Diabetes Mellitus in Elderly Patients

Is It Different?

JOHN E. MORLEY, M.B., B.Ch. Diabetes mellitus in elderly patients is exceedingly common, with a
ARSHAG D. MOORADIAN, M.D. prevalence in the United States of 6.9 percent in men older than 65 years
MARK J. ROSENTHAL, M.D. and 8.9 percent in women older than 65 [I]. Among persons older than
FRAN E. KAISER, M.D. 80, 16 to 20 percent have diabetes mellitus [2]. The National Nursing
Sepulveda, California Home Survey estimated that 14.5 percent of nursing home residents
have diabetes mellitus [3]. In the United Kingdom, two thirds of all diabetic
and
patients who are hospitalized are older than 65 years [4]. Diabetes
Los Angeles, California
mellitus is often missed in the elderly, as demonstrated by a screening
program in a Canadian old people’s home, where 32 percent of the
residents were reclassified as diabetic over a three-year period [5].
Furthermore, diabetic residents of nursing homes have a higher rate of
hospitalization for diabetic complications compared with ambulatory
diabetic patients older than 65 [6]. Thus, diabetes mellitus represents one
of the major chronic disorders of the growing elderly population. Despite
these impressive numbers, little attention has been paid to the special
needs of elderly diabetic patients [7].

GLUCOSE INTOLERANCE OF AGING

An increased response to an oral glucose load in elderly persons com-
pared with that in younger subjects has become a well-recognized
phenomenon [8] since the original report by Spence [9] in the early
1920s (Figure 1). Mild glucose intolerance occurs with increasing fre-
quency with advancing age. In one epidemiologic study, after patients
with frank diabetes mellitus were excluded, 3 percent of patients aged 18
to 24 years had a plasma glucose level of more than 160 mg/dl one hour
after an oral glucose load, whereas elevated glucose levels occurred in
16 percent of those 45 to 54, 36 percent of those 65 to 74, and 42
percent of those 75 to 79 [lo]. A similar glucose intolerance, but to a
lesser degree, also occurs with a physiologic mixed meal [ 111. Due to
this increasing hyperglycemia with age, (approximately 1 to 2 mg/dl
increase in fasting glucose level and 5 to IO mg/dl increase in the two-
From the Geriatric Research, Education and hour postprandial glucose level with each decade over 50) the diagnos-
Clinical Center, Sepulveda Veterans Administra- tic criteria for diabetes mellitus in an elderly patient require a random
tion Medical Center, Sepulveda, California, and blood glucose level of more than 200 mg/dl or two fasting blood glucose
the Department of Medicine, University of Cali-
fornia, Los Angeles, California. Dr. Kaiser is a levels of more than 140 mg/dl.
John A. Hartford Faculty Development Award Recently, two studies have shown that there is an increase in glycosyl-
Fellow in Geriatric Medicine. Requests for re- ated hemoglobin levels in elderly subjects with normal results on glucose
prints should be addressed to Dr. John E. Morley, tolerance testing [ 11,121. This suggests that glycosylation of proteins
Geriatric Research, Veterans Administration
occurs in association with the hyperglycemia of aging [ 131. Protein
Medical Center, 16111 Plummer Street, Sepul-
veda, California 91343. Manuscript submitted glycosylation has been thought to play a role in the pathogenesis of
February 2, 1987, and accepted March 3, 1987. microvascular disease. Further, the hyperglycemia of aging has been

September 1987 The American Journal of Medicine Volume 83 533

DIABETES MELLITUS IN ELDERLY
-220
l 210 --
‘200 - -
t aged 60 to 75, it has been shown that there is a direct
‘19Q
-lm F# r. - -.-
c _.__..
."OL.. -
t
_---
.lOO.-. t-1 L--
.0')3---
I
_.__,__
,I t
Figure 7. This early graph by Spence [9] published in
1920/1921 shows the elevated glucose response to a 50 g
oral glucose load in the elderly (Group I) compared with that
in normal young adults. One elderly subject (/I) was discov-
ered to have diabetes mellitus at the time of testing.
clearly associated with macrovascular disease. The Bed-
ford Survey [ 141 showed a significant increase in athero-
sclerotic cardiovascular disease in subjects with the glu-
cose intolerance of aging. From a practical standpoint,
the elevated glycosylated hemoglobin levels in some nor-
mal elderly subjects suggest that care needs to be taken
in using this parameter as a measure of diabetes control in
elderly patients. Recently, we have found that measure-
ment of fructosamine may be a better screening test for
diabetes in elderly subjects (unpublished observation).
