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Biomedical subjects

R A Rizza

Publications and source records attributed to R A Rizza.

At least 19 recordsLinked to original sources
PubMed1991

Use of human ultralente as the basal insulin component in treatment of patients with IDDM.

To determine the suitability of a single subcutaneous evening injection of human ultralente (UL) as the basal component of an intensive insulin therapy program, insulin concentrations were measured in five insulin-dependent diabetic volunteers over a 40-h period. Each patient had been maintained on a human UL-based program for at least one month prior to the study. All short-acting insulin was withheld during the study. The onset of action of human UL was 2 to 4 h, and a broad, variable peak was observed between 6 and 12 h after each injection. We concluded that human UL does not provide constant basal insulin concentrations. When human UL is considered as part of an intensive insulin therapy program, this potential disadvantage must be weighed against the potential advantage of low antigenicity.

Adult↗
PubMed1991

Comparison of extracellular and net glucose oxidation measured isotopically and by indirect calorimetry during high and low glucose turnover.

To determine the extent to which glucose oxidation measured by indirect calorimetry reflects glucose oxidation measured isotopically, subjects were studied during a 6-h hyperinsulinemic euglycemic clamp (1 mU.kg-1.min-1) and during infusion of saline. [6-14C]glucose was infused on both occasions. Breath was collected for determination of the specific activity of carbon dioxide, oxygen consumption, and carbon dioxide production. Glucose turnover during hyperinsulinemia was approximately eightfold higher than during saline infusion. During the final 1.5 h of the hyperinsulinemic glucose clamp, oxidation measured isotopically remained slightly but consistently lower (P less than 0.05) than that measured by indirect calorimetry (13.8 +/- 1.1 vs 16.5 +/- 1.7 mumol.kg-1.min-1, respectively). In contrast, during the saline infusion, glucose oxidation measured isotopically did not differ from that measured by indirect calorimetry (8.3 +/- 0.6 vs 7.2 +/- 2.8 mumol.kg-1.min-1, respectively). We conclude that although net glucose oxidation measured isotopically was slightly lower than that measured by indirect calorimetry, both techniques provide similar estimates of glucose oxidation over a wide range of glucose disposal.

Adult↗
PubMed1991

The nocturnal increase in growth hormone is not the cause of the nocturnal increase in serum osteocalcin.

Osteoblast activity, as measured by the serum osteocalcin (OC) concentration, increases at night in both normal women and women with postmenopausal osteoporosis. Because there is also a physiological increase in GH during deep sleep and the nocturnal increases in serum OC and GH concentrations both become less pronounced with advancing age, we used somatostatin (SMS) infusion to evaluate the effect of suppression of the nocturnal GH increase on the expected increase in serum OC. Serum OC levels were measured during an 8-h iv infusion of SMS and during a similar infusion of isotonic saline (control night) in five young women (mean age +/- SE, 21 +/- 2 yr). SMS significantly (P less than 0.05) decreased secretion of endogenous GH. The mean increases in serum OC concentration were similar during SMS infusion and control nights. Furthermore, the nocturnal pattern of increase in serum OC levels during GH or saline infusions did not differ. From these data, we conclude that the nocturnal increases in serum OC and GH levels are not related.

Adult↗
PubMed1991

Contribution to postprandial hyperglycemia and effect on initial splanchnic glucose clearance of hepatic glucose cycling in glucose-intolerant or NIDDM patients.

Excessive amounts of glucose enter the systemic circulation when patients with non-insulin-dependent diabetes mellitus (NIDDM) eat a carbohydrate-containing meal. To determine the contribution of hepatic glucose cycling (defined as the net effect of glucose/glucose-6-phosphate cycling and uptake and release of glucose from hepatic glycogen) to postprandial hyperglycemia, diabetic, glucose-intolerant, and nondiabetic subjects were fed mixed meals. The meal contained both [2-3H]glucose (an isotope that is extensively detritiated during hepatic glucose cycling) and [6-3H]glucose (an isotope that is not detritiated during hepatic glucose cycling). Of the 50 g of carbohydrate contained in the meal, approximately 4-8 g underwent hepatic glucose cycling. Although total cycling of ingested glucose did not differ between diabetic, glucose-intolerant, and nondiabetic subjects (361 +/- 67 vs. 494 +/- 106 vs. 322 +/- 44 mumol.kg-1.5 h-1, respectively), the data suggested that hepatic cycling was increased in the diabetic and glucose-intolerant individuals but not in the nondiabetic subjects during the first 2 h after eating. Hepatic cycling during the first 2 h after eating was correlated with the prevailing glucagon concentration (r = 0.6, P less than 0.01) and increased (P less than 0.05) as hepatic glucose release increased. Hepatic glucose cycling had a marked effect on the measurement of so-called initial splanchnic glucose uptake. Nevertheless, however measured, initial splanchnic glucose uptake was not decreased and, if anything, was increased in diabetic and glucose-intolerant patients. Integrated postprandial hepatic glucose release increased (r less than 0.01) with the severity of fasting hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1990

Underestimation of glucose turnover corrected with high-performance liquid chromatography purification of [6-3H]glucose.

