| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original Studies |
Department of Medicine (B.A.), Lund University, S-205 02 Malmö, Sweden; and Institute of Systems Science and Biomedical Engineering (G.P.) (LADSEB-CNR), I-35127 Padua, Italy
Address all correspondence and requests for reprints to: Dr. Bo Ahrén, Department of Medicine, Malmö University Hospital, S-205 02 Malmö, Sweden. E-mail: bo.ahren{at}medforsk.mas.lu.se
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
2) (11, 17). Potential explanations for these different results might be offered. First, many studies lack an age standardization in the different study groups and have included a large age range in the respective young (Y) and elderly (E) age groups. This could increase the variability of the results because the cut-off age for altered insulin sensitivity or secretion is unknown. Second, a difference in degree of other age-related variables between the studied groups, like obesity or physical activity, might be of importance because such factors age-independently affect the tissue sensitivity to insulin (18, 19). Third, a significantly higher 2-h glucose value in the oral glucose tolerance test (OGTT) in the older group exists in some studies, even though the older subjects did not meet the criteria for IGT (5, 11, 12). This might complicate interpretation of the results because, in IGT, a combination of low insulin sensitivity and insulin secretion is usually found (11, 20). This would imply that changes in insulin secretion and insulin action are not necessarily caused by the aging process per se but to the glucose intolerance.
The purpose of this study was to explore whether insulin secretion and insulin sensitivity are altered by age when the influences of glucose intolerance, as judged by OGTT and body mass index (BMI), are strictly controlled. Furthermore, the study also controlled for gender influences and (by studying Caucasians only) for possible influences caused by differences in ethnic origin of the subjects. The FSIGT with minimal model analysis was performed to obtain measurements of SI, insulin secretion, SG, and hepatic extraction of insulin (21, 22). The metabolic parameters were also related to circulating levels of leptin [the adipocyte hormone that, in rodents, has been shown to regulate body weight by reducing food intake and increasing energy expenditure (23, 24)] and the islet hormones, glucagon and pancreatic polypeptide (PP), because the potential impact of these hormones on the age-related changes in glucose metabolism has not been determined before.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
We studied two different groups of Caucasian subjects. Both groups were recruited from a health-screening program in the city of Malmö. The E group consisted of 20 subjects [10 women and 10 men; age, 63 yr plus 6 months (±5 months, means ± SD)], and the Y group consisted of 20 subjects [10 women and 10 men; age, 27 yr plus 10 months (±10 months, means ± SD)]. The BMI was 25.2 ± 1.7 kg/m2 in the E group and 24.9 ± 2.1 kg/m2 in the Y group (mean ± SD, not significantly different). A 75-g OGTT, using WHO criteria (25), was undertaken in all subjects. For this test, the subjects attended the clinic in the morning, after an overnight fast. Capillary blood glucose samples were obtained directly before and 2 h after a 75-g oral glucose load. The 2 h were spent in a semirecumbent position. All subjects were found to have normal glucose tolerance, defined using WHO reference values (25; 2-h blood glucose after oral glucose load <7.8 mmol/L). All subjects were healthy, without any current or past history of any significant illness (including endocrine disorders, ischemic heart disease, or hypertension). All subjects had normal liver and thyroid function tests; none were taking any medication known to affect glucose tolerance; none had a family history of diabetes. All subjects received oral and written information concerning the aims and methods of the study, and they signed a consent declaration before the start of the study. The study protocol was approved by the Ethics Committee of Lund University.
FSIGT
FSIGT was undertaken in all subjects 6–8 weeks after the OGTT. Subjects attended the clinic in the morning, after an overnight fast. A catheter was inserted into an antecubital vein for blood sampling and into a contralateral antecubital vein for glucose injection. Basal samples were drawn at -10 min and at -1 min. At time 0, glucose (300 mg/kg) was injected in 1 min, and then additional samples were collected at 3, 4, 5, 6, 8, 10, 15, 20, 25, 30, 40, 60, 80, 100, 120, 150, and 180 min.
