Diminished insulin clearance during late pregnancy in patients with Type I diabetes mellitus

1998 ◽  
Vol 95 (3) ◽  
pp. 317-323 ◽  
Author(s):  
Anders O. BJÖRKLUND ◽  
Ulf K. C. ADAMSON ◽  
Per-Eric S. LINS ◽  
L. Magnus R. WESTGREN
Keyword(s):  
Diabetes Mellitus ◽  
Steady State ◽  
Blood Glucose ◽  
Clearance Rate ◽  
Insulin Infusion ◽  
Type I Diabetes ◽  
Type I ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Insulin Levels

1.Intensive insulin treatment of patients with Type I diabetes mellitus during pregnancy is associated with a high frequency of serious hypoglycaemic events. A potential change in insulin metabolism during pregnancy may affect both the frequency and the severity of insulin-induced hypoglycaemia. 2.In 10 patients with Type I diabetes, during the third trimester of pregnancy and 5 to 13 months after delivery, hypoglycaemia was induced by the hyperinsulinaemic hypoglycaemic clamp technique. A constant high-dose intravenous insulin infusion was administered for 150 ;min and arterial blood glucose was clamped at 2.2 ;mmol/l by counterregulation with intravenous glucose. During the experiment venous samples were collected for later analysis of free plasma insulin, whereby the metabolic clearance rate of insulin could be calculated. 3.The desired blood glucose level was approached after approximately 60 ;min of insulin infusion. After just 30 ;min the insulin levels were significantly higher during pregnancy compared with after delivery. In addition, the steady-state insulin level from 90 to 150 ;min was significantly higher during pregnancy. 4.From the steady-state insulin levels at 90 to 150 ;min, the metabolic clearance rate of insulin was calculated, being 24% higher after delivery. 5.We conclude that there is a decreased metabolic clearance rate of insulin during pregnancy. This might be due to altered blood-flow distribution, decreased hepatic insulin extraction and relative increase in body fat during pregnancy. A decreased clearance of insulin will contribute to the risk for serious hypoglycaemic events in patients with Type I diabetes during pregnancy.

Validation of a new method for determination of free fatty acid turnover

1987 ◽  
Vol 252 (3) ◽  
pp. E431-E438 ◽  
Author(s):  
J. M. Miles ◽  
M. G. Ellman ◽  
K. L. McClean ◽  
M. D. Jensen
Keyword(s):  
Steady State ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Clearance Rate ◽  
Experimental Period ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
State Equations ◽  
Tracer Methods

The accuracy of tracer methods for estimating free fatty acid (FFA) rate of appearance (Ra), either under steady-state conditions or under non-steady-state conditions, has not been previously investigated. In the present study, endogenous lipolysis (traced with 14C palmitate) was suppressed in six mongrel dogs with a high-carbohydrate meal 10 h before the experiment, together with infusions of glucose, propranolol, and nicotinic acid during the experimental period. Both steady-state and non-steady-state equations were used to determine oleate Ra ([3H]oleate) before, during, and after a stepwise infusion of an oleic acid emulsion. Palmitate Ra did not change during the experiment. Steady-state equations gave the best estimates of oleate inflow approximately 93% of the known oleate infusion rate overall, while errors in tracer estimates of inflow were obtained when non-steady-state equations were used. The metabolic clearance rate of oleate was inversely related to plasma concentration (P less than 0.01). In conclusion, accurate estimates of FFA inflow were obtained when steady-state equations were used, even under conditions of abrupt and recent changes in Ra. Non-steady-state equations, in contrast, may provide erroneous estimates of inflow. The decrease in metabolic clearance rate during exogenous infusion of oleate suggests that FFA transport may follow second-order kinetics.

scholarly journals Acute Hypoxia Suppresses Exogenous Glucose Rate Of Appearance And Metabolic Clearance Rate During Steady-state Aerobic Exercise

2020 ◽  
Vol 52 (7S) ◽  
pp. 597-597
Author(s):  
Lee M. Margolis ◽  
Marques A. Wilson ◽  
Claire C. Whitney ◽  
Christopher T. Carrigan ◽  
Nancy E. Murphy ◽  
...  
Keyword(s):  
Steady State ◽  
Aerobic Exercise ◽  
Clearance Rate ◽  
Acute Hypoxia ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Exogenous Glucose

Sitagliptin (Januvia)