The reasons for the glucose intolerance of aging and
the increased prevalence of diabetes mellitus in elderly
persons are multifactorial. Much of the glucose intoler-
ance, however, can be explained by the increase in
adipose tissue that occurs with age. At autopsy, there is
no alteration in total pancreatic insulin content with age,
and the amount of islet tissue is unchanged with advanc-
ing age up to the age of 87 [8]. Multiple studies have
shown that there is increased insulin secretion in re-
sponse to glucose or a mixed meal, suggesting the pres-
ence of insulin resistance [8]. Some of the increase in
insulin levels in elderly subjects may be due to the de
crease in insulin degradation [ 151 and removal that occurs
with age [ 161. In some elderly subjects, there is a de-
534 September 1987
PATIENTS-MORLEY ET AL
crease in the insulin-to-glucose ratio, suggesting mild
pancreatic insufficiency [8]. A number of investigators
have reported a decreased efficiency of insulin-stimulated
- -. .- glucose disposal with advancing age [ 171. In healthy men,
relationship between maximal aerobic capacity and the
insulin-stimulated glucose clearance rate [ 181. In most
studies [ 19-2 11, receptors have been shown not to de-
- crease with advancing age. However, a study by Pagan0
et al [22] did suggest that there may be a reduction in
insulin receptors in the adipocytes of older subjects. In an
animal study, it was shown that adipocytes from aged
Fisher rats have cellular insulin resistance on the basis of
multiple post-binding defects involving both the glucose
transport system and more distal intracellular processes
[23]. Thus, the glucose intolerance of aging appears to be
---. y-i-.- -. 1 ..-L- -
predominantly due to a post-receptor defect. Although the
predominant defect producing the hyperglycemia of aging
-\ , INO- 4 !J! 1\';,-:,
.._ -_--- .,A.
iqt is insulin resistance, Chen et al [24] have shown that in an
-_r-._-
elegant study elderly subjects also have a defect in sec-
ond-phase beta cell response. The multifactorial nature of
I I the development of the hyperglycemia of aging and the
development of type II diabetes in elderly persons is
illustrated in Table I.
PROGNOSIS OF DIABETES IN ELDERLY
PATIENTS
The majority of diabetic patients with onset in middle age
or later years have hyperglycemia uncomplicated by sig-
nificant ketoacidosis (type II diabetes mellitus). It should
be remembered that in patients with poorly controlled
type II diabetes who are not eating well, ketones will be
present in the urine (but not in the serum). The prognosis
for type II diabetes is not particularly good, with one series
finding that 44 percent of patients were dead within 10
years of diagnosis [25]. Furthermore, type I diabetes with
presentation as ketoacidosis can occur in elderly patients
and in patients with long-standing type II diabetes mellitus
who have “pancreatic exhaustion” and conversion to
type I. Overall lo-year mortality rates increase with ad-
vancing age at onset of diabetes. However, there is no
statistically significant increase in mortality due to diabe-
tes when the diagnosis is made beyond the age of 75
years [26]. Nevertheless, diabetic complications can im-
pinge significantly on the patients’ quality of life (impact of
amputations, blindness, and fatigue related to poor glu-
cose control), making it important to pay careful attention
to diabetes control, no matter what the age at onset. In
addition, there tends to be a shorter interval to the appear-
ance of microvascular complications in elderly patients
compared with that in younger diabetic patients. With
improved care for elderly persons in general and im-
proved life expectancy, it is likely that there will be a
greater difference in mortality in the older age groups if
glucose control is not maintained into late life.
The American Journal of Medicine Volume 83

GLUCOSE COUNTER-REGULATION
Avoidance of hypoglycemia is a paramount concern of
clinicians caring for older diabetic patients and probably
contributes to the lax attitude concerning tight glucose
control in this group. Without much published evidence,
the consensus is that advanced age confers greater risks
of complications from hypoglycemia, including misdiag-
nosis of neuroglycopenic symptoms as primary neurolog-
ic events. Age-associated neuroendocrine changes could
theoretically increase the likelihood of hypoglycemia.
Basal levels of the counter-regulatory hormones, cortisol
and growth hormone, are not altered with age, but the
dynamic responses are changed [27,28]. Basal plasma
catecholamines increase with age [29], but receptor-
cyclase responsiveness is diminished [30].
Nighttime hypoglycemia is often a clinical concern in
older diabetic patients, and nocturnal glucose regulation
has been studied among elderly subjects [3 1,321 as an
indicator of the effects of neuroendocrine changes. De-
spite continued fasting, plasma glucose and insulin re-
quirements increase in patients with insulin-dependent as
well as in those with non-insulin-dependent diabetes dur-
ing the early morning hours [33,34], perhaps in relation to
the post-sleep growth hormone surge [3 1,35,36]. In light
of the known blunting of growth hormone responses [27],
we [37] and others [32] have studied morning glucose and
insulin metabolism in elderly nondiabetic subjects. Among
young subjects, we detected a small rise in plasma glu-
cose values between 6 and 8 A.M. that was absent in
certain healthy older subjects. Meneilly et al [32] found no
difference in glucose production and disposal rates be-
tween dawn and mid-morning in a small number of
healthy elderly subjects. Although the relevance of factors
involved in the dawn phenomenon to glucose counter-
regulation is still unclear, older diabetic patients treated
with insulin may lack the relative early morning protection
against hypoglycemia.
Growth hormone and cortisol responses to hypoglyce-
mia are variably reported to be decreased in older sub-
jects [38,39]. However, glucagon and epinephrine, which
are generally presumed to be the most important factors
in the counter-regulatory response to hypoglycemia, have
only recently been investigated in elderly persons. No
age-related differences in response to modest hypoglyce-
mia were seen [40], but the magnitude of the counter-
regulatory response was related to the nadir glucose
levels [38,41]. Although a degree of insufficiency in
counter-regulatory responses may occur, the existing lit-
erature does not demonstrate that older persons have a
marked risk of profound hypoglycemia merely by virtue of
their age.
