Biomedical subjects

L Tappy

Publications and source records attributed to L Tappy.

At least 37 records · Page 2Linked to original sources

PubMed2001

Counterregulatory responses to hypoglycemia in patients with maturity-onset diabetes of the young caused by HNF-1alpha gene mutations (MODY3).

Mutations of HNF-1alpha lead to severe beta cell dysfunction, resulting in decreased glucose-induced insulin secretion. HNF-1alpha is also expressed in liver, kidney and pancreatic alpha cells, but the functional consequences of HNF-1alpha mutations in these organs remain unknown. We therefore assessed the counterregulatory responses to hypoglycemia in six patients with HNF-1alpha mutations (MODY3), five patients with non-insulin-dependent diabetes mellitus (NIDDM) and in nine healthy controls. Plasma glucagon concentrations and endogenous glucose production were measured every 15 min during a hyperinsulinemic clamp with progressive hypoglycemia. Plasma glucagon concentrations were similar at basal glycemia (73+/-6, 69+/-5 and 69+/-7 ng/l) and reached peak values of 88+/-9, 88+/-11 and 89+/-7 ng/l at a glycemia of 3.6 mmol/l in MODY3 patients, patients with NIDDM and controls respectively (NS). Suppression of endogenous glucose production by insulin was blunted in MODY3 patients (3.3+/-1.2 micromol/kg per min) and in patients with NIDDM (4.4+/-0.6 micromol/kg per min) compared with controls (1.7+/-0.5 micromol/kg per min, P<0.05 compared with both MODY3 patients and patients with NIDDM). During hypoglycemia, endogenous glucose production increased to 8.6+/-2.1, 8.8+/-0.7 and 7.0+/-1.0 micromol/kg per min in MODY3 patients, patients with NIDDM and controls respectively (all NS). These data indicate that mutations of HNF-1alpha in MODY3 do not result in a decreased glucagon secretion or alterations of glucose production during hypoglycemia.

Blood Glucose↗

PubMed2001

In normal men, free fatty acids reduce peripheral but not splanchnic glucose uptake.

Raising plasma free fatty acid (FFA) levels reduces muscle glucose uptake, but the effect of FFAs on splanchnic glucose uptake, total glucose output, and glucose cycling may also be critical to producing lipid-induced glucose intolerance. In eight normal volunteers, we measured glucose turnover and cycling rates ([2H7]glucose infusion) during a moderately hyperglycemic (7.7 mmol/l) hyperinsulinemic clamp, before and after ingestion of a labeled (dideuterated) oral glucose load (700 mg/kg). Each test was performed twice, with either a lipid or a saline infusion; four subjects also had a third test with a glycerol infusion. As shown by similar rates of exogenous glucose appearance, the lipid infusion did not reduce first-pass splanchnic glucose uptake (saline 1.48+/-0.18, lipid 1.69+/-0.17, and glycerol 1.88+/-0.17 mmol/kg per 180 min; NS), but it reduced peripheral glucose uptake by 40% (P < 0.01 vs. both saline and glycerol infusions). Before oral ingestion of glucose, total glucose output was similarly increased by the lipid and glycerol infusions. Total glucose output was significantly increased by FFAs after oral ingestion of glucose (saline 3.68+/-1.15, glycerol 3.68+/-1.70, and lipid 7.92+/-0.88 micromol x kg(-1) x min(-1); P < 0.01 vs. saline and P < 0.05 vs. glycerol). The glucose cycling rate was approximately 2.7 micromol x kg(-1) x min(-1) with the three infusions and tended to decrease all along the lipid infusion, which argues against a stimulation of glucose-6-phosphatase by FFAs. It is concluded that in situations of moderate hyperinsulinemia-hyperglycemia, FFAs reduce peripheral but not splanchnic glucose uptake. Total glucose output is increased by FFAs, by a mechanism that does not seem to involve stimulation of glucose-6-phosphatase.

Adult↗

PubMed2001

[Physiopathology of obesity].

