Relative importance of amino acid infusion as a means of sparing protein in surgical patients

We performed isotopic infusions in 51 surgical patients to investigate the effectiveness of different substrates to conserve protein. All patients were initially studied in the basal state and then the effects of glucose infusion (GL, N = 13), lipid infusion (LIP, N = 11), or amino acid infusion (AA, N = 17) were determined. Ten patients receiving total parenteral nutrition (TPN) were also studied. The basal value for net protein catabolism (NPC) in GL patients was 1.53 +/- 0.4 (SEM) g/kg/day decreasing to 1.39 +/- 0.4 g/kg/day during glucose infusion (p less than 0.01). The basal NPC in the LIP group was 2.04 +/- 0.4 g/kg/day decreasing to 1.72 +/- 0.3 g/kg/day during lipid infusion (p less than 0.01). In the TPN patients the NPC was 0.79 +/- 0.46 g/kg/day whereas in the AA patients the basal value for NPC was 1.37 +/- 0.14 g/kg/day decreasing to -0.77 +/- 0.11 g/kg/day during amino acid infusion (p less than 0.0005). From our study we conclude that: (1) All substrates commonly used in intravenous feeding have the capacity to spare protein. (2) Protein sparing was more pronounced when a balanced amino acid infusion was used than with either glucose or lipid infusion alone. (3) This effect is not solely due to insulin secretion as larger insulin responses were seen with both GL and TPN patients. (4) These results may have implications for peripheral vein feeding with amino acid solutions where there is a contraindication for full TPN or the lack of resources for administering it.     

Continuous insulin infusion in hyperglycaemic very-low-birth-weight infants receiving parenteral nutrition

Continuous infusion of insulin was used to improve glucose tolerance in 30 premature (26.4+/-1.4 weeks) very-low-birth-weight (750+/-211.3 g) hyperglycaemic infants receiving parenteral nutrition. Infusion of insulin was started at 159.1+/-67 h of life; while glycaemia was 12.1+/-3.3 mmol/l. Normoglycaemia was restored within 31.4h (range 2-134 h). A maximum insulin dose of 0.4 (range 0.07-4.2)IU/kg/h was required to control the blood glucose, the mean cumulative doses of insulin required was 3.27 IU/kg (range 0.09-18.1). The mean glucose infusion rate during insulin treatment was 20.3+/-1.7 g/kg/day; lipid was 4.6+/-1.1 g/kg/day and non-protein caloric intake 121.7+/-16.5 kcal/kg/day. Infants reach 85 kcal/kg/day of non-protein energy intake at 179.5+/-71.2 h after birth. During continuous insulin infusion, enteral feeding was started in all infants at 124.9+/-75.8 h of life. Insulin was continued for 317.7+/-196.6 h. Only two infants lost weight during the first week of treatment, the remaining infant gained weight steadily. In conclusion, continuous insulin infusion can rapidly and safely improve intravenous glucose tolerance, allowing higher caloric intake and growth in very-low-birth-weight infants who develop hyperglycaemia during total parenteral nutrition.     

Impact of enteral and parenteral nutrition on hepatic and muscle glucose metabolism

Liver and muscle metabolism were assessed in dogs adapted to long-term total parenteral (TPN) and enteral (TEN) nutrition. Studies were done in 13 conscious long-term catheterized dogs in which sampling (artery, portal and hepatic vein, and iliac vein), infusion catheters (inferior vena cava, duodenum), and transonic flow probes (hepatic artery, portal vein, and iliac artery) were implanted. Fourteen days after surgery dogs were grouped to receive TPN or TEN. After 5 days of TPN/TEN, substrate balances across the liver and limb were assessed. The liver was a marked net consumer of glucose in both groups (23.6 +/- 3.3 vs 22.6 +/- 2.8 micromol x kg(-1) x min(-1), TPN vs TEN) despite near normoglycemia (6.5 +/- 0.3 vs 6.7 +/- 0.2 mmol/L). Arterial insulin levels were higher during TEN (96 +/- 6 vs 144 +/- 30 pmol/L; p < .05). The majority (79 +/- 13 vs 76% +/- 7%) of the glucose taken up by the liver was released as lactate. Despite higher insulin levels during TEN the nonsplanchnic tissues consumed a lessor quantity of glucose (25.9 +/- 3.3 vs 16.1 +/- 3.9 micro x mol x kg(-1) x min(-1)). In summary, the liver undergoes a profound adaptation to TPN and TEN making it a major site of glucose uptake and conversion to lactate irrespective of the route of nutrient delivery. However, the insulin requirements are higher with TEN possibly secondary to impaired peripheral glucose removal.     

