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

Disclosures

Endocr Pract. 2006;12(4):388-393. 

In This Article

Results

Body mass index (P = 0.194) did not change significantly over time. In contrast, A1C decreased (P<0.005) during the same interval, whereas creatinine increased slightly (P<0.001) ( Table 1 and Fig. 1).

Effects of the duration of diabetes on body mass index (A), hemoglobin A1c (B), and plasma creatinine concentration (C). P values refer to the Wilcoxon signed rank test of the median of the subject-specific slopes versus zero. The median trajectory is represented by the thick line constructed from the median subject-specific intercept and slope.

In order to determine whether insulin secretion decreased with increasing duration of diabetes, the fasting, 6-minute, and postglucagon increment in C-peptide concentrations were analyzed versus years since onset of diabetes, as determined from the patients' medical records. For the group as a whole, the median slope of fasting C-peptide, 6-minute C-peptide, and postglucagon increment in C-peptide concentrations versus duration of diabetes all were negative (P<0.01), an indication of a small but significant decrease in insulin secretion over time (Fig. 2). As is evident from Figure 3, however, insulin secretion did not decrease in all subjects. The subject-specific slopes of fasting C-peptide concentration versus duration of diaaabetes was less than or equal to -0.01 nmol/L per year (that is, decreased over time) in 45 study subjects, greater than or equal to 0.01 nmol/L per year (increased over time) in 20 subjects, and between -0.01 and 0.01 nmol/L per year (remained essentially unchanged) in 24 subjects (Fig. 3 A). The slope of the 6-minute C-peptide concentration versus duration of diabetes was less than or equal to -0.01 nmol/L per year in 51 study subjects (that is, declined over time), greater than or equal to 0.01 nmol/L per year in 20 subjects (increased over time), and between -0.01 and 0.01 nmol/L per year in 18 subjects (remained essentially unchanged) (Fig. 3 B). Similarly, the slope of post-glucagon increment in C-peptide concentration versus duration of diabetes was less than or equal to -0.01 nmol/L per year in 41 study subjects (that is, decreased over time), greater than or equal to 0.01 nmol/L per year in 16 subjects (increased over time), and between -0.01 and 0.01 nmol/L per year in 32 subjects (remained essentially unchanged) (Fig. 3 C).

Effects of the duration of diabetes on the pattern of change of the fasting (A), 6-minute (B), and postglucagon increment in C-peptide concentrations (C). P values refer to the Wilcoxon signed rank test of the median of the subject-specific slopes versus zero. The median trajectory is represented by the thick line constructed from the median subject-specific intercept and slope.

Histograms of slopes versus the duration of diabetes for the fasting (A), 6-minute (B), and postglucagon increment in Cpeptide concentrations (C). Vertical lines indicate arbitrary cutoffs for slopes that decreased (slopes less than -0.01 nmol/L), increased (slopes greater than 0.01 nmol/L), or were essentially unchanged (slopes between -0.01 and 0.01 nmol/L).

Of interest, initial fasting C-peptide, 6-minute C-peptide, and postglucagon increment in C-peptide concentrations were higher (P<0.01) in patients whose subsequent slope was less than -0.01 nmol/L (that is, decreased) than in those patients whose slope was greater than -0.01 nmol/L.

To determine whether the fasting, 6-minute, and post-glucagon increment in C-peptide concentrations were related to plasma glucose level at the time of testing, we ascertained the relationship between these variables for each study subject by using linear regression analysis. Although the resultant slopes (0.002, 0.003, and 0.001 nmol/L per mg/dL of glucose) were significantly different from zero (P<0.05), as was evident from the small size of the slope, the effect of the prevailing fasting glucose concentration on plasma C-peptide concentration was small.

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