Obesity results from an imbalance between energy intake and energy expenditure. Human studies indicate that obese individuals have an increased basal metabolic rate secondary to an increased fat-free mass. A blunted dietary thermogenesis is observed but is not of sufficient magnitude to lead to a major weight gain. Indirect evidence suggests that physical activity may be low in obese individuals. In healthy lean subjects, overfeeding leads to a stimulation of spontaneous physical activity. The ensuing increase in energy expenditure may play a role in the prevention of weight gain. This response, however, shows a high interindividual variability. There is overall little evidence that major alterations of energy expenditure are present in obese individuals. It is likely that an alteration of mechanisms of food intake control plays a prominent role in the pathogenesis of this disease.

Energy Intake↗

PubMed2000

Effect of liver transplantation on hepatic glucose metabolism in a patient with type I glycogen storage disease.

BACKGROUND: In type I glycogenosis, mutation of the glucose-6-phosphatase gene results in absent glucose-6-phosphatase activity in liver cells leading to fasting hypoglycemia. Liver transplantation is expected to normalize glucose homeostasis. METHODS: Endogenous glucose production (6,6 2H2 glucose) was measured after an overnight fast and during exogenous 13C-labeled glycerol infusion in a patient with glycogenosis type I 24 months after liver transplantation and in a group of healthy subjects. RESULTS: Compared with healthy subjects, the glycogenosis patient had normal fasting glucose production and glucose and insulin concentrations after liver transplantation, but mildly elevated plasma glucagon concentrations. Gluconeogenesis from exogenous glycerol (13C glucose synthesis) was similar and did not lead to enhancement of glucose production in both healthy controls and the patient. CONCLUSIONS: Liver glucoregulatory function is restored by orthotopic liver transplantation in type I glycogenosis.

Adolescent↗

PubMed2000

Postprandial hepatic glycogen synthesis in liver transplant recipients.

BACKGROUND: The liver plays a central role in glucose homeostasis by releasing glucose in the fasting state and by taking up and converting into glycogen part of the glucose absorbed from the gastrointestinal tract after meal ingestion. METHODS: To determine whether the hepatic denervation that accompanies liver transplantation interferes with these functions, we assessed glucose tolerance to an oral glucose load in seven patients at 2-6 weeks after orthotopic liver transplantation, in six patients after kidney transplantation, and in six healthy controls. Hepatic glycogen synthesis was non-invasively assessed over the 4 hours after ingestion of a glucose load by monitoring hepatic uridine diphosphoglucose turnover with 13C galactose and acetaminophen. RESULTS: Liver and kidney transplant recipients had increased postprandial glucose concentrations but normal hepatic uridine diphosphoglucose turnover, indicating an unaltered hepatic glycogen synthesis. CONCLUSIONS: These results indicate that denervated liver transplants have an adequate glucoregulatory function. Postprandial hyperglycemia in liver transplant recipients is therefore not due to alterations of liver glucose metabolism.

Adult↗

PubMed2000

Assessment of postprandial hepatic glycogen synthesis from uridine diphosphoglucose kinetics in obese and lean non-diabetic subjects.

BACKGROUND: Obese patients are frequently characterized by insulin resistance and decreased insulin-mediated glycogen synthesis in skeletal muscle. Whether they also have impaired postprandial hepatic glycogen synthesis remains unknown. AIM: To determine whether postprandial hepatic glycogen synthesis is decreased in obese patients compared to lean subjects. METHODS: Lean and obese subjects with impaired glucose tolerance were studied over 4h after ingestion of a glucose load. Hepatic uridine diphosphoglucose kinetics were assessed using 13C-galactose infusion, with monitoring of urinary acetaminophen-glucuronide isotopic enrichment to estimate hepatic glycogen kinetics. RESULTS: Estimated net hepatic glycogen synthesis amounted to 18.6 and 22.6% of the ingested load in lean and obese subjects, respectively. CONCLUSION: Postprandial hepatic glycogen metabolism is not impaired in non-diabetic obese subjects.

Adult↗

PubMed2000

Effects of short-term carbohydrate or fat overfeeding on energy expenditure and plasma leptin concentrations in healthy female subjects.

