Current Diabetes Reviews - Volume 17, Issue 3, 2021

Background: Chronic hyperglycemia and related complications involving peripheral nerves in diabetes are one of the most severe microvascular complications with an average prevalence of 50–60%. Diabetic neuropathy is among the vascular disorders of diabetes, the most debilitating and crippled, lethal condition impacting patients’s quality of life. Methods: In the present review article, several hypotheses associated with the pathogenesis of Diabetic Peripheral Neuropathy (DPN) have been introduced, among them metabolic pathways associated with polyol pathway, oxidative stress, production of reactive oxygen species (ROS) amplified under chronic hyperglycemic conditions and activation of transcription factor Nuclear factor-ΚB (NF- ΚB). The review article also possesses pathogenetic and pharmacologic treatments along with others, including acupressure, lidocaine, and capsaicin for DPN. Conclusion: It may be concluded that we can combat the pathogenesis of DPN with different suggested treatments.

Background: Obesity resulted by imbalance between the intake of energy and energy consumption can lead to growth and metabolic disease development in people. Both in obese men and animal models, several studies indicate that obesity leads to male infertility. Objective: This review has discussed some mechanisms involved in obesity-induced male infertility. Methods: Online documents were searched through Science Direct, Pubmed, Scopus, and Google Scholar websites dating from 1959 to recognize studies on obesity, kisspeptin, leptin, and infertility. Results: Obesity induced elevated inflammatory cytokines and oxidative stress can affect male reproductive functions, including spermatogenesis disorders, reduced male fertility power and hormones involved in the hypothalamus-pituitary-gonadal axis. Conclusion: There is significant evidence that obesity resulted in male infertility. Obesity has a negative effect on male reproductive function via several mechanisms such as inflammation and oxidative stress.

Background: Health information technology helps patients to take better care of themselves and improves health status of patients with chronic diseases, such as diabetes. Objective: This study aimed to identify factors influencing the use of health information technology in diabetes management. Methods: This was a review study conducted in 2019. To obtain the related articles, databases, including Scopus, Web of Science, Proquest, and PubMed, were searched and the time frame was between 2010 and 2018. Initially, 1159 articles were retrieved and after screening, 28 articles were selected to be included in the study. Results: Factors influencing the use of health information technology in diabetes management could be divided into the motivational and inhibitory factors, and each of them could be categorized into five groups of organizational, technical, economic, individual, and ethical/legal factors. The motivational factors included training, system ease of use, economic support, having computer literacy, and maintaining privacy and confidentiality. The inhibitory factors included a lack of long-term planning, technical problems, inadequate financial resources, old age, and concerns over confidentiality issues. Conclusion: Identifying motivational and inhibitory factors can help to make better use of technology for diabetes management. This approach, in turn, can improve the acceptability of the technology and save cost, reduce long-term complications of diabetes, and improve the quality of life in diabetic patients.

Background: The major cardiovascular outcome trials on glucagon-like peptide one-receptor agonists have examined its effect on hospitalization of subjects with heart failure; however, very limited trials have been conducted on subjects with reduced left ventricular ejection fraction (r- LVEF) as a primary outcome. Objective: We have conducted a systematic review of two major (FIGHT and LIVE) placebo-controlled trials of liraglutide and its clinical effect on the ejection fraction of subjects with heart failure. Methods: Medline data was retrieved for trials involving liraglutide from 2012 to 2020. The inclusion criteria for trials were: subjects with or without type 2 diabetes mellitus (T2DM), subjects with heart failure with rLVEF, major trials (phase II or III) on liraglutide, trials included liraglutide with defined efficacy primary outcome of patients with heart failure with rLVEF. The search was limited to the English language, whereby two trials [FIGHT and LIVE] had been included and two trials were excluded due to different primary outcomes. Participants (541) had been randomized for either liraglutide or placebo for 24 weeks. Results: In the FIGHT trial the primary intention-to-treat, sensitivity, and diabetes subgroup analyses have shown no significant between-group difference in the global rank scores (mean rank of 146 in the liraglutide group versus 156 in the placebo group; Wilcoxon rank-sum P=.31), number of deaths, re-hospitalizations for heart failure, or the composite of death or change in NT-pro BNP level (P= .94). In the LIVE trial, the change in the left ventricular ejection fraction (LVEF) from baseline to week 24 was not significantly different between treatment groups. The overall discontinuation rate of liraglutide was high in the FIGHT trial (29%, 86) as compared to that in the LIVE trial (11.6%, 28). Conclusion: FIGHT and LIVE trials have demonstrated that liraglutide use in subjects with heart failure and rLVEF was implicated with an increased adverse risk of heart failure-related outcomes.

