Acta Medica Scandinavica. Vol. 178, fasc. 2, 1965

From the First Medical Service, Sahlgrenska sjukhuset, University of Goteborg, Goteborg, Sweden

Blood Glucose, Free Fatty Acids and Intravenous Glucose Tolerance Test in Obese Patients on Different Diets

BY

PER BJORNTORP, ANDERS JONSSON and BERTIL HOOD

The dependence of the glucose-tolerance test on the diet preceding it is well estab- lished. A delayed disappearance has been noted after a low-carbohydrate diet, with a return to normal after a period on a diet adequate in calories and high in carbohydrate (1, 5, 7, 9, 10, 15, 16). Excess carbohydrate causes no further change (5).

An abnormally slow rate of disappear- ance of glucose loads in obesity has been observed by several authors (1,2, 14, 18). “Stable” obesity has been thought espe- cially to pre-dispose to this abnormality (1 3,14). Diabetic-type glucose-tolerance curves have been observed in the ab- sence of glucosuria and with a nor- mal fasting blood sugar (14). T h e diet before the tests does not seem to have been controlled in all of these studies.

Dole (7) observed abnormally high fasting levels of free fatty acids in venous blood in obesity. This finding has later been repeatedly confirmed (3, 6, 12).

In the present investigation blood glucose, free fatty acids and glucose

Submitted for publication February 9, 1965.

tolerance have been determined in obese patients while dietary conditions have been varied and defined.

Material Seventeen patients with pronounced obesity, weighing between 82.6 and 140.1 (average 110.2) kg, 14 women and 3 men, ages 18 -61 years were included. All were more than 35 yo above “desirable” weight (1 1). None suffered from infections during investigation, and none of the patients had glucosuria or were on drug treatment. Most of the patients had gall-stones and a previous history of gall- bladder disease but none had laboratory evidence of biliary obstruction.

All patients were hospitalized during in- vestigation. On admission 7 patients were given an ordinary 2,500-calorie diet with the addition of carbohydrate meals between ordi- nary meals for at least three days before investigation. They were then given a 500- calorie diet and investigations were again performed after at least a week. The other 10 patients were directly given the 500-calorie diet and were not examined on the higer calorie diet.

Eight medical students or patients, clini- cally free from metabolic disorders, weighing

175

176 PER BJORNTORP ET AL.

TABLE I. 'Fasting blood-sugar values and intravenous glucose-tolerance k-values for obese patients and normals. Mean f S. D. Within parentheses are values for the patients on the diet containing 500 cal., who were also investigated on the 2,500 cal. diet

Obesity

2,500 cal. diet 500 cal. diet Normals

Fasting blood sugar (mg 9 7 h 7 89%12 (90f9) per 100 ml blood) n = 8 n=16 (n=8)

7 7 k 15 n = 7

K-values' 0.95f0.23 0.84%0.24 (0.76f0.21) 1.40% 0.20 n = 8 n=10 (n=8) n = 7

Rate of glucose disappearance, according to Amatuzio et al. (1).

TABLE 11. Serum free fatty acids (pEq/l) after different fasting periods, for obese patients and nor- mals. Mean f S.D. Within parentheses are values for the patients on the diet containing 500 cal., who were also investigated on the 2,500 cal. diet

~ ~ ~~~ ~

Obesity

Hours fasting 2,500 cal. diet 500 cal. diet Normals

11 784& 183 926%175 (982f225) 631h150 n = 8 n=17 (n=8) n=8

14 832 & 278 968k191 (1,030&212) 618h267 n = 8 n=17 (n=8) n = 8

17 938f 197 941 f 2 0 4 (938f207) 794f 3 14 n = 8 n=17 (n=8) n= 8

20 1,016h298 1,009&297 (1,122f 120) 906%261 n = 8 n=17 (N=8) n = 8

61.9 to 74.8 (average 66.0) kg, 5 men and 3 women, ages 22-45 years, served as a healthy control group.

Methods The intravenous glucose-tolerance test was performed as described by Goldberg and Luft (5). Glucose was analyzed enzymati- cally in capillary blood (8).

Estimation of free fatty acids during pro- longed fasting was performed a t 11, 14, 17, a n d 20 hours after the start of fasting, During

this period the patients were allowed to walk and to drink water, but not to smoke or per- form heavy work. Free fatty acids were deter- mined in serum from blood drawn from the antecubital vein (4).

Results

Table I gives the fasting blood-sugar values and the intravenous glucose-toler- ance test k-values for the both groups. The fasting blood-sugar value did not

INTRAVENOUS GLUCOSE-TOLERANCE TEST IN OBESITY 1 77

differ significantly (p > 0.05) either be- tween groups or between the obese on different diets. K-values were in all cases above 1.10 in the normals. In the obese on the 2,500-calorie diet with in between meals the average was lower than the normal value, although not significantly different statistically. Four had a k-value below 0.90. On the calorie-restricted diet a still lower average k-value was found, although not statistically signifi- cantly lower than that for the obese on a higher calorie diet. In all cases, how- ever, the k-value fell after changing from a high- to a low-calorie diet. The lowest value noted was 0.56.

