Current Diabetes Reviews - Volume 16, Issue 4, 2020

The rising epidemic of type 2 diabetes mellitus & associated complications is a serious cause of concern for humanity. Glucagon-like peptide-1 receptor agonists commonly abbreviated as GLP-1 RAs, emerged as a promising therapeutic class based on incretin therapy that regulates glucose metabolism through multiple mechanisms. In the present study, various investigational & clinically used GLP-1 RAs have been reviewed with emphasis on their efficacy, structural modifications, adverse effects and toxicities. Various clinical trials justifying their efficacy have also been included, which highlighted the potential of GLP-1 RAs over conventional anti hyperglycaemic agents through a study of pooled effect on glycemic efficacy and weight-loss. The significant potency and appreciable safety of GLP-1 RAs manifested their potential as a logical approach for the management of type 2 diabetes.

Background: Despite efforts to control hyperglycemia, diabetes management is still challenging. This may be due to focusing on reducing hyperglycemia and neglecting the importance of hyperinsulinemia; while insulin resistance and resultant hyperinsulinemia preceded diabetes onset and may contribute to disease pathogenesis. Objective: The present narrative review attempts to provide a new insight into the management of diabetes by exploring different aspects of glycemic index and dietary insulin index. Results: The current data available on this topic is limited and heterogeneous. Conventional diet therapy for diabetes management is based on reducing postprandial glycemia through carbohydrate counting, choosing foods with low-glycemic index and low-glycemic load. Since these indicators are only reliant on the carbohydrate content of foods and do not consider the effects of protein and fat on the stimulation of insulin secretion, they cannot provide a comprehensive approach to determine the insulin requirements. Conclusion: Selecting foods based on carbohydrate counting, glycemic index or glycemic load are common guides to control glycemia in diabetic patients, but neglect the insulin response, thus leading to failure in diabetes management. Therefore, paying attention to insulinemic response along with glycemic response seems to be more effective in managing diabetes.

Diabetes is a globally prevalent chronic metabolic disease characterized by blood glucose levels higher than the normal levels. Sugar, a common constituent of diet, is also a major factor often responsible for elevating the glucose level in diabetic patients. However, diabetic patients are more prone to eat sweets amongst the human population. Therefore, we find a popular consumption of zero or low-calorie sweeteners, both natural and artificial. But, the uses of these sweeteners have proved to be controversial. Thus, the purpose of this review was to critically analyze and highlight the considerations needed for the development of sugar-free or low-calorie products for diabetic patients. For this purpose, various measures are taken such as avoiding sugary foods, using natural nectar, artificial sweeteners, etc. It cannot be ignored that many health hazards are associated with the overconsumption of artificial sweeteners only. These sweeteners are high-risk compounds and a properly balanced consideration needs to be given while making a diet plan for diabetic patients.

Background: A few Randomized Controlled Trials (RCTs) have evaluated the use of liraglutide in Type 1 Diabetes (T1D). Through the present systematic review and meta-analysis, we aim at critically appraising and summarizing those RCTs, providing precise effect estimates. Methods: We searched major databases and grey literature from their inception to October 2018, for RCTs with a duration ≥ 12 weeks, comparing liraglutide with placebo or any other comparator as adjunct to insulin in patients with T1D, investigating major efficacy and safety endpoints. This review is reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Results: We included 5 trials with 2,445 randomized participants. Liraglutide provided modest reductions in HbA1c, with liraglutide 1.8 mg producing the greatest decrease (MD = -0.24%, 95% CI -0.32 to -0.16, I2=0%). Significant weight reduction, up to 4.87 kg with liraglutide 1.8 mg was also observed (95% CI -5.31 to -4.43, I2=0%). Decrease in total daily insulin dose, primarily driven by a decrease in bolus insulin requirements, was demonstrated. Liraglutide decreased non-significantly the odds for severe hypoglycemia (OR=0.80, 95% CI 0.57-1.14, I2=0%), while it increased significantly the odds for gastrointestinal adverse events (for nausea, OR=4.70, 95% CI 3.68-6.00, I2=37%, and for vomiting, OR=2.50, 95% CI 1.54-4.72, I2=27%). A significant increase in heart rate was also demonstrated. No association with diabetic ketoacidosis or malignancies was identified. Conclusion: In patients with T1D, liraglutide might prove be an adjunct to insulin, improving glycemic control, inducing body weight loss and decreasing exogenous insulin requirements and severe hypoglycemia.

