Current Diabetes Reviews - Volume 16, Issue 5, 2020

Introduction: Diabetes leads to multiple organ defects and cellular dysfunctions such as increased expression of sodium-glucose like transporters (SGLTs). These transporters contribute to glucose homeostasis through glucose reabsorption in the proximal renal tubule. When inhibited, it results in reduced hyperglycemia, increased glucosuria and decreased HbA1c. Aims: This review article summarizes the positive and adverse effects of the three main SGLT inhibitors used in Europe, on different organs with the aim of providing useful information to clinicians in order to select the adapted SGLT inhibitor in regard to patient health problems. Discussion: Recently, SGLT pharmacological inhibitors have been developed to manage hyperglycemia in diabetic patients. SGLT inhibitors like canagliflozin, dapagliflozin, empagliflozin were approved by the Food and Drug Administration (FDA) in 2013 for use in Europe. Beyond their impact on glucose re-uptake by the kidney, these inhibitors exert beneficial pleiotropic effects. Nevertheless, several studies have recently warned the scientific community regarding adverse effects of these agents. Therefore, clinicians should consider these effects to adapt the treatment regarding patients’ health. Conclusion: The use of SGLT inhibitor in the treatment of type 2 diabetes should be considered with the perspective of general health state of the patient. In fact, SGLT inhibitors promote pleiotropic effects, among which some are beneficial for certain organs while some are deleterious.

Background: For centuries, humans have used medicinal plants in the management of both acute and chronic diseases. Currently, the practice of using medicinal plants to manage diseases is becoming increasingly-common; especially in medium to low-income economies where the cost of, or ease of access to orthodox medications are limitations to their effective and sustained use. Diabetes mellitus is a chronic disease whose prevalence continues to increase worldwide. An aspect of diabetes mellitus that causes significant morbidity is its neurological complications, which are known to be associated with an enormous economic burden and reduction in quality of life. Objectives: While research continues to demonstrate that a wide range of plants that are indigenous to Africa have significant antihyperglycaemic properties, scientific information on the neurobehavioural and/or neuromorphological effects of these plants appear to be lacking. Also, their possible benefits in the prevention or amelioration of the neurological complications of diabetes mellitus remain generally unexamined. Methodology: In this narrative review, we the examine available scientific literature dealing with the neurobehavioural and/or neuromorphological profiles of selected African plants with substantiated antihyperglycaemic properties; aiming to highlight their potential applications in the prevention and management of the neurological complications of diabetes mellitus. Results: This review demonstrates that a number of the African plants with antidiabetic properties also exhibit central nervous system effects. Conclusion: While the neurobehavioural and neuromorphological effects of some of these plants had been investigated in animal models of DM; their possible roles in the prevention or amelioration of the neurological complications of DM are yet to be established.

Type 1 diabetes mellitus (T1DM), an autoimmune disorder, is becoming widespread with approximately 97,700 children in India and 490,000 children worldwide affected. There are various etiological factors contributing to the expansion of its incidence on different geographical locations. Hence, the articles published in reputed journals were studies and data were collected for analyzing the etiology and prevention of T1DM. It has been observed that hybrid insulin peptides act as key antigens for the autoreactive T cells and cause the loss of self-tolerance in humans. The association of coxsackievirus B has been observed with the onset of T1DM. Accurate identification of the trigger can lead to the development of appropriate preventive measures. It can become a base for advance studies to prevent T1DM in humans. This review will highlight the causes and some preventive actions which can be considered to eliminate T1DM.

Introduction: Type 2 Diabetes (T2D) is a major health problem worldwide. This metabolic disease is indicated by high blood glucose levels due to insufficient insulin production by the pancreas. An inflammatory response occurs as a result of the immune response to high blood glucose levels as well as the presence of inflammatory mediators produced by adipocytes and macrophages in fat tissue. This low and chronic inflammation damages the pancreatic beta cells and leads to insufficient insulin production, which results in hyperglycemia. Hyperglycemia in diabetes is thought to cause dysfunction of the immune response, which fails to control the spread of invading pathogens in diabetic subjects. Therefore, diabetic subjects are known to more susceptible to infections. The increased prevalence of T2D will increase the incidence of infectious diseases and related comorbidities. Objective: This review provides an overview of the immunological aspect of T2D and the possible mechanisms that result in increased infections in diabetics. Conclusion: A better understanding of how immune dysfunctions occur during hyperglycemia can lead to novel treatments and preventions for infectious diseases and T2D comorbidities, thus improving the outcome of infectious disease treatment in T2D patients.