OBJECTIVE: To determine the effects of excess carbohydrate or fat intake on plasma leptin concentrations and energy expenditure. DESIGN: Ten healthy lean females were studied: (a) during a 3 day isoenergetic diet (ISO); (b) during 3 day carbohydrate overfeeding (CHO OF); and (c) during 3 day fat overfeeding (FAT OF). During each test, basal metabolic rate, the energy expended during mild physical activity and recovery, and 24 h energy expenditure (24 h EE) were measured with indirect calorimetry. The concentrations of glucose and lactate were monitored in subcutaneous interstitial fluid over a 24 h period using microdialysis. Plasma hormone and substrate concentrations were measured in a blood sample collected in the morning of the fourth day. RESULTS: CHO OF increased plasma leptin concentrations by 28%, and 24 h EE by 7%. Basal metabolic rate and the energy expended during physical activity were not affected. FAT OF did not significantly change plasma leptin concentrations or energy expenditure. There was no relationship between changes in leptin concentrations and changes in energy expenditure, suggesting that leptin is not involved in the stimulation of energy metabolism during overfeeding. Interstitial subcutaneous glucose and lactate concentrations were not altered by CHO OF and FAT OF. CONCLUSIONS: CHO OF, but not FAT OF, increases energy expenditure and leptin concentration.

3-Hydroxybutyric Acid↗

PubMed2000

Effects of glucocorticoids on hepatic sensitivity to insulin and glucagon in man.

AIMS: This study was undertaken to determine the effects of a short-term dexamethasone treatment on hepatic sensitivities to insulin and glucagon. METHODS: Eleven healthy subjects were studied during one or several of four protocols. In all protocols, somatostatin was infused continuously to inhibit pancreatic hormone secretion. In protocol 1, basal insulin was infused over 300 min while glucagon was infused at a rate of 0.5 mg/kg(-1)/min(-1)during 180 min, then at a rate of 1.5 ng/kg(-1)/min(-1)during 150 min. In protocol 2, the same experiment was performed after a 2 day treatment with 8 mg/day dexamethasone. In protocol 3, the two-step glucagon infusion was performed during insulin infusion at a rate aimed to reproduce the hyperinsulinemia observed during protocol 2. In protocol 4, continuous basal insulin and low glucagon (0.5 mg/kg(-1)/min(-1)) were infused over 330 min. RESULTS: In protocol 1, plasma glucose rose transiently by 2.0 +/- 0.3 mmol/l when the glucagon rate was increased and glucose production increased by 1.4 +/- 0.5 micromol/kg(-1)/min(-1). In protocol 2, the insulin infusion rate (1.85 +/- 0.36 nmol/kg(-1)/min(-1)) required to maintain glycemia was 3.3-fold higher than during protocol 1. Glucagon-induced stimulation of glycemia (by 1.47 +/- 0.5 mmol/l) and endogenous glucose production (by 0.8 +/- 0.3 micromol/kg(-1)/min(-1)) were blunted, but not abolished. In protocol 3, endogenous glucose production was suppressed by 75% by hyperinsulinemia and was not stimulated when the glucagon infusion rate was increased. In protocol 4, endogenous glucose production did not change significantly with time. CONCLUSION: These results indicate that high dose glucocorticoids induce a marked hepatic insulin resistance. Stimulation of glucose production by hyperglucagonemia was maintained in spite of hyperinsulinemia which can be attributed to either hepatic insulin resistance and/or increased hepatic glucagon sensitivity.

Adult↗

PubMed2000

Effects of enteral carbohydrates on de novo lipogenesis in critically ill patients.