Introduction: Accidental fall is a serious problem in older adults. The incidence of accidental fall increases by any dysfunction in the proprioceptive system. The function of the proprioceptive system usually is much affected in people with Diabetes Mellitus (DM), particularly in older ages. However, proprioceptive exercise significantly improves the balance control in older adults, no systematic review demonstrated its effectiveness in improving the balance control in older adults with DM. Thus, this systematic review was conducted to examine the effectiveness of adding proprioceptive exercise to any balance training in older adults with DM. Methods: A systematic search was performed in five major databases. The inclusion criteria of this search included older adults with DM, peripheral neuropathy, randomized control trial, and proprioceptive dysfunction. The exclusion criterion of this search included any study where participants had a history of a disease that might affect the balance control such as ataxia, stroke, and Parkinsonism. The outcome of interest was the importance of including proprioceptive exercise in increasing the effectiveness of balance training in older adults with DM. Results: Nine RCTs met the inclusion criteria for this systematic review. Seven studies of these nine studies included randomization details. Only two studies included the blindness, and only one of them included double blindness. The description of the withdrawal of participants was shown in eight studies. All the included studies used a control group and accomplished the homogeny between subjects in the both groups. Conclusion: This systematic review showed that proprioceptive exercise is a vital component that should be included in any balance training to gain short-term improvement in the balance control in older adults with DM.

Background: Diabetes is a multifactorial disease and a major cause for many microvascular and macrovascular complications. The disease will ultimately lead to high rate mortality if it is not managed properly. Treatment of diabetes without any side effects has always remained a major challenge for health care practitioners. Introduction: The current review discusses the various conventional drugs, herbal drugs, combination therapy and the use of nutraceuticals for the effective management of diabetes mellitus. The biotechnological aspects of various antidiabetic drugs are also discussed. Methods: Structured search of bibliographic databases for previously published peer-reviewed research papers was explored and data was sorted in terms of various approaches that are used for the treatment of diabetes. Results: More than 170 papers including both research and review articles, were included in this review in order to produce a comprehensive and easily understandable article. A series of herbal and synthetic drugs have been discussed along with their current status of treatment in terms of dose, mechanism of action and possible side effects. The article also focuses on combination therapies containing synthetic as well as herbal drugs to treat the disease. The role of pre and probiotics in the management of diabetes is also highlighted. Conclusion: Oral antihyperglycemics which are used to treat diabetes can cause many adverse effects and if given in combination, can lead to drug-drug interactions. The combination of various phytochemicals with synthetic drugs can overcome the challenge faced by the synthetic drug treatment. Herbal and nutraceuticals therapy and the use of probiotics and prebiotics are a more holistic therapy due to their natural origin and traditional use.

Background: Insulin is known to have direct and indirect effects on cell cycle progression, proliferation and metastatic activities. We performed a dose-response meta-analysis to investigate the association between hyperinsulinemia and all-cause cancer related mortality. Methods: A systematic literature search was conducted on MEDLINE and SCOPUS databases to include all published articles up to January 2019. Combined hazard ratios (HRs) with 95% Confidence Intervals (CIs) were estimated using DerSimonian and Laird random-effects models. A dose-response analysis was also conducted to further explore insulin’s relationship with cancer-related mortality. Results: We identified seven studies, with a total of 23,990 participants, who reported the association between hyperinsulinemia and cancer-related mortality. Results from the eligible studies indicated that higher fasting insulin levels were not associated with an increased risk of cancer mortality (pooled HR: 1.14, 95% CI: 0.99-1.32), however, significant heterogeneity was present (I2 = 60.3%, P heterogeneity = 0.001). A subgroup analysis based on gender demonstrated a significant association between fasting insulin level and cancer mortality in men (pooled HR: 1.92, 95% CI: 1.23-3.01, P heterogeneity = 0.281). Conclusion: This dose-response meta-analysis showed a direct significant association between fasting insulin level and cancer mortality in men.

