Pancreatic beta cell homeostasis is crucial for the synthesis and secretion of insulin; disruption of homeostasis causes diabetes, and is a treatment target. Adaptation to endoplasmic reticulum (ER) stress through the unfolded protein response (UPR) and adequate regulation of autophagy, which are closely linked, play essential roles in this homeostasis. In diabetes, the UPR and autophagy are dysregulated, which leads to beta cell failure and death. Various studies have explored methods to preserve pancreatic beta cell function and mass by relieving ER stress and regulating autophagic activity. To promote clinical translation of these research results to potential therapeutics for diabetes, we summarize the current knowledge on ER stress and autophagy in human insulin-secreting cells.

Background Although the proportion of older patients with type 2 diabetes mellitus (T2DM) has increased, few studies have reported the factors affecting glucose levels in older patients with long-standing T2DM. This study assessed the determinants of glycemic control in older adults with T2DM of a duration of ≥10 years, including muscle mass, muscle quality, and β-cell function. Methods This was a prospective study of older patients aged ≥60 years with a T2DM duration of ≥10 years. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index, handgrip strength (HGS), and body composition through bioelectrical impedance analysis were assessed. The primary outcome was a composite of: (i) increment of glycated hemoglobin (HbA1c) from the baseline ≥0.6% and (ii) HbA1c ≥ 9% at any time point during the follow-up period. To find the predicting determinants of the outcome, we performed the Cox proportional hazard analysis. Results Among 100 patients (mean age, 64.0 ± 8.6 years; median duration of diabetes, 20 [interquartile range (IQR), 17–23] years; median HbA1c at baseline, 7.1 [IQR, 6.7–7.4] %), the primary outcome was observed in 40 (40.0%) patients during 4.0 (IQR 2.3–5.0) years of follow-up. A Cox proportional hazards model adjusted for age, sex, baseline HbA1c, obesity, duration of DM and anti-diabetic medication at baseline showed that low HGS and insulin resistance at the baseline were independent determinants of the primary outcome (hazard ratio [HR] = 2.23 [95% confidence interval (CI), 1.06–4.72] and 2.39 [95% CI, 1.18–4.83], respectively). Sex stratification confirmed that HGS and muscle mass were independent determinants of the primary outcome only in women (HR per quartile, 0.58 [95% CI, 0.37–0.93] and 0.46 [95% CI, 0.25–0.85], respectively). `. Conclusions Low HGS and insulin resistance were independent risk factors for aggravated glycemic control among older patients with long standing T2DM.

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Hemichorea has been reported in subjects with hyperglycemia and the recurrent was rarely reported. We identified clinical presentation and course of hypeglycemic hemichorea in six cases, one of whom experienced recurrence. Mean age was 77.2 years and five were women. Duration of diabetes was 1-35 years. Initial HbA1c levels were 9.3%-13% and most patients had poor compliance. Five patients undertook brain magnetic resonance imaging and high signal intensities of basal ganglia was observed in T1-weighted images. All patients were treated with insulin, and four patients were treated with dopamine-receptor blockers. Mean duration of hemichorea was 69 days. One patient’s hemichorea was recurred after 2 months from the time when the first event was resolved and then finally diagnosed with vasculitis. The prognosis of hyperglycaemic hemichoerea seemed to be good. However, we should consider other cause such as vasculitis when the symptom was recurred after adequate glycaemic control.