Review

Vol.4 No.1 Article

Shyang-Rong Shih

et al

Taiwan Geriatrics & Gerontology

The Effects of Aging on Glucose Metabolism

Shyang-Rong Shih1, Chin-Hsiao Tseng1,2,3,4
Abstract
Type 2 diabetes mellitus is the most common chronic metabolic disease/disorder in
the elderly. The prevalence and incidence of impaired glucose tolerance and diabetes
mellitus increase with aging. In Taiwan, the prevalence of diabetes mellitus increases
with age and is approximately 20% in those aged 65 years or older. The incidence of
diabetes mellitus is also increasing in Taiwan. In an epidemiologic study which showed
an average incidence of 9.3 per 100,000 population in those aged <35 and 725.8 per
100,000 population in those aged 65 years. Responsible mechanisms of age-related
glucose intolerance include decreased insulin sensitivity and decreased -cell function.
Decreased -cell function may be related to glucotoxicity and mitochondrial dysfunction.
Insulin resistance is related to mitochondrial dysfunction and increased intramyocytic
triglyceride. Decreased number of insulin receptors, decreased AMP-activated protein
kinase (AMPK) activity, decreased adiponectin and increased leptin are other postulated
factors. Further studies are necessary to examine these hypotheses, to find out the key
afflicting factors, and to work up as the target.
(Taiwan Geriatrics & Gerontology 2009; 4(1): 27-38)
Key words: aging, glucose intolerance, diabetes mellitus, insulin sensitivity,
insulin resistance

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital
Yun-Lin Branch, Yun-Lin, Taiwan.
2
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
3
Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital,
Taipei, Taiwan.
4
Department of Medical Research and Development, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin,
Taiwan.
Correspondence to: Chin-Hsiao Tseng, No. 7 Chung-Shan South Road, Taipei, Taiwan. Department of Internal
Medicine, National Taiwan University Hospital
E-mail: ccktsh@ms6.hinet.net
27

The Effects of Aging on Glucose Metabolism

4 1

determinant for the incidence of DM. Peak

Introduction

incidence was noted at the age of 55-64

years and decreased slightly after the age

Type 2 diabetes mellitus (DM) is the

most common chronic metabolic disease in

of 65 years [5]. In both sexes, the incidence

the elderly [1]. The prevalence and incidence

(per 100,000 population) read 9.3, 144.9,

of impaired glucose tolerance and DM

547.2, 937.0 and 725.8 for those aged <35

increase with aging [2]. The incidence of

years, 35-44, 45-54, 55-64 and 65 years,

new cases is 10 times greater for the elderly

respectively [5].

than for persons aged under 45 in one study

Incidence of cardiovascular and

[3]. In the Belgian Elderly Diabetes Survey,

peripheral vascular complications and the

the prevalence of impaired fasting glucose

rate of mortality from cardiovascular

(IFG) is approximately 4%, and of DM

causes are twice greater for elderly DM

10%, most of which (80%) was undiagnosed

patients than for their non-DM counterparts

[2]. DM shows little gender preference

[7]. Furthermore, elderly diabetic patients

although it becomes slightly more frequent

face a higher risk of developing hypertension

in women with advancing age [4].

[8-11], and macro- and micro-vascular

complications [12-19]; they also suffer a

In Taiwan, the prevalence and

incidence of diabetes mellitus show a

higher mortality rate than younger diabetic

similar association with aging [5,6]. In a

patients [20,21]. In a 10-year prospective

national survey of 6,600 residents in 2002,

population study of 406 subjects, the

the age-standardized (to the World Health

respective ten-year total mortality of

Organization year 2000 population)

subjects with normal glucose tolerance and

prevalence was 6.6% (unpublished data).

that of subjects with DM were 49% and

The prevalence increased with age and was

72% in men, and 24% and 65% in women

approximately 20% in residents aged 65

[22]; and the respective ten-year

years (unpublished data). As for the

cardiovascular mortality rates for the normal

incidence of type 2 DM in Taiwan, it had

and DM groups were 19% and 44% in

been observed to sustain an upward trend

men, and 8% and 35% in women [22].

during the period of 1992- 1996 [5]. The

Excess mortality was observed in both sexes

average yearly incidence during that

when DM existed at 70 years of age, and in

period was 187.1 per 100,000 population

men when impaired glucose tolerance

for men and 218.4 per 100,000 population

(IGT) existed at this age. The excess

for women. Age is an important

mortality in men could solely, and in

women partly, be explained by
28

Vol.4 No.1

Shyang-Rong Shih

et al

Taiwan Geriatrics & Gerontology

cardiovascular causes [22]. In another

among the elderly with rises in fasting and

study of the burden of mortality of diabetes

especially postprandial blood glucose

in the year 2000, 29% of all deaths in DM

levels that directly correlate with age [24].

