Current Diabetes Reviews - Volume 16, Issue 8, 2020

Diabetes mellitus is associated with an increased risk of micro and macrovascular complications. During hyperglycemic conditions, endothelial cells and vascular smooth muscle cells are exquisitely sensitive to high glucose. This high glucose-induced sustained reactive oxygen species production leads to redox imbalance, which is associated with endothelial dysfunction and vascular wall remodeling. Nrf2, a redox-regulated transcription factor plays a key role in the antioxidant response element (ARE)-mediated expression of antioxidant genes. Although accumulating data indicate the molecular mechanisms underpinning the Nrf2 regulated redox balance, understanding the influence of the Nrf2/ARE axis during hyperglycemic condition on vascular cells is paramount. This review focuses on the context-dependent role of Nrf2/ARE signaling on vascular endothelial and smooth muscle cell function during hyperglycemic conditions. This review also highlights improving the Nrf2 system in vascular tissues, which could be a potential therapeutic strategy for vascular dysfunction.

Background: Diabetes mellitus (DM) is a complex disease with significant impression in today's world. Aside from the most common types recognized over the years, such as type 1 diabetes (T1DM) and type 2 diabetes (T2DM), recent studies have emphasized the crucial role of genetics in DM, allowing the distinction of monogenic diabetes. Methods: Authors did a literature search with the purpose of highlighting and clarifying the subtypes of monogenic diabetes, as well as the accredited genetic entities responsible for such phenotypes. Results: The following subtypes were included in this literature review: maturity-onset diabetes of the young (MODY), neonatal diabetes mellitus (NDM) and maternally inherited diabetes and deafness (MIDD). So far, 14 subtypes of MODY have been identified, while three subtypes have been identified in NDM - transient, permanent, and syndromic. Discussion: Despite being estimated to affect approximately 2% of all the T2DM patients in Europe, the exact prevalence of MODY is still unknown, accentuating the need for research focused on biomarkers. Consequently, due to its impact in the course of treatment, follow-up of associated complications, and genetic implications for siblings and offspring of affected individuals, it is imperative to diagnose the monogenic forms of DM accurately. Conclusion: Currently, advances in the genetics field allowed the recognition of new DM subtypes, which until now, were considered slight variations of the typical forms. Thus, it is imperative to act in the close interaction between genetics and clinical manifestations, to facilitate diagnosis and individualize treatment.

Background: We thought to delve deeper into seven meta-analyses of major clinical trials focusing on Glucagon-Like Peptide-One Receptor Agonist (GLP-1 RA) cardioprotective effect. Aim: We explored the role of GLP-1 RA in cardiovascular risk protection as the primary outcome in subjects with type 2 diabetes mellitus. Methodology: The current review has explored and critically appraised seven meta-analyses of placebo- controlled randomized clinical trials (RCT-s) involving GLP-1 RA used in diabetes that has exhibited major cardiovascular events as the primary outcome. Results: Based on the participants-intervention-comparison and outcomes (PICO), the total number of the participants in this review were (138750), the intervention was conducted with GLP-1 RA, the comparator was a placebo and the outcome was major cardiovascular events. The overall evidence for the cardioprotective effect of GLP-1 RA in diabetes was very clear in subjects with the cardiovascular risk of varying degrees. Most of the currently reviewed meta-analyses have not shown cardioprotection with GLP-1 RA in subjects with diabetes exhibiting high cardiovascular risk or medical history of cardiovascular diseases. Patient variability, in addition to potency parameters, will be the key to a successful member of the class. There will be avenues for selection of a candidate based on the suitability to patient preferences and characteristics. Conclusion: The RCT-s for GLP-1 RA should characterize cardiovascular risk in subjects with diabetes such that disparities between established cardiovascular risk (high, moderate and low) or medical history of cardiovascular disease have been accounted for in subgroup analysis.

