Current issues in fructose metabolism.

The ingestion of fructose, particularly in refined form, has significantly increased in the North American diet over the last two decades. The unique way in which fructose is metabolized has given rise to much research examining whether fructose is advantageous in appetite control, exercise endurance, and disease states such as diabetes. Overall, there is very little evidence that modest amounts of fructose have detrimental effects on carbohydrate and lipid metabolism in nondiabetic or NIDDM subjects or that its use is particularly advantageous compared to that of other sugars. However, fructose can cause insulin and triglyceride levels to rise dramatically, and hence be potentially harmful, in a subgroup of NIDDM subjects who have concomitant pronounced hypertriglyceridemia. Large doses of fructose should also be avoided by subjects with gout because of the hyperuricemia which may result. No evidence exists that fructose has any clear advantages over glucose in regard to exercise endurance. Similarly there is no conclusive evidence that physiologic amounts of dietary fructose exacerbate copper deficiency or aid in weight control.

Long-term effects of dietary fructose on carbohydrate metabolism in non-insulin-dependent diabetes mellitus.

The effect of dietary fructose on glycemic control in subjects with diabetes mellitus is controversial. Therefore our aim was to conduct a long-term study to examine the effects of dietary fructose on glucose tolerance and insulin sensitivity and to delineate the mechanisms for the effects observed. Six subjects with non-insulin-dependent diabetes mellitus (NIDDM) who were being treated by diet alone consumed 13% of their calories as fructose incorporated into mixed meals in place of sucrose for 3 months as inpatients on a metabolic ward. The following parameters were measured: (1) weekly fasting plasma-glucose concentrations, (2) postprandial serum glucose and insulin levels after four sugar tolerance tests, (3) basal hepatic glucose production, and (4) hepatic and whole-body insulin sensitivity determined during a hyperinsulinemic, euglycemic clamp. When modest amounts of fructose were substituted for sucrose in the diet for 3 months, basal hepatic glucose output remained unchanged (12.84 +/- 1.83 nmol/kg/min v 12.51 +/- 2.00 nmol/kg/min) as did hepatic insulin sensitivity (92% +/- 4% v 93% +/- 4% suppression) and peripheral glucose disposal (22.52 +/- 4.56 nmol/kg/min v 25.80 +/- 9.45 nmol/kg/min) to a 860 pmol/m2/min insulin infusion at euglycemia (4.8 mmol/L). Fructose feeding also did not alter fasting plasma-glucose concentrations or postprandial plasma glucose and insulin responses to oral glucose or fructose loads or to mixed meals containing either sucrose or fructose. In conclusion, substitution of physiologic amounts of sucrose by fructose for prolonged periods is unlikely to have adverse effects on glucose metabolism in diabetic subjects who are being treated with diet alone.

Lipid metabolism in non-insulin-dependent diabetes: effects of long-term treatment with fructose-supplemented mixed meals.

Using fructose in the diabetic diet remains controversial primarily because of the potential for adverse effects on serum lipids. Therefore, lipid metabolism was evaluated in five NIDDM subjects (as inpatients) for 3 mo before and after ingestion of mixed meals containing 13% of calories as fructose. Triglyceride (TG) transport in very-low-density lipoproteins (VLDL) was assessed by multicompartmental analysis of VLDL-TG specific activity after injection of 3H-2-glycerol. There were no deleterious changes in lipid metabolism after fructose supplementation. The fructose diet produced no changes in serial free fatty acids (from 0.39 +/- 0.04 to 0.51 to 0.12 mmol/L), total cholesterol (from 5.43 +/- 0.52 to 5.53 +/- 0.57 mmol/L), high-density lipoproteins (from 0.91 +/- 0.08 to 0.93 +/- 0.08 mmol/L), low-density lipoproteins (from 3.10 +/- 0.52 to 2.92 +/- 0.47 mmol/L), VLDL-TG production (from 2.11 +/- 0.36 to 2.07 +/- 0.30 mmol/h), and fractional catabolic rate (from 0.186 +/- 0.014 to 0.196 +/- 0.03/h). Physiologic amounts of fructose are unlikely to have adverse effects on lipid metabolism when consumed by these diabetic subjects in place of sucrose in mixed meals for a prolonged period.

Postprandial metabolic responses to the influence of food form.

To determine whether differences in the metabolic response to two common starches could be eliminated by altering the physical form of food, 12 normal and 6 noninsulin-dependent diabetic (NIDDM) subjects were studied after consumption of test loads of whole and blended rice and potato. In normal and NIDDM subjects the lower postprandial glycemia and insulinemia of whole rice was eliminated and became similar to that of whole potato, which was unaffected by blending. The glucagon responses were unchanged and similar in both groups under all study conditions. In both normal and NIDDM subjects the glucose and insulin response to a particular starch is not a stable feature dependent on the unique characteristics of the starch molecule but is affected by food processing and the form in which it is presented to the gastrointestinal tract.

