In this Editorial I will try to highlight some new insights in the pathophysiology of various aspects of the elderly male diabetic, with special emphasis on what affects the management of this growing population.
What causes the increased incidence of type 2 diabetes in aging males?
The incidence of type 2 diabetes increases with aging. At age 40 the prevalence is about 3–5%, whereas at age 60 it has increased to 20–30%. Aged individuals also show a marked increase in the incidence of impaired glucose tolerance, even in the absence of the diagnosis of type 2 diabetes.
What accounts for this almost 10-fold increase? Insulin resistance seems to be the predominant factor, though impairment in beta cell function is also seen in the aging population. In a recent study, Imbeault et al. demonstrated that visceral obesity was the major factor in the worsening of glucose tolerance with aging Citation[1]. Maneatis noted that when adjustments were made for body weight and physical activity, there was no significant association between age and glucose tolerance Citation[2]. Thus, age only accounts for 6% of the effect on glucose intolerance in males, whereas body weight and physical activity were the major etiological factors in the increased incidence of diabetes with aging Citation[3]. Obesity is not the only hallmark of the insulin resistance seen in elderly males with type 2 diabetes. Furthermore, elderly men may have less obesity; the distribution of the fat is more important. Abdominal fat accumulation, even in the absence of severe obesity, is associated with increased insulin resistance and type 2 diabetes Citation[4]. Thus, even the use of waist circumference may not be useful, since it measures overall obesity more than intra-abdominal fat deposition.
Why are many aging males with type 2 diabetes still undiagnosed?
According to the National Health and Nutrition Examination Survey (NHANES III), diabetes is diagnosed in ∼13% of people between the ages of 60–75 and undiagnosed in ∼10% of the same population. This was particularly prevalent in men and individuals with hypertension, high BMIs and large waist circumference Citation[5]. One of the factors is that the American Diabetes Association's criteria for the diagnosis still rely on fasting blood glucose. In many individuals, the first abnormality to appear is an elevated post-meal blood glucose, which is commonly missed unless a GTT or 2 hour post-glucose/meal blood glucose is used. Thus, the exclusive use of fasting blood glucose for screening is being debated. Diagnosing type 2 diabetes or impaired glucose tolerance in elderly individuals has substantial public health implications and implications for the individual Citation[6]. Kanaya et al. have included the measurement of serum triglycerides as an added screening criterion, since hypertriglyceridemia is commonly found in individuals with metabolic syndrome, prediabetes and type 2 diabetes Citation[7].
What are the consequences of diabetes in the aging male?
Besides the usual complications of diabetes that include microvascular and macrovascular diseases such as retinopathy, nephropathy and cardiovascular disorders, cognitive abilities are affected more by diabetes than by aging alone. Thus, the presence of diabetes over a four year period significantly affected cognitive testing that was not due to hypertension or due to medications Citation[8]. The impact of these findings on the quality of life in elderly diabetic patients needs to be seriously considered when managing these patients in the home environment.
What important hormonal changes are specific to elderly men?
In a group of men over the age of 60, low testosterone levels were associated with a reduction in mitochondrial function, which can lead to abnormalities in fat metabolism, and impaired insulin action, which leads to a worsening of the glucose tolerance and frank diabetes, and suggests that androgen replacement therapy may indeed improve the metabolic syndrome and/or type 2 diabetes seen in elderly men. These findings need, of course, to be verified by further studies Citation[9].
How do elderly diabetics respond to hypoglycemia?
When older diabetic men, especially those on sulfonylureas and/or insulin, develop hypoglycemia, they are less likely to experience prior warning symptoms as the blood glucose falls. This is due to impaired cognitive impairment during the hypoglycemia Citation[10].
Conclusion
In conclusion, the primary care physician and geriatrician should be aware of many of the differences between young diabetics versus elderly diabetic males, and between elderly non-diabetics and the elderly male diabetic. As outlined above, the differences are critical to both diagnosis as well as management of this growing population.
References
- Imbeault P, Prins J B, Stolic M, Russell A W, O'Moore-Sullivan T, Després J P, Bouchard C, Tremblay A. Aging per se does not influence glucose homeostasis: in vivo and in vitro evidence. Diabetes Care 2003; 26: 480–484
- Maneatis T, Condie R, Reaven G M. Effect of age on plasma glucose and insulin responses to a test mixed meal. J Am Geriatr Soc 1982; 30: 178–182
- Reaven G. Age and glucose intolerance: effect of fitness and fatness. Diabetes Care 2003; 26: 539–540
- Goodpaster B H, Krishnaswami S, Resnick H, Kelley D E, Haggerty C, Harris T B, Schwartz A V, Kritchevsky S, Newman A B. Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care 2003; 26: 372–379
- Harris M I, Flegal K M, Cowie C C, Eberhardt M S, Goldstein D E, Little R R, Wiedmeyer H -M, Byrd-Holt D D. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in US adults: the third national health and nutrition examination survey, 1988–1994. Diabetes Care 1998; 21: 518–524
- Resnick H E, van Eijk J TM, Bauer D C, Newman A B, Pahor M, Franse L V, Di Bari M, Shorr R I. type 2 diabetes in older well-functioning people: who is undiagnosed? Data from the health, aging, and body composition study. Diabetes Care 2001; 24: 2065–2070
- Kanaya A K, Wassel Fyr C L, de Rekeneire N, Shorr R I, Schwartz A V, Goodpaster B H, Newman A B, Harris T, Barrett-Connor E. Predicting the development of diabetes in older adults: the derivation and validation of a prediction rule. Diabetes Care 2005; 28: 404–408
- Fontbonne A, Berr C, Ducimetière P, Alpérovitch A. Changes in cognitive abilities over a 4-year period are unfavorably affected in elderly diabetic subjects: results of the epidemiology of vascular aging study. Diabetes Care 2001; 24: 366–370
- Pitteloud N, Mootha V K, Dwyer A A, Hardin M, Lee H, Eriksson K -F, Tripathy D, Yialamas M, Groop L, Elahi D, et al. Relationship Between Testosterone Levels, Insulin Sensitivity, and Mitochondrial Function in Men. Diabetes Care 2005; 28: 1636–1642
- Matyka K, Evans M, Lomas J, Cranston I, Macdonald I, Amiel S A. Altered hierarchy of protective responses against severe hypoglycemia in normal aging in healthy men. Diabetes Care 1997; 20: 135–141