High Glucose Intake Research Articles

Perinatal taurine depletion causes autonomic dysregulation in rats on a high glucose diet

Perinatal taurine deficiency causes significant dysregulation of the sympathetic nervous system. This study tests the hypothesis such dysregulation causes sympathetic overactivity in perinatal taurine depleted, young male rats on high glucose intake. Female Sprague-Dawlay dams were either taurine depleted (beta-alanine 3% in tap water; TD) or untreated (control, C) from conception to weaning. Their male offspring were fed normal rat chow with either 5% glucose in drinking water (TD with glucose, TDG; C with glucose, CG) or tap water alone (TDW and CW). At 7–8 weeks of age, male offspring were implanted with femoral arterial and venous catheters and 2–3 days later were tested in a conscious, unrestrained state. Renal sympathetic nerve function was tested one day later under thiopental anesthesia. Compared to the control, body weight was slightly lower in TD and TDG rats, but heart and kidney to body weight ratios were not different. Plasma sodium levels also tended to be lower in taurine depleted rats. Fasting and non-fasting plasma potassium, blood urea nitrogen, plasma creatinine, hematocrit, fasting blood glucose, and glucose tolerance were not significantly different among groups. Mean arterial pressures were higher in TDG compared to all other groups (CW, 101±3 mm Hg; CG, 96±3 mm Hg; TDW, 98±2 mm Hg; TDG, 110±2 mm Hg; P<0.05). TDW vs. CW displayed lower resting sympathetic nervous system activity, but glucose supplementation significantly increased it only in TDG. Perinatal taurine depletion also blunted baroreflex function and high glucose intake decreased it in TD but not C rats. These findings indicate that in male rats on a high glucose diet, perinatal taurine depletion causes autonomic dysfunction.

Effect of high glucose intake and insulin resistance on oxidative stress and arterial pressure in the rat

Effect of high glucose intake and insulin resistance on oxidative stress and arterial pressure in the rat

A glucose-rich diet shortens longevity of mice

High plasma levels of glucose and insulin over long time periods play an important role in the genesis of diabetic complications. There is evidence that the long term consumption of glucose-rich diet by rats is detrimental to insulin sensitivity. We investigated the effect of a glucose-rich diet on longevity of 70 female mice which were compared to 70 mice on a control diet. The average age of death of the control group was 568 ± 139 days compared to 511 ± 170 for the glucose group and the seven oldest mice of the control group died at age 890 ± 52 days, while the seven oldest mice of the glucose group died at 833 ± 49 days. These differences are statistically significant ( P ≤ 0.05). Our work shows that a life-long intake of a diet with 20% of total energy derived from glucose leads to a significant reduction of the average and maximal life-span in female mice and thus, supports previous observations of detrimental effects of high glucose intake over long periods.

Influence of calorie source on the physiological response to parenteral nutrition in malnourished rabbits

The present study was designed to investigate whether calorie source influences sodium and water metabolism and sympathetic activity during parenteral nutrition (PN). 20 New Zealand rabbits were starved until a mean weight loss of 18% was achieved and then re-fed for 6 days with 2 formulae of PN with different glucose-fat proportions. In the Glucose group (n = 9), 70% of non-protein calories were given as glucose while in the Lipid group (n = 11), 70% of non-protein calories were administered as lipids. Rabbits with a high glucose intake showed significantly higher weight gain (151 ± 87 vs. 52 ± 7 g, P = 0.01), water cumulative balance (542 ± 132 vs. 411 ± 87 ml; P = 0.02) and urinary metanephrine excretion (0.42 ± 0.12 vs. 0.30 ± 0.1 μmol/d, P = .03). Only in this group, urinary metanephrines correlated positively with water and sodium balances (r2 = 0.6; P = 0.02 and r2 = 0.7; P = 0.009 respectively). The Glucose group showed 2 different responses and in a second experiment 10 additional rabbits were added to this group to allow a statistical analysis of the response pattern: half of the animals increased their extracellular water (ECW) compartment while the remaining animals did not. The former group had higher sodium balance (13.9 ± 8 vs. 4.3 ± 5; P = 0.004) and wet lung weight (8.9 ± 0.9 vs. 7.9 ± 0.8; P < 0.05) after re-feeding and, at the beginning of PN, their serum aldosterone concentration were also higher (221 ± 11 vs. 130 ± 47 pmol/l; P < 0.05). In conclusion, glucose based PN appears to increase sympathetic activity and induce spurious weight gain due to markedly positive wate and sodium balances. Plasma aldosterone concentration at the end of starvation period influences sodium retention and ECW expansion during high glucose re-feeding.