Background: The modern society is extremely prone to many life-threatening diseases, which can be easily controlled as well as cured if diagnosed at an early stage. The development and implementation of a disease diagnostic system have gained huge popularity over the years. In the current scenario, there are certain factors such as environment, sedentary lifestyle, genetic (hereditary) are the major factors behind the life threatening diseases such as ‘diabetes.’ Moreover, diabetes has achieved the status of the modern man’s leading chronic disease. So one of the prime needs of this generation is to develop a state-of-the-art expert system which can predict diabetes at a very early stage with a minimum of complexity and in an expedited manner. The primary objective of this work is to develop an indigenous and efficient diagnostic technique for detection of diabetes. Method & Discussion: The proposed methodology comprises of two phases: In the first phase The Pima Indian Diabetes Dataset (PIDD) has been collected from the UCI machine learning repository databases and Localized Diabetes Dataset (LDD) has been gathered from Bombay Medical Hall, Upper Bazar Ranchi, Jharkhand, India. In the second phase, the dataset has been processed through two different approaches. The first approach entails classification through Adaboost, Classification via Regression (CVR), Radial Basis Function Network (RBFN), K-Nearest Neighbor (KNN) on Pima Indian Diabetes Dataset and Localized Diabetes Dataset. In the second approach, Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) have been applied as a feature reduction method followed by using the same set of classification methods used in the first approach. Among all of the implemented classification methods, PCA_CVR achieves the maximum performance for both the above mentioned datasets. Conclusion: In this article, comparative analysis of outcomes obtained by with and without the use of PCA and LDA for the same set of classification method has been done w.r.t performance assessment. Finally, it has been concluded that PCA & LDA both are useful to remove the insignificant features, decreasing the expense and computation time while improving the ROC and accuracy. The used methodology may similarly be applied to other medical diseases.

Background: The vast majority of individuals diagnosed with diabetes are low/middle income and may have access to only three of the 11 oral hypoglycemic medications (OHMs) due to cost: metformin intermediate release (IR) or extended release (ER), sulfonylureas (glimepiride, glipizide, glyburide), and pioglitazone. Sulfonylureas and pioglitazone have had significant controversy related to potential adverse events, but it remains unclear whether these negative outcomes are class, drug, or dose-related. Objective: We conducted a narrative review of low-cost OHMs. Methods: We evaluated the maximum recommended (MAX) compared to the most effective (EFF) daily dose, time-to-peak change in HbA1c levels, and adverse events of low-cost oral hypoglycemic medications. Results: We found that the MAX was often greater than the EFF: metformin IR/ER (MAX: 2,550/2,000 mg, EFF: 1,500–2,000/1,500–2,000 mg), glipizide IR/ER (MAX: 40/20 mg, EFF: 20/5 mg), glyburide (MAX: 20 mg, EFF: 2.5–5.0 mg), pioglitazone (MAX: 45 mg, EFF: 45 mg). Time-to-peak change in HbA1c levels occurred at weeks 12–20 (sulfonylureas), 25–39 (metformin), and 25 (pioglitazone). Glimepiride was not associated with weight gain, hypoglycemia, or negative cardiovascular events relative to other sulfonylureas. Cardiovascular event rates did not increase with lower glyburide doses (p<0.05). Glimepiride and pioglitazone have been successfully used in renal impairment. Conclusion: Metformin, glimepiride, and pioglitazone are safe and efficacious OHMs. Prescribing at the EFF rather than the MAX may avoid negative dose-related outcomes. OHMs should be evaluated as individual drugs, not generalized as a class, due to different dosing and adverse-event profiles; Glimepiride is the preferred sulfonylurea since it is not associated with the adverse events as others in its class.

Background & Introduction: Patient’s self-management behaviors are essential to control diabetes. Studies have demonstrated that health educational interventions can improve some aspects of glycemic control and clinical outcomes, however, it is unclear which education theories underlying these interventions improve effectiveness. In this review of the literature, we aimed to assess the efficacy of health education and promotion theories, or models, to improve self-care and self- management behaviors among patients with type 2 diabetes (T2D). Methods & Results: Eight scientific databases (Web of Science, PubMed, Scopus, Magiran, Google Scholar, Medlib, ProQuest and Scientific Information Database) were searched to identify a published academic article from 2010 to 2019. We included quasi-experimental, clinical trial and randomized clinical trial studies. A total of 26 studies including data from 3879 patients with T2D met the inclusion criteria. We found that the PRECEDE (7/26, 26.92%) and Health Belief Models (7/26, 26.92%) were the most common models used to assess the efficacy of health education and health promotion models. Conclusion: Overall, health promotion and education theories and models have been used as a useful instrument for improving the self-care behaviors and self-management behaviors among patients with T2D.

