Hypoglycemia in diabetes: The dark side of diabetes treatment. A patient‐centered review

Hypoglycemia is a frequent occurrence in patients with diabetes who are treated with insulin and insulin secretagogues. Hypoglycemia is the limiting factor that prevents patients from achieving the glycemic control known to reduce the microvascular complications of diabetes. Recurrent episodes of hypoglycemia can lead to impaired awareness of hypoglycemia where the first symptom of a low blood sugar is unconsciousness. The fear of hypoglycemia has a significant effect on the quality of life of patients and their families. In the acute setting, hypoglycemia can kill, and clinical trials have demonstrated that a single episode of severe hypoglycemia increases the risk of subsequent mortality and cardiovascular events. Clinicians must make efforts to recognize and prevent hypoglycemia in order to prevent the adverse events associated with this event. Patient education is central to these efforts. Recent developments in glucose monitoring and drug development have provided more approaches that can be used to reduce the risk of hypoglycemia in patients with diabetes.     

Concentrated insulins: History and critical reappraisal

The earliest marketed insulins were crude acidic formulations with concentrations of ≤10 units/mL. Since the early 1920s, insulins have improved continually, via bioengineering, process, and chemical modifications. Today, most insulin formulations have a concentration of 100 units/mL (U100). However, more concentrated insulin formulations (200, 300, and 500 units/mL; U200, U300, and U500, respectively) are also available. There is a tendency to assume that concentrated insulins are similar, both to each other and to their U100 counterparts, but this is not always the case: two concentrated insulins, namely insulin degludec U200 and insulin lispro U200, are bioequivalent to their U100 counterparts, whereas regular human insulin U500 and insulin glargine U300 are not. The advent of these concentrated insulins offers greater opportunities to provide tailored therapy for patients; it also introduces potential confusion, and highlights the need for prescriber and patient education. Precise and accurate dedicated insulin delivery devices are also necessary for the safe use of these concentrated insulins. Although some clinicians only use concentrated insulin with obese and severely insulin‐resistant patients, other patients would also benefit from the reduced injection volume associated with concentrated insulins, or the modified time‐action profile of some concentrated insulins. The aim of this review is to enhance understanding of the historic development and the safe and effective use of concentrated insulins in clinical practice.     

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.