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Hyperglycemia is the core pathologic finding in DM and control of hyperglycemia is a cornerstone of diabetes treatment. However, it is important to recognize that blood pressure control and lipid control appear to be as important (if not more important) in preventing and minimizing most end-organ complications of diabetes. Thus, when prioritizing interventions in medically complex older adults with diabetes, focusing first on blood pressure is a reasonable approach in most patients.
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Glycemic control targets—
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Hemoglobin A1c (HbA1c) has been shown to correlate closely with average glucose levels and are strongly predictive of microvascular complications. A reasonable rule of thumb is that each 1% increase or decrease in HbA1c is equivalent to a corresponding approximately 30 mg/dL change in average glucose levels, as shown in Table 42–1.
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The goals of glycemic treatment differ in healthy and frail older patients, resulting in different recommended glycemic targets. Studies suggest that tight glycemic control to HbA1c ≤7% decreases the rates of microvascular complications over 8 years. Thus, the ADA recommends HbA1c <7% for healthy older adults with an extended life expectancy.
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However, tighter glycemic control has also been associated with increased rates of hypoglycemia and mortality. For older patients with limited life expectancy, tight glycemic control exposes them to a higher risk of adverse events with little chance that they would survive to benefit from decreases in microvascular complications. Because very poor glycemic control can lead to immediate symptoms such as fatigue, older patients with limited life expectancy should receive glycemic treatment that is aimed at avoiding symptomatic hyperglycemia while minimizing the risk of hypoglycemia. A recent guideline from the AGS suggests an HbA1c target of 8% for older adults. For older adults who are healthy, with few comorbidities, few functional limitations and extended life expectancy, HbA1c target of 7% to 8% is appropriate. Conversely, for older adults with extensive comorbidities, functional limitations and limited life expectancy, HbA1c target of 8% to 9% is appropriate (Table 42–2).
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Brown
AF, Mangione
CM, Saliba
D, Sarkisian
CA California Healthcare Foundation/American Geriatrics Society Panel on Improving Care for Elders with Diabetes. Guidelines for improving the care of the older person with diabetes mellitus.
J Am Geriatr Soc. 2003;51(5 Suppl Guidelines):S265-–S280.
CrossRef
[PubMed: 12694461]
+
Inzucchi
SE, Bergenstal
RM, Buse
JB
et al American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).
Diabetes Care. 2012;35(6):1364-–1379.
CrossRef
[PubMed: 22517736]
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Management of Diabetes Mellitus Update Working Group.
VA/DoD Clinical Practice Guideline for the Management of Diabetes Mellitus. Version 4.0. Washington, DC: Veterans Health Administration and Department of Defense; 2010.
+
Nathan
DM, Kuenen
J, Borg
R, Zheng
H, Schoenfeld
D, Heine
RJ A1c-Derived Average Glucose Study Group. Translating the A1C assay into estimated average glucose values.
Diabetes Care. 2008;31(8):1473-–1478.
CrossRef
[PubMed: 18540046]
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Ray
KK, Seshasai
SR, Wijesuriya
S
et al Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials.
Lancet. 2009;373(9677):1765-–1772.
CrossRef
[PubMed: 19465231]
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Glycemic control targets in hospitalized patients—
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Many older patients with diabetes are admitted to the hospital, most often for conditions other than diabetes. The goals for glycemic control in older hospitalized patients are to maintain euglycemia, avoid adverse events, and return to a stable outpatient regimen as soon as feasible. However, the stress of acute illness and frequent preprocedural fasting can make maintaining euglycemia challenging in hospitalized patients. In noncritically ill patients, the ADA recommends a fasting (premeal) glucose target of 90–140 mg/dL and a random glucose target of <180 mg/dL. The mainstays of glycemic treatment in hospitalized older adults are insulin and volume repletion.
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Although initial studies suggested improved outcomes in critically ill surgical patients with tight glycemic control (glucose levels of 80–110 mg/dL), subsequent studies have not shown similar benefits. The ADA recommends glucose levels between 140 and 180 mg/dL in both medical and surgical ICU patients.
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Moghissi
ES, Korytkowski
MT, DiNardo
M
et al American Association of Clinical Endocrinologists; American Diabetes Association. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control.
