CONSIDERACIONES CLINICAS
Extraído Diabetes Care 2017
The Pathophysiology of Hyperglycemia in Older
Adults: Clinical Considerations
+Author
Affiliations
1.
Corresponding authors: Pearl G. Lee, pearllee@med.umich.edu, and Jeffrey B. Halter, jhalter@med.umich.edu.
Diabetes Care 2017
Apr; 40(4): 444-452. https://doi.org/10.2337/dc16-1732
Abstract
Nearly a quarter of older adults in the
U.S. have type 2 diabetes, and this population is continuing to increase with
the aging of the population. Older adults are at high risk for the development
of type 2 diabetes due to the combined effects of genetic, lifestyle, and aging
influences. The usual defects contributing to type 2 diabetes are further
complicated by the natural physiological changes associated with aging as well
as the comorbidities and functional impairments that are often present in older
people. This paper reviews the pathophysiology of type 2 diabetes among older
adults and the implications for hyperglycemia management in this population.
Introduction
Diabetes
is one of the leading chronic medical conditions among older adults, with high
risk for vascular comorbidities such as coronary artery disease, physical and
cognitive function impairment, and mortality. Despite decades of effort to
prevent diabetes, diabetes remains an epidemic condition with particularly high
morbidity affecting older adults. In fact, nearly 11 million people in the U.S.
aged 65 years or older (more than 26% of adults aged 65 years or older) meet
current American Diabetes Association criteria for diabetes (diagnosed and
undiagnosed), accounting for more than 37% of the adult population with
diabetes . At the same
time, adults 65 years or older are developing diabetes at a rate nearly
three-times higher than younger adults: 11.5 per 1,000 people compared with 3.6
per 1,000 people among adults aged 20–44 years old . However,
increasing research in diabetes and aging has improved our understanding of the
pathophysiology of diabetes and its association with aging and led to the
development of a number of antihyperglycemic medications. The mechanism of
diabetes complications has been previously reviewed . The current
paper reviews the pathophysiology of type 2 diabetes among older adults and the
implications for hyperglycemia management in this population.
Pathophysiology
of Type 2 Diabetes
Type
2 diabetes is by far the most prevalent form of diabetes in older adults and is
an age-related disorder. The criteria for diagnosing diabetes are the same for
all age groups because the risks of diabetes-related complications are
associated with hyperglycemia over time across all age groups . Older adults
are at high risk for the development of type 2 diabetes due to the combined
effects of genetic, lifestyle, and aging influences. These factors contribute
to hyperglycemia through effects on both β-cell insulin secretory capacity and
on tissue sensitivity to insulin. The occurrence of type 2 diabetes in an older
person is complicated by the comorbidities and functional impairments
associated with aging.
Hyperglycemia
develops in type 2 diabetes when there is an imbalance of glucose production
(i.e., hepatic glucose production during fasting) and glucose intake (i.e.,
food ingestion) as opposed to insulin-stimulated glucose uptake in target
tissues, mainly skeletal muscle. Multiple factors in an older person contribute
to such an imbalance of glucose regulation. Although
resistance to peripheral insulin action contributes to altered glucose
homeostasis, current evidence has found that the direct effect of aging on
diabetes pathophysiology is through impairment of β-cell function, resulting in
a decline in insulin secretion.
Genetics
There
is a strong genetic predisposition to type 2 diabetes . The genetic
susceptibility to type 2 diabetes is polygenic, involving a number of variants,
where each allele has a modest effect on the risk of disease in an individual
person. Genome-wide association studies, linkage analysis, candidate gene
approach, and large-scale association studies have identified ∼70 loci conferring susceptibility to type 2 diabetes . These
genetic alleles appear to affect the risk of type 2 diabetes primarily through
impaired pancreatic β-cell function, reduced insulin action, or obesity risk.