Effect of age on substrate oxidation during total parenteral nutrition

OBJECTIVE: Parenteral nutrition is increasingly used in the elderly. Aging is accompanied by metabolic changes that can modify substrate use. We compared substrate oxidation during cyclic total parenteral nutrition (TPN) in elderly and middle-aged patients. METHODS: Twelve elderly patients (eight women, four men; 72 +/- 5 y) and 12 middle-aged patients (nine women, three men; 39 +/- 13 y) who were on cyclic TPN for intestinal failure were investigated while in stable condition after at least 15 d of TPN. No patient was diabetic. Indirect calorimetry was performed during fasting and every 30 min during the 3 h of TPN infusion and 3 h after infusion, allowing the measurement of nutrient oxidation. Blood samples were obtained every hour for the measurement of glucose, insulin, triacylglycerols, and free fatty acids. RESULTS: In the fasting state, resting energy expenditure was significantly higher in the elderly patients than in the middle-aged patients (39.3 +/- 8.1 versus 31.9 +/- 4.3 kcal/kg of fat-free mass per day, P = 0.008). During TPN, lipid oxidation was significantly higher in the elderly patients than in the middle-aged patients (1.09 +/- 0.17 versus 0.84 +/- 0.27 mg x kg(-1) x min(-1), P = 0.011); glucose oxidation was significantly lower in the elderly patients than in the middle-aged patients (2.19 +/- 0.93 versus 3.22 +/- 1.54 mg x kg(-1) x min(-1), P = 0.038). Areas under the curves of glycemia and free fatty acids were significantly higher in the elderly patients. CONCLUSION: In the elderly, TPN was associated with significantly higher lipid oxidation and lower glucose oxidation than in younger patients. TPN formulas and flow rates should therefore be adapted in the elderly.     

Postoperative parenteral nutrition while proactively minimizing insulin resistance

OBJECTIVE: We compared the metabolic effects of postoperative total parenteral nutrition (TPN) and hypocaloric glucose after treatment with oral carbohydrates preoperatively and epidural anesthesia to proactively minimize postoperative insulin resistance. METHODS: Thirteen patients undergoing colorectal resections were given oral carbohydrates preoperatively and epidural anesthesia and randomized to TPN or hypocaloric glucose during and after surgery. Insulin sensitivity (hyperinsulinemic clamp [0.8 mU x kg(-1) x min(-1)], normoglycemic clamps [4.5 mM]), and glucose kinetics (6,6(2)H2-D-glucose), were studied before and on postoperative day 3. Indirect calorimetry was performed and nitrogen excretion in urine was measured. Values are presented as mean +/- standard deviation. Analysis of variance, planned comparison, and Bonferroni's correction were used for statistical analysis. RESULTS: Three days after surgery insulin-stimulated whole-body glucose disposal decreased by 24 +/- 11% versus 28 +/- 23% in patients receiving TPN and hypocaloric glucose, respectively (P < 0.05 for both, not significant between groups). Endogenous glucose production during insulin stimulation was increased only in the glucose group after surgery (P < 0.05 versus before). After surgery, insulin-stimulated glucose oxidation was higher after treatment with TPN, whereas fat oxidation was lower (P < 0.05 for both versus glucose treatment). Fat oxidation increased in the glucose group at basal after surgery (P < 0.05 versus before). Nitrogen balance was less negative after treatment with TPN (P < 0.01). CONCLUSIONS: Treatment with TPN does not seem to improve postoperative peripheral insulin sensitivity in patients with minor insulin resistance after pretreatment with preoperative carbohydrates and perioperative epidural anesthesia. Hypocaloric nutrition results in changes in substrate utilization and nitrogen balance resembling starvation, whereas TPN attenuates these changes.     

Evaluation of nonglucose carbohydrates in parenteral nutrition for diabetic patients.

