Effects of Duration of Type 2 Diabetes Mellitus on Insulin Secretion

Farhad Zangeneh, MD; Puneet S. Arora, MD; Peter J. Dyck, MD; Lynn Bekris; Ake Lernmark, PhD; Sara J. Achenbach; Ann L. Oberg, PhD; Robert A. Rizza, MD


Endocr Pract. 2006;12(4):388-393. 

In This Article

Patients and Methods

The design of the Rochester Diabetic Neuropathy Study has been previously described in detail.[10] Beginning January 1, 1986, all subjects with known diabetes (N = 870) who resided within Rochester, Minnesota, were invited to join the study. Of the 456 patients who agreed to participate, 99 had a fasting C-peptide concentration and an increment in C-peptide level of less than 0.17 nmol/L at 6 minutes after intravenous injection of 1 mg of glucagon at study entry or had detectable anti-GADA65 or IA-2 antibodies[11,12,13] and, therefore, were classified as having type 1 diabetes. Of the remaining 357 patients, 89 (51 men and 38 women) had plasma C-peptide concentrations (fasting and at 6 minutes after intravenous administration of 1 mg of glucagon) measured at entry and every 2 years for at least 6 years (median, 12 years; range, 6 to 14) beginning in 1985 and ending in 2001. This provided the opportunity to assess the pattern of change in insulin secretion over time. The results from these 89 study subjects are included in the current report.

Plasma C-peptide concentrations were measured by radioimmunoassay (Linco Research, St. Louis, MO). The C-peptide intra-assay coefficient of variation was 6.1% at 0.24 nmol/L, 6.1% at 0.52 nmol/L, and 7.1% at 0.73 nmol/L. The C-peptide interassay coefficient of variation was 8.9% at 0.41 nmol/L, 8.2% at 1.66 nmol/L, and 7.1% at 4.2 nmol/L. Of note, C-peptide concentrations measured in 1993 and 1994 were excluded from analyses because of a transient but substantial decrease in all values measured during those years, implying assay drift. Plasma glucose and creatinine were measured by using a colorimetric assay. A1C concentrations were measured by affinity chromatography (Glyc-Affin; Isolab, Akron, OH; normal range, 4.0% to 6.3%).

Summary data are expressed as medians and interquartile ranges. The least squares slope of the study end points versus time was calculated for each subject, as was the least squares slope for the regression of plasma glucose level versus C-peptide concentration. The median of these slopes was compared with zero by using the Wilcoxon signed rank test to determine whether there was a significant change in insulin secretion over time. Slopes representing a decrease, an increase, or no change in insulin secretion were arbitrarily defined as less than or equal to -0.01, greater than or equal to 0.01, or between -0.01 and 0.01 nmol/L, respectively.


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