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Endocrine disorders and diabetes in Japan
ELSEVIER
Diabetes Research and Clinical Practice, 24 Suppl. (1994) S129-S133
Endocrine disorders and diabetes in Japan Yutaka Seine*, I-k00 Imura Depattment of Metabolism and Clinical Nutrition, Kyoto Uniwrsity Faculty of Medicine, 54 Syogoin Kawahnra-cho, Sakyo-ku, Kyoto, 606-01 Japan
Abstract The frequency of glucose intolerance including diabetes and IGT in endocrine diseases was compared between Japan and foreign countries. It was revealed that the frequency of diabetes in endocrine diseases is generally higher in Japan than in foreign countries. In addition, plasma irdin response to glucose was exaggerated in Cushing’s syndrome with glucose into!;rance, but was impaired in acromegaly and pk.eochromocytoma with glucose intolerance. Keywords: Diabetes mellitus; Endocrine diseases; Acromegaly; Cushing’s syndrome; Pheochromocytoma; nism; Insulinogenic index
1. Intro&xtion It is generally accepted that diabetes is a metabolic disorder resulting from either an absolute or a relative deficiency in insulin action. Diabetes which develops in subjects with an hereditary predisposition and without other known causes is regarded as primary diabetes. On the other hand, a state of deficient insulin action caused by known basic diseases or by postnatal diseases is designated secondary diabetes. Since there is no established means for assessing hereditary predisposition, it is usually difficult to distinguish between primary diabetes and secondary diabetes precipitated by certain diseases, and it is possible that many patients with secondary diabetes might have hereditary predisposition to diabetes mellitus as well. Endocrine disorders such as acromegaly, Cushing’s syndrome, primary hyperaldosteronism and pheochromocytoma xe
*Corresponding 771 6601.
author, Tel.: 81 75 751 3562; Fax: 81 75
Primary hyperaldostero-
known to accompany diabetes. We describe here the prevalence of diabetes and insulin secretion in endocrine diseases in Japan.
2. Frequency of diabetes
Foreign data is cited from: Kozak, G.P., and Cooppan, R. (1985). In: A. Marble et al. (Eds.), Joslin’s diabetes (12th ed.). Lea and Febiger, Philadelphia, pp. 784. Japanese data is cited from: Tomita, A. (1985) Report of Ministry of Health & Welfare. In: Jpn. Diabetes Sot. (Ed.), Tonyobyogaku no Shinpo. Shindan to Chiryo Co, Tokyo, pp. 103; and Yoshida, S. (1992), Report of Ministry of Health & Welfare. In: Jpn. Diabetes Sot. (Ed.), Tonyobyogaku no Shinpo. Shindan to Chiryo Co, Tokyo, pp. 119. Acromegdy (Table I). As shown in Table 1, a high frequency of glucose intolerance in acromegaly is observed. The frequency of dia-
0X8-8227/94/$07.00 0 1994 Elsevier Science Ireland Ltd. All r&Ms reserved SSDI 0168-8227(94)00906-B
S130
2! Seh
H. hum
/Disks
Rev. Ch.n. Rack 24 Suppl @X’4) Sl29-SI33
Tabk i-
Frequency of diabetes mellitus in aCrOmegaly
Foreign cou&ries
Japan
Author
No.
Frequency of diabetes (%/a)
Frequency of impaired glucox tolerance (%j
Dividoff&cushing CoggeshaUand Root Gordon et al. Ballintine et al. Emmer, Gordon and Roth Ministry of Health and Welfare
loo 153 100 44 50 770
12 17 18 14 (20) 46
20 45 60’
-
67’ Tomita Yoshida
28 15
61 33
21 33
-
aIncludes diabetes and IGT. Table 2 Frequency of diabetes mellitus in Chshing’s syndrome
Foreigncountries
Japan
Author
No.