OBJECTIVE: There is little information on the advantages of nonglucose carbohydrates in total parenteral nutrition (TPN) for diabetic patients. The aim of this study is to evaluate glycemic control and insulin requirements in diabetic patients who received TPN with different sources of carbohydrates, and to determine whether insulin requirements are different when septic and non-septic diabetic patients are studied. MATERIALS AND METHODS: One-hundred and thirty-eight patients were randomly divided into two groups receiving either glucose (G), n=71, or glucose-fructose-xylitol 2:1:1 (GFX), n=67. There were no differences between the demographic or anthropometric characteristics of the groups, nor between the patients with diabetes mellitus type 1 and type 2, nor the initial TPN composition. Acceptable glycemic control was considered when glycemia reached <200 mg/dl. RESULTS: Glycemic control was attained in 79.7% of patients (74.6 vs 85.1%), in the same period of treatment. At the end of treatment, insulin requirements were not different (45+/-19 vs 45+/-26 UI/day) in both groups, while similar amounts of carbohydrates (191+/-36 vs 187+/-45 g/day) were infused. The ratio insulin/body weight and insulin/carbohydrates were equal in both groups. In the GFX group nonseptic and septic patients needed less and more insulin, respectively, than their counterparts in the G group. No major adverse events related to carbohydrate infusions were observed. CONCLUSIONS: Either G or GFX could be used in TPN for diabetic patients, providing glycemic control in most cases with similar insulin requirements. GFX mixtures were slightly more beneficial to attain glycemic control in nonseptic patients, but septic diabetic patients had higher insulin needs in this group.     

Splanchnic glucose balance and insulin resistance in the early postoperative phase of cardiac surgery

The splanchnic balance of glucose was studied in the basal state and at three levels of "clamped" hyperinsulinemia (260 +/- 23, 510 +/- 59, 3875 +/- 367 mU/liter) in 24 patients (43-70 years of age), who had undergone coronary surgery about 1 hr previously. The splanchnic balance of glucose in the basal state was negative in all patients (-1.6 +/- 0.3 mg/kg/min) and was changed into a zero-balance within 30 min when 0.15 or 0.3 U/kg/hr of insulin was infused. At an insulin infusion rate of 1.0 U/kg/hr the net splanchnic glucose balance was turned into a significant positive balance of an average 0.9 +/- 0.3 mg/kg/min.     

Total parenteral nutrition in very low birth weight infants with Travasol 10% blend C

Ten very low birth weight (VLBW) infants (birth weight: 994 +/- 66 g, gestational age: 27 +/- 0.5 wk) requiring total parenteral nutrition (TPN) were studied in order to evaluate their metabolic response to the amino acid solution Travasol 10% blend C. These patients received the solution at a constant rate, providing 2.61 +/- 0.02 g/kg/day of amino acids and 76 +/- 1 kcal/kg/day. Plasma amino acids analysis was performed after 4.6 +/- 0.3 day of infusion and compared to values reported previously with Travasol blend B. The new solution (blend C) showed a significantly lower (p less than 0.001) glycinemia (485 +/- 24 vs 993 +/- 69 mumol/liter), methioninemia (39 +/- 2 vs 114 +/- 12 mumol/liter) and phenylalaninemia (67 +/- 3 vs 92 +/- 5 mumol/liter) related to the lower intake of these amino acids. Despite the provision of 47.5 mmol/liter of serine with blend C no changes in plasma level (182 +/- 15 vs 196 +/- 41 mumol/liter) were noted. The increased molar arginine/glycine ratio (blend C: 0.48 vs blend B 0.22) could have contributed to keep ammoniemia within normal levels (55.1 +/- 4.2 mumol/liter). Wide variations in insulin response (9.9 to 26.4 microU/ml) allowed for a correlation between its plasma concentration and those of sensitive amino acids, underlining its role in protein metabolism. Despite the immaturity of the study population no short-term metabolic imbalance has been encountered with the Travasol blend C solution.     

Platelet glutathione peroxidase activity in long-term total parenteral nutrition with and without selenium supplementation.