BACKGROUND: Conversion of glucose into lipid (de novo lipogenesis; DNL) is a possible fate of carbohydrate administered during nutritional support. It cannot be detected by conventional methods such as indirect calorimetry if it does not exceed lipid oxidation. OBJECTIVE: The objective was to evaluate the effects of carbohydrate administered as part of continuous enteral nutrition in critically ill patients. DESIGN: This was a prospective, open study including 25 patients nonconsecutively admitted to a medicosurgical intensive care unit. Glucose metabolism and hepatic DNL were measured in the fasting state or after 3 d of continuous isoenergetic enteral feeding providing 28%, 53%, or 75% carbohydrate. RESULTS: DNL increased with increasing carbohydrate intake (f1.gif" BORDER="0"> +/- SEM: 7.5 +/- 1.2% with 28% carbohydrate, 9.2 +/- 1.5% with 53% carbohydrate, and 19.4 +/- 3.8% with 75% carbohydrate) and was nearly zero in a group of patients who had fasted for an average of 28 h (1.0 +/- 0.2%). In multiple regression analysis, DNL was correlated with carbohydrate intake, but not with body weight or plasma insulin concentrations. Endogenous glucose production, assessed with a dual-isotope technique, was not significantly different between the 3 groups of patients (13.7-15.3 micromol * kg(-1) * min(-1)), indicating impaired suppression by carbohydrate feeding. Gluconeogenesis was measured with [(13)C]bicarbonate, and increased as the carbohydrate intake increased (from 2.1 +/- 0.5 micromol * kg(-1) * min(-1) with 28% carbohydrate intake to 3.7 +/- 0.3 micromol * kg(-1) * min(-1) with 75% carbohydrate intake, P: < 0. 05). CONCLUSION: Carbohydrate feeding fails to suppress endogenous glucose production and gluconeogenesis, but stimulates DNL in critically ill patients.

Adult↗

PubMed2000

Effect of diets high or low in unavailable and slowly digestible carbohydrates on the pattern of 24-h substrate oxidation and feelings of hunger in humans.

BACKGROUND: The pattern of substrate utilization with diets containing a high or a low proportion of unavailable and slowly digestible carbohydrates may constitute an important factor in the control, time course, and onset of hunger in humans. OBJECTIVE: We tested the hypothesis that isoenergetic diets differing only in their content of unavailable carbohydrates would result in different time courses of total, endogenous, and exogenous carbohydrate oxidation rates. DESIGN: Two diets with either a high (H diet) or a low (L diet) content of unavailable carbohydrates were fed to 14 healthy subjects studied during two 24-h periods in a metabolic chamber. Substrate utilization was assessed by whole-body indirect calorimetry. In a subgroup of 8 subjects, endogenous and exogenous carbohydrate oxidation were assessed by prelabeling the body glycogen stores with [(13)C]carbohydrate. Subjective feelings of hunger were estimated with use of visual analogue scales. RESULTS: Total energy expenditure and substrate oxidation did not differ significantly between the 2 diets. However, there was a significant effect of diet (P: = 0.03) on the carbohydrate oxidation pattern: the H diet elicited a lower and delayed rise of postprandial carbohydrate oxidation and was associated with lower hunger feelings than was the L diet. The differences in hunger scores between the 2 diets were significantly associated with the differences in the pattern of carbohydrate oxidation among diets (r = -0.67, P: = 0. 006). Exogenous and endogenous carbohydrate oxidation were not significantly influenced by diet. CONCLUSIONS: The pattern of carbohydrate utilization is involved in the modulation of hunger feelings. The greater suppression of hunger after the H diet than after the L diet may be helpful, at least over the short term, in individuals attempting to better control their food intake.

Adult↗

PubMed2000

Intestinal absorption in patients after cardiac surgery.

OBJECTIVES: We designed this study to assess intestinal absorption in patients with adequate or altered hemodynamic status after cardiac surgery and to test clinical tolerance to early enteral nutrition. DESIGN: Prospective, descriptive study. SETTING: Surgical intensive unit in a university teaching hospital. PATIENTS: Cardiac surgery patients, age 64+/-10 yrs (mean +/-SD) were subdivided into two groups according to hemodynamic status: group I, 16 patients with adequate hemodynamic status; group II, 23 patients with hemodynamic failure. These groups were compared with healthy controls (group III, n = 6). INTERVENTIONS: Paracetamol pharmacokinetic study on days 1 and 3 with nasogastric or postpyloric paracetamol administration. Early postpyloric or conventional gastric nutrition in group II. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations were measured on days 1 and 3, and area under the curve (AUC) was calculated. Absorption was strongly reduced on day 1 in all patients after gastric administration (lower peak paracetamol and AUC), but normal after postpyloric delivery. Duration of anesthesia and of circulatory bypass did not affect paracetamol absorption. On day 3, AUC was close to normal in case of hemodynamic failure. Peak absorption on day 1 was negatively correlated with opiate dose (r2 = 0.176, p = .008). Hypocaloric enteral nutrition was well tolerated. CONCLUSIONS: The close-to-normal AUC, during low cardiac output, despite lower peak paracetamol, shows absorption was not suppressed, only delayed, because of decreased pyloric motility. The decrease on day 1 can be attributed to opiates, known to alter pyloric function and to slow down the intestinal transit.

