Amelioration of Diabetes and Striking Rarity of Acidosis in Patients with Kimmelstiel-Wilson Lesions

Zubrod, C. Gordon; Eversole, Stanton L.; Dana, George W.

doi:10.1056/nejm195110042451402

Cited by 97 publications

(16 citation statements)

References 10 publications

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“…With this caveat, our results call into question whether decreasing insulin requirements among patients with diabetes and advanced CKD can be explained by decreased renal insulin clearance alone. 5,6,30 Differences in mean whole-body insulin clearance by CKD status were modest in our study, even at the lowest eGFRs. Our data suggest that nonrenal insulin clearance may decrease in patients with advanced CKD who develop progressive insulin resistance.…”

Section: Discussioncontrasting

confidence: 53%

“…3,4 In addition, patients with diabetes have been noted for .60 years to require lower doses of therapeutic insulin at low levels of GFR. 5,6 More recently, mild-moderate CKD has been associated with increased rates of hypoglycemia, 7 particularly with intensive diabetes therapy. 8 Decreased renal insulin clearance has been cited as a likely cause of these observations.…”

mentioning

confidence: 99%

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Impaired Glucose and Insulin Homeostasis in Moderate-Severe CKD

Zelnick

Afkarian

Ayers

et al. 2016

JASN

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Kidney disease leads to clinically relevant disturbances in glucose and insulin homeostasis, but the pathophysiology in moderate-severe CKD remains incompletely defined. In a cross-sectional study of 59 participants with nondiabetic CKD (mean eGFR =37.6 ml/min per 1.73 m 2 ) and 39 healthy control subjects, we quantified insulin sensitivity, clearance, and secretion and glucose tolerance using hyperinsulinemiceuglycemic clamp and intravenous and oral glucose tolerance tests. Participants with CKD had lower insulin sensitivity than participants without CKD (mean[SD] 3.9[2.0] versus 5.0 [2.0] mg/min per mU/ml; P,0.01). Insulin clearance correlated with insulin sensitivity (r=0.72; P,0.001) and was also lower in participants with CKD than controls (876 [226] versus 998 [212] ml/min; P,0.01). Adjustment for physical activity, diet, fat mass, and fatfree mass in addition to demographics and smoking partially attenuated associations of CKD with insulin sensitivity (adjusted difference, 20.7; 95% confidence interval, 21.4 to 0.0 mg/min per mU/ml) and insulin clearance (adjusted difference, 285; 95% confidence interval, 2160 to 210 ml/min). Among participants with CKD, eGFR did not significantly correlate with insulin sensitivity or clearance. Insulin secretion and glucose tolerance did not differ significantly between groups, but 65% of participants with CKD had impaired glucose tolerance. In conclusion, moderate-severe CKD associated with reductions in insulin sensitivity and clearance that are explained, in part, by differences in lifestyle and body composition. We did not observe a CKD-specific deficit in insulin secretion, but the combination of insulin resistance and inadequate augmentation of insulin secretion led to a high prevalence of impaired glucose tolerance.

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Section: Discussioncontrasting

confidence: 53%

mentioning

confidence: 99%

Impaired Glucose and Insulin Homeostasis in Moderate-Severe CKD

Zelnick

Afkarian

Ayers

et al. 2016

JASN

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“…Our conclusion that the rate of insulin degradation is decreased in patients with renal failure is not a new one, and this possibility was first advanced to explain the apparent decrease in insulin requirements of patients with diabetic nephropathy (21). Considerable evidence has accumulated since that time indicating that the kidney plays a major role in insulin degradation, and this has been the topic of a recent excellent review article (2).…”

Section: Discussionmentioning

confidence: 98%

Derivation of a three compartment model describing disappearance of plasma insulin-131I in man

Silvers¹,

Swenson²,

Farquhar³

et al. 1969

J. Clin. Invest.

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Veterans Administration Hospital, Palo Alto, California 94305 AB S T R A C T Insulin-LuI was administered intravenously to normal subjects, to patients with maturityonset diabetes and normal renal function, and to nondiabetic patients with renal failure. The ensuing plasma disappearance curves of immunoprecipitable radioactive insulin were determined, and these data were analyzed in a variety of ways. Firstly, fractional irreversible loss rates of insulin from plasma were calculated and found to be greatly diminished in patients with renal failure (t4 = 39 min), as compared with normal (t4 = 15 min) and diabetic subjects (ti = 12 min). Secondly, plasma insulin-2'I disappearance curves were resolved into sums of three exponentials by the method of "peeling," and values for the resultant three slopes and half-lives were determined. Patients with normal renal function had similar values for all parameters, while those patients with renal failure were differentiated on the basis of the slope of the last component, with a prolongation of its half-life to 275 min (approximately twice normal). Finally, a three pool model was formulated to describe the kinetics of plasma insulin disappearance in man. representing plasma (pool 1), interstitial fluid (pool 2), and all tissues in which insulin is utilized and degraded (pool 3). The proposed model adequately describing the disappearance curves of insulin-'I observed in all patients indicated that volumes (per cent body weight) of pool 1 (4.04) and pool 2 (10.11), calculated on the basis of the model and the experimental data, corresponded closely to estimates of plasma and interstitial fluid vol- umes obtained by independent means. It also demonstrated that patients with renal failure were characterized by a decreased removal rate of insulin from pool 3 and an increased recycling rate of insulin from pool 3 to pool 2. It is concluded that the proposed model represents a reasonable description of the kinetics of insulin distribution and degradation, and that its use provides quantitative insights into the physiology of insulin metabolism.

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“…Certainly the loss of a potent insulin inhibitor in the urine of diabetic nephrotics might well play a role in the decreased insulin requirements of these patients. Other possible explanations for improved carbohydrate tolerance in diabetics with nephrosis have been reported (20,21).…”

Section: Mechanism Of Action Of Insulin-inhibitory Albumin Prepamentioning

confidence: 99%