We have recently reported that during infusion of commercially available [6-3H]glucose, a radioactive nonglucose contaminant may accumulate in plasma causing errors in the measurement of glucose turnover. To determine whether purification of this tracer by HPLC (high-performance liquid chromatography) before infusion would eliminate the contaminant in plasma and remove the underestimation of glucose turnover reported during hyperinsulinemia, four normal subjects each underwent two 5-h euglycemic clamps during infusion of insulin (1 mU.kg-1.min-1). Glucose turnover was measured with either commercially available [6-3H]glucose or with HPLC-purified [6-3H]glucose. HPLC analysis of samples from the clamps done with commercially available [6-3H]glucose showed that 9.7% of the infused tracer and 26% of the "plasma glucose 3H radioactivity" were contaminants. In contrast, no contaminant was observed in the plasma during infusion of HPLC-purified [6-3H]glucose. During the last hour of the clamp, mean glucose turnover using commercially available [6-3H]glucose was less (P less than 0.01) than the mean glucose infusion rate (7.6 +/- 0.3 vs. 10.5 +/- 0.3 mg.kg-1.min-1) yielding apparent "negative" (P less than 0.001) hepatic glucose release. In contrast, when HPLC-purified [6-3H]glucose was employed, glucose turnover equaled the glucose infusion rate (10.4 +/- 0.9 vs. 10.2 +/- 0.9 mg.kg-1.min-1) and hepatic glucose release was no longer negative. We conclude that removal of a tritiated nonglucose contaminant in [6-3H]glucose by HPLC yields correct estimations of glucose turnover at steady state.

Adult↗
PubMed1990

Lack of effect of gastric inhibitory polypeptide on hepatic and extrahepatic insulin action.

To assess the influence of enteric factors on insulin action, seven lean healthy subjects were studied under conditions of hyperinsulinemic euglycemic glucose clamp, double isotope administration, and enteral vs. parenteral glucose infusion. In random order, glucose and mannitol radiolabeled with [2-3H]glucose were infused intraduodenally for 4 h while the systemic rate of glucose turnover was assessed by [6-14C]glucose. During the final hour of the study, plasma glucose, insulin, C-peptide, glucagon, cholecystokinin, and neurotensin were similar under both experimental conditions. Despite an increase in gastric inhibitory polypeptide concentration during combined enteral and iv glucose infusion to levels that mimicked meal ingestion, total glucose infusion rate, insulin-induced stimulation of glucose uptake, and insulin-induced suppression of hepatic glucose release were comparable to those observed during iv glucose administration. These data indicate that under conditions of modest hyperinsulinemia and euglycemia, gastric inhibitory polypeptide did not influence hepatic or extrahepatic insulin action.

Adult↗
PubMed1990

Lack of growth hormone effect on insulin-associated suppression of insulinlike growth factor binding protein 1 in humans.

Insulinlike growth factor binding protein 1 (IGFBP-1) has been shown to modulate the metabolic and mitogenic actions of the growth hormone (GH)-dependent peptide insulinlike growth factor I. Previous studies showed that levels of IGFBP-1 are regulated by insulin. The relative role of GH in the regulation of IGFBP-1 levels is less well defined and was examined in our study with a contiguous two-part protocol. Overnight (part A) and pre- and post-morning meal (part B) blood samples were obtained from eight healthy adults during a constant infusion of saline (SAL) or 4 micrograms.kg-1.min-1 GH. Five of eight subjects were restudied with glucose (GLUC) infused during part B (SAL + GLUC) to match glucose and insulin to levels observed during GH infusion. During SAL infusion, IGFBP-1 levels measured by specific radioimmunoassay showed a marked immediate decline after the evening meal in part A, with a subsequent nocturnal rise of 2.4- to 17.3-fold. GH infusion resulted in a similar meal-induced fall in IGFBP-1 levels but led to a delayed nocturnal rise in IGFBP-1, which was associated with elevated postprandial insulin concentrations. During part B, changes in plasma IGFBP-1 levels showed a similar pattern, with a delayed postprandial increase observed during both GH and SAL + GLUC infusions. The half-life of IGFBP-1 disappearance was calculated at approximately 2 h for all three infusion groups. Comparison of venous and arterialized blood samples showed no consistent pattern of difference, arguing against peripheral tissue clearance or compartmentalization as the mechanism for the rapid rise and fall in IGFBP-1 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effect of insulin on oxidation of intracellularly and extracellularly derived glucose in patients with NIDDM. Evidence for primary defect in glucose transport and/or phosphorylation but not oxidation.

