Current Diabetes Reviews - Volume 16, Issue 6, 2020

Introduction: Hypertriglyceridemia (HTG) is one of the most common metabolic disorders leading to pancreatitis and cardiovascular disease. HTG develops mostly due to impaired metabolism of triglyceride-rich lipoproteins. Although monogenic types of HTG exist, most reported cases are polygenic in nature. Aim: This review article is focused on the classification of Primary HTG and the genetic factors behind its development with the aim of providing clinicians a useful tool for early detection of the disease in order to administer proper and effective treatment. Discussion: HTG is often characterized by a complex phenotype resulting from interactions between genetic and environmental factors. In many instances, the complexity, perplexing causes, and classification of HTG make it difficult for clinicians to properly diagnose and manage the disorder. Better availability of information on its pathophysiology, genetic factors involved, environmental causes, and their interactions could help in understanding such complex disorders and could support its effective diagnosis and treatment. Conclusion: The current review has summarized the case definition, epidemiology, pathophysiology, clinical presentation, classification, associated genetic factors, and scope of genetic screening in the diagnosis of primary HTG.

Diabetes is a chronic condition; those with diabetes are at high risk of developing diabetes complications. One important approach to tackle the diabetes burden is to screen for undiagnosed diabetes and to identify factors that lead to the risk of developing diabetes in the future. The earlier identification of individuals at risk of developing diabetes is crucial for delaying or preventing the onset of type 2 diabetes. Numerous studies have demonstrated that circulating concentrations of branch chain amino acids (BCAAs) predict the risk for developing diabetes; thus, contributing to the recent resurgence of interest in these common analytes. The present review aimed to address the recent findings regarding BCAAs and their role in insulin resistance and diabetes. Recent studies demonstrate that BCAAs are strongly associated with a number of pathological mechanisms causing insulin resistance and type 2 diabetes. The research findings related to BCAA signaling pathways and metabolism broaden our understanding of this topic. However, it remains unclear how increased levels of BCAAs will assist in the prediction of future insulin resistance or type 2 diabetes. Future research needs to determine whether BCAAs are a causative factor for insulin resistance and type 2 diabetes, or just a biomarker of impaired insulin action.

Background: Gestational Diabetes Mellitus (GDM) is a health problem that is increasing around the world. Introduction: Prevention of GDM, rather than treatment, could have several benefits in terms of both health and economic cost. Even a slight reduction in maternal glucose in non-diabetic women, particularly in women at high risk for GDM, may have significant benefits for pregnancy results and the future health of off-springs. Probiotics are a relatively new intervention, which are assessed by mothers’ metabolism, and can reduce blood sugar levels, prevent gestational diabetes and reduce the maternal and fetal complications resulting from it. The aim of this study was to review the studies on the prevention of gestational diabetes and assess the potential beneficial effects of probiotics on gestational diabetes and their possible mechanism of action. Methods: Articles compiled through clinical trials indexed in PubMed, Science Direct, Cochran, and Medlib between 2000 and 2017, with the keywords probiotics, prevention, and gestational diabetes mellitus were selected. Results: Considering the potential of probiotics in the modulation of gut microbiota, naturalization increases intestinal permeability, regulation of pro-inflammatory mediators’ secretion and thereby controlling local and systemic inflammation results in decreasing intestinal permeability, enhancing the immune system. It likely has the ability to prevent or control diabetes during pregnancy although confirmatory studies are still needed. Conclusion: Experimental and clinical evidence support the supposition that the modulation of the gut microbiota via probiotic microorganisms could be effective in the prevention of gestational diabetes mellitus.

Stress threatens the homeostasis and mobilizes a plethora of adaptive physiological and behavioral changes via the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. The HPA axis influences the pituitary gland, hypothalamus and adrenal gland via a complex set of positive and negative feedback system. The feedback system operates in a well regulated neuroendocrine manner to reestablish the threatened body equilibrium. The HPA axis secreted major product is a glucocorticoid (cortisol) which is kept within a physiologically optimal range and serves to accomplish the various physiological functions crucial for survival. In chronically stressed individuals dishabituation of HPA axis is followed by increased release of glucocorticoids and catecholamines. Higher secretion of glucocorticoids influences glucose metabolism by promoting gluconeogenesis in the liver, suppressing glucose uptake (adipocytes and skeletal muscles), promoting lipolysis in adipocytes, suppressing insulin secretion, inflicting insulin resistance and inflammation. These biological changes alter neuroendocrine mechanisms and lead to maladaptive congregation of events that form the underlying cause of development of Type 2 diabetes (T2D). The currently reviewed evidences advocate that targeting stress mediated hypersecretion of glucocorticoids may be a viable approach for the treatment of T2D and to reinstate glucose homeostasis.

