Mechanism of glucose intolerance during fasting: differences between lean and obese subjects.

Oral glucose tolerance tests were performed on 14 lean and 14 obese nondiabetic subjects before and after a 6-day fast. In addition, insulin tolerance tests were performed on 8 lean and 8 obese subjects before and after starvation. Both in lean and obese subjects glucose tolerance deteriorated during starvation, but much more so in the lean population. During fasting, insulin elevation after a glucose load was significantly delayed in lean subjects but not in the obese. Circulating levels of factors known to affect glucose tolerance, such as glucagon, growth hormone, free fatty acids, and ketone bodies were higher in fasting lean than in fasting obese individuals. In normals fasting resulted in a significant decrease of the blood glucose response to insulin injection, whereas in fasting obese subjects glucose response was unchanged. The results obtained suggest that the effect of fasting on insulin release and insulin sensitivity was more pronounced in lean than in obese subjects, which resulted in greater deterioration of glucose tolerance in the lean population.

Comparison between glucose and a combination of glucose, fructose, and xylitol as carbohydrates for total parenteral nutrition of surgical intensive care patients.

The effects of four day periods of infusions of 600 gm/24 hours glucose and 600 gm/24 hours of a combination of glucose, fructose, and xylitol were compared. This study was performed during total parenteral nutrition of twelve postoperative patients with major complications. The mean plasma glucose level was significantly lower during the infusion of the combination of sugars (154.2+/-19.5 mg/100 ml versus 193.9+/-15.0 mg/100 ml[p is less than 0.005). Furthermore, the required dosage of exogenous insulin was significantly lower (18.9+/-12.3 units/day versus 43.7+/-19.7 units/day [p is less than 0.01). Mean renal carbohydrate losses were 0.85 per cent during glucose infusion and 1.7 per cent during infusion of the combination. The influence of both infusion regimes on values for pH, base excess, lactate, pyruvate, free fatty acids, insulin, sodium, potassium, chloride, magnesium, phosphorus, bilirubin, alkaline phosphatase, SGOT, and SGPT 0.85 has been investigated. No clinical side effects were observed. It is concluded that the administration of the investigated combination of glucose, fructose, and xylitol is justified in patients in whom hyperglycemia during infusion of glucose alone is difficult to control with insulin.

[Parenteral hyperalimentation (author's transl)]. / Hyperkalorische Ernährung

Intravenous hyperalimentation allows complete nutrition and anabolism in patients who cannot be fed by the oral route. However, several complications have been reported, e.g. septicaemia and hyperglycaemina. In 51 intensive-care patients receiving hyperalimentation, 18% were found to be hyperglycaemic in spite of insulin administration. Hyperglycaemia was frequently associated with stress. In 8 patients undergoing major surgery, which was chosen as a stress model, decreased insulin and increased glucagon, growth hormone and cortisone levels were observed. These findings could explain stress-induced glucose intolerance. In a further experiment, 8 intensive-care patients were given alternative intravenous feedings with either 600g of a mixture of glucose, fructose and xylitol in a ration of 1:2:1 or 600g glucose per day. During both regimens insulin administration was required in 4 patients, but the insulin dosage was lower with the mixture. Plasma glucose during glucose infusion was 205+/-25mg/100ml(M+/-SEM) and the sum of plasma glucose, fructose and xylitol during infusion of the mixture was 176+/-33mg/100ml, the difference being of borderline significance (p less than 0.05). The advantages and disadvantages of infusable substrates are summarized on the basis of the available literature and it is concluded that, in general, glucose is preferable. However, if hyperglycaemia is difficult to control, partial replacement of glucose by glucose substitutes or fat emulsions may be advantageous. A routine infusion programme for central venous feeding is suggested. Causes and prevention of side-effects are reviewed. In many patients receiving central venous nutrition less hazardous and less expensive methods could be used such as nasogastric tube feeding, elemental diet or peripheral venous nutrition.

[Metabolic regulation in surgical patients]. / Stoffwechselregulation bei chirurgischen Patienten.

