Immunoreactive Insulin and C‐Peptide Responses to Various Insulin Secretory Stimuli in Subjects with Type 2 Diabetes and in Control Subjects during Continuous Glucose Monitoring
Authors: Ahrén Bo , Schersten Bengt , Agardh Carl‐David , Lundquist Ingmar 
Published: August 2010

ABSTRACT. Immunoreactive insulin (IRI) and C‐peptide secretory responses to terbutaline, glucagon, glucose and a standardized meal were investigated in fasted non‐diabetic control subjects and newly discovered insulin‐independent (type 2) diabetic subjects, during continuous monitoring of plasma glucose concentrations. The β‐adrenoceptor agonist terbutaline (125 μg i.v.) induced a prompt insulin secretory response in controls as well as in diabetics. The diabetic group was heterogeneous with regard to the C‐peptide and IRI responses after this secretagogue. Diabetics with the highest fasting plasma glucose levels had reduced C‐peptide responses to terbutaline. On the contrary, diabetics with the lowest plasma glucose had C‐peptide responses within the range of the control group. Glucagon (250 μg i.v.) induced a pronounced IRI and C‐peptide response in controls as well as in diabetics. In diabetics, the acute C‐peptide response was slightly decreased (by about 35%), whereas the total response during 30 min after glucagon injection was more markedly decreased (by about 65%). No correlation was seen between the degree of C‐peptide secretory derangement and fasting plasma glucose after glucagon stimulation. Glucagon induced also an elevation of plasma glucose levels. However, the continuous glucose monitoring revealed that the IRI and C‐peptide responses preceded the rise in plasma glucose. Furthermore, there was no apparent difference in plasma glucose response to glucagon between the controls and the diabetics. A small load of glucose (6 g. i.v.) induced an immediate insulin secretory response in the controls, whereas the diabetics had totally abolished IRI and C‐peptide responses to glucose. After meal intake, diabetics had decreased IRI and C‐peptide secretory responses during the first 2 hours (about 20 and 45%, respectively) and a slower glucose disappearance rate. Thus, newly discovered type 2 diabetics seem to have totally abolished IRI and C‐peptide secretory responses to a small (6 g) dose of i.v. glucose, while non‐glucose stimuli, such as terbutaline and glucagon, give close to normal (IRI) or moderately diminished (C‐peptide) responses. These results suggest, that determination of the acute IRI and/or C‐peptide secretory responses after a low dose (6 g) of i.v. glucose might be a useful test in the classification of early type 2 diabetes. This simple test leads to plasma glucose levels within the physiological range, and also to levels seen after glucagon and food intake. Furthermore, the secretory response of the insulin cells to terbutaline was lowest in diabetics with the highest levels of circulating glucose. Therefore, the insulin response to terbutaline seemed to give a better differentiation of the degree of metabolic derangement than the insulin secretory response to glucagon or glucose, the C‐peptide levels being a more reliable index of insulin secretory activity than the IRI levels.