20%and 40%, respectively (12,13). Com-pared with individuals ,65 years ofage, hospital discharge rates related todiabetes are 1.5- and 2.4-fold higheramong subjects aged 65–74 and .75years, respectively (14). The Atheroscle-rosis Risk in Communities (ARIC) Study,with a follow-up period longer than20 years, recently reported higher rates

of hospitalization with increasing age insubjects with and without diabetes,with rates of hospitalization 3.1 timeshigher in individuals with diagnosed di-abetes compared with those without ahistory of diabetes (15) (Fig. 1). In thehospital, the prevalence of hyperglycemia(defined as blood glucose .140 mg/dL[7.8 mmol/L]) in patients over the age of65 years is reported in more than 70% ofcritically ill and cardiac surgery patients(16,17) and in about one-third of generalmedicine and surgery patients (7,18).

ECONOMIC BURDEN

Adults over 65 years of age account formore than one-third of all U.S. commu-nity hospital stays (19). In 2012, esti-mates from national surveys, medicalstandard analytical files, and claims da-tabases for the commercially insuredpopulation in the U.S indicated thatthe total cost of diabetes was approxi-mately $245 billion (20). Approximately59% of health care expenditures attrib-uted to diabetes are related to healthresources used by the population olderthan 65 years of age, much of which ispaid by the Medicare programs. The es-timated average annual excess expendi-ture for patients with diabetes aged65 years and above was $11,825 peryear, which is twice the expenditurefor patients younger than 65 years ofage. In addition, elderly patients with

hyperglycemia and diabetes are lesslikely to be discharged to home, fre-quently requiring transfer to a transitionalcare unit or nursing home facility, increas-ing medical costs (7). Similarly, elderlyresidents with diabetes in long-termcare facilities have significantly highernumber of comorbidities, cardiovasculardisease, kidney disease, visual impair-ment, and foot problems (including am-putations) and havehigher odds of havingemergency room visits compared withresidents without diabetes (21,22).

PATHOPHYSIOLOGY

Hyperglycemia is commonly present inpatients with acute medical or surgicalconditions, resulting from the metabolicand hormonal changes associated withincreased circulating counterregulatoryhormones (cortisol, catecholamines,growth hormone, and glucagon) andproinflammatory cytokines that inter-fere with carbohydrate metabolism,leading to excessive hepatic glucoseproduction and reduced glucose uptakein peripheral tissues (Fig. 2) (10,23). Inaddition, physiological changes in olderadults contribute to the increased prev-alence of hyperglycemia and diabetes(24,25). Aging is associated with re-duced glucose-induced insulin releaseand increased insulin resistance in pe-ripheral tissues, primarily in muscleand adipose tissue (26). Increasing agealso tends to be associated with abdom-inal obesity and increased circulatinglevels of free fatty acids and inflamma-torymarkers, specifically tumor necrosisfactor a and interleukin 6, which are as-sociated with increased insulin resis-tance in the elderly (27,28). Furthercontributors to the development of hy-perglycemia in the elderly are the use ofmedications with adverse effects on car-bohydratemetabolism such as diuretics,b-blockers, and glucocorticoids.

Several mechanisms explain the detri-mental effects of hyperglycemia (Fig. 2).Hyperglycemia causes osmotic diuresisthat leads to hypovolemia, decreased glo-merular filtration rate, and prerenal azote-mia. Hyperglycemia is associated withimpaired leukocyte function, including de-creased phagocytosis, impaired bacterialkilling, and chemotaxis, leading to hospitalinfections and poor wound healing. In ad-dition, acute hyperglycemia results in theactivation of nuclear factor kB (NF-kB),the production of proinflammatory

Figure 1—Longitudinal data on all-cause hospitalizations in the ARIC Study (15). Data are pre-sented according to diabetes and HbA1c categories.

510 Inpatient Hyperglycemia in Older Adults Diabetes Care Volume 40, April 2017

cytokines, and oxidative stress, leadingto increased vascular permeabilityand mitochondrial dysfunction (29,30).Furthermore, hyperglycemia impairs en-dothelial function by suppressing for-mation of nitric oxide and impairingendothelium-dependent, flow-mediateddilation (30).

