Current Diabetes Reviews - Volume 14, Issue 6, 2018

Background: Across the world, the economic and health costs of diabetes are rising at an alarming rate. Each year in the United States, billions of dollars are spent on T2 Diabetes mellitus (T2DM) treatments, but such treatments are not always effective and can lead to adverse events. Many pharmacological treatments exist to control the primary and secondary symptoms of T2DM, but these medications are not always efficacious, do little to treat secondary T2DM symptoms, and often carry adverse side effects. Traditional Chinese Medicine (TCM) is a form of alternative medicine that is becoming appealing to western healthcare systems because of its comprehensive, holistic approach to managing T2DM patients. Methods: Works across TCM printed texts, clinical trial databases, medical association practice guidelines, and the existing literature on TCM and western diabetes treatments (in print and online) are reviewed. Results: Conventional pharmaceutical therapies for T2DM are not efficacious enough to maintain satisfactory blood glucose levels for all patients, and even patients who maintain stable blood glucose levels may still suffer from secondary T2DM symptoms as well as from the side effects of their medications. TCM therapies have demonstrated promising results in T2DM clinical studies without causing the types of side effects associated with standard pharmaceutical treatments. In addition, the economic burden of TCM diabetes treatments on patients and payers is oftentimes less than that of pharmaceutical regimens. Conclusion: TCM approaches can be a viable alternative approach to treatment in the modern U.S. healthcare landscape, but a number of obstacles impede its assimilation into western health systems.

Background: Diabetes Mellitus (DM) is a disorder of glucose metabolism marked by hyperglycemia, glycosuria, hyperlipidemia, negative nitrogen balance and ketonaemia. DM is a major healthcare problems today and its treatment costs billions of dollars worldwide annually. The cases of diabetes have increased rapidly in recent years throughout the world. Currently, for the management of Type-1 Diabetes Mellitus (TIDM), Multiple Daily Insulin (MDI) injections is the most popular treatment. Oral administration of insulin is the most suitable and attractive as compared to subcutaneous route but unfortunately cannot be utilized for the administration of peptides and proteins due to poor epithelial permeability and enzymatic degradation within the gastrointestinal tract. Since many years, extensive research has been carried out to explore the potential ways of insulin administration based on novel methods such as liposome, microsphere, nanoparticle, mouth dissolving strips, sprays exploiting oral and pulmonary route. These next generation efficient therapies for T1DM may help to improve the quality of life of diabetic patients especially in Insulin Dependent Diabetes Mellitus (IDDM). Conclusion: This review emphasizes on the most recent progress made in the development of oral insulin delivery formulations, and focuses on key lessons and implications from studies undertaken till date with the oral insulin formulations. Further, this review analyzes effectiveness of the advancements, applications and limitations of the technologies in delivering insulin to the targeted site through oral administration.

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new pharmacotherapeutic class for the treatment of Type 2 Diabetes Mellitus (T2DM). Objective: To evaluate beneficial effects of the SGLT2 inhibitors on metabolic, cardiovascular, and renal outcomes. Methods: A Pub-Med search (1966 to July 2017) was performed of published English articles using keywords sodium-glucose co-transporter 2 inhibitors, canagliflozin, dapagliflozin, and empagliflozin. A review of literature citations provided further references. The search identified 17 clinical trials and 2 meta-analyses with outcomes of weight loss and blood pressure reduction with dapagliflozin, canagliflozin, or empagliflozin. Three randomized trials focused on either empagliflozin or canagliflozin and reduction of cardiovascular disease and progression of renal disease. Results: SGLT2 inhibitors have a beneficial profile in the treatment of T2DM. They have evidence of reducing weight between 2.9 kilograms when used as monotherapy to 4.7 kilograms when used in combination with metformin, and reducing systolic blood pressure between 3 to 5 mmHg and reducing diastolic blood pressure approximately 2 mmHg. To date, reduction of cardiovascular events was seen specifically with empagliflozin in patients with T2DM and a history of cardiovascular disease. In the same population, empagliflozin was associated with slowing the progression of kidney disease. Moreover, patients with increased risk of cardiovascular disease treated with canagliflozin have decreased risk of death from cardiovascular causes, nonfatal MI, or nonfatal stroke. Data regarding these outcomes with dapagliflozin are underway. Conclusion: SGLT2 inhibitors demonstrate some positive metabolic effects. In addition, empagliflozin specifically has demonstrated reduction in cardiovascular events and delay in the progression of kidney disease in patients with T2DM and a history of cardiovascular disease. Further data is needed to assess if this is a class effect.

