Current Diabetes Reviews - Volume 18, Issue 9, 2022

Despite substantial investment in research and treatment options, diabetes mellitus remains a pressing public health concern with potential epidemic proportions globally. There are reports that by the end of 2040, 642 million people will be suffering from diabetes. Also, according to an estimation, 1.6 million deaths were caused directly by diabetes in 2016. Diabetes is a metabolic disorder characterized by impaired glucose regulation in the body due to the destruction of pancreatic β-cells or insulin resistance. Genetic propensity, unhealthy and imbalanced diet, obesity and increasing urbanization are the common risk factors for diabetes. Besides this, it has been reported that environmental pollutants like organic pesticides, heavy metals, and air pollutants act as strong predisposing factors for diabetes owing to their highly bio-accumulative nature. These pollutants disturb glucose homeostasis either by up-regulating or down-regulating the expression of diabetic marker genes like insulin (INS) and glucokinase (GCK). Unfortunately, the molecular mechanism of the role of pollutants in causing diabetes is not very clear. This mechanistic review provides evidence of different environmental determinants, including persistent organic pollutants (POPs), air pollutants, toxic metals, etc., in inducing diabetes and proposes a framework for the possible mechanisms involved. It also illuminates the current status and future challenges, which will not only broaden our understanding but can also be a reasonable platform for further investigation.

Diabetes mellitus type 1 (T1DM) is an autoimmune disease characterized by a markedly elevated cardiovascular (CV) risk due to premature atherosclerosis. Previous studies have shown that intense glycemic control reduces the incidence of CV disease. Antiplatelet therapy is considered to be a very important therapy for secondary prevention of recurrent atherothrombotic events in patients with DM, while it may be considered for primary prevention in individuals with T1DM with additional CV risk factors. The aim of the present review is to summarize existing literature data regarding the thrombotic risk in T1DM patients and discuss current treatment strategies.

Type 2 diabetes mellitus remains a growing health concern, affecting more than 420 million people globally. Preventing and treating diabetes require a better understanding of the associated risk factors. Sleep-disordered breathing, especially obstructive sleep apnea (OSA), is likely a contributor to the pathogenesis and aggravation of poor glycemic control. We review key epidemiological data that address the link between OSA and type 2 diabetes and present the current proposed pathophysiological mechanisms underlying this association. Several biological pathways are linking OSA and an increased propensity to diabetes. We review the impact of current treatment strategies for OSA based on the association between diabetes and sleep apnea.

Background: Obesity and diabetes are global epidemics resulting in a range of comorbidities. Both have been linked to an increased risk of hormonal imbalance, cancer, and other significant disorders, which are a concerning trend for cancer rates in the backdrop of rising obesity and diabetes rates worldwide. Around 1 in 10 persons in the United States and Canada have serious illnesses correlated to type 2 diabetes and early death. It is believed that the US economy alone spends $245 billion annually due to this health burden. Lifestyle modification with intermittent fasting protocol and proper diet helps lower blood glucose level, maintain the body mass index, and reduce inflammation, which is the main cause of all chronic diseases. Methods: We searched case series and clinical trials on type 2 diabetes, insulin resistance, cancer, thyroid, cardiovascular disease, or other inflammatory diseases in response to intermittent fasting in the PubMed, MEDLINE, and Google Scholar databases. Objective: In this review, we have focused on intermittent fasting-based approaches that are becoming more widely accepted for improving health and reducing unwanted effects in patients with type 2 diabetes, cancer, cardiovascular disease, neurodegenerative disease, obesity, thyroid, and hormonal imbalance; it is also contemplated whether intermittent fasting can be considered as a non-medicinal therapeutic option for persons suffering from chronic diseases. Conclusion: Intermittent fasting successfully reversed diabetes, thyroid, and high blood pressure, elevated lipid levels, and maintained the body mass index; also, studies have shown that it has been instructed to be followed for the treatment and prevention of cancer and neurodegenerative diseases.

Stress creates disharmony in the body's natural environment and thus causes an imbalance in the normal physiological system. The term diabetes describes a group of metabolic disorders, characterized and identified by the presence of hyperglycemia. Essential factors identified to initiate hyperglycemia are excess body weight, high cholesterol, high blood pressure, and lifestyle changes like stress, genetics, etc. Different types of stress and related conditions like depression, anxiety, etc., cause pancreatic β-cell dysfunction and insulin resistance, the prime risk factors in the progression of type 2 diabetes. The neuroendocrine system plays a pivotal role in countering psychological stress is the hypothalamus-pituitary-adrenal (HPA) axis, which secretes glucocorticoids (GCs), e.g., cortisol is the principal stress-responsive natural steroid hormone. The stress system essentially hampers the body's homeostasis and develops serious clinical manifestations. Glucocorticoids exert a strong physiological impact on glucose metabolism directly or indirectly, cause hyperglycemic effect and play an important role in the development of type 2 diabetes observed in patients suffering from chronic stress, Cushing’s syndrome, or patients on long term GCs therapy. This review provides a clear outline on the pathways and mechanisms of stress-linked type 2 diabetes.