Use of alternative sweeteners in diabetic diet.

Alternative sweeteners are widely advocated and used. However, there is insufficient scientific information to determine whether alternative sweeteners aer of value in the management of diabetes, either in improving dietary adherence or in contributing to the achievement or maintenance of a lower body weight. Each of the available sweeteners has advantages and disadvantages; no one is preferred. Recommendations about alternative-sweetener use should be tailored to the specific dietary and life-style patterns of the individual.

Metabolic consequence of two-week fructose feeding in diabetic subjects.

We studied the metabolic effects of 2-wk fructose feeding as the sweetener in the diet of seven non-insulin-dependent diabetic individuals. The data demonstrated reduced postprandial hyperglycemia to an oral glucose challenge after 14 days without a significant difference in insulin response. There was no change in the markedly blunted glucose response to a fructose challenge but a significantly lower insulin response (area under the 3-h curve) was observed after 14 days of fructose feeding. There was reduced postprandial hyperglycemia after 14 days of fructose feeding with test meals as compared with baseline, without significant differences in insulin response. We also found no significant difference in free fatty acids, cholesterol, high-density lipoprotein (HDL) cholesterol, pyruvate, lactate, or uric acid after fructose feedings. There was a 13% increase in triglyceride levels after 14 days in 5 subjects with initial fasting hypertriglyceridemia (greater than 150 mg/dl). Insulin receptor binding to isolated adipocytes did not change after 14 days of fructose feeding.

The metabolic effects of 2-week fructose feeding in normal subjects.

Be studied the metabolic effects of 2 wk of fructose feeding as the sweetener in the diet of 11 normal individuals. The data demonstrated 1) no adverse effects of the fructose containing diet on triglyceride, pyruvate, lactate, or uric acid metabolism; 2) no apparent adaptation in the metabolism of fructose; 3) markedly flattened postprandial serum glucose and insulin responses to pure fructose; and 4) a modest decline in postprandial glucose and insulin levels after ingestion of standard fructose containing mixed meals as compared to sucrose-containing mixed meals.

The effects of oral fructose, sucrose, and glucose in subjects with reactive hypoglycemia.

We have evaluated the acute effects of orally administered 100-g loads of fructose, sucrose, or glucose given as drinks and of 100-g loads of fructose and sucrose given in cakes on the postprandial serum glucose, insulin, and cortisol responses in seven subjects with reactive hypoglycemia. We defined reactive hypoglycemia as a serum glucose nadir of 65 mg/dl or less, symptoms compatible with hypoglycemia occurring at or after the serum glucose nadir, a hypoglycemic index of greater than 1.0, and a rise in serum cortisol to greater than 20 micrograms/dl after the serum glucose nadir. The data demonstrated that (1) pure fructose given as a drink resulted in relatively flat serum glucose and insulin responses and did not cause a hypoglycemic reaction in any of the subjects, compared with the glucose drink, which caused a hypoglycemic reaction in any of the subjects; (2) ingestion of pure sucrose as a drink elicited significantly flatter serum glucose and insulin responses than did the glucose drink and was associated with some episodes of chemical hypoglycemia and symptoms, but did not result in a hypoglycemic reaction by our definition in any patient; and (3) ingestion of fructose cake led to serum glucose and insulin responses that were lower than those caused by ingestion of sucrose cake, but ingestion of neither fructose nor sucrose cake led to a hypoglycemic reaction by our definition in any patient. In conclusion, the use of fructose as a sweetening agent given either alone, in a drink, or with other nutrients in a cake resulted in markedly flatter serum glucose and insulin responses in subjects with reactive hypoglycemia. Fructose may thus prove useful as a sweetening agent in the dietary treatment of selected patients with reactive hypoglycemia.

Comparison of the metabolic responses to fructose and sucrose sweetened foods.

We studied the acute effects of oral ingestion of fructose and sucrose sweetened cakes and ice creams on postprandial serum glucose and insulin responses in 10 normal subjects, six subjects with impaired glucose tolerance, and 10 noninsulin-dependent diabetic subjects. The data demonstrate that: 1) ingestion of fructose cakes and ice creams resulted in lower serum glucose and insulin responses than did the sucrose cakes and ice creams in all study groups; 2) when comparing cakes to ice creams, the serum glucose and insulin responses after ice cream ingestion were lower than responses after cake ingestion. In conclusion, when fructose is incorporated as a sweetener in a complex food product, it is associated with significantly lower serum glucose and insulin responses as compared to comparable sucrose sweetened foods.