Analyses
Capillary blood glucose samples from the OGTT were chilled at 4 C and sent to the central laboratory at the hospital, where they were analyzed using an automatic glucose oxidase method. Samples for measurement of insulin were taken in prechilled tubes, for determination of glucose, leptin, and PP in prechilled tubes containing 0.084 mL EDTA (0.34 mol/L) and for determination of C-peptide and glucagon in prechilled tubes containing 0.084 mL EDTA (0.34 mol/L) and aprotinin (250 kallikrein-inhibiting units/mL blood; Bayer, Leverkusen, Germany). Leptin, PP, and glucagon were determined in fasting samples only. A total of 390 mL blood were taken during the test. All blood samples were immediately centrifuged at 5 C, and serum or plasma was frozen at -20°C until analyses. Serum insulin concentrations were analyzed with a double-antibody RIA technique. Guinea pig antihuman insulin antibodies, human insulin standard, and mono-125I-tyr-human insulin tracer (Linco Res. Inc., St. Charles, MO) were used. Plasma C-peptide concentrations were analyzed with a double-antibody RIA technique using guinea pig antihuman C-peptide antibodies, 125I-labeled human C-peptide, and human C-peptide standard (Linco). Plasma glucose concentrations were determined using the glucose oxidase method. Baseline samples, i.e. before injecting glucose, were also taken for analysis of leptin, glucagon, and PP. Plasma leptin was analyzed with a double-antibody RIA using rabbit antihuman leptin antibodies, 125I-labeled human leptin as tracer and human leptin (Linco) as standard (26). Glucagon levels were measured with a double-antibody RIA, in duplicate, using guinea pig antihuman glucagon antibodies specific for pancreatic glucagon, 125I-glucagon as tracer, and glucagon standard (Linco). PP was determined with a double-antibody RIA using rabbit antihuman PP antibodies (Linco), 125I-labeled human PP (Peninsula Laboratories, Merseyside, England), and human PP (Linco) standard (27). All measurements were performed in duplicate.
Data analysis
FSIGT data were analyzed with the minimal model technique (21, 22, 28, 29) that provides parameters SI and SG
(glucose effectiveness). SG can be factored out into two
components: SG at basal insulin (BIE) and SG at
zero insulin, i.e. glucose disappearance rate per
se (GEZI) (30). The C-peptide minimal model (22) and that of
posthepatic insulin provide the parameters BSR (basal B cell secretion
rate), the fractional clearance of C-peptide, and first-phase insulin
secretion (1) and 2, which are the
dynamic suprabasal first- and second-phase B cell sensitivity to
glucose, respectively. Total B cell insulin secretion was calculated
per unit volume as the integral of C-peptide secretion rate throughout
the 3-h duration of the experiment, and hepatic insulin extraction as
the percent difference between total B cell insulin secretion and the
posthepatic insulin delivery (22). The areas under the curve (AUC) for
insulin and C-peptide were calculated using the trapezoidal rule. The
acute insulin response to glucose (AIRG) and the acute
C-peptide response to glucose (ACPG) were calculated by
averaging the suprabasal concentration of insulin or C-peptide between
3 and 10 min after glucose injection. We also calculated two indices:
the disposition index, by multiplying SI times
AIRG (31); and the B cell adaptation index, by multiplying
SI times 1 (20). The disposition index
(SI times AIRG) weighs SI with the
ambient peripheral insulin during the first phase. It is a peripheral
measurement and does not necessarily reflect pancreatic secretion of
insulin. The adaptation index (SI times 1),
on the other hand, relates SI directly to a descriptor of B
cell function, because 1 is a direct prehepatic variable
that derives from C-peptide (22) and involves the active mechanism of
the B cells to release insulin under a glucose stimulation. The
adaptation index, therefore, tells us how the pancreas reacts to a
possible alteration in SI. It should be emphasized that the
FSIGT was performed without additional injection of tolbutamide or
insulin (21), because it was recently shown that SI is the
same in the different protocols (32), providing that there is
sufficient insulin, as was the case in our study; whereas
SG may be different, because it depends upon the amount of
insulin present (32, 33). In our case, however, SG
estimations also can be used, because insulin pattern and amount are
not different in the two groups.
