Introduction

Diabetes increases in prevalence in older populations. One quarter of adults aged 65 years and over in the United States has diabetes (CDC). Further, approximately half of the older adult population has prediabetes (CDC). Large population studies also suggest that many older adults have undiagnosed diabetes (Cowie et al., 2009). Diabetes prevalence is also increased among older adults with physical frailty (Walston et al., 2002). In fact, there is evidence of an association between insulin resistance and physical frailty even in those without diabetes (Barzilay et al., 2007).  

Impact of Glucose Metabolism on Frailty 

Frailty alters glucose-insulin dynamics in a manner that suggests the presence of increased insulin resistance in frail individuals. Such a mechanism would impact dynamic handling of nutrients more than stable baseline conditions. Both insulin levels and peak glucose levels were higher in physically frail women after a 2-hour oral glucose tolerance test, although the fasting levels had not been different (Kalyani et al., 2012; Goulet et al., 2009). Similarly, frail older adults who underwent a mixed meal test had a more exaggerated and prolonged glucose response than non-frail controls (Serra-Prat et al., 2009).  Although weight loss is associated with the development of physical frailty, in cross sectional studies, those with physical frailty are more like to be obese than non-frail individuals (Hubbard et al., 2010).

Insulin resistance may in fact be a risk factor for frailty. In the Women’s Health and Aging Study, older women who at baseline were in the highest A1C category (≥8%) had a 3-fold greater risk of developing frailty during follow up compared to otherwise similar women the lowest A1C category (<5.5%) (Blaum et al., 2009).   

Research should consider the potential for bidirectional interactions between insulin resistance and frailty. For example, frail older adults have a higher burden of inflammatory markers that may impact glucose metabolism by changing adipose function. High blood glucose levels may, in turn, further activate pathways that cause muscle catabolism, worsening the declines in grip strength and gait speed which are key features of physical frailty. 

Applying Knowledge of Frailty to Treatment of Diabetes  

The multifactorial nature of this relationship suggests that interventions on either side may improve both. Future studies are needed to investigate whether interventions that improve frailty status may also reduce the burden of diabetes and, conversely, whether glucose-lowering treatments may prevent frailty in older adults.

References:

  • Center for Disease Control. National Diabetes Statistics Report 2020: Estimates of Diabetes and Its Burdens in the United States
  • Cowie CC, et al Full accounting of diabetes and pre-diabetes in the U.S. population in 1988–1994 and 2005–2006 Diabetes Care 2009: 32:287–294
  • J. Walston, M.A. McBurnie, A. Newman, et al., Cardiovascular Health Study. Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Arch Intern Med, 162 (2002), pp. 2333-2341
  • J.I. Barzilay, C. Blaum, T. Moore, et al. Insulin resistance and inflammation as precursors of frailty: the Cardiovascular Health Study. Arch Intern Med, 167 (2007), pp. 635-641
  • R.R. Kalyani, R. Varadhan, C.O. Weiss, et al. Frailty Status and Altered Glucose-Insulin Dynamics. J Gerontol A Biol Sci Med Sci. 2012 Dec;67(12):1300-6. doi: 10.1093/gerona/glr141
  • E.D. Goulet, A. Hassaine, I.J. Dionne, et al. Frailty in the elderly is associated with insulin resistance of glucose metabolism in the postabsorptive state only in the presence of increased abdominal fat. Exp Gerontol, 44 (2009), pp. 740-744
  • M. Serra-Prat, E. Palomera, P. Clave, et al. Effect of age and frailty on ghrelin and cholecystokinin responses to a meal test. Am J Clin Nutr, 89 (2009), pp. 1410-1417
  • R.E. Hubbard, I.A. Lang, D.J. Llewellyn, et al. Frailty, body mass index, and abdominal obesity in older people. J Gerontol A Biol Sci Med Sci, 65 (2010), pp. 377-381
  • C.S. Blaum, Q.L. Xue, J. Tian, et al. Is hyperglycemia associated with frailty status in older women? J Am Geriatr Soc, 57 (2009), pp. 840-847.