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Insulin therapy in the elderly type 2 diabetic patient
Diuhete.~ Research und Clinical Practice, Suppl.
24
(1988)24-28
Elsevier
DRC SO108
Insulin therapy in the elderly type 2 diabetic patient W. Berger Departnwnt of’hternal
Key words: Type 2 diabetes;
Medicine.
Insulin therapy
One of the most difficult problems in the treatment of diabetes is the appropriate use of insulin in the elderly type 2 diabetic patient. The difficulties consist of defining the so-called secondary failure of oral antidiabetic drug therapy and in establishing the therapeutic goal. ‘Secondary failure’ of oral antidiabetic drug therapy is defined by the degree of hyperglycemia and the presence and severity of clinical symptoms. In symptomatic hyperglycemia, fasting blood glucose concentrations consistently above 11 mmol/l, polyuria, polydipsia and weight loss are unmistakable symptoms of a critical deficit of insulin secretion. There is general agreement as to the indication for insulin therapy in symptomatic hyperglycemia. In the asymptomatic hyperglycemia of the elderly, the indication for insulin therapy is less clear. At a glance, acceptance of even pronounced hyperglycemia in the older type 2 diabetic patients, as long as they remain asymptomatic, stands to reason. Rigorous blood glucose control is unlikely to significantly influence the course of micro- and macrovascular complications in this age group. Furthermore insulin therapy is difficult to administer to these patients. Address fiir Innere
for correspondence: Medizin,
Professor
Kantonsspital
W. Berger, Abteilung
Basel, 4031 Basel. Switzer-
land.
016%8227/88/$03.50
Kanfonsspital, Basrl, S~tir-_erkand
Q, 1988 Elsevier Science Publishers
In this presentation we will focus on asymptomatic hyperglycemia, i.e., with a fasting blood glucose concentration range between 8 and 12 mmol/l, which most often is not associated with the classical signs of decompensation but where more subtle signs of insulin deficiency, mostly of a psychosomatic nature, may occur. In overweight subjects the upper limit of the asymptomatic glucose range may be as high as 15 mmol/l. It is not widely recognized that more or less pronounced alterations of the psychic state precede the metabolic decompensation caused by insulin deficiency. These symptoms comprise a depressive mood, apathy, fatigue and inertia. The similarity of these symptoms caused by insulin deficiency to other symptoms of old age leads to a diagnostic dilemma which can only be overcome pragmatically by a trial with insulin therapy. This problem is illustrated in a study which we performed in our outpatient clinic [l]. We investigated 15 type 2 diabetics, all of whom had attended our outpatient clinic over a long period and showed fasting blood glucose values of over 9 mmol/l but otherwise felt free of complications. All patients were offered a trial insulin therapy with the option of returning to the original oral antidiabetic therapy. Insulin
B.V. (Biomedical
Division)
therapy
produced
a slight initial
reduc-
25 tion of the fasting blood glucose concentration from 14 to 11 mmol/l which subsequently reached 8 mmol/l. Concomitantly hemoglobin Ai, (HbA1,)
the dangers
fell from 10 to 8%. Despite the modest decrease in blood glucose concentration which occurred during the first 6 weeks the wellbeing of the patients improved markedly during this period. This improvement in wellbeing was most pronounced in six
patient and the nurse and often causes anxiety, and such therapy may be felt to be a heavy burden in the last years of life. The risk of hypoglycemia is a
patients in whom the depressive mood prevailing during oral antidiabetic drug treatment disappeared completely. This improvement in wellbeing was so pronounced that when the participants were asked if they would reconsider oral antidiabetic drug therapy after 2 months on insulin, only seven of the 15 patients considered oral antidiabetics an alternative to the trial insulin therapy, while at the end of the R-month study only two patients wanted to resume oral antidiabetic therapy. Obviously the participants valued the advantages of insulin therapy higher than the disadvantages brought about by the insulin injections. Interestingly, these elderly patients objected more to the dietary restrictions than to the injection of insulin.