Statistics
Model parameters were calculated by the computer program MINMOD (34) and by a specific program for B cell secretion (35). The iv glucose elimination rate was quantified with the glucose tolerance index, KG, calculated as the slope of the natural logarithm of glucose concentration vs. time from 10–30 min. Statistical analysis was performed with the SPSS (Statistical Package for the Social Sciences) for Windows system. Differences in mean values between groups were analyzed by means of ANOVA for repeated measurements for the glucose, insulin, and C-peptide concentrations during the FSIGT, and of unpaired Student’s t test for the clinical parameters and parameters calculated from the FSIGT. Statistical significant difference was assumed at P < 0.05. Pearson’s product-moment correlation was used to estimate linear relationships between variables. All data and results are given as mean ± SEM, unless otherwise stated.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Fasting blood glucose levels in the E subjects were 4.9 ±
0.1 mmol/L vs. 4.5 ± 0.1 mmol/L in the Y subjects
(P = 0.040) when performing the OGTT. The respective
2-h blood glucose values were 6.1 ± 0.3 mmol/L and 6.1 ±
0.3 mmol/L (not significant). Plasma C-peptide levels were higher in
the E subjects (P = 0.034), whereas serum insulin
levels did not differ between the two groups (Table 1
).
|
Immediately after the glucose injection, plasma glucose, serum
insulin, and plasma C-peptide rose rapidly, with peak levels after 3
min; then the levels declined (Fig. 1).
Plasma glucose levels were higher in E than in Y individuals at each
individual time point from min 15 after glucose administration through
min 120 (P = 0.028 or less), and KG was
significantly lower in E than in Y subjects (P =
0.019). Serum insulin levels did not differ significantly between the
groups at any individual time point, whereas plasma C-peptide levels
were significantly elevated in the E subjects, both at basal preglucose
injection and at all time points from 60 min after glucose challenge
and throughout the 180-min study period (P = 0.030 or
less). Similarly, AIRG, ACPG, and
AUCinsulin did not differ between the two groups, whereas
AUCC-peptide was higher in the E subjects
(P = 0.020). The parameter 1 did not
differ between the groups (P = 0.952), whereas
2 was lower in the E subjects (P =
0.034). Furthermore, BSR showed a higher value in E subjects than in Y
subjects (P = 0.026), whereas total amount of released
insulin throughout the 180-min study period did not differ between the
groups.
|
).
Furthermore, hepatic insulin extraction was higher in the E than in the
Y subjects (P = 0.013). Finally, both the disposition
index (SI x AIRG; 184 ± 22
10-4 min-1 in E subjects vs.
242 ± 47 10-4 min-1 in the Y subjects,
P = 0.277) and the adaptation index (SI x
1; 102 ± 14 min-2/mmol/L in E
vs. 98 ± 12 min-2/mmol/L in Y subjects,
P = 0.83) were not different between the groups. In
contrast, the product SI x 2 was lower in
the E subjects (0.38 ± 0.06 10-4
min-3/(mmol/L) vs. 0.74 ± 0.13
10-4 min-3/(mmol/L) of Y subjects,
P = 0.016).
|
To study whether parameters from the FSIGT could explain the
reduced KG, a univariate correlation analysis was
undertaken across both groups, correlating the parameters that were
altered by age (i.e. baseline plasma glucose levels,
SG, 2, and hepatic insulin extraction rate)
with KG. It was found that SG correlated
positively (r = 0.579, P < 0.001) and hepatic
insulin extraction correlated negatively (r = -0.414,
P = 0.003) with KG, whereas no significant
correlation was found between KG and baseline plasma
glucose (r = -0.21, P = 0.136) or
2 (r = 0.13, P = 0.369). It was
also found that SG correlated negatively with hepatic
insulin extraction (r = -0.54, P < 0.001). A
partial correlation analysis revealed that SG and
KG correlated significantly with each other also when
removing the correlation that is caused by their mutual association
with hepatic insulin extraction (r = 0.508, P =
0.001). Also, estimates of 1 correlated with
KG, such as AIRG (r = 0.433,
P = 0.005), serum insulin at min 3 (r = 0.431,
P = 0.005), and the increase in serum insulin at min 3
(r = 0.452, P = 0.003). Furthermore, both the
disposition index (r = 0.633, P < 0.001) and the
adaptation index (r = 0.443, P = 0.004) correlated
with KG.