Background: When considering the administration of glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, or metformin, it is important to understand their weight loss effect as well as the degree of muscle loss caused by each drug in clinical practice. Objective: To comparatively examine the effects of GLP-1RAs and oral antidiabetic drugs, including SGLT2 inhibitors and metformin, on muscle mass and body weight in patients with type 2 diabetes via a network meta-analysis of randomized controlled trials. Methods: We included randomized controlled trials evaluating the effects of antidiabetic drugs on muscle mass and body weight. Mean difference (MD) and 95% confidence intervals (CIs) were calculated using a random-effects network meta-analysis. Results: Of the studies identified, 18 randomized controlled trials (1, 363 subjects) satisfied the eligibility criteria. In all studies, the effects of these drugs on fat-free mass (FFM) were evaluated. Therefore, FFM, which is used as an alternative index of muscle mass, was included in the study. Semaglutide (MD: -1.68, 95% CI: -2.84 to -0.52), dapagliflozin (-0.53, -0.93 to -0.13), and canagliflozin (-0.90, -1.73 to -0.07) showed a significant decrease in FFM compared with the placebo. Metformin did not show a significant decrease in FFM compared with the placebo. When compared with the placebo, semaglutide, dapagliflozin, ipragliflozin, and canagliflozin showed a significant weight loss. Conclusion: Although semaglutide, dapaglifrozin, and canagliflozin have a large weight loss effect, it is important to pay attention to muscle loss because a decrease in FFM was observed.

Background: Many people are still getting affected by uncontrolled glycemic events during hospital admission, which encompasses hypoglycemia, hyperglycemia, and high glycemic variability. Introduction: Primary studies have shown an association of glycemic dysregulation with increased length of hospital stay and mortality among overall patients, however, there is no systematic review of current evidence on the association between uncontrolled in-hospital glycemia in patients with diabetes and health outcomes. This study aimed to systematically review the current evidence on the association between uncontrolled in-hospital glycemia in patients with diabetes and health outcomes. Methods: The association between glycemic dysregulation and health outcomes for inpatients with diabetes was systematically reviewed. PubMed, Embase, and LILACS databases were searched. Two independent reviewers were involved in each of the following steps: screening titles, abstracts, and fulltexts; assessing the methodological quality; and extracting data from included reviews. Descriptive analysis method was used. Results: Seven cohort studies were included, and only two had a prospective design, consisting of 7,174 hospitalized patients with diabetes. In-hospital occurrence of hypoglycemia, hyperglycemia, and glycemic variability were assessed, and outcomes were mortality, infections, renal complications, and adverse events. Among the exposure and outcomes, an association was observed between severe hypoglycemia and mortality, hyperglycemia and infection, and hyperglycemia and adverse events. Conclusion: In-hospital uncontrolled glycemia in patients with diabetes is associated with poor health outcomes. More studies should be conducted for proper investigation because diabetes is a complex condition. Effects of glycemic dysregulation should be investigated on the basis of overall health of a patient instead from only organ-target perspective, which makes the investigation difficult.

