Clinical Science (1971) 41, 453-458.
SEASONAL INFLUENCE ON INSULIN SECRETION
INMAN
M. FAHLEN, A. ODEN, P. BJORNTORP AND G. TIBBLIN
First Medical Service, Sahlgren's Hospital, and
Department of Mathematics, University of Gothenburg, Gothenburg
(Received 4 May 1971)
SUMMARY
I. The seasonal variation of fasting blood glucose, peroral glucose tolerance, fasting
plasma insulin and triglycerides and the sum of insulin values during glucose tolerance
test was studied in 100 patients who had suffered a myocardial infarction. These
patients comprised a population of all men who had suffered a myocardial infarction
below the age of 55 years and had survived.
2. The material was divided into four numerically equal groups covering two dark,
cold periods and two warm, light periods of the year.
3. Lower fasting blood glucose and insulin values during glucose tolerance test as
well as a trend to higher glucose tolerance were found during the warm, light part of
the year in comparison with winter. Triglycerides and fasting insulin values did not
vary significantly in these infarction patients. The variation could not be explained
by a difference in age or body weight between the groups.
4. It is suggested that glucose tolerance and insulin secretion are subjected to
seasonal variation in man as has previously been shown in laboratory animals.
In metabolic studies of disease it is necessary to be aware of possible seasonal variations.
Seasonal changes must be taken into account in establishing normal values as well as in
considering the effects of therapy. This has been stressed by several workers as far as plasma
lipids are concerned (Thorp, 1963; Paloheimo, 1961; Carlson & Lindstedt, 1969; Fyfe,
Dunnigan, Hamilton & Rae, 1968). Studies in the experimental animal have shown lower
insulin resistance during summer (Culhane, 1928; Young, 1965; Arvill & Ahren, 1967). The
incidence of diabetes in man during summer has been reported to be lower than in winter
(Adams, 1926; Danowski, 1957; Gamble & Taylor, 1969), but a seasonal variation of plasma
insulin concentration in man has apparently not been reported. This study will demonstrate
such a variation in patients who have suffered a myocardial infarction.
Correspondence: Dr P. Bjorntorp, First Medical Service, Sahlgren's Hospital, University of Gothenburg,
Gothenburg, Sweden.
453
454
M. Fahlen et al.
MATERIALS AND METHODS
The study was performed retrospectively on results of plasma insulin concentration obtained
from 107 men with myocardial infarction during the period 1 January 1968 to 31 May 1969
(Berchtold, Bjorntorp, Gustafson, Lindholm, Tibblin & Wilhelmsen, 1971). These patients
comprised all men below the age of 55 years who had suffered a myocardial infarction in the
city of Gothenburg, Sweden, and had survived. After discharge from hospital the patients
obtained similar instructions from a special myocardial infarction clinic. Moderate physical
activity was prescribed in the form of short walks and patients were recommended to avoid bed
rest. Obvious dietary abnormalities were corrected with a recommendation to adhere to a
Swedish normal diet (Blix, Wretlind, Bergstrom & Westin, 1965). Treatment of hypertension,
heart failure and hyperlipaemia foIlowed ordinary routine.
Measurements were made 3 months after myocardial infarction. The patients were instructed
to fast and to avoid smoking for 12 h before the investigation. A peroral glucose tolerance test
was performed with 100 g of glucose. Blood glucose (Levin & Linde, 1962) and plasma insulin
(Hales & Randle, 1963) were determined before and 30, 60, 90 and 120 min after the ingestion
of glucose. Fasting values of triglycerides (Carlson, 1959) were also measured. Sum of insulin
and sum of glucose were calculated as the sum of values obtained at 0, 30, 60, 90 and 120 min.
Seven of the patients had overt diabetes and were therefore excluded from the study. The
remaining 100 were investigated for seasonal influence and aIlocated to four numericaIly equal
groups (I-IV) covering the year.
