Mechanisms of the age-associated deterioration in glucose tolerance: contribution of alterations in insulin secretion, action, and clearance.

@article{Basu2003MechanismsOT,
  title={Mechanisms of the age-associated deterioration in glucose tolerance: contribution of alterations in insulin secretion, action, and clearance.},
  author={Rita Basu and Elena Breda and Ann L. Oberg and Claudia C. Powell and Chiara Dalla Man and Ananda Basu and Janet L. Vittone and George G. Klee and Puneet S. Arora and Michael D. Jensen and Gianna Toffolo and Claudio Cobelli and R. Rizza},
  journal={Diabetes},
  year={2003},
  volume={52 7},
  pages={
          1738-48
        }
}
Glucose tolerance decreases with age. For determining the cause of this decrease, 67 elderly and 21 young (70.1 +/- 0.7 vs. 23.7 +/- 0.8 years) participants ingested a mixed meal and received an intravenous injection of glucose. Fasting glucose and the glycemic response above basal were higher in the elderly than in the young participants after either meal ingestion (P < 0.001) or glucose injection (P < 0.01). Insulin action (Si), measured with the meal and intravenous glucose tolerance test… 

Figures and Tables from this paper

Effects of Age and Sex on Postprandial Glucose Metabolism

Age and sex impact on insulin secretion, insulin action, hepatic insulin extraction, and glucose effectiveness, resulting in substantial differences in the regulation of postprandial glucose metabolism in men and women and in elderly and young subjects is determined.

Effect of lowering postprandial hyperglycemia on insulin secretion in older people with impaired glucose tolerance.

Short-term improvement of chronic hyperglycemia does not reverse beta-cell dysfunction in older people with IGT, and measures of insulin secretion and acute insulin response to intravenous glucose remained unchanged and impaired.

Pathogenesis of Pre-Diabetes

It is concluded that postprandial hyperglycemia in individuals with early diabetes is due to lower rates of glucose disappearance rather than increased meal appearance or impaired suppression of EGP, regardless of their fasting glucose.

Decrease in glucose-stimulated insulin secretion with aging is independent of insulin action.

It is suggested that prolonged hyperglycemic stimulation can be a tool to identify functional defects in insulin secretion, particularly in the context of the hyperbolic relationship with insulin action, in elderly subjects or those at risk for type 2 diabetes.

Effects of Nonglucose Nutrients on Insulin Secretion and Action in People With Pre-Diabetes

Whereas glucose-induced insulin secretion is impaired in people with abnormal glucose tolerance, nonglucose nutrient–induced secretion is intact, suggesting that a glucose-specific defect in the insulin secretory pathway is an early event in the evolution of type 2 diabetes.

Effect of Aging on Glucose Homeostasis

Insulin secretion normally decreases at a rate of ∼0.7% per year with aging; this decrease in β-cell function is accelerated about two-fold in people with impaired glucose tolerance—first phase to a greater extent than second phase; aging per se has no effect on insulin sensitivity independent of changes in body composition.

The Influence of Cortisol and Age Differences on the Development of Insulin Resistance and Dyslipidemia in Euthyroid Patients

Investigating the influence of serum cortisol and age differences on insulin resistance and the associated lipid disturbances in euthyroid adults found there was significant correlation between cortisol and insulin resistance at older ages.

Factors influencing insulin sensitivity during hyperinsulinemic-euglycemic clamp in healthy Korean male subjects

The results suggest that age is not a critical determinant of insulin sensitivity, while fasting insulin and C-peptide levels, OGTT 2-hour glucose level, and Matsuda index are predictable markers of insulinensitivity in healthy Koreans.
...

References

SHOWING 1-10 OF 57 REFERENCES

Influence of Aging on Hepatic and Peripheral Glucose Metabolism in Humans

It is concluded that age-related glucose intolerance develops despite slowed glucose absorption and is characterized by delays in the initial rise in insulin levels, the suppression of HGO, and the rise in peripheral glucose uptake, which is predominantly the result of impaired peripheral glucose utilization.

Influence of Age on Clearance of Insulin in Man

The results indicate the value of evaluating C1 as one determinant of circulating insulin level in states of abnormal insulin physiology and reconcile the discrepancy between in vivo and in vitro studies of glucose-induced insulin release.

Age-related reduction in glucose elimination is accompanied by reduced glucose effectiveness and increased hepatic insulin extraction in man.

  • B. AhrénG. Pacini
  • Medicine, Biology
    The Journal of clinical endocrinology and metabolism
  • 1998
SG seems most related to age-dependent impairment of glucose elimination, whereas leptin, glucagon, and PP do not seem to contribute, whereas SI and first-phase insulin secretion seem normal.

Relationship between glucose tolerance and glucose-stimulated insulin response in 65-year-olds.

Aberrations in early and late phase glucose-stimulated insulin responses appear to be present in older subjects with even mildly decreased glucose tolerance, at least up to age 70 years.

Glucose Intolerance and Aging: Evidence for Tissue Insensitivity to Insulin

In conclusion, under the present experimental conditions, employing intravenous glucose and/or insulin, impaired tissue sensitivity to insulin is the primary factor responsible for the decrease in glucose tolerance observed with advancing age.

Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age.

In healthy older men up to the age of 73 yr, insulin sensitivity and glucose tolerance are affected primarily by the regional body fat distribution, not age, obesity, or VO2max.

Pathogenesis of age-related glucose intolerance in man: insulin resistance and decreased beta-cell function.

The studies suggest that the diminished glucose tolerance of aging in normal weight men has multifactorial causality, and both beta-cell dysfunction and insulin resistance are important.

The effect of age on insulin response and glucose utilization during four hyperglycemic plateaus

Effects of Aging on Insulin Secretion

Physiological hyperinsulinemia of aging is caused by increased insulin secretion rather than decreased insulin clearance as demonstrated under basal conditions and in response to mixed meals.

Characterization of the insulin resistance of aging.

The studies suggest that aging may be associated with a postreceptor defect in insulin action manifested by decreased whole-body tissue sensitivity to insulin without a change in tissue responsiveness.
...