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Carbohydrate Metabolism

Jeffrey B. Halter

10.1002/cphy.cp110107

Source: Supplement 28: Handbook of Physiology, Aging

Originally published: 1995

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Epidemiology of Age‐Related Changes of Carbohydrate Metabolism
2 Mechanisms for Age‐Related Changes of Carbohydrate Metabolism
2.1 Normal Regulation of Glucose Metabolism
2.2 Effects of Aging
2.3 Confounding Factors
3 Diabetes Mellitus
3.1 Mechanisms for Development of Non‐Insulin‐Dependent Diabetes Mellitus
3.2 Metabolic Consequences of Diabetes Mellitus
3.3 Long‐Term Consequences of Diabetes Mellitus
Figure 1. Figure 1.

Plasma glucose (upper) and insulin (lower) levels before and following oral ingestion of 100 g of glucose in healthy old (n = 18) and young (n = 18) subjects matched for relative body weight and socioeconomic group. Subjects were eating an ad libitum diet that included approximately 10% fewer total calories and 15% fewer carbohydrate calories in the old subjects.

From Chen et al. 31 with permission
Figure 2. Figure 2.

Model illustrating key features of the feedback control system for regulation of steady‐state plasma glucose levels. A key feature of this system is that changes of hormone secretion or hormone sensitivity will be modulated to minimize change in the glucose concentration and to maintain peripheral glucose utilization.

From Pfeifer et al. 159 with permission
Figure 3. Figure 3.

Comparison of serum glucose levels and insulin secretion rates estimated by analysis of C‐peptide kinetics in elderly (solid circle, n = 10) and young (open circle, n = 6) healthy subjects. Studies were carried out during a stepped I.V. glucose infusion designed to match circulating glucose levels between groups and to achieve levels similar to those during an OGTT. While no differences were observed in absolute insulin secretion rates between groups, the elderly group had a lower relative increase of insulin secretion.

From Gumbiner et al. 72 with permission
Figure 4. Figure 4.

Comparison of the acute insulin response (AIR) to a 5‐g I.V. arginine bolus as a function of the plasma glucose level in exercise‐trained older subjects (solid circle, n = 14) and exercise‐trained younger subjects (open square, n = 11). Short‐term glucose infusions were used to achieve elevated circulating glucose levels in subjects. *P < 0.01, **P < 0.005 for comparison of AIRs at similar glucose levels between old and young subjects. Both subject groups had similar sensitivities to insulin as measured during a frequently sampled IVGTT protocol.

From Kahn et al. 95 with permission
Figure 5. Figure 5.

Comparison of dose–response curves for insulin levels achieved during a euglycemic clamp protocol vs. glucose infusion rate needed to maintain euglycemia in healthy, nonobese young (n = 17) and old (n = 10) subjects. Experimental data extrapolated to known basal hepatic glucose production rates for young and old subjects. Glucose infusion rates were similar in young and old at the highest insulin level tested but significantly lower in the old at the low insulin infusion rate.

From Rowe et al. 182 with permission
Figure 6. Figure 6.

Top: Comparison of glucose transport activities, as measured by uptake of 2 deoxyglucose (2dG), in epitrochlearis muscle from female Long‐Evans rats of varying age. *P < 0.01, and †P < 0.001 vs. muscles from 1‐month old rats. Values are mean ± standard error for five to eight muscles per group, except for basal uptake in 1‐month‐old rats where n = 14. Bottom: Glut 4 immunoreactive protein content compared in homogenates of epitrochlearis muscle from rats of varying age. Values are mean ± standard error for nine to ten muscles per group. *P < 0.05 vs. muscles from 1‐month‐ old rats.

From Gulve et al. 71 with permission
Figure 7. Figure 7.

Comparison of plasma glucose levels during an I.V. glucose tolerance test in healthy young (n = 7) and old (n = 7) subjects. Upper panel: IVGTT results in the absence of infusion of epinephrine (EPI). Lower panel: The slower decline of glucose levels in the old subject group during EPI infusion. Circulating EPI levels were comparable in both subject groups during EPI infusion.

From Morrow et al. 136 with permission
Figure 8. Figure 8.

Comparison of effects of increasing doses of epinephrine in healthy young (n = 7) and old (n = 7) subjects. SG is a measure of glucose effectiveness obtained from minimal model analysis of IVGTT results. Epinephrine infusion reduced SG values in both subject groups. This effect was greater in the old than the young.