Background: Cardiovascular disease (CVD), the main macro vascular complication of type 2 diabetes (T2D), increases the risk of death significantly in patients with T2D. Introduction: Most of the patients with T2D do not have obvious CVD symptoms. Due to the paucity of data, CVD screening in asymptomatic patients with T2D remains highly controversial. Methods: This has driven a panel of experts to establish a novel consensus on how to approach patients with T2D at high CVD risk. The panel formulated a stepwise algorithm by which patients with T2D undergo initial risk stratification into low, intermediate and high risk using the ASCVD calculator. In patients with intermediate risk, coronary artery calcium measurement is used to further stratify those patients into new low and high-risk categories. Results and Conclusion: The panel recommends using standard diabetes care in low risk patients and using SGLT2 inhibitors and GLP1 agonists with cardio protective effect, on top of standard care, in high risk individuals.

Background: Technological developments concerning the treatment of Type 1 Diabetes Mellitus have been rapid in the latest years. Insulin infusion systems along with continuous glucose monitoring, as well as long-acting insulin analogues, are part of this progress. Objective: The aim of this study is to present the illness perceptions in type 1 diabetes mellitus, with or without the use of an insulin pump. Sexual life and body image among therapy groups subjected to subcutaneous insulin infusion (CSII) therapy and multiple daily injections (MDI) therapy were also examined. Methods: A modified version of the Brief Illness Perception Questionnaire was used. One hundred and nine adults with type 1 diabetes mellitus, (males / females ratio 1:2.3) completed the online survey. Thirty six of them (33%) used CSII therapy and 73 of them (67%) used MDI therapy. Results: Statistically important differences among the CSII and MDI therapy groups were found in treatment control, illness comprehensibility, representations of control, representation of body image and in the perception of sex life. There was no statistically significant difference among the different types of therapy for participants’ negative perception of diabetes. Discussion and Conclusion: Negative perceptions of MDI users in treatment control, illness comprehensibility, representations of control, body image and sex life with the insulin pump, differentiate CSII and MDI therapy groups to a significant degree. According to the research, these parameters seem to interfere with accepting CSII therapy for MDI users and discourage them.

Background: Insulin resistance initiated in peripheral tissues induces type 2 diabetes (T2D). It occurs when insulin signaling is impaired. Introduction: Phosphatidylinositol 3-kinases (PI3K) are important for insulin signaling. Single nucleotide polymorphisms of the PI3K gene have been associated with T2D. Methods: We have investigated the association of Glu545Lys and His1047Tyr mutations of phosphatidylinositol- 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene with T2D. We have screened 103 T2D patients and 132 controls for Glu545Lys mutation, and 101 T2D patients and 103 controls for the His1047Tyr mutation from a Saudi cohort using AS-PCR. Results: Our results indicated that there is no association between the GA genotype of rs104886003 (Glu545Lys) and T2D, OR= 0.15 (95% CI: 0.007-3.28), RR= 0.29(0.02-3.72), P value= 0.23. The A allele is also not associated with T2D diabetes, OR= 1.01(95% CI: 0.70-1.46), RR=1.00(0.85-1.18), P value=0.91. Results showed that CT genotype of rs121913281 (His1047Tyr) was not associated with T2D, OR=0.94(95% CI: 0.23-3.9), RR= 0.97(0.48-1.97), P-value = 0.94, and T allele was also not associated with T2D, OR=1.06 (95% CI: 0.71-1.56), RR= 1.02(0.84-1.24), P-value =0.76. Conclusion: We conclude that the A allele of rs104886003 may not be associated with T2D. The T allele of rs121913281 may also not associated with T2D. However, future studies with larger sample sizes and in different populations are recommended.

Background: Obesity-induced chronic inflammation is a key component in the pathogenesis of insulin resistance and type-2 diabetes. Objective: This study aimed to evaluate the effect of swimming exercise on pancreatic expression levels of inflammatory cytokines, miR-146a and NF-ΚB in type-2 diabetic male rats. Methods: Twenty- eight male Wistar rats were divided into four groups: control (Con), exercise, diabetes and diabetic exercise (n = 7). Diabetes induction performed by the combination of high-fat diet (HFD, 4 weeks) and streptozotocin (35 mg/kg. ip). After induction of diabetes, the rats swam in the exercise groups for 12 weeks. Then, blood and tissue samples were collected. Results: Our results indicated a significant increase in expression levels of miR-146, NF-ΚB and inflammatory cytokines (IL-6, TNF-α, and IL-1β) while a significant decrease in pancreatic expression levels of TRAF6 and IRAK1 in diabetic group as compared to the control group. In contrast, swimming exercise resulted in a significant decrease in expression levels of miR-146a, NF-ΚB and inflammatory cytokines and a significant increase in expression levels of TRAF6 and IRAK1 in the exercise-diabetic group compared to the diabetic group. Conclusion: Our results indicated a significant increase in expression levels of miR-146, NF-ΚB and inflammatory cytokines (IL-6, TNF-α, and IL-1β) while a significant decrease in pancreatic expression levels of TRAF6 and IRAK1 in diabetic group as compared to the control group. In contrast, swimming exercise resulted in a significant decrease in expression levels of miR-146a, NF-ΚB and inflammatory cytokines and a significant increase in expression levels of TRAF6 and IRAK1 in the exercise-diabetic group compared to the diabetic group.