Background: Type 2 diabetes continues to be a significant burden to patients and health systems globally. Addressing this condition from an alternative perspective, patients and various other stakeholders from three northern Mississippi communities co-created patient-centered research questions focused on type 2 diabetes management. Objective: The objective of this scoping review was to explore current literature focusing on nine patient- centered research questions to establish current knowledge and identify future research needs in the area of type 2 diabetes. Methods: A scoping review was conducted to obtain an overview of research related to the study purpose. The PubMed database was searched from March 2013 to March 2018 to identify patient-centered studies focused on type 2 diabetes and relevant to one of the nine research questions. Results: A total of 33 studies were identified and included. For five of the research questions, there was either no previous research literature or only “related” studies could be identified. These largely unexplored topics included how the understanding of guidelines by healthcare providers, specialty, and communication of medication side-effects impact patients’ understanding and outcomes, the impact of improving patients’ preparedness to communicate with providers, and whether younger patients require weight management programs that account for this populations’ needs. Conclusion: This lack of previous literature presents a unique opportunity to partner with patients to conduct this study and help improve the management of type 2 diabetes.

Background: Exercise training is vital for glycaemic control in patients with type 2 diabetes mellitus (T2D). While the positive effects of supervised exercise training are well established, unsupervised training may offer an alternative and more sustainable means of realising the benefits of exercise away from a resource-heavy supervised setting. Objective: To evaluate the available literature and compare the efficacy of supervised and unsupervised exercise training programs on glycemic control in patients with T2D. Methods: CINAHL, MEDLINE, PubMed, and EMBASE, searched from inception to 20 July 2018. Only studies that included both supervised and unsupervised training were included. Results: Four studies, involving 115 participants, were included. One compared supervised with unsupervised exercise training and three investigated the efficacy of unsupervised training following supervised training. While supervised training is effective for improving glycaemic control in patients with T2D, unsupervised training may not maintain these changes. Included studies lacked detail relating to the supervised and unsupervised training programs. Conclusions: Given that exercise is a critical component for maintenance of glycaemic control in patients with T2D, and because unsupervised training has been shown to be effective in improving clinical outcomes in other disease populations, further research is warranted to compare supervised and unsupervised exercise training in patients with T2D. It is important that future studies report standardised and detailed descriptions of key elements that form the basis of supervised and unsupervised exercise training groups.

Background: Kidney transplant recipients may develop post-transplant diabetes mellitus (PTDM). Dipeptidyl peptidase 4(DPP-4) inhibitors are evolving agents in the management of patients with diabetes mellitus. Aim: To evaluate the efficacy and safety of DPP-4 inhibitors in the management of post-transplant diabetes mellitus (PTDM) in renal transplant recipients. Methods: We performed a systematic search of the electronic databases using keys words and Mesh terms. Data were extracted and reviewed using structured proforma. A comprehensive review of the eligible studies was performed independently by each of two reviewers; conflicts were resolved by the third reviewer. The primary efficacy endpoint was the difference in glycosylated hemoglobin (HbA1c) comparing any of the DPP-4 inhibitors to either placebo or other hypoglycaemic agent. The primary safety endpoints were the worsening of graft functions and change in Tacrolimus trough level. We performed the Random effect model using standardised mean difference. Results: We identified seven studies that were eligible for the systematic review; only one study compared Sitagliptin to insulin Glargine. One study involved head to head comparison of three DPP-4 inhibitors. The other five studies were pooled in the meta-analysis. DPP-4 inhibitors had a favourable glycemic effect as measured by HbA1c when compared to either placebo or oral anti-hyperglycemic medications (standardised mean difference in HbA1c = -0.993, 95% CI= -1.303 to -0.683, P=0.001). DPP-4 inhibitors use did not result in significant change in eGFR ((standardised mean difference = 0.147, 95% CI= -0.139 - 0.433, p=0.312).) nor Tacrolimus level (standardised Mean Difference= 0.152, 95% CI= -0.172 to 0.477, P=0.354). Conclusion: Current evidence supports the short term efficacy and safety of DDP-4 inhibitor agents in the management of post transplantation diabetes mellitus (PTDM) in kidney transplant recipients. However, more RCTs are required to investigate the long-term safety and efficacy of these agents in kidney transplant recipients.