Background: Poorly managed diabetes mellitus increases health care expenditures and negatively impacts health outcomes. There are 34 million people living with diabetes in the United States with a direct annual medical cost of $237 billion. The patient-centered medical home (PCMH) was introduced to transform primary care by offering team-based care that is accessible, coordinated, and comprehensive. Although the PCMH is believed to address multiple gaps in delivering care to people living with chronic diseases, the research has not yet reported clear benefits for managing diabetes. Objective: The study reviews the scientific literature about diabetes mellitus outcomes reported by PCMHs, and understands the impact of team-based care, interdisciplinary communication, and care coordination strategies on the clinical, financial, and health-related outcomes. Methods: The systematic review was performed according to the Cochrane method and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Eight databases were systematically searched for articles. The Oxford Centre for Evidence-based Medicine Levels of evidence and the Critical Appraisal Skills Programme systematic review checklist were used to evaluate the studies. Results: The search resulted in 596 articles, of which 24 met all the inclusion criteria. Care management resulted in more screenings and better preventive care. Pharmacy-led interventions and technology were associated with positive clinical outcomes, decreased utilization, and cost savings. Most studies reported decreased emergency room visits and less inpatient admissions. Conclusion: The quality and strength of the outcomes were largely inconclusive about the overall effectiveness of the PCMH. Defining and comparing concepts across studies was difficult as universal definitions specific to the PCMH were not often applied. More research is needed to unpack the care model of the PCMH to further understand how the individual key components, such as care bundles, contribute to improved outcomes. Further evaluations are needed for team-based care, communication, and care coordination with comparisons to patient, clinical, health, and financial outcomes.

Background: Peripheral neuropathy is a major and chronic complication of diabetes mellitus affecting more than 50% patients suffering from diabetes. There is the involvement of both large and small diameter nerve fibres leading to altered somatosensory and motor sensations, thereby causing impaired balance and postural instability. Objective: The aim of this study is to assess the effects of exercises on posture and balance in patients suffering from diabetes mellitus. Methods: Mean changes in Timed Up and Go test (TUGT), Berg Balance Scale and Postural Sway with eyes open and eyes closed on Balance System were primary outcome measures. RevMan 5.3 software was used for the meta-analyses. Eighteen randomized controlled trials met the selection criteria and were included in the study. All the studies ranked high on the PEDro Rating scale. The risk of bias was assessed by the Cochrane collaboration tool of risk of bias. Included studies had a low risk of bias. Sixteen RCT’s were included for the meta-analysis. Results: Results of meta-analysis showed that there was a statistically significant improvement in TUGT with p≤ 0.05 and substantial heterogeneity (I2 = 84%, p < 0.00001) in the experimental group as compared to control group. There was a statistically significant difference in Berg Balance Scale scores and heterogeneity of I2 = 62%, p < 0.00001 and significant changes in postural stability (eyes open heterogeneity of I2 = 100%, p =0.01 and eyes closed, heteogeneity I2 = 0%, p =0.01). Sensitivity analysis causes a change in heterogeneity. Conclusion: It can be concluded that various exercises like balance training, core stability, Tai-Chi, proprioceptive training, etc. have a significant effect on improving balance and posture in diabetic neuropathy.

Objective: This study focused to systematically extract, summarize and analyse the data on the effect of lifestyle modification on leptin resistance and quality of life in metabolic syndrome. Methods: The systematic search was done using PubMed, Cochrane Database, EMBASE, Science Direct, CINAHL, Springer link, Web of Science from 2000-2018. English language articles and quantitative studies focusing on leptin resistance and quality of life were included. Random effect analysis was adopted to pool data and estimate 95% CI. The meta-analysis was done separately for leptin resistance and quality of life which included a total of 9 studies on both RCTs and Non-RCTs. Results: The meta-analysis of RCTs reported insignificant effect of lifestyle modification on leptin resistance in metabolic syndrome when compared to comparison group (-5.94(-14.28, 2.41). Two clinical trials showed a significant effect with pooled data (5.52(2.14, 8.91). Meta-analysis of RCTs focusing on quality of life showed significant effect on mental component (4.89 (0.16, 9.62) of quality of life (2.36 (-3.67, 8.39) when compared to comparison group. Conclusion: This meta-analysis suggested that lifestyle modification has a potential to improve leptin resistance and mental component of quality of life in metabolic syndrome. However, more clearly defined studies are required to come to a stronger conclusion.