Aims: Investigation thyroid dysfunction and autoimmunity in pregnant women with gestational diabetes mellitus. Background: This article was written to evaluate the thyroid function and anti-thyroid peroxidase (anti- TPO) antibodies in pregnant women with gestational diabetes mellitus (GDM). Methods: A total of 252 women with GDM and 252 healthy pregnant women were enrolled. Thyroid tests, including TSH, FreeT3, Free T4, and anti-TPO were performed for all women at 24–28 weeks of gestation. Data analysis was then carried out using SPSS ver. 22. Results: There was a significant difference between the experimental group (38.4%) and the control group (14.06%) in terms of the prevalence of subclinical hypothyroidism (p= 0.016). The frequency of anti-TPO was higher in the experimental group than the control group and positive anti-TPO was observed in 18.6% of women with GDM and 10.3% of healthy pregnant women (P= 0.008). Conclusion: Thyroid disorders are observed in pregnant women with GDM more frequently than healthy individuals and it may be thus reasonable to perform thyroid tests routinely.

Background: Recent studies have suggested that hyperglycaemia influences the bile acid profile and concentrations of secondary bile acids in the gut. Introduction: This study aimed to measure changes in the bile acid profile in the gut, tissues, and faeces in type 1 Diabetes (T1D) and Type 2 Diabetes (T2D). Methods: T1D and T2D were established in a mouse model. Twenty-one seven-weeks old balb/c mice were randomly divided into three equal groups, healthy, T1D and T2D. Blood, tissue, urine and faeces samples were collected for bile acid measurements. Results: Compared with healthy mice, T1D and T2D mice showed lower levels of the primary bile acid, chenodeoxycholic acid, in the plasma, intestine, and brain, and higher levels of the secondary bile acid, lithocholic acid, in the plasma and pancreas. Levels of the bile acid ursodeoxycholic acid were undetected in healthy mice but were found to be elevated in T1D and T2D mice. Conclusion: Bile acid profiles in other organs were variably influenced by T1D and T2D development, which suggests similarity in effects of T1D and T2D on the bile acid profile, but these effects were not always consistent among all organs, possibly since feedback mechanisms controlling enterohepatic recirculation and bile acid profiles and biotransformation are different in T1D and T2D.

Background: Diabetic foot is a major public health problem and their complications are an imperative cause of morbidity and mortality in diabetes. Objective: To evaluate the rate of recurrence of foot ulcers post two years of follow-up, including the associated risk factors in the patients attending the diabetic foot clinic at the National Center for Diabetes, Endocrinology, and Genetics (NCDEG), Amman, Jordan. Methods: A historical cohort design was adopted for the patients who presented for the first time to the diabetic foot clinic at the NCDEG. Every patient who came to the clinic was reviewed by using his or her medical files with respect to diabetic foot-related complaints. Patients were classified under four categories: (1) Recurrent foot ulcers (2) chronic foot ulcer (3) free of recurrence, and (4) no foot ulcers. Among the four groups, group 1 (recurrent foot ulcers, n=76) and group 3 (free of recurrence, n=54) were included for the analysis. Results: Among the 141 patients who presented to the diabetic foot clinic during the two-year study period, 76 (53.9%) of them experienced ulcer recurrences, 54 (38.3%) were recurrence-free, and 11 (7.8%) had chronic ulceration. The two-year recurrence rate was 58.5%. The presence of deformity and osteomyelitis were the statistically significant independent risk factors for recurrent foot ulceration. Conclusion: This study of recurrences was clearly related to the type and complications of the ulcers rather than to the other variables. Recurrent foot ulceration is linked to the presence of osteomyelitis and/or deformities.