Adaptation to reduced SI
Plotting AIRG vs. SI, we
obtained the characteristic hyperbolic function, which did not differ
between E and Y subjects (Fig. 2). There
was also a similar significant negative correlation between
SI and 1 in the two groups (in E subjects,
r = -0.46, P = 0.046; in Y subjects, r =
-0.52, P = 0.018). This shows that neither
SI nor its relation to 1 was disturbed in
the E subjects.
|
Plasma levels of leptin and glucagon did not differ between E and
Y subjects, whereas plasma PP was significantly higher in E subjects
(Table 2
). Plasma leptin was, as expected, higher in females than in
males (Table 2) and correlated significantly to BMI in both males
(r = 0.717, P < 0.001) and females (r =
0.789, P < 0.001). After adjustment for BMI, plasma
leptin levels correlated significantly to fasting insulin and
C-peptide, to AUCinsulin and AUCC-peptide, to
AIRG, and to fasting glucagon in both genders
(P < 0.05). Plasma glucagon showed significant
correlation with baseline circulating levels of insulin (r = 0.57,
P < 0.001) and C-peptide (r = 0.54,
P < 0.001), as well as with AIRG (r =
0.58, P < 0.001), ACPG (r = 0.54,
P < 0.001), AUCinsulin (r = 0.49,
P = 0.001), AUCC-peptide (r = 0.43,
P = 0.006), SI (r = -0.41,
P = 0.008), and plasma leptin (r = 0.36,
P = 0.037) but not with other metabolic parameters
obtained in the FSIGT or with plasma PP (r = 0.03,
P = 0.854). Plasma PP did not display any gender
difference (89.0 ± 10.6 pg/mL in males vs. 99.2
± 17.6 pg/mL in females, P = 0.625) and did not show
any significant correlation with BMI, with the metabolic parameters
obtained in the FSIGT, or with plasma leptin or glucagon.
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
2 decreased by age. In contrast, glucose sensitivity of
1, posthepatic delivery of insulin, and SI
were not altered in the E subjects. Finally, hepatic insulin extraction
increased by age. The most impressive difference between the E and Y subjects was the low SG in the E subjects. Previous studies also including subjects with IGT have not demonstrated any age-related influence on SG (11, 13), whereas one study has shown impairment of insulin-independent glucose uptake under basal conditions in elderly subjects (39). The clinical importance of the reduced SG in the E subjects in our study is supported by the finding that SG correlated to the glucose elimination rate. In the E subjects in the present study, it was GEZI that was reduced, when compared with the Y subjects. This means that the impairment seems to be ascribed to the totally insulin-independent processes. Other evidences for this are the unchanged insulin sensitivity indices, both at BIE and under dynamic insulin conditions (SI). Theoretically, the reduced SG might reside in the liver (decreased glucose uptake or failure of suppression of glucose production), in the peripheral muscle tissue (decreased glucose uptake), or in the central nervous system. It might be speculated that the reduced glucose uptake is executed in the central nervous system, because it has been demonstrated that the brain weight is reduced by aging, being 7% less at 80 than at 20 yr of age (40); and the glucose transport in the brain is reduced by aging in rats (41). However, the minimal model does not allow differentiation between the potential sites for the reduced SG in the elderly. The reduction of SG, in studies using the minimal model, has recently been a topic stimulating discussions as to whether it is a true physiological phenomenon or just a model artifact (32, 33, 42, 43). In fact, reduction of SG might be accompanied by, and may be caused by, a reduction of the prevailing insulin concentrations, (32, 33, 43). In the present study, however, insulin was not different between the groups; and therefore, the observed differences in SG between the two groups seem to be valid, and its reduction seems to be unrelated to factors other than age.
Several previous studies have demonstrated reduced insulin sensitivity in old age (3, 4, 5, 6, 7, 8, 9, 10, 11), whereas several other studies, using the same methodological protocols, failed to demonstrate any reduction in tissue insulin sensitivity by age (12, 13, 14, 15, 16). A difference between the FSIGT and hyperinsulinemic euglycemic clamp techniques is that they measure tissue sensitivity to insulin at different insulin levels: in the FSIGT, insulin concentrations are at lower, more physiological levels; whereas in the clamp studies, plasma insulin levels are usually elevated to 800–1000 pmol/L (3, 4, 5, 6, 7, 44). Studies using hyperinsulinemic clamp techniques have reported inhibition of insulin sensitivity in-old age groups by approximately 30% (45), whereas studies using lower rates of insulin have reported a higher degree of inhibition at old age (5, 6, 11). This would imply that it would be easier to detect changes in insulin sensitivity in old-age groups by techniques using lower levels of insulin, such as the FSIGT. Therefore, the lack of any difference in our present study seems to have other explanations. A possible explanation is that the subjects in our study all had normal 2-h glucose values in OGTT, whereas in previous studies, the older subjects have had manifest glucose intolerance (11). Therefore, it is possible that reduction in insulin sensitivity in several previous studies on subjects of old age (3, 4, 5, 6, 7, 45), is a sign of manifest oral glucose intolerance, rather than an effect of aging per se.