Frequency of diabetes (%I
Frequency of impaired glucuse tolerance (%‘a)
Lukenset al. Plot2 et al. Cope and Raker Spragueet al. Skillernand McCullagh Soffer et al. Minis* of Health and Welfare Tomita Yoshida
55 33 35 67 34 50 425 60 21
35 15 11 33 21 20
27 31 29 57 21 42 68a
62 48
32 19
Frequency of diabetes (o/o)
Frequency of impaired glucose tolerance (or01
‘Includes diabetes and IGT. Table 3 Frequency of diabetes mellitus in primary aldosteronism
Foreip countries
Japan
Author
No.
Corm et al. Ministry of Health and Welfare Tomita
39 319 30
54a 11 13
26 30
Frequencyof diabetes (%I
Frequencyof impaired glucose tolerance (%I
‘Includes diabetes and IGT Table 4 Frequency of diabetes mellitus in pheochromocytoma
Foreigncountries
Jam
Author
No.
Giffordet al. MinistryofHeaband Welfare Tomita
76 409 20
aIncludesdiabetes and IGT.
67’ 38 55
51 20
I! Seine, H. Inwra .I Diabetes Res. Clin. hct.
betcs in acromegaly in Japan is much higher than that in foreign countries. Gushing’s syndrome {iable 2). The frequency of diabetes in Cushing’s syndrome in Japan also is higher than in foreign countries. primary hyperaldosteronism (Table 3). The frequency of glucose intolerance in primary hyperaldosteronism reported by Conn et al. was 54%. In Japan, the frequency of diabetes in primary hyperaldosteronism is 10 to 15%. Pheochromocytoma (Table 4). A high frequency of glucose intolerance is noted in pheochrotlocytoma in both foreign countries and Japan. The frequency of diabetes in pheochromocytoma is very high in Japan. We conclude that the frequency of diabetes in endocrine diseases is generally higher in Japan than in foreign countries. 3. Insulin secretion in em&tine
s131
50 g glucose loadiig in acromega!y, Gushing’s syndrome, and pheochromocytoma with diabetes mellitus [1,2]. Acromegaly. M patients examined in the present study had elevated plasma growth hormone levels of more than 20 ng/ml. In patients with severe diabetes whose fasting plasma glucose levels exceeded 10 mM/l, plasma insulin response to oral glucose loading was markedly diminished (Fig. 1). On the other hand, in acromegalic patients with mild glucose intolerance whose fasting plasma glucose levels were beiow 8.8 mM/l, the plasma insulin rose gradually following oral glucose loading, reaching the mean peak level at 60 min (F-8. 1). C&zing’s syndrome. Fig. 2 illustrates plasma glucose and plasma IRI levels after oral glucose loading in patients with Cushg’s syndrome. An was exaggerated plasma insulin response observed, with the mean peak !evel occurring 90 min after glucose loading. Pheochromocytomu. Seven patients with proven pheochromocytoma exhibited either low or de-
diseases with
diabetes mellitus
We have mezured
24 Suppl. (19941 S?29-SI33
plasma insulin response to
lnsulinogenic
22.2
(30’)
Index
&
MILD DIABETICTYPE
-=+=-
SEVERE
DIAEETIC
: lYPE:
0.54 0 . 1 6
16.7
plasma
t
600
glucose
I
plasma
insulin
11.1
300 5.5
PM
mM 0
:
I
I
3o
I
I
I
6o
90
120
1
180
0
I
0
I
30
,
60
I
I
90
120
Time 50g
of
1
186
in
minutes
glucose
Fig. 1. Plasma glucose and insulin levels following oral glucose administration in patients with acromegaly. Mean + S.E. are shown.
Y. S&w, H. Imum
S132
/Diabetes
Rar.
Clin.
Ract.