APACHE↗

PubMed2000

Effects of cardiogenic shock on lactate and glucose metabolism after heart surgery.

BACKGROUND: Hyperlactatemia is a prominent feature of cardiogenic shock. It can be attributed to increased tissue production of lactate related to dysoxia and to impaired utilization of lactate caused by liver and tissue underperfusion. The aim of this prospective observational study was to determine the relative importance of these mechanisms during cardiogenic shock. PATIENTS: Two groups of subjects were compared: seven cardiac surgery patients with postoperative cardiogenic shock and seven healthy volunteers. METHODS: Lactate metabolism was assessed by using two independent methods: a) a pharmacokinetic approach based on lactate plasma level decay after the infusion of 2.5 mmol x kg(-1) of sodium lactate; and b) an isotope dilution technique for which the transformation of [13C]lactate into [13C]glucose and 13CO2 was measured. Glucose turnover was determined using 6,62H2-glucose. RESULTS: All patients suffered from profound shock requiring high doses of inotropes and vasopressors. Mean arterial lactate amounted to 7.8 +/- 3.4 mmol x L(-1) and mean pH to 7.25 +/- 0.07. Lactate clearance was not different in the patients and controls (7.8 +/- 3.4 vs. 10.3 +/- 2.1 mL x kg(-1) x min(-1)). By contrast, lactate production was markedly enhanced in the patients (33.6 +/- 16.4 vs. 9.6 +/- 2.2 micromol x kg(-1) x min(-1); p < .01). Exogenous [13C]lactate oxidation was not different (107 +/- 37 vs. 103 +/- 4 mmol), and transformation of [13C]lactate into [13C]glucose was not different (20.0 +/- 13.7 vs. 15.2% +/- 6.0% of exogenous lactate). Endogenous glucose production was markedly increased in the patients (1.95 +/- 0.26 vs. 5.3 +/- 3.0 mg x kg(-1) x min(-1); p < .05 [10.8 +/- 1.4 vs. 29.4 +/- 16.7 micromol x kg(-1) x min(-1)]), whereas net carbohydrate oxidation was not different (1.7 +/- 0.5 vs. 1.3 +/- 0.3 mg x kg(-1) x min(-1) [9.4 +/- 2.8 vs. 7.2 +/- 1.7 micromol x kg(-1) x min(-1)]). CONCLUSIONS: Hyperlactatemia in early postoperative cardiogenic shock was mainly related to increased tissue lactate production, whereas alterations of lactate utilization played only a minor role. Patients had hyperglycemia and increased nonoxidative glucose disposal, suggesting that glucose-induced stimulation of tissue glucose uptake and glycolysis may contribute significantly to hyperlactatemia.

Acidosis, Lactic↗

PubMed2000

Effects of mental stress on insulin-mediated glucose metabolism and energy expenditure in lean and obese women.

The effects of the sympathetic activation elicited by a mental stress on insulin sensitivity and energy expenditure (VO(2)) were studied in 11 lean and 8 obese women during a hyperinsulinemic-euglycemic clamp. Six lean women were restudied under nonselective beta-adrenergic blockade with propranolol to determine the role of beta-adrenoceptors in the metabolic response to mental stress. In lean women, mental stress increased VO(2) by 20%, whole body glucose utilization ([6,6-(2)H(2)]glucose) by 34%, and cardiac index (thoracic bioimpedance) by 25%, whereas systemic vascular resistance decreased by 24%. In obese women, mental stress increased energy expenditure as in lean subjects, but it neither stimulated glucose uptake nor decreased systemic vascular resistance. In the six lean women who were restudied under propranolol, the rise in VO(2), glucose uptake, and cardiac output and the decrease in systemic vascular resistance during mental stress were all abolished. It is concluded that 1) in lean subjects, mental stress stimulates glucose uptake and energy expenditure and produces vasodilation; activation of beta-adrenoceptors is involved in these responses; and 2) in obese patients, the effects of mental stress on glucose uptake and systemic vascular resistance, but not on energy expenditure, are blunted.