hypoglycemia, often brought about by dietary mistakes. Analysis of the severe insulin hypoglycemic
The experience of a 76-year-old watchmaker exemplifies the favorable results of our study. He reported that shortly after commencement of insulin therapy, and in the absence of spectacular improvement of glycemia he could again produce the fine parts of the clockwork at his turning lathe. To exclude a placebo effect, oral antidiabetic therapy was resumed, resulting in an acceptable fasting blood glucose of 9-10 mmol/l in this moderately obese patient. On this therapy no dramatic changes in wellbeing occurred. Nevertheless, this patient asked me to prescribe insulin therapy again because he felt more productive with this type of therapy. Only 2 days after recommencement of insulin therapy he reported that he had enjoyed a musical performance on television the previous evening, an experience which never occurred during oral antidiabetic drug treatment. Apart from the obvious beneficial effects of insulin therapy in the elderly. one has to be aware of
and adverse
effects of insulin
in these patients. The initiation of insulin in elderly diabetics is time-consuming
therapy therapy for the
major drawback of insulin therapy. Elderly diabetic patients especially are at risk of developing severe
emergency admissions to the Cantonal Hospital in Base1 from 1981 to 1985 showed that 35% of the 173 emergency admissions were diabetics aged over 70. This age group represents only 15% of all insulin-treated patients. The potential risk of hypoglycemia during insulin therapy makes it necessary to periodically reconsider the dosage and even the indication for insulin therapy. The improvement of metabolic control by insulin therapy leads to a reduction of insulin resistance and an improvement of B-cell function so that exogenous insulin can be reduced or even omitted. A valuable index for assessing whether insulin therapy can be discontinued is the estimation of residual insulin secretion by C-peptide determinations. In a study of 45 type II diabetic patients we found a good correlation between fasting C-peptide values and the necessity of insulin therapy for the ensuing 3 years. We also found that C-peptide values have to be considered in the context of the concomitant blood glucose concentration. Oral antidiabetic treatment
was successful
with the following
blood
glucose (BG): C-peptide values: BG 7- 8 mmol/l: C-peptide 2 0.4 nmol/l; BG 8- 9 mmol/l: C-peptide 2 0.47 nmol/l; BG 9-10 mmol/l: C-peptide 2 0.55 nmol/l; BG 10-I I mmol/l: C-peptide 2 0.62 nmol/l; BG 1 l-12 mmol/l: C-peptide 2 0.7 nmol/l [2]. The transient need for insulin substitution is illustrated by the following case report. In a patient born in 1907 and suffering from diabetes since 1961, insulin therapy became necessary in 198 1 because fasting blood glucose values surpassed 11 mmolil. The simultaneous C-pep-
26 c
-PEPTIDE
PmOlII
1000
0
fasting
Q2l
after 1 mg Glucagon iv
800
600
400
200
0 28.1.81
22.10.81
27.582
13.9.83
Treatment
SH
SH
Insulin
Insulin
Fasting Bloodglucose
9.7
11.1
9.2
10.4
Fig.
1. Variability
of residual
insulin secretion
in a type 2 diabetic
mass index 26-28)
from
tide values were very low (0.3 nmol/l). However, during the years of insulin therapy the capacity to secrete insulin increased to such an extent that sulfonylurea therapy could be resumed (Fig. 1). While in the above case insulin therapy had no adverse side effects and could be regarded as an alternative to antidiabetic drug treatment, the following example shows that unrecognized over-insulinization can occur over the years under insulin therapy and produce stress-like symptoms which are attributed to recurrent but not recognized hypoglycemia: A dentist aged 70 was put on insulin (58 U lente insulin daily) 21 years ago when diabetes mellitus was detected by ketonuria and hyperglycemia. Over the last years, sporadically determined fasting blood glucose values were in the range of 312 mmol/l. The patient visited the clinic complaining of recurrent afternoon weakness. Blood glucose determinations at this time revealed a tendency for hypoglycemic episodes between 3
15.2.84 Insulin
27.11.84
3.9.85
17.4.66
Insulin
SH
SH
6.9
6.2
$8
7.0
subject (male, born in 1907. onset of diabetes
mellitus in 1961, body
1981 to 1986. SH: sulfonylurea.
and 6 p.m. Furthermore he reported that for years he had suffered from burning epigastric pain readily relieved by antacids. The fasting Cpeptide concentration was more than 1.0 nmol/l (blood glucose 10 mmol/l). Since this was indicative of sufficient insulin secretion, insulin was discontinued and almost ideal blood glucose values could subsequently be achieved by diet alone. The abnormal afternoon fatigue and evening inertia which he had experienced for years disappeared, as well as gastric acid hypersecretion. Over-insulinization may be overlooked because the symptoms are often similar to those of hyperglycemic decompensation, namely excessive thirst, nycturia, polyuria, hunger, dizziness, fatigue and headaches [3]. Another important aspect of insulin therapy is to recognize that even small doses of less than 10 units/day may be sufficient but essential for metabolic control. The following case report illustrates this aspect.
