Diabetic cystopathy: A review 综述：糖尿病性膀胱病

Herein we review and discuss epidemiological, clinical, and experimental studies on diabetic cystopathy, a common chronic complication of diabetes mellitus with a variety of lower urinary tract symptoms, providing directions for future research. A search of published epidemiological, clinical, or preclinical trial literature was performed using the key words “diabetes”, “diabetic cystopathy”, “diabetic bladder dysfunction”, “diabetic lower urinary tract dysfunction”, “diabetic detrusor instability”. The classic symptoms of diabetic cystopathy are decreased bladder sensation, increased bladder capacity, and impaired bladder emptying with resultant increased post‐void residual volume. However, recent clinical evidence indicates a presence of storage symptoms, such as overactive bladder symptoms. The pathophysiology of diabetic cystopathy is multifactorial, including disturbances of the detrusor, neuron, urothelium, and urethra. Hyperglycemia, oxidative stress, and polyuria play important roles in inducing voiding dysfunction in diabetic individuals. Treatment choice depends on clinical symptoms and urodynamic abnormalities. Urodynamic evaluation is the cornerstone of diagnosis and determines management strategies. Diabetes mellitus could cause a variety of lower urinary tract symptoms, leading to diabetic cystopathy with broadly varied estimates of the prevalence rates. The exact prevalence and pathogenesis of diabetic cystopathy remains to be further investigated and studied in multicenter, large‐scaled, or randomized basic and clinical trials, and a validated and standardized workup needs to be made, improving diabetic cystopathy management in clinical practice. Further studies involving only female diabetics are recommended.     

Role of premixed insulin analogues in the treatment of patients with type 2 diabetes mellitus: A narrative review (预混胰岛素类似物在2型糖尿病治疗中的作用：叙述性综述)

Because of the progressive nature of type 2 diabetes mellitus (T2DM), insulin therapy will eventually become necessary in most patients. Recent evidence suggests that maintaining optimal glycemic control by early insulin therapy can reduce the risk of microvascular and macrovascular complications in patients with T2DM. The present review focuses on relevant clinical evidence supporting the use of premixed insulin analogues in T2DM when intensifying therapy, and as starter insulins in insulin‐naïve patients. Our aim is to provide relevant facts and clinical evidence useful in the decision‐making process of treatment selection and individualized treatment goal setting to obtain sustained blood glucose control.     

Intracellular and extracellular adenosine triphosphate in regulation of insulin secretion from pancreatic β cells (细胞内外三磷酸腺苷对胰岛β细胞胰岛素分泌的调控作用)

Adenosine triphosphate (ATP) synthesis and release in mitochondria play critical roles in regulating insulin secretion in pancreatic β cells. Mitochondrial dysfunction is mainly characterized by a decrease in ATP production, which is a central event in the progression of pancreatic β cell dysfunction and diabetes. ATP has been demonstrated to regulate insulin secretion via several pathways: (i) Intracellular ATP directly closes ATP‐sensitive potassium channel to open L‐type calcium channel, leading to an increase in free cytosolic calcium levels and exocytosis of insulin granules; (ii) A decrease in ATP production is always associated with an increase in production of reactive oxygen species, which exerts deleterious effects on pancreatic β cell survival and insulin secretion; and (iii) ATP can be co‐secreted with insulin from pancreatic β cells, and the released ATP functions as an autocrine signal to modulate insulin secretory process via P2 receptors on the cell membrane. In this review, the recent findings regarding the role and mechanism of ATP synthesis and release in regulation of insulin secretion from pancreatic β cells will be summarized and discussed.     

Vitamin D and Type 2 diabetes mellitus (维生素D与2型糖尿病)

Based on increasing evidence from animal and human studies, vitamin D deficiency is now regarded as a potential risk factor for Type 2 diabetes mellitus (T2DM). Vitamin D is involved in the pathogenesis of pancreatic β‐cell dysfunction, insulin resistance, and systemic inflammation, conditions that contribute to the development of T2DM. Vitamin D can affect the progress of this disease directly through the activation of its own receptor, and indirectly via the regulation of calcium homeostasis. Observational studies have revealed the association between vitamin D deficiency and incident T2DM. More double‐blind randomized control studies that investigate the effects of vitamin D supplementation on insulin sensitivity, insulin secretion, and the occurrence of T2DM are needed.     

Who needs an artificial pancreas? (怎样的患者需要一个人工胰腺？)

The development of a closed‐loop “artificial pancreas” would be a welcome advance for both endocrinologists and diabetic patients struggling to attain near normal glycemic control. While great strides in automatically controlling blood sugar in the fasting, sedentary state have been made through complex mathematical modeling, management of blood sugar excursions due to food and exercise have been more problematic. An artificial pancreas is not feasible at this time because of limitations inherent in the currently available technology.     

Diabetes and cancer relationships (糖尿病与肿瘤的关联性)

Diabetes and cancer are both heterogeneous and multifactorial diseases with tremendous impact on health worldwide. Epidemiologic evidence suggests that certain malignancies may be associated with diabetes, as well as with diabetes risk factors and, perhaps, with certain diabetes treatments. Numerous biological mechanisms could account for these relationships. Insulin‐like growth factor (IGF)‐1, IGF‐2, IGF‐1 receptors, insulin, and the insulin receptor play roles in the development and progression of cancers. Although evidence from randomized controlled trials does not support or refute associations of diabetes and its treatments with either increased or reduced risk of cancer incidence or prognosis, consideration of malignancy incidence rates and the magnitude of the trials that would be required to address these issues explains why such studies may not be readily undertaken.     

Omeprazole improves the anti‐obesity and antidiabetic effects of exendin‐4 in db/db mice (奥美拉唑改善唾液素‐4 对db/db小鼠的减肥与降糖作用)*

Background: In addition to its glucoregulatory actions, exendin‐4, a stable glucagon‐like peptide‐1 receptor agonist, exhibits protective effects in the pancreas and anti‐obesity effects. Suitable combination treatment with other anti‐obesity or pancreas protective agents would be an effective approach to optimize these additional effects. In the present study, we investigated the effects of the addition of omeprazole, a proton pump inhibitor, to exendin‐4 in db/db mice, an experimental model of obesity and type 2 diabetes. Methods: The effects repeated dose treatment for 14 days with exendin‐4 (8 μg/kg, s.c.) and omeprazole (30 mg/kg, s.c.) on glycemic control, food intake, and body weight were determined in obese and hyperglycemic db/db mice. The effects of these treatments on plasma gastrin, ghrelin, and leptin levels were determined, along with effects on nausea‐like symptoms. The pancreatic effects of the repeated dose treatment were assessed by measuring %HbA1c in the circulation as well as pancreatic insulin and glucagon content and glucokinase activity. Results: Combination treatment resulted in significant decreases in plasma leptin and ghrelin levels after repeated dosing. Omeprazole improved the anorectic and body weight‐lowering effects and reversed the inhibitory effect of exendin‐4 on gastrin levels after repeated dose treatment. The 14‐day combination treatment significantly reduced glucose excursion and improved insulin levels, with a concomitant decrease in %HbA1c levels. It also improved glucokinase activity and pancreatic insulin content, with a significant decrease in glucagon content. Conclusions: Combined treatment with omeprazole with exendin‐4 reduces food intake and body weight gain, most likely through changes in plasma ghrelin and leptin levels, and improves pancreatic insulin and glucagon content by improving glucokinase activity.