Chronic sulfonylurea treatment and hyperglycemia aggravate disproportionately elevated plasma proinsulin levels in patients with type 2 diabetes.
It is established that disproportionately elevated plasma proinsulin levels occur in patients with Type 2 diabetes. In the present study, multivariate analysis was performed to determine what factors contributed to the disproportionately elevated plasma proinsulin levels in Japanese patients with Type 2 diabetes (n=276). Results from univariate analysis showed that both fasting proinsulin/C-peptide ratio and proinsulin/IRI ratio were approximately 2-fold higher in patients with Type 2 diabetes than those in healthy nondiabetic subjects (n=45). In patients with Type 2 diabetes, both proinsulin/C-peptide ratio and proinsulin/IRI ratio were significantly positively correlated with fasting plasma glucose level (FPG) and HbA1c. Neither proinsulin/C-peptide ratio nor proinsulin/IRI ratio was significantly correlated with BMI. Sulfonylurea-treated subjects had a significant elevation in both proinsulin/C-peptide ratio and proinsulin/IRI ratio compared with diet-treated subjects, whereas nonsulfonylurea hypoglycemic agent-treated subjects did not. Multivariate analysis confirmed that sulfonylurea treatment and FPG were significant determinants of both fasting proinsulin/C-peptide ratio (P=0.006 and P=0.030, respectively) and proinsulin/IRI ratio (P=0.003 and P=0.016, respectively) in patients with Type 2 diabetes. These results imply that disproportionate hyperproinsulinemia may reflect an excessive overwork of beta cells under chronic sulfonylurea treatment as well as hyperglycemia.
Inoguchi
T
T
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Umeda
F
F
Kakimoto
M
M
Sako
Y
Y
Ishii
H
H
Noda
K
K
Kunisaki
M
M
Imamura
M
M
Yu
H Y
HY
Etoh
T
T
Yoshikawa
H
H
Aoki
T
T
Hashimoto
T
T
Nawata
H
H
D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D005215:Fasting; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000097:blood*; D007328:Insulin / Q000097:blood; D008875:Middle Aged; D015999:Multivariate Analysis; D011384:Proinsulin / Q000097:blood*; D013453:Sulfonylurea Compounds / Q000009:adverse effects* / Q000627:therapeutic use
D002096:C-Peptide; D006442:Glycated Hemoglobin; D007328:Insulin; D011384:Proinsulin; D013453:Sulfonylurea Compounds