Showing papers by "Richard N. Bergman published in 1986"
TL;DR: This 'minimal modelling approach' fits two mathematical models with FSIGT glucose and insulin data: one of glucose disappearance and one of insulin kinetics, and MINMOD is the computer program which identifies the model parameters for each individual.
725 citations
TL;DR: The correlation between S1 measures by clamp and IVGTT methods provides one step toward validation of the minimal model for studies of insulin action in man and in eight euglycemic women with a wider range of adiposity.
Abstract: Although the minimal-model-based insulin sensitivity index (S1) can be estimated from the results of a simple 180-min intravenous glucose tolerance test (IVGTT), its relationship to widely accepted but technically more difficult clamp-based techniques has not been resolved in humans. Therefore we measured S1 by standard IVGTT, modified IVGTT, and clamp methods in 10 nondiabetic men with %IBW of 109 +/- 12 (mean +/- SD). In the euglycemic clamp studies, insulin was infused to bring insulin levels (IRI) from basal, 8 +/- 4 microU/ml, to plateaus of 21 +/- 5 and 35 +/- 6 microU/ml. S1[clamp], measured as the increase in glucose (G) clearance per increase in IRI [delta INF/(delta IRI X G)], averaged 0.29 +/- 0.09 ml/kg X min per microU/ml. In the IVGTT studies, 300 mg/kg G was given as an i.v. bolus, and G and IRI were measured for 180 min; in the modified (mod) IVGTT, tolbutamide (300-500 mg) was given i.v. 20 min after the G to observe the effect of an IRI peak on G removal after G level was free of initial "mixing" effects. The S1 estimated by computer did not differ significantly between standard [(6.9 +/- 3.4) X 10(-4) min-1 per microU/ml] and modified [(6.7 +/- 3.5) X 10(-4) min-1 per microU/ml] tests, indicating no bias due to the differing insulin patterns and levels. There was a strong positive correlation between S1 (mod IVGTT) and S1(clamp): r = 0.84; N = 10; P less than 0.002. The correlation between S1(standard IVGTT) and S1(clamp) was 0.54, suggesting the modified test is less "noisy." Nonetheless, in eight euglycemic women with a wider range of adiposity, S1(standard IVGTT) has been significantly correlated with %IBW (r = -0.72) and basal IRI (r = -0.84). The correlation between S1 measures by clamp and IVGTT methods provides one step toward validation of the minimal model for studies of insulin action in man.
281 citations
TL;DR: Abnormalities of carbohydrate metabolism with secondary effects on fat and protein metabolism have been identified, in several populations of patients with common cancers, which offer potential points of intervention which may enhance nutritional therapy as rehabilitation and as a potential biological modifier of the response of specific cancers to chemotherapy, radiation therapy, or surgery.
Abstract: A number of common metastatic cancers are associated with marked weight loss at the time of diagnosis. Cancer patients with weight loss at the time of diagnosis have decreased mean survival compared to similar cancer patients without weight loss. Provision of excess calories alone does not appear to change median survival in patients with advanced cancer and many patients either maintain body weight or lose weight while receiving calories which would be predicted to result in weight gain. The authors recently have extended their studies to head and neck cancer patients without detectable metastatic disease in order to detect systemic metabolic effects of a localized tumor. These patients failed to gain weight despite the administration of apparently adequate calories by continuous enteral alimentation. Abnormalities of carbohydrate metabolism with secondary effects on fat and protein metabolism have been identified, in several populations of patients with common cancers. These abnormalities offer potential points of intervention which may enhance nutritional therapy as rehabilitation and as a potential biological modifier of the response of specific cancers to chemotherapy, radiation therapy, or surgery.
89 citations
TL;DR: The analysis suggests that glucose enhances the metabolic flux to glycogen by inducing a build up of glucose 6-phosphate via combined effects of mass action and glucose-6-ph phosphatase inhibition and activating glycogen synthase and that fructose enhances glycogen accumulation by retaining glycogen via phosphorylase inhibition.
52 citations
TL;DR: The importance of putative forebrain glucoreceptors to the systemic response to hypoglycemia is investigated, implying that important glucose-sensitive receptors are located elsewhere in the body.