Background: It is undeniable that diabetes may cause several health complications for the population. Many of these complications are associated with poor glycemic control. Due to this, strategies to handle this problem are of great clinical importance and may contribute to reducing the various complications from diabetes. Objective: The aim of this study was to compare the effectiveness of the passion fruit peel flour versus turmeric flour on glycemic control. Methods: This is a systematic review and meta-analysis following the PRISMA protocol. The following inclusion criteria were applied: (1) Case-control studies, cohort studies, and clinical trials, due to the improved statistical analysis and, in restrict cases, cross-sectional studies; (2) Articles published in any language. The databases used for the search were PubMed, Scopus, Web of Science, Cochrane, and LILACS. A bias analysis and a meta-analyses were undertaken using R Studio (version 3.3.1) using effect- size models. Results: A total of 565 studies were identified from which 11 met the inclusion and exclusion criteria. Through isolated analysis, the effectiveness of turmeric flour on glycemic control was in the order of 0.73 CI (Confidence Interval) (from 0.68 to 0.79) and the effectiveness of passion fruit peel flour was 0.32 CI (0.23 to 0.45). The joint analysis resulted in 0.59 CI (0.52 to 0.68). The assessment of blood glucose was by glycated hemoglobin levels. All values were significant at a p < 0.05 level. Conclusion: Both interventions showed significant effects on glycemic control.

Background: The body of evidence on gene-environment interaction (GEI) related to type 2 diabetes (T2D) has grown in the recent years. However, most studies on GEI have sought to explain variation within individuals of European ancestry and results among ethnic minority groups are inconclusive. Objective: To investigate any interaction between a gene and an environmental factor in relation to T2D among ethnic minority groups living in Europe and North America. Methods: We systematically searched Medline and EMBASE databases for the published literature in English up to 25th March 2019. The screening, data extraction and quality assessment were performed by reviewers independently. Results: 1068 studies identified through our search, of which nine cohorts of six studies evaluating several different GEIs were included. The mean follow-up time in the included studies ranged from 5 to 25.7 years. Most studies were relatively small scale and few provided replication data. All studies included in the review included ethnic minorities from North America (Native-Americans, African- Americans, and Aboriginal Canadian), none of the studies in Europe assessed GEI in relation to T2D incident in ethnic minorities. The only significant GEI among ethnic minorities was HNF1A rs137853240 and smoking on T2D incident among Native-Canadians (Pinteraction = 0.006). Conclusion: There is a need for more studies on GEI among ethnicities, broadening the spectrum of ethnic minority groups being investigated, performing more discovery using genome-wide approaches, larger sample sizes for these studies by collaborating efforts such as the InterConnect approach, and developing a more standardized method of reporting GEI studies are discussed.

Objectives: To determine the prevalence of, and factors associated with, people with foot deformities, among patients with diabetes in Jordan. Methods: A cross-sectional study was conducted on 1000 diabetic participants recruited from the National Center for Diabetes, Endocrinology, and Genetics in Jordan. Participants had their feet clinically examined to detect the following foot deformity outcomes: Hallux valgus, claw/hammer toe, prominent metatarsal heads, limited joint mobility, pes cavus, Charcot foot, and amputations. Sociodemographic and health variables were also collected from participants’ interviews, medical records, or clinical examination. Logistic regression was used to analyse associations between variables and each foot deformity outcome. Results: Of the 1000 diabetic patients: Hallux valgus was found in 17.4%, claw\hammer toe in 16%, prominent metatarsal head in 14.2%, limited joint mobility in 9.4%, pes cavus in 3.2%, Charcot foot in 2.1%, and amputations in 1.7%. Hallux valgus was associated with gender (p=0.012), age (p<0.01) and shoe choices (p=0.031); claw\hammer toe was associated with age (p=0.04), retinopathy (p<0.001), sensory and painful neuropathy (p<0.001); limited joint mobility was associated with age only (p=0.001); Charcot foot was associated with glycemic control (p=0.016), hypertension (p<0.000), sensory neuropathy (p<0.001), and painful neuropathy (p<0.001); and, amputations were associated with duration of diabetes (p<0.043), sensory neuropathy (p=0.001), and painful neuropathy (p=0.001). Conclusion: Prevalence of different foot deformities in Jordan variedbetween 1.7% - 17.4%. Sociodemographic factors such as age, gender and shoes choices or presence of diabetes-related microvascular complications (neuropathy and retinopathy) or hypertension were independently associated with foot deformities among the Jordanian diabetic population.

