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P Felig

Publications and source records attributed to P Felig.

At least 55 records · Page 3Linked to original sources
PubMed1982

Influence of long-term insulin infusion pump treatment of type I diabetes on diabetic retinopathy.

Isolated case reports have suggested short-term beneficial effects of subcutaneous insulin infusion pump treatment on background and proliferative diabetic retinopathy. To evaluate this question further, 30 eyes of 15 Type I diabetic patients were evaluated prospectively before and after 11--23 months (mean 18.1 months) of pump treatment. In each patient plasma glucose and total glycosylated hemoglobin fell to normal or near normal levels. The ten eyes without diabetic retinopathy at entry remained without. Four of 20 eyes with diabetic retinopathy at entry advanced by modified Early Treatment Diabetic Retinopathy Study (ETDRS) classification, including one eye that progressed from background to proliferative diabetic retinopathy. No eyes with diabetic retinopathy improved their modified ETDRS classification. One eye progressed to blindness; no other eye lost vision. Six eyes had laser treatment prior to insulin pump treatment; four of these and two more required laser during pump treatment. Two eyes had vitreous hemorrhages prior to pump treatment; one of these and four others hemorrhaged during pump treatment. No eyes with diabetic retinopathy showed regression of microvascular changes. The data suggest prolonged restoration of near normal glucose metabolism with the insulin pump does not reverse established diabetic retinopathy. Whether pump treatment slows the progression, or prevents the development, of diabetic retinopathy remains to be established.

Adolescent↗
PubMed1982

Influence of fibre ingestion on carbohydrate utilization and absorption.

To evaluate the mechanism whereby the addition of fibre to the diet lowers postprandial plasma glucose levels, the effects of ingestion of 10 g guar gum, a non-absorbable storage polysaccharide, on carbohydrate utilization and absorption were examined in healthy subjects. Total glucose utilization independent of gastrointestinal absorption of glucose was determined by the hyperglycaemic clamp technique in which constant hyperglycaemia is maintained with a variable intravenous infusion of glucose. Net splanchnic glucose uptake was also measured. As compare to a control study without guar, ingestion of guar failed to increase total glucose utilization or the uptake of glucose by splanchnic tissues. In contrast, when guar was ingested together with 25 g D-xylose, a non-metabolizable pentose, blood xylose levels were 25-40% lower than when xylose was ingested alone (P less than 0.01). We conclude that the plasma-glucose-lowering effects of high-fibre diets are a consequence of decreased carbohydrate absorption rather than increased total glucose utilization or augmented uptake of glucose by the liver.

Adult↗
PubMed1982

Influence of physical training on insulin release and glucose utilization by islet cells and liver glucokinase activity in the rat.

The effect of physical training on insulin release and glucose utilization by perifused islets and on liver glucokinase activity was examined in rats that exercised spontaneously by running (in wheel cage) up to 4-6 mi/day for 36 +/- 4 days and in sedentary controls kept in standard cages. Perifusion of islets with 4 mM glucose resulted in comparable rates of insulin release from islets obtained from trained and sedentary control rats. In contrast, when the perifusion glucose concentration was raised to 10 mM, the biphasic increase in insulin release was 40-50% lower in the trained rats as compared with untrained rats. This decrease in glucose-stimulated insulin release occurred in the face of comparable rates of glucose utilization by islets from control and trained rats. Glucose phosphorylation by liver homogenates from trained rats was reduced at all concentrations of glucose examined (0.5-100 mM). The calculated glucokinase activity was diminished by 40%, whereas hexokinase activity was decreased by 15% in the livers from trained rats. We conclude that 1) hypoinsulinemia induced by exercise training is due to decreased sensitivity of the beta-cell to the stimulant action of glucose independent of changes in islet cell utilization of glucose, and 2) exercise training results in a diminution of liver glucokinase activity that may be a consequence of the hypoinsulinemia.

Animals↗
PubMed1982

Lactate and glucose exchange across the forearm, legs, and splanchnic bed during and after prolonged leg exercise.

