Current Diabetes Reviews - Volume 18, Issue 8, 2022

Metformin is an old, inexpensive, and relatively safe anti-diabetic medication that can decrease the risk of several types of cancer in patients with diabetes. Recent meta-analyses have revealed that metformin markedly decreased the incidence of colorectal adenoma, advanced adenoma, and colorectal cancer (CRC) among patients with diabetes. Potential mechanisms by which metformin may decrease colorectal cancer risk include its effects on ameliorating intestinal inflammation and dysbiosis, suppressing major proliferative pathways, preventing DNA replication, accelerating tumor cells apoptosis, inhibiting intra-tumor angiogenesis and epithelial-mesenchymal transition (EMT), increasing tumor-infiltrating lymphocytes and CD68+ tumor-associated macrophages, and enhancing T cells cytotoxic activity. It is well-known that metformin can improve overall survival and CRC-specific survival among patients with diabetes and CRC. Interestingly, metformin decreases the incidence of colonic adenoma in patients with acromegaly and reduces the incidence of inflammatory bowel disease (IBD) among patients with diabetes, which can indirectly lower the risk of CRC. Results of phase II clinical trials have revealed that metformin can enhance the anti-cancer effects of chemotherapeutic agents, such as 5-Fluorouracil (5-FU) and irinotecan on refractory CRC. Furthermore, metformin decreases the risk of new polyps and adenomas in patients without diabetes. Regarding the results of previous preclinical and clinical studies, it is rational to assess the effect of metformin in normoglycemic patients with CRC and expand its clinical application for treating CRC or preventing it in a high-risk population.

Dipeptidyl peptidase-4 inhibitors (DDP-4Is) or gliptins have been extensively studied in recent years. These studies have shown the safety and efficacy of gliptins in managing hyperglycemia in diabetic patients. However, there is an ongoing debate on whether DDP-4Is are associated with a higher risk for developing heart failure. It is expected that long-term data from patients who are currently prescribed DDP-4Is will provide a clearer understanding of their potential benefits. This should also help guide the development of future guidelines. The focus of this perspective is on associations between the “use of DPP-4Is” and “increased risk of heart failure”. Thus, we examine several key publications and reviews on clinical trials on this class of oral antidiabetic medications. For this communication, the pertinent literature has been critically analyzed to provide an evidence-based overview of the evolving concept of DPP-4Is-induced risk of heart failure.

Diabetes mellitus and Alzheimer’s disease are considered the most prevalent diseases in older ages worldwide. The main pathology of Alzheimer’s disease is highly related with accumulation of misfolded proteins that lead to neuronal dysfunction in the brain. On the other hand, diabetes mellitus is associated with alteration of insulin signaling, which could cause the reduction of glucose uptake, metabolic prohibition of energy consuming cells, as well as suppression of glucose to fat conversion in the liver. In spite of having seemingly different pathological features, both diseases share common underlying biological mechanisms. Besides, the epidemiological and environmental links between these two diseases should not be overlooked. In this study, we aim to review shared pathological mechanisms of Alzheimer’s disease and diabetes mellitus, including impaired glucose metabolism, increased Amyloid-Beta (Aβ) production, impaired lipid metabolism, mitochondrial dysfunction, increased inflammation and elevated oxidative stress. Furthermore, we discuss epidemiological association between these two diseases and also review animal investigations, which have evaluated the potential links between the two diseases.

Background: Lifestyle modification, along with medication, has improved the quality of life of patients with type 2 diabetes (T2D), but the treatment of diabetes in women still lacks a gender-centric approach. Methods: Expert opinions to improve diabetes management in women were collated from the open discussion forum organized by the sixth Jothydev’s Professional Education Forum Diabetes Convention, which included global diabetes care experts and the general public. The review is also based on the studies published in electronic databases such as PubMed and Google Scholar that discussed the problems and challenges faced by the Indian diabetes care sector in treating women with diabetes. Results: The complex interplay of biological, socioeconomic, psychosocial, and physiological factors in women with type 2 diabetes has not been well addressed to date. Biological factors such as neurohumoral pathways, sex hormones, genetic predisposition as well as gender-based environmental and behavioural differences must be considered for modern personalized diabetes treatment. Most importantly, pregnant women with diabetes deserve special attention. This vulnerable phase has a marked impact on the future health of both the mother and the offspring. Conclusion: The review provides an overview of the challenges and issues that exist in the clinical management of diabetes and its complications among women in India. Women-centric clinical approaches should be encouraged for the effective management of diabetes in Indian women.