CLINICAL PRESENTATION

Elderly patients are less likely to experi-ence typical symptoms of hyperglycemia,such as polyuria and polydipsia, becausethe renal threshold for glycosuria in-creases with age and the thirst mecha-nisms are more likely to be impaired.Elderly patients often present withweight loss and fatigue; however, thesesymptoms frequently go unnoticed or areattributed to old age, failure to thrive, orconfusion (21).Elderly patients differ according to

the time of diabetes onset. Patients withlonger duration of diabetes have a muchgreater burden of microvascular diseaseand worse glycemic control than patientswith shorter duration of disease (31). Also,

the interaction of age and duration of di-abetes (age3 duration) has been asso-ciated with end-stage renal disease, eyedisease, lower-limb amputation, stroke,heart failure, and mortality (32), sug-gesting that older patients with longerduration of diabetes admitted to thehospital are a particularly vulnerablepopulation.

The two leading causes of hospital ad-missions in older adults with diabetesare cardiovascular disorders (coronaryartery disease, angina, heart failure,and stroke) and respiratory diseases(pneumonia and chronic obstructivepulmonary disease (33,34). They arefollowed by diseases of the digestiveand genitourinary systems, with diabe-tes as the primary diagnosis (34).

Of great interest is the increasingnumber of admissions due to adversedrug reactions in the elderly (aged65 years or older) adults accounting formore than 700,000 emergency depart-ment visits and 120,000 hospitalizationsin the U.S. each year (34). Older adults(aged 65 years or older) are twice as

likely as others to come to emergencydepartments for adverse drug events(over 177,000 emergency visits eachyear) and nearly seven times more likelyto be hospitalized after an emergencyvisit. Data from the National ElectronicInjury Surveillance System–CooperativeAdverse Drug Event Surveillance Proj-ect (NEISS-CADES) (2007 through 2009)estimated that about half of the hospitaladmissions for adverse drug reactionswere for adults older than 65 years ofage and half of these hospitalizationswere for people over the age of 80 years(35). Four medications or medicationclasses were implicated (alone or incombination) in 67.0% (95% confi-dence interval [CI], 60.0–74.1) of hospi-talizations: warfarin (33.3%), insulin(13.9%), oral antiplatelet agents (13.3%),and oral hypoglycemic agents (10.7%).Among older Medicare beneficiarieswith diabetes, hospital admissions forhypoglycemia now outpace those for hy-perglycemia (36), which is likely the resultof increased efforts to intensify glycemiccontrol over the past decade.

Figure 2—Pathophysiology of hyperglycemia and its complications in older adults. TG, triglycerides.

care.diabetesjournals.org Umpierrez and Pasquel 511

GLYCEMIC CONTROL TRIALS INELDERLY POPULATIONS

The results of observational and ran-domized trials in hospitalized patientswith and without a history of diabeteshave reported a strong association be-tween hyperglycemia and poor clinicaloutcome in all patients including the el-derly. Few studies, however, have re-ported on the impact of hyperglycemiaand its treatment on hospital outcomesin elderly patients, and most random-ized clinical trials that examined theeffect of inpatient glycemic control onoutcomes excluded frail older persons(11,37–39). A large observational cohortstudy that included 250,040 admissionsfrom 173 medical, surgical, and cardiacintensive care units, of whom 66% ofpatients were older than 60 years ofage, reported that hyperglycemia wassignificantly associated with increasedmortality in critically ill individuals, inde-pendent of severity of illness (40). Com-pared with normoglycemic individuals,adjusted odds of mortality [odds ratio(95% CI)] for mean glucose 146–199,200–300, and .300 mg/dL were 1.82(1.74–1.90), 2.13 (2.03–2.25), and 2.85(2.58–3.14), respectively.Although patients in subacute care

units may not necessarily representacutely ill patients in the hospital, thedemographic characteristics are compa-rable to elderly hospitalized patients.We recently reported the results of aprospective randomized controlled trialevaluating the efficacy and safety of di-abetes treatment in elderly patientswith type 2 diabetes admitted to long-term care facilities, with .90% of themadmitted to subacute care units (41). Atotal of 150 patients (aged 796 8 years,duration of diabetes 8.2 6 5.1 years)with a randomization glucose of 194 697 mg/dL were treated with low-dosebasal insulin (glargine, starting dose 0.1units/kg/day) or oral antidiabetic drug(OAD) therapy as per primary care providerdiscretion for 26 weeks. Both groups re-ceived supplemental rapid-acting insulin be-fore meals for blood glucose .200 mg/dL.There were no differences in themean fast-ing glucose, hospital complications, or mor-tality between treatment groups. A majorfinding in our study is that treatmentwith a low dose of basal insulin and OADresulted in a similar frequency of hypoglyce-mia, with;30% of patients experiencing