Selenium (Se) is not routinely included in total parenteral nutrition (TPN) solution; thus, patients receiving long-term TPN may be at risk of Se deficiency, which may cause fatal cardiomyopathy. Platelet glutathione peroxidase (GSH-Px) activity, as well as Se levels and GSH-Px activity in plasma and erythrocytes during prolonged TPN, was measured in six patients with chronic gastrointestinal disease. During the time course of TPN, Se administration was discontinued for 12 weeks, and then resupplemented for another 12 weeks. Before the study period, all Se indices had been maintained within the normal range. After discontinuation of Se supplementation, a significant decrease in platelet GSH-Px activity was observed after 1 week (from 64 +/- 7 [mean +/- SD] to 39 +/- 5 U/g of protein). After resupplementation, it increased after 1 week (from 44 +/- 9 to 65 +/- 10 U/g of protein). Plasma Se indices significantly changed within 3 weeks after withdrawal and reintroduction of Se (Se: from 136 +/- 28 to 75 +/- 14 and from 61 +/- 22 to 125 +/- 33 micrograms/L; GSH-Px: from 236 +/- 50 to 140 +/- 36 and from 128 +/- 32 to 220 +/- 64 U/L). Erythrocyte Se indices showed no significant changes during the study period. The results demonstrate that platelet GSH-Px activity is the most sensitive index of Se status in TPN patients.     

Parenteral nutrition for marrow transplant recipients: evaluation of an increased nitrogen dose

The use of total parenteral nutrition in bone marrow transplant (BMT) recipients is well recognized. These patients as a result of treatment with chemotherapy and immunosuppressive agents undergo catabolic stress. The metabolic effect of an increased nitrogen dose during total parenteral nutrition (TPN) was studied in 28 BMT patients. Patients were given TPN formulas providing a nitrogen intake of either 267 +/- 44 mg of N/kg/d or 330 +/- 60 mg of N/kg/d. Total calories, nonprotein and protein, were held constant at 40 kcal/kg/d for all patients. Data was collected for three periods posttransplant beginning at 3 days posttransplant through day 16. Both study TPN formulas improved patient weight and TIBC values over baseline. Nitrogen balance (NB) values were not significantly different at any study period. However, an overall group effect favored the H-N formula (p less than 0.01). BMT patients undergo catabolic stress which was reflected by average values of 24-hour urine urea nitrogen increasing from 8.1 +/- 4 g/d at baseline to 19.8 +/- 7.2 g/d at period 3 (p less than 0.01). The H-N formula did not differentially increase blood urea nitrogen or serum creatinine levels. Metabolic cart measures also showed no increase in metabolic rate, oxygen consumption, carbon dioxide production, or percent contribution of protein to total metabolic expenditure. Providing a caloric intake of 40 kcal/kg/d was excessive, where 30 to 35 kcal/kg/d would meet metabolic demands. Pertinent clinical outcomes including length of stay, relapse rate, and survival were monitored, but no conclusions could be drawn in this study. The H-N formula was more effective in reducing loss of lean body mass without causing detrimental metabolic effects in BMT patients.     

Effect of glutamine-enriched total parenteral nutrition in patients with acute pancreatitis

BACKGROUND: The management of acute pancreatitis (AP) frequently includes parenteral nutrition, but conditionally essential amino acids such as glutamine are not included in conventional total parenteral nutrition (TPN).AIM: This study was conducted to determine whether the inclusion of glutamine has a beneficial effect in patients with AP receiving TPN. METHODS: In a randomized, controlled study 28 patients with AP received either a standard TPN with 1.5 g/kg body weight protein or an isonitrogen, isocaloric TPN which contains 0.3 g/kg L -alanine- L -glutamine. Patients were assessed for nutritional and inflammatory parameters, infectious complications, length of TPN, length of hospital stay (LOS) and cost of TPN. RESULTS: There were no side-effects related to glutamine substitution observed. Glutamine was associated with a significant increase of cholinesterase, albumin and lymphocyte count in AP as well a decrease of C-reactive protein compared to standard TPN at day 14. There was a reduced length of TPN (10 [6-16] vs 16 [10-18] days, P<0.05) and a trend of reduced LOS (21 [14-32] vs 25 [19-40] days) in AP patients receiving glutamine. The overall cost per patient for TPN did not differ (gln+: 929+/-586 vs gln-: 981+/-507 euro/patient). CONCLUSION: Our results suggest that glutamine substitution is beneficial and does not increase the overall cost of parenteral feeding in patients with acute pancreatitis.     

Metabolic effects of high-carbohydrate, high-fiber diets for insulin-dependent diabetic individuals.