Genome-wide
association studies have consistently found that p16INK4a,
a cyclin-dependent kinase inhibitor (CDKI), encoded by the Cdkn2a locus,
is associated with type 2 diabetes risks . Expression
of p16INK4a was
increased in aging mice , and an
additional copy of p16INK4awas associated with markedly reduced pancreatic
islet cell proliferation . β-Cell
proliferation was increased in p16INK4a knockout
mice. Therefore, p16INK4a increases
with age and appears to mediate an age-associated decline in the replicative
capacity of mouse islets; p16INK4a could
be a potential link between aging, metabolic derangements, and β-cell failure
in type 2 diabetes.
Effects
of Aging
Impaired
Insulin Secretion, Insulin Resistance, and Their Interaction
In
the setting of genetic and lifestyle-related risk factors, aging contributes to
the development of type 2 diabetes through impaired β-cell function and
impaired β-cell adaptation to insulin resistance leading to
impaired insulin secretion . Studies
in rodents and humans have found that aging may exert a distinct influence on
β-cell turnover as well as function.
In
older patients who have developed diabetes, autoimmune destruction of β-cells
is rarely observed. Limited pathologic investigation suggests that total β-cell
mass may be moderately reduced, but severe loss of β-cell mass is uncommon.
Pancreatic β-cell mass in adult humans exists in a dynamic state such that the
cells can undergo compensatory changes to maintain euglycemia. Aging is thought
to be associated with reduced capacity to regenerate β-cells, as suggested by
studies involving rodents and humans . On the one
hand, for example, the β-cell toxin streptozotocin, partial pancreatectomy, or
exendin-4 were more effective in stimulating β-cell proliferation in younger
mice (younger than 12 months old) than in older mice . On the
other hand, the age-associated decline in β-cell function in older rats has
been shown to be reversible with glucagon-like peptide 1 (GLP-1; exendin)
treatment , suggesting
stimulation of β-cell regeneration . In humans,
the baseline β-cell population and appropriate association with other islet
cell types is established before 5 years of age . Other
studies using C14 or
Ki67 have found that human adult β-cell turnover is very low . Similarly
among middle-aged and older adults, minimal β-cell regeneration was observed
after a mean follow-up period of 1.8 ± 1.2 years after a 50% partial
pancreatectomy: β-cell mass and new β-cell formation were not increased, and
β-cell turnover was unchanged . The
follow-up time of this study may have been too short for human β-cells to
replicate, but other studies have also found evidence of slow β-cell
proliferation in humans with advancing age . The decline
in β-cell replication was directly associated with a decrease in the expression
of a transcription factor known as the pancreatic and duodenal homeobox 1
. Thus, the
overall evidence suggests that human β-cells survive for a long time and are
unlikely to be replenished by replications once adulthood is reached . Several
age-related potential molecular pathways have been found to restrict β-cell
regeneration. For example, the replication refractory period, the time between
cell divisions (G0 stage of cell cycle), appears to lengthen with age ; the
replicative capacity of β-cells might be reduced due to accumulation of DNA
mutations with aging.
Therefore,
β-cell function in human adults might be enhanced in the setting of
hyperglycemia or insulin resistance to maintain euglycemia. Pancreatic β-cells
appear to primarily compensate for limited replication capacity through
hyperplasia and hypertrophy. However, a number of studies have demonstrated a
decline in β-cell function and insulin secretion with age in rodents . In humans, the
insulin secretion rate in response to glucose was significantly and
progressively decreased in older individuals, with the greatest impairment in
older individuals with impaired glucose tolerance compared with older
individuals with normal glucose tolerance or with younger individuals matched
for degree of insulin resistance . In fact, a
50% reduction in β-cell secretory capacity has been observed in older men
compared with younger men in response to arginine stimulation .
Impaired
pancreatic β-cell adaptation to insulin resistance appears to be an important
contributing factor to age-related glucose intolerance and risk for diabetes.
