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Plasma glycerol and free fatty acid concentrations decrease following oral glucose consumption, but changes in the rate of lipolysis during an oral glucose tolerance test (OGTT) have not been documented in conjunction with changes in fatty acid (FA) oxidation or reesterification rates in healthy individuals. After a 12-h overnight fast, 15 young (21–35 yr; 7 men and 8 women) and 14 older (60–80 yr; 7 men and 7 women) participants had the forearm vein catheterized for primed continuous infusion of [1,1,2,3,3-2H]glycerol. A contralateral hand vein was catheterized for arterialized blood sampling. Indirect calorimetry was performed simultaneously to determine total FA and carbohydrate (CHO) oxidation rates (Rox). Total FA reesterification rates (Rs) were estimated from tracer-measured lipolytic and FA oxidation rates. After a 90-min equilibration period, participants underwent a 120-min, 75-g OGTT. Glycerol rate of appearance (Ra), an index of lipolysis, decreased significantly from baseline 5 min postchallenge in young participants and 30 min in older participants. At 60 min, FA Rox decreased in both groups, but was significantly higher in older participants. Between 5 and 90 min, CHO Rox was significantly lower in older participants. In addition, FA Rs was significantly lower in older participants at 60 and 90 min. The area under the curve (AUC) for FA Rox was greater than that for FA Rs in older, but not in young participants. Our results indicate that, in aging, the postprandial suppression of lipolysis and FA oxidation are delayed such that FA oxidation is favored over CHO oxidation and FA reesterification. NEW & NOTEWORTHY: To our knowledge, our investigation is the first to demonstrate changes in lipolysis during an oral glucose tolerance test (OGTT) in healthy young and older individuals. Plasma glycerol and free fatty acid concentrations changed after glycerol rate of appearance (Ra), indicating that plasma concentrations are incomplete surrogates of the lipolytic rate. Moreover, simultaneous determinations of substrate oxidation rates are interpreted to indicate that metabolic inflexibility in aging is characterized by delayed changes in postprandial substrate utilization related to the lipolytic rate. [ABSTRACT FROM AUTHOR]

Platelet activation and related cardiovascular complications are the hallmarks of type 2 diabetes (T2D). We investigated the mechanism of platelet activation in T2D using MS‐based identification of differentially expressed platelet proteins with a focus on glycosylated forms. Glycosylation is considered one of the common post‐translational modifications in T2D, and N/O‐linked glycosylation of glycoproteins (GPs)/integrins is known to play crucial roles in platelet activation. Our platelet proteome data revealed elevated levels of GPs GPIbα, GPIIbIIIa, GPIV (CD36), GPV and integrins in T2D patients. T2D platelets had elevated N‐linked glycosylation of CD36 at asparagine (Asn)408,417. Enrichment analysis revealed a close association of glycosylated CD36 with thrombospondin‐1, fibrinogen and SERPINA1 in T2D platelets. The glycosylation of CD36 has previously been reported to increase cellular uptake of long‐chain fatty acids. Our in silico molecular docking data also showed a favorable binding of cholesterol with glycosylated Asn417 CD36 compared to the non‐glycosylated form. We further investigated the CD36:LDL cholesterol axis in T2D. Elevated levels of oxidized‐low density lipoprotein (oxLDL) were found to cause significant platelet activation via CD36‐mediated stimulation of Lyn‐JNK signaling. Sulfo‐N‐succinimidyl oleate, an inhibitor of CD36, effectively inhibited oxLDL‐mediated platelet activation and adhesion in vitro. Our study suggests increased glycosylation of CD36 in T2D platelets as a potential route for oxLDL‐mediated platelet activation. The oxLDL:CD36 axis may thus be exploited as a prospective target to develop therapeutics against thrombosis in T2D. [ABSTRACT FROM AUTHOR]