Abstract: The response to insulin-induced hypoglycemia includes increased plasma levels of glucagon, epinephrine, norepinephrine, cortisol, and growth hormone. This integrated response is thought to be mediated via sympathetic afferent pathways emanating from the ventromedial hypothalamus. However, the precise loci of the receptors that sense glucopenia are not known. In this study, we investigated the importance of putative forebrain glucoreceptors to the systemic response to hypoglycemia. Three protocols were performed. Protocol 1: the systemic response was observed in conscious dogs to hypoglycemia induced by infusion of insulin at a high rate (150 mU/min). Protocol 2: the effect of concomitant bilateral, intracarotid glucose infusion on the response to intravenous insulin was examined. Intracarotid glucose infusion rates were chosen to yield central euglycemia in the face of systemic hypoglycemia. Protocol 3: as a control for protocol 2, glucose was infused at low rates into the systemic circulation, yielding hypoglycemia in both central and systemic blood. When insulin was infused at 150 mU/min, without glucose replacement (protocol 1; N = 6), plasma insulin increased from 14 +/- 3 to 335 +/- 35 microU/ml at 60 min (P less than 0.001). Glucose fell from basal (104 +/- 3 mg/dl) to 38 +/- 3 mg/dl (P less than 0.001). Significant increases were observed in epinephrine (basal, B: 63 +/- 8; steady state, SS: 1762 +/- 582 pg/ml; P less than 0.007), norepinephrine (B: 209 +/- 33, SS: 650 +/- 133 pg/ml; P less than 0.01), and glucagon (B: 256 +/- 35, SS: 467 +/- 35 pg/ml; P less than 0.03). In addition, endogenous glucose production (Ra) increased from 72 +/- 4 to 108 +/- 9 mg/min (P less than 0.02) despite frank hyperinsulinemia. Infusion glucose into the carotid arteries at 204 +/- 10 mg/min (protocol 2; N = 7) during a 4-h systemic insulin infusion was sufficient to prevent jugular hypoglycemia [jugular glucose, Gj, B: 100 +/- 3, SS (90-160 min): 101 +/- 3 mg/dl; P greater than 0.70], but not peripheral hypoglycemia (Gp, B: 102 +/- 2, SS: 55 +/- 3 mg/dl; P less than 0.001). Despite carotid glucose replacement, counterregulatory responses were still observed in epinephrine (B: 98 +/- 14, SS: 466 +/- 127 pg/ml; P less than 0.04) and norepinephrine (B: 213 +/- 19, SS: 474 +/- 133 pg/ml; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
40 citations
TL;DR: It is demonstrated that the presence of coordinated oscillations in glucose and insulin, during glucose infusion, are associated with more efficient disposal of glucose than when oscillations are suppressed, suggesting that oscillations may play an important role in theefficient disposal of administered nutrient and may be an important component of normal glucose tolerance.
Abstract: Oscillations in plasma concentrations of glucose and insulin as well as the rates of glucose disposal by liver and periphery have been observed in dogs during states of net glucose anabolism. To examine whether the existence of oscillations is important for efficient disposal of nutrients, we compared constant glucose infusion (with plasma glucose and insulin oscillations) to experiments in which glucose oscillations were suppressed using the glucose clamp. Mean glucose levels attained were the same for the two protocols (142 +/- 2 for constant glucose infusion at 10.8 +/- 0.4 mg X kg-1 X min-1, 144 +/- 1 mg/dl for clamps, P = 0.35). Despite matched mean glucose, integrated plasma insulin was 36.3 +/- 3.2 mU X ml-1 X 600 min in controls but higher in clamps (53.8 +/- 9.1 mU X ml-1 X 600 min, P = 0.017). Despite 48% higher insulin, total glucose disposed during the 10-h clamps was not greater than during constant glucose infusion (clamps, 162.1 +/- 10.7 g/600 min; infusions, 154.4 +/- 7.5 g/600 min; P = 0.19). These studies demonstrate that the presence of coordinated oscillations in glucose and insulin, during glucose infusion, are associated with more efficient disposal of glucose than when oscillations are suppressed. The results suggest that oscillations may play an important role in the efficient disposal of administered nutrient and may be an important component of normal glucose tolerance.
21 citations