The metabolic effects of high-carbohydrate (70%), high-fiber (70 g) (HCHF) and low-carbohydrate (39%), low-fiber (10 g) (LCLF) diets were examined for 10 subjects with insulin-dependent diabetes mellitus (IDDM). After a 1-wk control period subjects on a metabolic ward were randomly allocated to HCHF or LCLF diets for 4 wk. After a 6-wk washout period subjects re-entered the metabolic ward for 4 wk on the alternate diet. Artificial-pancreas studies were performed on each diet for measurement of insulin requirements. Compared with the LCLF diet, the HCHF diet reduced basal insulin requirements (P less than 0.025), increased carbohydrate disposed of per unit insulin (P less than 0.0008), and lowered total (P less than 0.0004) and high-density-lipoprotein cholesterol (P less than 0.0013). Glycemic control and other lipid fractions did not differ significantly. These results suggest that in IDDM patients, HCHF diets enhance peripheral glucose disposal, decrease basal insulin requirements, and lower total cholesterol without altering glycemic control or triglycerides.     

Tissue carnitine concentrations after total parenteral nutrition with and without L-carnitine supplementation

The concentrations (mumoles/g dry weight) of total carnitine (TC), free carnitine (FC) and acylcarnitine (AC) were determined in skeletal muscle, heart, liver, kidney and brain cortex of male mini pigs (4000-5000 g) after seven days of total parenteral nutrition (TPN) with amino acids 5% (3.0g/kg/d), glucose (25g/kg/d) and lipids 20% (4g/kg/d). This regime was administered with L-carnitine supplementation (1.5 mg/kg/d; n = 7) (group 1) and without it (n = 5) (group 2). Orally alimented animals (n = 5) served as controls (group 3). (Average carnitine intake: 3 mg/d) Carnitine free TPN affected only the concentrations in muscle. TC was markedly reduced (3.6 +/- 0.8) when compared with oral controls (5.8 +/- 0.7) (p<0.01). This decrease was exclusively due to AC, whereas FC concentrations remained almost unchanged. In group 1 the concentrations of TC in skeletal muscle, heart and brain cortex were higher than in both the other groups. The increase was mainly due to AC and FC remained unchanged in heart and brain. The concentrations in liver and kidney were not affected by either carnitine free or carnitine supplemented TPN. AC, determined as described, consists almost entirely of acid soluble acetyl-carnitine, the major product of fatty acid oxidation. Since the AC concentrations were almost exclusively altered by the two TPN-regimes we conclude that the observed changes reflect regulatory changes of fatty acid oxidation. Thus the decrease of muscle TC in group 2 is considered a consequence of an insulin induced down regulation (plasma insulin: mean 20 muU/ml; maximum: 60 muU/ml) of fatty acid oxidation in consequence of high glucose intake (25 g/kg/d). The increased TC concentrations after carnitine supplemented TPN are discussed to reflect an enhancement of oxidative degradation of fatty acids as a pharmacological effect of L-carnitine.     

Continuous infusion of insulin in hyperglycemic low-birth weight infants receiving parenteral nutrition with and without lipid emulsion

The efficiency of a continuous infusion of insulin in improving glucose tolerance was compared in two groups of very low-birth weight infants (mean +/- SEM birth weights 757 +/- 40 vs 828 +/- 80 g and gestational ages 27.6 +/- 0.7 vs. 27.2 +/- 0.5 weeks) receiving total parenteral nutrition with and without the addition of lipid emulsion to the nutrition regimen. The mean +/- SEM cumulative doses of insulin (0.87 +/- 0.1 vs 1.15 +/- 0.3 U/kg) and hours required to decrease the blood glucose level to 120 mg/dL (9.1 +/- 0.8 vs 9.5 +/- 1.0 hours) were similar. Insulin was delivered with a syringe pump used for other routine purposes in the neonatal intensive care unit. Continuous intravenous insulin infusion is an effective, inexpensive, safe method for maintaining glucose homeostasis in low-birth weight infants who develop hyperglycemia as a consequence of total parenteral nutrition.     

Molybdenum requirements in low-birth-weight infants receiving parenteral and enteral nutrition.

