Anna Giulia Cattaneo, M.D.
Impaired glucose homeostasis plays a role of importance in
aged individuals, its manifestations varying from light, often
unrecognized hyperglycemia, up to one of most frequent causes
of hospital admission and even as a mortality predictive value
after stroke or acute cardiac ischemia. Not only higher glycemic
values, but even more dangerous hypoglycemic episodes can
disturb the frail equilibrium of older patients. The aim of
this work is to point out the importance, for the primary
care physician and for the taking care of such subjects, to
prevent major hypo-or hyperglycemic episodes, and to recognize
the co-occurring risk factors that warrant aggressive intervention.
Despite of extremely simple counteracting measures, the ethiopathogenesis
of this phenomenon and prediction of its subsequent evolution
is a troubleshoot for the physician, who must choice between
a cautious waiting for an eventual impairement and shift into
pathological conditions, or a series of diagnostic choices
that could be time- and money-consuming, disturbing for the
frail equilibrium of the aged patient and often frustrating.
Knowledge of main events associated to hyperglycemia development
and their frequence in the elderly should be of good help
Diagnosis of hyperglycemia in the elderly and its predictive
The high prevalence of accidental hyperglycemia, impaired
glucose tolerance and even diabetes mellitus in old subjects
are so widely experienced, that age-adjusted laboratory reference
values for basal or loaded glycemia have been early introduced
into practice. When the occurrence of hyperglycemia has been
detected and confirmed, first and main attention should be
payed to the possibility of a so called iatrogenic diabetes.
The number of drugs possibly responsible for hyperglycemia
is very wide, including many among those commonly used in
the elderly, like some hypertensive, diuretics, hypnotics,
antidepressant or antipshycotic, analgesic and antirheumatic
agents. Every times hyperglycemia occurs the entire therapy
should be reconsidered, and a careful anamnestic query for
automedication should be done, the defect being reverted simply
by removing the not tolerated drug.
On the contrary and despite of the simplicity of tests required
to ascertain its presence, hyperglycemia due to type II diabetes
remains frequently unrecognized: it has been estimated that
in a large managed care organization located in USA, as many
as 18% of patients having laboratory fingerprinting for diabetes
remains undiagnosed (Edelman D.,Eff. Clin.Pract. 2002, 5,
Because of its high risk for complications at the cardiac
and vascular, renal, ocular and horthopedic (diabetic foot
development) level, early diagnosis and care are recommended.
The use of simple risk score based on data commonly available
in the primary care and related to the HbA1 levels has been
proposed by Meigs JB et al. (Diabetes Care 2002, 25, 977-983).
The metabolic or X-syndrome, as defined by the World Ealth
Organization is the association of overweight, hypertension,
diabetes and hyperlipidemia. It is highly prevalent in general
population, even more in the older subjects, and strictly
associated to a risk for cardiovascular disease (CVD).(Meigs
JB., Am.J.Manag.Care , 2002, 8, S283-292). This syndrome seems
to associate main risk factors for developing type II diabetes,
that can be divided into two groups: the primary ones, like
obesity, age, number of pregnancy, genetic background and
the secondary ones, namely hyperinsulinemia, hyperglycemia,
dyslipidemia, hypertension. The most predictive for the development
of diabetes appear to be obesity and hyperinsulinemia.
Hyperglycemia may develop or worse at the onset of acute
stroke and myocardial infarct: in both cases its severity
is a predictor of mortality at the short-as well long-course,
expecially if not adequately treated at the time of the acute
Instead, only a minor role should be abscribed to endocrine
pathologies associated with hyperglycemia, whose prevalence
is low in the old people, even lower than in the younger or
in the middle aged..
Hypoglycemic risk in the elderly.
Hypoglycemia accounts for a relatively high number of emergency
requiring hospital admission: it occurs by far more frequently
as a consequence of unadequate therapy in diabetes management.
The role of hypoglycemia in disturbing the frail homeosthasis
of the aged body should be underlined, because of the longer
survival of aged people, namely of those affected by various
chronic pathologies included diabetes and impaired liver function,
made by far more frequent the observation of iatrogenic hypoglycemic
insults. The diffuse hypothesis that the the majority, if
not all cases of diabetes in the aged should be classified
as the non-insulin requiring, or type II diabetes mellitus,
should be revisited in the light of general amelioration of
geriatric care and frequent observation of cases of insulin-dependent
diabetes mellitus in the old and very old. If this phenomenon
should be abscribed to a shift from type II to true type I
diabetes, or if a reclassification of the entire syndrome
should be mandatory, is obviously not the question of this
rapid review, but may only be the result of improved ethiopatologic
To prevent severe if not even fatal hypoglycemia in old patients,
a careful insulin scheduling, when necessary, should include
preparations characterized by shorter half-life and minimal
risk for nocturnal episodes. The short half-life sulfamides,
and molecules tolerated in renal and liver function impairement
should be of first choice for geriatric care. Administration
of drugs to reduce lipidemia associated to hypoglycemic drugs
should be carefully done, because of the possibility of suddenly
lowering of glycemic values.