Background: Nowadays, there is an accumulated data about the relation between hypomagnesemia (low Serum Mg level < 0.7 mmol/l) and diabetes. Objective: In this study, we aimed to determine the prevalence of hypomagnesemia in a carefully diagnosed diabetes patients and to show how some factors could contribute to the prevalence of low serum Mg level among the population under study. Methods: In short, 62 patients of both type 1 and 2, who attended AL-Sadir medical city/ diabetes and endocrinology centre during the period of the study were included in the study. A detailed history was taken and participants were informed verbally about the procedure of this study. Serum magnesium and creatinine were measured using standardized methods. Results: The overall prevalence of the hypomagnesemia, among diabetic population involved in this study, was 29.03 % and it was nearly similar in male (29.41 %) and female (28.57 %). The means(SD) of serum Mg level were similar in type 1 and type 2 diabetic patients. Other difference in prevalence among other characteristics has been reported. Within all participants, gender (r = -0.02), fasting blood glucose (r = -0.514) and metformin use (r = -0.014) were negatively correlated with serum Mg level, in contrast to other variables, which were positively correlated. While among type 1 DM, age (r= 0.193), serum creatinine (r= 0.031) and insulin use (r= 0.217) were positively correlated with serum Mg level. In contrast, others were negatively correlated. In type 2 DM, age (r = -0.283) and fasting blood glucose (r = -0.496) were negatively correlated with serum Mg level. On the other hand, other variables were positively correlated with serum Mg level. Conclusion: Hypomagnesemia prevalence was detected in nearly one-third of the diabetic population, which is quite high prevalence. Some factors have shown to play an essential role in this prevalence. A large study is warranted to address this issue.

Background: The exact relationship between the different TCF7L2 gene polymorphisms and the development of diabetic nephropathy (DN) remains unclear. Objective: To investigate the association of TCF7L2 rs12255372 (G/T) gene polymorphism and diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). Methods: 100 patients with T2D (50 patients without DN and 50 patients with DN) and 50 age and sex-matched healthy controls (HC) were enrolled in the study. Genotyping for the rs12255372 (G>T) polymorphism in the TCF7L2 gene was performed by real-time PCR. Results: The rs12255372 polymorphism showed a statistically significant difference between HC and patients with and without DN in both the genotype and allele frequency. However, the rs12255372 polymorphism genotype or allele frequency was not statistically different between patients with DN and those patients without DN. The G allele was found to be higher in patients and the T allele was higher in HC suggesting that the G allele was the risk allele for developing T2D & DN and that the T allele was protective. Conclusion: rs12255372 TCF7L2 gene polymorphism was strongly associated with type 2 diabetes mellitus and DN. The association between rs12255372 polymorphism and DN was a mere reflection of a complicated diabetes mellitus rather than a direct independent association.

Background and Aim: The last decade has seen the emergence of a new condition, describing the coexistence of obesity and sarcopenia, termed Sarcopenic Obesity (SO). The aim of this study was to assess the potential association between SO and reduced Resting Energy Expenditure (REE). Methods: Body composition and REE were measured using a bioimpedance analyser (Tanita BC-418) and Indirect Calorimeter (Vmax Encore 229), respectively in 89 adults with overweight or obesity of both genders, referred to the Outpatient Clinic of the Department of Nutrition and Dietetics at Beirut Arab University (Lebanon). Participants were then categorized on the basis of having SO or not. Results: Thirty-nine of the 89 participants met the criteria for SO (43.8%), and these participants displayed a significantly lower REE per unit body weight than those in the group without SO (19.02 ± 2.26 vs. 20.87 ± 2.77; p = 0.001). Linear regression analysis showed that the presence of SO decreases REE by 1.557 kcal/day for each kg of body weight (β = -1.557; CI = -0.261 – (-0.503); p = 0.004), after adjusting for age and gender. Conclusion: SO appears to be present in a high proportion of treatment-seeking adults with overweight or obesity of both genders, and it seems to be associated with a reduced REE, compared with those without SO. Future studies are needed to clarify whether this may influence clinical outcomes.

Background and Aim: An accurate estimation of Resting Energy Expenditure (REE) in patients with obesity is crucial. Therefore, our aim was to assess the validity of REE predictive equations based on body composition variables in treatment-seeking Arab adults with obesity. Methods: Body composition and REE were measured by Tanita BC-418 bioimpedance and Vmax Encore 229 IC, respectively, and predictive equations based on fat mass and fat-free mass were used in REE estimations among 87 adults of both genders, in the Outpatient Clinic in the Department of Nutrition and Dietetics at Beirut Arab University (Lebanon). The mean differences between the measured and estimated REE values were calculated to assess the accuracy, and the Bland-Altman method was used to assess the level of agreement. Results: Ten predictive equations were included. In males, all the predictive equations gave significantly different estimates of REE when compared to that measured by IC. On the other hand, in females, the mean difference between the REE value estimated by Huang and Horie-Waitzberg equations and that measured using IC was not significant, and the agreement was confirmed using Bland-Altman plots. Conclusion: Huang and Horie-Waitzberg equations are suggested for accurate REE estimation in females; however, new validated REE estimation equations for males in this population are still needed.