Diabetes mellitus is the most prevalent malady, becoming a leading public health concern around the world. It is a chronic endocrine metabolic disturbance that is accompanied by the commencement of a sequence of complications. The liver primarily serves as the body’s glucose or fuel reserve and also maintains standard blood sugar concentration. Hepatic gluconeogenesis, glycolysis and glycogenesis are the key contributors to fasting or post-prandial hyperglycaemia in type 2 diabetes mellitus subjects. So, regulating these channels could be a viable approach for mitigating hyperglycaemia in type 2 diabetes mellitus. Few potential synthetic drugs that precisely target hepatic glucose-producing metabolic pathways are presently available, but they have some serious negative effects like hypoglycaemia, hepatosteatosis and lactic acidosis. Therefore, scientists have veered to herbal products because of their edible nature, costeffectiveness and fewer side effects. Natural products and their isolated phytochemicals are progressively being employed to manage hyperglycaemia by modulating the enzyme’s activity and regulating transcription factors concerned with hepatic glucose synthesis. We reviewed the potential effects of isolated bioactive phytochemicals on interesting targets that affect hepatic glucose homeostasis in diabetes. This study illustrates the benefit and feasibility of developing liver-specific drugs through secondary metabolites to restore hyperglycaemia.

Background and Aims: Diabetes mellitus, cardiovascular diseases, obesity, and dyslipidaemia are considered risk factors for more severe forms of COVID-19 infection. Statins have been widely used in such patients to prevent the occurrence of cardiovascular events and the associated mortality. However, statin use has been suggested to promote a more severe form of infection. This review aims to investigate the association between statin use and poor outcomes in COVID-19 patients with diabetes. Methods: Literature search was performed in PubMed, CENTRAL, Scopus, and pre-print databases (MedRxiv and BioRxiv), and studies published up to March 6th, 2021 have been reviewed. Selected studies were then assessed for risk of bias with the Newcastle Ottawa Scale. Result: Four studies were included in the final analysis; all were retrospective studies. Two studies reported a decreased risk of mortality with statin use, while one study reported opposite findings. The other one did not find a significant association between statin use and poor COVID-19 outcomes. Conclusion: Available data suggest that statins may be safely administered to diabetic COVID-19 patients as the majority of evidence signifies statins to confer benefits and improve clinical outcomes in COVID-19 patients.

Background: Type 1 diabetes is the most common endocrine condition among adolescents. Diabetes self-management can be challenging during adolescence. Objective: The objective of this study is to understand how adolescents and their parents manage type 1 diabetes in Jordan. Methods: Constructivist grounded theory methodology principles were used to achieve the study aim. A total of 48 participants were recruited using purposive and theoretical sampling techniques, including adolescents and their parents. Data were collected (October 2016 - April 2017) using 38 semi-structured, audio-recorded interviews (one-to-one or joint interviews based on participants’ preferences). Data were collected and analyzed concurrently using different levels of coding, constant comparative analysis, and memo writing. This study was approved by relevant ethics committees from the University of Manchester and Jordan University Hospital. Results: The theme of living with diabetes is presented and discussed in this article. Culture emerged as the central theme; two aspects of culture are presented in this article: collectivism and cultural beliefs. Conclusion: This study identified that diabetes self-management could be influenced by the culture in which Jordanian adolescents live in as well as being shaped by their religious beliefs. These findings are potentially transferable to other Arab and non-Arab countries that share similar cultural aspects and religious beliefs.

Background: The rate of mortality is increasing in diabetic patients due to diabetes-associated complications. The common complications include neuropathy, nephropathy, retinopathy, foot ulcer, slow wound healing, kidney dysfunction, amputation, dysfunction of organs, frequent infections, sepsis, skin diseases, hearing impairment, cardiovascular disorders, etc. These complications can be diagnosed following some common symptoms such as increased thirst, frequent urination, extreme hunger, unexplained weight loss, fatigue, irritability, blurred vision, slow-healing sores, etc. This survey was designed to study the prevalence of various complications in a group of diabetic patients so that effective treatment options could be developed against the most prevalent complications. Methods: This cross-sectional study was conducted in 2019 in a tertiary care hospital of Karachi after the approval of the ethical committee of the hospital as well as in the University of Karachi. To perform this study, a questionnaire was designed comprised of different questions related to diabetic complications. The consent form was attached to each questionnaire in which the patient agreed to participate voluntarily in this survey. The diabetic patients who visited the General Physician OPD were the subjects of this survey. All designed questions included in the questionnaire were asked either directly from the patients or their attendants. Results: A total of 160 diabetic subjects were part of the study range between the ages of 11 to 90 years. Out of 160 patients, 52 were males, and 108 were females. Among all subjects, 124 (78 %) patients were type 2 while 57 (36 %) were type 1 diabetic patients. 117 (73 %) showed confusion of mind, 104 (65 %) complained of blood pressure, 105 (66 %) had hypertension, 106 (66 %) had eye damage (retinopathy), 96 (60 %) were facing trouble focusing vision, and 70 (44 %) were experiencing seizures, 63 (39 %) patients had laser treatment, 68 (43 %) showed wounds on foot and slow wounds healing, 49 (31 %) were having kidney damage (nephropathy), 79 (49 %) had pain in legs or knee, 35 (22 %) and 26 (16 %) complained of heart problems and liver damage respectively. Some patients were found to deal with more hunger, i.e., 99 (62 %) patients, 118 (74 %) were experiencing frequent urine desire, 138 (86 %) showed fatigue, 123 (77 %) complained of thirst, 35 (22 %) had nausea, 30 (19 %) had a frequent cold, 36 (23 %) had skin problems, 17 (11 %) patients showed frequent vomiting, 19 (12 %), 13 (8 %) and 16 (10 %) were experiencing acne formation, stroke and nerve damage (neuropathy) respectively. Conclusion: All age groups showed diabetes-associated complications and different abnormal body conditions. However, the age groups ranging from thirty to eighty years showed more complications. The most prevalent complications reported were retinopathy, nephropathy, diabetic wounds on the foot, slow wound healing, seizures, hypertension, neuropathy, skin infections, cardiovascular disorders, liver damage, and stroke in both types of diabetic patients. Our survey may aid in pointing out the most prevalent diabetic complications prevailing in our population so that effective treatment options could be developed to reduce these life-threatening complications.