Although aging per se has a minimal effect on insulin action directly , many older
individuals develop insulin resistance as a result of diminished physical
activity, obesity, and loss of lean body mass, particularly those with a
disproportional loss of skeletal muscle over adipose tissue. Age had no
independent effect on insulin sensitivity when controlled for obesity;
age-related reductions in insulin sensitivity are likely the result of an
age-related increase in adiposity rather than a consequence of advanced
chronological age .
Insulin
resistance with aging appears to reflect predominantly lifestyle factors such
as poor diet and diminished physical activity. These changes lead to decreased
lean body mass and increased adiposity, particularly visceral adiposity, with
aging. More than 35% of U.S. adults aged 60 years or older are obese, having a
BMI of 30 kg/m2 or
greater. An absolute
or relative increase of body adiposity, particularly central body adiposity,
often associated with advancing age, appears to account in large part for the
age-related increase in insulin resistance . Even among
adults without diabetes, intraabdominal fat mass correlates with insulin
resistance and age after controlling for obesity . However,
insulin resistance is more closely associated with abdominal adiposity than
with age . In addition
to excessive caloric intake, increased body adiposity is partly related to a
sedentary lifestyle, which is common among older adults; for example, only 12%
of adults aged 75 or older engage in 30 min of physical activity 5 or more days
per week, and 65% report no leisure time physical activity . Increasing
physical activity in older adults reduces insulin resistance , reduces the
risk of developing diabetes , and
improves glycemic control in people with diabetes .
Low-grade
inflammation and stress-response changes associated with obesity and aging are
likely to contribute to the increased risk of type 2 diabetes among older
adults . Aging and
obesity are both thought to be independently associated with the development of
low-grade inflammation , and
proinflammatory cytokines, such as C-reactive protein, interleukin 6, and tumor
necrosis factor-α, have been found to inhibit insulin signaling and increase
insulin resistance and risk of type 2 diabetes.
The
role of mitochondrial function in aging and type 2 diabetes remains unclear.
Older adults were found to have a decrease in mitochondrial function compared
with younger adults (i.e., decreased ATP synthesis); however, older adults with
normal glucose tolerance had similar ATP production level compared with older
adults with impaired glucose tolerance . On the
other hand, exercise reverses age-related declines in mitochondrial oxidative
capacity and ATP production, which may be part of the underlying mechanism
through which exercise improves insulin sensitivity .
There is
a maladaptive response to insulin resistance in the setting of impaired β-cell
function leading to further impairment of insulin secretion and progression to
impaired glucose tolerance and type 2 diabetes. Hyperglycemia, in turn,
contributes directly to insulin resistance and impairs pancreatic β-cell
function, effects described as glucose toxicity . Such
glucose toxicity sets up a vicious cycle of maladaptive mechanisms leading to
further deterioration of β-cell function and more severe insulin resistance.
Comorbidities
and Their Effect on Insulin Sensitivity and Secretion
Coexisting
illness is another factor that can affect insulin sensitivity and insulin
secretion in an older person. Hypertension, for example, is common in older
people and has been associated with diminished insulin sensitivity .
Furthermore, any acute illness can precipitate hyperglycemia because of effects
of stress hormones to cause insulin resistance combined with the α-adrenergic
effects of catecholamines released during stressful illness to inhibit insulin
secretion.
Medications
used in treating chronic medical conditions may induce or increase insulin
resistance or worsening hyperglycemia among patients with diabetes.
Glucocorticoids, for example, promote hepatic gluconeogenesis, thus increasing
hyperglycemia, and contribute to insulin resistance by increasing visceral fat
and promoting proteolysis, lipolysis, free fatty acid production, and fat
accumulation in the liver .
Impaired
glucose regulation over time leads to overt diabetes, which in turn leads to
microvascular or macrovascular complications. Diabetes-associated
complications, along with other comorbidities prevalent among older adults,
such as arthritis, cognitive impairment, and depression, may contribute to
decreased physical activity and disability (49). All of
these changes can further impair glucose regulation and adversely affect
glycemic management.