BACKGROUND: Molybdenum (Mo) is an essential trace element required by three enzymatic systems, yet there are no reports of Mo deficiency in infants. Low-birth-weight infants (LBW) might be at risk for Mo deficiency because they are born before adequate stores for Mo can be acquired, they have rapid growth requiring increased intakes, and they frequently receive supplemental parenteral nutrition (SPN) and total parenteral nutrition (TPN) unsupplemented with molybdenum. METHODS: To investigate Mo requirements of LBW infants (n = 16; birth weight, 1336+/-351 g; gestational age, 29.8+/-2.5 weeks; M+/-SD), the authors collected all feeds, urine, and feces prior to TPN (baseline, n = 16, collections = 16), during TPN (n = 9, collections = 19), during SPN (n = 13, collections = 17), and after one week of full oral feeds (FOFs) of formula or human milk (FOF, n = 16, collections = 16). RESULTS: Infant weights at collection times were: 1.3+/-0.3 g, 1.27+/-0.4 g, 1.4+/-0.3 g, and 1.7+/-0.5 g, respectively. Mo intake was 0.03+/-0.1 microg/d, 0.34+/-0.1 microg/d, 1.25+/-1.7 microg/d, and 6.1+/-2.5 microg/d. Mo output was 0.64+/-0.6, 0.34+/-0.5, 0.68+/-0.8, and 4.1+/-2.5 microg/d. Mo balance at these times was -0.60+/-0.5, -0.001+/-0.5, 0.57+/-1.9, and 2.0+/-2.9 microg/d. Mo balance increased with time, yet some infants were always in negative balance, even though Mo intakes exceeded recommendations. CONCLUSIONS: The authors speculate that an intravenous intake of 1 microg/kg/d (10 nmol/kg/d) and an oral intake of 4-6 microg/kg/d (40-60 nmol/kg/d) would be adequate for the LBW infant.     

Recovery of [13C]-bicarbonate as respiratory 13CO2 in parenterally fed infants

Ten infants on continuous total parenteral nutrition (TPN) were infused with NaH13CO3 for 6 h in order to assess the amount of 13C recovered as breath 13CO2. Protein intake was 2.8 +/- 0.3 g/kg/d and non-protein energy intake 107 +/- 4 kcal/kg/d (447 +/- 18 kJ/kg/d), provided either as glucose alone or as an isoenergetic glucose-lipid mixture. In the five infants receiving glucose as the sole non-protein energy source, total CO2 production (559 +/- 50 mumol/kg/min), natural 13C abundance of breath CO2 (-11.8 +/- 0.6 delta % versus PDB) and basal 13CO2 production (6.1 +/- 0.6 mumol/kg/min) were higher than in the five infants infused the glucose-lipid mixture (465 +/- 30 mumol/kg/min, P less than 0.02; -16.1 +/- 0.5 delta %, P less than 0.01 and 5.0 +/- 0.3 mumol/kg min, P less than 0.02, respectively). There was a good agreement, in the glucose-infused infants, between the net glucose oxidation rate measured by indirect calorimetry (25.6 +/- 2 g/kg/d) and the glucose oxidation rate estimated from the 13C natural abundances of breath CO2 and infused substrates (23.5 +/- 3 g/kg/d). Steady state 13C enrichment of breath CO2 was reached in all infants after 120 min infusion and ranged from 11.0 to 21.5 delta % over baseline. Steady state 13C enrichment was negatively related to total CO2 production (r = -0.72; P less than 0.02). In contrast, steady state 13CO2 production in excess of baseline was only correlated to bicarbonate infusion rate (r = 0.95; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term parenteral nutrition in unrestrained nonhuman primates: an experimental model

A freely mobile jacket and tether system was developed for the investigation of total parenteral nutrition (TPN)-induced metabolic bone disease and complications of prolonged TPN in 12 Macaca fascicularis nonhuman primates. The animals received TPN for 49 +/- 7 d (means +/- SEM), providing 82 +/- 2 kcal.kg-1.d-1. Serum glucose increased from 3.6 +/- 0.2 mmol/L at baseline to 8.3 +/- 1.9 mmol/L (p less than 0.01) during TPN, and serum albumin decreased from 38 +/- 1 g/L at baseline to 29 +/- 1 g/L (p less than 0.001) during 2.75% amino acid TPN and 30 +/- 2 g/L (p less than 0.01) during 5% amino acid TPN infusion. No significant changes were seen in serum prealbumin, total protein, bilirubin, alanine aminotransferase, and 5'-nucleotidase during TPN infusion. Major complications included catheter sepsis, hyperglycemia, diarrhea, and premature death in six animals. Thus, metabolic complications of prolonged TPN support may be investigated in a freely mobile nonhuman primate.     