1
urea (SU)
> 1ZOO/”
FBG
(mmol, I) (nmol,l)
metformin
SU or
diet metformin
physical
wellbeing
is also indicated and emotional
I>: insulin therapy
weight
to
if it improves
reduction
results compared C: if IBW > 120% reinforce
insulin alone.
reduction
reduction +
reduction + +
7.0 0.35
( > 60 Uday)
0.3
6.0
which must be
0.4
X.0
is
try to omit
insulin dose by 50% and/or if more stable control
su +
requirement
0.25
5.0
secretion
control,
SU treatment
for 2 weeks, to be continued
Weight
only if it reduces
try SU and insulin
B: in case of high insulin
C-Peptide
Weight
+insulin
> 7.8 mmol,
I
reduction
reduction If FBG
related
weight
weight
basal insulin
to the FBG:
a sufficient
+
Weight
reduction
for successful
of good metabolic
Prerequisite
insulin.
A: after 3 months
SU + Metformin
weight
Diet +
su +
Diet +
Diet +
Diet and insulin
insulin
insulin (in general
sulfonyldefinitely)
Diet +
>11
Diet +
I
Diet
6.5-7.4
> 8.5
7.9-l
A,, (HbAt,)
7.558.5
6.7-7.8
and hemoglobin _____
2 DIABETES
I lo-120%
(%) 16.5
(FBG)
OF TYPE
Diet
HbA,,
< 6.7
blood glucose
FBG (mmol/l)
Fasting
FOR THE TREATMENT
weight (IBW)
Ideal body
GUIDELINES
TABLE
Y.0 0.47
0.55
10.0
28 A patient aged 65 had suffered for 10 years from type 2 diabetes. Originally he was treated with
(1) So-called asymptomatic
hyperglycemia (fasting blood glucose concentrations exceeding 8 mmol/l) in elderly patients is often associated with reduced wellbeing and a trial of insulin
diet alone and later with antidiabetic drugs. Once the blood glucose concentration exceeded 11 mmol/l and fatigue developed, insulin therapy was started. With 8 units of insulin his blood sugar decreased, but because of afternoon hypoglycemia the dose had to be divided into two injections. Increasing the insulin dose to 10 and 12 units caused prolonged hypoglycemic episodes, and decreasing it to 6 and 4 units caused hyperglycemia. Because of this low insulin requirement, insulin was discontinued and 75 mg glibornuride was given. After a short time the fasting blood glucose increased to 15 mmol/l and thirst and polyuria developed. Four weeks after resumption of insulin therapy, with 8 units per day, blood glucose values were again normalized and wellbeing was reestablished.
(2)
therapy should be given. The need for this type of therapy has to be reevaluated from time to time. C-peptide values can help to distinguish /I-cell failure.
in
References M., Staffelbach,
Schweiz.
Med. Wochenschr.
stimmung diirftigkeit. Schwandt.
The main aspects of insulin therapy 2 diabetics are the following.
in elderly type
0..
Sonnenberg,
G.E.
et al.
(1979) Vor- und Nachteile der lnsulintherapie bei alteren mit Diabetikern Hyperglykimie. asymptomatischer Keller. U., Pasquel,
Conclusion
diet failure and
can be very small and (3) The insulin requirement even small doses may have to be split into two daily injections. regular blood glu(4) To detect over-insulinization cose measurements at different times are indispensable.
Straumann,
Table 1 summarizes the therapeutic strategy type 2 diabetes as practised in our clinic.
between
iiberhandlung
bei Diabetikern Schweiz. P. and
zur Beurteilung
Med. Wochenschr. Richter,
bei Diabetikern
Med. Wochenschr.
109, 1816-1820.
M. and Berger, W. (1987) C-Peptid-Beder lnsulinbe-
117. 187-192.
W. (1980) Chronische
Insulin-
im Erwachsenenalter.