Adrenergic beta-Antagonists↗

PubMed2000

Effects of fructose on hepatic glucose metabolism in humans.

Hepatic and extrahepatic insulin sensitivity was assessed in six healthy humans from the insulin infusion required to maintain an 8 mmol/l glucose concentration during hyperglycemic pancreatic clamp with or without infusion of 16.7 micromol. kg(-1). min(-1) fructose. Glucose rate of disappearance (GR(d)), net endogenous glucose production (NEGP), total glucose output (TGO), and glucose cycling (GC) were measured with [6,6-(2)H(2)]- and [2-(2)H(1)]glucose. Hepatic glycogen synthesis was estimated from uridine diphosphoglucose (UDPG) kinetics as assessed with [1-(13)C]galactose and acetaminophen. Fructose infusion increased insulin requirements 2.3-fold to maintain blood glucose. Fructose infusion doubled UDPG turnover, but there was no effect on TGO, GC, NEGP, or GR(d) under hyperglycemic pancreatic clamp protocol conditions. When insulin concentrations were matched during a second hyperglycemic pancreatic clamp protocol, fructose administration was associated with an 11.1 micromol. kg(-1). min(-1) increase in TGO, a 7.8 micromol. kg(-1). min(-1) increase in NEGP, a 2.2 micromol. kg(-1). min(-1) increase in GC, and a 7.2 micromol. kg(-1). min(-1) decrease in GR(d) (P < 0. 05). These results indicate that fructose infusion induces hepatic and extrahepatic insulin resistance in humans.

Adult↗

PubMed2000

Major reduction in plasma Lp(a) levels during sepsis and burns.

Plasma levels of lipoprotein(a) [Lp(a)], an atherogenic particle, vary widely between individuals and are highly genetically determined. Whether Lp(a) is a positive acute-phase reactant is debated. The present study was designed to evaluate the impact of major inflammatory responses on plasma Lp(a) levels. Plasma levels of C-reactive protein (CRP), low density lipoprotein cholesterol, Lp(a), and apolipoprotein(a) [apo(a)] fragments, as well as urinary apo(a), were measured serially in 9 patients admitted to the intensive care unit for sepsis and 4 patients with extensive burns. Sepsis and burns elicited a major increase in plasma CRP levels. In both conditions, plasma concentrations of Lp(a) declined abruptly and transiently in parallel with plasma low density lipoprotein cholesterol levels and closely mirrored plasma CRP levels. In 5 survivors, the nadir of plasma Lp(a) levels was 5- to 15-fold lower than levels 16 to 18 months after the study period. No change in plasma levels of apo(a) fragments or urinary apo(a) was noticed during the study period. Turnover studies in mice indicated that clearance of Lp(a) was retarded in lipopolysaccharide-treated animals. Taken together, these data demonstrate that Lp(a) behaves as a negative acute-phase reactant during major inflammatory response. Nongenetic factors have a major, acute, and unexpected impact on Lp(a) metabolism in burns and sepsis. Identification of these factors may provide new tools to lower elevated plasma Lp(a) levels.

Adult↗

PubMed2000

Mechanisms of postprandial hyperglycemia in liver transplant recipients: comparison of liver transplant patients with kidney transplant patients and healthy controls.