glucose ,70 mg/dL. These results sug-gest that starting with a low daily doseof basal insulin of ;0.1 units/kg is suffi-cient tomaintain blood glucose levels in areasonable range in elderly patients. Un-fortunately, no prospective studies havebeen conducted in hospitalized elderlypatients with diabetes, and these resultscannot necessarily be extrapolated to theinpatient setting.

INPATIENT HYPOGLYCEMIA

Hypoglycemia is common in hospital-ized elderly patients and is associatedwith poor outcomes. In general medi-cine and surgical patients with diabetes,hypoglycemia occurs in 12–38% of pa-tients with type 2 diabetes receiving in-sulin therapy (11,24,38,39,42,43). Incritically ill patients enrolled in clinicaltrials, the prevalence of severe hypogly-cemia (glucose #40 mg/dL) ranged be-tween 5 and 18.7% with intensiveglycemic control (17,44–46). The Nor-moglycemia in Intensive Care Evaluation–Survival Using Glucose AlgorithmRegulation (NICE-SUGAR) trial reportedthat among 6,026 patients, a total of2,714 (45.0%) patients had hypoglyce-mia (45). During follow-up, mortalitywas 23.5% in patients without hypogly-cemia, 28.5% in subjects with moderatehypoglycemia (41 to 70 mg/dL [2.3to 3.9 mmol/L]) and 35.4% in thosewith severe hypoglycemia (,40 mg/dL[2.2mmol/L]). The hazard ratio for deathwith adjustment for treatment assign-ment, as compared with those withouthypoglycemia, was 1.81 (95% CI 1.59–2.07) for moderate hypoglycemia and3.21 (95% CI 2.49–4.15) for patientswith severe hypoglycemia (46).

Hospitalized patients who are elderlyare especially vulnerable to the adverseeffects of inpatient hypoglycemia (47).Several observational and randomizedclinical trials have reported that hypo-glycemia in elderly patients is associatedwith longer length of stay and increasedhospital mortality (48–50). In a study ex-clusively involving hospitalized patientsaged 70 years or older, Kagansky et al.(48) reported that hypoglycemia is com-mon and associated with twofold in-creased mortality during hospitalizationand during 3-month follow-up. Similarly,Shilo et al. (49) reported that in patientsaged 65 years and older admitted toacute medical and geriatric wards, hypo-glycemia (mean glucose 39 6 7 mg/dL)

was a predictor of mortality [odds ratio3.67 (95% CI 1.2–11.2)] even after theadjustment for other risk factors.

Many risk factors contribute to de-velopment of inpatient hypoglycemia(Table 1). Treatment with insulin is themost common risk factor for inpatient hy-poglycemia (47,51). Other risk factors in-clude use of sulfonylurea therapy, failureto adjust insulin to nutritional intake,and changes to hospital routine (51,52).Interruptions in usual nutritional intakeand changes in medications frequentlyoccurduring hospitalization and canpreci-pitate hypoglycemia when hypoglycemicagents are used. Elderly people aremore prone to hypoglycemia during hos-pitalization because of the higher rateof comorbidities such as renal failure,malnutrition, malignancies, dementia,and frailty (48,53). In addition, older hos-pitalized patients often experience fail-ure of regulatory mechanisms, especiallyin stress situations, such as reduced re-lease of glucagon and epinephrine in re-sponse to hypoglycemia (54). In addition,despite a comparable prolongation ofreaction time induced by hypoglycemia,elderly patients fail to perceive neurogly-copenic and autonomic hypoglycemicsymptoms (55), which can delay the re-sponse to correct a hypoglycemic episodeby the hospital staff.