Older diabetic patients may also have unrecognized
hypoglycemia. Autonomic neuropathy in young patients
with type I diabetes is associated with decreased adrener-
September
DIABETES MELLITUS IN ELDERLY PATIENTS-MORLEY ET AL
TABLE I Factors in Pathogenesis of Hyperglycemia
of Aging and Development of Type II
Diabetes Mellitus In Elderly Patients
Increased insulin resistance
Postreceptor defect
Possible receptor defect (type II)
Increased adipose tissue
Decreased exercise
Altered insulin levels
Decreased second-phase insulin release
Decreased insulin-to-glucose ratio
Altered dietary habits
Increased insulin degradation and removal
gic responsiveness to hypoglycemia and hence more
frequent neuroglycopenic manifestations [4 11. Advanced
age may be linked to a higher incidence of neuropathy, but
the significance for glucose counter-regulation has not
been studied. Whether long-term neurologic effects might
be caused by repeated episodes of unrecognized hypo-
glycemia has not been investigated and is at least of
theoretic concern, Cognitive function can be significantly
impaired by repeated hypoglycemia [42].
ACUTE DlABETlC COMPLlCATlONS
In one study [43], uncontrolled diabetes mellitus resulted
in death in approximately 3 percent of subjects younger
than 50 years. Over the age of 50, the mortality rate
increased with each decade (16 percent for 50 to 59, 18
percent for 60 to 69, 23 percent for 70 to 79, and 41
percent for 80 to 89). It should be noted that, in this series,
the mortality rate was twice as high in older patients with
ketoacidosis as in those with hyperosmolar coma. Hyper-
osmolar nonketotic diabetic coma was first described by
Dreschfeld in 1886. This condition occurs predominantly
in patients more than 60 years of age. Institutionalized
patients and those with dementia who fail to experience
thirst or are unable to express their need for water are
particularly prone to this condition [44]. A number of drugs
commonly prescribed for elderly patients have been im-
plicated in the pathogenesis of hyperosmolar coma.
These include diphenylhydantoin, thiazide diuretics, pro-
pranolol, cimetidine, and furosemide. The gastric stasis
and generalized debility of these patients often lead to
aspiration as a complication. Associated clinical findings
are hypothermia, hypotension, and vascular occlusions.
OCULAR COMPLICATIONS
Diabetic retinopathy occurs commonly in older patients
with type II diabetes mellitus. In the Framingham Study,
19 percent of 231 diabetic patients aged 55 to 84 had
retinopathy [45]. The prevalence tends to increase with
advancing age, with more than 25 percent of patients
older than 75 years of age having retinopathy. A recent
1987 The American Journal of Medicine Volume 83 535
DIABETES MELLITUS IN ELDERLY PATIENTS-MORLEY ET AL
study in patients between 55 and 75 years with type II
diabetes found a correlation between retinopathy and
duration of diabetes and diabetic control (as measured by
glycosylated hemoglobin levels) [46]. There was no cor-
relation with age per se, although macular edema tends to
occur more commonly in older patients with retinopathy.
Unlike the situation in younger diabetic patients, no corre-
lation between either diastolic or systolic hypertension
and retinopathy could be demonstrated.
Bresnick et al [47] have shown that patients with
retinopathy may also have color vision deficiency. They
found that diabetic subjects made significantly more er-
rors on color interpretation of urinary test results than did
age-matched control subjects. Such errors on urinary and
blood glucose testing have practical importance, in that
they can lead to major mistakes in the adjustment of
insulin dosages. Color vision should be tested whenever
diabetic patients visit their physicians, and those with
abnormal color vision should be sent to an ophthalmolo-
gist for exclusion of early proliferative retinopathy and
should be provided with a glucometer for determining
blood glucose values.
Diabetic patients have an increased incidence of cata-
racts [48,49]. Glucose is converted by aldose reductase
into sorbitol, which is associated with cataract formation,
and inhibition of aldose reductase may slow cataract
development in diabetic patients [50]. Both the Framing-
ham Eye Study and the Health and Nutrition Examination
Survey found cataracts to be approximately three times
more common in persons 50 to 69 years old with diabe-
tes than in the same age group without diabetes [49].
However, in diabetic patients older than 70 years, there
was no increased prevalence of cataracts (found in the
Framingham Study) and only a 1.9 fold increase in the
Health and Nutrition Examination Survey. Cataract surgery
is advised in all those with visual acuity of 20/50 or less or
with functional impairment due to their decreased vision.
Diabetes mellitus is 2.3 times more common in pa-
tients with intraocular pressure of more than 2 1 mm Hg in
at least one eye [51]. Glaucoma (increased intraocular
pressure plus visual field defects) occurs with increased
frequency in diabetic patients, and patients with glaucoma
have an increased prevalence of diabetes and abnormal
glucose tolerance results [52]. These studies suggest that
glaucoma treatment should be initiated in all diabetic
patients with ocular hypertension, as diabetes appears to
increase optic nerve susceptibility to field defects. Instilla-
tion of medication into the conjunctival cul-de-sac is
equivalent to intravenous administration [53]. Thus, timo-
lol maleate, a beta blocker used for the treatment of
glaucoma, can blunt diabetic patients’ responses to hypo-
glycemia and may cause impotence. In one 65-year-old
patient, timolol eyedrops were associated with the devel-
opment of neuroglycopenia and grand mal seizures [54].
