Oral glucose tolerance test in the assessment of glucose-tolerance in the elderly people
SIR—Assessment of glucose tolerance in the elderly has been in the focus of research due to the increased incidence of diabetes type 2 in this population. Approximately 13% of adults older then 70 years have diabetes, and 11% of adults between the ages of 60 and 74 years remain undiagnosed [1]. Factors that may predispose to glucose intolerance in the aged are weight gain, decreased physical fitness, decreased insulin secretion and lack of glucagon suppression. The Baltimore Longitudinal Study of Aging documented a prominent decline in glucose tolerance after the age of 60 years with both fasting and postprandial concentrations being higher in elderly compared to younger subjects [2]. Although the prevalence of diabetes is highest among people older than 65 years of age, the prevalence of obesity in this age group is only 14%, compared to 24% for men and women in their fifties [3]. Obesity is a marker of insulin resistance. However, it appears that ageing may be associated with dissociation between obesity and glucose intolerance. Senescence, per se, is associated with a progressive decline in insulin clearance and a subtle decrease in insulin secretion [4]. It appears that older individuals do not have the ability to increase insulin secretion to the degree necessary to prevent glucose intolerance. Insulin-mediated glucose disposal also decreases with age and correlates significantly with the decreased physical activity in the elderly. Finally, irregularities in glucagon secretion may initiate glucose intolerance. Lack of suppression of glucagon secretion in the elderly may cause hyperglycaemia by increasing hepatic glucose release [5]. Therefore, the aim of the present study was to assess glucose tolerance in healthy, non-obese, moderately active elderly subjects.Forty-eight subjects aged 60–90 years, were recruited from the outpatient geriatric clinic of the ‘Zvezdara’ University Hospital during their regular annual visit. All subjects underwent a medical evaluation which included a medical history. Subjects with cardiovascular, renal or hepatic disease, diabetes, endocrine disorders, or those on medication that could influence carbohydrate metabolism were excluded from the study. All participants were moderately active, meaning that they had two exercise sessions of 30 min/week or walked at least 1 km daily. They were non-obese, according to the body mass index (BMI) with less than 25 kg/m2. All subjects had their waist circumference measured. A greater waist circumference, a marker of metabolic syndrome, was not an exclusion criterion. All participants were non-smokers and consumed alcohol moderately (less than 2 alcohol units/day). The control group consisted of 45 non-obese healthy health care workers in the age group 30–45 years. Each participant gave an informed consent for participating in the study. The study was approved by the ethical committee of the ‘Zvezdara’ University Hospital.
A 75-g oral glucose tolerance test (OGTT) was performed in the morning after an overnight fast. Blood samples were collected from the venous catheter placed in the antecubital vein at 0, 60 and 120 min for glucose, insulin, c-peptide and glucagon levels. Participants remained seated for the entire testing period. Plasma glucose was measured using an automated glucose oxidase reaction (Glucose Analyser, Ames). Plasma samples were centrifuged at 4°C, separated and stored at –20°C until assay. Plasma insulin was determined by a commercially available radioimmuno-assay (RIA) kit (Pharmacia, Uppsala, Sweden, normal reference range 0–20 mU/l). Plasma c-peptide was measured by RIA kit provided by Behring (normal reference range 0.3–0.9 nmol/l). Plasma glucagon concentrations were measured by RIA by use of reagents purchased from Novo Nordisk (normal reference range 50–220 pgr/ml).
All analyses were done with the use of the statistical software package SPSS, version 10.0. Differences in baseline characteristics between elderly and control subjects were tested by Student's t-test. Pearson's correlation coefficients were calculated to evaluate the relation between age or waist circumference and glucose or hormone levels during OGTT. Linear regression analysis was performed for variables with significant relationship. Data were presented as mean ± SD; a P value <0.05 was considered statistically significant.