Insulin-stimulated glucose oxidation is decreased in patients with non-insulin-dependent diabetes mellitus (NIDDM). It is not known whether this decrease is due to a primary defect in the oxidative pathway or is secondary to impaired glucose transport and/or phosphorylation. To address this issue, glucose oxidation was measured under steady-state conditions at low (approximately 270 pmol) and high (approximately 17 mumol) insulin concentrations in seven patients with NIDDM and seven healthy nondiabetic subjects matched for sex, age, and obesity. Glucose oxidation was measured simultaneously by indirect calorimetry and the isotopedilution technique. Although glucose oxidation and nonoxidative storage were lower (P less than 0.05) in diabetic than nondiabetic subjects during the low- and high-dose insulin infusions, oxidation of intracellularly derived glucose, estimated by subtracting the rate of oxidation measured isotopically (i.e., glucose oxidation derived from the extracellular space) from that measured by indirect calorimetry (i.e., total glucose oxidation), did not differ in diabetic and nondiabetic subjects during the low-dose insulin infusion (3.3 +/- 0.1 vs. 3.0 +/- 0.1 mumol.kg-1.min-1). Both techniques provided identical estimates of glucose oxidation during the high-dose insulin infusion. Impaired oxidation of extracellularly but not intracellularly derived glucose strongly suggests that the cause of decreased glucose oxidation in patients with NIDDM is secondary to impaired glucose transport and/or phosphorylation rather than a primary abnormality in the oxidative pathway.

Adult↗
PubMed1990

Pattern of postprandial carbohydrate metabolism and effects of portal and peripheral insulin delivery.

The importance of portal insulin delivery in the regulation of postprandial carbohydrate metabolism is uncertain. To address this question, three groups of dogs were studied: one group in which pancreatic venous drainage was transected and reanastomosed (portal insulin delivery), one in which the pancreatic drainage was transected and anastomosed to the inferior vena cava (peripheral insulin delivery), and one that received only a sham operation. Plasma insulin was greater (P less than 0.05) during peripheral insulin delivery than in either the portal or sham groups, respectively, before and after meal ingestion. On the other hand, C-peptide concentrations did not differ between groups, resulting in a higher (P less than 0.001) insulin to C-peptide ratio in the peripheral group. This indicated that the hyperinsulinemia in the peripheral group was due to decreased insulin clearance rather than increased insulin secretion. Isotopically determined splanchnic uptake of ingested glucose, postprandial suppression of hepatic glucose release, incorporation of CO2 into glucose (a qualitative measure of gluconeogenesis), and total-body glucose uptake were virtually identical in all groups. Similarly, plasma lipid, beta-hydroxybutyrate, and lactate concentrations did not differ between groups. Our data indicate that, despite differences in systemic insulin concentration, portal and peripheral insulin delivery comparably regulate hepatic and extrahepatic carbohydrate metabolism after meal ingestion.

Animals↗
PubMed1990

Hepatic and extrahepatic responses to insulin in NIDDM and nondiabetic humans. Assessment in absence of artifact introduced by tritiated nonglucose contaminants.

