Glucose Intolerance in Uremia

DeFronzo, Ralph A.; Tobin, Jordan D.; Andres, Reubin

doi:10.1172/jci109144

Cited by 270 publications

(54 citation statements)

References 38 publications

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“…Serum C-peptide was significantly suppressed in both groups indicating that the endogenous insulin production had been suppressed, and hypoglycaemia did not occur in any subjects during the study. This finding of our patients with only mild to moderate CRF is in agreement with previous observations in patients with end-stage CRF [2][3][4][5][6][7][8][9][10][11][12].…”

Section: Discussionsupporting

confidence: 94%

Insulin resistance and hyperinsulinaemia in mild to moderate progressive chronic renal failure and its association with aerobic work capacity

et al. 1995

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Summary Tissue sensitivity to insulin and aerobic work capacity was measured in patients with mild to moderate progressive chronic renal failure. Twentynine non-diabetic patients with a glomerular filtration rate of 25 ml-min -1 9 1.73 m -2 (11-43) (median, range) and 15 sex, age, and body mass index matched control subjects with normal renal function were studied. Fasting blood glucose was comparable and in the non-diabetic range in the two groups as was the oral glucose tolerance test. Patients demonstrated hyperinsulinaemia both during fasting (p < 0.01) and during the test (p < 0.02). The tissue sensitivity to insulin, expressed by the amount of glucose infused during the last 60 min of a 120-rain hyperinsulinaemia euglycaemic clamp (M-value) and the M/I ratio, was significantly lower in the patients than in the control subjects (M-value 404 + 118 vs 494 _+ 85 mg glucose/kg body weight, p < 0.02) (M/I ratio 1.77 + 0.71 vs 2.57 + 0.70 (mg/(kgBW -min) per pmol/1. 100, p < 0.001). The maximal aerobic work capacity was significantly lower in the patients than in the control subjects (24 + 8 vs 32 + 11 ml O2/(kg body weight-min), p < 0.02) and positively correlated to the M-value and the M/I ratio in both groups. In conclusion, not only patients with end-stage chronic renal failure but also those with mild to moderate progressive chronic renal failure are insulin resistant and hyperinsulinaemic. The tissue sensitivity to insulin is correlated to the maximal aerobic work capacity suggesting that these patients might benefit from physical training programmes. [Diabetologia (1995) 38: 565-572]

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Section: Discussionsupporting

confidence: 94%

Insulin resistance and hyperinsulinaemia in mild to moderate progressive chronic renal failure and its association with aerobic work capacity

et al. 1995

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“…29 On the other hand, diabetes is known to be frequently associated with ESRD. 30 Diabetic patients with advanced renal failure have a mediocre vascular prognosis, related in particular to macroangiopathies and increased arterial stiffness. 31 Finally, increased plasma levels of homocysteine 13,14 and ET 11,12 are a common feature in subjects with chronic renal failure.…”

Section: Discussionmentioning

confidence: 99%

“…First, we have already noted the role of an increased calcium phosphate product in the mechanism of aortic calcifications. 30 Second, in diabetic subjects, vascular lesions are related not only to the numerous metabolic anomalies linked to this pathological condition 31 but also to the induction of tissue damage via slow, irreversible changes in extracellular molecules due to hyperglycemia, particularly covalent modifications and the resulting advanced glycation end products. 37 Third, homocysteine has also been shown to enhance smooth muscle cell proliferation and even alter elastic tissue.…”

Section: Discussionmentioning

confidence: 99%

Influence of Biochemical Alterations on Arterial Stiffness in Patients With End-stage Renal Disease

Blacher

Demuth

Guérin

et al. 1998

ATVB

190

115

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Abstract-The incremental elastic modulus of the common carotid and radial arteries is increased in patients with end-stage renal disease (ESRD), independently of blood pressure, wall stress, and the presence of atherosclerotic alterations. Whether biochemical factors may be involved in the arterial changes and related to renal dysfunction remain largely ignored. To assess this question, we measured aortic (carotid-femoral), upper-limb (carotid-radial), and lower-limb (femoral-tibial) pulse wave velocity (PWV) in 74 ESRD patients undergoing hemodialysis in comparison with 57 control subjects similar in age, sex ratio, and mean blood pressure. We evaluated arterial blood presure by sphygmomanometry, aortic calcifications and cardiac mass by echography, and routine biochemical parameters, total plasma homocysteine, and plasma endothelin levels by standard techniques. In the population of patients with ESRD, on the basis of multiple stepwise regression analysis, aortic PWV was positively and independently correlated with systolic blood pressure (PϽ.0001), age (PϽ.0001), prevalence of aortic calcification (Pϭ.0004), and the prevalence of diabetes mellitus (Pϭ.0043). Upper-limb PWV was influenced exclusively by mean blood pressure (PϽ.0001). Lower-limb PWV was positively and independently correlated with plasma total homocysteine (Pϭ.0004) and plasma endothelin (Pϭ.0187) only. At any vascular site, PWV was not independently correlated with tobacco consumption; plasma levels of cholesterol, triglyceride, fibrinogen, or hemoglobin; body mass index; or the presence of bilateral nephrectomy. Finally, plasma homocysteine was independently correlated with cardiac mass (Pϭ.0022). This study provides evidence that in ESRD patients, the stiffness of the arterial wall and cardiac mass are strongly influenced by biochemical factors related to the kidney alterations and are independent of age and blood pressure level. Increased plasma endothelin and homocysteine may be specifically involved in the vascular damage of lower limbs. (Arterioscler Thromb Vasc Biol. 1998;18:535-541.)