High blood glucose levels can cause fluctuations in visual
536 September 1987 The American Journal of Medicine
acuity due to osmotic pressure changes in the lens.
Improving visual acuity is one reason for improving diabet-
ic control in elderly diabetic patients.
Diabetes mellitus is .associated with cranial nerve pal-
sies [55]. In diabetic third nerve palsies, the pupillary
responses are usually spared. When the palsy is associ-
ated with pain, the Westergren erythrocyte sedimentation
rate should be determined to exclude Tolosa-Hunt syn-
drome (painful unilateral nerve palsies) and temporal ar-
teritis [56]. Intracranial aneurysms must always be con-
sidered in the differential diagnosis of third nerve palsies.
Diabetic third nerve palsies tend to resolve spontaneously
within three months [57].
As a practical matter, the eyes of elderly diabetic
patients should be screened at least annually not only to
detect the development of retinopathy and cataracts but
also to exclude the development of increased intraocular
pressure and deteriorating color vision. It should be re-
membered that internists, diabetologists, and medical res-
idents are much less accurate in the detection of prolifera-
tive retinopathy (49 percent) than are ophthalmologists
(96 percent) [58]. Diabetic patients with impaired vision
should be provided with specialized syringes to allow
them to measure their insulin accurately.
NERVOUS SYSTEM COMPLICATIONS
Pirart [59] has clearly demonstrated that the development
of diabetic neuropathy is related to the duration of the
diabetes. In addition, his data suggest that neuropathy
tends to develop later in diabetic patients who are younger
than 40 years at disease onset than in those who are older
when diabetes is diagnosed. This is not surprising, as
postmortem studies have suggested that, although early
diabetic neuropathy may be related to changes in the
polyol pathway, late neuropathic changes are predomi-
nantly due to ischemic changes [60]. Of clinical relevance
is that diabetic patients are unusually resistant to the loss
of vibration perception [61]. Therefore, when this is pre-
sent, other causes of posterior column disease should be
considered, especially vitamin B12 deficiency, which may
occur without anemia [62].
Of particular concern is the frequency of pain in diabet-
ic patients. In one outpatient study, 18 percent of diabetic
patients complained of pain compared with a control
population in whom pain was a major complaint in only 3
percent [63]. Recent animal and human studies have shed
some light on these findings. It is now well recognized that
endogenous opioids (endorphins) play a role in the regula-
tion of pain perception [64]. Animal studies have shown
that elevations of blood glucose alter the responsiveness
to opiates, most probably by altering opioid receptor
binding [65,66]. In a study of humans, we showed that
glucose infusion lowered the threshold at which normal
subjects perceived pain [67]. We also found that patients
with type II diabetes mellitus, despite an increased level
Volume 83

for stimulus detection (due to early, clinically undetectable
neuropathy), could tolerate less pain than age-matched
control subjects. In support of these findings, Boulton and
colleagues [68] reported that maintenance of normal 24-
hour blood glucose levels by use of continuous subcuta-
neous insulin infusion resulted in symptomatic relief in
patients with painful diabetic neuropathy and was accom-
panied by a significant improvement in pain scores.
In 1955, Garland [69] described a syndrome of pro-
gressive weakness and wasting of the pelvic girdle and
thigh muscles that is characteristically asymmetric and
associated with severe pain, with minimal sensory
changes. This condition, called diabetic amyotrophy, clas-
sically occurs in older men with mild diabetes and usually
resolves spontaneously within one year.
Diabetic neuropathic cachexia also occurs in diabetic
patients older than 60 and is associated with severe pain,
peripheral neuropathy, and profound weight loss [70]. It is
more common in men than in women and is associated
with marked emotional lability and anorexia. However,
depression does not appear to be causal but rather secon-
dary to the development of the syndrome. Like diabetic
amyotrophy, this diabetic complication appears to be self-
limiting.
A painful diabetic neuropathy in elderly patients that
can cause diagnostic problems is intercostal mononeu-
ropathy. These mononeuropathies often mimic the pain of
cardiac or abdominal medical emergencies [7 11. Clinical
diagnosis depends on the awareness of the existence of
this syndrome and demonstration that pinching or stroking
the skin in the anatomic distribution of the nerve elicits
dysesthesia. Diagnosis can be confirmed by electromye-
lography.
The gravest neurologic complication in elderly diabetic
patients is a cerebrovascular accident. Epidemiologic and
postmortem studies have shown an increased incidence
of ischemic stroke in diabetic patients, and the greater
risk cannot be totally ascribed to the increased preva-
lence of hypertension in diabetes [72-751. Recent studies
have suggested that ele sted glucose levels at the time of
a stroke are associatec with a poorer rehabilitative out-
come [76]. This appears to be true whether the glucose
level is increased because the patient has diabetes melli-
tus or whether the increase is secondary to central ner-
vous system-induced hyperglycemia. Animal studies sug-
gest that hyperglycemia may be toxic to neuronal function
and that elevated blood-brain glucose concentrations en-
hance the severity of ischemic brain damage [77-791,
thus supporting the case for tight glucose control during
the acute and recovery periods following cerebrovascular
accidents. However, controlled trials supporting interven-
tion with insulin infusions are not yet available.