Under normal conditions, insulin secretion and insulin sensitivity
display a hyperbolic relation, in that insulin secretion experiences a
compensatory increase when insulin sensitivity is reduced (21, 36, 44).
In IGT, the increase in insulin secretion is inadequate when insulin
sensitivity is reduced (44), and it is primarily the first phase
insulin secretion that is inadequately increased (20, 46). We found
that in the E subjects, the measures of 1 were not
significantly different from those of Y subjects (AIRG and
1), confirming previous studies (4, 10, 11, 12, 17); and the
hyperbolic relation between SI and 1 was not
different between E and Y subjects (Fig. 2). Hence, it seems that the E
subjects had normal 1 and normal adaptive capacity for
changes in SI.
In contrast, the E group had a diminished glucose sensitivity for the
second phase insulin secretion, which begins approximately 10–15 min
after glucose administration, confirming previous reports (10, 17). The
molecular basis for this B cell defect remains to be established. It
could be speculated that this B cell defect in the E subjects would
contribute to the reduced glucose elimination rate, in spite of the
normal 1. This, in turn, would make these subjects more
vulnerable for deterioration of the glucose tolerance if tissue
sensitivity to insulin is reduced, even though the first phase insulin
secretion would experiences a compensatory increase. In spite of the
glucose sensitivity in the second phase insulin secretion being reduced
in old age, the total amount of insulin released during the second
phase was increased, as evident by the increased
AUCC-peptide. It could be argued that the reduction of
2, despite an increase of the total
AUCC-peptide, may be interpreted as a model biased result.
However, our evidence is justified by reminding that the sensitivity to
glucose of the second-phase B cell secretion (2)
quantifies a dynamic process, i.e. the ability of the
pancreas to suprabasally release insulin under a dynamic stimulation
(22, 28, 35). Because of the simultaneously increase of hepatic
extraction of insulin, the resulting peripheral serum insulin levels
were not significantly different between the groups. This should have
provided a similar glucose-lowering effect in the two groups. Hence,
the physiological significance of the reduced glucose sensitivity of
second-phase B cell secretion in the E subjects remains to be
established.
In the E group, the 180-min plasma C-peptide levels after glucose administration were elevated, as compared with the Y group. This may give the impression that the disappearance rate of C-peptide was reduced in the E subjects. However, this was caused by elevated baseline levels, because plasma C-peptide at 180 min had returned to baseline levels in all subjects. Also, the model-derived clearance of C-peptide was not different in the two groups. This study also demonstrated an increased hepatic insulin extraction in the E subjects. This increased extraction rate correlated to the reduction in SG and, therefore, also to the reduction in glucose elimination, which yields the speculation that there is a direct link between these two parameters. However, more studies are required to establish these mechanisms and to clarify how this increase occurs and to identify the signals that generate it. A hepatic insulin extraction rate of 70–80% might seem high, because it is known that the liver degrades approximately 50% of insulin during the first passage (47). However, our figure represents the extraction rate of insulin during the entire 180-min period, which is the integrated result of several passages through the liver.
In this study, we also measured leptin and the two islet hormones, glucagon and PP. We found that leptin levels were higher in females than in males and correlated to insulin and glucagon, which are well-known phenomena (24, 48, 49). We found, however, that leptin levels were not different in the Y and E subjects, suggesting that, in humans, there is no age-related change in circulating leptin. Similarly, plasma glucagon levels were not different between the two age groups. Although it is well established that glucagon increases circulating glucose levels and also stimulates insulin secretion (50), its potential involvement in glucose intolerance is not known. However, a close relationship between insulin and glucagon secretion seems to exist under normal conditions, and consequently, we confirmed that plasma glucagon correlates to parameters of insulin secretion. We found also that fasting glucagon correlated negatively with SI but did not correlate to SG.