Hormonal and substrate responses to a standard meal in normal and hypertriglyceridemic subjects.

Postprandial plasma insulin, glucose, growth hormone, cortisol and free fatty acid responses to a standard mixed meal were determined and compared to fasting plasma triglyceride levels in normal and hypertriglyceridemic subjects. The hypertriglyceridemic subjects had significantly higher postprandial plasma insulin levels than did normals, but no significant differences were seen between the two groups to any of the other variables. Postprandial plasma insulin levels were highly correlated to fasting plasma triglyceride levels, but there was no significant correlation between any of the other variables and fasting plasma triglyceride levels.

Comparison of serum glucose, insulin, and glucagon responses to different types of complex carbohydrate in noninsulin-dependent diabetic patients.

We have studied the acute effects of oral ingestion of dextrose, rice, potato, corn, and bread on postprandial serum glucose, insulin, and glucagon responses in 20 diabetic subjects with nonketotic, noninsulin requiring fasting hyperglycemia. The carbohydrate loads were all calculated to contain 50 g of glucose. The data demonstrate that 1) dextrose and potato elicited similar postprandial serum glucose responses whereas rice and corn elicited lower responses, with bread intermediate; 2) postprandial insulin responses were relatively flat but rice ingestion led to significantly lower insulin responses than did potato; 3) urinary glucose excretion during the 3 h after carbohydrate ingestion was greatest following dextrose and least after rice and corn. In conclusion, there is a range in the magnitude of postprandial hyperglycemia after ingestion of different complex carbohydrates in diabetic patients with fasting hyperglycemia and emphasis on the use of the less hyperglycemic starches could be of therapeutic value in controlling hyperglycemia.

Effects of oral fructose in normal, diabetic, and impaired glucose tolerance subjects.

We studied the acute effects of oral ingestion of 50-g loads of dextrose, sucrose, and fructose on post-prandial serum glucose, insulin, and plasma glucagon responses in 9 normal subjects, 10 subjects with impaired glucose tolerance, and 17 non-insulin-dependent diabetic subjects. The response to each carbohydrate was quantified when the respective carbohydrate was given alone in a drink or when given in combination with protein and fat in a test meal. The data demonstrate that (1) fructose ingestion resulted in significantly lower serum glucose and insulin responses than did sucrose or dextrose ingestion in all study groups, either when given alone or in the test meal; (2) although fructose ingestion always led to the least glycemic response compared with the other hexoses, the serum glucose response to fructose was increased the more glucose intolerant the subject; (3) urinary glucose excretion during the 3 h after carbohydrate ingestion was greatest after dextrose and least after fructose in all groups. In conclusion, fructose ingestion results in markedly lower serum glucose and insulin responses and less glycosuria than either dextrose or sucrose, both when given alone or as a constituent in a test meal. However, as glucose tolerance worsens, an increasingly greater glycemic response to fructose is seen.

Postprandial hormonal responses to different types of complex carbohydrate in individuals with impaired glucose tolerance.

We have studied the effects of dextrose, rice, potato, corn, and bread on postprandial plasma glucose, insulin and glucagon responses in 11 subjects with impaired glucose tolerance. All carbohydrate loads were calculated to contain 50 g of glucose. The data demonstrate that 1) dextrose and potato elicited similar plasma glucose responses whereas rice, and bread elicited lower responses with corn intermediate; 2) dextrose and potato elicited similar plasma insulin responses whereas rice gave lower responses, with bread and corn intermediate; 3) all of the carbohydrate loads suppressed plasma glucagon with dextrose causing the greatest suppression. In conclusion, there is a range of plasma glucose, insulin, and glucagon responses to different complex carbohydrates in subjects with impaired glucose tolerance and the differences in plasma glucose responses may be of therapeutic value in controlling hyperglycemia.

Postprandial plasma-glucose and -insulin responses to different complex carbohydrates.

We have studied the effects of dextrose, rice, potato, corn, and bread on postprandial plasma glucose and insulin responses in 16 subjects. All carbohydrate loads were calculated to contain 50 gm. of glucose. The data demonstrate (1) that dextrose and potato elicited similar plasma glucose responses whereas rice, corn, and bread elicited lower responses; (2) similarly, dextrose and potato elicited similar and greater plasma insulin responses than rice and corn, with the response to bread being intermediate; (3) when the study group was divided in half, on the basis of each subject's one-hour plasma glucose response to dextrose, the differences in the plasma glucose and insulin responses were greater in the subjects with the highest glucose response to dextrose than in the low responders. In conclusion, there is a range of plasma-glucose and insulin responses to different complex carbohydrates, with rice and corn producing the lowest response curves. Furthermore, these differences are accentuated in patients with reduced glucose tolerance.