Background: Type 2 diabetes (T2D) is a preventable condition. Targeting those who are at risk of getting this disease is essential. Objective: To examine T2D risk among university students in Malaysia and determine its relationship with socio-demographic characteristics and physical activity. Methods: The study was conducted cross-sectionally on 390 students selected using quota sampling method from 13 faculties in Universiti Kebangsaan Malaysia. A short form of the International Physical Activity Questionnaire and Finnish Diabetes Risk Score were used to measure the physical activity and T2D risk. Results: The T2D risk was found to be low (M = 5.23, SD = 3.32) with more than two-third of the student population at the low risk level while a significant proportion of 23.8%, 5.6% and 0.3% having slightly elevated, moderate and high risk respectively. The T2D risk was significantly related to their age (rho = 0.197, p < 0.000), gender (U = 12641, p = 0.011), ethnic group (Χ2 = 18.86, p < 0.000), marital status (Χ2 = 6.597, p = 0.037), residence (U = 10345, p = 0.008), academic year (Χ2 = 14.24, p = 0.007) and physical activity (rho = -0.205, p < 0.000 and Χ2 = 13.515, p = 0.001). Of these, only age (β=0.130) and physical activity (β=-0.159) remained significant in the regression analysis. Conclusion: The findings call for a radical change in the nursing practice to target the amendable factors that are significant in order to prevent the progression of the risk towards type 2 diabetes.

Background: Diabetes mellitus (DM) is one of the most prevalent metabolic diseases in the UAE. During the last two decades, the United Arab Emirates (UAE) has experienced tremendous development in all fields including DM research. The present study sheds light on the growth in DM research in UAE and represents a guide for DM researchers to create more focused future directions in DM research. Objectives: The main objective of the present study is to investigate and document the changes that occurred in DM research in the UAE over the last two decades. Methods: Several research databases were reviewed and all the articles that involved any form of DM research within the UAE were selected. Inclusion criteria were: (i) Research studies related to DM and conducted by institutions based in UAE (ii) Research studies related to DM and conducted in the population of UAE and (iii) Research articles related to DM and the authors (principal investigators or co-investigators) are from UAE. Results: Between the years of 1996 and 2000, there was an average of 6.4 articles about DM being published per year. This pattern changed dramatically between years 2011 to 2015 where an average of 22.8 articles were being published. In addition, a significant increase was noticed in the year 2015 with 42 articles published per year. It was also found that 46.8% articles involved clinical study, 12.1% were basic research, 17.5% cross-sectional studies, 8.91% reviews, 8.2% were cohort and all the other types of research represented about 5.58%. Conclusion: Significant progress has been noticed in DM research in the UAE during the last two decades. Based on the findings of the present study, more focus should be given to the case reports and clinical trials.

Aim: The aim of this study is to examine the relationship between inflammatory markers, and diabetic retinopathy in type II diabetic patients. Methods: The study was a cross-sectional study included 150 type 2 diabetic patients who were divided into 3 groups. 50 in each group are divided as Diabetic patients without retinopathy (DM, n=50), nonproliferative diabetic retinopathy patients (NPDR, n=50), proliferative diabetic retinopathy patients (PDR, n=50). All the patients were subjected to complete clinical examination and laboratory investigations, such as fasting and postprandial blood glucose, serum creatinine, lipid profile tests, glycosylated haemoglobin (HbA1c), fasting insulin, serum inflammatory markers (TNF-alpha, C-reactive protein) and serum VEGF. Results: The study revealed from the multivariate analysis that age, duration and WHR (waist-hip ratio) are potent risk factors responsible for the risk of Diabetic retinopathy. Similarly, serum creatinine, CRP, TNF- alpha and VEGF are significantly higher in diabetic patients with retinopathy compared to diabetic patients without retinopathy. Conclusion: The study concluded that inflammation was associated with severe diabetic retinopathy in patients with well-controlled diabetes. A possible relationship was provided between the risk factors and biomarkers which are responsible for Diabetic retinopathy. Hence, modifying the risk factors risk and development of severe diabetic retinopathy can be reduced.