Implications
for Management of Type 2 Diabetes Among Older Adults
General
Approach
The
complexity of diabetes and its management requires a collaborative effort by a
team of health care providers, which may include physicians, nurse
practitioners, nurses, dietitians, pharmacists, social workers, and mental
health professionals. Patients and family members must also assume an active
role . When
developing a treatment plan, in addition to targeting the various factors
involved in the pathophysiologic pathways of type 2 diabetes, providers should
address other relevant comorbid conditions that are common among older adults
and can easily affect the ability of the patient to manage diabetes. Aging is
associated with increasing risk of developing geriatric syndromes, such as
visual impairment, cognitive impairment, and functional impairment, and
diabetes is also associated with an increased risk of retinopathy and deficits
in cognitive and physical functioning . Geriatric
syndromes will in turn affect the ability of older adults to manage their
diabetes. Such limitations may affect a patient’s ability to obtain food or
medications, to exercise, or to see his or her health care providers.
Because
older adults with diabetes are quite heterogeneous with respect to their health
status and available care support, the goal for hyperglycemia management should
be individualized based on their comorbidities and physical and cognitive
function status. A comprehensive geriatric assessment will help
the providers to assess an older patient’s ability to safely follow a complex
diabetes treatment plan. Given that type 2 diabetes develops after years of
metabolic abnormalities, a thorough medical evaluation in search for existing
diabetes complications is warranted even when a new diagnosis is made in an
older adult. The clinical assessment is used to recommend individualized
glycemic, blood pressure, and lipid goals for older adults with diabetes. An
interdisciplinary expert panel that included geriatricians, endocrinologists,
and other diabetes health care providers was convened by the American Diabetes
Association at a Consensus Development Conference on Diabetes and Older Adults
in 2012. This group developed a framework to set diabetes treatment goals based
on individual patients’ comorbidities and physical and cognitive function
status .
Lifestyle
Interventions
Lifestyle
interventions, including regular physical activity and mild-moderate weight
loss, are the first-line intervention for diabetes prevention and for treatment
of hyperglycemia in older people. Lifestyle interventions are particularly
effective in reducing the risk of developing diabetes among older adults and are also
beneficial in improving diabetes management among older adults . Lifestyle
interventions can reduce insulin resistance and thereby help reverse the
vicious cycles . However,
there is no evidence that lifestyle interventions can reverse the effects of
aging on β-cells; thus, such interventions may delay, but are not likely to
completely prevent, the ultimate development of hyperglycemia.
Physical
Activity
Regular
physical activities for older adults with diabetes, particularly activities of
moderate to vigorous intensity, can improve insulin sensitivity . Regular
physical activities are a useful adjunct to drug therapy to manage glucose
levels and may well contribute to enhanced effectiveness of glucose-lowering
agents. Furthermore, increasing physical activity as part of a lifestyle
intervention is effective in reducing physical functioning impairment among
patients with diabetes, improving glucose, lipid, and blood pressure control,
and enhancing weight loss .
Traditionally,
aerobic training activities have been recommended for older adults, given their
benefits in cardiorespiratory fitness. Evidence also supports regular
whole-body resistance training for older adults with type 2 diabetes. As
previously discussed, the pathophysiology of type 2 diabetes involves insulin resistance,
and the main tissues in the body that are sensitive to insulin are muscles and
adipose cells. Resistance training changes body composition (e.g., increases
skeletal muscle mass), improves insulin sensitivity, and reduces HbA1c .
In
fact, physical activity programs that include both aerobic and resistance
training improve glycemic levels more than aerobic or resistance training alone
. Thus, the
American Diabetes Association recommends that all adults with diabetes should
perform at least 150 min/week of moderate-intensity aerobic physical activity,
spread over at least 3 days/week with no more than 2 consecutive days without
exercise. As part of the exercise routine, resistance training should be
performed at least twice weekly .