Two groups of normal male subjects were given an infusion of insulin and an infusion of epinephrine + insulin respectively. Blood glucose, plasma free fatty acids (FFA), insulin, growth hormone, cortisol, and urinary catecholamines were determined. Continuous indirect calorimetry was used to measure metabolic rate and oxidation rates of carbohydrate and lipids. The first group (n equals 7) received a 30-minute insulin infusion (0.1 IU/kg). While blood glucose and plasma FFA decreased, carbohydrate oxidation and metabolic rate significantly increased after some delay, whereas lipid oxidation decreased. The increase in carbohydrate oxidation amounted to 5 g/120 min. The decrease in blood glucose during insulin administration did not correlate with the increase in carbohydrate oxidation. In the second group (n equals 7), a 150-minute epinephrine infusion (900 mug in 500 ml saline) was administered, and superimposed upon it, a similar insulin infusion initiated after 60 min. Epinephrine alone increased blood glucose and plasma FFA levels, and decreased insulinemia. The rise in the metabolic rate was sharp and significant. After a short but significant increase the oxidation rate of carbohydrate decreased, whereas that of lipids markedly rose. This increase significantly correlated with that in FFA. Addition of insulin markedly decreased the elevated FFA levels and lowered blood glucose. After some delay this was followed by a marked increase in carbohydrate oxidation and a decrease in lipid oxidation. In this test the total increase in carbohydrate oxidation was 11 g/120 min. In comparison with the insulin test, this double amount seems to correlate well with the higher blood glucose levels measured before insulin administration. The results suggest that insulin indirectly stimulates carbohydrate oxidation by facilitating glucose transport into the cells and lowering FFA levels, and that epinephrine favours lipid oxidation through its lipolytic effects and its suppression of insulin release.

Oral tolerance tests with 30 and 50 g of xylitol were performed in 10 normal subjects adapted to taking this pentitol. A 50 g oral glucose tolerance test served as control. Continuous indirect calorimetry was carried out in 7 of these subjects to measure the effects on the metabolic rate and on the oxidation rates of carbohydrate and fat. A small and short rise in serum xylitol and low quantitites of xylitol excretion in urine were observed in both xylitol tests. Xylitol caused a small but statistically significant increase in blood glucose and plasma insulin concentrations. Plasma free glycerol diminished significantly. After xylitol the metabolic rate rose throughout the test period but the total increase was only half of that after glucose administration. There was no significant influence of xylitol on the oxidation rates of carbohydrate and lipids. The total increase in carbohydrate oxidation during 2 1/2 hours amounted to one fourth of that caused by glucose. It is suggested that xylitol, during the first two hours after ingestion, charges the body's metabolism much less than equal amounts of glucose. Therefore, the use of xylitol as a sweetener in the diet of diabetic patients seems to be justified.

Postoperative parenteral nutrition can only be optimally effective if the characteristics of post-traumatic metabolism are taken into account. Two main possibilities are discussed for the carbohydrate component of parenteral nutrition during this phase: glucose with high doses of insulin or non-glucose carbohydrates (sugar substitutes) possibly in a suitable combination with glucose. The risks as well as the technical and organisational problems involved in the use of them are discussed and the authors prefer the second of the two alternatives. Possible side effects of non-glucose carbohydrates are pointed out and it is shown how these can be avoided by observing dose guidelines. So far a combination of frucose : glucose : xylitol in a ratio of 2 : 1 :1 with a total dose of 0.50 g/kg/hour has been studied most thoroughly. This combination normalises the fat metabolism and improves glucose tolerance without requiring exogenous insulin. Experiences with this combination as well as individual non-glucose carbohydrates on operated patients have been given continuously for up to 7 days and in some cases even for several weeks. No side effects, no deviations from a steady state and no abnormal changes of the laboratory values occurred. The authors are of the opinion that non glucose carbohydrates are necessary if the facilities for frequent blood sugar controls are not available.

The use of continuous indirect calorimetry in the course of a 100 g OGTT in 10 normal subjects has shown that carbohydrate oxidation rises with the secondary fall in blood glucose, suggesting that it could result from glucose stored under the influence of insulin. The experimental increase in FFA by a neutral fat infusion in 8 normal subjects decreased this oxidation in spite of the insulin rise. In a group of 5 non-obese, non-ketotic insulin-deficient diabetics, carbohydrate oxidation was found to be normal and directly correlated with plasma glucose levels. On the other hand, in 7 obese diabetics with high plasma insulin levels carbohydrate oxidation was found to be low, suggesting that carbohydrate intolerance could result from the non-oxidation of glucose. This study shows heterogeneity of diabetes, since glucose intolerance could result from non-oxidation of glucose as well as from insufficient pancreatic secretion.