The presence of renal failure, sepsis(49,53), and low albumin level (56) arepredictive markers of hypoglycemia in el-derly hospitalized patients. Under normalconditions, renal glucose release accountsfor 20–40% of overall gluconeogenesis

Table 1—Factors contributing to inpa-tient hypoglycemia in older adults withdiabetesMedications: insulin, sulfonylureas, glinides,

quinolones

Intensive glycemic control

Inappropriate insulin dosing and medicationerrors

Poor coordination of insulin administrationand food delivery

Interruption of enteral nutrition orparenteral nutrition infusion

Hypoglycemia unawareness

Renal insufficiency

Liver failure

Severe illness, sepsis

Dementia

Frailty

Medical and surgical procedures

512 Inpatient Hyperglycemia in Older Adults Diabetes Care Volume 40, April 2017

and, in conditions such as fasting and hy-poglycemia, can increase two- to three-fold. In patients with renal insufficiency,decreased renal gluconeogenesis, lack ofgluconeogenic substrates with decreasedfood intake, decreased renal degradationand excretion of insulin, and impairmentof counterregulatory hormonal responsescan all lead to hypoglycemia.Recent studies have reported that the

increased mortality rates associatedwith inpatient hypoglycemia may notbe caused directly by hypoglycemia perse but may instead be due to the associa-tion between hypoglycemia and more se-vere illness (47,57,58). These studies haveshown that in patients with and withoutdiabetes, mortality was higher only amongthosewith spontaneoushypoglycemia andnot in iatrogenic-induced hypoglycemia(i.e., insulin therapy). Thus, it is possiblethat antihyperglycemic therapy mayunmask a propensity to develop hypogly-cemia in the severely ill rather thandirectlycause death. As elderly patients are at in-creased risk of comorbidities and inpatientmortality, it has not been possible to de-termine if hypoglycemia is a marker ofseverity of illness or a direct cause of mor-tality.

GLYCEMIC TARGETS

In the absence of specific recommenda-tions for the inpatient management ofdiabetes and hyperglycemia in olderadults, we recommend to follow generalclinical guidelines for adult patients butwith emphasis in preventing hypoglyce-mia. For inpatient glycemic control, theAmerican Diabetes Association’s Stan-dards of Medical Care in Diabetesd2016recommends target glucose levels be-tween 140 and 180 mg/dL (7.8 and10 mmol/L) for most intensive care unit(ICU) patients (59). More stringent goals,such as 110–140 mg/dL (6.1–7.8 mmol/L),may be appropriate for select patients,such as cardiac surgery patients and pa-tients with acute ischemic cardiac or neu-rological events, provided the targets canbe achievedwithout significant hypoglyce-mia. The Society of Thoracic SurgeonsBlood Glucose Guideline Task Force rec-ommended that patients with or withoutdiabetes who have persistently elevatedserum glucose .180 mg/dL (10 mmol/L)during the perioperative period shouldreceive intravenous (IV) insulin infusionsto maintain serum glucose ,180 mg/dL(10 mmol/L) (60). In agreement with less

aggressive targets, two recent random-ized controlled trials in cardiac surgery pa-tients failed to demonstrate that intensiveinsulin therapy targeting glucose between100–140 mg/dL reduces hospital compli-cations compared with a target of 140–180 mg/dL (61,62).

A glucose target between 140 and180 mg/dL (between 7.8 and 10.0 mmol/L)was recommended for most patients innoncritical care units (59). Patients with aprior history of successful glycemic controlin the outpatient setting in the absence ofhypoglycemiamaybemaintainedwithaglu-cose target below 140 mg/dL (7.8 mmol/L).For avoidance of hypoglycemia, daily in-sulin dosage adjustment is usually nec-essary when glucose values fall below100 mg/dL (5.6 mmol/L) (8). The admis-sion HbA1c concentration was recentlyshown to be a good predictor of inpa-tient glycemic control and risk ofhypoglycemia ,70 mg/dL (3.9 mmol/L)in insulin-treated patients with type 2diabetes (64). In this study, patients ad-mitted with HbA1c levels ,7% were athigher odds for hypoglycemia (63).

Higher glucose ranges may be accept-able in terminally ill patients, in patientswith severe comorbidities, and in in-patient care settings where frequentglucosemonitoring or close nursing super-vision is not feasible. These recommenda-tions, in agreementwith Endocrine Societyrecommendations (8) for inpatient man-agement of hyperglycemia and diabetesin non-ICU settings, suggest the need ofindividualization of glycemic targetsbased on the patient’s clinical status,risk of hypoglycemia, and presence of co-morbidities.