According to research, Alzheimer’s disease (AD) is considered a metabolic illness caused by defective insulin signaling, insulin resistance, and low insulin levels in the brain. Type 3 diabetes has been postulated for AD because reduced insulin signaling has molecular and physiological consequences that are comparable to type I and type 2 diabetes mellitus, respectively. The similarities between type 2 diabetes and Alzheimer’s disease suggest that these clinical trials might yield therapeutic benefits. However, it is important to note that lowering your risk of Alzheimer’s dementia, whether you have diabetes or not, is still a multidimensional process involving factors like exercise, smoking, alcohol, food, and mental challenges. The current aim is to show that the relationship between T3D and AD is based on both the processing of amyloid-β (Aβ) precursor protein toxicity and the clearance of Aβ, which are the results of impaired insulin signaling. The brain’s metabolism, with its high lipid content and energy needs, places excess demands on mitochondria and appears more susceptible to oxidative damage than the rest of the body. Current data suggests that increased oxidative stress relates to amyloid-β (Aβ) pathology and the onset of AD.

Introduction: Diabetes mellitus (DM) comprises differential clinical phenotypes ranging from rare monogenic to common polygenic forms, such as type 1 (T1DM), type 2 (T2DM), and gestational diabetes, which are associated with cardiovascular complications. Also, the high- -risk prediabetic state is rising worldwide, suggesting the urgent need for early personalized strategies to prevent and treat a hyperglycemic state. Objective: We aim to discuss the advantages and challenges of Network Medicine approaches in clarifying disease-specific molecular pathways, which may open novel ways for repurposing approved drugs to reach diabetes precision medicine and personalized therapy. Conclusion: The interactome or protein-protein interactions (PPIs) is a useful tool to identify subtle molecular differences between precise diabetic phenotypes and predict putative novel drugs. Despite being previously unappreciated as T2DM determinants, the growth factor receptor-bound protein 14 (GRB14), calmodulin 2 (CALM2), and protein kinase C-alpha (PRKCA) might have a relevant role in disease pathogenesis. Besides, in silico platforms have suggested that diflunisal, nabumetone, niflumic acid, and valdecoxib may be suitable for the treatment of T1DM; phenoxybenzamine and idazoxan for the treatment of T2DM by improving insulin secretion; and hydroxychloroquine reduce the risk of coronary heart disease (CHD) by counteracting inflammation. Network medicine has the potential to improve precision medicine in diabetes care and enhance personalized therapy. However, only randomized clinical trials will confirm the clinical utility of network- oriented biomarkers and drugs in the management of DM.

The aim of the present study was to review the streptozotocin-nicotinamide (STZ-NA) diabetes model. Type 2 diabetes is more prevalent (90-95%) in adults than type 1. Experimentally- induced diabetes models may be established by chemicals, viral agents, insulin antibodies, surgery, etc. The most advisable and prompt method to induce diabetes is using chemicals, and STZ and alloxan are widely used chemicals. STZ has proven to be a better diabetogenic agent than alloxan because alloxan has many drawbacks, as it induces only type 1 diabetes, has a high mortality rate in rats, and causes ketosis in animals. Moreover, it has lesser selectivity towards β-cells, and the diabetes-induced is reversible. STZ can be used to induce both type 1 and type 2 diabetes. It is noted that the genotoxic behavior of STZ in animals is accomplished through a reduction of nicotinamide adenine dinucleotide (NAD+) in pancreatic β-cells via the GLUT2 (Glucose transporter 2), which can cause cellular damage by DNA (Deoxyribonucleic acid) strand breaks that lead to cell death. NA is a biochemical precursor of NAD+, and it is a poly-ADP-ribose-polymerase-1 (PARP- 1) inhibitor. NAD+ is an important redox reaction co-enzyme for the production of adenosine triphosphate (ATP) and many other metabolic pathways. Extreme DNA damage contributes to the over-activation of PARP-1, loss of cellular resources, and necrotic cells death. Some studies have expressed that NA can protect pancreatic β-cells against the severe cytotoxicity of STZ. The review concluded that the STZ-NA model is dependent on the competency of NA to attain partial protection against the β-cytotoxic essence of STZ to induce type-2 diabetes.