The net exchange of glucose and lactate across the leg and the splanchnic bed and the arterialdeep venous (A-DV) differences for these substrates in the forearm were determined in healthy subjects during 3-3.5 h of leg exercise (bicycle ergometer) at 58% maximum O(2) uptake and during a 40-min post-exercise recovery period. Leg glucose uptake rose 16-fold during exercise and throughout the exercise period exceeded splanchnic glucose output. The latter reached a peak increment (3.5 times basal) at 90 min and fell by 60% during the third hour. As a result, blood glucose declined 40%, reaching frank hypoglycemia (blood glucose, <45 mg/dl) in 50% of subjects at 3.5 h. Splanchnic lactate uptake rose progressively during exercise to values four times the basal rate at 3 h in association with a rise in arterial lactate to 1.5 mM. There was, however, no significant net output of lactate from the legs beyond 90 min of exercise. In contrast, the A-DV lactate difference in the forearm became progressively more negative throughout exercise, reaching values three times the basal level at 3.5 h. The rise in arterial lactate during exercise was proportional to the elevation in plasma epinephrine, which rose ninefold. During recovery, splanchnic lactate uptake rose further to values six times the basal rate, whereas lactate output by the legs was no greater than in the basal state. The A-DV lactate difference in the forearm became even more negative than during exercise, reaching values four times basal. During exercise as well as recovery, forearm uptake of blood glucose could account for no more than 25-67% of forearm lactate release. Leg glucose uptake during recovery was threefold to fivefold higher than in the basal state in the face of plasma insulin concentrations that were 60% below basal and in association with a respiratory exchange ratio of 0.7. We conclude that (a) during prolonged leg exercise at 58% maximum O(2) uptake an imbalance between splanchnic glucose production and leg glucose utilization results in a fall in blood glucose that may reach hypoglycemic levels in healthy subjects; (b) there is a marked increase in the uptake of lactate by the splanchnic bed that cannot be attributed to increased output of lactate from the exercising legs; (c) lactate is released by forearm muscle and, together with other relatively inactive muscle, may be an important source of the increased lactate turnover during and after prolonged leg exercise; (d) the increasingly negative A-DV lactate difference in the forearm cannot be accounted for by uptake of blood glucose, suggesting the breakdown of glycogen in forearm muscle during and after leg exercise; (e) increased glucose uptake by the legs in association with hypoinsulinemia during recovery suggests an increase in insulin sensitivity that permits glycogen repletion in previously exercising muscle in the absence of food ingestion; and (f) the evidence for increased lactate output in the forearm and augmented glucose uptake in the legs during recovery raises the possibility that after leg exercise glycogen stores are decreasing in muscle that was relatively inactive (e.g., that of the forearm) while increasing in the previously exercising leg muscles.

Adult↗
PubMed1982

Role of the kidney in the metabolism of fructose in 60-hour fasted humans.

Arterial (A) and renal venous (RV) concentrations and net splanchnic exchange of glucose, fructose, lactate, pyruvate, glycerol, and alanine were studied in the basal state and during a 135-min intravenous infusion of fructose at 2 mmol/min in healthy subjects after a 60-h fast. After 45 min of the fructose infusion, somatostatin (9 microgram/min) was infused for 60 min to induce hypoglucagonemia. Fructose infusion resulted in a net uptake of this hexose by the kidney as well as the splanchnic bed. Estimated renal uptake of fructose could account for the disposal of 20% of the administered fructose load while splanchnic uptake accounted for 38%. The fructose infusion resulted in a rise in blood glucose of 0.9 mmol/L, a 35% increase in net glucose output from the splanchnic bed, and a consistent net output of glucose from the kidney (A-RV = -0.17 +/- 0.05 mmol/L as compared with 0 +/- 0.03 in the basal state, P less than 0.02). Net glucose release from the kidney could account for 55% of the net renal uptake of fructose. The fructose infusion also resulted in a marked change in renal lactate balance from a net uptake in the basal state (A - RV = 0.05 +/- 0.01 mmol/L) to a net output during fructose administration (A - RV = -0.10 +/- 0.04). Administration of somatostatin resulted in a fall in arterial glucagon levels and a 35% decrease in splanchnic glucose output but failed to alter the arterial-renal venous difference for glucose observed during the fructose infusion. We conclude that in 60-h fasted man: (a) intravenous infusion of fructose results in a net uptake of this hexose by the kidney as well as the liver, (b) this uptake is accompanied by stimulation of renal as well as hepatic glucose production and renal production of lactate, and (c) hypoglucagonemia inhibits splanchnic but not renal glucose output during fructose infusion. These data indicate that the kidney is an important site of fructose disposal and that glucose and lactate are end products of renal fructose metabolism.

