Search

A model of carbohydrate metabolism has been implemented as a causal probabilistic network, allowing explicit representation of the uncertainties involved in the prediction of 24-h blood glucose profiles in insulin-dependent diabetic subjects. The parameters of the model were based on experimental data from the literature describing insulin and carbohydrate absorption, renal loss of glucose, insulin-independent glucose utilisation and insulin-dependent glucose utilisation and production. The model can be adapted to the observed glucose metabolism in the individual patient and can be used to generate predicted 24-h blood glucose profiles. A penalty is assigned to each level of blood glucose, to indicate that high and low blood glucose levels are undesirable. The system can be asked to find the insulin doses that result in the most desirable 24-h blood glucose profile. In a series of 12 patients, the system predicted blood glucose with a mean error of 3.3 mmol/l. The insulin doses suggested by the system seemed reasonable and in several cases seemed more appropriate than the doses actually administered to the patients.

Objective: To assess the effect of selective beta 1-blockade (atenolol and betaxolol) and nonselective beta-blockade (propranolol) on glucose turnover in subjects with insulin-dependent (type I) diabetes mellitus during moderate exercise., Research Design and Methods: Five subjects with type I diabetes were infused with insulin and then exercised for 1 h, after pretreatment with each of the three drugs or saline and, on a separate day, after withdrawal of insulin. Glucose turnover was measured using tritiated glucose., Results: Plasma glucose, initially 9.2 +/- 0.5 mmol/L (mean +/- SE) when insulin infused and 14.0 +/- 0.8 when insulin was withdrawn, fell on exercise by 3.4 +/- 1.1 mmol/L (P < 0.05) saline, 4.0 +/- 0.8 mmol/L (P < 0.01) with betaxolol, 3.8 +/- 0.7 mmol/L (P < 0.01) with atenolol, 5.0 +/- 0.6 mmol/L (P < 0.005) with propranolol, and 1.7 +/- 1.0 mmol/L (NS) when insulin was withdrawn. Propranolol, but not the other beta-blockers, caused a significantly greater fall in glucose on exercise than during the control study. Glucose appearance rate (Ra) was similar basally and rose to an almost identical level in all five groups during exercise. Glucose disappearance rate (Rd) rose similarly during exercise, except after propranolol when the rise was significantly greater than with saline (P < 0.01). Failure of glucose to change significantly during exercise when insulin had been withdrawn was associated with the smallest rise in Rd and the highest nonesterified fatty acid concentrations. Propranolol and betaxolol, but not atenolol, reduced nonesterified fatty acids., Conclusions: We conclude that the greater fall in glucose on exercise after beta-blocking drugs is probably largely a direct effect of beta 2-blockade on muscle, increasing the exercise-induced rise in Rd glucose. This offers support to the use of beta 1-specific drugs, where beta-blockade is necessary in type I diabetes.

Glucose intolerance, sometimes severe enough to cause frank diabetes mellitus, is a frequent feature of Cushing's syndrome. The primary cause of the hyperglycaemia, whether due to glucose over-production or under-utilization, remains unresolved. We therefore measured glucose turnover using an intravenous bolus of 3-3H glucose in 14 normoglycaemic patients with Cushing's syndrome and 14 control subjects. Seven of the patients with Cushing's syndrome were also restudied post-operatively. Plasma glucose concentrations were similar in all three groups whereas glucose metabolic clearance rate (MCR) (1.80 +/- 0.06 ml/min/kg) and glucose turnover rate (9.09 +/- 0.36 mumol/min/kg) were significantly reduced in patients with Cushing's syndrome compared to normal subjects (2.21 +/- 0.1; P less than 0.001; 10.90 +/- 0.50; P less than 0.01) and rose post-operatively to normal values (2.35 +/- 0.14 ml/min/kg; 11.07 +/- 0.48 mumol/min/kg). We conclude from these results that the hyperglycaemia sometimes found in Cushing's syndrome may be primarily due to decreased utilization rather than increased glucose production.