24 SuppL
(1994)
SAW-S133
lnsulinogenic
16.7
index
(30')
1.37
11.1 900
600 5.5
plasma
glucose 300
mM
PM
0
0
~
--------1
30
0
60 7-
90 I
lb
-
30
6Q
90
of
160
120
Time
A s&J
d
1
0
1 iQ
in
minutes
glucose
Fig. 2. Plasma glucose and insulin levels following oral glucose administration in patients with Cushing’s syndrome. Mean f SE. are shown.
lnsulinogenic
Index
(30’)
0.18
16 .I 600
1.1 .l
300 5 .5
plama
glucose
mM 0
PM I
1
I
90
120
180
0
d
30.
60
90’
120
lime
SOg of
180
in
minutes
glucose
Fig. 3. Plasma glucose and insulin levels following oral glucose administration in patients with pheochromocytoma. are shown.
Mean
+ S.E.
s133
Fig. 4. The insuhogenic bdices at 30 min of oral glucose loading in normal subjec@, patients with diabetes mellitus, and patients with endocrine disorders with diabetes.
layed plasma insulin
ponse to oral
Fig. 4 shows the insulin
impaired initial insulin
indices in patients with primary diabetes, hyperthyroidism and liver diseases and concluded that the insulinogenic index 30 min was definitely low in primary diabetes. have also studied the amine diseases with values as meaload were 1.43
were 0.18 + 0.12 in
Y. and Laura, (197% The Seino, Y., Ike&i, F& w-----rr 1 onQLc,, I, or. Metab. insulinogenic index in secondary diabetes. Res. 7,107-115. Seine, Y., Kurahachi, H., Goto, Y., Taminato, T., ikeda, M. and hura, H. (1975) Comparative insutiogenic effect5 of glucose arginine and ghcagon in patients with diabetes mellh endocrine disorders and liver disease. Acta. Diabetol. Lat. l&89-99. tier, H.S., Allen, E.W., HexTon, A.L.Fr. and Brennan, .T. (1967) Insulin secretion in response to g@e m&us: relation of delayed initial release to carbo -. 3. Clin. Invest. 46,
secretory responses in patients with glucose intoIerance due to extra-pancreatic causes. Comparison with idiopathic diabetes mellitus. Endocrind. .Tpn. 28, ~7-49$.
Diabetes Research and Clinical Practice, 24 Suppl. (1994) S129-S133
Endocrine disorders and diabetes in Japan Yutaka Seine*, I-k00 Imura Depattment of Metabolism and Clinical Nutrition, Kyoto Uniwrsity Faculty of Medicine, 54 Syogoin Kawahnra-cho, Sakyo-ku, Kyoto, 606-01 Japan
Abstract The frequency of glucose intolerance including diabetes and IGT in endocrine diseases was compared between Japan and foreign countries. It was revealed that the frequency of diabetes in endocrine diseases is generally higher in Japan than in foreign countries. In addition, plasma irdin response to glucose was exaggerated in Cushing’s syndrome with glucose into!;rance, but was impaired in acromegaly and pk.eochromocytoma with glucose intolerance. Keywords: Diabetes mellitus; Endocrine diseases; Acromegaly; Cushing’s syndrome; Pheochromocytoma; nism; Insulinogenic index
1. Intro&xtion It is generally accepted that diabetes is a metabolic disorder resulting from either an absolute or a relative deficiency in insulin action. Diabetes which develops in subjects with an hereditary predisposition and without other known causes is regarded as primary diabetes. On the other hand, a state of deficient insulin action caused by known basic diseases or by postnatal diseases is designated secondary diabetes. Since there is no established means for assessing hereditary predisposition, it is usually difficult to distinguish between primary diabetes and secondary diabetes precipitated by certain diseases, and it is possible that many patients with secondary diabetes might have hereditary predisposition to diabetes mellitus as well. Endocrine disorders such as acromegaly, Cushing’s syndrome, primary hyperaldosteronism and pheochromocytoma xe
*Corresponding 771 6601.
author, Tel.: 81 75 751 3562; Fax: 81 75
Primary hyperaldostero-
known to accompany diabetes. We describe here the prevalence of diabetes and insulin secretion in endocrine diseases in Japan.