Objective: This study aimed to determine the prevalence of insulin resistance among women with polycystic ovary syndrome (PCOS), describe the clinical and biochemical characteristics of women with PCOS, and determine the association between Antimullerian Hormone (AMH) and PCOS. Patients and Methods: In a clinical case series, 544 women with PCOS were included in this study. Body mass index (BMI), Homeostasis Model Assessment (HOMA), Quantitative Insulin Sensitivity Check Index (QUICKI), and Matsuda index were calculated. Sixty-three women with PCOS and 50 age- and BMI-matched control patients underwent blood sampling for AMH level. Results: The most common clinical presentation of PCOS in this study was menstrual irregularity followed by hirsutism and infertility. There was no statistically significant difference in the clinical presentation or hormonal profile in women with PCOS according to different BMI categories. The prevalence of insulin resistance among women with PCOS was 37.7%, 69.3%, and 75.8% using HOMA, QUICKI, and Matsuda index, respectively. Furthermore, the Matsuda index had the highest detection rate of insulin resistance, especially in underweight women with PCOS (94.1%). AMH levels in women with PCOS were significantly higher than that in the control group (P-value = 0.015). Conclusion: Insulin resistance is prevalent among women with PCOS. The detection rate of insulin resistance varies according to the insulin sensitivity index used. Menstrual irregularity was the most common presentation of PCOS. Women with PCOS have significantly higher levels of AMH levels compared to women in the control group.

Aim: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated several extra-pancreatic benefits in addition to glycemic control. This study retrospectively evaluates the realworld clinical effectiveness of dulaglutide as add-on therapy in overweight patients with inadequately controlled type 2 diabetes mellitus (T2DM). Materials and Methods: This single-center study included overweight adult patients (N, 85; women, 45) with inadequately controlled T2DM (mean glycated hemoglobin [HbA1c] (standard deviation [SD]), 7.55 [0.43] %; and body mass index [BMI] [SD], 29.01 [2.30] kg/m2) treated with dulaglutide (1.5 mg) once weekly as an add-on therapy. Follow-up improvements in outcomes were analyzed using the paired t-test. Subgroup analysis was performed for selected outcomes. Safety parameters were also evaluated. Results: At the 20-week follow-up, dulaglutide based therapy demonstrated a significant reduction (P<.001) in HbA1c, body weight and BMI, with a mean reduction (MR [SD]) of 0.45 [0.38] %, 5.06 [2.33] kg, and 1.82 [0.81] kg/m2, respectively, in the overall population. Similarly, reduction in urine albumin/creatinine ratio [U-ACR] (6.04 [15.53] mg/g), cholesterol (3.24 [4.14] mg/dL), triglycerides (16.60 [12.39] mg/dL), very-low-density lipoprotein [VLDL] (3.31 [2.48] mg/dL), serum glutamicoxaloacetic transaminase (1.80 [2.92] U/L) and glutamic-pyruvic transaminase (8.00 [5.64] U/L) was also significant (P<.05). Target HbA1c of <7% was achieved in 40% of patients. Reduction in HbA1c and body weight was significant across all subgroups analyzed. Predominantly, gastrointestinal adverse events were reported. Conclusion: Dulaglutide as an add-on therapy was well tolerated with significant improvement in HbA1c, body weight, BMI, U-ACR, lipid fractions and serum transaminases in overweight Indian patients with T2DM.

