Korean Diabetes Journal 2001;25(2):113-124.
Published online April 1, 2001.
Serum Proinsulin, Proinsulin/Total Insulin Ratio and Insulin Resistance in Elderly-onset Type 2 Diabetes.
Yoon Ju Oh, Young Ju Park, Young Wan Kim, Sung Ki Kim, Seong Bin Hong, Yoe Joo Kim, Mi Rim Kim, Moon Suk Nam, Yong Seong Kim
Department of Internal Medicine, College of Medicine, Inha University, Inchon, Korea.
Abstract
BACKGROUND
It is well known that the concentration of serum proinsulin and the ratio of proinsulin/total insulin (P/I) are elevated in type 2 diabetes. Proinsulin is produced by the ribosome in pancreatic beta cells, undergoes maturation in Golgi body and exists in the form of secretory granules. Immature granules possess disproportionately large amount of proinsulin. When there is increased demand of insulin caused by diabetes, higher level of proinsulin is secreted from immature granules of dysfunctioning beta cells. Thus, the elevated concentration of proinsulin and the increased ratio of P/I are considered to be the markers of pancreatic dysfunction and predictors for the future development of diabetes. The elderly-onset type 2 diabetes is also thought to develop due to both dysfunction of insulin secretion by impaired beta cell with aging and increased insulin resistance in peripheral tissue due to less muscle mass and more fat. However, it is still controversial as to which mechanism is predominant in the development of type 2 diabetes. METHODS: We measured the levels of fasting blood glucose, serum proinsulin and specific human insulin by using radioimmunoassay kit, and calculated the P/I ratio and insulin sensitivity index in normal adults (40or=60, n=35) and also in the newly-diagnosed elderly type 2 diabetes (age>or=60, n=24). RESULTS: The concentration of serum proinsulin and the ratio of P/I in normal adults over age 40 were 7.70+/-6.08 pmol/L and 0.13+/-0.10, respectively. The concentration of proinsulin in the normal adult, normal elderly and elderly diabetes group were 6.50+/-3.71, 11.17+/-8.30 and 16.75+/-11.68 pmol/L. The differences among three groups were statistically significant (p= 0.0001). The P/I ratios for each of the three groups were 0.11+/-0.05, 0.17+/-0.12 and 0.16+/-0.08 (p=0.0004). P/I ratios in the elderly control and elderly diabetes were higher than that of the normal adult group. Insulin sensitivity index (ISI, 10,000/(basal glucose X basal insulin)) of elderly diabetes (1.19+/-0.89) was lower when compared with the indices of other groups (40or=60 control; 2.27+/-1.11, p=0.0001). CONCLUSION: Although the age-related reduction of pancreatic insulin secretory function attributes to the pathogenesis of old-age onset type 2 diabetes, it appears that the decreased insulin sensitivity may serve as more important factor in the development of the disease.
Key Words: Proinsulin, Proinsulin/total insulin ratio, Insulin resistance, Elderly-onset type 2 diabetes


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