Cross-sectional and Longitudinal Analyses of Factors Contributing to the Progressive Loss of the β-cell Function in Type 2 Diabetes.
OBJECTIVE
Type 2 diabetes is a progressive disease characterized by insulin resistance and insulin secretory dysfunction. In this study, we assessed the factors contributing to an insulin secretory defect in type 2 diabetes patients.


METHODS
The subjects consisted of 382 patients with type 2 diabetes, aged 57±13 years. We estimated the β-cell function using 6-min post-glucagon increments in C-peptide (ΔCPR).


RESULTS
A significant inverse correlation was observed between the time since the diagnosis of diabetes and ΔCPR. A simple liner regression analysis showed that ΔCPR decreases at a rate of 0.056 ng/mL/year. According to a multiple regression model, body mass index (BMI) and log (triglyceride) were positively correlated with ΔCPR. Time since the diagnosis of diabetes, diabetes in 1st degree relatives, the presence of diabetic retinopathy, and HbA1c were inversely correlated with ΔCPR. In 50 patients who underwent the glucagon stimulation test twice, the ΔCPR decreased from 2.27±1.47 to 1.72±1.08 ng/mL over a period of 6.5±0.9 years. A multiple regression analysis revealed the BMI and fasting plasma glucose level to be significant contributing factors to the decline in ΔCPR.


CONCLUSIONS
The duration of diabetes, a low BMI, genetic factors, and the presence of microangiopathy may be associated with β-cell dysfunction in diabetic patients. The observations in this study suggest that obese subjects showed a rapid decline in the β-cell function despite an initial high CPR response. Environmental factors causing insulin resistance and glucotoxicity may therefore be involved in progressive β-cell failure.
Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Japan.
Hitomi
H
Nakayama
Tomoko
T
Kato
Satoshi
S
Nakayama
Hiroh
H
Kaku
Kazuhisa
K
Muraishi
Ichiro
I
Tokubuchi
Kento
K
Hara
Tamotsu
T
Kato
Nobuhiko
N
Wada
Munehisa
M
Tsuruta
Tsuyoshi
T
Ohki
Kayo
K
Tanaka
Kenshi
K
Mitsuzaki
Yuji
Y
Tajiri
Kentaro
K
Yamada
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005934:Glucagon / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000150:complications / Q000378:metabolism*; D012044:Regression Analysis; D013851:Thinness / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D002096:C-Peptide; D005934:Glucagon; D006442:Glycated Hemoglobin; D007328:Insulin; D014280:Triglycerides; C517652:hemoglobin A1c protein, human