Aspects of glucose homeostasis in uremia as assessed by the hyperinsulinemic euglycemic clamp technique

Schmitz, O.; Alberti, K. G. M. M.; Christensen, N. J.; Hasling, C; Hjøllund, Elisabeth; Beck‐Nielsen, Henning; Ørskov, Hans

doi:10.1016/0026-0495(85)90213-6

Cited by 41 publications

(25 citation statements)

References 24 publications

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“…Basal plasma glucagon was considerably elevated in our patients and significantly suppressed during the clamp in both groups. This finding is in agreement with results of previous studies in patients with end-stage CRF [3] and would seem to rule out that hyperglucagonaemia contributes to the insulin resistance. Basal serum NEFA as well as the suppression during insulin infusion were identical in the two groups, as found in other studies [3].…”

Section: Discussionsupporting

confidence: 83%

“…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: 83%

“…GH levels were normal in our patients both basally and during hyperinsulinaemia and thus did not seem to contribute to insulin resistance. In contrast GH levels are elevated in patients with endstage CRF [3]. Basal plasma glucagon was considerably elevated in our patients and significantly suppressed during the clamp in both groups.…”

Section: Discussionmentioning

confidence: 62%

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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: 83%

Section: Discussionsupporting

confidence: 83%

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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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“…The insulin resistance syndrome is operative in patients with hypertension, especially that associated with obesity, as well as among individ-uals with non-insulin-dependent diabetes mellitus and endstage kidney disease. 30,31 Previous research has identified several potential components of the cardiovascular risk factor cluster in these patients, which may contribute to the accelerated atherosclerosis including hyperinsulinemia, resistance to insulin-mediated glucose disposal, a complex dyslipidemia, and elevations of plasminogen activator inhibitor-1. 32 We have been intrigued by evidence that many of these patients appear to be resistant to the nonesterified fatty acid-lowering action of insulin and have a more active renin-angiotensin-aldosterone axis.…”

Section: Discussionmentioning

confidence: 99%

Signaling Events Mediating the Additive Effects of Oleic Acid and Angiotensin II on Vascular Smooth Muscle Cell Migration

et al. 2001

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Abstract-Obese hypertensive patients with cardiovascular risk factor clustering and increased risk for atherosclerotic disease have increased plasma nonesterified fatty acid levels, including oleic acid (OA), and a more active renin-angiotensin-aldosterone system. Vascular smooth muscle cell (VSMC) migration and proliferation participate in the development of atherosclerotic plaque. OA and angiotensin (Ang) II induce synergistic mitogenic responses in VSMCs through sequential signaling pathways dependent on the activation of protein kinase C (PKC), oxidants (reactive oxygen species, ROS), and extracellular signal-regulated kinase (ERK) activation. We tested the hypotheses that (1) OA and Ang II have additive or synergistic effects on VSMC migration and (2) PKC, ROS, and mitogen-activated protein kinase are critical signaling molecules. OA at 100 mol/L increases VSMC migration 60Ϯ10% over control (PϽ0.001). Ang II (10 Ϫ9 mol/L) increases VSMC migration by 62Ϯ13% and 73% over control, respectively (PϽ0.01). Coincubation of cells with OA and Ang II produces a nearly additive increase in VSMC cell migration at 107Ϯ20% (PϽ0.01). Increases in VSMC migration induced by OA alone and combined with Ang II were reduced by PKC inhibition and downregulation. VSMC migration in response to OA alone and with Ang II was also inhibited by N-acetyl-cysteine, MEK inhibition, and ERK antisense. VSMC migration in response to OA alone or combined with Ang II is dependent on activation of PKC, ROS, and ERK activation, further raising the possibility that increased plasma nonesterified fatty acids and an activated renin-angiotensin-aldosterone system in subjects with the risk factor cluster contribute to accelerated atherosclerosis through a PKC, ROS, and ERK-dependent signaling pathway.