Given the high prevalence of coronary
artery disease in older patients with diabetes, which may be asymptomatic or
atypical in symptoms, it is important for such patients to have medically
supervised stress testing before entering any challenging exercise training
program. Additional issues to consider in an older person participating in an
exercise program include the potential for foot and joint injury with upright
exercise, such as jogging, unstable comorbidities, autonomic neuropathy,
peripheral neuropathy, or foot lesions that may predispose to injures, and the
ability to promptly identify and treat hypoglycemia, which can be induced by
exercise if the patient is on insulin or a sulfonylurea. Therefore, each
patient’s exercise prescription needs to be individualized based on his or her
capability to safely participate in an exercise program.
Obesity
and Diet
Even
a modest to moderate body weight loss (5–10% of initial body weight) increases
insulin sensitivity and improves glucose tolerance in obese individuals as well
as in those with impaired glucose tolerance or type 2 diabetes . As part of
diabetes management, the American Diabetes Association recommends that
overweight adults with type 2 diabetes lose 2–8 kg weight through lifestyle
changes . Recent
studies have not substantiated previous concerns about the risks of weight loss
among older adults, where older adults who intentionally lost weight by
combining caloric restriction and exercise had minimal reduction in lean muscle
mass and actually had increased bone density and improvement in physical
function compared with individuals who lost weight by caloric restriction alone
or by exercise alone . Hence,
weight loss programs for older adults with diabetes should incorporate caloric
restriction with physical activity.
Caloric
restriction is appropriate for healthier overweight and obese older diabetes
patients as part of management of hyperglycemia but is not appropriate for some
older patients who are at risk for undernutrition already. More pressing
dietary issues for these patients are how to maintain adequate caloric intake
and coordinate food intake with administration of glucose-lowering agents
appropriately to avoid hypoglycemia. Older adults with mobility limitation or
who lack transportation are likely to have limited access to healthy and fresh
food . Social
isolation (i.e., living alone, eating alone), poverty, and functional reliance
on others to purchase food are all risk factors for decreased food intake. The
presence of impaired cognitive function may make following a dietary
prescription particularly difficult. Furthermore, dietary habits established
for a lifetime and often with a cultural background may be particularly
difficult to modify. Problems with taste and oral health, which are common in
older people, may further limit adaptation to a prescribed diet . Oral health
problems can be exacerbated by diabetes, which may increase the rate of
periodontal disease. Xerostomia is also more common in older people owing to
decreased salivary gland flow and is sometimes exacerbated by coexisting
medication use.
Medications
in the Management of Hyperglycemia
Most
medications to treat hyperglycemia in older adults with type 2 diabetes target
one or more of the pathophysiological impairments of age-related type 2
diabetes: reducing hepatic glucose production, increasing insulin secretion,
increasing insulin sensitivity, decreasing glucagon secretion, increasing
incretin levels, and decreasing satiety. Unfortunately, older patients are
often underrepresented in large clinical trials; therefore, data on
antihyperglycemic medications are often extrapolated from younger populations .
Treatment
of older adults with diabetes needs to account for the progression of type 2
diabetes over time . Because of
the age-related decline of β-cell function, maintaining target levels of
glycemic control may necessitate escalation of drug doses or the addition of
other antihyperglycemic agents . Thus,
medications that target the β-cells, such as sulfonylureas or GLP-1–related
drugs, are likely to become less effective over time. Medications such as
metformin, thiazolidinediones (TZDs), and sodium glucose transporter 2 (SGLT2)
inhibitors may help to reverse some of the vicious cycles contributing to
hyperglycemia but do not directly address the effects of aging on β-cells.
Treatment choices should be tailored to the specific situation of the
individual patient, as determined in part by the initial comprehensive
assessment of the patient’s comorbidities, cognition, functional status, care
support, and financial situation . Although it
is common for an older adult to have multiple comorbidities, impairment in
cognition or functional status, and limited financial support, a strong
supportive care system may be sufficient to help the patient to safely
implement a complex medical treatment.