patients older than 64 years were attributable

Fasting blood glucose increases by 1 to 2

to diabetes [23]. DM accounted respectively

mg/dL and postprandial blood glucose up

for 5.6% and 8.2% of all-cause deaths

to 15 mg/dL per decade in age [24]. Most

among male and female residents older

diabetic patients belong to the category of

than 64 years in Southeast Asia [23]. The

type 2 DM, especially when diabetes is

relative risk of dying for 60-79 year-old

diagnosed in the elderly [2]. Responsible

individuals with diabetes is 2.25 times

mechanisms of age-related glucose

greater than for the elderly people without

intolerance include: 1) decreased insulin

diabetes [23].

sensitivity, either from receptor

abnormalities, decreased exercise, or

In this paper we will review the current

knowledge about the effects of aging on

increased adiposity; 2) decreased -cell

glucose metabolism.

function; and 3) altered dietary habits and

decreased insulin-to-glucose ratio [24].

Rises in Fasting and Postprandial

Other factors that can adversely affect

Blood Glucose

glucose tolerance in aging include drug

use, interfering conditions from associated

Glucose tolerance tends to be markedly

diseases, and other stressful conditions

impaired in the elderly. Most studies have

commonly encountered during acute

revealed impaired glucose metabolism

hospitalization [2] (Table 1).

Table 1

Potential Mechanisms Responsible for Age-related Glucose Intolerance

Possible mechanism
Intrinsic factors
Impaired -cell function
Decreased insulin sensitivity

Extrinsic factors

Possible contributing factors

-cell glucotoxicity
Age-related mitochondrial dysfunction
Decreased insulin receptor number
Age-related mitochondrial dysfunction
Increased intramyocellular triglyceride
Decreased AMPK activity
Decreased adiponectin
Increased leptin
Decreased exercise level
Increased adiposity
Drugs
Associated diseases or other stressful conditions

29

The Effects of Aging on Glucose Metabolism

4 1

alteration in glucose metabolism in obese

Impaired -cell Function

middle-aged patients with type 2 DM [27,

28]. It is reasonable that since impaired

Reductions in both early and late

-cell function is observed in obese

phases of insulin release are well documented

middle-aged patients with type 2 DM, it

in the elderly with type 2 DM [2,24].

must play some role in obese elderly DM

In the Belgian Elderly Diabetes

patients. Mitochondrial energy metabolism

survey, most participants had normal or

plays a critical role in glucose-induced

higher than normal insulin sensitivity and

insulin secretion [29]. Age-associated

normal or moderately decreased -cell

reduction in mitochondrial function has

function, whereas participants with IFG or

been demonstrated to affect insulin

DM had significantly decreased -cell

sensitivity [29]. Whether it may also affect

function and insulin sensitivity [2].

insulin secretion forms a subject deserving

Secretory defects in -cell seem to be a

further studies.

common occurrence in the elderly.

Meneilly et al. compared healthy lean

Decreased Insulin Sensitivity

and obese elderly with type 2 DM lean and

obese elderly [26]. Lean elderly type 2 DM

Evidence of decrease in insulin sensitivity

patients showed a profound impairment in

Although several studies suggested

glucose-induced insulin release but mild

resistance to insulin-mediated glucose

normal or higher than normal insulin

disposal [26]. It was suggested that decreased

sensitivity in the elderly [2], most studies

-cell function was attributed to the toxic

showed the transition from the normal

effects of chronic hyperglycemia, the so

state to overt type 2 DM in aging was

called -cell glucotoxicity [25]. Adversely,

typically characterized by deterioration in

obese elderly type 2 DM patients reported

glucose tolerance [1, 29]. Petersen et al.

