Current Diabetes Reviews - Volume 14, Issue 4, 2018

Background: Currently, there is an epidemic expansion of obesity rates worldwide. The increasing number of obese individuals associated with the aging of population leads to increasing number of individuals with type 2 diabetes mellitus (T2DM) at the same rate. The traditional factors that link obesity to T2DM are related to genetics, hypercaloric diet, sedentary lifestyle, and stress. Individuals from lower Socioeconomic Status (SES) have restricted autonomy and opportunities that could lead to more stress and consequently increase in stress hormones, such as cortisol, catecholamines, glucagon, and growth hormone, which might ultimately change fat deposition, increasing visceral fat and increasing the risk of T2DM development. Methods: We conducted a review of the literature on the effects of low SES and the risk of developing T2DM in obese persons. Results: 191 studies were found. The obesity of lower SES individuals is more central than that for individuals from higher socioeconomic position. It is also proposed that the quality of food seems to be lower, with more intake of fat and simple carbohydrates and less of fruits, vegetables and whole wheat bread, in the more disadvantaged social classes. The lower income neighborhoods, without exercise facilities and unsafety are also associated with higher indices of physical inactivity. Cross sectional and prospective studies confirm the relationship between lower socioeconomic status and obesity and diabetes. The lower SES is associated to metabolic implications that are linked to insulin resistance and possibly may also interfere with the ability of beta cell to secrete insulin and change the gut microbiota, increasing even more the future risk of developing diabetes.

Introduction: Angioedema is a potentially fatal adverse drug reaction of some medications, as swellings of the upper airways can cause death by asphyxiation. Angiotensin converting enzymeinhibitors are widely known to cause angioedema but less is known about the association between dipeptidyl peptidase-4 inhibitors (gliptins) and angioedema. Dipeptidyl peptidase-4 inhibitors are antidiabetic drugs used to improve glycaemic control. They, as a class effect, inadvertently affect the degradation of the vasoactive kinins bradykinin and substance P, both of which can cause angioedema due to vasodilatation and increase in vascular permeability in the capillaries. Objective: To assess the risk and pathomechanism of angioedema due to inhibition of dipeptidyl peptidase- 4 inhibitors when used as monotherapy and in combination with angiotensin converting enzymeinhibitors. Method: PubMed, Embase, the Cochrane Library, PubMed Central, Web of Science, Google Scholar and clinicaltrials.gov were searched using different combinations of keywords “angioedema”, “dipeptidyl peptidase 4”, “dipeptidyl peptidase 4 inhibitors”, “gliptins”, “bradykinin”, “substance P” and “angiotensin converting enzyme-inhibitors”. Original research papers were preferably used as references and their bibliographies were used to further the search for original research results. Results: Both angiotensin converting enzyme and dipeptidyl peptidase-4 are major enzymes in the degradation pathway of bradykinin and substance P, and when inhibited pharmacologically – especially at the same time – the theoretical risk of angioedema is increased due to accumulation of vasoactive kinins. Conclusion: Treatment with dipeptidyl peptidase-4 inhibitors must be carefully considered and monitored especially during concurrent treatment with angiotensin converting enzyme-inhibitors or when treating patients with a known predisposition to angioedema.

Background: Diabetes mellitus is the main reason of morbidity and mortality worldwide. In recent years great attention has been paid to bioactivity of natural products due to their potential pharmacological utilization. Echinochrome is a natural compound isolated from sea urchins and possesses many biological effects. The hypoglycemic activity of echinochrome reported in many recent experiments. Objective: In our study, we tried to collect all the possible hypoglycemic mechanism of echinochrome. Conclusion: The hypoglycemic effect of echinochrome involving four main pathways; regeneration of pancreas, decrease insulin resistant, increase insulin production and improve glucose homeostasis.