RESULTS
Mean age and weight for each group are shown in Table 1. Groups I and IV cover the darker,
colder time of the year and groups II and III the warmer lighter part (Table 1). Comparisons
between the groups were therefore only made between these two types of groups: I versus II,
I versus III, II versus IV, III versus IV.
Sum of insulin showed a positively skewed distribution. The other variables were apparently
normaIly distributed and so were the logarithmic values of sum of insulin. Mean values
± SEM of fasting glucose, sum of glucose, fasting insulin, log sum of insulin and fasting
triglycerides are shown in Table 1.
The comparisons between groups I-IV were made by using Student's t test. The probability
of obtaining one or more false significances in a series of statistical tests will be referred to as
the simultaneous significance level. At four comparisons between groups I-IV at a simultaneous
significance level P, significance was assumed if any single comparison gave significance by the
t test at the level P/4 (MiIler, 1966). In the present investigation P was chosen equal to 0'05 and
0·01.
By this method fasting glucose and log (sum of insulin) were the only variables that showed
significant seasonal changes (Table 2). Like log (sum of insulin) and fasting glucose, sum of
glucose showed the lowest values in groups II and III (Fig. 1). The values offasting insulin and
triglycerides did not apparently foIlow this pattern.
DISCUSSION
In the statistical approach to the question of seasonal variation of metabolic results it is a
455
Seasonal influence on insulin
TABLE 1. Data on four equal groups of patients with myocardial infarction studied during different
periods of the year; means±SEM
Group I
Group II
Group IV
Group III
No. of patients
25
25
25
25
Time period
1 Jan.-15 April 16 April-ll June 12 June-8 Aug. 9 Aug.-31 Dec.
Age (Years)
51·H1·31
50·H1·02
49'9±0'9O
50'2±0'9O
Body weight (kg)
80·2±2·29
76'9±2'07
77·2±1·92
78'8±2-34
Fasting blood glucose
75-6±l-70
77-:l±3'28
70'4±2'19
64'6±2'02
(mg/100 ml)
548·7± 24·30
46N±24·11
Sum of blood glucose during 571'0±35'33
490·4± 25-82
glucose tolerance test
(mg/100 ml)
14'H2'17
14'7±2'21
Fasting plasma insulin
ll'H 1'25
10'3± 1'21
(pV/ml)
Log (sum of plasma insulin) 2·5434±0·0415 2-4521 ± 0'0366 2·5208±0·0942 2·6582± 0'0459
(455'2)
(283'2)
(331'7)
during glucose tolerance test
(349'5)
(numerical values) (PV/rnI)
150,3± 11-42
159'2± 12-49
Fasting plasma triglycerides
155'0±1l'06
151'4± 11-39
(mg/IOO ml)
E
0
0
:::::
Cl
E
Boe________
---------------------'.------------.---.--------.
-----
700
C>
t-
~
E
<,
500
:::>
::l...
l--I
~
300
0
0
C>
Vool
G__________
TG_
<,
'"
E
100
_
.
J
BI.
I
..
II
E
0
_
....
III
Q
<,
Cl
E
50 -;;
1Il
30
...
.3-
..
IV
a4
S
0
E
<,
:::>
I
::====--==-'
.. .
70 :::
N
1Il
10
D
FIG. 1. Metabolic variables in patients with myocardial infarction studied during different periods
of the year. BG, Fasting blood glucose; 1:G, sum of blood glucose values during glucose tolerance
test; 1:1, sum of plasma insulin values during glucose tolerance test; TG, fasting plasma triglycerides; BI, fasting plasma insulin.
I
IV
I
IV
I
IV
I
IV
I
IV
I
IV
I
IV
Age
Weight
Fasting blood glucose
Sum of blood glucose during
glucose tolerance test
Fasting plasma insulin
Log (sum of plasma insulin)
during glucose tolerance test
Fasting plasma triglycerides
P<O·9
P<O·8
P<O·9
P<O'2
P<O'l
P<O·9
P<O·02
P<O·025
P<O·OO5
P<O'OOI
P<O·4
P<O·3
P<O·98
P<O·7
III
n.s., non significant;
P<O·95
P<O·7
P<O·2
P<O·OOI
P<O·7
P<O·3
P<O·l
P<O·2
P<O·l
P<O·I
P<O·6
P<O·6
P<O·2
P<O·2
II
P-values of ordinary
r-test
*, significant.
n.s.
n.s.
n.s.
