Maintaining physiological state for exceptional survival: What is the normal level of blood glucose and does it change with age?

Abstract

The levels of blood glucose (BG) in humans tend to increase with age deviating from the norm specified for the young adults. Such elevation is often considered as a factor contributing to an increase in risks of disease and death. The proper use of intervention strategies coping with or preventing consequences of BG elevation requires understanding the roles of external forces and intrinsic senescence in this process. To address these issues, we performed analyses of longitudinal data on BG collected in the Framingham Heart Study using methods of descriptive statistics and statistical modeling. The approach allows us to separate effects of persistent external disturbances from "normal" aging-related changes due to the senescence process. We found that the BG level corresponding to the lowest mortality risk tends to increase with age. The changes in the shape of the mortality risk with age indicate the aging-related decline in resistance to stresses affecting the BG level. The results show that analyzing longitudinal data using advanced methods may substantially increase our knowledge on factors and mechanisms responsible for aging-related changes in humans.

Fig. 1

Average trajectories of blood glucose for females and males in the FHS (pooled data for exams 1–25).

Fig. 2

Average trajectories of blood glucose for long-lived and short-lived females and males in the FHS (pooled data for exams 1–25; “LS” means lifespan).

Fig. 3

Average trajectories of blood glucose for long-lived and short-lived non-diabetic females and males in the FHS (pooled data for exams 1–25; “LS” means lifespan).

Fig. 4

The quadratic hazard model applied to data on blood glucose in the FHS: Estimates of the mean allostatic states $(f_t^1)$, the physiological norms (f_t), and the quadratic hazard terms $({\mu }_t^{11}\text{and}{\mu }_t^{12})$ for different ages (t).

Fig. 5

Age-specific ranges of values of BG with minimal mortality rates (upper panels) and minimal relative risks (RR) of death (lower panels) estimated for females and males in the FHS data using the quadratic hazard model. The labels on the lines denote the values of an increase in the mortality rate (respectively, in the relative risk) compared to the minimal values at respective ages (f_t). The dotted lines correspond to the age trajectory of the normal level of BG, f_t, approximated by a linear function.

Fig. 6

The norm of blood glucose for females and males in the FHS estimated by a semiparametric extended Cox-type model.