Perlmuter et al [80] have shown that cognitive dysfunc-
tion is impaired in patients aged 55 to 74 years with non-
insulin-dependent diabetes in comparison with an age-
September
DIABETES MELLITUS IN ELDERLY PATIENTS-MORLEY ET AL
matched nondiabetic control group. Their studies suggest-
ed that the major deficiency was due to a defect in
memory retrieval rather than to attention or encoding
deficits, The cognitive performance deficit was related to
the degree of diabetic control as measured by glycosylat-
ed hemoglobin levels. In animal studies, we have found
that mice with streptozotocin-induced diabetes mellitus
have markedly impaired memory retrieval with minimal
impairment of acquisition (unpublished observations). In
view of the importance of educational programs in the
management of diabetes mellitus, this cognitive impair-
ment in older patients with type II diabetes may compli-
cate adherence to medical regimens. Mental status
should be carefully tested in all elderly diabetic patients,
and those who are found to have impairment should
receive special memory aids such as calendars-or pill-
boxes, if they are taking oral agents.
Finally, the occurrence of depression in elderly diabetic
patients needs attention. Blazier and Williams [81] report-
ed that 14.7 percent of community-dwelling persons over
the age of 65 had significant depressive symptoms. Al-
though there is no evidence that depression is more
common in elderly diabetic patients than in the general
population [80], depression is easily missed in older per-
sons. Depression is a treatable cause of dementia. Fur-
thermore, depression in elderly persons often responds to
extremely low doses of antidepressants, making it a readi-
ly treatable disorder [82]. When possible, antidepressants
with low anticholinergic activity, such as trazodone or
desipramine, should be used in elderly diabetic patients to
avoid precipitation of acute urinary retention or glaucoma.
Impotence occurs commonly in diabetic patients [83].
Diabetes appears to be responsible for impotence in IO to
20 percent of older impotent patients presenting to pri-
mary care physicians [84,85]. Although impotence in
diabetes has been classically attributed to the presence of
autonomic and/or sensory neuropathies, recent studies
have highlighted the fact that vascular disease may be a
major cause of impotence in diabetic patients, who are
particularly prone to accelerated atherosclerosis [86,87].
Patients with type II diabetes mellitus have also been
shown to have an increased mean prolactin level and an
above-average incidence of hyperprolactinemia [88],
which may play a role in the pathogenesis of their impo-
tence. Abnormal results on glucose tolerance testing are
commonly reported in older impotent men [89,90], sug-
gesting that the hyperglycemia of aging may be associ-
ated with the development of impotence. Direct intracor-
poreal injections of papaverine produce erections ade-
quate for sexual intercourse in most diabetic men
(unpublished observations). However, the safety and effi-
cacy of long-term self-injections have not been deter-
mined. Reported side effects related to hypotension sec-
ondary to systemic vasodilatory effects of papaverine
include myocardial infarction and cerebrovascular acci-
1987 The American Journal of Medicine Volume 83 537
DIABETES MELLITUS IN ELDERLY PATIENTS-MORLEY ET AL
dents. In our experience, most older impotent diabetic
men are best treated by the implantation of a semi-rigid
penile prosthesis, provided both the patient and his part-
ner wish to continue having intercourse [83].
FOOT COMPLICA’IIONS
In the 39th year of his reign, King Azo became affected
with gangrene of his feet; he did not seek the guidance of
the Lord, but resorted to physicians. He rested with his
forefathers in the 4 1st year of his reign.
II Chronicles XVI: 12- 14
The “Achilles heel” in all diabetic patients is the feet. This
is even more so in elderly diabetic patients whose failing
vision prevents visualization of the feet, which cannot be
felt because of a sensory neuropathy. Additionally, arthri-
tis may prevent bending down to touch the feet. Thus, at
every visit to their physicians, elderly diabetic patients
should take off their shoes and socks and have their feet
examined. Although the loss of manual dexterity in older
diabetic patients can make this a tedious, time-consuming
process, careful attention to the feet of diabetic patients
represents one of the most cost-effective preventive
medicine approaches. Elderly diabetic patients should not
cut their own toenails, as more often than not they finish
up cutting themselves. Attention to the feet in diabetic
patients represents an intellectually boring pursuit, as
stressed by Joslin: I‘. . . if you wish to avoid gangrene; you
must enter into all these minutiae” [9 I].
RENAL COMPLICATIONS
It is well recognized that creatinine clearance diminishes
with advancing age [92]. Hypertension-which, acting
synergistically with diabetes, can produce renal failure-
is also common in elderly persons [I]. It would be predict-
ed that elderly diabetic patients have a greater risk of
diabetic neuropathy. In Pirart’s study [59], neuropathy
occurred slightly more often in older diabetic patients
during the first five years following diagnosis. Another
potential problem is the effect of the interaction between
aging and diabetic neuropathy in determining the appro-
priate doses of various drugs. Careful monitoring of serum
drug levels is essential under these circumstances. It
should also be remembered that patients with diabetes
have particular risk for the development of acute tubular
necrosis following intravenous injection of radiographic
contrast agents [92]. This risk relates both to the level of
creatinine clearance (a risk markedly increased in pa-
tients with a creatinine clearance of less than 25 ml/
minute) and to the degree of hydration of the patient. It is
important to note that hypodipsia occurs with normal
aging, making the elderly particularly prone to dehydration
[=I.