Background: Peripheral neuropathy affects about 50% of the diabetic population. The manifestations range from pain, numbness, paresthesia and ulceration in the extremities and it is the major cause of non-traumatic amputations. Currently there is no effective treatment for peripheral neuropathy. With the prevalence of obesity and type 2 diabetes and associated complications reaching epidemic levels, there is a critical need for finding a treatment to preserve nerve function. Introduction: This article will review the potential for fish oil as a treatment for diabetic peripheral neuropathy. Methods: A through search of the PubMed database was performed and relevant articles on the topic were included in this review. Results: Many studies support a role for fish oil in cardiovascular health. However, less information is available regarding the effect of fish oil on diabetes complications including neuropathy. Pre-clinical studies from my laboratory using diabetic rodent models have demonstrated that fish oil can slow progression and reverse diabetic neuropathy as determined by examining multiple endpoints. Mechanistically fish oil has been shown to have anti-inflammatory properties. Lowering the omega-6/omega-3 fatty acid ratio has been shown to be anti-thrombotic. Moreover, metabolites of eicosapentaenoic and docosahexaenoic acids, the main polyunsaturated fatty acids found in fish oil, commonly referred to as resolvins and neuroprotectin have been shown to be neuroprotective and can stimulate neuron outgrowth in vitro. Conclusion: Additional studies are required but existing data suggests that dietary enrichment with omega-3 fatty acids contained in fish oil may be beneficial treatment for diabetic neuropathy.

Background: Individuals with Type II Diabetes (T2D) have to manage blood glucose levels to sustain health and longevity. Artificial sweeteners (including aspartame) are suggested sugar alternatives for these individuals. The safety of aspartame in particular, has long been the centre of debate. Although it is such a controversial product, many clinicians recommend its use to T2D patients, during a controlled diet and as part of an intervention strategy. Aspartame is 200 times sweeter than sugar and has a negligible effect on blood glucose levels, and it is suggested for use so that T2D can control carbohydrate intake and blood glucose levels. However, research suggests that aspartame intake may lead to an increased risk of weight gain rather than weight loss, and cause impaired blood glucose tolerance in T2D. Objective: This review consolidates knowledge gained from studies that link aspartame consumption to the various mechanisms associated with T2D. Method: We review literature that provides evidence that raise concerns that aspartame may exacerbate T2D and add to the global burden of disease. Result: Aspartame may act as a chemical stressor by increasing cortisol levels, and may induce systemic oxidative stress by producing excess free radicals, and it may also alter gut microbial activity and interfere with the N-methyl D-aspartate (NMDA) receptor, resulting in insulin deficiency or resistance. Conclusion: Aspartame and its metabolites are safe for T2D is still debatable due to a lack of consistent data. More research is required that provides evidence and raise concerns that aspartame may exacerbate prevalence of pathological physiology in the already stressed physiology of T2D.

Background: With cardiovascular disease accounting for approximately 50% of deaths in patients diagnosed with type 2 diabetes, it is pertinent to initiate anti-diabetic medications with cardiovascular benefits. This systematic clinical review critically examines the clinical therapeutic effect of lixisenatide. Methods: Data were gathered from articles indexed in PubMed, Google Scholar and Medline from 2010 - 2017, with the following search terms, "lixisenatide" and “GLP-1 receptor agonist”. Studies written in the English language were included. Results: Thirteen clinical studies which evaluated the efficacy of lixisenatide were analyzed. Results from these studies showed that lixisenatide is an effective monotherapy in the reduction of glycated hemoglobin (A1C), Postprandial Glucose (PPG) and Fasting Blood Glucose (FPG). As an add-on therapy to metformin or sulfonylureas and insulin, it was found to be clinically effective compared to placebo. In all reviewed trials, there were higher proportions of patients who achieved A1C < 7% or < 6.5% compared to placebo without a corresponding increase in weight. Finally, the use of lixisenatide was not associated with an increased risk of cardiovascular events. The most common adverse events in all lixisenatide groups were nausea, vomiting, and diarrhea. Conclusion: Lixisenatide appears to be safe and effective therapy for the management of type 2 diabetes mellitus. It is not associated with either the risk of cardiovascular events or symptomatic hypoglycemia. Finally, lixisenatide may be best used as an adjunct therapy for patients who are inadequately controlled with other diabetic medications, or select group of patients at risk of insulin induced obesity, hypertension or heart failure.