An interesting observation in this study, was that plasma levels of PP were significantly elevated in the E subjects without any relation to gender or to the parameters of the FSIGT. This is a novel finding, the relevance of which needs to be studied. The function of PP is not completely known. Its circulating levels are increased during hypoglycemia (51), and circulating PP has been shown to reflect vagal nerve activity (52). Whether the increase in PP in old age might be involved in the reduction in SG and glucose elimination rate is possible, but no evidences confirming such an assumption were found in this study, because circulating PP did not correlate to SG or to glucose elimination rate.
We conclude that, in carefully selected elderly (64 yr) and young (27 yr) subjects of both genders and with no difference in glucose tolerance between the groups, old age is associated with reduced SG, increased hepatic insulin extraction, and a reduced glucose sensitivity in the second phase of insulin secretion. Old age is also associated with high plasma PP levels but no change in plasma leptin or glucagon. We suggest that the impaired elimination of glucose in old subjects with maintained normal glucose tolerance is caused mainly by reduced SG and impaired second phase insulin secretion.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
Received March 23, 1998.
Revised June 3, 1998.
Accepted June 9, 1998.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  G. Pacini, M. Ahren, and B. Ahren Reappraisal of the intravenous glucose tolerance index for a simple assessment of insulin sensitivity in mice Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2009; 296(5): R1316 - R1324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Matveyenko, J. D. Veldhuis, and P. C. Butler Adaptations in pulsatile insulin secretion, hepatic insulin clearance, and {beta}-cell mass to age-related insulin resistance in rats Am J Physiol Endocrinol Metab, October 1, 2008; 295(4): E832 - E841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Chang, M. J. Smith, A. T. Galecki, C. J. Bloem, and J. B. Halter Impaired {beta}-Cell Function in Human Aging: Response to Nicotinic Acid-Induced Insulin Resistance J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3303 - 3309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Basu, C. Dalla Man, M. Campioni, A. Basu, G. Klee, G. Toffolo, C. Cobelli, and R. A. Rizza Effects of age and sex on postprandial glucose metabolism: differences in glucose turnover, insulin secretion, insulin action, and hepatic insulin extraction. Diabetes, July 1, 2006; 55(7): 2001 - 2014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Gennarelli, V. Rovei, R. F. Novi, J. Holte, F. Bongioanni, A. Revelli, G. Pacini, P. Cavallo-Perin, and M. Massobrio Preserved Insulin Sensitivity and {beta}-Cell Activity, but Decreased Glucose Effectiveness in Normal-Weight Women with the Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3381 - 3386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Utzschneider, D. B. Carr, R. L. Hull, K. Kodama, J. B. Shofer, B. M. Retzlaff, R. H. Knopp, and S. E. Kahn Impact of Intra-Abdominal Fat and Age on Insulin Sensitivity and {beta}-Cell Function Diabetes, November 1, 2004; 53(11): 2867 - 2872. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Utzschneider, D. B. Carr, S. M. Barsness, S. E. Kahn, and R. S. Schwartz Diet-Induced Weight Loss Is Associated with an Improvement in {beta}-Cell Function in Older Men J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2704 - 2710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zamboni, E. Zoico, F. Fantin, M. P. Panourgia, V. Di Francesco, P. Tosoni, B. Solerte, R. Vettor, and O. Bosello Relation Between Leptin and the Metabolic Syndrome in Elderly Women J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2004; 59(4): M396 - M400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Basu, E. Breda, A. L. Oberg, C. C. Powell, C. Dalla Man, A. Basu, J. L. Vittone, G. G. Klee, P. Arora, M. D. Jensen, et al. Mechanisms of the Age-Associated Deterioration in Glucose Tolerance: Contribution of Alterations in Insulin Secretion, Action, and Clearance Diabetes, July 1, 2003; 52(7): 1738 - 1748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Chang and J. B. Halter Aging and insulin secretion Am J Physiol Endocrinol Metab, January 1, 2003; 284(1): E7 - E12. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Isidori, F. Strollo, M. Morè, M. Caprio, A. Aversa, C. Moretti, G. Frajese, G. Riondino, and A. Fabbri Leptin and Aging: Correlation with Endocrine Changes in Male and Female Healthy Adult Populations of Different Body Weights J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1954 - 1962. [Abstract] [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