It is well established that patients with non-insulin-dependent diabetes mellitus (NIDDM) are resistant to insulin. However, the contribution of hepatic and extrahepatic tissues to insulin resistance remains controversial. The uncertainty may be at least in part due to errors introduced by the unknowing use in previous studies of impure isotopes to measure glucose turnover. To determine hepatic and extrahepatic responses to insulin in the absence of these errors, steady-state glucose turnover was measured simultaneously with [6-3H]- and [6-14C]glucose during sequential 5- and 4-h infusions of insulin at rates of 0.4 and 10 mU.kg-1.min-1 in diabetic and nondiabetic subjects. At low insulin concentrations, [6-3H]- and [6-14C]glucose gave similar estimates of glucose turnover. Hepatic glucose release was equal to but not below zero in the nondiabetic subjects, but persistent glucose release (P less than 0.001) and decreased glucose uptake (P less than 0.001) was observed in the diabetic patients. At high insulin concentrations, both isotopes underestimated glucose turnover during the 1st h after initiation of the high-dose insulin infusion. More time (P less than 0.05) was required to reachieve steady state in NIDDM than nondiabetic subjects. At steady state, [6-3H]- but not [6-14C]glucose systematically underestimated (P less than 0.05) glucose turnover in both groups due to the presence of a tritiated nonglucose contaminant. The percentage of radioactivity in plasma due to tritiated contaminants was linearly related to turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effects of meal ingestion on plasma amylin concentration in NIDDM and nondiabetic humans.

Recent interest has focused on the potential role of amylin in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). This 37-amino acid peptide is found in extracellular amyloid deposits in approximately 50% of pancreatic islets of patients with NIDDM and has been shown to inhibit skeletal muscle glycogen synthesis in vitro. Immunocytochemical studies have colocalized amylin and insulin within beta-cell secretory granules in nondiabetic humans, provoking the following questions. Is amylin cosecreted with insulin? Are circulating amylin concentrations higher in patients with NIDDM either before or after food ingestion? To answer these questions, we developed a sensitive and specific immunoassay to measure plasma concentrations of amylin in humans. Use of this assay indicated that, in lean nondiabetic subjects, glucose ingestion resulted in an increase (P less than 0.001) in the plasma concentration of amylin (from 2.03 +/- 0.22 to 3.78 +/- 0.39 pM) and insulin (from 48.3 +/- 3.1 to 265 +/- 44 pM). There was a significant correlation between the concentrations of insulin and amylin (r = 0.74, P less than 0.001) and the increase in insulin and amylin concentration (r = 0.65, P less than 0.005). Fasting concentrations of amylin did not differ in diabetic and weight-matched nondiabetic subjects and showed a similar pattern of change after ingestion of a mixed meal. We conclude that amylin is secreted in response to ingestion of either glucose or a mixed meal and circulates at concentrations that do not differ in patients with NIDDM and nondiabetic subjects. It remains to be determined whether amylin at physiological concentrations influences carbohydrate metabolism and if so whether its effects differ in diabetic and nondiabetic humans.

Adult↗
PubMed1990

Differences between prebreakfast and late afternoon glycemic responses to exercise in IDDM patients.

Little information is available regarding the optimal timing of exercise in insulin-dependent diabetes mellitus (IDDM) patients. In this study, six IDDM patients receiving ultralente-based intensive insulin therapy were studied during 30 min of exercise (approximately 60% VO2max), before breakfast, and at 1600. On two other occasions, they were studied at rest. Plasma glucose increased from 6.7 +/- 0.4 to 9.1 +/- 0.4 mM during morning exercise (P less than 0.01). In contrast, mean plasma glucose did not change during afternoon exercise (delta = 0.3 +/- 0.5 mM, NS); however, there was a 0.3- to 1.0-mM decrease in three subjects. The observed difference in the glycemic response to exercise could not be explained on the basis of changes in plasma glucagon, growth hormone, norepinephrine, or epinephrine. Plasma cortisol was higher (P less than 0.02) in the morning than in the afternoon, and plasma free-insulin concentrations were lower (P less than 0.05). These data indicate that the risk of exercise-induced hypoglycemia is lowest before breakfast. The reason for the divergent glycemic responses to exercise is not entirely clear but may be related to the observed differences in free-insulin concentrations. Because of the lower risk of hypoglycemia, our results suggest prebreakfast exercise may be preferable for some IDDM patients receiving intensive insulin therapy. Whether these findings are relevant to patients receiving other types of insulin therapy will require further investigation.

Adult↗
PubMed1989

Diversion of the gastroduodenal vein: an in situ model of systemic insulin drainage.