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“…This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. glucose was determined by the "hyperglycemic clamp" technique (10). Plasma glucose concentration was increased to 125 mg/100 ml above the basal level by the intravenous administration of a priming infusion of glucose given in a logarithmically decreasing manner during 14 min.…”

Section: Methodsmentioning

confidence: 99%

Influence of hyperinsulinemia, hyperglycemia, and the route of glucose administration on splanchnic glucose exchange

DeFronzo

Ferrannini

Hendler

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

257

163

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The effects of hyperinsulinemia, hyperglycemia, and the route of glucose administration on total glucose utilization and on net splanchnic glucose exchange were studied in 20 normal volunteers with the hepatic venous catheter technique. Euglycemic hyperinsulinemia [induced by a priming plus continuous infusion of insulin resulting in plasma insulin levels of ,units (international)/ml and a variable glucose infusion] caused a 5-to 6-fold increase above basal in total glucose turnover. However, net splanchnic glucose uptake (0.5 ± 0.2 mg/kg per min) accounted for only 4-5% of total glucose utilization. When hyperglycemia (223 + .1 mg/dl) was induced in addition to hyperinsulinemia by the intravenous infusion of glucose, splanchnic glucose uptake increased 100% to 1.0-1.1 mg/kg per min but was still responsible for only 10-14% of total glucose utilization. In other studies hyperglycemia (223 + 2 mg/dl) was maintained constant by a variable intravenous infusion of glucose for 4 hr and oral glucose (1.2 gm/kg) was administered at 1 hr. After the oral glucose, net splanchnic glucose uptake increased to values 6-fold higher than with intravenous glucose despite unchanged plasma glucose levels and plasma insulin concentrations well below those observed in the studies with euglycemic hyperinsulinemia. The results indicate that hyperinsulinemia or hyperglycemia induced by intravenous infusion of glucose or insulin causes minimal net uptake of glucose by the splanchnic bed despite marked stimulation of total glucose turnover. In contrast, administration of glucose by the oral route has a marked stimulatory effect on net splanchnic glucose uptake. These findings suggest that orally consumed glucose causes the release of a gastrointestinal factor that enhances insulin-mediated glucose uptake by the liver.The liver has long been recognized to play a central role in blood glucose homeostasis (1)(2)(3)(4). However, the factors that regulate hepatic glucose uptake still remain controversial. The pioneering studies of Soskin and Levine (5) suggested that hyperglycemia per se was responsible for the switch of the liver from a glucose-producing to a glucose-assimilating organ. However, subsequent in vivo studies by Madison (3) and Felig and Wahren (2, 4) indicated that this switch is dependent upon the presence of hyperinsulinemia. More recently Bergman (6) has reemphasized the importance of hyperglycemia in the regulation of hepatic glucose uptake and has suggested that concommitant hyperinsulinemia enhances its effect. What role, if any, the route of glucose administration (i.e., oral versus intravenous) has in determining hepatic glucose uptake has not been established. The present study was consequently undertaken to evaluate the relative effects of hyperglycemia, hyperinsulinemia, and the route of glucose administration on net splanchnic glucose uptake. Euglycemic Hyperinsulinemia. The effect on splanchnic glucose balance of hyperinsulinemia at a basal plasma glucose concentration was determined by the "insulin cla...

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Glucose Intolerance in Uremia

Cited by 270 publications

References 38 publications

Insulin resistance and hyperinsulinaemia in mild to moderate progressive chronic renal failure and its association with aerobic work capacity

Insulin resistance and hyperinsulinaemia in mild to moderate progressive chronic renal failure and its association with aerobic work capacity

Influence of Biochemical Alterations on Arterial Stiffness in Patients With End-stage Renal Disease

Influence of hyperinsulinemia, hyperglycemia, and the route of glucose administration on splanchnic glucose exchange

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