Background: The recent report of The World Health Organization on diabetes has stressed on the burden of diabetes on low/middle income countries. Recent studies advocated the importance of funding more research on diabetes and insulin in these countries. Recently, the European Research Council advocated the importance of gold Open Access (OA) publishing, where the funded research should be immediately accessible. In this study, we aim to assess funding for insulin research, where we will compare the OA status between funded and unfunded research. Methods: We used Scopus database to assess insulin research published from January 1st, 1999 to December 31st, 2018. Our bibliometric analysis consisted of three main sections: analysis of all publications on insulin, analysis of funded insulin publications, and analysis of unfunded insulin publications. Results: We found a total of 388,202 publications, of which only 83,180 (21.4%) were funded. USA produced around 30.1% of the total publications, and the National Institute of Health (NIH) was the major funder with 18.6% of all publications. Of the funded publications, 29,143 (35%) were OA publications, compared to 97,347 (31.9%) of the unfunded publications. We didn’t find a significant difference in OA status between funded and unfunded research. Conclusion: In concordance with the European Research Council’s decision to support gold OA publishing model, we found that only 35% of the funded and 31.9% of the unfunded insulin research were OA. Although the funded research is increasing in China, most of it is produced in high income countries. This highlights the importance of allocating more funds to low/middle income countries.

Background: The specific treatment recommendations for type 2 diabetes mellitus (T2DM) differ based on a particular guideline. The goal of pharmacotherapy is to achieve the target HbA1c and fasting and postprandial blood glucose levels to avoid disease complications. Objective: To evaluate the profile of T2DM patients on different antidiabetic treatment regimens and the factors leading to dose escalation in these patients. Methods: A prospective descriptive study was conducted at Kasturba Medical College Hospital, Mangalore, a tertiary care teaching hospital, over a period of one year. The study population comprised of patients with T2DM for ≥5 years. The demographic and clinical data were collected during the baseline and follow-up visits. Results: Of the 119 patients studied, 59.7% were males; 32.8% were ≥65 years of age. A significant decrease in the fasting blood glucose (FBG) on follow-up was seen (p = 0.028) in patients on sulfonylurea and metformin combination. A significant decrease in the glycated haemoglobin (HbA1c) was seen in patients on sulfonylurea with metformin and pioglitazone (p = 0.011); sulfonylurea with metformin, pioglitazone, and sitagliptin (p = 0.026); and metformin with insulin (p = 0.001). Patients who received dose escalation had a longer duration of the disease (p = 0.042), higher FBG (p = 0.039) and HbA1c (p = 0.05). Conclusion: A combination of metformin with sulfonylurea was the preferred first-line treatment; insulin was added when HbA1c was >9. Patients who received dose escalation had a longer duration of the disease and higher FBG and HbA1c.

Background and Aims: A number of significant positive and negative signals emerged from the CANVAS Program and CREDENCE trial with the use of canagliflozin. These signals are confusing. A Likelihood of being Helped of Harmed (LHH) analysis was conducted to determine the risk, benefit ratio associated with canagliflozin use and address the signals as a continuum. Materials and Methods: LHH was calculated from the number needed to treat (NNT) and number needed to harm (NNH) available from the absolute risk reductions reported with the outcomes of interest, in these two trials. Results: In the CANVAS Program, LHH for major adverse cardiovascular events (MACE) points at a significant benefit with canagliflozin use in comparison to amputation (1.65), fractures (1.65) and euglycaemic diabetic ketoacidosis (euDKA) (16.67) risks. Only genital fungal infections were significant more in both sexes (0.21-M and 0.1-F) when LHH was matched against the positive outcomes. In contrast, the hHF benefits were outweighed by amputation (0.95) and fracture risks (0.95). In CREDENCE trial, the LHH for Primary composite, Renal composite and MACE, all supported the benefits in comparison to any adverse events encountered in the trial. The LHH from pooled data (CANVAS Program and CREDENCE trial) was in favour of all the benefits (hHF and renal composites) except for MACE matched against amputation (0.66). Conclusion: The outcome benefits were in favour of canagliflozin in comparison to all reported adverse events, when hHF and renal composite were under consideration, in both the individual and pooled LHH analysis. However, the MACE benefits were overwhelmed by amputation risk in the pooled analysis.

Introduction: Obesity management is a critical global issue. It is essential to evaluate visceral adiposity which is associated with metabolic syndrome and cardiovascular disease. Aim: This study aims at precisely evaluating the necessity of visceral adipose tissue in obesity management. Methods: We assessed the validity of visceral fat area (VFA) measurement using bioelectrical impedance analysis (BIA) with computed tomography (CT) as a reference in obese subjects. Although VFABIA exhibited significant correlation with VFACT, the difference between VFACT and VFABIA increased with an advancing degree of obesity. Result and Conclusion: The BIA device seemingly underestimated VFA in obese subjects compared with the normal-weight subjects.