MANAGEMENT OFHYPERGLYCEMIA IN THE ICU

Several strategies have been used toachieve glycemic control in critical caresettings. The short half-life of IV insulin(,15 min) allows flexibility in adjustingthe infusion rate in the event of unpre-dicted changes in nutrition or the patient’shealth. In most patients, the use of contin-uous insulin infusion (CII) lowers bloodglucose levels to target range in less than4– 8 h and allows for rapid dose titration inaccordance with changes in clinical status.The Society of Critical Care Medicine andThe Society of Thoracic Surgeons recom-mend that a glucose level .180 mg/dLshould trigger initiation of insulin ther-apy, titrated to maintain glucose values

between 140 mg/dL and 180 mg/dL whileavoiding hypoglycemia (60,64). A largenumber of CII protocols for the treatmentof medical and surgical patients in the ICUare reported in the literature (65).Recently,computer-based algorithms aiming todirect the nursing staff in adjusting insu-lin infusion rates have become commer-cially available. Although the use ofcomputer-based algorithms has been as-sociated with lower rates of hypoglyce-mia, glycemic variability, and a higherpercentage of glucose readings withintarget range, no studies have reportedreduction in hospital complications ormortality compared with treating patientswith the standard regimens (9,64). The useof subcutaneous insulin has not been for-mally studied in ICU patients and should beavoided in critical ill patients, in particularduring hypotension or shock.

MANAGEMENT OFHYPERGLYCEMIA INNONCRITICAL CARE SETTINGS

Subcutaneous insulin is the preferredagent for glycemic control in non-ICU set-tings. Formostpatients innon-ICU settings,subcutaneous insulin therapywith basal in-sulin once or twice daily, alone or in com-bination with prandial insulin, is effectiveand safe. The use of sliding scale insulin isnot acceptable as the single regimen in pa-tientswith diabetes, as it results in undesir-able hypoglycemia and hyperglycemia andincreased risk of hospital complications.Selecting the treatment regimen in elderlypatients is based on patient’s nutritionalstatus, bodyweight, andhypoglycemia risk.

Basal Prandial RegimenPatients with adequate oral intake shouldreceive a basal prandial regimen dividedhalf as basal and half as prandial insulinstarting at a total daily dose (TDD) of 0.3units per kg (Fig. 3). Half of the TDD shouldbe given as basal insulin once daily andhalfas rapid acting insulin before meals. Sev-eral studies have shown that basal-bolusregimen results in better glycemic controland in lower rates of perioperative compli-cations compared with sliding scale insulintherapy alone (11,38).

Multiple doses of NPH and regular in-sulin were compared with basal-bolusregimen with insulin analogs in two con-trolled trials in medical patients with type 2diabetes (37,43). Both studies reported thattreatment with NPH and regular insulin re-sulted in similar improvements in glycemic

care.diabetesjournals.org Umpierrez and Pasquel 513

control and no difference in the rate of hy-poglycemic events or in hospital length ofstay, compared with basal-bolus regimen.However, becauseNPHhas a peakof action;8–12 h after injection, there is risk of hy-poglycemia in patients with poor oral in-take. In one of the studies, the number ofsevere hypoglycemic episodes was higherin patients receiving human insulin com-pared with insulin analogs (43). In a morerecent study, the use of premixed humaninsulin in elderly patients (mean age ;70years) in general medicine and surgeryareas resulted in a threefold higher rate ofhypoglycemia compared with the use ofbasal-bolus regimen with insulin analogs,indicating that premixed formulationsshould be avoided in the hospital setting(66).

Basal-Bolus RegimenMost elderly patients have reduced oralintake due to lack of appetite, acute ill-ness, medical procedures or surgicalinterventions. In such patients, thestarting insulin total daily dose shouldbe reduced to 0.1–0.15 units/kg/day,given mainly as basal insulin (39). If nec-essary, additional rapid-acting insulinanalogs or short-acting insulin is admin-istered as correctional insulin coveragefor glucose levels .180 mg/dL (10mmol/L) before meals and at bedtime.The recently reported Basal Plus trial(39) randomized patients with type 2 di-abetes to receive a basal-bolus regimenwith glargine once daily and glulisine

before meals and to a basal plus regi-men with glargine once daily andsupplemental doses of glulisine for cor-rection of hyperglycemia per slidingscale. This trial reported that the use ofbasal insulin at a starting dose of 0.25 or0.15 units/kg/day in patients younger orolder than age 70 years, respectively, re-sulted in similar improvement in gly-cemic control and in the frequency ofhypoglycemia compared with a standardbasal-bolus regimen. These results indi-cate that the basal plus correction regi-men is preferred for patients with poororal intake, whereas a basal-prandial(basal-bolus) insulin regimen may bepreferred for patients with good nutri-tional intake.