Physical characteristics of subjects are presented in Table 1. A significant difference was observed in the waist circumference between the elderly and younger subjects, although BMI and weight were not significantly different. The rise in blood glucose levels following an OGTT was not significantly different in the 1st hour, but was significantly higher in the 2nd hour in the group of elderly subjects. The response was, however, within normal limits according to the WHO criteria [6] indicating normal glucose tolerance in both elderly and control subjects. Insulin response during OGTT was significantly lower in elderly subjects in the 1st hour. During the 2nd hour, insulin levels declined significantly in both groups, but less so in the group of control subjects (Table 1). Hence, insulin levels were significantly lower in the 1st hour and significantly higher in the 2nd hour of OGTT in elderly subjects. C-peptide levels increased significantly in both groups, but less so in the elderly in the 1st hour of OGTT. C-peptide levels were similar in elderly and younger subjects at 120 min, but the fall in c-peptide levels from 60 to 120 min was greater in younger subjects, again, maybe indirectly indicating insulin resistance. Fasting serum glucagon levels were significantly higher in the elderly. They remained significantly higher and unsuppressed during the OGTT in the group of elderly subjects.
|
A significant correlation was observed between waist circumference and insulin level at 60 min (R = 0.301;P = 0.013), age and glucose level at 120 min (R = 0.403;P = 0.001), age and insulin level at 60 (R = –0.339;P = 0.005) and 120 min (R = 0.341;P = 0.004), age and c-peptide level at 60 min (R = –0.378;P = 0.001), and age and glucagon level at 60 (R = 0.345;P = 0.004) and 120 min (R = 0.257;P = 0.034). Linear regression analysis revealed a strong relation of waist circumference with insulin level at 60 min, age with glucose level at 120 min, age with insulin level at 60 and 120 min, age with c-peptide level at 60 min, and age with glucagon level at 60 and 120 min.
Our study has shown that maintenance of glucose tolerance in non-obese healthy elderly subjects differs from that in non-obese younger subjects. Higher fasting and stimulated glucose levels during OGTT may be the consequence of abdominal obesity or hormonal changes: lack of suppression of glucagon in the presence of relative insulin insufficiency.
Age-related increase in adiposity and decrease in physical activity are related to decreased insulin action with ageing [7]. Elderly participants in our study were moderately physically active, but had a significantly greater waist circumference than younger subjects. This may indicate greater visceral obesity, in spite of normal weight. Goodpaster et al. [8] have shown in the Pittsburgh Study that regional adipose tissue distribution is the key determinant of insulin resistance. That visceral obesity, more than age, per se, correlates with glucose intolerance, has also been shown in the study of Imbeault et al. [9]. Hence, normal weight elderly with abdominal obesity, such as our group, may still be at an increased risk for developing diabetes. Higher fasting and stimulated glucose values could indicate insulin resistance, which was not evaluated in our study. Imbeault et al. [9] also noted higher fasting plasma glucose levels in elderly, even after correction for visceral fat accumulation, suggesting that other factors contribute to the impaired glucose homeostasis in ageing.
Although in line with the present WHO criteria for normal glucose tolerance, the measured higher glucose levels could also indicate an imbalance in hormones regulating glucose metabolism. In physiological conditions ingestion of carbohydrates causes a rise in glucose and insulin secretion that in turn suppresses glucagon secretion. The two hormones act in concert to minimise the postprandial rise in glucose. A disturbance in glucose tolerance may be a consequence of the decrease and delay in insulin rise, or an increase in glucagon secretion and action.
The effect of age on insulin secretion has not been well defined. Basal insulin secretion, measured by the c-peptide level, and insulin secretory response to any increment in plasma glucose are decreased with age [10]. This is in line with insulin and c-peptide responses in the 1st hour of OGTT in our study. Higher insulin levels in the 2nd hour of OGTT in the elderly could indicate a defect in the insulin action or insulin clearance. The study of Basu et al. [11] elegantly showed that the age-associated deterioration in glucose tolerance is a consequence of insulin secretion, action and clearance.
Irregularities in glucagon response to postprandial hyperglycaemia may exist many years before glucose intolerance gets manifest [12]. Our elderly subjects had higher fasting and stimulated glucagon levels. Lack of suppression of glucagon could cause higher glucose levels by impairing glucose and insulin-induced inhibition of endogenous glucose production [13]. However, the role of glucagon in the development of glucose intolerance is dependent on insulin secretion. When insulin secretion is adequate, glucagon increase does not cause hyperglycaemia [14]. If relative insulin deficiency is present, such as in the elderly, lack of glucagon suppression can impair glucose tolerance [15].