Background: To investigate the effects of probiotics on glucose metabolism and body mass index (BMI), and compare the efficacy of probiotic food with the probiotic supplement in patients with type 2 diabetes mellitus using a meta-analysis of randomized, controlled trials. Methods: Online databases Embase, Web of Science, and PubMed were searched until November 2019 to identify eligible articles. Fourteen trials were included. Results: Probiotic consumption reduced fasting plasma glucose (FPG) (SMD=-0.38, 95% CI: -0.76 to 0.01), glycosylated hemoglobin (HbA1c) (SMD=-0.64, 95% CI: -0.91 to -0.38), fasting insulin concentration (SMD=-0.48, 95% CI, -0.81 to -0.15), HOMA-IR (SMD=-1.01, 95% CI, -1.51 to -0.52), and BMI (SMD=-0.02, 95%CI, -0.17 to 0.13) in intervention groups compared with control groups. Subgroup analysis was conducted to trials with probiotic foods and probiotic supplements. Both of probiotic foods (SMD: -0.65, 95% CI: -1.04 to -0.26; SMD: -1.17, 95% CI: -2.14 to -0.20, respectively) and supplements (SMD: -0.64, 95% CI: -1.01 to -0.27; SMD: -0.98, 95% CI: -1.55 to -0.40, respectively) made significant reduction in HbA1c and HOMA.IR. Meta-analysis of trials with probiotic foods found non-significant changes in FBG and fasting insulin concentration (SMD: 0.11, 95% CI: -0.52 to 0.75; SMD: -0.14, 95% CI: -0.48 to 0.20, respectively); however the changes in trials with probiotic supplements were significant (SMD: -0.73, 95% CI: -1.22 to -0.23; SMD: -0.57, 95% CI: -0.97 to -0.17, respectively). Probiotic foods cause a non-significant raise in BMI (SMD: 0.23, 95% CI: -0.03 to 0.49); however, meta-analysis of trials with probiotic supplements found a non-significant reduction in BMI (SMD: -0.13, 95% CI: -0.31 to 0.04). Conclusion: The present meta-analysis suggests that consuming probiotics could improve glucose metabolism and affect body weight, with a potentially greater effect when probiotics are used as supplements.

Background: Glycated haemoglobin (HbA1c) is the gold standard measurement in the screening, diagnosis and monitoring of diabetes mellitus. Saudi Arabia has a high prevalence of diabetes mellitus that is expected to rise, and the HbA1c test is commonly used in the screening, diagnosis and monitoring of diabetes. Objective: This study aims to assess the impact of age and gender on HbA1c levels, and the influence of menopausal status on HbA1c variation in a large group of Saudis. Methods: Age, gender, and HbA1c results of 168,614 Saudi adult individuals were obtained from their medical records. Patients’ records were extracted irrespective of their status regarding the presence of diabetes and the status of glycaemic control. Linear regression models were used for predicting HbA1c from age and gender, and their interaction term. HbA1c levels were compared between genders in different age groups and different HbA1c categories. Results: There was a statistically significant positive correlation between age and HbA1c levels, where for each ten years increase in age, HbA1c increased by 0.35%. Although the overall mean HbA1c in women was significantly lower than in men (P < 0.001), women showed a significant increase in HbA1c with older age compared to men (B = 0.014, P < 0.001). Furthermore, the mean HbA1c levels in the age group > 50 years was significantly higher than before that age (P < 0.001). Thus, HbA1c increased by 1.118% in age > 50 years group compared to age ≤ 50 years, and this increase in HbA1c was significantly higher in women compared to men (B = 0.495, P < 0.001). Conclusion: HbA1c levels are lower in women before the estimated menopausal age, which should be taken into consideration when using HbA1c for screening, diagnosis, and monitoring of diabetes in Saudi adult women. The short lifespan of red blood cells, due to loss of blood through menstruation, in women before menopause age, is a possible reason for these variations.

Objective: Radiographic imaging is an important diagnostic tool in diabetic foot osteomyelitis (DFO). It is unknown whether DFO cases diagnosed with conventional X-ray versus positive Magnetic Resonance Imaging (MRI) differ regarding epidemiology and treatment outcome. Theoretically, signs of inflammation on MRI without bone lesions might be easier to treat. Methods: Our clinical pathway for diabetic foot infections discourages the use of MRI for the diagnosis of DFO. We compared the epidemiology and therapy of non-amputated DFO with positive features on conventional X-ray, MRI, or both. Radiology specialists interpreted the images. The intraoperative aspect of bone during amputation and the results of bone cultures were considered the gold standard for DFO diagnosis. Results: We prospectively followed 390 DFO episodes in 186 adult patients for a median of 2.9 years and performed 318 conventional X-rays (median costs 100 Swiss Francs; 100 US$) and 47 (47/390; 12%) MRI scans (median 800 Swiss Francs; 800 US $). Among them, 18 episodes were associated with positive MRI findings but lacked bone lesions on X-ray. After debridement, the median duration of systemic antibiotics was 28 days for MRI-only episodes and 30 days for X-ray-positive cases (Wilcoxonranksum- test; p=0.26). The corresponding median numbers of surgical debridements were 1 and 1; and recurrence was witnessed in 25% and 28%, respectively. In multivariate logistic regression analysis, MRI-only episodes did not alter the remission rate (odds ratio 0.5, 95%CI 0.1-5.2). Conclusion: According to our clinical pathway, DFO episodes with positive MRI findings only did not differ epidemiologically from the remaining DFO cases and did not influence the choice of therapy nor remission rate.