Organophosphate (OP) pesticides are extremely poisonous and they affect the glucose breakdown in numerous and mechanism. There are higher evidence of stimulating diabetes mellitus through OP pesticides especially the type II diabetes. The upsurge in the level of glucose (hyperglycemia), and insulin resistance along with their related outcomes are discussed in this review. The data related to investigational and clinical techniques endorse a connection amid such molecular mechanism and compounds of OPs. Numerous studies conducted till March 2018 have reported OP’ exposures and diabetes-related outcomes. The acute and chronic exposure in case of these insecticides and diabetesrelated outcomes are defined in this study. Initially, it was declared that OPs prompt to hyperglycemia. Then, a high association of glucose in blood beside insulin was found out. The affirmation from some clinical as well as investigational studies supported a connection amid exposure to OP and diabetes, yet in maximum number of instances, non-specific diabetes occurs.

Background: Self-care is essential for the prevention of complications in patients with diabetes, but several authors report that even with health education programs, the incidence of complications in patients with diabetes continues to increase. Objective: We aimed to examine adherence to self-care strategies and the repercussions of adherence on the clinical profiles of individuals with type 2 diabetes. Methods: We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We searched for related studies in 4 databases: PubMed, Web of Science, Scopus, and Latin American and Caribbean Health Science Literature (LILACS). We included observational studies in English and Portuguese that evaluated the effects of selfcare in individuals with type 2 diabetes. Results: The search resulted in the identification of 615 articles, of which 34 met all the inclusion criteria. General self-care was considered unsatisfactory. Physical exercise was classified as the self-care activity that was performed less frequently by individuals with type 2 diabetes mellitus; adherence to medication was the most frequent behavior among volunteers. Conclusion: The studies indicated poor adherence of the population to good self-care practices, reflected by the increase in complications related to DM.

Introduction & Background: Protein carbamylation is a non-enzymatic and irreversible posttranslational process. It affects functions of numerous enzymes, hormones and receptors playing several roles in diabetes pathogenesis by changing their native structures. Detrimental consequences of oxidative protein damage comprise, but are not limited to glyoxidation, lipoxidation and carbonylation reactions. Since the carbamylated plasma proteins are strongly related to the glycemic control parameters of diabetes, they may have an additive value and emerge as potential biomarkers for the follow up, prognosis and treatment of diabetes mellitus. Methods & Results: To conduct our systematic review, we used PubMed and Semantic Scholar, and used ‘Protein carbamylation and diabetes’ and ‘Protein carbamylation and atherosclerosis’ as keywords and looked into about five hundred manuscripts. Manuscripts that are not in English were excluded as well as manuscripts that did not mention carbamylation to maintain the focus of the present article. Similar to glycation, carbamylation is able to alter functions of plasma proteins and their interactions with endothelial cells and has been shown to be involved in the development of atherosclerosis. Conclusion: At this stage, it seems clear that protein carbamylation leads to worse clinical outcomes. To improve patient care, but maybe more importantly to improve healthcare-prevention, we believe the next stage involves understanding how exactly protein carbamylation leads to worse outcomes and when and in what group of people anti-carbamylation therapies must be employed.

Background: There is no data available on the best insulin treatment to counteract the effects of glucose excursions due to a moderate alcohol intake associated with portions of slight fat and protein-containing food, as often the case during social happenings or “happy hours”. Introduction: This study analyzes the glycemic control and quality of life in 8 adult type 1 diabetic (T1D) patients on insulin-pump therapy which were invited to consume a traditional Italian aperitif (“Spritz” and chips). Methods: Patients consumed Spritz aperitif twice: using their habitual bolus, based on carbohydrates (CHO) counting (V1), or with a personalized, advanced bolus (V2) calculated from insulin/Kcal derived from Fats and Proteins (FPU). Post-prandial glucose was continuously monitored; glucose incremental areas (iAUC), glucose peak and time to peak, and estimated change from V1 to V2 from repeated- measures models were computed. Each patient fulfilled validated questionnaires on quality of life, knowledge about diabetes and CHO counting. Results: After the educational program, a reduced iAUC (0-80 min: -306, p=ns; 40-80 min: -400, p=0.07) due to greater (p=0.03) and prolonged double-wave insulin boluses was observed. Blood glucose peak and time to peak were also reduced. Moreover, improvements in the psycho-affective dimension, as well as in the alimentary knowledge were detected. Conclusion: Therefore, a personalized educational program on CHO + FPU counting together with insulin bolus management can improve glycemic control during social consumption of alcohol, with positive reflections on the psycho-affective dimension. Further studies are mandatory to confirm such preliminary results.