PERSISTENT HYPERINSULINEMIC HYPOGLYCEMIA OF INFANCY (PHHI): PARTIAL AND COMPLETE CLINICAL REMISSION AFTER LONG-TERM OCTREOTIDE TREATMENT

Moderate to severe PHHI usually requires near-total pancreatectomy to avoid hypoglycemia induced brain damage. We treated 13 such patients with octreolide over the last 6 y. Seven subsequently underwent partial pancreatectomy: 2 had inadequate response due to sepsis, 1 failed to respond to combined octreotide/glucagon/diazoxide and 4 because their family situation did not permit chronic octreotide treatment. Data on the remaining 6 pts on chronic octreotide treatment without pancreatectomy are reported here. Frequent feedings with high glucose intake (11-13 mg/kg/min) and raw cornstarch at night were required in all patients, whereas 2 also required gastrostomy due to poor feeding. Octreotide was started immediately in 5 of 6 patients since previous experience indicates that diazoxide is rarely effective in severe disease. Octreotide was given in 3-4 daily sc injections in 3 patients, and continuous sc infusion (Medix insulin infuser) in 3. All patients had acute G1 symptoms (vomiting, abdominal distcntion, steatorrhea) and weight loss after beginning the drug. This responded partially to oral pancreatic enzyme treatment, and remitted after 2-4 weeks. Asymptomatic gallstones were discovered at routine ultrasound in 1 patient after 1 y of treatment. Growth rate decreased in all during the first 2-6 months, but normalized subsequently as did body weight. All patients have normal psychomotor development for age, however 2 are <1 year old. Every 6-12 months an attempt was made to stop octreotide treatment or switch to diazoxide. Five patients stopped octreotide after 8.5 m to 5.5 y; 1 switched to diazoxide (3y), 2 required per-cutaneous gastrostomy, and 1 (5.5 y old) required no further treatment. The remaining 2 (age 4M-1.5y) are still treated with octreotide. We conclude that with octreotide treatment pancreatectomy can be avoided in some patients. However, efficacy is partial, and close follow-up with repeated blood glucose determinations, frequent feedings, gastrostomy and hospital admissions during acute illnesses may still be necessary. Most can eventually stop octreotide and enter complete or partial remission.

GLUCOSE METABOLISM IN A TERM INFANT WITH TRANSIENT HYPERINSULINISM

Large amounts of glucose have to be infused in infants with transient hyperinsulinism. The metabolism of the high glucose intake has not been determined. We studied glucose metabolism in an infant with transient hyperinsulinism without maternal diabetes. Gest. age 41 wks, birthweight 3475 g. Hypoglycemia was observed on day 1 (glucose 0,2 mmol/l with convulsions. Insulin levels decreased from 90 mU/l on day 1 to 7 on day 11. Glucose metabolism was measured by indirect caloriuetry (ID) and stable isotope technique (U - 13C glucose) on day 6 and 11. Results CHO int. = total carbohydrate intake, MR = metabolic rate, RQ = resp. quotient, CHO util. = carbohydrate utilization, measured by ID, Ra = rate of appearance of glucose, Glue. oxid. = glucose oxid. measured by U-13 C glucose, NOD = non-oxidative glue, disposal.Conclusions: 1. Glucose oxidation was not increased despite high glucose intake. 2. Hypoglycemia is not due to increased oxidation but to non-oxidative disposal. 3. There is a high conversion of glucose into fat.

Effects of glucose on nitrogen balance during high nitrogen intake in malnourished patients

1. The effects of increasing glucose intake on nitrogen balance, energy expenditure and fuel utilization were measured in 12 malnourished adult patients receiving parenteral nutrition with constant, very high nitrogen intake (500 mg of N/kg), high (105 kJ/kg) or low (30 kJ/kg) glucose intake and constant fat intake (7 kJ/kg). Each patient received each diet for 8-day periods in random order. 2. Energy balance and nitrogen balance were determined daily. Blood samples, taken at admission, during 5% (w/v) dextrose (D-glucose) infusion and at the end of days 7 and 8 of each diet, were analysed for urea, glucose, lactate, triacylglycerols, fatty acids, glycerol, 3-hydroxybutyrate, insulin and glucagon. 3. The effect of increasing glucose intake was to increase nitrogen balance by 0.60 +/- 0.25 (SEM) mg/kJ. At zero energy balance, nitrogen balance was 48 mg day-1 kg-1. This confirms findings of previous studies: that the effects of glucose on nitrogen balance are greater at high than at low nitrogen intakes, and that, in malnourished patients, unlike in normal adults, markedly positive nitrogen balance can be achieved at zero or negative energy balances. 4. Changes in nitrogen balance were due almost entirely to changes in urea excretion. 5. The high nitrogen intake markedly increased plasma insulin and glucagon concentrations and reduced glycerol, fatty acid and 3-hydroxybutyrate concentrations, independent of any glucose effect. Glucagon concentrations were significantly decreased by added glucose intake, an effect not previously seen at low nitrogen intakes. At this high nitrogen intake, the effects of added glucose appear to be mediated by both insulin and glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)