Insulin is the key hormone of carbohydrate metabolism, it also influences the metabolism of fat and proteins. It lowers blood glucose by increasing glucose transport in muscle and adipose tissue and stimulates the synthesis of glycogen, fat, and protein. The anabolic action of insulin is antagonized by the catabolic action of glucagon. This hormone stimulates glycogenolysis and gluconeogenesis. The molar insulin: glucagon ratio is a parameter for an anabolic or a catabolic situation. Epinephrine also antagonizes insulin action. Like glucagon it stimulates glycogenolysis. In addition it reduces the insulin sensitivity of peripheral tissues and inhibits the release of insulin. Growth hormone decreases glucose uptake in muscle and adipose tissue gluconeogenesis in liver. In the presence of insulin, growth hormone stimulates protein synthesis. The net metabolic effects of a single hormone are directly related to the activity of other synergistic or antagonistic hormones.

Aims: Oral glucose tolerance tests (oGTT) are widely used for the diagnosis of diabetes. It is well known that the reproducibility of oGTT is poor and that a number of factors have an impact on the outcome of this diagnostic test. It appears as if one aspect, the oral glucose solution (OGS) used has not achieved much attention. Very little is published about this, despite the fact that apparently most often not a pure and freshly prepared glucose solution is used but a ready‐to‐use solution prepared by a (pharmaceutical) company. Methods: A literature search was performed to find respective publications. Results: It appears as if no or only a small number of not adequately designed clinical‐experimental studies have been performed comparing different OGS head‐to‐head. Conclusions: The composition of such OGS, including the excipients added to improve taste and smell, can have an impact on blood glucose increase after drinking the given OGS. Such factors can also have an impact on endogenous insulin secretion. If significant differences in the blood glucose excursions exist depending on which OGS is used, this calls for the use of a standardized OGS in oGTT to have a comparable outcome everywhere. [ABSTRACT FROM AUTHOR]

Aims: Oral glucose tolerance tests (oGTT) are widely used for the diagnosis of diabetes. It is well known that the reproducibility of oGTT is poor and that a number of factors have an impact on the outcome of this diagnostic test. It appears as if one aspect, the oral glucose solution (OGS) used has not achieved much attention. Very little is published about this, despite the fact that apparently most often not a pure and freshly prepared glucose solution is used but a ready-to-use solution prepared by a (pharmaceutical) company., Methods: A literature search was performed to find respective publications., Results: It appears as if no or only a small number of not adequately designed clinical-experimental studies have been performed comparing different OGS head-to-head., Conclusions: The composition of such OGS, including the excipients added to improve taste and smell, can have an impact on blood glucose increase after drinking the given OGS. Such factors can also have an impact on endogenous insulin secretion. If significant differences in the blood glucose excursions exist depending on which OGS is used, this calls for the use of a standardized OGS in oGTT to have a comparable outcome everywhere., (© 2022 Diabetes UK.)

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Plasma free fatty acids (FFA) play important physiological roles in skeletal muscle, heart, liver and pancreas. However, chronically elevated plasma FFA appear to have pathophysiological consequences. Elevated FFA concentrations are linked with the onset of peripheral and hepatic insulin resistance and, while the precise action in the liver remains unclear, a model to explain the role of raised FFA in the development of skeletal muscle insulin resistance has recently been put forward. Over 30 years ago, Randle proposed that FFA compete with glucose as the major energy substrate in cardiac muscle, leading to decreased glucose oxidation when FFA are elevated. Recent data indicate that high plasma FFA also have a significant role in contributing to insulin resistance. Elevated FFA and intracellular lipid appear to inhibit insulin signalling, leading to a reduction in insulinstimulated muscle glucose transport that may be mediated by a decrease in GLUT-4 translocation. The resulting suppression of muscle glucose transport leads to reduced muscle glycogen synthesis and glycolysis. In the liver, elevated FFA may contribute to hyperglycaemia by antagonizing the effects of insulin on endogenous glucose production. FFA also affect insulin secretion, although the nature of this relationship remains a subject for debate. Finally, evidence is discussed that FFA represent a crucial link between insulin resistance and β-cell dysfunction and, as such, a reduction in elevated plasma FFA should be an important therapeutic target in obesity and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Examines the potential contribution of diuretics for the occurrence of thiamine deficiency. Clinical manifestation of Vitamin B[sub 1] deficiency disease; Mechanism for the diuretic-induced growth of thiamine excretion; Pathophysiologic and clinical importance for the increased urinary losses of thiamine.