Background: Vitamin D (VD) deficiency has been related to several endocrine metabolic and cardiovascular diseases. The effect of VD supplementation on blood pressure (BP) in patients with diabetes is controversial. Objective: The aim of this study was to evaluate high-dose vitamin D supplementation effects on blood pressure of normotensive patients with diabetes mellitus 1 (DM1) patients by 24-hour ambulatory blood pressure monitoring (ABPM). Methods: We performed a clinical trial including 35 DM1 normotensive patients, who received doses of 4,000 or 10,000 IU/day of cholecalciferol for 12 weeks according to previous VD levels. They underwent 24-hour ABPM, along with glycated hemoglobin, creatine, lipids profile and PCRus dosage before and after VD supplementation. Results: We found an expressive reduction of systolic and diastolic morning blood pressures (117±14 vs 112±14, p<0,05; 74±9 vs 70±10 mmHg, p<0,05, respectively) with no changes in other pressoric markers. Besides, we noticed a relationship between levels of VD after supplementation and diastolic morning blood pressure (r= -0,4; p<0.05). Conclusion: Our study suggests an association between supplementation of high doses of vitamin D and the reduction of morning blood pressure in normotensive DM1 patients.

Introduction: Diabetes mellitus is a well-known risk factor for cardiovascular disease because of the accelerated process of atherosclerosis. Obesity is an established risk factor and has gained immense importance in recent studies as an important risk factor for clinical cardiovascular disease, yet the fundamental component stays unclear. Calf circumference is another form for lean mass and peripheral subcutaneous fat and is inversely associated with the occurrence of carotid plaques (CP). Multiplicative and opposite effects of both Calf Circumference (CC) and Waist Circumference (WC) in the event of CP suggest that the two measures should be taken into account commonly while assessing vascular risk profile. Aims & Objectives: To ascertain if waist to calf circumference ratio (WCR) is a marker of carotid atherosclerosis in patients with type 2 diabetes mellitus, and the correlation between waist to calf circumference ratio and carotid intima-media thickness (CIMT ) in patients with Type 2 diabetes. Materials and Methods: A cross-sectional study at Hospital affiliated to Kasturba Medical college Mangalore from Sept 2016 to Sept 2018. Patients with type 2 DM as per ADA criteria, age >18years, are recruited for the study. Results and Discussion: In our study, with 150 population, 25 patients had carotid atherosclerosis and 20 patients had CIMT>1.1. The waist circumference in patients with CA is in the range of 93.07, and 99.85 & the CC in patients with CA is in the range of 29.49 to 31.25. The WCR in patients with CA is in the range of 3.12 to 3.26. The difference was statistically significant with a p-value of <0.05. In our study, it was found that WC and WCR correlated well with carotid atherosclerosis, and surprisingly, calf circumference also correlated with carotid atherosclerosis but not as significant as both WC and WCR. Conclusion: To conclude, in our population-based study of 150 subjects, we found that carotid atherosclerosis is significantly more in people with increased waist calf circumference ratio. WCR may be a new, useful, and practical anthropometric index that facilitates the early identification of diabetic subjects with high risk for cardiovascular disease. Validation of this finding in individual populations is required. Future studies should test the association of calf circumference with carotid intima-media thickness and carotid plaques using better measures than ultrasound, such as magnetic resonance imaging. Further research focusing on underlying mechanisms in the role of lean mass and peripheral fat mass is required.