Background: Type 2 Diabetes Mellitus (T2DM) is turning out to be a global health crisis. Currently available literature clearly indicates an increased risk of type 2 diabetes amongst South Asian population. Objective: The objective of this narrative review is to explore the non-modifiable and modifiable risk factors of T2DM in South Asian population, including their beliefs, attitudes, socio economic and cultural barriers and also to explore the possible implications in designing culture specific diabetes prevention and management programs. Methods: This narrative review is based upon the data from individual studies and review article known to the authors. Additional relevant studies were identified through PubMed search on Englishlanguage papers published in 2000-2017 using the relevant keywords. Where appropriate, the reference lists of key papers were reviewed to identify additional studies of interest. Results: Many genetic and environmental risk factors such as diet, physical inactivity, and sleep contribute to the increased prevalence of diabetes in the ethnic group. Providing mere knowledge about diabetes and these risk factors might not be sufficient in this particular ethnic group. It is essential to address their beliefs, attitudes and the cultural barriers faced. Conclusion: To overcome the health disparity in the South Asian ethnic group, various risk factors associated with diabetes, and the challenges faced are to be considered while designing future diabetes prevention and management strategies.

Background: Diabetic Retinopathy is a leading cause of sight-threatening complication, which occurs due to a number of physiological and metabolic abnormalities during later stages of diabetes. Many of these abnormal changes are consistent with altered oxidative stress, inflammation, genetic set up, advanced glycation end products, and hematological changes. So the altered levels of different biomolecules related to these changes serve as important biomarkers to assess better evaluation and early treatment of this disease. Some treatments like laser therapy may be fast and specific but are more expensive, limited and can result in severe contraindications. Several other novel treatment strategies have been evolved recently besides classical approaches like control over hyperglycemia, hypertension, lipid profile to control diabetic retinopathy. These precise treatments are based on targeting the elevated biomarkers in retina. Such treatments include use of anti-VEGF therapy, intravitreal corticosteroids, gamigliptin and flavonoids. Conclusion: The present review discusses the latest updates on diabetic retinopathy, common etiology, different biomarkers and current treatments. In conclusion, perfection and proper supervision of diabetes and early treatment of diabetic retinopathy are crucial in controlling the occurrence and severity of this disease.

Introduction: Although hypovolemia remains the most relevant problem during acute decompensated diabetes in its clinical manifestations (diabetic ketoacidosis, DKA, and hyperglycemic hyperosmolar state, HHS), the electrolyte derangements caused by the global hydroelectrolytic imbalance usually complicate the clinical picture at presentation and may be worsened by the treatment itself. Aim: This review article is focused on the management of dysnatremias during hyperglycemic hyperosmolar state with the aim of providing clinicians a useful tool to early identify the sodium derangement in order to address properly its treatment. Discussion: The plasma sodium concentration is modified by most of the therapeutic measures commonly required in such patients and the physician needs to consider these interactions when treating HHS. Moreover, an improper management of plasma sodium concentration (PNa+) and plasma osmolality during treatment has been associated with two rare potentially life-threatening complications (cerebral edema and osmotic demyelination syndrome). Identifying the correct composition of the fluids that need to be infused to restore volume losses is crucial to prevent complications. Conclusion: A quantitative approach based on the comparison between the measured PNa+ (PNa+ M) and the PNa+ expected in the presence of an exclusive water shift (PNa+ G) may provide more thorough information about the true hydroelectrolytic status of the patient and may therefore, guide the physician in the initial management of HHS. On the basis of data derived from our previous studies, we propose a 7-step algorithm to compute an accurate estimate of PNa+ G.

Background/Aim: Diabetes mellitus is a non-communicable disease which has become a major global public health issue. This systematic review summarized epidemiological studies related to the prevalence, risk factors, complications, incidence, knowledge, attitude and practices of Diabetes Mellitus (DM) among Arab population in the United Arab Emirates (UAE). Methods: PubMed, Scopus databases, Science direct, Wiley online library, and other local journals were searched to identify relevant literature using appropriate keywords to retrieve studies conducted in the UAE. Search limits were restricted to studies in English language, between 2007 and 2016, and on UAE population (both citizens and expatriates). Results: Electronic database search yielded 24 studies about the prevalence, incidence, complications, risk factors, knowledge, attitudes and practices of diabetes, including cross sectional studies (n =18), population-based survey (n = 1), retrospective cohort studies (n = 3), qualitative (n=1), and randomized controlled trial (n = 1). Countrywide prevalence estimates of Diabetes Mellitus were reported to be high. The major determinants of Diabetes Mellitus involved hypertension, physical inactivity, sedentary lifestyle, and unhealthy diet. Conclusion: Even though past evidences have promulgated the role of numerous causative factors, the epidemiological implications of some of the risk factors including family history, educational level, and the use of alcohol remain elusive. This systematic review signifies epidemiology of Diabetes Mellitus in the United Arab Emirates and suggests that extra efforts are needed for preventive and curative strategies in order to decrease the burden of this non-communicable disease.