2. Frequency of diabetes
Foreign data is cited from: Kozak, G.P., and Cooppan, R. (1985). In: A. Marble et al. (Eds.), Joslin’s diabetes (12th ed.). Lea and Febiger, Philadelphia, pp. 784. Japanese data is cited from: Tomita, A. (1985) Report of Ministry of Health & Welfare. In: Jpn. Diabetes Sot. (Ed.), Tonyobyogaku no Shinpo. Shindan to Chiryo Co, Tokyo, pp. 103; and Yoshida, S. (1992), Report of Ministry of Health & Welfare. In: Jpn. Diabetes Sot. (Ed.), Tonyobyogaku no Shinpo. Shindan to Chiryo Co, Tokyo, pp. 119. Acromegdy (Table I). As shown in Table 1, a high frequency of glucose intolerance in acromegaly is observed. The frequency of dia-
0X8-8227/94/$07.00 0 1994 Elsevier Science Ireland Ltd. All r&Ms reserved SSDI 0168-8227(94)00906-B
S130
2! Seh
H. hum
/Disks
Rev. Ch.n. Rack 24 Suppl @X’4) Sl29-SI33
Tabk i-
Frequency of diabetes mellitus in aCrOmegaly
Foreign cou&ries
Japan
Author
No.
Frequency of diabetes (%/a)
Frequency of impaired glucox tolerance (%j
Dividoff&cushing CoggeshaUand Root Gordon et al. Ballintine et al. Emmer, Gordon and Roth Ministry of Health and Welfare
loo 153 100 44 50 770
12 17 18 14 (20) 46
20 45 60’
-
67’ Tomita Yoshida
28 15
61 33
21 33
-
aIncludes diabetes and IGT. Table 2 Frequency of diabetes mellitus in Chshing’s syndrome
Foreigncountries
Japan
Author
No.
Frequency of diabetes (%I
Frequency of impaired glucuse tolerance (%‘a)
Lukenset al. Plot2 et al. Cope and Raker Spragueet al. Skillernand McCullagh Soffer et al. Minis* of Health and Welfare Tomita Yoshida
55 33 35 67 34 50 425 60 21
35 15 11 33 21 20
27 31 29 57 21 42 68a
62 48
32 19
Frequency of diabetes (o/o)
Frequency of impaired glucose tolerance (or01
‘Includes diabetes and IGT. Table 3 Frequency of diabetes mellitus in primary aldosteronism
Foreip countries
Japan
Author
No.
Corm et al. Ministry of Health and Welfare Tomita
39 319 30
54a 11 13
26 30
Frequencyof diabetes (%I
Frequencyof impaired glucose tolerance (%I
‘Includes diabetes and IGT Table 4 Frequency of diabetes mellitus in pheochromocytoma
Foreigncountries
Jam
Author
No.
Giffordet al. MinistryofHeaband Welfare Tomita
76 409 20
aIncludesdiabetes and IGT.
67’ 38 55
51 20
I! Seine, H. Inwra .I Diabetes Res. Clin. hct.