Diabetes Care. 2009;32(6):1119-–1131.
CrossRef
[PubMed: 19429873]
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Nonpharmacologic Treatments
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Dietary intervention is an integral component of diabetes treatment. For patients with diabetes and a body mass index >30 kg/m2, caloric restriction with the goal of weight loss is recommended. There is no role for caloric restriction in patients who are not overweight or obese. A wide variety of diets with varying macronutrient (carbohydrates, proteins, fats) proportions have been studied, but there is little data to suggest one diet is superior to another. Current ADA dietary recommendations mirror the American Heart Association recommendations and suggest (a) limiting saturated fat (<7% of total calories), (b) minimizing trans fats, and (c) limiting cholesterol intake (<200 mg/day). Medical nutritional therapy provided by a registered dietician is a covered Medicare benefit.
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It is important to recognize that for some older adults with diabetes, caloric or dietary restriction may be especially difficult or even harmful. First, changes in diet may be especially challenging for older patients who have established dietary habits over a lifetime. Second, older adults with functional difficulties who have difficulty shopping for groceries and preparing food are at risk for undernutrition; recommending a restricted range of foods may lead to weight loss or micronutrient deficiencies. Third, older adults with diabetes are at higher risk for periodontal disease and xerostomia, which may limit their ability to adapt to a new diet. Thus, dietary modifications should be approached with caution in nonobese older patients with diabetes.
+
Klein
S, Sheard
NF, Pi-Sunyer
X
et al American Diabetes Association; North American Association for the Study of Obesity; American Society for Clinical Nutrition. Weight management through lifestyle modification for the prevention and management of type 2 diabetes: rationale and strategies: a statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition.
Diabetes Care. 2004;27(8):2067-–2073.
CrossRef
[PubMed: 15277443]
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Regular exercise has been shown in improve glycemic control, blood pressure, lipids and contribute to weight loss. The ADA recommends that older adults with diabetes should strive to achieve 150 minutes per week of moderate-intensity exercise. For older patients with functional impairments who are unable to accomplish this, the ADA recommends maximizing their physical activity to reap some of the benefits of exercise. Because older patients with diabetes are at high risk for CVD, exercise regimens should start with low-intensity physical activity and gradually increase in intensity and duration.
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Colberg
SR, Sigal
RJ, Fernhall
B
et al American College of Sports Medicine; American Diabetes Association. Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement executive summary.
Diabetes Care. 2010;33(12):2692-–2696.
CrossRef
[PubMed: 21115771]
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Pharmacologic Therapy (Table 42–3)
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Most guidelines recommend metformin as first-line oral therapy for type 2 DM because it is efficacious (decreasing HbA1c approximately 1.5%), is not associated with weight gain or hypoglycemia, and appears to be associated with decreased cardiovascular complications compared to sulfonylureas. Large registry-based observational data suggests that patients taking metformin were at 15% to 21% decreased hazard of cardiovascular complications compared to patients taking glyburide or glipizide. Furthermore a 5-year randomized trial showed 46% decreased risk of cardiovascular outcomes in patients treated with metformin versus glipizide.
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Mild renal insufficiency (serum creatinine >1.5 mg/dL or creatinine clearance <30 mL/min) has been a relative contraindication to metformin because of the concern for lactic acidosis. However, lactic acidosis appears to be exceedingly rare with metformin, with an incidence of less than 1 per 10,000 person-years of treatment. A recent Cochrane review of 347 studies representing 126,000 patients found that metformin was not associated with an increased risk of lactic acidosis compared to other anti-hyperglycemic medications.
+
Hong
J, Zhang
Y, Lai
S
et al SPREAD-DIMCAD Investigators. Effects of
metformin versus
glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease.
Diabetes Care. 2013;36(5):1304-–1311.
CrossRef
[PubMed: 23230096]
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Nathan
DM, Buse
JB, Davidson
MB
et al American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes.
Diabetes Care. 2009;32(1):193-–203.
CrossRef
[PubMed: 18945920]
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Qaseem
A, Humphrey
LL, Sweet
DE, Starkey
M, Shekelle
P Clinical Guidelines Committee of the American College of Physicians. Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians.