Six Type 1 (insulin-dependent) diabetic subjects were studied in order to determine the contribution of recycling of glucose carbon to the overproduction of glucose which is characteristic of the fasting hyperglycaemia produced by insulin withdrawal. The subjects were studied on two occasions, once after an overnight insulin infusion and once following 24 h of insulin withdrawal. The difference in turnover rates of 1-14C-glucose and 3-3H-glucose was used as a measure of glucose recycling. Insulin withdrawal caused a marked metabolic derangement with a rise in non-esterified fatty acids from 0.69 +/- 0.23 to 1.11 +/- 0.21 mmol/l (mean +/- SEM, p less than 0.05), total ketones from 0.27 +/- 0.06 to 2.06 +/- 0.51 mmol/l (p less than 0.01), cortisol from 341 +/- 43 to 479 +/- 31 nmol/l (p less than 0.05) and growth hormone from 1.1 +/- 0.3 to 19 +/- 5 mu/l (p less than 0.05). Glucose turnover rose from 13.8 +/- 2.3 mumol.kg-1.min-1 at a glucose of 6.9 +/- 0.7 mmol/l in the insulin infused study to 25.8 +/- 4.4 mumol.kg-1.min-1 (p less than 0.05) at a glucose of 16.4 +/- 0.7 mmol/l in the insulin withdrawn study. Recycling also rose from 3.0 +/- 0.4 mumol.kg-1.min-1 to 9.4 +/- 2.2 mumol.kg-1.min-1 (p less than 0.05) when insulin withdrawn, accounting for 23 +/- 3% and 36 +/- 3% of glucose turnover, respectively. We conclude that in the severely insulin deficient Type 1 diabetic subject recycling of glucose carbon is a major contributor to the excess glucose production.

We have compared disposal of an oral glucose load in 12 normal subjects and 10 c-peptide-negative, type I-diabetic subjects, who were treated with insulin (by overnight intravenous insulin infusion followed by a dose of subcutaneous insulin prior to the oral glucose load) to achieve a blood glucose profile that approximated the glucose intolerance commonly seen in insulin-treated diabetics. We used a combination of the dual-isotope and forearm techniques, together with whole-body indirect calorimetry, to quantify the various determinants of glucose tolerance. The diabetic subjects had impaired glucose tolerance in that, despite similar fasting plasma glucose levels (5.46 +/- 0.17 mmol/L v 5.35 +/- 0.10 mmol/L in the normal subjects), they had a higher peak glucose (14.3 +/- 1.2 mmol/L v 10.0 +/- 0.7 mmol/L P less than .01) and area under the glucose curve (2,483 +/- 197 mmol.min/L v 1,525 +/- 43 mmol.min/L P less than .001). Up to 120 minutes after the oral glucose load, the amount of glucose entering the systemic circulation exceeded that leaving by 14.6 +/- 2.3 g in the diabetics and only by 2.6 +/- 0.5 g in the normal subjects (P less than .001), accounting for the higher plasma glucose peak in the diabetics. Total systemic glucose appearance rates were significantly greater in the diabetics between 60 and 120 minutes, and endogenous glucose production suppressed more slowly in diabetics than in the normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Although muscle is considered to be the most important site for postprandial glucose disposal, the metabolic fate of oral glucose taken up by muscle remains unclear. We, therefore, employed the dual isotope technique (intravenous, [6-3H]-glucose; oral, [1-14C]glucose), indirect calorimetry, and forearm balance measurements of glucose, lactate, alanine, pyruvate, O2, and CO2 in nine normal volunteers to determine the relative importance of muscle glycogenic, glycolytic, and oxidative pathways in disposal of an oral glucose load. During the 5 h after glucose ingestion (1 g/kg), 37 +/- 3% (24.9 +/- 2.3 g) of the load was oxidized and 63 +/- 3% (42.8 +/- 2.7 g) was stored. At least 29% (19.4 +/- 1.3 g) was taken up by splanchnic tissues. Muscle took up 26% (17.9 +/- 2.9 g) of the oral glucose coincident with a 50% reduction in its oxidation of fat. 15% of the oral glucose taken up by muscle (2.5 +/- 0.9 g) was released as lactate, alanine, or pyruvate; 50% (8.9 +/- 1.4 g) was oxidized, and 35% (6.4 +/- 2.3 g) was available for storage. We conclude that muscle and splanchnic tissues take up a comparable percentage of an oral glucose load and that oxidation is the predominant fate of glucose taken up by muscle, with storage in muscle accounting for less than 10% of the oral load. Thus, contrary to the prevailing view, muscle is neither the major site of storage nor the predominant site of disposal of an oral glucose load.