The concentration of circulating hormones and substrates was determined in 7 patients before, during and after major elective surgery. On the basis of these and other of our studies, as well as data in the literature, a tentative scheme of postoperative and post-traumatic metabolism has been drawn up. It is based on the classical division into a "shock phase", a catabolic healing phase and an anabolic healing phase. The adjustment of intravenous feeding to these metabolic phases is discussed.

[Breath acetone and ketonemia in normal- and overweight subjects during total fasting (author's transl)]. / Aceton in der Atemluft und Ketone im Venenblut bei vollständigem Fasten normal-und übergewichtiger Personen

In subjects of ideal weight (7 males and 7 females) total whole blood ketones and breath acetone were determined during a 6 day fast, and in obese subjects (8 males, 18 females) during 6-28 days of fasting. Development of starvation ketosis was significantly slower in overweight than in normal weight subjects. Breath acetone concentration was up to blood ketone levels of 4 mMol/1 a linear function of the blood ketone concentration, beyond that level, however, an additional exponential component became apparent. The highest acetone elimination found was 4.46 mg/min, corresponding to 6.4 g acetone and 11.2 g acetoacetic acid in 24 hours. Hence the decarboxylation of acetoacetic acid to acetone may be an additional mechanism for the lowering of ketoacidosis in starvation.

[Carbohydrate intolerance during complete fasting]. / Kohlenhydratintoleranz bei vollständigem Fasten.

In the first part of the study oral glucose tolerance tests (GTT) or insulin tolerance tests (ITT) were performed in 22 lean and 22 obese nondiabetics before and after fasts of at least 6 days' duration. Deterioration of glucose tolerance was greater in lean than in obese individuals. Plasma levels of factors known to influence glucose tolerance (glucagon, growth hormone, free fatty acids, ketones) were significantly higher in fasting lean than in fasting obese subjects. Furthermore, delayed insulin rise (GTT) and decreased insulin sensitivity (ITT) were observed after starvation in lean subjects but not in the obese, which could explain the greater deterioration of glucose tolerance in the lean population. In the second part of the study glucose and fructose tolerance were compared during 4-hour infusions of these substrates (0.5 g/kg/h) in 8 normal subjects before and after two 4-day fasts. After starvation, glucose as well as fructose infusion resulted in plasma levels of the infused hexose significantly higher than in control, and the rise in plasma lactate and pyruvate was delayed. These results contradict the view widely held in the literature, that fructose metabolism remains unimpaired in the fasting state.

Postoperative tolerance to glucose and sugar substitutes.

In 51 surgical intensive-care patients, who were given 400 to 650 g glucose per day i.v., 18% of arterial blood sugar values were found to be above 250 mg/100 m1 in spite of frequent insulin administration. In 8 lobectomized patients increased plasma levels of pancreatic glucagon, cortisol, and growth hormone were observed which may in part explain postoperative glucose intolerance. In addition previous carbohydrate deprivation was found to impair glucose tolerance. Several measures are suggested to reduce the incidence of hyperglycemia during i.v. glucose feeding. In a further study 24 cholecystectomized or vagotomized patients received in alternate sequence either a combination of glucose (G), fructose (F) and xylitol (X), the G/F/X-ratio being 1/2/1, or glucose alone for 5 days. The infusion rate was 1.42 g carbohydrate/kg/24 hrs. On operation day and was increased by the same amount every day up to 7.14 g/kg/24 hrs. Tolerance was good in both groups but urinary losses of infused substrates were higher in the group receiving the GFX-combination. It is concluded that after surgery of intermediate magnitude the GFX-combination offers no advantage over glucose alone. However, in severely ill patients, where glucose intolerance is more pronounced, further carefully monitored studies with sugar substitutes appear of interest.