betcs in acromegaly in Japan is much higher than that in foreign countries. Gushing’s syndrome {iable 2). The frequency of diabetes in Cushing’s syndrome in Japan also is higher than in foreign countries. primary hyperaldosteronism (Table 3). The frequency of glucose intolerance in primary hyperaldosteronism reported by Conn et al. was 54%. In Japan, the frequency of diabetes in primary hyperaldosteronism is 10 to 15%. Pheochromocytoma (Table 4). A high frequency of glucose intolerance is noted in pheochrotlocytoma in both foreign countries and Japan. The frequency of diabetes in pheochromocytoma is very high in Japan. We conclude that the frequency of diabetes in endocrine diseases is generally higher in Japan than in foreign countries. 3. Insulin secretion in em&tine
s131
50 g glucose loadiig in acromega!y, Gushing’s syndrome, and pheochromocytoma with diabetes mellitus [1,2]. Acromegaly. M patients examined in the present study had elevated plasma growth hormone levels of more than 20 ng/ml. In patients with severe diabetes whose fasting plasma glucose levels exceeded 10 mM/l, plasma insulin response to oral glucose loading was markedly diminished (Fig. 1). On the other hand, in acromegalic patients with mild glucose intolerance whose fasting plasma glucose levels were beiow 8.8 mM/l, the plasma insulin rose gradually following oral glucose loading, reaching the mean peak level at 60 min (F-8. 1). C&zing’s syndrome. Fig. 2 illustrates plasma glucose and plasma IRI levels after oral glucose loading in patients with Cushg’s syndrome. An was exaggerated plasma insulin response observed, with the mean peak !evel occurring 90 min after glucose loading. Pheochromocytomu. Seven patients with proven pheochromocytoma exhibited either low or de-
diseases with
diabetes mellitus
We have mezured
24 Suppl. (19941 S?29-SI33
plasma insulin response to
lnsulinogenic
22.2
(30’)
Index
&
MILD DIABETICTYPE
-=+=-
SEVERE
DIAEETIC
: lYPE:
0.54 0 . 1 6
16.7
plasma
t
600
glucose
I
plasma
insulin
11.1
300 5.5
PM
mM 0
:
I
I
3o
I
I
I
6o
90
120
1
180
0
I
0
I
30
,
60
I
I
90
120
Time 50g
of
1
186
in
minutes
glucose
Fig. 1. Plasma glucose and insulin levels following oral glucose administration in patients with acromegaly. Mean + S.E. are shown.
Y. S&w, H. Imum
S132
/Diabetes
Rar.
Clin.
Ract.
24 SuppL
(1994)
SAW-S133
lnsulinogenic
16.7
index
(30')
1.37
11.1 900
600 5.5
plasma
glucose 300
mM
PM
0
0
~
--------1
30
0
60 7-
90 I
lb
-
30
6Q
90
of
160
120
Time
A s&J
d
1
0
1 iQ
in
minutes
glucose
Fig. 2. Plasma glucose and insulin levels following oral glucose administration in patients with Cushing’s syndrome. Mean f SE. are shown.
lnsulinogenic
Index
(30’)
0.18
16 .I 600
1.1 .l
300 5 .5
plama
glucose
mM 0
PM I
1
I
90
120
180
0
d
30.
60
90’
120
lime
SOg of
180
in
minutes
glucose
Fig. 3. Plasma glucose and insulin levels following oral glucose administration in patients with pheochromocytoma. are shown.
Mean
+ S.E.
s133
Fig. 4. The insuhogenic bdices at 30 min of oral glucose loading in normal subjec@, patients with diabetes mellitus, and patients with endocrine disorders with diabetes.
layed plasma insulin
ponse to oral
Fig. 4 shows the insulin
impaired initial insulin
indices in patients with primary diabetes, hyperthyroidism and liver diseases and concluded that the insulinogenic index 30 min was definitely low in primary diabetes. have also studied the amine diseases with values as meaload were 1.43
were 0.18 + 0.12 in
Y. and Laura, (197% The Seino, Y., Ike&i, F& w-----rr 1 onQLc,, I, or. Metab. insulinogenic index in secondary diabetes. Res. 7,107-115. Seine, Y., Kurahachi, H., Goto, Y., Taminato, T., ikeda, M. and hura, H. (1975) Comparative insutiogenic effect5 of glucose arginine and ghcagon in patients with diabetes mellh endocrine disorders and liver disease. Acta. Diabetol. Lat. l&89-99. tier, H.S., Allen, E.W., HexTon, A.L.Fr. and Brennan, .T. (1967) Insulin secretion in response to g@e m&us: relation of delayed initial release to carbo -. 3. Clin. Invest. 46,
secretory responses in patients with glucose intoIerance due to extra-pancreatic causes. Comparison with idiopathic diabetes mellitus. Endocrind. .Tpn. 28, ~7-49$.