adequate circulating insulin but marked

studied healthy elderly and young people

resistance to insulin-mediated glucose

matched for lean body mass and fat mass

disposal in the study [26]. Other studies

[29]. The elderly subjects had slightly

further suggest that fasting hyperinsulinemia,

higher plasma glucose concentration and

impaired first- and second-phase insulin

significantly higher plasma insulin

release, increased fasting hepatic glucose

concentration during the test of oral glucose

output, and resistance to insulin-mediated

tolerance. Basal glucose production rates

glucose disposal are all involved in the

were similar while glucose infusion rates

30

Vol.4 No.1

Shyang-Rong Shih

et al

Taiwan Geriatrics & Gerontology

required to maintain euglycemia and

by impairment of the action of insulin on

insulin-stimulated rates of peripheral

target cells, owing to alterations at both

glucose uptake were about 40% lower in

the receptor and the postreceptor levels

the elderly subjects during hyperinsulinemic-

[30].

euglycemic clamp [29]. These suggest that

Intramyocellular triglycerides, mitochondria

the elderly are relatively insulin resistant.

and insulin resistance

Alterations of insulin receptors and

Intramuscular fat and hepatic steatosis

postreceptor levels

are strongly related to insulin resistance

Bolinder et al. used subcutaneous

[31, 32]. Hydrolysis of triglycerides

adipose tissue from healthy subjects to

located within the myocytes is postulated to

study the influence of aging on insulin

trigger an increase in long-chain acyl CoA

action [30]. They found that insulin

diacylglycerol, which in turn can activate

binding per cell in the older group was

protein kinase C, thereby impairing insulin

50% lower than the one in the younger

signaling [33, 34]. This further leads to

group, essentially owing to a decrease in

reduced insulin-stimulated muscle glucose

the number of insulin receptors [30].

transport activity, reduced glycogen synthesis

Insulin sensitivity, as reflected by the

in muscle, and impaired suppression of

degree of antilipolysis and stimulation of

glucose production by insulin in the liver

glucose oxidation, was 10 to 20 times

[35, 36]. Sinha et al. used 1H nuclear

lower in the older subjects. Basal lipolysis

magnetic resonance spectroscopy to study

and the maximum anti-lipolysis effect of

the intramyocellular (IMCL) and

insulin were similar in the young and the

extramyocellular (EMCL) triglycerides of

old groups. The basal rate of glucose

the soleus muscle [37]. They found that

oxidation in the older subjects was less

both the IMCL and EMCL triglycerides

than one-half that for the young group, and

were significantly greater in the obese

the maximum level of insulin-induced

adolescents than in the lean control

glucose oxidation was lower by about

subjects. There was a strong inverse

75%. Age was significantly and negatively

correlation between IMCL triglycerides

correlated with the number of insulin

and insulin sensitivity, which persisted

receptors, basal production of

14

after adjusting for percent total body fat

CO2, and

the maximal level of insulin-induced

and abdominal subcutaneous fat mass but

glucose oxidation [30]. Aging is accompanied

not when adjusting for visceral fat. IMCL

31

The Effects of Aging on Glucose Metabolism

4 1

and EMCL triglycerides are significantly

muscle were also observed in the elderly

associated with visceral fat mass, implying

[29]. This may be a contributing factor to

that intracellular lipid accumulation might

the increased content of triglycerides in

be a result of an increased flux of free fatty

muscle and liver.

acids into muscle from the enlarged

The AMP-activated protein kinase (AMPK)

visceral adipose depot [37].

According to the study of Petersen et
al., increased fat accumulation in muscle

AMPK, as a chief regulator of

and liver tissue was detected with nuclear

whole-body energy balance [40], plays a

magnetic resonance (NMR) in the elderly,

crucial role in regulating mitochondrial

and insulin resistance was suggested by

biogenesis and fatty-acid oxidation. Once

hyperinsulinemic-euglycemic clamp [29].

activated in skeletal muscle, AMPK exerts

Hepatic insulin resistance, however, was

control in part by regulating fatty-acid

not observed during the clamp. Another

oxidation through the phosphorylation of

study also showed that hepatic glucose

acetyl-CoA carboxylase 2 and mitochondrial

output is similar in healthy or DM and lean

biogenesis through increasing the expression

or obese old people [26]. These studies

of proteins vital for proper mitochondrial

together suggest that age-associated insulin

functions such as citrate synthase and

resistance is mainly attributable to reduced

succinate dehydrogenase [41, 42]. In an

insulin-stimulated muscle glucose

animal study, acute stimulation of AMPK

metabolism but not hepatic insulin

activity by 5-aminoimidazole-4- carboxamide-

resistance [26, 29].

1--D-ribofuranoside and exercise was

blunted in skeletal muscle of old rats.