More than half of the diabetic patients with renal papil-
lary necrosis are over the age of 60 [94]. Further, the
538 September 1987 The American Journal of Medicine
classic findings of flank pain and high fever are not
necessarily present in elderly patients. In renal papillary
necrosis, blood cultures usually reveal the responsible
bacterial or fungal organism. Aggressive antibiotic thera-
py can improve the outcome in this condition.
Nonsteroidal anti-inflammatory drugs inhibit intra-renal
prostaglandin synthesis, leading to sodium and water re-
tention and worsening hypertension [l]. They can also
lead to deterioration in glomerular filtration. In older dia-
betic patients with mild renal insufficiency, nonsteroidal
anti-inflammatory drugs can precipitate severe hyperkale-
mia secondary to hyporeninemic hypoaldosteronism [95].
As such, it is clear that nonsteroidal anti-inflammatory
agents should be used with great caution in elderly diabet-
ic patients. Sulindac appears safer than other nonsterokial
anti-inflammatory agents, perhaps because it has less of
an inhibitory effect on intra-renal prostaglandins than do
the other agents [96]. Sulindac is also a potent aldose
reductase inhibitor [97] and has recently been shown to
be protective of the blood-retinal barrier in early diabetic
retinopathy [50]. This aldose reductase inhibitory properly
of sulindac makes it an even more attractive nonsteroidal
anti-inflammatory agent in diabetes.
INFECTIOUS COMPLlCATiONS
The most dramatic of the infections specific to elderly
diabetic patients is malignant,otitis externa [98,99]. This
infection is due to Pseudomonas aeruginosa and has a
mortality rate of more than 50 percent. It presents with
pain and purulent drainage from the ear, tenderness and
swelling of surrounding tissues, and polyps in the floor of
the external auditory canal. Facial nerve palsies occur
early in the course of the disease. Treatment consists of
parenteral carbenicillin or ticarcillin together with tobra-
mycin or gentamicin, as well as surgical debridement.
Necrotizing fasciitis, a condition in which aerobic bati-
teria such as Staphylococcus aureus or Pseudomonas act
synergistically with anaerobic organisms, e.g. Bacter-
oides, is a life-threatening condition seen especially
among elderly diabetic patients [ 1001. Candidiasis occurs
commonly in both diabetic patients and the elderly. Isolat-
ed T cell defects against Candida occur in the elderly,
often making this a difficult infection to eradicate [62].
Candidal esophagitis can lead to severe anorexia and
weight loss. Life-long treatment may be necessary in
elderly diabetic patients, in view of the difficulty in eradi-
cating this infection. Choledochal disease occurs three
times more commonly in elderly persons than in younger
subjects [I], and diabetic patients appear to be at particu-
lar risk for the development of cholecystitis associated
with gallstones.
Tuberculosis occurs commonly in elderly persons and
can produce devastating epidemics in nursing home pop-
ulations [ 10 11. In a survey from New York City, diabetes
was second only to alcoholism as a major factor in
Volume 83

tuberculosis reactivation [ 1021. Abnormal glucose toler-
ance has been reported to occur in as many as 40
percent of patients with tuberculosis [ 1031. Thus, elderly
patients with tuberculosis should be screened for diabe-
tes. All elderly diabetic patients should have tuberculin
skin testing. If the first result is negative, the test should be
repeated IO days later to elicit the booster phenomenon.
This will avoid the subsequent erroneous treatment of
patients with false-positive tuberculin conversion. It
should be remembered that anergy occurs in as many as
40 percent of normal elderly subjects [ 1041 and as many
as 60 percent of institutionalized elderly persons [105],
making the interpretation of skin test results difficult in this
population.
All elderly diabetic patients should be vaccinated
against influenza at least once a year [ 1061. Since the
antibody response in elderly persons is poor and since the
influenza peak occurs in January and February, it has
been suggested that it may be prudent to vaccinate twice
a year, in October and January. Amantidine prophylaxis is
recommended in elderly diabetic patients who have hy-
persensitivity to egg protein or prior severe reactions
associated with influenza vaccination. Amantidine thera-
py should be considered for all elderly diabetic patients
with an influenza-like illness. Amantidine toxicity is en-
hanced with impaired renal function, and a reduced dos-
age of 100 mg per day is recommended for persons aged
65 years or older. Pneumococcal vaccinations are rec-
ommended to be given once for all diabetic patients
[107]. Again, because of the poor antibody response in
elderly persons, this appears to be inadequate. A recent
study of patients in Denver undergoing dialysis has sug-
gested that yearly pneumococcal vaccination may be
reasonable in immunocompromised patients [ 1081. A
prudent approach to elderly diabetic patients would be to
measure pneumococcal antibody titers yearly and re-
vaccinate when the titers are no longer detected. Side
effects from pneumococcal vaccination are related to
high antibody titers [ 1071.