From Morrow et al. 136 with permission
Figure 9. Figure 9.

Summary of factors which may contribute to the high rate of diabetes mellitus and impaired glucose tolerance among elderly people.

From Halter 75 with permission
Figure 10. Figure 10.

Effect of a 6‐month program of exercise training (ET) on insulin sensitivity in 13 older subjects. Insulin sensitivity was determined from minimal model analysis of frequently sampled IVGTT.

From Kahn et al. 94 with permission
Figure 11. Figure 11.

Regression analysis of tissue sensitivity to insulin (SI) in relation to mean arterial blood pressure (MABP), body mass index (BMI), and plasma norepinephrine level for healthy normotensive and hypertensive subjects aged 38–78 yr, adjusted for co‐factor of blood pressure group. Dashed line is the regression line for normotensive subjects; solid line, for hypertensive subjects. In both groups, SI was inversely related to blood pressure and BMI but not to plasma norepinephrine.

From Supiano et al. 201 with permission
Figure 12. Figure 12.

Prevalence of NIDDM by age of onset among a group of 112 African Americans with or without the Z + 4 glucokinase allele (log‐survival test, P = 0.0014).

From Chiu et al. 32 with permission
Figure 13. Figure 13.

Theoretical model describing the feedback effect of insulin resistance in individuals with normal pancreatic β‐cell function, resulting in maintenance of euglycemia. In contrast, individuals with impaired pancreatic β‐cell function are unable to adapt to insulin resistance, resulting in a vicious cycle in which hyperglycemia develops and leads to further deterioration of β‐cell function and more severe insulin resistance.
Figure 14. Figure 14.

Comparison of the increase from baseline of plasma glucose levels during infusion of epinephrine (EPI) in patients with NIDDM (n = 9) and normal subjects (n = 20). In addition to having a greater overall hyperglycemic response, the first significant increase of plasma glucose (*) occurred earlier in the NIDDM patients.

From Ortiz‐Alonso et al. 152 with permission
Figure 15. Figure 15.

General scheme for the process of nonenzymatic glycosylation and subsequent formation of advanced glycosylation end‐products resulting from the Maillard reaction.

From Monnier 131 with permission
Figure 16. Figure 16.

Relationship between age and level of pentosidine in collagen among nondiabetic subjects from whom skin samples were obtained at autopsy. The regression line for this relationship and 95% confidence interval are shown (y = 0.002 x2 + 0.214x + 5.69, r = 0.86).

From Sell and Monnier 191 with permission


Figure 1.

Plasma glucose (upper) and insulin (lower) levels before and following oral ingestion of 100 g of glucose in healthy old (n = 18) and young (n = 18) subjects matched for relative body weight and socioeconomic group. Subjects were eating an ad libitum diet that included approximately 10% fewer total calories and 15% fewer carbohydrate calories in the old subjects.

From Chen et al. 31 with permission


Figure 2.

Model illustrating key features of the feedback control system for regulation of steady‐state plasma glucose levels. A key feature of this system is that changes of hormone secretion or hormone sensitivity will be modulated to minimize change in the glucose concentration and to maintain peripheral glucose utilization.

From Pfeifer et al. 159 with permission


Figure 3.

Comparison of serum glucose levels and insulin secretion rates estimated by analysis of C‐peptide kinetics in elderly (solid circle, n = 10) and young (open circle, n = 6) healthy subjects. Studies were carried out during a stepped I.V. glucose infusion designed to match circulating glucose levels between groups and to achieve levels similar to those during an OGTT. While no differences were observed in absolute insulin secretion rates between groups, the elderly group had a lower relative increase of insulin secretion.

From Gumbiner et al. 72 with permission


Figure 4.

Comparison of the acute insulin response (AIR) to a 5‐g I.V. arginine bolus as a function of the plasma glucose level in exercise‐trained older subjects (solid circle, n = 14) and exercise‐trained younger subjects (open square, n = 11). Short‐term glucose infusions were used to achieve elevated circulating glucose levels in subjects. *P < 0.01, **P < 0.005 for comparison of AIRs at similar glucose levels between old and young subjects. Both subject groups had similar sensitivities to insulin as measured during a frequently sampled IVGTT protocol.

From Kahn et al. 95 with permission


Figure 5.

