Restoration of Normal Lipid and Aminoacid Metabolism in Diabetic Patients Treated With a Portable Insulin-Infusion Pump

Tamborlane, W. V.; Sherwin, R S; Genel, Myron; Felig, Philip

doi:10.1016/s0140-6736(79)92226-8

Cited by 171 publications

(64 citation statements)

References 18 publications

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“…Analysis of studies in which the amino acid and lipid concentrations were measured in type 1 diabetic patients on conventional or intensive insulin treatment (25,26) suggests that the metabolic abnormalities of islet-transplanted patients with partial function are comparable with those of (25)(26)(27). However, in the latter group, metabolic control was obtained at the expense of a high prevalence of hypoglycemia (27), whereas no hypoglycemic episode was seen in islet-transplanted patients.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Effects of Restoring Partial β-Cell Function After Islet Allotransplantation in Type 1 Diabetic Patients

et al. 2001

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Successful intraportal islet transplantation normalizes glucose metabolism in diabetic humans. To date, full function is not routinely achieved after islet transplantation in humans, with most grafts being characterized by only partial function. Moreover, the duration of full function is variable and cannot be sufficiently predicted with available methods. In contrast, most grafts retain partial function for a long time. We hypothesized that partial function can restore normal protein and lipid metabolism in diabetic individuals. We studied 45 diabetic patients after islet transplantation. Labeled glucose and leucine were infused to assess whole-body glucose and protein turnover in 1) 6 type 1 diabetic patients with full function after intraportal islet transplantation (FF group; C-peptide > 0.6 nmol/l; daily insulin dosage 0.03 ± 0.02 U · kg -1 body wt · day -1 ; fasting plasma glucose < 7.7 mmol/l; HbA 1c ≤ 6.5%), 2) 17 patients with partial function (PF group; C-peptide > 0.16 nmol/l; insulin dosage < 0.4 U · kg -1 body wt · day -1 ), 3) 9 patients with no function (NF group; C-peptide < 0.16 nmol/l; insulin dosage > 0.4 U · kg -1 body wt · day -1 ), and 4) 6 patients with chronic uveitis as control subjects (CU group). Hepatic albumin synthesis was assessed in an additional five PF and five healthy volunteers by means of a primed-continuous infusion of [3,3,3-2 H 3 ]leucine. The insulin requirement was 97% lower than pretransplant levels for the FF group and 57% lower than pretransplant levels for the PF group. In the basal state, the PF group had a plasma glucose concentration slightly higher than that of the FF (P = 0.249) and CU groups (P = 0.08), but was improved with respect to the NF group (P < 0.01). Plasma leucine (101.1 ± 5.9 µmol/l) and branched-chain amino acids (337.6 ± 16.6 µmol/l) were similar in the PF, FF, and CU groups, and significantly lower than in the NF group (P < 0.01). During insulin infusion, the metabolic clearance rate of glucose was defective in the NF group versus in the other groups (P < 0.01). Both the basal and insulin-stimulated proteolytic and proteosynthetic rates were comparable in the PF, FF, and CU groups, but significantly higher in the NF group (P = 0.05). In addition, the PF group had a normal hepatic albumin synthesis. Plasma free fatty acid concentrations in the PF and FF groups were similar to those of the CU group, but the NF group showed a reduced insulin-dependent suppression during the clamp. We concluded that the restoration of ~60% of endogenous insulin secretion is capable of normalizing the alterations of protein and lipid metabolism in type 1 diabetic kidney recipients, notwithstanding chronic immunosuppressive therapy. The results of the present study indicate that "success" of islet transplantation may be best defined by a number of metabolic criteria, not just glucose concentration/metabolism alone. Diabetes 50:277-282, 2001

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Section: Discussionmentioning

confidence: 99%

Metabolic Effects of Restoring Partial β-Cell Function After Islet Allotransplantation in Type 1 Diabetic Patients

et al. 2001

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“…8,17 ± 19 Further supporting this thesis, we have recently demonstrated in experimental animals a direct relationship between the plasma ratio free TRPaLNAA and the brain Oral 5-HTP in NIDDM C Cangiano et al serotonin concentrations, 34 thus con®rming previously reported data. 35 Branched-chain amino acids, which represent the major component of plasma LNAA have been found to be signi®cantly increased in NIDDM patients, 20,21 probably secondary to insulin resistance in peripheral tissues. 36 In the present study, the signi®cant reduction of the ratio in plasma free TRPaLNAA observed in NIDDM patients suggests that in the brain, tryptophan concentrations and thus serotonin synthesis are likely to be decreased.…”

Section: Discussionmentioning

confidence: 99%

“…Although controversial, the predictability of brain TRP concentrations seems to be more appropriate when the ratio between free TRP and the other large neutral amino acids (LNAA) is considered. 8,17 ± 19 Since plasma branched-chain amino acids (BCAA), which compete with TRP for brain entry, have been found to be increased in NIDDM patients, 20,21 we hypothesize that brain tryptophan availability and serotonergic activity are depressed in NIDDM. This might, in turn, be responsible for the hyperphagia and disturbed eating behaviour.…”

