Importance of Beta Cell Function for the Treatment of Type 2 Diabetes

Yoshifumi Saisho, Yoshifumi Saisho

Abstract

Type 2 diabetes (T2DM) is characterized by insulin resistance and beta cell dysfunction. Recent evidence has emerged that beta cell dysfunction is a common pathogenetic feature of both type 1 and type 2 diabetes, and T2DM never develops without beta cell dysfunction. Therefore, treatment of T2DM should aim to restore beta cell function. Although the treatment of T2DM has greatly improved over the past few decades, remaining issues in the current treatment of T2DM include (1) hypoglycemia; (2) body weight gain; (3) peripheral hyperinsulinemia and (4) postprandial hyperglycemia, which are all associated with inappropriate insulin supplementation, again underpinning the important role of endogenous and physiological insulin secretion in the management of T2DM. This review summarizes the current knowledge on beta cell function in T2DM and discusses the treatment strategy for T2DM in relation to beta cell dysfunction.

Keywords: beta cell; insulin secretion; therapy; type 2 diabetes.

Figures

Figure 1
Figure 1
Correlation between baseline postprandial C-peptide index (PCPRI) and HbA1c (A) and glycated albumin (GA) (B) after two years. Reproduced with permission from [20].
Figure 2
Figure 2
Correlation between postprandial C-peptide index (PCPRI) and glycated albumin (GA) to HbA1c ratio in patients with type 2 diabetes (A) and type 1 diabetes (B). In Figure 2B, the data of patients with type 1 diabetes are superimposed on the data of those with type 2 diabetes (gray circles and dotted line). Reproduced with permission from [24].
Figure 3
Figure 3
Importance of controlling postprandial glycemic excursion. (A) If mean plasma glucose level is lowered without controlling postprandial glycemic excursion (gray line → black line), the risk of hypoglycemia between meals and during the night increases (arrows); (B) Lowering the mean glucose level with control of postprandial glycemic excursion (gray line → black line) results in a low risk of hypoglycemia. Note that mean plasma glucose levels are similar in both cases, indicating similar HbA1c in both cases.
Figure 4
Figure 4
Proposed concept of treatment strategy for type 2 diabetes (T2DM) in relation to functional beta cell mass. An α-glucosidase inhibitor is partly approved for use in patients with impaired glucose tolerance (IGT) in Japan. Medications not approved or marketed in Japan are not included in the figure. Reproduced with permission from [101]. Since currently no single therapy or agent can cure and even manage T2DM, an effective combination of current medications in addition to lifestyle modification aiming at reduction in beta cell workload is important to preserve or recover beta cell function.
Figure 5
Figure 5
Postprandial C-peptide index (PCPRI) in subjects according to obesity and time after diagnosis (0–4, 5–10, 11–17 and ≥18 years). There were significant differences in PCPRI between lean (open bars) and obese subjects (solid bars) in the first and second quartiles of time after diagnosis, but no significant differences were observed in the third and fourth quartiles. * p < 0.05 vs. obese subjects ≤4 years after diagnosis, + p < 0.05 vs. lean subjects ≤4 years after diagnosis, # p < 0.05 vs. lean subjects. Reproduced with permission from [123].
Figure 6
Figure 6
Hypothesis of change in beta cell function and mass during development of abnormal glucose tolerance. The magnitude of the increased demand for insulin due to insulin resistance caused by excess caloric intake and physical inactivity exceeds the magnitude of beta cell mass expansion, resulting in an increase in beta cell workload. In individuals who are susceptible to type 2 diabetes (T2DM), increased beta cell workload may lead to beta cell failure and the development of T2DM. Reproduced with permission from [101].

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