Comparison of dose–response curves for insulin levels achieved during a euglycemic clamp protocol vs. glucose infusion rate needed to maintain euglycemia in healthy, nonobese young (n = 17) and old (n = 10) subjects. Experimental data extrapolated to known basal hepatic glucose production rates for young and old subjects. Glucose infusion rates were similar in young and old at the highest insulin level tested but significantly lower in the old at the low insulin infusion rate.

From Rowe et al. 182 with permission


Figure 6.

Top: Comparison of glucose transport activities, as measured by uptake of 2 deoxyglucose (2dG), in epitrochlearis muscle from female Long‐Evans rats of varying age. *P < 0.01, and †P < 0.001 vs. muscles from 1‐month old rats. Values are mean ± standard error for five to eight muscles per group, except for basal uptake in 1‐month‐old rats where n = 14. Bottom: Glut 4 immunoreactive protein content compared in homogenates of epitrochlearis muscle from rats of varying age. Values are mean ± standard error for nine to ten muscles per group. *P < 0.05 vs. muscles from 1‐month‐ old rats.

From Gulve et al. 71 with permission


Figure 7.

Comparison of plasma glucose levels during an I.V. glucose tolerance test in healthy young (n = 7) and old (n = 7) subjects. Upper panel: IVGTT results in the absence of infusion of epinephrine (EPI). Lower panel: The slower decline of glucose levels in the old subject group during EPI infusion. Circulating EPI levels were comparable in both subject groups during EPI infusion.

From Morrow et al. 136 with permission


Figure 8.

Comparison of effects of increasing doses of epinephrine in healthy young (n = 7) and old (n = 7) subjects. SG is a measure of glucose effectiveness obtained from minimal model analysis of IVGTT results. Epinephrine infusion reduced SG values in both subject groups. This effect was greater in the old than the young.

From Morrow et al. 136 with permission


Figure 9.

Summary of factors which may contribute to the high rate of diabetes mellitus and impaired glucose tolerance among elderly people.

From Halter 75 with permission


Figure 10.

Effect of a 6‐month program of exercise training (ET) on insulin sensitivity in 13 older subjects. Insulin sensitivity was determined from minimal model analysis of frequently sampled IVGTT.

From Kahn et al. 94 with permission


Figure 11.

Regression analysis of tissue sensitivity to insulin (SI) in relation to mean arterial blood pressure (MABP), body mass index (BMI), and plasma norepinephrine level for healthy normotensive and hypertensive subjects aged 38–78 yr, adjusted for co‐factor of blood pressure group. Dashed line is the regression line for normotensive subjects; solid line, for hypertensive subjects. In both groups, SI was inversely related to blood pressure and BMI but not to plasma norepinephrine.

From Supiano et al. 201 with permission


Figure 12.

Prevalence of NIDDM by age of onset among a group of 112 African Americans with or without the Z + 4 glucokinase allele (log‐survival test, P = 0.0014).

From Chiu et al. 32 with permission


Figure 13.

Theoretical model describing the feedback effect of insulin resistance in individuals with normal pancreatic β‐cell function, resulting in maintenance of euglycemia. In contrast, individuals with impaired pancreatic β‐cell function are unable to adapt to insulin resistance, resulting in a vicious cycle in which hyperglycemia develops and leads to further deterioration of β‐cell function and more severe insulin resistance.



Figure 14.

Comparison of the increase from baseline of plasma glucose levels during infusion of epinephrine (EPI) in patients with NIDDM (n = 9) and normal subjects (n = 20). In addition to having a greater overall hyperglycemic response, the first significant increase of plasma glucose (*) occurred earlier in the NIDDM patients.

From Ortiz‐Alonso et al. 152 with permission


Figure 15.

General scheme for the process of nonenzymatic glycosylation and subsequent formation of advanced glycosylation end‐products resulting from the Maillard reaction.

From Monnier 131 with permission


Figure 16.

Relationship between age and level of pentosidine in collagen among nondiabetic subjects from whom skin samples were obtained at autopsy. The regression line for this relationship and 95% confidence interval are shown (y = 0.002 x2 + 0.214x + 5.69, r = 0.86).

From Sell and Monnier 191 with permission
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Article Title: Carbohydrate Metabolism
 

How to Cite

Jeffrey B. Halter. Carbohydrate Metabolism. Compr Physiol 2011, Supplement 28: Handbook of Physiology, Aging: 119-145. First published in print 1995. doi: 10.1002/cphy.cp110107