A technique of diversion of the gastroduodenal vein in a canine model is described to compare long-term metabolic effects of systemic versus portal pancreatic endocrine drainage. The vein was transected at its entrance into the portal vein and either diverted to the inferior vena cava (systemic group) or reanastomosed to the portal vein (portal group). All remaining venous drainage of the pancreas was interrupted. An additional group of animals underwent laparotomy without manipulation of pancreatic vasculature (sham group). Fasting peripheral insulin and glucose values were determined 3 months postoperatively. Fasting insulin values were significantly higher in the systemic group (mean 10.7 +/- 1.06 U/ml) than in the portal (5.8 +/- 0.70, P = 0.002) and sham (6.4 +/- 0.68, P = 0.01) groups. Fasting glucose values were not significantly different in the three groups. At sacrifice, venous thrombosis was noted in one systemically diverted dog (6.7%). All other anastomoses were patent. No significant collateralization was apparent in any group. No significant complications were noted. This procedure simulates the hormonal milieu created by heterotopic pancreatic transplantation while preserving pancreatic innervation and exocrine function, and serves as an excellent model for investigating the effects of systemic hyperinsulinemia on protein, carbohydrate, and lipid metabolism.

Animals↗
PubMed1989

Assessment of the postprandial pattern of glucose metabolism in nondiabetic subjects and patients with non-insulin-dependent diabetes mellitus using a simultaneous infusion of [2(3)H] and [3(3)H] glucose.

Glucose turnover determined with tritiated isotopes of glucose is subject to potential error due to glucose/glucose-6-phosphate cycling and/or cycling through glycogen. To determine the extent to which these processes alter the apparent pattern of postprandial glucose metabolism, we measured glucose turnover simultaneously with [2(3)H] glucose (an isotope that minimally cycles through glycogen but is extensively detritiated during glucose/glucose-6-phosphate cycling) and [3(3)H] glucose (an isotope that is not detritiated during glucose/glucose-6-phosphate cycling but can cycle through glycogen). Glucose turnover was measured in patients with non-insulin-dependent diabetes mellitus (NIDDM) and nondiabetic subjects both before and after ingestion of a carbohydrate meal isotopically with labeled [6(14)C] glucose. In the postabsorptive state hepatic glucose appearance was higher (P less than .05) when determined with [2(3)H] glucose than with [3(3)H] glucose in the diabetic patients, but not in the nondiabetic subjects. After glucose ingestion the integrated responses of glucose appearance, systemic entry of ingested glucose, and hepatic glucose release all were higher (P less than .05) when determined with [2(3)H] glucose compared to [3(3)H] glucose in both the diabetic and nondiabetic subjects. However, the absolute difference between glucose turnover measured with [2(3)H] and [3(3)H] glucose were similar in the diabetic and nondiabetic subjects. Both isotopes provided a similar assessment of postprandial carbohydrate metabolism, indicating that either isotope can be used with equal efficacy to compare postprandial carbohydrate metabolism in patients with NIDDM and nondiabetic subjects.

Adult↗
PubMed1989

Influence of body fat distribution on free fatty acid metabolism in obesity.

UNLABELLED: In order to determine whether differences in body fat distribution result in specific abnormalities of free fatty acid (FFA) metabolism, palmitate turnover, a measure of systemic adipose tissue lipolysis, was measured in 10 women with upper body obesity, 9 women with lower body obesity, and 8 nonobese women under overnight postabsorptive (basal), epinephrine stimulated and insulin suppressed conditions. RESULTS: Upper body obese women had greater (P less than 0.005) basal palmitate turnover than lower body obese or nonobese women (2.8 +/- 0.2 vs. 2.1 +/- 0.2 vs. 1.8 +/- 0.2 mumol.kg lean body mass (LBM)-1.min-1, respectively), but a reduced (P less than 0.05) net lipolytic response to epinephrine (59 +/- 7 vs. 79 +/- 5 vs. 81 +/- 7 mumol palmitate/kg LBM, respectively). Both types of obesity were associated with impaired suppression of FFA turnover in response to euglycemic hyperinsulinemia compared to nonobese women (P less than 0.005). These specific differences in FFA metabolism may reflect adipocyte heterogeneity, which may in turn affect the metabolic aberrations associated with different types of obesity. These findings emphasize the need to characterize obese subjects before studies.

Adipose Tissue↗
PubMed1989

Underestimation of glucose turnover measured with [6-3H]- and [6,6-2H]- but not [6-14C]glucose during hyperinsulinemia in humans.

