Reappraisal of metallothionein: Clinical implications for patients with diabetes mellitus

Reactive oxygen and nitrogen species (ROS and RNS, respectively) are byproducts of cellular physiological processes of the metabolism of intermediary nutrients. Although physiological defense mechanisms readily convert these species into water or urea, an improper balance between their production and removal leads to oxidative stress (OS), which is harmful to cellular components. This OS may result in uncontrolled growth or, ultimately, cell death. In addition, ROS and RNS are closely related to the development of diabetes and its complications. Therefore, numerous researchers have proposed the development of strategies for the removal of ROS/RNS to prevent or treat diabetes and its complications. Some molecules that are synthesized in the body or obtained from food participate in the removal and neutralization of ROS and RNS. Metallothionein, a cysteine‐rich protein, is a metal‐binding protein that has a wide range of functions in cellular homeostasis and immunity. Metallothionein can be induced by a variety of conditions, including zinc supplementation, and plays a crucial role in mediating anti‐OS, anti‐apoptotic, detoxification, and anti‐inflammatory effects. Metallothionein can modulate various stress‐induced signaling pathways (mitogen‐activated protein kinase, Wnt, nuclear factor‐κB, phosphatidylinositol 3‐kinase, sirtuin 1/AMP‐activated protein kinase and fibroblast growth factor 21) to alleviate diabetes and diabetic complications. However, a deeper understanding of the functional, biochemical, and molecular characteristics of metallothionein is needed to bring about new opportunities for OS therapy. This review focuses on newly proposed functions of a metallothionein and their implications relevant to diabetes and its complications.     

Diabetes in developing countries

There has been a rapid escalation of type 2 diabetes (T2D) in developing countries, with varied prevalence according to rural vs urban habitat and degree of urbanization. Some ethnic groups (eg, South Asians, other Asians, and Africans), develop diabetes a decade earlier and at a lower body mass index than Whites, have prominent abdominal obesity, and accelerated the conversion from prediabetes to diabetes. The burden of complications, both macro‐ and microvascular, is substantial, but also varies according to populations. The syndemics of diabetes with HIV or tuberculosis are prevalent in many developing countries and predispose to each other. Screening for diabetes in large populations living in diverse habitats may not be cost‐effective, but targeted high‐risk screening may have a place. The cost of diagnostic tests and scarcity of health manpower pose substantial hurdles in the diagnosis and monitoring of patients. Efforts for prevention remain rudimentary in most developing countries. The quality of care is largely poor; hence, a substantial number of patients do not achieve treatment goals. This is further amplified by a delay in seeking treatment, “fatalistic attitudes”, high cost and non‐availability of drugs and insulins. To counter these numerous challenges, a renewed political commitment and mandate for health promotion and disease prevention are urgently needed. Several low‐cost innovative approaches have been trialed with encouraging outcomes, including training and deployment of non‐medical allied health professionals and the use of mobile phones and telemedicine to deliver simple health messages for the prevention and management of T2D.     

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.