Effect of Hyperglycemia<i>per se</i>on Glucose Disposal and Clearance in Noninsulin-Dependent Diabetics*

Best, James D.; Beard, James C.; Taborsky, Gerald J.; Halter, Jeffrey B.; Porte, Daniel

doi:10.1210/jcem-56-4-819

Cited by 14 publications

(7 citation statements)

References 14 publications

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“…Thus, we demonstrated that mean (± SEM) MCR G was slightly higher (2.76 verses 2.51 mg/ kg/min) when 13 patients were studied at lower as compared with higher steady-state glucose concentration. 7 Similarly, Best et al 15 studied 7 patients with NIDDM, and demonstrated a 13% increase in MCR G when insulin clamps were performed at plasma glucose levels averaging 96 mg/dl as compared with 194 mg/dl. The results of these two studies suggest that use of glucose MCR to compare in vivo insulin action before and after control of hyperglycemia in patients with NIDDM will lead to an approximate 10% overestimate of MCR G at the lower plasma glucose level.…”

Section: Discussionmentioning

confidence: 95%

Insulin Therapy in Obese, Non-insulin-dependent Diabetes Induces Improvements in Insulin Action and Secretion that Are Maintained for Two Weeks After Insulin Withdrawal

et al. 1984

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The effects of rigorous insulin treatment on insulin action (insulin clamp) and secretion (plasma insulin response to glucose) were studied in 13 obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Improvements were documented in fasting (P less than 0.0001) and postprandial (P less than 0.0001) plasma glucose concentrations, insulin secretion after oral glucose (P less than 0.001), and insulin action (P less than 0.005) after 30 days of therapy. Mean integrated plasma insulin response to glucose increased 2.5-fold after insulin therapy, but this improvement varied considerably from patient to patient. Insulin action also increased with insulin treatment and the resulting values were no longer significantly different from a weight- and age-matched group of subjects with normal glucose tolerance. However, there was considerable patient-to-patient variation in the degree to which insulin action was enhanced. The insulin-induced improvements in glucose tolerance persisted for at least 2 wk after insulin withdrawal, and were associated with continued increased insulin secretion and insulin action. In conclusion, control of hyperglycemia for 1 mo led to improvements in both insulin secretion and action in a series of obese patients with NIDDM that persisted for at least 2 wk after cessation of therapy.

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Section: Discussionmentioning

confidence: 95%

Insulin Therapy in Obese, Non-insulin-dependent Diabetes Induces Improvements in Insulin Action and Secretion that Are Maintained for Two Weeks After Insulin Withdrawal

et al. 1984

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“…Recent data show that glucose uptake follows saturation kinetics. Thus, glucose clearance is not independent of plasma glucose concentration, indicating that the use of glucose clearance under some circumstances may be misleading (24, 25,26). The MCR of ketone bodies (MCRK) (the volume of blood irreversibly and completely cleared of ketone bodies) was calculated according to MCRK = Na-D-j3-OHB infusion rate/(X Ketone body concentration at equilibrium -basal ketone body concentration) (14).…”

Section: Methodsmentioning

confidence: 99%

Effect of ketone bodies on glucose production and utilization in the miniature pig.

