Kinetic Analysis of Plasma Insulin Disappearance in Nonketotic Diabetic Patients and in Normal Subjects

185

A B S T R A C T Tissue sensitive to insulin and insulin binding to monocytes were evaluated in 15 nonobese maturity-onset diabetics and in 16 healthy controls. Insulin sensitivity was determined by the insulin clamp technique in which the plasma insulin is acutely raised and maintained 100 .U/ml above the fasting level and plasma glucose is held constant at fasting levels by a variable glucose infusion. The amount of glucose infused is a measure of overall tissue sensitivity to insulin.In the diabetic group, the fasting plasma glucose concentration (168±4 mg/dl) was 85% greater than controls (P < 0.01) whereas the plasma insulin level (15±1 ,U/ml) was similar to controls. During the insulin clamp study, comparable plasma insulin levels were achieved in the diabetics (118±5) and the controls (114±5 ,uU/ml). However, the glucose infusion rate in the diabetics (4.7±0.4 mg/kg min) was 30% below controls (P < 0.01). Among the diabetics, the glucose infusion rate correlated directly with the fasting plasma glucose level (r = 0.57, P < 0.05). In five diabetic subjects, glucose metabolism was similar to controls, and these diabetics had the highest fasting glucose levels. When they were restudied after prior normalization (with insulin) of the fasting plasma glucose (100±1 mgldl), the glucose infusion rate during the insulin clamp was 30% lower than observed in association with hyperglycemia (P < 0.01). Studies that employed tritiated glucose to measure endogenous glucose production indicated comparable 90-95% inhibition of hepatic glucose production during hyperinsulinemia in the diabetic and control subjects.1251-insulin binding to monocytes in the diabetics (5.5±0.6%) was 30% below that in controls (P < 0.01).

Section: -Insulin Binding To Monocytessupporting

confidence: 91%

Insulin Sensitivity and Insulin Binding to Monocytes in Maturity-Onset Diabetes

DeFronzo¹,

Deibert²,

Hendler³

et al. 1979

185

“…The values of fasting posthepatic insulin delivery rate calculated from the clamp in our lean subjects are similar to those previously obtained in lean, healthy volunteers by direct measurement of plasma insulin clearance with radioiodinated insulin (44). Assuming 50% liver extraction (42) ]) falls well within the range measured by Polonsky et al (13) with the use of C-peptide kinetics and deconvolution analysis.…”

Section: ϫ2supporting

confidence: 85%

Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR).

Ferrannini

Natali²,

Bell³

et al. 1997

860

460

Insulin resistance and insulin hypersecretion are established features of obesity. Their prevalence, however, has only been inferred from plasma insulin concentrations. We measured insulin sensitivity (as the whole-body insulin-mediated glucose uptake) and fasting posthepatic insulin delivery rate (IDR) with the use of the euglycemic insulin clamp technique in a large group of obese subjects in the database of the European Group for the Study of Insulin Resistance (1,146 nondiabetic, normotensive Caucasian men and women aged 18-85 yr, with a body mass index (BMI) ranging from 15 to 55 kg·m Ϫ 2 ). Insulin resistance, defined as the lowest decile of insulin sensitivity in the lean subgroup (608 subjects with BMI Յ 25 kg·m Ϫ 2 ), was present in 26% of the obese subgroup (538 subjects with a mean BMI of 29 kg·m Ϫ 2 ). Insulin sensitivity declined linearly with BMI at an age-and sex-adjusted rate of 1.2 mol·min Ϫ 1 ·kg FFM Ϫ 1 per BMI unit (95% confidence intervals ϭ 1.0-1.4). Insulin hypersecretion, defined as the upper decile of IDR, was significantly ( P Ͻ 0.0001) more prevalent (38%) than insulin resistance in the obese group. In the whole dataset, IDR rose as a function of both BMI and insulin resistance in a nonlinear fashion. Neither the waist circumference nor the waistto-hip ratio, indices of body fat distribution, was related to insulin sensitivity after adjustment for age, gender, and BMI; both, however, were positively associated ( P Ͻ 0.001) with insulin hypersecretion, particularly in women.In nondiabetic, normotensive obese subjects, the prevalence of insulin resistance is relatively low, and is exceeded by the prevalence of insulin hypersecretion, particularly in women with central obesity. In the obese with preserved insulin sensitivity, risk for diabetes, cardiovascular risk, and response to treatment may be different than in insulin resistant obesity. ( J. Clin. Invest. 1997. 100:1166-1173.)

“…Despite decreased blood glucose and increased plasma insulin, the disappearance of [3H]insulin from the plasma should not have been affected to any significant extent, provided that the insulin-removal mechanisms remained unsaturated over the range of insulin variations induced. We think that this is most likely the case because of reports that disappearance of 125I-insulin under basal conditions and during glucose infusion was the same (25) and the immunoreactive insulin curves obtained after infusing large amounts of either unlabeled or labeled hormone (15,(23)(24)(25) were essentially the same, apart from a scale factor. Finally, the results in the present studies show that changes in IDV for [3H]insulin occur following presaturation of the receptor compartment with native insulin (Table III) and that labeled material can be displaced from the receptor compartment of unlabeled insulin (Fig.…”

Section: Discussionmentioning

confidence: 83%

“…However, interpretation of the results ofthese studies has been severely handicapped by doubts concerning the authenticity of the radioiodinated insulins used in the majority of these studies (23,24,(27)(28)(29). Although new techniques for labeling and purifying radioiodinated insulins (30)(31)(32) have yielded tracers of value for pharmacokinetic studies, even these preparations may not be fully homogenous.…”

Section: Discussionmentioning

confidence: 99%

Increased Clearance and Degradation of [3H]Insulin in Streptozotocin Diabetic Rats

Philippe¹,

Halban²,

Gjinovci³

et al. 1981

A B S T R A C T The role of the insulin-receptor compartment in the pharmacokinetics of intravenously injected insulin in rats was studied. Since when the animals were again hyperglycemic and hypoinsulinemic. This suggests that down-regulation of insulin receptors had occurred during insulin therapy. These results confirm that a specific compartment for insulin exists (the insulin-receptor compartment) and that this compartment plays an important role in insulin clearance.