THERMOREGULATORY DISTURBANCES
It is well recognized that thermoregulatory disturbances
occur commonly in elderly persons. A number of physio-
logic concomitants of aging put elderly subjects at particu-
lar risk for the development of hypothermia. These in-
clude impaired central recognition of temperature fluxes,
diminished resting peripheral blood flow, decreased mo-
bility, decreased muscle mass, decreased shivering, de-
creased vasoconstriction, and impaired autonomic ner-
vous system function. Hypothermia is a known complica-
tion of both hypoglycemia [ 1091 and diabetic ketoacidosis
[ 1 lo] in elderly persons. Diabetic patients have been
reported to be more commonly hospitalized with hypo-
thermia than are members of the general population
[ 111,112]. Recently Neil et al [ 1131 found that female
September
DIABETES MELLITUS IN ELDERLY PATIENTS-MORLEY ET AL
diabetic patients were admitted 7.9 times more frequently
for hypothermia than would be predicted. Even after acute
diabetic emergencies were excluded the ratio was 6.4.
Thus, diabetes appears to be an important risk factor for
the development of hypothermia in elderly women ex-
posed to low environmental temperatures.
NUTRIENT STATUS
Since 1674, when Sir Thomas Willis suggested that dia-
betic patients should eat gummy and starchy foods, the
intricate relationship between nutrition and diabetes has
been well recognized. Uncontrolled diabetes mellitus is a
catabolic state that leads to major nutrient wastage. This
state can be readily reversed by insulin therapy. Elderly
persons appear to be particularly at risk for the develop-
ment of trace element deficiency [ 1141. Diabetes can
further compound this situation; for example, type II dia-
betes mellitus is associated with hyperzincuria and im-
paired zinc absorption [ 1151. In a recent study, we found
that zinc replacement in patients with type II diabetes and
zinc depletion improved T cell function, as measured by
the T lymphocyte response to phytohemagglutinin [ 1161.
Zinc also has been shown to play a role in wound healing
[ 1141, and zinc supplementation accelerated the rate of
healing of leg ulcers in zinc-deficient elderly subjects
[ 1171. Although it is well recognized that zinc can alter
taste perception, we could show no effect of zinc on taste
perception in patients with type II diabetes [I 161. Thus,
zinc status should be assessed in all elderly diabetic
patients.
A number of studies have suggested a role for chromi-
um in the glucose intolerance of elderly subjects [ 1181.
However, few of these studies have been well controlled.
Recently a preliminary study in healthy elderly volunteers
suggested that a combination of chromium and nicotinic
acid improved glucose tolerance, whereas chromium and
nicotinic acid by themselves were ineffective [ 1191.
Urinary loss of magnesium is common in poorly con-
trolled diabetes [ 1181. Diabetes mellitus was found to be
the disease most frequently associated with hypomagne-
semia in a general medical clinic [120]. Hypomagnese-
mia in elderly patients may worsen cardiac failure and
increase the chances of digoxin toxicity.
Because as many as 70 percent of elderly persons
take vitamin supplements, it is important to remember
that vitamin C in large doses interferes with glucose
measurements and thus can hamper the monitoring of
diabetic control [ 1181.
lshida et al [ 12 1] have shown that bone mass is re-
duced in 26 percent in patients with type II diabetes. It is
possible that this diabetic osteopenia is related to de-
creased vitamin D concentrations, but there are conflict-
ing data on this point [70]. Poor diabetic control is associ-
ated with hypophosphatemia, which further exacerbates
calcium loss from bone.
1987 The American Journal of Medicine Volume 83 539
DIABETES MELLITUS IN ELDERLY PATIENTS-MORLEY ET AL
TREATMENT OF DIABETES IN ELDERLY
PATIENTS
The treatment of diabetes in elderly persons follows the
same principles as in younger persons. In general, the
blood glucose level should be maintained between 100
and 200 mg/dl, while avoiding unnecessary episodes of
hypoglycemia. Lipson [ 1221 has clearly enumerated the
factors that interfere with optimal treatment of diabetes in
elderly patients. These include alterations in vision, taste,
and smell; difficulties in food preparation and consump-
tion secondary to tremor, arthritis, and poor dentition;
hypodipsia; altered renal and hepatic function; cognitive
and psychiatric impairment; decreased physical activity;
interaction with multiple medications and other disease
processes; and poverty.
Although weight-reducing diets are of potential benefi-
cial value for obese patients with type II diabetes, most
elderly diabetic patients are not overweight and the intro-
duction of a weight-reducing diabetic diet in those over the
age of 70 can have disastrous consequences. Recently, it
has been noted that the combination of weight loss and
low weight represents a major poor prognostic factor in
elderly subjects [ 123,124]. Further, high-fiber diets,
which are in vogue for the treatment of younger diabetic
patients [125], are contraindicated in elderly immobile
patients with diabetes. As eloquently described by Brock-
lehurst [ 1261, high-fiber diets aggravate the terminal res-
ervoir syndrome responsible for much of the constipation
seen in institutionalized elderly persons. The addition of
some fiber to the diets of elderly obese diabetic patients
may help smooth the glycemic response to the meals
[ 1271. The exclusion of simple sugars is the cornerstone
of dietary treatment in elderly patients with mild diabetes.
Counterbalancing this with the introduction of a low-level
physical exercise program may be sufficient to control
diabetes in many elderly patients. Weight-bearing exer-
cise in elderly diabetic patients will also produce salutato-
ry effects on the osteopenia commonly present. In gener-
al, the so-called “specialized” diabetic diets sold in su-
permarkets are expensive, and dietary counseling needs
to take economic status into account.