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“…Insulin sensitivity, on the other hand, is attenuated in patients with renal impairment, not only in those with endstage renal failure, but also in patients in earlier stages of renal impairment (7)(8)(9). However, to date the metabolic consequences of reduced insulin clearance and diminished insulin sensitivity on pharmacokinetic and pharmacodynamic properties of regular insulin or rapid acting insulin analogues have never been studied in type 1 diabetic patients.…”

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confidence: 98%

Impact of Diabetic Nephropathy on Pharmacodynamic and Pharmacokinetic Properties of Insulin in Type 1 Diabetic Patients

et al. 2001

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OBJECTIVE -To quantify pharmacokinetic and pharmacodynamic properties of regular insulin and insulin lispro in type 1 diabetic patients with and without overt diabetic nephropathy.RESEARCH DESIGN AND METHODS -In this double-blind, two-way cross-over, euglycemic (5 mmol/l) glucose clamp study, we investigated the metabolic response to subcutaneous injections of regular insulin and insulin lispro (0.2 U/kg) in 12 type 1 diabetic patients with overt diabetic nephropathy (proteinuria Ͼ500 mg/24 h and/or serum creatinine Ͼ1.5 mg/dl; NP group) and in a control group of 12 type 1 diabetic patients with normal renal function (DC group). [DC]). The overall metabolic effect of regular insulin but not of insulin lispro was lower in patients with diabetic nephropathy than in diabetic control patients (967 vs. 1,510 mg/kg, respectively). RESULTSCONCLUSIONS -Although insulin levels are higher in patients with overt diabetic nephropathy, the metabolic response to regular insulin is reduced. Insulin lispro maintains its characteristic pharmacokinetic and pharmacodynamic properties in patients with overt diabetic nephropathy. Diabetes Care 24:886 -890, 2001I nsulin therapy in type 1 diabetic patients with overt diabetic nephropathy is characterized by two features: while suffering from a considerably increased risk of severe hypoglycemic episodes (1,2), they show poorer metabolic control than diabetic patients with normal renal function (3). The increased hypoglycemic risk may be partially explained by the decline in renal insulin clearance, as 30 -80% of systemically circulating insulin is removed by the kidneys (4). A reduction of insulin clearance has been described in nondiabetic patients with end-stage renal failure (5,6) and mild to moderate renal impairment (7); however, until now, it has not been studied in patients with diabetic nephropathy.Insulin sensitivity, on the other hand, is attenuated in patients with renal impairment, not only in those with endstage renal failure, but also in patients in earlier stages of renal impairment (7-9). However, to date the metabolic consequences of reduced insulin clearance and diminished insulin sensitivity on pharmacokinetic and pharmacodynamic properties of regular insulin or rapid acting insulin analogues have never been studied in type 1 diabetic patients.In view of the diminished clearance of insulin in patients with altered renal function, the use of a rapid-acting insulin analogue might theoretically be advantageous because of its shorter duration of action, leading to a reduced incidence of hypoglycemic episodes (10,11). Therefore, the aim of this study was to quantify pharmacokinetic and pharmacodynamic summary measures for regular insulin and insulin lispro in type 1 diabetic patients with and without overt diabetic nephropathy. RESEARCH DESIGN AND METHODS PatientsFor this study, 12 type 1 diabetic patients fulfilling the following inclusion criteria were recruited: age 20 -50 years; GHb Ͻ10%; overt diabetic nephropathy (defined according to the modified Mogensen criteria...

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Aspects of glucose homeostasis in uremia as assessed by the hyperinsulinemic euglycemic clamp technique

Cited by 41 publications

References 24 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

Signaling Events Mediating the Additive Effects of Oleic Acid and Angiotensin II on Vascular Smooth Muscle Cell Migration

Impact of Diabetic Nephropathy on Pharmacodynamic and Pharmacokinetic Properties of Insulin in Type 1 Diabetic Patients

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