Age-associated reductions in
mitochondrial number and function were

Mitochondrial biogenesis in response to

demonstrated, possibly resulted from

chronic activation of AMPK with

age-associated accumulation of mutations

-guanidinopropionic acid feeding was

in control sites for mitochondrial DNA

also diminished in old rats. These results

replication [38]. In vitro, decrease of state

suggest that aging-associated reductions in

II mitochondrial respiration was detected

AMPK activity may be a major contributing

in isolated mitochondria of elderly people

factor in the reduced mitochondrial function

[39]. In vivo, an approximately 40%

and dysregulated intracellular lipid

reduction in mitochondrial oxidation

metabolism associated with aging [43].

assessed by 13C NMR and phosphorylation

activity assessed by

31

Leptin and adiponectin

P NMR in skeletal
32

Vol.4 No.1

Shyang-Rong Shih

Leptin is a peptide synthesized mainly

et al

Taiwan Geriatrics & Gerontology

IMCL triglycerides [29]. Further studies

by white adipose tissue and positively

are necessary to confirm the above

related to insulin resistance independent of

postulations and perhaps to work up for

the degree of adiposity [44]. Adiponectin

the target therapy.

is a protein produced by adipocytes and

Acknowledgements

inversely related to the degree of adiposity

and insulin resistance [45, 46]. Decreased

The authors would like to thank the

adiponectin levels is a risk factor of type 2

DM in the general population [47, 48]. In a

following institutes for their continuous

study focusing on elderly people, both

support on the epidemiologic studies of

fasting insulin and homeostasis model

diabetes mellitus and arsenic-related health

assessment of insulin resistance (HOMA)

hazards: the Department of Health

showed significant positive correlation

(DOH89-TD-1035; DOH97-TD-D-113-

with leptin and negative correlation with

97009), the National Taiwan University

adiponectin in elderly men and women

Hospital Yun-Lin Branch

[49]. Leptin and adiponectin alone explained

(NTUHYL96.G001) and the National

up to 38% of HOMA variance in multiple

Science Council

linear regression analysis [49]. Leptin and

(NSC-86-2314-B-002-326,

adiponectin are also strictly related to

NSC-87-2314-B-002-245,

insulin resistance independent of body fat

NSC88-2621-B-002-030,

and body fat distribution in the elderly

NSC89-2320-B002-125,

people as in the general population [49]

NSC-90-2320-B-002-197,
NSC-92-2320-B-002-156,
NSC-93-2320-B-002-071,

Conclusions

NSC-94-2314-B-002-142,
Prevalence of impaired glucose

NSC-95-2314-B-002-311 and

metabolism among the elderly is high [2].

NSC-96-2314-B-002-061-MY2), Taiwan.

Possible responsible mechanisms include

References

decreased -cell function and increased

insulin resistance [2]. Decreased -cell

1. King H, Aubert RE, Herman WH:

function may be related to glucotoxicity

and mitochondrial dysfunction while

Global burden of diabetes, 1995-2025:

insulin resistance is associated with

prevalence, numerical estimates, and

mitochondrial dysfunction and increased

projections. Diabetes Care 1998; 21:

33

The Effects of Aging on Glucose Metabolism

1414-31.

4 1

9. Tseng CH: Body mass index and blood

2. Hermans MP, Pepersack TM, Godeaux

pressure in adult type 2 diabetic

LH, Beyer I, Turc AP: Prevalence and

patients in Taiwan. Circ J 2007; 71:

determinants of impaired glucose

1749-54.

metabolism in frail elderly patients:

10. Tseng CH: Exogenous insulin use and

the Belgian Elderly Diabetes Survey

hypertension in adult patients with

(BEDS). J Gerontol A Biol Sci Med Sci

type 2 diabetes mellitus. Arch Intern

2005; 60: 241-7.

Med 2006; 166: 1184-9.

3. Morrow LA, Halter JB: Diabetes

11. Tseng CH: Higher risk of hypertension

mellitus in the older adult. Geriatrics

in indigenous type 2 diabetic patients

1988; 43 (Suppl): 57-65.

in Taiwan. J Hypertens 2006; 24:

4. Meneilly GS, Tessier D: Diabetes in

1817-21.

the elderly. Diabet Med 1995; 12:

12. The Global Lower Extremity

949-60.

Amputation Study Group (Tseng CH

5. Tseng CH, Tseng CP, Chong CK, et al:

as principle investigator in Taiwan).

Increasing incidence of diagnosed type

Epidemiology of lower extremity

2 diabetes in Taiwan: analysis of data

amputation in centers in Europe, North

from a national cohort. Diabetologia

America and East Asia. Br J Surg

2006; 49: 1755-60.