Top Drugs ◽  
2015 ◽  
Author(s):  
Jie Jack Li
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Type Ii Diabetes ◽  
Kidney Diseases ◽  
Type I Diabetes ◽  
Glycosylated Hemoglobin ◽  
Insulin Injection ◽  
Type I ◽  
Type Ii ◽  
Ancient Times

Diabetes has been known since antiquity. In fact, the term “diabetes mellitus” comes from the Greek meaning “siphon and honey” due to the excess excretion (siphon or faucet) of hyperglycemic (sweetened, or honeyed) urine associated with diabetes. In ancient times, diabetes was mostly type I, which usually manifests acutely in the young, secondary to certain underlying insults (possibly infections) to the islet cells of the pancreas resulting in an absolute lack of insulin. Insulin was discovered by Banting and Best in 1921, and insulin injection has literally saved millions of lives since then. With the wondrous efficacy that insulin bestows, type I diabetes is largely controlled because type I diabetes is insulindependent. However, type II diabetes, a more prevalent form of diabetes, is not insulin-dependent. In ancient times, when nutrition was scarce and obesity was not prevalent, type II diabetes mellitus (T2DM) was extremely rare. Indeed, type II diabetes is a disease more frequently associated with maturity, obesity, and gradually increasing blood glucose concentrations, and it may be asymptomatic for some time, only discovered on routine glucose screening. In fact, with the increasing body weight of the general population of the developed world, type II diabetes is becoming an epidemic. Serious complications of diabetes include nephropathy (kidney diseases), neuropathy (nerve damage), and retinopathy (blindness). Diabetes is the most common cause of blindness and amputation in the elderly in the United States. Oral diabetes drugs are required for most type II diabetic patients. Diabetes drugs may be classified into four categories: (a) agents that augment the supply of insulin such as sulfonylureas; (b) agents that enhance the effectiveness of insulin such as biguanides and thiazolidinediones; (c) GLP agonists; and (d) DPP4 Inhibitors. The efficacy of all the antidiabetic drugs can be monitored by measuring glycosylated hemoglobin (HaA1c) as a long term marker of elevated blood glucose. The amount of HaA1c reflects the average level over the last 120 days, the life span of a red blood cell, and should remain below 7%.

Pharmacokinetics and organ-specific metabolism of calcitonin gene-related peptide in sheep

1988 ◽  
Vol 118 (1) ◽  
pp. 25-31 ◽  
Author(s):  
K. G. Braslis ◽  
A. Shulkes ◽  
D. R. Fletcher ◽  
K. J. Hardy
Keyword(s):  
Steady State ◽  
Clearance Rate ◽  
Half Life ◽  
Calcitonin Gene Related Peptide ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Related Peptide ◽  
Modes Of Action ◽  
Calcitonin Gene ◽  
Organ Specific

ABSTRACT Calcitonin gene-related peptide (CGRP) is a product of the calcitonin gene with a widespread distribution in neural tissue of the brain, gut and perivascular nerves. Infusion of CGRP produces multiple biological effects, but the physiological significance of these findings will be influenced by the sites and rates of CGRP metabolism. The metabolic clearance rate and half-life of disappearance of human CGRP were estimated in conscious sheep after infusing CGRP at 1 or 5 pmol/kg per min to steady-state conditions. The particular organs involved in the clearance of CGRP were assessed by measuring the inflow and outflow concentrations across the liver, gut, kidney, lung and brain. The metabolic clearance rate at steady state was 22·6 ± 2·1 (s.e.m.) and 15·0±1·7 ml/kg per min for the 1 and 5 pmol/kg per min doses respectively. The half-life of disappearance was bi-exponential: 3·6±0·3 min for the first phase and 13·6±1·0 min for the second phase. High-pressure liquid chromatography of plasma at equilibrium revealed only a single peak coeluting with CGRP(1–37): no immunoreactive metabolites were detected. These pharmacokinetic values are intermediate between that of a neurotransmitter and a hormone and are therefore consistent for a peptide with both circulatory and neurotransmitter modes of action. The kidney, with an arterial–renal vein gradient of 14%, and the liver, with a portal– hepatic vein gradient of 25%, were the major organs involved in the clearance of CGRP. The specific organ clearance, however, accounted for only one-third of the whole body metabolic clearance rate of CGRP, suggesting that other more generalized degradative systems are involved, such as endothelial-bound enzymes of blood vessels. This information on clearance and organ-specific metabolism should form a basis for evaluating the physiological roles and modes of action of CGRP. J. Endocr. (1988) 118,25–31

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