Background: Obesity is a growing health problem worldwide. It is associated with serious medical and psychosocial comorbidities that increase the risk of mortality. However, strong evidence confirms lifestyle-modification programs as the cornerstone treatment for excess weight and obesity. The aim of this systematic review was to assess the effectiveness of the lifestyle-modification programs for weight management delivered in Arabic-speaking countries. Methods: The PubMed database was searched, and studies conducted in humans were identified and screened as per the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Data were collated using meta-analysis and a narrative approach. Results: Of the 1057 articles retrieved, six studies, conducted in four Arab countries, comprising a total of 444 adolescent and adult participants of both genders with overweight and obesity, met the inclusion criteria and were reviewed. Most studies that assessed weight loss at 6-month follow-up showed no significant reduction in body weight. Meta-analysis confirmed that the lifestyle-modification programs delivered were no more effective than other treatments. Only one article reported significant weight-loss maintenance after 12 months of follow-up. However this was a prospective non-controlled study in which the weight loss maintained (=4%) did not conform to the standard for clinical significance (>10%). Conclusion: Lifestyle-modification programs for weight management delivered in Arabic-speaking countries seem lacking in effectiveness due to methodological weaknesses in program adaptation, a lack of expert clinical supervision before and during implementation, and the presence of barriers to lifestyle modification, especially for women. Future studies should bear these features in mind.

Background: Recent studies reported that Fat Mass and Obesity-associated gene (FTO) single nucleotides polymorphisms (SNPs), especially rs9939609, have association with obesity and type 2 diabetes mellitus. On the other hand, many researches confirmed that leptin, an adipocytokine, is related to the obesity and Body Mass Index (BMI) in patients who suffered from Type 2 Diabetes (T2DM). Objective: In this study, the correlation of FTO rs9939609 polymorphism and leptin level was investigated in the obese women who suffered from T2DM. Methods: In case-control study, metabolic and anthropometric parameters, and leptin level of 38 obese diabetic and 38 non-diabetic women were investigated. Genotyping of rs9939609 FTO gene was completed by sequencing of PCR amplicons for all cases. Results: According to the results, FBS, age, HbA1c, insulin level, HOMA index and leptin level showed statistically significant difference between diabetic and non-diabetic women (P < 0.05). Based on the adjusting of FTO rs9939609 SNP with anthropometric and metabolic parameters, no significant difference was found between the three genotypes (AA, TA and TT) in non-diabetic women (P > 0.05). But, in the diabetic group, only TC had significant difference and mean of TC was higher in mutant genotypes (AA and TA) than wild genotype (TT). Also, BMI, insulin, LDL and HDL showed negative correlation with leptin level in both groups but these correlations were not statistically significant. Conclusion: The results of our study (with little sample size) showed that the mean of leptin level in diabetic women was lower than non-diabetic women (significant difference). However, the level of leptin was not statistically significant between three genotypes, and odds ratio of rs9939609 was higher in diabetic women in comparison with non-diabetic women.

Background: Studies on a structured method used by pharmacists to provide comprehensive, evidence-based diabetes care are lacking. The aim of this study was to prioritise, rank and construct validate indicators categorised as seven treatment factors utilised in the management of type 2 diabetes namely: Cholesterol, blood pressure and glycaemia control; medication and lifestyle management; cardiovascular risk management and patient education using the Delphi process. Methods: A Delphi questionnaire consisted of 29 Part 1 and nine Part 2 indicators which were incorporated into a tool called Simpler™. The indicators were mainly sourced from American, Australian and Malaysian diabetes management guidelines. Diabetes experts were asked to rank indicators in the order of importance in Part 1. In Part 2, indicators had to be chosen for inclusion into Simpler™ using a fivepoint Likert scale. The consensus level was pre-set at 60%. Results: A three round Delphi process was used to validate all 38 indicators by 12 experts from Australia and Malaysia: five pharmacists, four doctors, two endocrinologists and a diabetes nurse. Consensus was reached for 93.1% (27/29) of the Part 1 indicators and all nine Part 2 indicators (100%). Five out of nine indicators in Part 2 questionnaire obtained consensus disagreement for inclusion into the Simpler ™ tool. Conclusion: The Simpler™ tool is the first structured diabetes multifactorial tool to address all seven evidence-based factors. The tool was refined and validated by multi-disciplinary health professionals from Australia and Malaysia. Pharmacists can use the Simpler™ tool to facilitate evidence-based comprehensive individualised care among type 2 diabetes patients.