Background: Diabetes mellitus is a significant risk factor for lower extremity amputations (LEA), both alone and in combination with peripheral vascular disease and infection. Currently, in Africa, more than half of the cases do not meet the recommended blood glucose control levels to prevent complications suggesting that the risk of complications is high. Objective: The study aims to estimate hospitalization costs of diabetes-related lower extremities amputation for patients consulted at a referral hospital in 2015/16. Methods: The study was a retrospective analysis using a mixed costing approach and based on 2015/16 financial year data inflated to 2020 at a 32-bed vascular unit of a quaternary care health facility. Patient level data were extracted from the hospital information system for length of stay, medication provided, laboratory and radiological investigations, and other clinical services offered. Results: The total summative cost for managing all 34 patients amounted to $ 568 407 or a mean unit cost per patient of $ 16 718 based on 2015/16 prices, and when adjusted to 2020, prices amounted to $ 728 997 or $ 21 441 per patient. The mean unit cost per patient for foot amputation was $ 12 598 based on 2015/16 prices, and when adjusted to 2020, prices amounted to $ 16 157 per patient, whilst the mean cost per patient for lower limb amputation was $ 16 718 based on 2015/16 prices, and when adjusted to 2020 prices, amounted to $ 21 441 per patient. Conclusion: Hospital costs associated with diabetes related amputation varied by whether the patient was admitted to intensive care unit or not, and the major cost drivers were general ward costs, compensation of employees, and radiology services. A comprehensive audit of the referral process and care process at the facility level as well as technical efficiency analysis, is required to identify inefficiencies that could reduce hospital costs for managing diabetes complications.

Objective: The study was conducted to investigate the effects of hydroxychloroquine, an anti-inflammatory drug, which was recently approved and used as an add on oral antidiabetic drug for uncontrolled Type 2 Diabetes Mellitus (DM) on an adequate dose of sulfonylurea and metformin on the progression of diabetic retinopathy (DR) in subjects with Rheumatoid Arthritis and Type 2 Diabetes Mellitus. The primary objective was to evaluate the effect of hydroxychloroquine on the onset of Diabetic Retinopathy (DR) and progression of the disease. Best-corrected visual acuity (BCVA) charts with 3 or more lines worsening of visual acuity and the development of clinically significant macular edema (CSME) were added as secondary objectives as described in the Early Treatment Diabetic Retinopathy Study (ETDRS). Methods: This retrospective analysis was done from medical records of all Rheumatoid Arthritis (RA) patients who also had T2DM and were treated with hydroxychloroquine (HCQ) 400 mg OD or 200 mg BID (N=65) and received ophthalmologic care at an endocrinology clinic in India up to a mean follow-up of 3.5±0.5 years and matched subjects taking any other disease-modifying antirheumatic drugs (DMARD) and pioglitazone (N=34). Results: Baseline characteristics were similar in both the groups, with matched glycated haemoglobin (9.1 % and 9.2 % respectively, p=0.127). In both groups, over 3.5 years, HbA1c was reduced significantly. No new cases of DR were detected in the HCQ group, whereas 2 patients had developed DR in the pioglitazone group. At the base line visit, mild non-proliferative Diabetic Retinopathy (NPDR) was present in 18 eyes and 14 eyes in the HCQ and pioglitazone groups, respectively. Progression to moderate NPDR over 3.5 years occurred in 2 out of 18 (11 %) eyes in the HCQ group and 8 out of 14 (57 %) eyes in the pioglitazone group, respectively, representing a significant relative risk reduction (p=.001). No patients had progressed from mild NPDR to severe NPDR in the HCQ group, whereas 2 eyes had progressed from mild NPDR to severe NPDR in the pioglitazone group. None of the patients in either arm developed diabetic macular oedema. Conclusion: Progression of DR from mild to moderate NPDR or severe NPDR may be delayed by HCQ. Large scale randomised prospective clinical trial is required to establish the risk-benefit profiles of HCQ in T2DM.