Müller¹,

Paschen²,

Seitz³

1984

J. Clin. Invest.

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As bstract. The effect of ketone bodies on glucose production (Ra) and utilization (Rd) was investigated in the 24-h starved, conscious unrestrained miniature pig. Infusing Na-DL-3-OH-butyrate (Na-DL-f-OHB) and thus shifting the blood pH from 7.40 to 7.56 resulted in a decrease of Ra by 52% and of Rd by 45%, as determined by the isotope dilution technique. Simultaneously, the concentrations of arterial insulin and glucagon were slightly enhanced, whereas the plasma levels of glucose, lactate, pyruvate, alanine, a-amino-N, and free fatty acids (FFA) were all reduced. Infusion ofNa-bicarbonate, which yielded a similar shift in blood pH, did not mimick these effects. Infusion of equimolar amounts of the ketoacid, yielding a blood pH of 7.35, induced similar metabolic alterations with respect to plasma glucose, Ra, Rd, and insulin; however, plasma alanine and a-amino-N increased.Infusing different amounts of Na-DL-3-OHB resulting in plasma steady state levels of ketones from 0.25 to 1.5 mM had similar effects on arterial insulin and glucose kinetics. No dose dependency was observed.Prevention of the Na-DL-3-OHB-induced hypoalaninemia by simultaneous infusion of alanine (1 ttmol/kg X min) did not prevent hypoglycemia.Infusion of Na-DL-l-OHB plus insulin (0.4 mU/kg in plasma glucose and Ra; however, on infusion of somatostatin plus Na-DL-3-OHB, hypoglycemia and the reduced Ra were maintained.In the anaesthetized 24-h starved miniature pig, Na-DL-3-OHB infusion decreased the hepatic exchange for glucose, lactate, and FFA, whereas the exchange for glycerol, alanine, and a-amino-N as well as liver perfusion rate were unaffected. Simultaneously, portal glucagon and insulin as well as hepatic insulin extraction rate were elevated. Leg exchange for glucose, lactate, glycerol, alanine, a-amino-N, and FFA were decreased, while ketone body utilization increased.Repeated infusion of Na-DL-3-OHB at the fourth, fifth, and sixth day of starvation in the conscious, unrestrained mini-pig resulted in a significant drop in urinary nitrogen (N)-excretion. However, this effect was mimicked by infusing equimolar amounts of Na-bicarbonate. In contrast, when only the ketoacid was given, urinary Nexcretion accelerated.To summarize: (a) Ketone bodies decrease endogenous glucose production via an insulin-dependent mechanism; in addition, ketones probably exert a direct inhibitory action on gluconeogenesis. The ketone bodyinduced hypoalaninemia does not contribute to this effect. (b) The counterregulatory response to hypoglycemia is reduced by ketones. (c) As a consequence of the decrease in Ra, glucose utilization declines during ketone infusion.(d) The insulin-stimulated MCR for glucose is not affected by ketones. (e) Ketones in their physiological moiety do not show a protein-sparing effect.

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“…5). Because measurements of MCR have been shown to underestimate insulin action by 10-15% at higher glucose levels (9,12), the lack of a significant acarbose-induced increase in MCR underlines the fact that the improvement in diabetic control was not due to a decrease in insulin resistance.…”

Section: Combined Sulfonylurea'acarbose In Niddmmentioning

confidence: 99%

Effect of Acarbose on Carbohydrate and Lipid Metabolism in NIDDM Patients Poorly Controlled by Sulfonylureas

et al. 1990

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The ability of acarbose to lower plasma glucose concentration was studied in 12 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were poorly controlled by diet plus sulfonylurea drugs. Patients were studied before and 3 mo after the addition of acarbose to their treatment program, and a significant improvement in glycemic control was noted. Although the decrease in fasting plasma glucose concentration was modest (12.0 +/- 0.8 to 10.8 +/- 0.3 mM), average postprandial plasma glucose concentration decreased by 3.4 mM. When acarbose therapy was discontinued in 5 patients, plasma glucose levels rapidly returned toward pretreatment levels. In addition to the improvement in glycemia, acarbose treatment also led to a significant reduction in HbA1c (7.4 +/- 0.2 to 6.4 +/- 0.2%, P less than 0.01) and triglyceride (2.4 +/- 0.1 to 2.1 +/- 0.1 mM, P less than 0.01) concentrations. Neither the plasma insulin response to meals nor insulin-stimulated glucose uptake improved with acarbose therapy, consistent with the view that acarbose improves glycemic control by delaying glucose absorption. Considerable individual variation was noted in the response to acarbose, and the results in 4 patients were dramatic, with striking reductions in both fasting and postprandial glucose concentrations. The addition of acarbose to patients with NIDDM not well controlled by sulfonylureas appears to have significant clinical benefit.

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Effect of Hyperglycemiaper seon Glucose Disposal and Clearance in Noninsulin-Dependent Diabetics*

Cited by 14 publications

References 14 publications

Insulin Therapy in Obese, Non-insulin-dependent Diabetes Induces Improvements in Insulin Action and Secretion that Are Maintained for Two Weeks After Insulin Withdrawal

Insulin Therapy in Obese, Non-insulin-dependent Diabetes Induces Improvements in Insulin Action and Secretion that Are Maintained for Two Weeks After Insulin Withdrawal

Effect of ketone bodies on glucose production and utilization in the miniature pig.

Effect of Acarbose on Carbohydrate and Lipid Metabolism in NIDDM Patients Poorly Controlled by Sulfonylureas

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