Apart from drug-induced hypoglycemia, most frequent causes
of this kind of emergency in the aged are serious hepatic
damage, like in ethylic cyrrosis, and paraneoplastic syndromes
or metastatic tumors of the adrenal. In these cases, hypoglycemia
could develop rapidly and severe enough to reach the convulsive
level before any counteraction is adopted, if the event has
not been expected and planned in advance. In chronic liver
diseases glucose homeostasis is disturbed in a complex way,
and both hper- or hypoglycemia could be observed, in relation
to the entity of the parenchimal damage, glycogen storage
ability and enzymatic function of the residual liver. In particular,
hypoglycemia is not usually so severe and frequent in hepatopathies
other than ethylic cyrrosis: however in a near future, when
a number of survivors to drug abuse should enter in the geriatric
condition, a shift of this problem, eventually associated
with chronic hepathitis B or with direct drug toxicity, could
be observed. In survivors from HIV infection adrenal impairement
should be expected (Gonzales-Gonzales JG, Int.I.STD AIDS 2001,
The third more frequent cause of hypoglycemia, the panhypopituitarism
due to the Sheenan syndrome, is out of geriatric implicances.
In many cases the alteration of charbohydrate metabolism
found in elderly patients is so light that pharmacological
care is probably pleonastic: a cautious behaviour based on
moderate prevention is usually the only required intervention.
Classical measures adopted in these events are based on dietary
counseling, encouraged physical activity, moderate consumption
of alchoolics and fats, and a more frequent control of glycemic
values, eventually with the addition of postprandial values
and glycated hemoglobin testing. An additive precaution could
be the hormonal replacement for postmenopausal women.
The prevention of all aging-related disturbances and diseases
could be a frustrating thing if the problem is posed, as frequently
done, when the aging process has reached its advanced phases:
in this case the only prevention appears to be the preservation,
as long as possible of affected functions from rapid deterioration.
The ideal prevention should involve early detection and removal,
if possible, of risk factors in the young, education to safe
life and periodic control of principal parameters diagnostic
for the most probable pathologies, adjusted for age, sex,
and personal features. The ideal is never or quite never realised
in the human experience: for this reason the taking-care must
be able to make compromises.
In the particular case of hyperglycemic syndromes, the current
opinion is that optimal prevention of development or further
impairement of hyperglycemic syndromes is based on obesity
avoidance or reduction, careful and moderate control of glycemic
levels by means of dietary measures and exercise, and control
of hypertension and dislipidemia (so called X-syndrome). This
is true in the old as well in the younger people, and the
apparent simplicity of preventive measures should be priced
by a very low number of escaping cases. The contrary is the
true: therefore two possibilities can be taken into account.
The one is that preventive measures have minor efficacy that
postulated on the basis of results of defectively-planned
trials. The other that not avoidable factors, like genetic
congenital or acquired damage, specific life span with its
consequences, or not modifiable aggressive ambient conditions
are palying a role.
More simple could be to limit the efforts to care the present
conditions. In old people, insulin requirement is generally
limited to final phases of their pancreatic defect, and develops
late or very late in life. A good control is generally reached
by a cautious use of perpherically-acting hypoglycemic agents,
like biguanides, sometimes in association with sulphanylureas.
It is mandatory for the counselor and for the taking care
to take into the mind and prevent the possibilities of lactic
acidosis, evenience possible with the first type of drug,
and of severe, if not fatal hypoglycemic events, with the
second. These eveniences are very dangerous because of the
frailty of the aged body, and their occurrence is frequent
enough to be very widely known among people devoid to the
care of these patients, even if not specialists. Their prevention
is based on frequent detection of principal parameters for
lactacidemia, avoidance of use of drugs with higher toxic
potential, like fenfluramine, and the preference for molecules
more tolerated, like the analogous metformine; use of molecules
with shorter life, well metabolized by the aged in which some
degree of renal impairement is often seen. In old people with
cardiac damage or impairement the use of biguanides should
be avioded, and the preference given, if prudent, to a cautious
therapy with insulin. Accurate education of people living
with the patients is very important, whithout dangerous overoptimism
or imprudent behaviour: light stress is a good price for a
correct prevention of hypoglycemic episodes, potentially destructives.
Attention should be payed by the therapist in choicing associated
therapy, eventually required for control of hypertension or
any other coexhisting condition.
The prevention of alchoolic cyrrosis is only based on very
early prevention of alchool continuative abuse, the same is
true for hepatic diseases due or associated to hazardous behaviour
, like drug or B-hepatitis in drug abusers. The difficulties
to succed in this type of prevention are intuitive, and in
my opinion more linked to question of crime prevention that
to true sanitary problems: the role of the physician should
be restaured and limited to the intervention on the organ
failure and its consequences.