2000; 87: 328-37.

6. Tseng CH, Chong CK, Heng LT,

13. Tseng CH: Prevalence and risk factors

Tseng CP, Tai TY: The incidence of

of peripheral arterial obstructive

diabetes mellitus in Taiwan. Diabetes

disease in Taiwanese type 2 diabetic

Res Clin Pract 2000; 50 (suppl 2):

patients. Angiology 2003; 54: 331-8.

14. Tseng CH: Prevalence and risk factors

S61-S64.

of diabetic foot problems in Taiwan: a

7. Harris MI: Epidemiology of diabetes

mellitus among the elderly in the

cross-sectional survey of non-type 1

United States. Clin Geriatr Med 1990;

diabetic patients from a nationally

6: 703-19.

representative sample (Letters;

Observations). Diabetes Care 2003;

8. Tseng CH: Parental history of

26: 3351.

hypertension and diabetes and

15. Tseng CH, Chong CK, Sheu JJ, Wu

prevalence of hypertension in type 2

diabetic patients: a study of a national

TH, Tseng CP: Prevalence and risk

sample in Taiwan. Eur J Clin Invest

factors for stroke in type 2 diabetic

2007; 37: 870-7.

patients in Taiwan: a cross-sectional

34

Vol.4 No.1

Shyang-Rong Shih

et al

Taiwan Geriatrics & Gerontology

survey of a national sample by

amputation: a 6. 5-year follow-up

telephone interview. Diabet Med 2005;

study in Taiwan. Atherosclerosis 2008;

22: 477-82.

197: 111-7.

16. Tseng CH: Correlation of uric acid and

22. Agner E, Thorsteinsson B, Eriksen M:

urinary albumin excretion rate in

Impaired glucose tolerance and

patients with type 2 diabetes mellitus

diabetes mellitus in elderly subjects.

in Taiwan. Kidney Int 2005; 68:

Diabetes Care 1982; 5: 600-4.

796-801.

23. Roglic G, Unwin N, Bennett PH, et al:

17. Tseng CH: Prevalence of

The burden of mortality attributable to

lower-extremity amputation among

diabetes. Diabetes Care 2005; 28:

patients with diabetes mellitus: Is

2130-5.

height a factor? CMAJ 2006; 174:

24. Samos LF, Roos BA: Diabetes mellitus

319-23.

in older persons. Med Clin North Am

18. Tseng CH, Tseng CP, Chong CK,

1998; 82: 791-803.

Cheng JC, Tai TY: Independent

25. Meneilly GS, Dawson K, Tessier D:

association between triglycerides and

Alterations in glucose metabolism in

coronary artery disease in Taiwanese

the elderly patient with diabetes.

type 2 diabetic patients. Int J Cardiol

Diabetes Care 1993; 16: 1241-8.

2006; 111: 80-5.

26. Meneilly GS, Elliott T, Tessier D,

19. Tseng CH, Chong CK, Tseng CP, Tai

Hards L, Tildesley H: NIDDM in the

TY: The association between urinary

elderly. Diabetes Care 1996; 19:

albumin excretion and peripheral

1320-5.

arterial disease in Taiwanese elderly

27. DeFronzo RA: Pathogenesis of type 2

patients with type 2 diabetes mellitus.

(non-insulin dependent) diabetes

Age Ageing 2008; 37: 77-82.

mellitus: a balanced overview.

20. Tseng CH: Mortality and causes of

Diabetologia 1992; 35: 389-97.

death in a national sample of diabetic

28. Reaven GM: Banting lecture 1988.

patients in Taiwan. Diabetes Care

Role of insulin resistance in human

2004; 27: 1605-9.

disease. Diabetes 1988; 37: 1595-607.

21. Tseng CH, Chong CK, Tseng CP,

29. Petersen KF, Befroy D, Dufour S, et

Cheng JC, Wong MK, Tai TY:

al: Mitochondrial dysfunction in the

Mortality, causes of death and

elderly: possible role in insulin

associated risk factors in a cohort of

resistance. Science 2003; 300: 1140-2.

diabetic patients after lower-extremity

30. Bolinder J, Ostman J, Arner P:

35

The Effects of Aging on Glucose Metabolism

4 1

Influence of aging on insulin receptor

Assessment of skeletal muscle

binding and metabolic effects of

triglyceride content by 1H nuclear

insulin on human adipose tissue.

magnetic resonance spectroscopy in

Diabetes 1983; 32: 959-64.

lean and obese adolescents:

31. Krssak M, Falk PK, Dresner A, et al:

relationships to insulin sensitivity,

Intramyocellular lipid concentrations

total body fat, and central adiposity.

are correlated with insulin sensitivity

Diabetes 2002; 51: 1022-7.

in humans: a H NMR spectroscopy

38. Michikawa Y, Mazzucchelli F,

study. Diabetologia 1999; 42: 113-6.