Adult↗
PubMed1982

Increased peripheral insulin sensitivity and muscle mitochondrial enzymes but unchanged blood glucose control in type I diabetics after physical training.

Nine male, insulin-dependent diabetic patients participated in a 16-wk training program consisting of 1 h of jogging, running, ball games, and gymnastics, performed 2-3 times/wk. The training resulted in an 8% increase of maximal oxygen uptake (P less than 0.01). Insulin sensitivity as determined by the insulin clamp technique increased 20% (P less than 0.05). Glycosylated hemoglobin showed no change (10.4 +/- 0.7% versus 11.3 +/- 0.5%), 24-h urinary glucose excretion was not reduced, and home-monitored urine tests were unchanged. The frequency of hypoglycemic attacks did not change during the training period and body weight remained constant. There was a 14% fall in plasma cholesterol (P less than 0.01) and a rise in the proportion of HDL-cholesterol from 24 +/- 2% to 30 +/- 3% (P less than 0.01). Thigh muscle oxidative capacity increased, as indicated by a 24% increase in succinate dehydrogenase activity (P less than 0.05). The number of capillaries/muscle fiber increased 15% (P less than 0.01). However, as the mean muscle fiber cross-sectional area increased to a similar extent (11%, P less than 0.05), capillary density (cap x mm-2) was unchanged. In conclusion, this study demonstrates that physical training in insulin-dependent diabetics results in increased peripheral insulin sensitivity, a rise in muscle mitochondrial enzyme activities, decreased total plasma cholesterol levels, and unchanged blood glucose control. The findings suggest that in the absence of efforts to alter dietary regulation and insulin administration, physical training consisting of 2-3 weekly bouts of moderate exercise may not of itself improve blood glucose control in type I diabetes.

Adult↗
PubMed1982

Intensive ambulatory treatment of insulin-dependent diabetes.

The therapy for insulin-dependent diabetes has been changing in the last 3 years with the increasing application of intensive ambulatory treatment programs involving self-monitoring of blood glucose levels by the patient. Insulin is administered either as multiple manual daily injections or as a continuous subcutaneous infusion delivered by a portable pump. We discuss the implementation, efficacy, complications (including recent reports of deaths in pump-treated patients), and cost of such programs. The potential effectiveness in preventing the long-term complications of diabetes warrants offering a program of self-monitoring of blood glucose levels combined with multiple manual daily insulin injections as a routine treatment option to virtually all patients with insulin-dependent diabetes. Additional observations on safety and efficacy are needed before insulin pump treatment can be considered a routine option. Furthermore, whether intensive treatment involving either manual or pump administration of insulin alters the risk of hypoglycemia as compared with conventional management remains to be established.

Ambulatory Care↗
PubMed1981

Insulin-infusion-pump treatment of diabetes: influence of improved metabolic control on plasma somatomedin levels.

We examined whether changes in somatomedin accompany those seen in glucose and growth hormone during treatment with the insulin-infusion pump. somatomedin levels in eight insulin-dependent diabetics (13 to 29 years of age) were measured before and after 16 weeks of outpatient insulin-pump treatment, which lowered mean glucose from 245 +/- 21 to 100 +/- 5 mg per deciliter and total glycosylated hemoglobin from 16.2 +/- 1.2 to 9.7 +/- 0.3 per cent (mean +/- S.E.M.). During conventional insulin therapy, both total somatomedin and somatomedin C were within the normal range, despite elevations in growth hormone. Pump treatment resulted in a 70 to 75 per cent increase in both total somatomedin and somatomedin C (P less than 0.05) and a fall in growth-hormone concentrations. In the two growing adolescents, growth velocity doubled during 13 to 15 months of pump treatment. Our data suggest that the improved insulin delivery or metabolic control increases somatomedin levels despite a decrease in growth hormone. Thus, insulin-pump treatment may be useful in optimizing growth in diabetic children.