Lispro insulin treatment in comparison with regular human insulin in type 2 diabetic patients living in nursing homes

Lispro insulin has been demonstrated to be effective in reducing post-prandial blood glucose levels. Thirty Type 2 diabetic subjects (18 women and 12 men) living in nursing homes, aged 77 +/- 3 yr, mean systolic pressure 147 +/- 6 and diastolic 82 +/- 4 mmHg, body mass index 27.5 +/- 2 kg/m2, known diabetes duration 10.1+/- 0.7 yr, mean HbA1c 8.5 +/- 0.8%, fasting C-peptide 1.3 +/- 0.5 ng/ml, treated with intensive (4 insulin injections per day) therapy, mean insulin need 45 +/- 7 IU per day, with 2.0 +/- 0.6 hypoglycaemic (blood glucose level below 60 mg/dl) and 13 +/- 4 hyperglycaemic episodes (blood glucose level over 250 mg/dl) per wk, were studied. Their own informed consent or that provided by a family member was obtained before these patients took part in a therapy protocol divided into 3 four-mo periods; in the 1st and 3rd period regular insulin (75% of the total dose) was administered 30 min before each meal, in the second lispro insulin was administered immediately at the end of each meal, according to the carbohydrate quantity ingested with the meal. During the lispro treatment period there was a significant decrease of the mean daily blood glucose 166 +/- 12 regular vs 143 +/- 9 lispro; p<0.01, HbA1c 8.5 +/- 0.6 regular vs 7.6 +/- 0.5 % lispro; p<0.01, triglycerides 261 +/- 40 regular vs 218 +/- 20 mg/dl lispro; p<0.01, hypoglycaemic 2.1 +/- 0.2 regular vs 1.6 +/- 0.3 lispro; p<0.01 and hyperglicaemic 12 +/- 1 regular vs 8 +/- 0.3 lispro; p<0.01 episodes per wk. No statistical difference was recorded between the 1st and the 3rd treatment period. The lispro treatment produced a better metabolic control (mean blood glucose, HbA1c, triglycerides), better lifestyle (less hypo- and hyperglycaemic episodes), better nurse management (no waiting time before, but a more accurate calculation of the right dose administered immediately at the end of each meal). Lispro insulin seems to be a good therapeutic choice not only in Type 1, but also in the large population of elderly Type 2 diabetic patients.     

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.     

Effects of L-carnitine supplemented total parenteral nutrition on lipid and energy metabolism in postoperative stress

During episodes of trauma carnitine-free total parenteral nutrition (TPN) may result in a reduction of the total body carnitine pool, leading to a diminished rate of fat oxidation. Sixteen patients undergoing esophagectomy were divided randomly in two equal isonitrogenous groups (0.2 g/kg.day). Both received TPN (35 kcal/kg.day; equally provided as long-chain triglycerides and glucose) over 11 days without (group A) and with (group B) L-carnitine supplementation (12 mg/kg.day = 75 mumol/kg.day). Compared with healthy controls, the total body carnitine pool prior to the operation was significantly reduced in both groups, suggesting a state of semistarvation and muscle wasting. In group A the plasma levels of total carnitine and its subfractions (free carnitine, short- and long-chain acylcarnitine) remained stable during the study whereas in group B the total plasma carnitine concentration rose mainly due to an increase in free carnitine. In group A the cumulative urinary carnitine losses were 11.5 +/- 2.6 mmol (= 15.5 +/- 3.1% of the estimated total body carnitine pool). In group B 3.1 +/- 1.9 mmol (= 11.1 +/- 7.6%) of the infused carnitine was retained in the immediate postoperative phase until day 6, but this amount was completely lost at completion of the study period. No significant differences in the respiratory quotient or in the plasma levels of triglycerides, free fatty acids, and ketone bodies were observed, between or within the groups, before the operation and after 11 days of treatment. It is concluded that the usefulness of carnitine supplementation during postoperative TPN was not apparent in the present patient material.