When considering instead the hypoglycemic events, diverse
consideration should be made. In the case of hypoglycemic
consequences of inadequate therapy, it can generally be successfully
changed, with or whitout specialistic aid, and minor modifications
of the actual therapy, or a new, well planned therapeutic
strategy. The hypoglycemic spontaneous events observed in
cyrrosis or occuring in neoplastic patients can be instead
dramatic and unexpected events, at least in their beginning.
General conditions of cyrrotic, hypoglycemic prone subjects
are often very compromised, and even near the exitus, exspecially
in the case of older people. The social background of these
subjects is frequently refractory to any serious plane for
prevention, sometimes for cure too, and istitutionalitation
is frequently required. Finally, the hypoglycemic episodes
linked to paraneoplastic syndromes and metastatic tumors are
usually acute and even dramatic in their beginning, when they
start unespectedly in an environment frequently characterized
by stressed emotive reactions. People living with the patients
and taking care of him should be trained to recognize and
promptly counteract these eveniences, that can start in an
early phase of the disaese and occur many times. The rarity
of neoplastic syndromes associated with hypoglycemic events
is partially counteracted by the relatively higher frequency
of neoplasia in the elderly, expecially of type more frequently
causing hypoglycemia, like mesotheliomas, microcytomas or
tumor of enterochromoaffin cells.
The alterations of glucose metabolism frequent in the elderly
can be due to a primary disease, or be secondary to other
pathological conditions or to pharmacological or toxic agents.
No one of these condition is restricted to the old, but all
are common to the adult age and share the same ethiological
and diagnostic features. Even prevention and cure are similar,
the only true difference being the higher frequence of altered
homeostasis and the more severe consequences of a bad care,
linked to the fail of counteracting mechanism in the older.
Special attention should be payed to the consequences of hypoglycemic
events at the cardiac and cerebral level: both organs are
particularly frail in the elderly, and the evenience of an
acute myocardial infarct or of irreversible cerebral damage
subsequent to the insult should be possible
More readings on this subject
- 1. Alix M. Diabetes in the elderly patient.
Presse Med (2000), 29, 2150-2155 (in French)
- Bolk J, van der Ploeg T, Cornel JH,
Arnold AE, Sepers AE, Umans VA. Impaired glucose metabolism
predicts mortality after a myocardial infarction. Int J
Cardiol (2001), 79, 207-214
- Dexler AJ, Robertson C. Type 2 diabetes.
How new insights, new drugs are changing clinical practice.
Geriatrics (2001) 56, 32-33
- Edelman D. Outpatient diagnostic errors:
- Ford ES, Giles WH, Dietz WH. Prevalence
of the metabolic syndrome among US adults: findings from
the third National Health and Nutrition Examination survey.
JAMA (2002) 287, 356-359
- Holstein A, Plaschke A, Egberts EH.
Lower incidence of severe hypoglycemia in patients with
type 2 diabetes treated with glimepiride versus glibenclamide.
Diabetes Metab Res Rev (2001), 17, 467-473
- Imazu M, Sumii K, Yamamoto H, Toyofuku
M, Tadehara F, Okubo M, Kohno N, Onaka At, Hawaii-Los Angeles-
Hiroshima study. Diabetes Res Clin Pract. (2002), 57, 61-69
- Koller E, Schneider B, Bennett K, Dubitsky
G. Clozapine-associated diabetes. Am J Med (2001), 111,
- Lai SW, Li TC, Ng KC. Body mass index
and its related factors in the elderly. Ann Acad Med Singapore
(2001), 30, 397-400
- Lindenmayer JP, Nathan AM, Smith RC.
Hyperglycemia associated with the use of atypical antipsychotics.
J Clin Psichiatry (2001), 62 suppl. 23, 30-38
- Meigs JB. Epidemiology of the metabolic
syndrome, 2002. Am J Manag Care (2002), 8 suppl 11, S283-292
- Resnick He, Shorr RI, Kuller L, Franse
L, Harris TB. Prevalence and clinical implications of American
Diabetes Association-defined diabetes and other categories
of glucose dysregulation in older adults: the health, aging
and body composition study. J Clin Epidemiol (20019, 54,
- Sthal M, Berger W. Higher incidence
of severe hypoglycaemia leading to hospital admission in
Type 2 diabetic patients treated with long-acting versus
short-acting sulphonylureas. Diabet Med (1999), 16, 586-590
- Vauzelle-Kervoroedan F, Delcourt C,
Forhan A, Jougla E, Hatton F, Papoz L. Analysis of mortality
in French diabetic patients from death certificates : a
comparative study. Diabetes Metab (1999), 25, 404-411
- Williams LS, Rotich J, Qi R, Fineberg
N, Espay A, Bruno A, Fineberg SE, Tierney WR. Effects of
admission hyperglycemia on mortality and costs in acute
ischemic stroke. Neurology (2002), 59, 67-71
Department of Structural and Functional Biology, Insubrian
University, Via J.H.Dunant, 3, 21100 Varese, Italy
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