*
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
P<O·05
n.s.
n.s.
n.s.
*
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
P<O·Ol
Significance at simultaneous
significance level
(comparisons I versus II and
IV versus II)
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s,
n.s.
n.s.
*
*
*
*
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
P<O·OI
n.s.
n.s.
n.s.
n.s.
P<O'05
Significance at simultaneous
significance level
(comparisons I versus III and
IV versus III)
TABLE 2. Statistical analysis of differences in four groups of myocardial infarction patients studied during different periods of the year
(cf. Table I)
Vl
~
:-
$::l
~
.....
~'
-
~
~
~
0\
Seasonal influence on insulin
457
problem to know how to divide the material into suitable groups. If the material is divided
into too many groups the number of observations per group might be too small and there
is also a great risk that the difference of the means of two groups might be significant by
chance. On the other hand, if the material is divided into too few groups the degree or even
the presence of seasonal variation might be overlooked. This will for example be the
case if the seasons corresponding to the different groups cover similar parts of a cyclic
variation. In the present work the number of groups was necessarily restricted by the limited
number of observations and it was appropriate to use equal numbers of individuals in each
group.
The possibility of seasonal variation could be tested statistically by analysis of variance,
although with relatively few comparisons the use of simultaneous level of significance is
preferable (Miller, 1966).
Results from animal studies (Culhane, 1928; Young, 1965; Arvill & Ahren, 1967) and
information about the incidence of diabetes in man (Adams, 1926; Danowski, 1957; Gamble &
Taylor, 1969) suggests lower glucose values and lower insulin secretion during summer
months. This information made it reasonable to focus interest on the warmer and lighter
periods of the year compared with the colder and accordingly only comparisons examining
this possibility were made.
The finding of low fasting blood glucose values and high glucose tolerance with a low
insulin secretion during summer months cannot be explained by variations in body weight and
age. These observations are in good agreement with previous studies in the rabbit (Botschkareff
& Grigorieff, 1929; Culhane, 1928). In the lizard a decreased glucose tolerance was found
during autumn and winter concomitant with an increased capacity to store glycogen. It was
suggested that these findings indicated a decreased rate of carbohydrate utilization (di Maggio,
1963). Studies in vitroon insulin resistance have shown lower resistance in the rat heart (young,
1965) and in the levator ani of the rat (Arvill & Ahren, 1967) during summer months compared
with the rest of the year.
The seasonal control of insulin sensitivity in rat heart could be reproduced in the laboratory
by artificial light (Young, 1965). Hypothalamic-pituitary control was therefore suggested.
This fits well with the observation of lower adrenal activity in man during summer compared
with the rest of the year (Watanabe, 1964). As pituitary and adrenal hormones are known to
decrease pyruvate oxidation (Weil, Altszuler & Kessler, 1961; Fajans, 1961) this mechanism
of decreasing carbohydrate oxidation might be of importance in seasonal control of glucose
metabolism. Seasonal variations in infections such as with Coxsackie B virus (Taylor &
Gamble, 1970) and in physical activity (Bjorntorp, de Jounge, Sjostrom & Sullivan, 1970)
might also playa role.
Previous prospective population studies on healthy subjects have demonstrated lower
triglyceride values during summer months (Carlson & Lindstedt, 1969; Fyfe et al., 1968).
Such a variation cannot apparently be found in patients who have suffered a myocardial
infarction and are slightly hyperlipaemic as in the present study.
It should be observed that the design of the present investigation does not exclude the
possibility that subjects with high insulin secretion during winter are those who suffer a
myocardial infarction at that time and vice versa. This does not necessarily mean that the
general population has a seasonal variation of insulin and glucose like that described in the
present paper.
458
M. Fahlen et al.
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