Background: Paper-based and computer-based insulin infusion algorithms facilitate appropriate glycemic therapy. The data comparing these algorithms in the management of diabetic ketoacidosis in the intensive care unit (ICU) setting are limited. We aimed to determine the differences in time to diabetic ketoacidosis resolution and incidence of hypoglycemia between computer and paper-based insulin infusion. Methods: Single-institution retrospective review of patients admitted to the ICU with diabetic ketoacidosis between 4/1/2015 and 7/20/2018. Our institution introduced computer-based insulin infusion (Glucommander) to the intensive care unit on 3/28/2016. Patients were grouped into either paper-based group (preintervention) or a computer-based group (postintervention). Summary and univariate analyses were performed. Results: A total of 620 patients (paper-based=247; computer-based=373) with a median (IQR) age of 40 (26-56) years were included; 46% were male. Patients in the computer-based group were significantly older (p=0.003); otherwise, there were no significant differences in gender, race, body mass index and HbA1c. The mean (±SD) time to diabetic ketoacidosis resolution in the computer-based group was significantly lower than the paper-based group (p=0.02). The number of patients in the paper-based group who developed severe hypoglycemia (<50 mg/dl) was significantly higher {8% vs 1%; p<0.0001}. Conclusion: Our analyses demonstrate statistically significant decreases in time to DKA resolution and hypoglycemic events in DKA patients who were managed using a computer-based insulin infusion algorithm providing a more effective and safer option when compared to paper-based insulin infusion.

Background: There is a paucity of studies on health-related quality of life (HRQoL) and sarcopenic obesity (SO). Objective: This study aimed to assess the potential association between SO and impaired HRQoL. Methods: The ORWELL 97 questionnaire was used to assess HRQoL and body composition was measured using a bioimpedance analyser (Tanita BC-418) in 130 patients with obesity, referred to the Nutritional and Weight Management outpatient clinic of Beirut Arab University in Lebanon. Participants were then categorized on the basis of the absence or presence of SO. Results: Sixty-four of the 130 participants met the criteria for SO (49.2%) and displayed significantly higher total ORWELL 97 scores than those in the group without SO (64.00 vs. 41.00, p=0.001), indicative of poorer HRQoL. Linear regression analysis showed that SO was associated with an increase in ORWELL 97 scores by nearly 24 units (β=24.35, 95% CI=11.45-37.26; p<0.0001). Moreover, the logistic regression analysis showed that SO increased the odds of clinically significant impairment of HRQoL (ORWELL 97 score ≥74.25) by nearly seven-fold (OR=7.37, 95% CI=1.92-28.39; p=0.004). Conclusion: Our findings show that the presence of SO was associated with increased impairment of HRQoL that reaches clinical significance when compared to obesity only. Future studies are needed to clarify whether this may influence clinical outcomes. If this is shown to be the case, weight management programs should incorporate additional strategies to improve HRQoL in individuals with SO.

Introduction: The typical factors precipitating diabetic ketoacidosis (DKA) include infections (30%), cessation of antidiabetic medication (20%), and a new diagnosis of diabetes (25%). The etiology remains unknown in 25% of cases. Less frequent causes cited in the literature include severe thyrotoxicosis and, infrequently, pericarditis. Few publications have described the role of human T lymphotropic virus type 1 (HTLV-1) in endocrine and metabolic disorders. Based on a clinical case associated with several endocrine and metabolic disorders, we suggest a potential role for HTLV-1, an endemic virus in the Amazonian area, and review the literature concerning the role of this virus in thyroiditis, pericarditis and diabetes mellitus. Case Report: A fifty-year-old Surinamese woman without any medical history was admitted for diabetic ketoacidosis. No specific anti-pancreatic autoimmunity was observed, and the C-peptide level was low, indicating atypical type-1 diabetes mellitus. DKA was associated with thyrotoxicosis in the context of thyroiditis and complicated by nonbacterial pericarditis and a Staphylococcus aureus subcutaneous abscess. The patient was infected with HTLV-1. Conclusion: To our knowledge, this uncommon association is described for the first time. Few studies have analyzed the implications of HTLV-1 infection in thyroiditis and diabetes mellitus. We did not find any reports describing the association of pericarditis with HTLV-1 infection. Additional studies are necessary to understand the role of HTLV-1 in endocrine and cardiac disorders.