Sulfonylureas can provide adequate blood glucose
control in many elderly diabetic patients. Chlorpropamide
is inadvisable for older diabetic patients because it reduc-
es free water clearance and produces an unacceptable
incidence of hyponatremia in elderly subjects [ 128,129].
Further, due to the long half-life of chlorpropamide, more
episodes of hypoglycemia occur than with other hypogly-
cemic agents [ 1301. Overall, the incidence of side effects
with chlorpropamide is twice that with other first-genera-
tion agents or with glyburide. Chlorpropamide is contrain-
dicated in all patients over 60 years.
Hypoglycemia occurs with approximately equal fre-
quency in patients using glyburide and in those using
540 September 1987 The American Journal of Medicine
glipizide [130]. The Swedish Adverse Drug Reactions
Advisory Committee register has clearly demonstrated
that elderly patients have a particular risk for the develop-
ment of hypoglycemia [ 13 11. The mean age of hypogly-
cemic patients was 75 years, with 21 percent of the
patients older than 80 years of age. Patients with hepatic
and/or renal impairment appeared to be particularly at
risk.
A theoretic advantage of second-generation sulfonylu-
reas in the elderly is that they carry little electrical charge
and are bound to albumin by van der Waal’s forces [ 1301.
First-generation sulfonylureas are bound to albumin by
ionic forces and, as such, are displaced by (and displace)
anionic drugs (such as salicylates, dicumarol, phenylbuta-
zone, and monoamine oxidase inhibitors) from albumin.
This can result in potentiation of hypoglycemia and other
toxic reactions in elderly patients, who often take many
other drugs. Both glyburide and glipizide can be adminis-
tered once daily, with little advantage to twice-daily dos-
age regimens [ 124,132,133].
Many elderly patients require insulin, and this therapy
should not be withheld because of the misguided view-
point that insulin injections represent an undue hardship.
Certainly, reduction in fatigue and frequent urination, to-
gether with improvement in the reduced visual acuity
associated with hyperglycemia, represent important qual-
ity-of-life issues. Although the use of insulin in elderly
patients needs to be individualized, many patients who
would benefit from this treatment are denied it by their
well-meaning physicians. Older diabetic patients have
been shown to err by 10 to 20 percent when measuring
their insulin [ 134,135]. For those patients who require the
use of a pre-measured mixed insulin regimen (intermedi-
ate-acting plus regular insulin), a buffered insulin prepara-
tion should be utilized, as unbuffered regular insulin
changes its properties, becoming more like an intermedi-
ate-acting insulin preparation.
With the alterations in renal tubular threshold that occur
in diabetes and with aging, together with a heightened
awareness of the need for better control than that indicat-
ed by merely measuring urine glucose spillage, it is now
clear that there is little place for urine testing in the
management of diabetic patients. Home blood glucose
monitoring should be offered to every elderly diabetic
patient who has sufficient visual acuity and is capable of
learning the procedure. The manifestations of hypoglyce-
mia in elderly persons can be subtle, making use of this
technique particularly important. Home blood glucose
monitoring should be supplemented by measurement of
glycosylated hemoglobin levels every two to three
months. It should be recognized that several factors com-
monly associated with diabetes in elderly patients may
alter glycosylated hemoglobin levels, including chronic
renal failure, hypoxia, and drugs such as high-dose salicy-
lates and opiates [ 1361.
Volume 83
 DIABETES MELLITUS IN ELDERLY PATIENTS-MORLEY ET AL

Finally, the key to management in elderly diabetic
patients is a team approach. Older diabetic patients need
to be seen more frequently and to have at least one home
visit for assessment of household safety and their ability to
prepare meals. Home help and a regular visiting nurse
may make the difference between a patient’s remaining
at home or being institutionalized. Psychologists may play
an important role in identifying early treatable depression.
Pharmacist-supplied specialized memory aids for cogni-
tively impaired older diabetic patients may prevent unnec-
essary hypoglycemia. A 24-hour hot-line will allow older
diabetic patients to ask and have answered questions that
may prevent weeks of subsequent hospitalization.
CONCLUSIONS
This review has highlighted the fact that diabetes in elderly
patients is surprisingly similar to that seen in younger
patients. Older diabetic patients appear to have just as
much, if not more, risk of micro- and macrovascular
complications. Good control of the diabetes appears to be
as important for retarding the development of these com-
plications and improving the quality of life. Older patients,
however, require more time from their clinicians and a
greater awareness about the pharmacologic properties of
the drugs used to treat them and the potentially hazardous
drug-drug interactions. In view of the paucity of research
into the natural history of diabetes in the elderly population
and the effects of treatment on quality of life, these
generalizations need to be recognized as such, and physi-
cians need to have an open mind to future developments
in this area. Finally, the consequences of the hyperglyce-
mia of aging are totally unknown. Is the hyperglycemia of
aging a state of accelerated aging? Does this hyperglyce-
mia accelerate the rate of collagen polymerization, DNA
breaks, and capillary basement membrane thickening?
Will aggressive treatment of the hyperglycemia of aging
turn out to be a true fountain of youth? These and other
questions make the pursuit of knowledge concerning the
consequences of diabetes mellitus in elderly patients one
of the most intellectually stimulating and clinically impor-
tant areas in modern medicine.

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