In table I1 the results of free fatty acid determinations are listed. Normals in- creased their venous blood level signifi- cantly (p < 0.02) between the 1 Ith and the 20th hour of fasting. The obese patients on a calorie-restricted diet had a significantly higher value at 11 hours of fasting than the normals (p < 0.01) This value did not increase over the following periods (p > 0.05) and was at 20th hour of the fast not significantly different from the corresponding value for the normals. In the 8 obese patients, who were on the higher calorie diet, comparisons were performed only be- tween their values on the two diets in question. On the 2,500-calorie diet with carbohydrate additions the obese pa- tients had a significantly lower l l-hour value (p < 0.02) than on the low-calorie diet, but not significantly different from the corresponding value in the normal group. The 20-hour fasting value in the obese on the higher calorie diet was signif- icantly higher than the 1 1 -hour value for the same group (p < 0.05), but not

12 453002. Acto Mad. Scand. Vol. 178

FREE FATTY ACIDS 1 PET!

- NORMALS

- _ - - O B E S I ~ Y , MOCAL

. . . .OBESITY 2500 CAL

20

H W R S OF FAST

Fig. 1 . Free fatty acid values (averages and standard deviations) after different times of fasting for normals and obese subjects on different diets.

significantly different from the corre- sponding value in the normal group or the obese group on calorie-restricted diet. The average values of free fatty acids for the obese on the higher calorie diet were, however, higher than the normals at each time measured. When compared on a relative basis the mean of all the observa- tions on the obese patients in the group in question is significantly higher (p < 0.01) than the mean for the normals. These results are also shown graphically in fig. 1.

Discussion

A diabetic-type glucose-tolerance test after a period of low caloric intake has been observed repeatedly (1, 5, 7, 9, 10,

178 PER BJORNTORP ET AL.

15, 16). This corresponds to a sluggish response of the plasma-insulin concentra- tion to oral glucose as measured by an immunological technique ( 1 7). An in- sensitivity of adipose tissue to insulin, primarily affecting the free fatty acid release mechanisms, has also been sug- gested (7). The same observation now made in obese patients on calorie-re- stricted diet might be a similar phenom- enon.

O n a diet adequte in calories and with addition of carbohydrates, the glucose- tolerance test in the obese patients on an average approached normal. This is probably only true for obesity when pa- tients with glucosuria and other signs of clinically overt diabetes mellitus have been excluded.

Free fatty acids in the group of obese patients on a calorie-restricted diet were high after 1 1 hours of fasting and did not increase during prolonged fasting. They were, however, not statistically different from the normal values after increasing calorie intake. The early increased levels on a low-calorie diet might correspond to the demonstrated impairment of glucose disappearance. A decreased glucose up- take in different tissues would account for the low k-values of the glucose-toler- ance tests, and an impairment of adi- pose tissue uptake of glucose could be thought to cause the higher levels of free fatty acids earlier during fasting. Glu- cose uptake in adipose tissue seems necessary for reesterification of fatty acids to triglycerides (1 8). When a decrease in adipose tissue glucose uptake thus occurs, an increased outflow of free fatty acids will result and hence also an increase in plasma free fatty acids.

The phenomenon of a high level of free fatty acids after about 12 hours of fasting and a very slow or no increase at all for the next 10 hours has earlier been described in obese patients (3, 6). The results reported in the present work emphasize the importance of defining diet before conclusions can be drawn about a possible derangement of free fatty acid metabolism in obesity.

O n an average the values for free fatty acids in obesity after a full diet were higher than in the normals. Whether this means an abnormality of free fatty acid metabolism in established obesity or is just a result of a larger number of fat cells, contributing to the plasma pool of free fatty acids, cannot be decided at present.

Summary

Blood glucose, free fatty acids and intra- venous glucose tolerance was determined in obese patients on diets containing ei- ther 500 calories or 2,500 calories with carbohydrate additions, and compared with the values for normals. No patients with glucosuria were included. Fasting blood sugar showed no differences. Intra- venous glucose disappearance showed no statistical differences but was in each case of obesity changed to a slower disappear- ance rate when the change of diet from higher calories to calorie restriction was introduced. After 11 hours of fasting the free fatty acids of the obese on a calorie- restricted diet were significantly higher than corresponding values for the nor- mals on a n ad libitum diet. When given the higher calorie diet with carbohydrate ad- ditions, the obese significantly decreased

INTRAVENOUS GLUCOSE-TOLERANCE TEST IN OBESITY 1 79

their 11-hour fasting free fatty acid level, which now no longer was signifi- cantly different from the normals. After 20 hours of fasting no significant differ- ences were found between groups or between the obese on different diets. However, all average values of free fatty acids taken at 1 1, 14, 17 and 20 hours of fasting were higher in the group of obese patients on the higher calorie diet than the corresponding normal values. When all values were compared on a relative basis the obese patients values were sig- nificantly higher. The importance of defining the diet in studies of lism in obesity is emphasized.

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