Recent studies indicate that hydrogen-labeled glucose tracers underestimate glucose turnover in humans under conditions of high flux. The cause of this underestimation is unknown. To determine whether the error is time-, pool-, model-, or insulin-dependent, glucose turnover was measured simultaneously with [6-3H]-, [6,6-2H2]-, and [6-14C]glucose during a 7-h infusion of either insulin (1 mU.kg-1.min-1) or saline. During the insulin infusion, steady-state glucose turnover measured with both [6-3H]glucose (8.0 +/- 0.5 mg.kg-1.min-1) and [6,6-2H2]glucose (7.6 +/- 0.5 mg.kg-1.min-1) was lower (P less than .01) than either the glucose infusion rate required to maintain euglycemia (9.8 +/- 0.7 mg.kg-1.min-1) or glucose turnover determined with [6-14C]glucose and corrected for Cori cycle activity (9.8 +/- 0.7 mg.kg-1.min-1). Consequently "negative" glucose production rates (P less than .01) were obtained with either [6-3H]- or [6,6-2H2]- but not [6-14C]glucose. The difference between turnover estimated with [6-3H]glucose and actual glucose disposal (or 14C glucose flux) did not decrease with time and was not dependent on duration of isotope infusion. During saline infusion, estimates of glucose turnover were similar regardless of the glucose tracer used. High-performance liquid chromatography of the radioactive glucose tracer and plasma revealed the presence of a tritiated nonglucose contaminant. Although the contaminant represented only 1.5% of the radioactivity in the [6-3H]glucose infusate, its clearance was 10-fold less (P less than .001) than that of [6-3H]glucose. This resulted in accumulation in plasma, with the contaminant accounting for 16.6 +/- 2.09 and 10.8 +/- 0.9% of what customarily is assumed to be plasma glucose radioactivity during the insulin or saline infusion, respectively (P less than .01). When corrected for the presence of the contaminant, glucose turnover determined with [6-3H]glucose during insulin infusion (9.5 +/- 0.6 mg.kg-1.min-1) no longer differed from either the glucose infusion rate or that determined with [6-14C]glucose. Therefore, the underestimation of glucose turnover during insulin infusion and negative glucose production rates observed with traditional methods to analyze plasma radioactivity and commercially available tracers is the result of an artifactual increase in [6-3H]glucose specific activity. The etiology of the underestimation of glucose turnover with [6,6-2H2]glucose remains to be determined.

Adult↗
PubMed1989

Effects of basal insulin supplementation on disposition of mixed meal in obese patients with NIDDM.

Basal insulin supplementation has been used as a therapy for patients with non-insulin-dependent diabetes mellitus (NIDDM) who require insulin. To determine whether basal insulin supplementation in addition to lowering postabsorptive plasma glucose concentration also improves the postprandial pattern of glucose disposition, glucose metabolism after ingestion of a solid mixed meal was assessed in obese patients with NIDDM before and after treatment with ultralente and compared with glucose metabolism observed in nondiabetic subjects. Splanchnic uptake of ingested glucose clearance was assessed by including [2-3H]glucose (a tracer that only minimally cycles through glycogen) in a solid mixed meal. Postprandial gluconeogenesis was estimated by measuring the rate of incorporation of carbon dioxide into glucose. Net glucose and lipid oxidation were measured by indirect calorimetry. Both splanchnic uptake of ingested glucose (27 +/- 1 vs. 14 +/- 2 g) and postprandial hepatic glucose release (51 +/- 5 vs. 24 +/- 3 g) were greater (P less than .001) in diabetic than in nondiabetic subjects. Although the percentage of postprandial hepatic glucose release accounted for by glucose synthesis from bicarbonate was similar in the two groups (25 +/- 2 vs. 35 +/- 5%), the absolute rate was greater in the diabetic patients (13 +/- 1 vs. 8 +/- 1 g; P less than .05). Postprandial glucose oxidation and glucose disposal (measured either isotopically or by the forearm-catheterization technique) were similar in both groups. However, total lipid oxidation was increased in the diabetic patients. (P less than .05). Two weeks of basal insulin supplementation lowered fasting glucose concentrations (from 219 +/- 22 to 144 +/- 21 mg/dl; P less than .01) and integrated postprandial glycemic response (from 814 +/- 68 to 621 +/- 72 min.mg.ml-1) but not to normal. Although circulating insulin concentrations were two- to threefold greater (P less than .02) after 3 mo of basal insulin supplementation, the postprandial pattern of glucose metabolism remained essentially the same. Basal insulin supplementation decreased (P less than .05) both splanchnic uptake of ingested glucose and hepatic glucose release. The addition of a preprandial injection of soluble insulin to basal insulin supplementation further suppressed (P less than .05) postprandial hepatic glucose release, thereby further improving postprandial glucose tolerance. These studies indicate that initial splanchnic glucose clearance, hepatic glucose release, and new glucose synthesis, as well as extrahepatic substrate metabolism, are altered in NIDDM after ingestion of a mixed meal.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Glucose↗