Background: Diabetes Mellitus (DM) and its complications are well studied; patients with diabetes may suffer from neuropathy and vascular issues, and associated with these, lower extremity ulceration. Ulcers are often refractory to treatment, and can be difficult for both patients and clinicians to manage. Such complications may lead to amputations, which in turn are a risk factor for death. However, in certain situations amputation may be the only option available, and may be used as reconstructive surgery, restoring function. The impacts of ulceration, amputation, use of prostheses, and other complications of diabetes on Quality of Life (QOL) are well studied. Similarly, the impact of QOL on overall health has been studied in some detail. Objective: Not as well understood are patient expectations regarding amputation and ulceration, and patient knowledge of these outcomes. Specifically, it is not fully understood how patients view these complications prior to their occurrence. In this review we survey the literature for studies discussing these attitudes. Our objective was to perform a systematic review of the medical literature to understand how patients understand and anticipate the potential negative outcomes of ulceration and amputation. We also aimed to identify areas where there are gaps in patient knowledge, which could be addressed by clinicians. Results: Our study yielded articles regarding impressions of patients with diabetes about their general health and outcomes. However, we did not discover much literature directly concerning attitudes toward catastrophic lower extremity outcomes before they occurred. We also identified that patients lack knowledge of management and complications of diabetes; both of these gaps provide an opportunity to better direct care for such patients.

Background: Gestational diabetes mellitus is any degree of glucose intolerance with first diagnosis during pregnancy; it affects 3-10% of pregnancies. The presence of diabetes-related autoantibodies has shown to be able to predict the development of type 1 diabetes before hyperglycemia arises. Objective: To recognize the prevalence of islet cell antibodies among a sample of Egyptian females with gestational diabetes and its possible relation to development of Type 1 diabetes within one year postpartum. Methods: Our cross sectional study was conducted on 150 Egyptian pregnant females with gestational diabetes aged 19-39 years diagnosed by 75-g 2-hour oral glucose tolerance test. All females were subjected to full history, thorough clinical examination and laboratory measurement of anti-islet cell antibodies. Those females with positive antibodies were followed up six months and one year after delivery for their fasting insulin, fasting blood glucose and two hours post prandial glucose levels. Results: The prevalence of pregnant females with gestational diabetes having positive anti islet cell antibodies was (44%), the prevalence of females diagnosed to have diabetes mellitus was (37.88%) six months and (51.52%) one year postpartum. Conclusion: The high prevalence of ICAs among pregnant Egyptian females with GDM and the risk of developing type 1diabetes later in life makes screening for ICA among women with GDM important to recognize those at risk of developing type 1 diabetes later in life.

Background: Recent studies suggest that glycemic variability could influence the risk of complications in Type 1 Diabetes Mellitus (T1DM). There are no data about the action of Vitamin D (VD) on glycemic variability. Our pilot study aims to evaluate glycemic variability and insulin needs in patients with T1DM supplemented with VD. Methods: 22 Patients received doses of 4000 and 10000 IU/day of cholecalciferol for 12 weeks, according to the patient's baseline VD levels and underwent continuous glucose monitoring system. Results: Correlations were found between percentage variation (Δ) of glycemia standard deviation (ΔSDG), calculated using continuous glucose monitoring, with Δ of basal (r = 0.6; p <0.01) and total insulin dose (r = 0.6; p <0.01). Correlations between VD status after supplementation and Δ of prandial (r = 0.5; p <0.05) and total insulin dose (r = 0.4; p <0.05) were found, suggesting that the dose of insulin needed by patients is lower when VD status is better. We divided patients in two subgroups: SDG improved (subgroup 1; N = 12 (55%)) and SDG worsened (subgroup 2; N = 10 (45%)). Group 1, compared to subgroup 2, required a lower insulin dose (Δbasal insulin dose = -8.0 vs. 6.3%; p <0.05) and had a lower frequency of hypoglycemia (27% vs. 64%, hypoglycemias/days evaluated; p <0.01). Conclusion: Our study suggests a relation between VD supplementation, improved glycemic variability, lower insulin needs and lower frequency of hypoglycemia in patients with T1DM.