Adolescent↗
PubMed1981

A rise in ambient temperature augments insulin absorption in diabetic patients.

The absorption rate of 125I-Actrapid insulin (6 U) from a subcutaneous injection site was examined in six insulin-dependent diabetic patients at ambient temperatures of 20 degrees C and 35 degrees C. During a 4-hr observation period, the insulin disappearance rate at 35 degrees C was 50%-60% greater than at 20 degrees C (p less than 0.01). Despite the small dose of insulin used, plasma glucose levels tended to be 1 to 2 mmole/liter lower at 35 degrees C than at 20 degrees C. These findings indicate that a rise in ambient temperature augments insulin absorption, in insulin-treated diabetic patients.

Absorption↗
PubMed1981

Influence of hyperthyroidism on splanchnic exchange of glucose and gluconeogenic precursors.

Arterial concentrations and splanchnic exchange of glucose, amino acids, lactate, pyruvate, and glycerol were determined in 14 hyperthyroid patients and 12 healthy controls. Seven of the patients were restudied after 5-12 mo of medical management at which time there was chemical and clinical evidence of a euthyroid state. The arterial level of glucose was slightly higher (+10%) in the patient group and the glycerol concentration was three times greater among the patients. The plasma levels of the glycogenic amino acids, alanine, glycine, and serine were decreased by 20-30%, while the concentrations of leucine, isoleucine, and tyrosine were increased by 20-80%. The levels of lactate and pyruvate were similar in patients and controls as were insulin and glucagon concentrations. Splanchnic glucose output in the patient group was 35% lower than in controls. However, total splanchnic uptake of glucogenic precursors was 100% higher than in controls and showed a direct linear correlation with serum triiodothyronine. Total precursor uptake could account for 75% of splanchnic glucose output in the patients, compared to 26% in controls. The increase in uptake of lactate, alanine, and other amino acids was due to a 35-80% rise in splanchnic fractional extraction plus a 20% rise in estimated hepatic blood flow. When the patients were restudied after medical treatment splanchnic exchange of glucose and glucose precursors had reverted to normal values. The present findings demonstrate that in hyperthyroidism (a) total splanchnic glucose output is reduced in relation to controls, (b) splanchnic uptake of gluconeogenic precursors is accelerated, largely due to a rise in fractional extraction of precursor substrates and to a smaller extent, as a result of an increase in hepatic blood flow, and (c) these changes revert to normal when a euthyroid state has been achieved.

Adult↗
PubMed1981

Turnover and splanchnic metabolism of free fatty acids in hyperthyroid patients.

The arterial concentration and turnover rate and the splanchnic exchange of FFA were examined after an overnight fast in a group of 11 female patients with clinical and laboratory evidence of hyperthyroidism. [14C]oleic acid was infused intravenously and the hepatic venous catheter technique was used. As compared with healthy control individuals, the arterial concentrations of FFA and oleic acid were elevated by 30--40% in the hyperthyroid group. Both the turnover rate and the fractional turnover of oleic acid were significantly increased. The turnover rate correlated directly with arterial concentration of oleic acid in both the control and the patient group but the slope was steeper in the patients. The splanchnic uptake of oleic acid was three times higher than in the control group. The augmented uptake was a consequence of elevated arterial concentrations and increased hepatic plasma flow, whereas fractional splanchnic uptake remained unchanged. Ketone body production was four- to fivefold greater in the patients and could be largely accounted for by increased splanchnic FFA uptake. In six patients studied after treatment resulting in a return to normal thyroid function, a significant reduction was observed in arterial FFA, estimated hepatic blood flow, oleic acid turnover, and ketone body production. It is concluded that hyperthyroidism is characterized by increased turnover and splanchnic uptake of FFA and augmented ketogenesis. These findings can be explained on the basis of elevated arterial FFA concentrations and increased blood flow, particularly to the splanchnic bed.

Adult↗
PubMed1981

Synergistic interaction between exercise and insulin on peripheral glucose uptake.