Section: Introductionmentioning

confidence: 99%

Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients

Cangiano¹,

Laviano²,

Ben

et al. 1998

Int J Obes

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OBJECTIVE: In obese patients, brain serotonergic stimulation via orally administered 5-hydroxy-tryptophan (5-HTP), the precursor of serotonin, causes decreased carbohydrate intake and weight loss. Since diabetes mellitus is associated with depressed brain serotonin, hyperphagia and carbohydrate craving, we hypothesized that in diabetic patients, orally administered 5-HTP stimulates brain serotonergic activity and thus normalizes eating behaviour. To test this hypothesis, we investigated whether in diabetic patients: 1) predicted brain serotonin concentrations are depressed as a result of decreased availability of the precursor, tryptophan; and 2) oral 5-HTP is effective in reducing energy and carbohydrate intake. SUBJECTS AND METHODS: 25 overweight non-insulin dependent diabetic outpatients were enrolled in a doubleblind, placebo-controlled study, and randomized to receive either 5-HTP (750 mgad) or placebo for two consecutive weeks, during which no dietary restriction was prescribed. Energy intake and eating behaviour, as expressed by macronutrient selection, were evaluated using a daily diet diary. Plasma amino acid concentrations and body weight, as well as serum glucose, insulin and glycosylated haemoglobin were assessed. RESULTS: 20 patients (nine from the 5-HTP group and 11 from the Placebo group) completed the study. Brain tryptophan availability in diabetic patients was signi®cantly reduced when compared to a group of healthy controls. Patients receiving 5-HTP signi®cantly decreased their daily energy intake, by reducing carbohydrate and fat intake, and reduced their body weight. CONCLUSIONS: These data con®rm the role of the serotonergic system in reducing energy intake, by predominantly inhibiting carbohydrate intake, and suggest that 5-HTP may be safely utilized to improve the compliance to dietary prescriptions in non-insulin dependent diabetes mellitus.

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“…In Type 1 (insulin-dependent) diabetic patients, continuous subcutaneous insulin infusion (CSII), using small portable pumps, has been proposed to attain this goal, with encouraging results [2][3][4][5]. A hazard of this treatment is the fortuitous interruption of the subcutaneous insulin delivery due to failure of the pump or delivery system.…”

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confidence: 99%

A 6-hour nocturnal interruption of a continuous subcutaneous insulin infusion: 1. Metabolic and hormonal consequences and scheme for a prompt return to adequate control

et al. 1983

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Summary. Interruption of a continuous subcutaneous insulin infusion, most often due to technical problems occurring during the night, is a not uncommon event whose metabolic consequences have received relatively little attention until now. We have therefore investigated the changes in blood glucose, plasma non-esterified fatty acids, 3-hydroxybutyrate, glucagon and free insulin in eight C-peptide negative Type 1 diabetic patients whose pumps were deliberately stopped between 23.00 h and 05.00 h. A control test with the pump functioning normally was carried out in each patient and the studies were randomized. Considering the values at 23.00 h as reference, interruption of the insulin infusion resulted in (1) a rapid decrease in plasma free insulin significant after 1 h and reaching a nadir of 6 + 2 mU/l after 6 h; (2) a rise in blood glucose which was significant at hour3 and reached 17.4+ 1.9 mmol/l at hour 6; (3) a moderate increase in plasma nonesterified fatty acids which remained in the range of 700-800 ~tmol/1; (4) an early and linear rise in plasma 3-hydroxybutyrate, significant after 1 h and averaging 1290_+ 140 gmol/1 after 6 h; (5) a late increase (hour 5) in plasma glucagon. The second aim of our study was to provide for the patient a precise scheme of insulin supplements administered via the pump and based on blood glucose monitoring (Dextrostix -Glucometer) and semi-quantitative evaluation of ketonuria (Acetest). Resetting the pump at its basal rate at 05.00h and giving insulin supplements (2-8 U) at 06.45 h (with the usual breakfast dose) and again at 10.00h have proved efficacious in restoring satisfactory metabolic control by noon the day after starting the experiment. These results form practical recommendations to patients undergoing this type of accident.

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Restoration of Normal Lipid and Aminoacid Metabolism in Diabetic Patients Treated With a Portable Insulin-Infusion Pump

Cited by 171 publications

References 18 publications

Metabolic Effects of Restoring Partial β-Cell Function After Islet Allotransplantation in Type 1 Diabetic Patients

Metabolic Effects of Restoring Partial β-Cell Function After Islet Allotransplantation in Type 1 Diabetic Patients

Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients

A 6-hour nocturnal interruption of a continuous subcutaneous insulin infusion: 1. Metabolic and hormonal consequences and scheme for a prompt return to adequate control

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