SUPPLEMENTAL/CORRECTIONDOSES OF REGULAR INSULIN(“SLIDING SCALE”)

The use of sliding scale insulin (SSI) con-tinues to be a common practice to correcthyperglycemia in hospitalized patients,including elderly patients. Potential advan-tages of SSI are convenience, simplicity,andpromptness of treatment. It is possiblethat in some patients with good glycemiccontrol treatedwith diet alone orwith oralantidiabetes agents before admission, theuse of SSI may be sufficient for glycemiccontrol over the short term. The use of aSSI regimen alone is faced with severalchallenges that include inadequate cover-age of glycemic excursions and increased

risk of complications (11,38). Several ran-domized multicenter trials comparing theefficacy and safety of SSI and basal insulinanalogs reported greater improvement inblood glucose control and reduction inhospital complications compared withthe use of SSI. In patients with poor nutri-tion intake, the use of a daily dose of basalinsulin in combination with SSI to correcthyperglycemia has been shown to be ef-fective in improving glycemic control andin preventing complications (39).

NONINSULIN THERAPIES

The use of noninsulin antihyperglyce-mic agents are not recommended forthe management of hyperglycemia inhospitalized patients. There are potentiallimitations to the use of most oral antidia-bet agents, including the slow onset of ac-tion, which may not allow rapid doseadjustment to meet the changing needsof the acutely ill patient, and risk of hypo-glycemia with insulin secretagogues (8). Inaddition, many patients have one or morecontraindications to the use of metforminupon admission including acute heart fail-ure or renal or liver failure, which mayincrease the risk of lactic acidosis (67). Theuse of thiazolidinediones may precipitateor worsen heart failure and peripheraledema.

There has been recent interest inusing incretin-based therapies in thehospital because they have few side ef-fects and are associated lower rates ofhypoglycemia compared with insulinregimens (68). A recent randomized,open-label pilot trial determined differ-ences in glycemic control betweentreatment with sitagliptin alone or incombination with basal insulin in non-cardiac patients with type 2 diabe-tes (69). Patients in the sitagliptingroup received a single daily dose of50–100 mg based on kidney function.Sitagliptin was well tolerated, and, in com-bination with supplemental (correctiondoses) rapid-acting insulin or in combina-tion with basal (glargine) insulin, resultedin no significant differences in mean dailyblood glucose, frequency of hypoglyce-mia, or the number of treatment failurescompared with a basal-bolus regimen.These results suggest that treatmentwith a dipeptidyl peptidase 4 inhibitoralone or in combination with basal in-sulin is safe,may represent an alternativefor the management of hyperglycemia inthe hospital, and may prove especially

Figure 3—Insulin therapy in hospitalized elderly patients with diabetes.

514 Inpatient Hyperglycemia in Older Adults Diabetes Care Volume 40, April 2017

useful in treating elderly patients withmild to moderate hyperglycemia. Similarresults were found in a multicenter trial(n = 279) (70) comparing sitagliptin plusbasal insulin with basal-bolus therapy inhospitalized patients and a study(NCT02182895, n = 70) enrolling patientswith good glycemic control (HbA1c,7.5%)comparing saxagliptin with insulin ther-apy. Both studies were presented at the76th Scientific Sessions of the AmericanDiabetes Association, New Orleans, LA,10–14 June 2016. Caution is recom-mended with the use of saxagliptinand alogliptin in patients with estab-lished heart or kidney disease becauseof a potential increased risk of heartfailure, according to a recent FDA safetycommunication.The sodium–glucose cotransporter

2 (SGLT2) inhibitors, a class of oral anti-diabetic agents that decrease concen-trations of plasma glucose by inhibitingproximal tubular reabsorption in thekidney, have been shown to be effectivein reducing HbA1c by ;0.6–1.0% with alow risk of hypoglycemia. These agents,however, have been associated with in-creased risk of urinary and genital tractinfections and dehydration and are con-traindicated in patients with impairedrenal function. In addition, an associa-tion has been reported between theuse of SGLT2 inhibitors and the develop-ment of diabetic ketoacidosis among pa-tients with type 1 and type 2 diabetes(71). These potential side effects makethe use of SGLT2 inhibitors less attrac-tive in acutely ill hospitalized patientswith hyperglycemia.