Dtsch.
105. 892-894.
24
(1988)24-28
Elsevier
DRC SO108
Insulin therapy in the elderly type 2 diabetic patient W. Berger Departnwnt of’hternal
Key words: Type 2 diabetes;
Medicine.
Insulin therapy
One of the most difficult problems in the treatment of diabetes is the appropriate use of insulin in the elderly type 2 diabetic patient. The difficulties consist of defining the so-called secondary failure of oral antidiabetic drug therapy and in establishing the therapeutic goal. ‘Secondary failure’ of oral antidiabetic drug therapy is defined by the degree of hyperglycemia and the presence and severity of clinical symptoms. In symptomatic hyperglycemia, fasting blood glucose concentrations consistently above 11 mmol/l, polyuria, polydipsia and weight loss are unmistakable symptoms of a critical deficit of insulin secretion. There is general agreement as to the indication for insulin therapy in symptomatic hyperglycemia. In the asymptomatic hyperglycemia of the elderly, the indication for insulin therapy is less clear. At a glance, acceptance of even pronounced hyperglycemia in the older type 2 diabetic patients, as long as they remain asymptomatic, stands to reason. Rigorous blood glucose control is unlikely to significantly influence the course of micro- and macrovascular complications in this age group. Furthermore insulin therapy is difficult to administer to these patients. Address fiir Innere
for correspondence: Medizin,
Professor
Kantonsspital
W. Berger, Abteilung
Basel, 4031 Basel. Switzer-
land.
016%8227/88/$03.50
Kanfonsspital, Basrl, S~tir-_erkand
Q, 1988 Elsevier Science Publishers
In this presentation we will focus on asymptomatic hyperglycemia, i.e., with a fasting blood glucose concentration range between 8 and 12 mmol/l, which most often is not associated with the classical signs of decompensation but where more subtle signs of insulin deficiency, mostly of a psychosomatic nature, may occur. In overweight subjects the upper limit of the asymptomatic glucose range may be as high as 15 mmol/l. It is not widely recognized that more or less pronounced alterations of the psychic state precede the metabolic decompensation caused by insulin deficiency. These symptoms comprise a depressive mood, apathy, fatigue and inertia. The similarity of these symptoms caused by insulin deficiency to other symptoms of old age leads to a diagnostic dilemma which can only be overcome pragmatically by a trial with insulin therapy. This problem is illustrated in a study which we performed in our outpatient clinic [l]. We investigated 15 type 2 diabetics, all of whom had attended our outpatient clinic over a long period and showed fasting blood glucose values of over 9 mmol/l but otherwise felt free of complications. All patients were offered a trial insulin therapy with the option of returning to the original oral antidiabetic therapy. Insulin
B.V. (Biomedical
Division)
therapy
produced
a slight initial
reduc-
25 tion of the fasting blood glucose concentration from 14 to 11 mmol/l which subsequently reached 8 mmol/l. Concomitantly hemoglobin Ai, (HbA1,)
the dangers
fell from 10 to 8%. Despite the modest decrease in blood glucose concentration which occurred during the first 6 weeks the wellbeing of the patients improved markedly during this period. This improvement in wellbeing was most pronounced in six
patient and the nurse and often causes anxiety, and such therapy may be felt to be a heavy burden in the last years of life. The risk of hypoglycemia is a
patients in whom the depressive mood prevailing during oral antidiabetic drug treatment disappeared completely. This improvement in wellbeing was so pronounced that when the participants were asked if they would reconsider oral antidiabetic drug therapy after 2 months on insulin, only seven of the 15 patients considered oral antidiabetics an alternative to the trial insulin therapy, while at the end of the R-month study only two patients wanted to resume oral antidiabetic therapy. Obviously the participants valued the advantages of insulin therapy higher than the disadvantages brought about by the insulin injections. Interestingly, these elderly patients objected more to the dietary restrictions than to the injection of insulin.