The treatment plan should minimize risk
for hypoglycemia, especially in frail, vulnerable older patients and when using
agents with high risk for hypoglycemia such as insulin and sulfonylureas. Thus,
emphasis on lifestyle interventions and classes of drugs that do not cause
hypoglycemia can often result in safe achievement of lower A1C targets,
especially early in the course of type 2 diabetes. As these safer interventions
become less effective as a result of progressive β-cell failure with aging,
insulin may be needed, and the A1C target may need to be higher to avoid
hypoglycemia. Sulfonylurea drugs should be used only with extreme caution in
any vulnerable older patient. Frequent follow-up should be provided to ensure
that the treatment program is progressing smoothly and that hypoglycemia does
not occur.
Biguanides
Metformin,
a biguanide, is the first-line oral medication for hyperglycemia for older
adults . Because
metformin’s mechanism of action predominately involves reducing hepatic glucose
production, it rarely causes hypoglycemia when used alone. Some older patients
may experience intolerable gastrointestinal discomfort, decreased appetite, and
modest weight loss associated with metformin.
Metformin
is contraindicated in patients with renal insufficiency, and the U.S. Food and
Drug Administration recommends against the use of metformin in patients with an
estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2.
Furthermore, metformin is recommended to be discontinued at the time of or
before an iodinated contrast imaging procedure in patients with an eGFR between
30 and 60 mL/minute/1.73 m2,
and can be restarted if the eGFR is stable 48 h after the imaging procedure.
Sulfonylureas
Sulfonylureas
are probably overused in older adults with type 2 diabetes. These drugs are
inexpensive, and their overall safety record is good. Their primary mechanism
of action is to enhance insulin secretion by β-cells of the pancreas.
Hypoglycemia is a serious risk, however, and conservative use is thus
recommended for older people. Glyburide is associated with a high risk for
hypoglycemia in older patients due to its long half-life so is not recommended
in this population. Other
sulfonylureas may be safer to use in older patients, but all have a
hypoglycemia risk. Another concern about use of sulfonylurea drugs in older
adults is a higher secondary failure rate than other drugs, probably related to
progressive β-cell dysfunction .
TZDs
TZDs
improve insulin sensitivity in skeletal muscle, reduce hepatic glucose
production, and have the advantages of low risk for hypoglycemia. However,
concerns over potential adverse effects associated with TZDs have been raised,
including increased risks of bladder cancer, weight gain, fluid retention, and
bone fractures . TZDS are
usually not considered as first-line antihyperglycemic agents.
GLP-1
Agents
GLP-1 is an incretin, an intestinal
hormone that is released as glucose levels increase with meals and cause
glucose-dependent insulin secretion; therefore, GLP-1 agents are unlikely to
cause hypoglycemia. Two classes of GLP-1 drugs are used clinically:
1.
The injectable GLP-1 receptor agonists
stimulate insulin section in a glucose-dependent fashion, suppress glucagon
output, slow gastric emptying, and decrease appetite. These agents have the
advantages of modest weight loss, but for some patients, the weight loss can be
too much and there may be resistance against performing injections.
2.
The oral dipeptidyl peptidase-4 (DPP-4)
inhibitors enhance circulating concentrations of active GLP-1.
When
used alone, both classes of GLP-1 agents rarely cause hypoglycemia, but high
cost may be prohibitive for some older adults. Pilot studies of myocardial
ischemia and animal studies suggested that GLP-1 agonists may improve
cardiovascular outcomes, but the results from two recent large trials are
mixed. Among patients with type 2 diabetes and high cardiovascular risk, the
rate of the first occurrence of death from cardiovascular causes, nonfatal
myocardial infarction, or nonfatal stroke was lower with liraglutide than with
placebo, but among
patients with type 2 diabetes and recent acute coronary syndrome, no
significant effect on the rate of major cardiovascular events was found with
lixisenatide compared with placebo.