[Metabolic differences between males and females and between normal and obese subjects during total fast]. / Der Stoffwechsel bei vollständigem Fasten. Unterschiedliches Verhalten bei Männern und Frauen sowie bei Normalpersonen und Adipösen

In 24 normal and 24 obese subjects of both sexes circulating substrates (blood sugar, free fatty acids, ketone bodies) and hormones (insulin, growth hormone, pancreatic glucagon) were determined during 6 days of total fast. In normals the blood sugar fell to lower levels than in the obese. Plasma free fatty acids and ketone concentrations rose faster in normal than in obese subjects, and faster in females than in males. Plasma insulin concentrations declined to a greater extent in obese than in normal subjects. In all groups studied a significant increase of the pancreatic glucagon level within 1-3 days of fasting was observed, however, its rise occurred faster in normal females than in males. Growth hormone (GH) rose significantly in normal males but not in obese males. Following high overnight fasting values in some normal females showed no significant increase in GH levels but significantly higher GH values than obese females after 1-6 days of fasting. After summarizing starvation-induced metabolic changes common to all study groups the respective differences found between males and females and between normal and obese subjects are discussed.

Acid-base patterns in lean and obese subjects during total fasting.

During prolonged starvation blood gas analyses on 24 lean and 78 obese subjects were performed. A statistically significant sex difference of acid-base status was found in that lean females were more acidotic after 4 - 6 days of fasting than lean males. This sex difference was abolished by severe and long-standing obesity, since females suffering from this condition were not significantly different from lean and obese males. Out of 78 obese patients fasted for 1 - 4 weeks 8 had one or more pH values below 7.30. It is concluded that regular blood gas analyses are indicated in all patients subjected to prolonged total fasting.

Nitrogen loss in normal and obese subjects during total fast.

Healthy volunteers of ideal weight (12 men and 12 women) were fasted for 6 days, and obese but otherwise healthy subjects (20 men, 28 women) for 6--28 days. In all groups studied a significant increase in urinary nitrogen loss from day 1 to day 3 of fasting was followed by a steady decrease. The early rise in urinary nitrogen excretion coincided with a rise in plasma glucagon levels, suggesting a relation of the latter to increased gluconeogenesis from amino acids. At equal weight greater nitrogen losses were found in men than in women, in both normal and obese subjects. In spite of much higher weight and larger energy expenditure and nitrogen loss in obese subjects however was not higher than in normal ones. Mean daily nitrogen losses varied from 14.5 g (normal and obese men early in starvation) to 3.0 g (obese women after a 4-weeks fast). Calculating the amount of calories derived from body protien (urinary nitrogen X 6.25 X 4.1)and taking total energy expenditure from tabular metabolic values, the contribution of protein to total calorie output was found to vary from 15% (normal men 6 day fast) to 5(obese women, 4th week of fasting). The clinical significance of nitrogen loss during therapeutic fasting is discussed.

On the mechanism of action of biguanides. evidence against an inhibition of gluconeogenesis from protein in normal fasting subjects.

The effect of phenformin on fuel homeostasis and on gluconeogenesis from protein was studied in 8 normal subjects who underwent two 4-day fasts 8-12 weeks apart. Each person received placebo or phenformin 50 mg every 12 hours for 3 days before and during the fasts. Circulating glucose, lactate, pyruvate, free fatty acid and ketone levels as well as urinary nitrogen excretion observed during placebo and phenformin treatment were not significantly different from each other. The lack of an effect of phenformin on urinary nitrogen excretion and plasma glucose level strongly suggests that gluconeogenesis from amino acids was unaltered by phenformin in these fasting subjects. The present findings are at variance with those by other authors which may be related to differences in methodology.

[Problems with hyperalimentation in intensive care units (author's transl)]. / 46. Probleme der parenteralen Ernährung in der Intensivpflege

The application of parenteral nutrition in patients in intensive care units can be limited by shock, septicemia and metabolic disorders. Stress- or trauma-induced glucose intolerance sometimes makes it difficult to maintain the caloric requirements with glucose. Sugar substitutes seem to be of advantage in these cases. Meticulous care is essential to avoid severe complications arising from the use of the central venous feeding catheters.