hypoglycemia, often brought about by dietary mistakes. Analysis of the severe insulin hypoglycemic
The experience of a 76-year-old watchmaker exemplifies the favorable results of our study. He reported that shortly after commencement of insulin therapy, and in the absence of spectacular improvement of glycemia he could again produce the fine parts of the clockwork at his turning lathe. To exclude a placebo effect, oral antidiabetic therapy was resumed, resulting in an acceptable fasting blood glucose of 9-10 mmol/l in this moderately obese patient. On this therapy no dramatic changes in wellbeing occurred. Nevertheless, this patient asked me to prescribe insulin therapy again because he felt more productive with this type of therapy. Only 2 days after recommencement of insulin therapy he reported that he had enjoyed a musical performance on television the previous evening, an experience which never occurred during oral antidiabetic drug treatment. Apart from the obvious beneficial effects of insulin therapy in the elderly. one has to be aware of
and adverse
effects of insulin
in these patients. The initiation of insulin in elderly diabetics is time-consuming
therapy therapy for the
major drawback of insulin therapy. Elderly diabetic patients especially are at risk of developing severe
emergency admissions to the Cantonal Hospital in Base1 from 1981 to 1985 showed that 35% of the 173 emergency admissions were diabetics aged over 70. This age group represents only 15% of all insulin-treated patients. The potential risk of hypoglycemia during insulin therapy makes it necessary to periodically reconsider the dosage and even the indication for insulin therapy. The improvement of metabolic control by insulin therapy leads to a reduction of insulin resistance and an improvement of B-cell function so that exogenous insulin can be reduced or even omitted. A valuable index for assessing whether insulin therapy can be discontinued is the estimation of residual insulin secretion by C-peptide determinations. In a study of 45 type II diabetic patients we found a good correlation between fasting C-peptide values and the necessity of insulin therapy for the ensuing 3 years. We also found that C-peptide values have to be considered in the context of the concomitant blood glucose concentration. Oral antidiabetic treatment
was successful
with the following
blood
glucose (BG): C-peptide values: BG 7- 8 mmol/l: C-peptide 2 0.4 nmol/l; BG 8- 9 mmol/l: C-peptide 2 0.47 nmol/l; BG 9-10 mmol/l: C-peptide 2 0.55 nmol/l; BG 10-I I mmol/l: C-peptide 2 0.62 nmol/l; BG 1 l-12 mmol/l: C-peptide 2 0.7 nmol/l [2]. The transient need for insulin substitution is illustrated by the following case report. In a patient born in 1907 and suffering from diabetes since 1961, insulin therapy became necessary in 198 1 because fasting blood glucose values surpassed 11 mmolil. The simultaneous C-pep-
26 c
-PEPTIDE
PmOlII
1000
0
fasting
Q2l
after 1 mg Glucagon iv
800
600
400
200
0 28.1.81
22.10.81
27.582
13.9.83
Treatment
SH
SH
Insulin
Insulin
Fasting Bloodglucose
9.7
11.1
9.2
10.4
Fig.
1. Variability
of residual
insulin secretion
in a type 2 diabetic
mass index 26-28)
from
tide values were very low (0.3 nmol/l). However, during the years of insulin therapy the capacity to secrete insulin increased to such an extent that sulfonylurea therapy could be resumed (Fig. 1). While in the above case insulin therapy had no adverse side effects and could be regarded as an alternative to antidiabetic drug treatment, the following example shows that unrecognized over-insulinization can occur over the years under insulin therapy and produce stress-like symptoms which are attributed to recurrent but not recognized hypoglycemia: A dentist aged 70 was put on insulin (58 U lente insulin daily) 21 years ago when diabetes mellitus was detected by ketonuria and hyperglycemia. Over the last years, sporadically determined fasting blood glucose values were in the range of 312 mmol/l. The patient visited the clinic complaining of recurrent afternoon weakness. Blood glucose determinations at this time revealed a tendency for hypoglycemic episodes between 3
15.2.84 Insulin
27.11.84
3.9.85
17.4.66
Insulin
SH
SH
6.9
6.2
$8
7.0
subject (male, born in 1907. onset of diabetes
mellitus in 1961, body
1981 to 1986. SH: sulfonylurea.
and 6 p.m. Furthermore he reported that for years he had suffered from burning epigastric pain readily relieved by antacids. The fasting Cpeptide concentration was more than 1.0 nmol/l (blood glucose 10 mmol/l). Since this was indicative of sufficient insulin secretion, insulin was discontinued and almost ideal blood glucose values could subsequently be achieved by diet alone. The abnormal afternoon fatigue and evening inertia which he had experienced for years disappeared, as well as gastric acid hypersecretion. Over-insulinization may be overlooked because the symptoms are often similar to those of hyperglycemic decompensation, namely excessive thirst, nycturia, polyuria, hunger, dizziness, fatigue and headaches [3]. Another important aspect of insulin therapy is to recognize that even small doses of less than 10 units/day may be sufficient but essential for metabolic control. The following case report illustrates this aspect.