Ann Intern Med. 2012;156(3):218-–231.
CrossRef
[PubMed: 22312141]
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Roumie
CL, Hung
AM, Greevy
RA
et al Comparative effectiveness of sulfonylurea and
metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study.
Ann Intern Med. 2012;157(9):601-–610.
CrossRef
[PubMed: 23128859]
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Salpeter
SR, Greyber
E, Pasternak
GA, Salpeter
EE Risk of fatal and nonfatal lactic acidosis with
metformin use in type 2 diabetes mellitus.
Cochrane Database Syst Rev. 2010;(4):CD002967.
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Schramm
TK, Gislason
GH, Vaag
A
et al Mortality and cardiovascular risk associated with different
insulin secretagogues compared with
metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study.
Eur Heart J. 2011;32(15):1900-–1908.
CrossRef
[PubMed: 21471135]
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The sulfonylureas in common use include glipizide and glyburide. Because sulfonylureas act predominantly by increasing pancreatic insulin secretion, weight gain is common and hypoglycemia may occur. Studies suggest that the risk of hypoglycemia is 1.5–2 times higher with glyburide than glipizide, possibly as a result of active metabolites; thus, glyburide should be avoided in older adults. Generally, most of the therapeutic effect occurs with half of the maximum recommended dose, and a decrease in HbA1c of 1% to 2% can be expected. Starting doses should be low, perhaps half that used for younger patients, and education regarding hypoglycemia provided. Sulfonylureas should be used with caution in patients with kidney disease since active metabolites are excreted slowly.
+
Gangji
AS, Cukierman
T, Gerstein
HC, Goldsmith
CH, Clase
CM A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of
glyburide with other secretagogues and with
insulin.
Diabetes Care. 2007;30(2): 389-–394.
CrossRef
[PubMed: 17259518]
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α-Glucosidase inhibitors—
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The α-glucosidase inhibitors acarbose (Precose) and miglitol (Glyset) inhibit the absorption of carbohydrates in the gut and decrease postprandial hyperglycemia. Consequently, they do not cause hypoglycemia or weight gain. Because α-glucosidase inhibitors are not systemically absorbed at usual doses (especially acarbose), they generally can be safely used in older adults and with either renal or hepatic insufficiency. The primary drawbacks of α-glucosidase inhibitors are gastrointestinal discomfort including flatulence and diarrhea, and low potency with HbA1c decreasing by approximately 0.5%.
+
Johnston
PS, Lebovitz
HE, Coniff
RF, Simonson
DC, Raskin
P, Munera
CL Advantages of alpha-glucosidase inhibition as monotherapy in elderly type 2 diabetic patients.
J Clin Endocrinol Metab. 1998;83(5):1515-–1522.
[PubMed: 9589648]
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The thiazolidinediones rosiglitazone (Avandia) and pioglitazone (Actos) act as insulin sensitizers. Thiazolidinediones have fallen out of favor as mounting evidence suggests increased cardiovascular risk, heart failure, and hepatotoxicity, especially with rosiglitazone.
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Meglitinides are short-acting insulin secretagogues that can decrease postprandial hyperglycemia. Repaglinide and nateglinide are the meglitinides available in the United States. Nateglinide appears to have a faster onset and shorter duration of action than repaglinide. There is limited experience with either drug in older adults, but they may be effective for patients with fasting euglycemia and postprandial hyperglycemia. Both medications should be taken before each meal, which may make medication adherence more difficult.
+
Black
C, Donnelly
P, McIntyre
L, Royle
PL, Shepherd
JP, Thomas
S Meglitinide analogues for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007;(2):CD004654.
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Incretin modulators: glucagon-like peptide-1 (GLP-1) analog and dipeptidyl peptidase-4 (DPP-4) inhibitors—
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Incretins, such as GLP-1 and DPP-4, are gastrointestinal hormones that modulate postprandial glucose homeostasis. Incretin modulators can decrease postprandial hyperglycemia by increasing glucose-dependent insulin secretion and slowing gastric emptying. Although these medications do not cause hypoglycemia when used alone, they may aggravate hypoglycemia when used with insulin or sulfonylureas.
