Contribution of impaired muscle glucose clearance to reduced postabsorptive systemic glucose clearance in NIDDM.

The reduced postabsorptive rates of systemic glucose clearance in non-insulin-dependent diabetes mellitus (NIDDM) are thought to be the consequence of insulin resistance in peripheral tissues. Although the peripheral tissues involved have not been identified, it is generally assumed to be primarily muscle, the major site of insulin-mediated glucose disposal. To test this hypothesis, we measured postabsorptive systemic and forearm glucose utilization and clearance in 15 volunteers with NIDDM and 15 age- and weight-matched nondiabetic volunteers.

Isotopic estimation of plasma glucose conversion to plasma lactate using [6-3H]glucose and [6-14C]glucose.

To determine whether [6-3H]glucose could be used to quantitatively estimate the rate of plasma glucose conversion to plasma lactate, we compared the relative transfer of [3H] and [14C]plasma glucose to plasma lactate in nine postabsorptive anesthetized rats infused to isotopic steady state with [6-3H]glucose and [6-14C]glucose. Glucose turnover (mumol/kg/min) measured with [6-3H]glucose (29.4 +/- 1.

Mechanism for underestimation of isotopically determined glucose disposal.

Use of [3H]glucose and a one-compartment model to determine glucose kinetics frequently underestimates the rate of glucose production (Ra). To assess to what extent an isotope effect, a tracer contaminant, or inadequacy of the model was responsible, we measured glucose Ra and forearm clearance of tracer and unlabeled glucose at various concentrations of plasma insulin (approximately 50, approximately 160, and approximately 1800 microU/ml) and plasma glucose (approximately 90, approximately 160, approximately 250, and approximately 400 mg/dl) under steady-state and non-steady-state conditions. Under isotopic steady-state conditions, the clearances of tracer and unlabeled glucose across the forearm were identical, and exogenous glucose infusion rates did not differ significantly from the isotopically determined glucose Ra (10.

Predominant role of gluconeogenesis in increased hepatic glucose production in NIDDM.

Excessive hepatic glucose output is an important factor in the fasting hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM). To determine the relative contributions of gluconeogenesis and glycogenolysis in a quantitative manner, we applied a new isotopic approach, using infusions of [6-3H]glucose and [2-14C]acetate to trace overall hepatic glucose output and phosphoenolpyruvate gluconeogenesis in 14 postabsorptive NIDDM subjects and in 9 nondiabetic volunteers of similar age and weight. Overall hepatic glucose output was increased nearly twofold in the NIDDM subjects (22.

Rates of appearance and disappearance of plasma lactate after oral glucose: implications for indirect-pathway hepatic glycogen repletion in man.

3-14C-lactate and 6-3H-glucose were infused to determine rates of plasma lactate appearance (Ra), disappearance (Rd) and conversion to plasma glucose following ingestion of 75 g glucose in 10 healthy volunteers. Lactate Ra (mumol/kg/min) increased from 10.2 +/- 0.

Quantification of the glycolytic origin of plasma glycerol: implications for the use of the rate of appearance of plasma glycerol as an index of lipolysis in vivo.

To assess whether plasma glycerol could be directly derived from plasma glucose, nine postabsorptive dogs were infused with [U-14C] glucose and [2-3H] glycerol to measure the rates of appearance of plasma glucose and glycerol and the conversion of plasma glucose to glycerol before (basal) and after two hours of infusion of glucose (45 mumol/kg/min). Basally (plasma glucose 4.9 +/- 0.

Determination of Krebs cycle metabolic carbon exchange in vivo and its use to estimate the individual contributions of gluconeogenesis and glycogenolysis to overall glucose output in man.

Current isotopic approaches underestimate gluconeogenesis in vivo because of Krebs cycle carbon exchange and the inability to measure intramitochondrial precursor specific activity. We therefore applied a new isotopic approach that theoretically overcomes these limitations and permits quantification of Krebs cycle carbon exchange and the individual contributions of gluconeogenesis and glycogenolysis to overall glucose output. [6-3H]Glucose was infused to measure overall glucose output; [2-14C]acetate was infused to trace phosphoenolpyruvate gluconeogenesis and to calculate Krebs cycle carbon exchange as proposed by Katz.

Comparison between monocomponent human insulin U-40 and U-100 in CSII treatment of type 1 diabetics.

A multicentric study has been carried out to compare the efficacy and the safety of monocomponent human insulins of different concentration (Novo Actrapid HM U-40 and U-100) in CSII-treated Type 1 diabetics. 15 males, all of whom had been diabetic for at least 2 yr, had been treated by CSII and were skillful in the self-monitoring of diabetes were selected for observation at 3 different clinical centres (Bologna, Chieti and Torino). After a 1-week period of insulin dose optimization, the patients were asked not to modify either basal or pre-prandial insulin infusion during the following 2 weeks in which they were treated alternately by U-40 or by U-100 insulin (7 days for each treatment in random sequence).