Total parenteral nutrition in the newborn: amino acids-energy interrelationships

As part of an ongoing study on the influence of intravenous glucose and fat on nitrogen metabolism we evaluated the relationship between the source of infused energy and plasma amino acid levels. Thirty-two studies were performed in 16 appropriate-for-gestational-age newborn infants (birth weight, 2150 +/- 115 g; means +/- SEM). In a crossover design each patient received two 6-d periods of isocaloric and isonitrogenous infusions, differing only by the source of calories (high or low fat intakes). For an energy intake of 80 kcal.kg-1.d-1 (335 kJ.kg-1.d-1) there was a significant hypoaminoacidemia (2338 +/- 185 vs 2937 +/- 196 mumol/L, high fat vs low fat) under the high-glucose intake. These data suggest that above an energy intake of 60 kcal.kg-1.d-1 (251 kJ.kg-1.d-1) there is a threshold at which changes in plasma amino acid levels are triggered by variations in the source of infused energy. Careful examination of all variables, including energy sources, is essential when aminograms are compared.

Effect of different post-exercise sugar diets on the rate of muscle glycogen synthesis

The effect of repeated ingestions of fructose, sucrose, and various amounts of glucose on muscle glycogen synthesis during the first 6 h after exhaustive bicycle exercise was studied. Muscle biopsies for glycogen determination were taken before and after exercise, and every second hour during recovery. Blood samples for plasma glucose and insulin determination were taken before and after exercise, and every hour during recovery. When 0.35 (low glucose: N = 5), 0.70 (medium glucose: N = 5), or 1.40 (high glucose: N = 5) g.kg-1 body weight of glucose were given orally at 0, 2, and 4 h after exercise, the rates of glycogen synthesis were (mean +/- SE) 2.1 +/- 0.5, 5.8 +/- 1.0, and 5.7 +/- 0.9 mmol.kg-1.h-1, respectively. When 0.70 g.kg-1 body weight of sucrose (medium sucrose: N = 5), or fructose (medium fructose: N = 7) was ingested accordingly, the rates were 6.2 +/- 0.5 and 3.2 +/- 0.7 mmol.kg-1.h-1. Average plasma glucose level during recovery were similar in low glucose, medium glucose, and high glucose groups (5.76 +/- 0.24, 6.31 +/- 0.64, and 6.52 +/- 0.24 mM), while average plasma insulin levels were higher with higher glucose intake (16 +/- 1, 21 +/- 3, and 38 +/- 4 microU.ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin Pump Therapy Improves Blood Glucose Control During Hyperalimentation

The present study investigated the feasibility of basal continuous subcutaneous insulin infusion (CSII) in four patients with postoperative sepsis or extensive burns during continuous enteral hyperalimentation with 2,500 to 3,000 calories/day, containing approximately 390 g of simple carbohydrates. The mean duration of CSII treatment was 16.8 days (range, seven to 32 days). The mean capillary blood glucose level fell from 322 +/- 52 mg/dL during pre-CSII therapy to 195 +/- 33 mg/dL during CSII therapy. Only 1.3% of 1,254 capillary blood glucose values were less than 60 mg/dL. Most values (61.6%) were between 61 and 200 mg/dL. The mean insulin infusion rate was 2.5 +/- 1.5 units/hr. These preliminary observations suggest that basal infusion CSII is a safe and effective means of improving blood glucose control in patients receiving enteral hyperalimentation despite the high glucose intake and presence of insulin resistance. Thus, CSII therapy can enhance the metabolic response to hyperalimentation without requiring an intravenous access route.

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

The concentrations (μmoles/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 μU/ml; maximum: 60 μU/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.

The effect of carbohydrate intake on the lipolytic rate in depleted patients

The effect of intravenous carbohydrate intake on glycerol turnover and fat metabolism was estimated in six nutritionally depleted surgical patients requiring total parenteral nutrition. Two diets were given. Nitrogen intake was the same in both diets. The calorie intake, adjusted by varying glucose intake, provided either 72% or 128% of the measured resting energy expenditure. Glycerol turnover was measured during administration of 5% dextrose solutions before starting total parenteral nutrition, and again after 4 days on each diet. Turnover rates of glycerol were closely correlated with plasma concentrations. However, fractional turnover rates were only two-thirds of normal values, indicating decreased clearance possibly due to decreased hepatic blood flow. Glycerol turnover, plasma free fatty acid concentrations, and the rate of fat oxidation declined progressively with increased glucose intake. When compared with these results, previous studies of injured and septic patients showed: higher values for glycerol turnover, FFA concentrations, and fat oxidation; poor correlation between glycerol turnover and concentration; inhibition of lipogenesis at high glucose intake; and high rates of norepinephrine excretion. The data suggest that in severe injury, counter regulatory hormones may almost completely block the effects of insulin on hormone sensitive lipase but have less influence on insulin stimulation of FFA esterification and inhibition of ketone body synthesis.