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Exenatide and liraglutide are the GLP-1 analogs available in the United States. Exenatide is a synthetic analog of exendin-4, a component of Gila Monster saliva. Exendin-4 is structurally similar to GLP-1 (which decreases postprandial hyperglycemia) but is resistant to DPP-4 degradation, leading to more prolonged action. Both GLP-1 analogs appear to decrease HbA1c by approximately 1%. Because of delayed gastric emptying, nausea and weight loss are common. Acute pancreatitis is a rare but serious complication.
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Sitagliptin, saxagliptin, and linagliptin are the DPP-4 inhibitors available in the United States. They lead to HbA1c decreases of approximately 0.5%. They are generally well tolerated with less nausea and weight loss than GLP-1 analogs. As with GLP-1 analogs, acute pancreatitis has also been observed with DPP-4 inhibitors.
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There is little clinical experience with these medications in older adults. Given their cost and uncertainty regarding long-term safety, they should not be considered first-line agents for older adults.
+
Shyangdan
DS, Royle
P, Clar
C, Sharma
P, Waugh
N, Snaith
A Glucagon-like peptide analogues for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2011;(10):CD006423.
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Insulin is required in all patients with type 1 diabetes, and in many patients with moderate or severe type 2 diabetes. There is more than 75 years of clinical experience with insulin. With proper dosing, it can be used safely in cases of renal or hepatic insufficiency, as well as in the hospital, nursing home, or as an outpatient. Disadvantages of insulin include the risk of hypoglycemia, weight gain, and patient psychological barriers to injection.
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Many different types of insulin have been developed to provide flexible treatment options for different patterns of hyperglycemia (Table 42–4). Commonly used longer-acting insulins include glargine and neutral protamine Hagedorn (NPH), which are used once or twice daily, respectively, to provide basal insulin for control of fasting glucose levels. Commonly used shorter-acting insulins include lispro and regular before meals to provide bolus insulin to control postprandial glucose levels. Insulin mixtures such as 70/30 (70% NPH and 30% regular) may help simplify insulin regimens for many patients. For many older patients with type 2 diabetes, once-daily long-acting insulin at nighttime, often in addition to metformin, may be a reasonable starting regimen.
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+
Holman
RR, Farmer
AJ, Davies
MJ
et al 4-T Study Group. Three-year efficacy of complex
insulin regimens in type 2 diabetes.
N Engl J Med. 2009;361(18):1736-–1747.
CrossRef
[PubMed: 19850703]
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Horvath
K, Jeitler
K, Berghold
A
et al Long-acting
insulin analogues versus NPH
insulin (human isophane
insulin) for type 2 diabetes mellitus.
Cochrane Database Syst Rev. 2007;(2):CD005613.
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Qayyum
R, Bolen
S, Maruthur
N
et al Systematic review: comparative effectiveness and safety of premixed
insulin analogues in type 2 diabetes.
Ann Intern Med. 2008;149(8): 549-–559.
CrossRef
[PubMed: 18794553]
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Singh
SR, Ahmad
F, Lal
A, Yu
C, Bai
Z, Bennett
H Efficacy and safety of
insulin analogues for the management of diabetes mellitus: a meta-analysis.
CMAJ. 2009;180(4):385-–397.
CrossRef
[PubMed: 19221352]
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Amylin is a peptide that is cosecreted with insulin and modulates glucose homeostasis by delaying gastric emptying, promoting satiety, and decreasing postprandial glucagon secretion. Pramlintide is the only amylin mimetic available in the United States; it is approved for subcutaneous use for patients with type 1 or 2 diabetes taking insulin. Although generally well-tolerated, its effect is modest, decreasing HbA1c approximately 0.5%. Pramlintide must be injected separately from insulin, complicating medication adherence.
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Riddle
M, Pencek
R, Charenkavanich
S, Lutz
K, Wilhelm
K, Porter
L Randomized comparison of
pramlintide or mealtime
insulin added to basal
insulin treatment for patients with type 2 diabetes.
Diabetes Care. 2009;32(9):1577-–1582.
CrossRef
[PubMed: 19502544]