Documentation of Hyperglucagonemia Throughout the Day in Nonobese and Obese Patients with Noninsulin-Dependent Diabetes Mellitus*

Abstract

Plasma glucose, insulin, FFA, glucagon, and GH concentrations were measured over an 8-h period in normal subjects and patients with noninsulin-dependent diabetes mellitus (NIDDM). Meals were consumed at 0800 h (20% of daily calories) and noon (40% of daily calories), and measurements were made hourly from 0800-1600 h. Day-long plasma glucose, insulin, and FFA concentrations were higher than normal (by two-way analysis of variance) in patients with NIDDM, whether obese or nonobese. In addition, day-long plasma glucagon concentrations were also higher than normal (by two-way analysis of variance) in both nonobese and obese patients with NIDDM. Furthermore, direct relationships were found between the total plasma glucagon response from 0800-1600 h and total plasma glucose (r = 0.57; P less than 0.001) and FFA (r = 0.30; P less than 0.06) responses. In contrast, plasma GH levels were not increased in patients with NIDDM. These data demonstrate that ambient plasma concentrations of both glucose and FFA are higher in patients with NIDDM, despite the fact that coexisting plasma insulin levels are equal to or higher than normal. The higher day-long plasma glucagon levels in patients with NIDDM may contribute to their higher plasma glucose and FFA concentrations.

Glucagon secretion in relation to insulin sensitivity in healthy subjects

“…This concept is important for understanding the key role of the islet beta cells for the development of IGT and type 2 diabetes: if beta cell compensation to insulin resistance fails, glucose homeostasis deranges, which will result in IGT and type 2 diabetes [3]. However, we, and others, have demonstrated that glucagon secretion is also important for the development of IGT and type 2 diabetes, in view of the hyperglucagonaemia and increased glucagon secretion which accompany these conditions [4][5][6][7][8][9][10][11][12]. This raises the issue of the relationship between insulin resistance and glucagon secretion under normal conditions.…”

“…Also, the augmented suppression by glucose would not be explained by such a mechanism. Interestingly, subjects with IGT and type 2 diabetes have reduced suppression by glucose of glucagon secretion [4][5][6][7][8][9][10][11][12]. It remains to be established whether failure of the augmenting action of glucose to suppress glucagon levels in insulin resistance represents the mechanism that initiates IGT.…”

“…It is, however, also known that type 2 diabetes is associated with elevated levels of glucagon [4][5][6] and defective suppression of glucagon secretion [4,7,8]. Also IGT is associated with impaired suppression of glucagon secretion [9][10][11].…”

“…Also IGT is associated with impaired suppression of glucagon secretion [9][10][11]. The subsequent relative hyperglucagonaemia is probably of importance for postprandial hyperglycaemia in diabetes due to increased hepatic glucose production [5,6,12]. In fact, Shah et al [13] have demonstrated that also in the absence of insulin resistance, glucose tolerance is critically dependent on normal suppression of glucagon secretion.…”

Association of fasting glucagon and proinsulin concentrations with insulin resistance

“…Day-long plasma glucagon concentrations are raised in patients with type 2 diabetes [1]. Impaired suppression of glucagon release can be detected in individuals with impaired glucose tolerance (IGT) and type 2 diabetes following intravenous [2] or oral glucose administration [3].…”