During endurance exercise, skeletal muscle relies mainly on both carbohydrate (CHO) and fat oxidation to cover energy needs. Numerous scientific studies have shown that increasing the exercise intensity leads to a progressive utilization of CHO. The latter will induce a state of glycogen depletion which is generally recognized as being a limiting factor for the continuation of strenuous exercise. Different dietary interventions have been proposed to overcome this limitation. A high-CHO diet during periods of intense training and competition, as well as CHO intake during exercise, are known to maintain a high rate of CHO oxidation and to delay fatigue. However, it has been recognized also that enhancing fatty acid (FA) oxidation during exercise induces a reduced rate of glycogen degradation, resulting in an improved endurance capacity. This is most strikingly observed as a result of frequent endurance exercise which improves a number of factors known to govern the FA flux and the oxidative capacity of skeletal muscle. Such factors are: (1) blood flow and capillarization; (2) lipolysis of triacylglycerol (TAG) in adipose tissue and circulating TAG and transport of FA from blood plasma to the sarcoplasm; (3) availability and rate of hydrolysis of intramuscular TAG; (4) activation of the FA and transport across the mitochondrial membrane; (5) the activity of enzymes in the oxidative pathway; (6) hormonal adaptations, i.e. sensitivity to catecholamines and insulin. The observation that the plasma FA concentration is an important factor in determining the rate of FA oxidation, and that some dietary factors may influence the rate of FA supply to muscle as well as to the mitochondria, has led to a number of dietary interventions with the ultimate goal to enhance FA oxidation and endurance performance. It appears that experimental data are not equivocal that dietary interventions, such as a high-fat diet, medium-chain TAG-fat emulsions and caffeine intake during exercise, as well as L-carnitine supplementation, do significantly enhance FA oxidation during exercise. So far, only regular endurance exercise can be classified as successful in achieving adaptations which enhance FA mobilization and oxidation. [ABSTRACT FROM PUBLISHER]

The hypothalamus receives a rich supply of adrenergic and noradrenergic nerve fibres from the brain stem, terminating in many hypothalamic regions, including the paraventricular nucleus, which is the site of the cell bodies of corticotrophin releasing factor (CRF) neurones in man. Experimental evidence has shown that an alpha 1 adrenoceptor mechanism stimulates adrenocorticotrophic hormone (ACTH) secretion in man. The site of action of this mechanism seems to be within the blood brain barrier, presumably modulating the secretion of the CRF complex. This mechanism is important in the control of ACTH secretion in some physiological conditions in healthy subjects. [ABSTRACT FROM PUBLISHER]

A comparison was made between isocaloric amounts of 24% glucose and 24% Triofusin (composed of 120 g fructose, 60 g glucose and 60 g xylitol per liter) during the course of a 6-day, 3-phase crossover study of 15 patients undergoing total parenteral nutrition. The patients received a total of 0.5 g carbohydrate per kg per day. Plasma glucose as significantly higher during glucose infusion (7-22 mmol/l, median: 9 mmol/l,) than during Triofusin infusion (5-16 mmol/l, median: 6 mmol/l). A moderate to severe glucosuria was detected in three patients during infusion of 24% glucose, and this declined considerably during the Triofusin period. The total renal carbohydrate loss during the glucose period was 0-143 g, median: 6 g per day, and during the Triofusin period was 6-68 g, median: 10 g per day. The nitrogen balance and carbamide production rate were the same in the two infusion regimes. Changes in biochemical liver parameters were observed in most of the patients, but these could not be attributed to parenteral nutrition. None of the patients developed symptoms of metabolic acidosis. There was a slightly but significantly higher urinary excretion of oxalate in the Triofusin period (0.1-1.1 mmol per day, median: 0.5 mmol per day) than in the glucose period (0.1-1.0 mmol per day, median: 0.4 mmol per day). Most of the patients exhibited a slightly increased urinary excretion of urate, irrespective of the infusion regimen. Serum urate remained normal. It was concluded that Triofusin infused in the described dosage is a suitable calorie source for parenteral nutrition, but that it does not present a distinct advantage over the use of pure glucose solution. In patients suffering from reduced glucose tolerance, however, Triofusin represents a more easily manageable calorie course. [ABSTRACT FROM AUTHOR]