The interaction of exercise and insulin on glucose metabolism was examined in 10 healthy volunteers. Four study protocols were used: study 1: plasma insulin was raised by approximately 100 microunits/ml while plasma glucose was maintained at basal levels for 2 h (insulin clamp). Study 2: subjects performed 30 min of bicycle exercise at 40% of VO2 max. Study 3: an insulin clamp was performed as per study 1. Following 60 min of sustained hyperinsulinemia, however, subjects exercised for 30 min as per study 2. Study 4: subjects were studied as per study 3 except that catheters were inserted into the femoral artery and vein to quantitate leg glucose uptake. During the 60-90 min period of hyperinsulinemia (study 1), glucose uptake averaged 8.73 +/- 0.10 mg/kg per min. With exercise alone (study 2), the increment in peripheral glucose uptake was 1.43 +/- 0.30 mg/kg per min. When hyperinsulinemia and exercise were combined (study 3), glucose uptake averaged 15.06 +/- 0.98 mg/kg per min (P less than 0.01) and this was significantly (P less than 0.001) greater than the sum of glucose uptake when exercise and the insulin clamp were performed separately. The magnitude of rise in glucose uptake correlated closely with the increase in leg blood flow (r = 0.935, P less than 0.001), suggesting that the synergism is the result of increased blood flow and increased capillary surface area to exercising muscle. More than 85% of total body glucose metabolism during studies 1 and 3 was accounted for by skeletal muscle uptake. These results demonstrate that (a) insulin and exercise act synergistically to enhance glucose disposal in man, and (b) muscle is the primary tissue responsible for the increase in glucose metabolism following hyperinsulinemia and exercise.

Adult↗
PubMed1981

Sensitivity of insulin secretion to feedback inhibition by hyperinsulinaemia.

The ability of insulin to inhibit its own secretion was examined in 15 normal subjects given an intravenous infusion of insulin in a dose of 0.25, 0.50, 1.0, 5.0 or 10.0 mU/kg/min for two hours. Arterial plasma insulin concentration achieved during the infusion segregated into three levels of hyperinsulinaemia: 35 +/- 1 (mean +/- SEM), 87 +/- 15 and 828 +/- 210 muU/ml. Plasma glucose concentration was kept constant at the basal level by a variable glucose infusion. Fasting C-peptide (0.29 +/- 0.02 pmol/ml) fell significantly in all subjects during hyperinsulinaemia and reached a concentration of 0.19 +/- 0.03 pmol/ml at 60 min and 0.14 +/- 0.03 at 120 min after the start of the insulin infusion. The C-peptide response was not related to the infusion dose nor to the steady state plasma insulin concentration. It is concluded that (a) basal insulin secretion as evaluated from C-peptide measurements is inhibited by small (24 +/- 3 muU/ml) physiological elevations in plasma insulin concentration independent of changes in plasma glucose, and (b) supraphysiological or even pharmacological elevations in plasma insulin do not result in a further decrease in endogenous insulin secretion above that achieved with mild hyperinsulinaemia.

Adult↗
PubMed1981

Efficacy of the insulin pump in the home treatment of pregnant diabetics.

The efficacy and feasibility of the insulin infusion pump in pregnancy were examined in seven class D to FR diabetics, maintained on the pump at home from 10 to 29 wk gestation until delivery. An improvement in glucose control was achieved within the first month and sustained to term. Home monitoring demonstrated a fall in mean blood glucose levels from 135 mg/dl range 98-175, prepump) to 104 mg/dl (range 84-120) and a 25-30% reduction in standard deviations during pump treatment. Furthermore, glycosylated hemoglobin levels were normalized in each patient. During periodic inpatient evaluations, mean 24-h plasma glucose levels were slightly, but not significantly, lower after pump treatment (97 vs 86 mg/dl). However, glycemic excursions were strikingly diminished; MAGE values and standard deviations fell by 45% and 34%, respectively. The total daily insulin dose required at the start of pump treatment was 31% less than the conventional dose used before the pump (P less than 0.002). Thereafter the insulin dose increased by approximately 2.5 U/wk, with the basal infusion remaining at 40% of the total dose throughout the pregnancy. All infants were born at term, had no macrosomia or neonatal problems, and had normal intravenous glucose tolerance tests at 2 h of age. We conclude that the insulin infusion pump, managed at home, is a highly efficient way to achieve normal or near-normal glucose levels in the pregnant diabetic.

Adult↗
PubMed1981

Exercise.

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Body Weight↗