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Insulin Resistance and β-Cell Dysfunction in Aging: The Importance of Dietary Carbohydrate^*

Veterans Administration Medical Center and the Department of Medicine, University of Washington Seattle, Washington 98108
the Department of Physiology and Biophysics, University of Southern California Los Angeles, California 90033

Address requests for reprints to: Daniel Porte, Jr., M.D., Seattle Veterans Administration Medical Center, 1660 South Columbian Way, Seattle, Washington 98108.

Aging is associated with a progressive decrease in glucose tolerance. This decrease is associated with insulin resistance and β-cell dysfunction. This study was performed to evaluate the possible role of dietary factors in the glucose intolerance of aging. Two groups of men were studied: one young (Y; n = 8; age range, 18–36 yr) and one elderly (E; n = 10; age range, 65–82 yr). Frequently sampled iv glucose tolerance tests were performed in random order: 1) during ad libitum home dietary conditions; 2) after a 3- to 5-day regimen of very high (85%) carbohydrate intake; and 3) after a 3- to 5-day regimen of low (30%) carbohydrate intake (Y only). From the frequently sampled iv glucose tolerance test data, we calculated the glucose disappearance rate (Kg) and metabolic parameters according to the minimal model method, including the insulin sensitivity index (S₁) and the first and second phase β-cell responsivity to glucose (₁ and ₂). The elderly men, while eating an ad libitum diet, were less tolerant to glucose than the young [mean Kg: E = 1.5 ± 0.2% (±SE) min^–1; Y = 2.3 ± 0.3% min^–1; P < 0.025], had relative insulin resistance (mean S₁: Y = 6.1 ± 1.1; E = 2.4 ± 0.7 min^–1 10^–4/(µU/mL) [0.85 ± 0.15 vs. 0.33 ± 0.10 min^–1 10^–4/(pmol/L)]; P < 0.01), and lesser second phase β-cell responsiveness to glucose (mean ₂: Y = 18.5 ± 3.6; E = 8.7 ± 2.7 (µU/mL)·min^–2/(mg/dL) [2390 ± 465 vs. 1120 ± 349 (pmol/L)·min^–2/(mmol/L)]; P < 0.05). A maximum improvement in Kg and S₁ occurred at 41% carbohydrate feeding in the young men, whereas in the elderly men there was a significant increase in both of these parameters while eating the very high (85%) carbohydrate diet. Thus, the difference in glucose tolerance between groups was corrected by the very high carbohydrate diet (mean Kg: Y = 2.2 ± 0.2%; E = 2.0 ± 0.3%/min; P > 0.5), as was the age-related difference in insulin sensitivity (mean S₁: Y = 5.6 ± 1.2; E = 4.4 ± 1.3 min^–1 10^–4/(µU/mL) [0.78 ± 0.17 vs. 0.61 ± 0.18 min^–1 10^–4/(pmol/L)]; P > 0.5). The increase in S₁ in the elderly men occurred in concert with a significant improvement in β-cell responsiveness to glucose (mean ₂: ad libitum = 8.7 ± 2.7; high carbohydrate = 22.0 ± 0.6 (µU/ml)·min^–2/(mg/dL) [1120 ± 349 vs. 2840 ± 78 (pmol/L)·min^–2/(mmol/L)]; P < 0.02). When the carbohydrate intake was 30%, the young men had decreases in mean Kg (to 1.6 ± 0.2%/min; P < 0.05 vs. ad libitum diet) and S₁ (to 3.9 ± 1.5 min^–1 10^–4/(µU/mL) [0.54 ± 0.21 min^–1 10^–4(pmol/L)]; P < 0.05 vs. ad libitum diet), while islet function remained unchanged. These studies demonstrate that the reduced glucose tolerance and insulin resistance of aged nonobese men are diet related, and that the differences from young men are much less when carbohydrate intake is high.

^* This work was supported by the V.A. and NIH Grants DK-29867, DK-12829, DK-17047, and RR-37.

Received December 11, 1987.

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