Impaired glucose tolerance or diabetes mellitus are frequent complications after organ transplantation, and are usually attributed to glucocorticoid and immunosuppressive treatments. Liver transplantation results in total hepatic denervation which may also affect glucoregulation. We therefore evaluated postprandial glucose metabolism in a group of patients with liver cirrhosis before and after orthotopic liver transplantation. Seven patients with liver cirrhosis of various etiologies, 6 patients having received a kidney transplant, and 6 healthy subjects were studied. Their glucose metabolism was evaluated in the basal state and over 4 hours after ingestion of a glucose load with 6.6 (2) H glucose dilution analysis. The patients with liver cirrhosis were studied before, and again 4 weeks (range 2-6) and 38 weeks (range 20-76, n=6) after orthotopic liver transplantation. Basal glucose metabolism was similar in liver and kidney transplant recipients. Impaired glucose tolerance was present in both groups, but postprandial hyperglycemia was exaggerated and lasted longer in liver transplant patients. Postprandial insulinemia was lower in liver transplant recipients, while C-peptide concentrations were comparable to those of kidney transplant recipients, indicating increased insulin clearance. Glucose turnover was not altered in both groups of patients during the initial 3 hours after glucose ingestion, but was higher in liver transplant early after transplantation during the fourth hour. Postprandial hyperglycemia remained unchanged in liver transplant recipients 38 weeks after liver transplantation, despite substantial reduction of immunosuppressive and glucocorticoid doses. We conclude that liver transplant recipients have severe postprandial hyperglycemia which can be attributed to insulinopenia (secondary, at least in part, to increased insulin clearance) and a late increased glucose turnover. These changes may be secondary to hepatic denervation.

Adult↗

PubMed2000

Counterregulatory responses to hypoglycemia in patients with glucokinase gene mutations.

The glucokinase gene is expressed not only in pancreatic B cells and in the liver, but also in pancreatic alpha cells, and in some cells of the central nervous system. A decreased glucokinase activity in the latter cell types may interfere with counterregulatory responses to hypoglycemia. In order to assess functional consequences of glucokinase mutations, counterregulatory hormones secretion and glucose production (6,6(- 2) H glucose) were monitored during an hyperinsulinemic clamp at about 2.4 pmol.kg(- 1).min(- 1) insulin with progressive hypoglycemia in 7 maturity onset diabetes of the young (MODY) type 2 patients, 5 patients with type 2 diabetes, and 13 healthy subjects. Basal glucose concentrations were significantly higher in MODY2 patients (7.6 +/- 0.4 mmol.l(- 1) ) and type 2 diabetic patients (12.4 +/- 2.3 mmol.l(- 1) ) than in healthy subjects (5.3 +/- 0.1 mmol.l(- 1), p<0.01) but counterregulatory hormones concentrations were identical. Insulin-mediated glucose disposal and suppression of endogenous glucose production at euglycemia were unchanged in MODY2 patients, but were blunted in type 2 diabetes. During progressive hypoglycemia, the glycemic thresholds of MODY2 patients for increasing glucose production (5.0 +/- 0.4 mmol.l(- 1) ) and for glucagon stimulation (4.5 +/- 0.4 mmol. l(- 1) ) were higher than those of healthy subjects and type 2 diabetic patients (3.9 +/- 0.1 and 4.1 +/- 0.1 mmol.l(- 1) respectively for glucose production and 3.7 +/- 0.1 and 3.5 +/- 0.1 mmol.l(- 1) for glucagon stimulation, p <0.02 in both cases). These results indicate that counterregulatory responses to hypoglycemia are activated at a higher plasma glucose concentration in MODY2 patients. This may be secondary to decreased glucokinase activity in hypothalamic neuronal cells, or to alterations of glucose sensing in pancreatic alpha cells and liver cells.

Adult↗

PubMed2000

[Nutrition and stress].

Acute illness induces major physiological responses, which favor the adaptation of the organism to stress and injury. The metabolic response plays key roles in maintenance of vital functions and promotion of the healing mechanisms. All the components of energy expenditure are modified, particularly the resting metabolism. The regulation of carbohydrate metabolism is also markedly altered. Such patients are characterized by fasting and postprandial hyperglycemia, insulin resistance, and by a stimulation of the hepatic glucose production in fasted and fed states. Lipolysis and increased fat oxidation are typically observed. Ketogenesis processes are inhibited, concurring to alter the adaptation to starvation. Protein turnover is stimulated with a preponderance of the catabolic processes, even during full nutritional support. This induces a state of resistance to feeding, leading to a progressive depletion of the fat free mass. Such progressive tissue catabolism cannot be reversed by hypercaloric nutrition or growth factors. Specific nutrients (aminoacids, micronutrients, PUFA) may offer interesting perspectives in stimulating immunity, improving the antioxidant balance or modulating the inflammatory response.

Acute Disease↗