Background: Insulin has recently received special attention concerning its use in COVID-19 patients. Although controversial, insulin can be able to worsen the prognosis of COVID-19 patients with Type 2 Diabetes Mellitus (T2DM) through an inflammatory pathway. This uncertain aspect brings a new perspective related to insulin use in this pandemic era. Objective: We tried to collect and analyze various studies related to this issue to provide a complete picture of the prognosis of insulin use in COVID-19 patients with T2DM. Methods: We comprehensively searched PubMed, Cochrane CENTRAL, Embase, EBSCO CINAHL, MEDLINE, and grey literature databases for studies investigating the effect of insulin on COVID-19 outcomes, including mortality, hospitalization, disease progression, other prognostic surrogates. Records were screened against the eligibility criteria. Results: 2556 articles were retrieved and were screened. A total of 8 studies were included in the final analysis. There are no studies with solid evidence supporting the effect of insulin treatment on the worsening of the prognosis of COVID-19 patients with T2DM. Although several studies have shown that insulin is associated with a poor prognosis, most studies have not considered confounders. This certainly makes it challenging to analyze the effects of insulin independently. Conclusion: We propose that COVID-19 patients with T2DM continue to receive insulin, but with careful observation of the risk of disease progression.

Background: The aim of this study was to evaluate the microarchitecture, composition and mechanical properties of cortical bone of rats with type I diabetes mellitus (TIDM) and submitted to insulin therapy (IT). Methods: Thirty rats were divided into three groups (n=10): non-diabetic, diabetic and diabetic+insulin. TIDM was induced by intravenous injection of streptozotocin. In diabetic+insulin group, 4IU insulin was administered twice per day (1I U at 7 am and 3I U at 7 pm). The animals were euthanized five weeks after TIDM induction; the tibiae were removed and submitted to microcomputed tomography (micro-CT, 8 μm), fourier transform infrared spectroscopy (FTIR) and dynamic microhardness indentation. Results: Micro-CT analysis showed that diabetic group had lower bone surface/tissue volume ratio (BS/BV) (p=0.018), cortical thickness (Ct.Th) (p<0.001) and degree of anisotropy (Ct.DA) (p=0.034) values compared to non-diabetic group. The diabetic group showed lower Ct.Th than diabetic + insulin group (p=0.018). The non-diabetic group had lower fractal dimension (Ct.FD) values compared to diabetic groups (p<0.001). The ATR-FTIR analyses showed lower values for all measured parameters in the diabetic group than the non-diabetic group (amide I ratio: p=0.046; crystallinity index: p=0.038; matrix:mineral ratios - M:MI: p=0.006; M:MIII: p=0.028). The diabetic+ insulin group showed a lower crystallinity index (p=0.022) and M:MI ratio (p=0.002) than nondiabetic and diabetic groups, respectively. The diabetic group showed lower Vickers hardness values than non-diabetic (p<0.001) and diabetic+insulin (p=0.003) groups. Conclusion: TIDM negatively affects bone microarchitecture, collagen maturation, mineralization and bone microhardness. Moreover, insulin minimized the effect of TIDM on cortical thickness and organic/mineral matrix.

Objective: The objective of this study is to evaluate the impact of the COVID-19 lockdown on glycemic control and accompanying laboratory parameters in patients with type 2 Diabetes Mellitus. Methods: This study is a retrospective cohort study that was done on a multicenter level. It was conducted during the lockdown in 341 individuals. HbA1c was tested to measure glycemic control immediately before and after the lockdown period that lasted for 13 weeks. Results: The primary outcome was the improvement of mean HbA1C after 13 weeks of lockdown compared to the pre-lockdown HbA1C. It was found that the mean HbA1C improved from 7.5±1.5 to 7.3±1.5 with a p-value of 0.001. Conclusion: Our study showed that patients with type 2 diabetes mellitus exhibited an improvement in their glycemic control after the period of lockdown.