[Changes in body composition in obese patients on a low-calorie diet].

Energy balance was studied on 4 obese hospitalized subjects kept on hypocaloric diet (489 Kcal - 54% CHO, 10,6% Fat, 35,4% Protein) for 18 +/- 3,7 days. Energy expenditure was measured trough heart-rate monitoring (individual calibrations before and after the study were performed) and nitrogen balance was computed to establish protein loss. Individual qualitative composition of body weight loss was then assessed: 71,4 +/- 5,23% could be attributable to fat loss, 9,38 +/- 3,32% to protein loss, 18,2 +/- 5,5% to water loss.

[Insulin secretion after a protein and lipid meal in healthy subjects].

Previous studies suggested that insulin requirement in type I diabetics could be split in a "basal" insulin requirement, mainly related to body weight and in a "post-prandial" insulin requirement, mainly related to carbohydrates intake. In the present study we wanted to investigate the occurrence and the magnitude of insulin response to protein only or fat only meals in normal subjects, trying to obtain some evidences for an insulin requirement possibly related to these substrates in diabetic subjects. Fat only meals did not evoke any insulin response while a small but significant increase in plasma insulin was observed after a protein only meal (from 16.

[Effects of rigid dietary restrictions on the control of blood sugar in obese type II diabetic patients].

The improvement of glycemic control obtained with weight loss in NIDDM obese diabetics is still lacking of a prediction formula to establish which would be the weight loss to possibly obtain a fasting normoglycemia. Nine NIDDM obese diabetics of both sexes (age 51 +/- 2,64 yrs; initial body weight 91,63 +/- 6,02 Kg., IBW 156,98 +/- 13,38%, fasting plasma IRI 27,58 +/- 6 microU/ml) were hospitalized and discontinued any therapy 10 days before the study.

[Modifications in the oscillation of substrates in obese subjects subjected to variations in the pattern of meal-timing].

In a group of obese subjects kept on hypocaloric diet during a period of 18 days, an eventual different behaviour of carbohydrates and lipids oxidation following to meal-timing manipulation (a single meal given only at 10.00 hr or at 18.00 hr of each day) has been studied by indirect calorimetry.

[Administration of semisynthetic human insulin by a spray injector].

The use of Jet injection in insulin administration pointed out the question whether this route could affect insulin absorption and plasma insulin profiles. To compare plasma insulin profiles following an administration of an identical insulin dose by jet injection or by conventional subcutaneous route (syringe with needle) 8 healthy subjects (age 24-28 yrs., non obese) were given at 09.

[Semisynthetic human insulin in the treatment of diabetes type I. Preliminary experience].

The recent availability of human insulin raised the question of evaluating its effectiveness in comparison with traditional animal insulins in the treatment of type I diabetics. 9 long-term CSII treated type I diabetics were shifted from pork insulin to human semisynthetic insulin and followed up to 8 months. The following parameters were evaluated: basal insulin infusion allowing morning blood glucose of 100-140 mg/dl and the serum insulin binding capacity (Bio-Merieux).

[Blood sugar control in diabetic patients bearing microinfusors: the importance of the dawn phenomenon].

Significant early morning hyperglycemia (the so-called "dawn phenomenon") has been observed in insulin-dependent diabetics who were otherwise well controlled. This phenomenon, if present, could lead to errors in adapting the basal insulin infusion in CSII treated diabetic patients, because a normal glucose level in the morning could be associated with asymptomatic hypoglycemic values in the night. In order to observe the occurrence and to quantify the magnitude of this phenomenon 14 well controlled CSII-treated type I diabetics were hospitalized for 1 night and samples for the determination of blood glucose (14 patients) and serum cortisol, free insulin and NEFA (8 patients) were drawn at 24.

[The role of dietary carbohydrates and proteins in the determination of postprandial insulin requirements, evaluated by artificial pancreas, in type I diabetics].

Aim of this work is to evaluate the relative role of ingested carbohydrates and proteins in determining post-prandial insulin requirement in type I diabetic patients by means of artificial pancreas 5 male diabetics were given two times a day a diet with a high amount of carbohydrates (140g) or with a high amount of proteins (120g) while connected to the Biostator. Basal and post-prandial required insulin was evaluated. Post-prandial insulin requirement after high proteins meals did not appear greater than basal requirement, while insulin requirement after high carbohydrates meals appeared statistically greater than basal requirement.

[Biphasic response of insulin secretion to arginine stimulation: daily changes].

8 healthy subjects were infused with arginine at h. 08 and h. 16 of different days in order to observe if some changes occurred in the biphasic insulin response according with the different times of the day.