HOSPITAL DISCHARGE PLANNING

The discharge period is often a furtheropportunity to improve the global careof the older patient with diabetes. Al-though insulin is used in the hospitalfor most patients with diabetes, manypatients do not require insulin after dis-charge. At discharge, most elderly pa-tients with type 2 diabetes who areclinically stable can, in the absence ofcontraindications, recommence oralmedications. Admission HbA1c has beenshown to help in tailoring diabetes treat-ment after hospital discharge (72). El-derly patients with acceptable diabetescontrol (HbA1c ,7.5–8%) could be dis-charged on their prehospitalizationtreatment regimen (oral agents and/orinsulin). Subjects with HbA1c between

8.0 and 10% could be discharged onoral agents plus basal insulin at 50% ofthe hospital basal dose. Patients withHbA1c .10% should be discharged on abasal-bolus regimen or on a combinationof preadmission oral agents plus 80% ofhospital basal insulin dose (72).

Patients who are either newly startedon diabetes medications or those withdiabetes who have treatment modifica-tions during the hospital stay are at riskfor medication errors and adverse ef-fects following hospital discharge if clearinformation about glycemic manage-ment is not provided at time of dis-charge (73). To avoid confusion andreduce the likelihood of readmission, itis important to effectively communicatethe discharge diabetes regimen to boththe patient (and/or the caregiver) aswell as the patient’s primary care physi-cian. Although glucose control may bebeneficial in decreasing diabetes com-plications, the risk of hypoglycemicevents can be detrimental in the elderlyand may lead to increased morbidityand mortality. Physicians should keepin mind that no randomized controlledtrials have shown benefits of tight gly-cemic control on clinical outcome andquality of life in ambulatory elderly pa-tients and in residents admitted to long-term care facilities. Until those studiesbecome available, we believe that safeand moderate glycemic control, mini-mizing the risk of hypoglycemic events,are indicated in elderly patients withdiabetes.

CONCLUSIONS

Both diabetes and hyperglycemia arecommon and are associated with in-creased risk of complications among el-derly hospitalized patients. Carefulattention to goal-directed glycemicmanagement can help avoid complica-tions of uncontrolled hyperglycemiaand hypoglycemia in these patients.Scheduled insulin therapy is recom-mended for the majority of patientswith type 2 diabetes in the hospital. Pa-tients treated with insulin prior to ad-mission can continue to receive theirusual home regimenmodified accordingto severity of illness, risk of hypoglyce-mia, and level of glycemic control. Forpatients not previously treated with in-sulin, weight-based dosing algorithmscan be used for calculation of basaland/or basal-bolus regimens as the

preferred treatment alternative in thehospital. Increasing evidence indicatesthat the use of dipeptidyl peptidase 4 in-hibitors alone or in combination withlow-dose basal insulin may representan effective and safe alternative to abasal-bolus insulin regimen. Providingpatients and their caregivers with theskills and information necessary to man-age their regimen as outpatients cancontribute to improved glycemic controlwhile lowering the risk for hypoglycemiaand readmission.

Funding and Duality of Interest. G.E.U. ispartly supported by research grants from theAmerican Diabetes Association (1-14-LLY-36),Public Health Service Grant UL1 RR025008from the Clinical and Translational ScienceAward program, and 1P30DK111024-01 fromthe National Institutes of Health and NationalCenter for Research Resources. G.E.U. has alsoreceived unrestricted research support for in-patient studies (to Emory University) fromMerck, Novo Nordisk, AstraZeneca, BoehringerIngelheim, and Sanofi, and has received consul-ting fees and honoraria for membership ofadvisory boards from Sanofi. F.J.P. has receivedconsulting fees from Merck and BoehringerIngelheim, and research support (to EmoryUniversity) from Novo Nordisk. No other poten-tial conflicts of interest relevant to this articlewere reported.

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