- Maintenance of glucose tolerance in non-obese healthy elderly subjects differs from that in non-obese younger subjects.
- Higher fasting and stimulated glucose levels during OGTT in the elderly may be the consequence of abdominal obesity, in spite of normal body mass index.
- Ageing is associated with a decrease in insulin secretion, action and clearance.
- Glucose intolerance in the elderly may be a consequence of lack of glucagon suppression in presence of relative insulin insufficiency.
None
1 Department of Medicine, Gerontology Clinic, ‘Zvezdara’ University Hospital, Medical School University of Belgrade, Belgrade, Serbia
2 Department of Medicine, Division of Endocrinology, ‘Zvezdara’ University Hospital, Medical School University of Belgrade, Belgrade, Serbia
* To whom correspondence should be addressed Email: davidovi{at}eunet.yu
References
- Mokdad AH, Ford ES, Bowman BA, et al. Diabetes trends in the US 1990–1998. Diabetes Care (2000) 23:1278–83.
[Abstract/Free Full Text] - Shimokata T, Muller DC, Flef JL, Sorkin J, Ziemba AJ, Andres R. Age as independent determinant of glucose tolerance. Diabetes (1991) 40:41–51.
- Mokdad AH, Serdula MK, Dietz WH, Bowman BA, Marks JS, Koplan JP. The spread of the obesity epidemic in the United States, 1991–1998. JAMA (1999) 282:1519–22.
[Abstract/Free Full Text] - Iozzo P, Beck-Nielsen H, Laako M, Smith U, Yki-Jarvinen H, Ferrannini E. Independent influence of age on basal insulin secretion in nondiabetic humans. J Clin Endocrinol Metab (1999) 84:863–8.
[Abstract/Free Full Text] - Stumvoll M, Meyer C, Kreider M, Perriello G, Gerich J. Effects of glucagon on renal and hepatic glutamine gluconeogenesis in normal postabsorptive humans. Metabolism (1998) 47:1227–32.[CrossRef][ISI][Medline]
- Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care (1997) 20:1183–97.[ISI][Medline]
- Reaven G. Age and glucose intolerance. Effect of fitmess and fatness. Diabetes Care (2003) 26:539–40.
[Free Full Text] - Goodpaster BH, Krishnaswami S, Resnick H, Kelley D. Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care (2003) 26:372–81.
[Abstract/Free Full Text] - Imbeault P, Prins JB, Stolic M, et al. Aging per se does not influence glucose homeostasis. Diabetes Care (2003) 26:480–4.
[Abstract/Free Full Text] - Jones CNO, Pei D, Sturis J, Polonsky KS, Chen YD-I, Reaven GM. Identification of an age-related defect in glucose-stimulated insulin secretion in non-diabetic women. Endocrinol Metab (1997) 4:193–200.
- Basu R, Breda E, Oberg AL, et al. Mechanism of the age associated deterioration in glucose tolerance. Diabetes (2003) 52:1738–48.
[Abstract/Free Full Text] - Henkle E, Manschikowski M, Koehler C, Wolfgang L, Hanefeld M. Impact of glucagon response on postprandial hyperglycemia in men with impaired glucose tolerance and type 2 diabetes mellitus. Metabolism (2005) 54:1168–73.[CrossRef][ISI][Medline]
- Lewis GF, Vranic M, Giacca A. Role of free fatty acids and glucagon in the peripheral effect of insulin on glucose production in humans. Am J Physiol (1998) 275:E177–86.[ISI][Medline]
- Frank JW, Camilleri M, Thomforde GM, Dinneen SF, Rizza RA. Effects of glucagon on postprandial carbohydrate metabolism in nondiabetic humans. Metabolism (1998) 47:7–12.[ISI][Medline]
- Shah P, Basu A, Basu R, Rizza R. Impact of lack of suppression of glucagon on glucose tolerance in humans. Am J Physiol (1999) 277:E283–90.[ISI][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||