1
urea (SU)
> 1ZOO/”
FBG
(mmol, I) (nmol,l)
metformin
SU or
diet metformin
physical
wellbeing
is also indicated and emotional
I>: insulin therapy
weight
to
if it improves
reduction
results compared C: if IBW > 120% reinforce
insulin alone.
reduction
reduction +
reduction + +
7.0 0.35
( > 60 Uday)
0.3
6.0
which must be
0.4
X.0
is
try to omit
insulin dose by 50% and/or if more stable control
su +
requirement
0.25
5.0
secretion
control,
SU treatment
for 2 weeks, to be continued
Weight
only if it reduces
try SU and insulin
B: in case of high insulin
C-Peptide
Weight
+insulin
> 7.8 mmol,
I
reduction
reduction If FBG
related
weight
weight
basal insulin
to the FBG:
a sufficient
+
Weight
reduction
for successful
of good metabolic
Prerequisite
insulin.
A: after 3 months
SU + Metformin
weight
Diet +
su +
Diet +
Diet +
Diet and insulin
insulin
insulin (in general
sulfonyldefinitely)
Diet +
>11
Diet +
I
Diet
6.5-7.4
> 8.5
7.9-l
A,, (HbAt,)
7.558.5
6.7-7.8
and hemoglobin _____
2 DIABETES
I lo-120%
(%) 16.5
(FBG)
OF TYPE
Diet
HbA,,
< 6.7
blood glucose
FBG (mmol/l)
Fasting
FOR THE TREATMENT
weight (IBW)
Ideal body
GUIDELINES
TABLE
Y.0 0.47
0.55
10.0
28 A patient aged 65 had suffered for 10 years from type 2 diabetes. Originally he was treated with
(1) So-called asymptomatic
hyperglycemia (fasting blood glucose concentrations exceeding 8 mmol/l) in elderly patients is often associated with reduced wellbeing and a trial of insulin
diet alone and later with antidiabetic drugs. Once the blood glucose concentration exceeded 11 mmol/l and fatigue developed, insulin therapy was started. With 8 units of insulin his blood sugar decreased, but because of afternoon hypoglycemia the dose had to be divided into two injections. Increasing the insulin dose to 10 and 12 units caused prolonged hypoglycemic episodes, and decreasing it to 6 and 4 units caused hyperglycemia. Because of this low insulin requirement, insulin was discontinued and 75 mg glibornuride was given. After a short time the fasting blood glucose increased to 15 mmol/l and thirst and polyuria developed. Four weeks after resumption of insulin therapy, with 8 units per day, blood glucose values were again normalized and wellbeing was reestablished.
(2)
therapy should be given. The need for this type of therapy has to be reevaluated from time to time. C-peptide values can help to distinguish /I-cell failure.
in
References M., Staffelbach,
Schweiz.
Med. Wochenschr.
stimmung diirftigkeit. Schwandt.
The main aspects of insulin therapy 2 diabetics are the following.
in elderly type
0..
Sonnenberg,
G.E.
et al.
(1979) Vor- und Nachteile der lnsulintherapie bei alteren mit Diabetikern Hyperglykimie. asymptomatischer Keller. U., Pasquel,
Conclusion
diet failure and
can be very small and (3) The insulin requirement even small doses may have to be split into two daily injections. regular blood glu(4) To detect over-insulinization cose measurements at different times are indispensable.
Straumann,
Table 1 summarizes the therapeutic strategy type 2 diabetes as practised in our clinic.
between
iiberhandlung
bei Diabetikern Schweiz. P. and
zur Beurteilung
Med. Wochenschr. Richter,
bei Diabetikern
Med. Wochenschr.
109, 1816-1820.
M. and Berger, W. (1987) C-Peptid-Beder lnsulinbe-
117. 187-192.
W. (1980) Chronische
Insulin-
im Erwachsenenalter.
Dtsch.
105. 892-894.