Bresolin N, Scarlato G, Attardi G:

Aging-dependent large accumulation

32. Seppala-Lindroos A, Vehkavaara S,

Hakkinen AM, et al: Fat accumulation

of point mutations in the human

in the liver is associated with defects

mtDNA control region for replication.

in insulin suppression of glucose

Science 1999; 286: 774-9.

production and serum free fatty acids

39. Trounce I, Byrne E, Marzuki S:

independent of obesity in normal men.

Decline in skeletal muscle

J Clin Endocrinol Metab 2002; 87:

mitochondrial respiratory chain

3023-8.

function: possible factor in ageing.

33. Kelley DE, Mandarino LJ: Fuel

Lancet 1989; 2: 44-5.

selection in human skeletal muscle in

40. Kimura N, Tokunaga C, Dalal S, et al:

insulin resistance: a reexamination.

A possible linkage between

Diabetes 2000; 49: 677-83.

AMP-activated protein kinase (AMPK)

34. Shulman GI: Cellular mechanisms of

and mammalian target of rapamycin

insulin resistance. J Clin Invest 2000;

(mTOR) signalling pathway. Genes

106: 171-6.

Cells 2003; 8: 65-79.

35. Boden G, Chen X, Ruiz J, White JV,

41. Bergeron R, Ren JM, Cadman KS, et

Rossetti L: Mechanisms of fatty

al: Chronic activation of AMP kinase

acid-induced inhibition of glucose

results in NRF-1 activation and

uptake. J Clin Invest 1994; 93:

mitochondrial biogenesis. Am J

2438-46.

Physiol Endocrinol Metab 2001; 281:

36. Roden M, Price TB, Perseghin G, et al:

E1340-6.

Mechanism of free fatty acid-induced

42. Zong H, Ren JM, Young LH, et al:

insulin resistance in humans. J Clin

AMP kinase is required for

Invest 1996; 97: 2859-65.

mitochondrial biogenesis in skeletal

37. Sinha R, Dufour S, Petersen KF, et al:

muscle in response to chronic energy

36

Vol.4 No.1

Shyang-Rong Shih

et al

Taiwan Geriatrics & Gerontology

deprivation. Proc Natl Acad Sci USA

low plasma concentration precedes a

2002; 99: 15983-7.

decrease in whole-body insulin

43. Reznick RM, Zong H, Li J, et al:

sensitivity in humans. Diabetes 2002;

Aging-associated reductions in

51: 1884-8.

AMP-activated protein kinase activity

47. Spranger J, Kroke A, Mohlig M, et al:

and mitochondrial biogenesis. Cell

Adiponectin and protection against

Metab 2007; 5: 151-6.

type 2 diabetes mellitus. Lancet 2003;

44. Margetic S, Gazzola C, Pegg GG, Hill

361: 226-8.

RA: Leptin: a review of its peripheral

48. Daimon M, Oizumi T, Saitoh T, et al:

actions and interactions. Int J Obes

Decreased serum levels of adiponectin

Relat Metab Disord 2002; 26: 1407-33.

are a risk factor for the progression to

45. Staiger H, Tschritter O, Machann J, et

type 2 diabetes in the Japanese

al: Relationship of serum adiponectin

Population: the Funagata study.

and leptin concentrations with body fat

Diabetes Care 2003; 26: 2015-20.

distribution in humans. Obes Res 2003;

49. Zoico E, Di Francesco V, Mazzali G,

11: 368-72.

et al: Adipocytokines, fat distribution,

46. Stefan N, Vozarova B, Funahashi T, et

and insulin resistance in elderly men

al: Plasma adiponectin concentration is

and women. J Gerontol A Biol Sci Med

associated with skeletal muscle insulin

Sci 2004; 59: M935-9.

receptor tyrosine phosphorylation, and

37

1,2,3

65
20% 35
9.3 65 725.8

C (protein
kinase C)
AMP-
(AMP-activated protein kinase, AMPK)(adiponectin)
(leptin)

20094(1)27-38

2 3

7
E-mail: ccktsh@ms6.hinet.net

38