SGLT-2
Inhibitors
SGLT-2 inhibitors allow the kidneys to
reabsorb most filtered glucose. SGLT-2 is found only in the proximal tubule of
the kidney and accounts for 90% of the reabsorption of glucose. SGLT-2
inhibitors are oral agents that lower glucose levels by increasing urinary
excretion of glucose. They are approved for use in both type 1 and type 2
diabetes. They are used once daily, result in modest lowering of A1C similar to
DPP-4 inhibitors, and rarely cause hypoglycemia. They are contraindicated in
chronic kidney disease. These agents increase urine volume and sodium
excretion, so usually lower blood pressure modestly but may cause volume
depletion. This volume effect may contribute to increased risk for diabetic
ketoacidosis in people with type 1 diabetes. There is increased risk for
genital yeast infection and urinary tract infection, likely resulting from the
induced glycosuria. Because of these adverse effects, relatively high cost, and
limited experience with these drugs in older adults, their use is usually
reserved for situations in which other classes of drugs are not tolerated.
Insulin
Because
β-cell dysfunction plays a major role in type 2 diabetes in older adults,
insulin replacement therapy may be necessary to achieve the goal for
hyperglycemia control, especially in patients with longer duration of type 2
diabetes with progressive β-cell dysfunction. The approach to use of insulin in
older adults with type 2 diabetes is to start with a once-daily, long-acting
insulin (basal insulin), with minimal peak or trough effect. Long-acting
agents, such as insulin glargine 100 and detemir insulin, have a lower
incidence of nocturnal hypoglycemia than shorter-acting insulin agents, even
among older adults .
Premeal
injections of a rapid-acting insulin analog can be added to the basal insulin, if
necessary, in older patients in whom the physician has determined can safely
administer insulin and monitor for hypoglycemia. Insulin aspart and insulin
lispro have a very rapid onset and short duration of action and are used just
before meals. They are less likely to result in postmeal hypoglycemia than
human regular insulin . These
rapid-acting insulin agents can be given within 20 min after starting a meal,
and hence, are particularly useful in older patients who may not eat regularly.
Combination
Therapy
Use
of combination antihyperglycemic agents in older patients may be necessary with
the progression of the disease. Combinations of different classes of drugs are
theoretically attractive because their different modes of action address
various aspects of the pathophysiology of hyperglycemia. For older patients who
have persistent hyperglycemia (above their individualized A1C target) with
lifestyle intervention and metformin (if not contraindicated), adding another
agent would be recommended. The options include adding an oral agent such as
short-acting sulfonylurea (i.e., glipizide), DPP-4 inhibitors , or SGLT2
inhibitors .
Alternatively, a basal insulin, such as glargine, may be added . If a
sulfonylurea is already being used, we would recommend tapering it to
discontinue because a combination of sulfonylurea and insulin greatly increases
the risk of hypoglycemia .
Conclusions
Older adults are at high risk for the
development of type 2 diabetes as a result of the combined effects of genetic,
lifestyle, and aging influences. Despite the advancement in understanding the
pathophysiology of type 2 diabetes, more research is needed to elucidate the
underlying molecular mechanisms of how aging is related to type 2 diabetes and
to diabetes-related complications . Prevention
of type 2 diabetes and treatment of hyperglycemia in older adults should
emphasize lifestyle interventions based on the pathophysiology of the
development of type 2 diabetes and their numerous benefits on the overall
health of older adults. With the aging of β-cell function, the addition of one
or more medications to achieve glycemic control targets may be needed. However,
the overall management of hyperglycemia needs to be individualized for older
adults based on individuals' likelihood of benefiting from tight control versus
the risks associated with implementing complex management regimens, especially
when insulin or a sulfonylurea drug is included. A comprehensive assessment
involving the individual’s comorbidities and geriatric syndromes, including
cognitive and functional status, can help tailor the treatment plan.
