Effect of obesity on declining beta cell function after diagnosis of type 2 diabetes: a possible link suggested by cross-sectional analysis

Abstract

Type 2 diabeTes is characterized by beta cell dysfunction and insulin resistance [1,2]. Recent studies have shown a deficit of beta cell mass in type 2 as well as type 1 diabetes [3][4][5][6], with emergence of the idea that beta cell dysfunction is the central pathophysiological mechanism of type 2 diabetes. Importantly, not only is there a beta cell deficit in patients with type 2 diabetes, but also this deficit has been shown to worsen with the duration of diabetes. The UK Prospective Diabetes Study (UKPDS) has shown that this progressive decline in beta cell function is associated with deterioration of blood glucose control irrespective of the treatment strategy [7]. Moreover, we and others have abstract. It has been reported that beta cell function progressively declines in patients with type 2 diabetes. The objective of this study was to assess the effect of obesity on declining beta cell function after diagnosis of type 2 diabetes. We conducted a cross-sectional study of 689 consecutive subjects with type 2 diabetes who were admitted to our hospital from 2000 to 2007. Fasting and postprandial serum C-peptide immunoreactivity (CPR) and urinary CPR levels had been measured during admission. The subjects were stratified according to BMI and time since diagnosis. CPR index was calculated as CPR (ng/mL) / plasma glucose (mg/dL) x 100. All CPR measurements were significantly higher in the 263 obese (BMI ≥25) subjects compared to the 426 lean subjects (BMI <25). There was a significant negative correlation between CPR indices and duration of diabetes, suggesting a progressive decline in beta cell function after diagnosis of type 2 diabetes. However, this decline was more apparent in obese subjects (postprandial CPR index 0.059/year) compared to lean subjects (0.025/year). The significant difference in serum CPR indices between the lean and obese subjects was lost in subjects more than 10 years after diagnosis. In conclusion, our observations suggest that beta cell function shows a greater progressive decline in obese subjects than in lean subjects with type 2 diabetes. Treatment of obesity may be an important strategy to preserve beta cell function in patients with type 2 diabetes.

Clinical features of slowly progressive type 1 (insulin-dependent) diabetes mellitus: a comparative study based on degree of obesity at diagnosis of diabetes

“…However, a comparison of the CPI in cases with the same degree of obesity and duration of DM as patients in our study could be done. In our study, the fasting CPI was 0.47 ± 0.30 at SPIDDM diagnosis in the obese group, whereas the index was reported to be 1.45 ± 0.84 in Japanese obese patients [16]. Patients in our study had obviously low fasting CPI, and postprandial values were similarly low.…”

Lower beta cell function relates to sustained higher glycated albumin to glycated hemoglobin ratio in Japanese patients with type 2 diabetes

“…Beta cell dysfunction is a hallmark of type 2 diabetes and progressively declines with disease duration [26,27]. The association between lower beta cell function and higher GA/HbA1c after 2 years observed in this study suggests that patients with lower beta cell function are exposed to sustained greater glucose excursion even after improvement of HbA1c by intensification of treatment.…”

Glycemic Variability and Oxidative Stress: A Link between Diabetes and Cardiovascular Disease?

“…Moreover, beta cell function progressively deteriorates during the course of the disease [117,118,119]. Therefore, to appropriately manage GV, it is important to preserve and recover beta cell function.…”