Current Diabetes Reviews - Volume 14, Issue 3, 2018

Background: Diabetes has turned into a pandemic disorder that is affecting millions of people worldwide. Industries are aggressively racing and pursuing research towards the discovery of antidiabetic drug and the current global sale of such drugs are ever on the increase. However, in spite of such massive level of expenditure thereof, WHO projects that by 2030, diabetes will rank as the 7th leading cause of mortality. Objective: It is in this context that we have reviewed here the various approaches available and possible towards diabetes management. This review also includes the WHO guidelines for controlling the glycemic levels, which must be known and followed by clinicians for a better diabetes management. Conclusion: Despite having a wealth of FDA-approved therapeutic options for type 2 diabetes majorities of the patients are not able to achieve the appropriate glycemic control due to various factors. The development of new options with actions at multiple foci of diabetic manifestation and better efficacy may potentially help in improving the current scenario of T2D management.

Introduction: Gastroparesis (a complication of both type 1 and type 2 diabetes mellitus) is delayed gastric emptying in the absence of a mechanical obstruction. Overall prevalence of Gastroparesis is close to 5 % in type 1 diabetes and 1 % in type 2 diabetes. It is unclear if good glycemic control leads to the delay of development and progression of gastroparesis. Methods: Gastric enteric neurons as well as Interstitial Cells of Cajal (ICC) are depleted, truncated and are surrounded by immune infiltrates composed of macrophages. There are associated vagal nerve innervation abnormalities, smooth muscle and Fibroblast Like Cell (FLC) dysfunctions. There is s decrease in HO-1 macrophages and increase in proinflammatory macrophages. Gastric electrical rhythm abnormalities and channelopathies have been implicated in the pathology of gastrointestinal diseases. Results: In patients with diabetes, the most common clinical symptoms include abdominal bloating and pain. Nuclear Medicine Gastric Emptying Scintigraphy (NMGES) is considered the gold standard for evaluation of gastroparesis. Conventional imaging techniques such as fluoroscopic evaluation of gastric emptying can only evaluate the presence or absence of an obstruction. Historically, solid gastric emptying has been the method for evaluation although recent data suggests that liquid gastric emptying may be altered without solid gastric emptying abnormality. It is paramount that a radiotracer for evaluating gastric emptying be tightly bound to ingested food (solid). The most frequent radiotracer used is Tc99msulfur colloid bound to egg whites. In an effort to standardize normal values across institutions, a consensus recommendation published in 2008 called for a 4- hour study utilizing a standardized meal. Conclusion: Nuclear Medicine Gastric Emptying Scintigraphy (NMGES) is the test of choice for evaluation of diabetic gastroparesis. Standard guidelines have been established for the performance and interpretation of the test.

Background: Diabetes is a demanding disease that is growing in prevalence. Improved outcomes for patients with diabetes are highly dependent on self-management skills and the ability to make lifestyle changes. Innovative healthcare approaches are necessary to meet these specific patient needs. A group care medical visit (GMV) combines diabetes check-ups with diabetes education in a supportive and patient centered environment that promotes effective self-management. GMVs are associated with improved diabetes outcomes including hemoglobin A1C, weight, and self-efficacy; however details of the methods by which content is delivered to achieve these outcomes remain vague. Introduction: Improved GMV diabetes outcomes may be the result of specific processes used in group care models. We seek to describe educational strategies, content, and qualities of facilitators that contribute to successful outcomes associated with diabetes GMVs. Methods: A review of the literature was conducted focusing on diabetes GMVs, specifically the educational strategies implemented, topics discussed, and facilitator qualities that contribute to successful outcomes. Results: We identified 260 citations containing information about GMVs in patients with diabetes. A total of 7 citations met inclusion criteria and additional 5 were found through reference lists and relevant papers. Conclusion: Diabetes GMV educational topics comprise standard themes of disease process, medication, nutrition, and exercise. Several programs, however, target the development and realization of individualized patient goals, giving the patient more involvement in the session. Methods for facilitation may hold the key to successfully activating patients to reach meaningful behavior change goals. In addition to using expert clinical skills in diabetes care, effective facilitators provide support, and empower patients to take ownership of their diabetes. Rigorous evaluation of best practices for both the type and methods of delivering content in GMVs is lacking. Translational research to evaluate the relative effectiveness of educational strategies can be leveraged toward the successful scale and spread of this innovative primary care model.

Introduction: Diabetes Mellitus (DM) is a metabolic disorder characterized by chronic hyperglycaemia, which is attributed to several life threatening complications including atherosclerosis, nephropathy, and retinopathy. The current therapies available for the management of DM mainly include oral antidiabetic drugs and insulin injections. However, continuous use of synthetic drugs provides lower healing with many side effects. Therefore, there is an urge for safe and efficient antidiabetic drugs for the management of DM. In the continuing search for effective antidiabetic drugs, marine algae (seaweeds) remains as a promising source with potent bioactivity. It is anticipated that the isolation, characterization, and pharmacological study of unexplored marine algae can be useful in the discovery of novel antidiabetic compounds with high biomedical value. Among marine algae, brown and red algae are reported to exhibit antidiabetic activity. Majority of the investigations on algal derived compounds controls the blood glucose levels through the inhbition of carbohydrate hydroloyzing enzymes and protein tyrosine phosphatase 1B enzymes, insulin sensitization, glucose uptake effect and other protective effects against diabetic complications. Conclusion: Based on the above perspective this review provides; profiles for various marine algae posessing antidiabetic activity. This study also highlights the therapeutic potential of compounds isolated from marine algae for the effective management of diabetes and its associated complications.

Background: The global epidemic of obesity will see normal weight adults constituting a mere one-third of the global population by 2025. Although appetite and weight are regulated by a complex integration of neurological, endocrine and gastrointestinal feedback mechanisms, there is a constant interaction between psychological state, physical impairment, presence of comorbid chronic disease and medications. Methods: We discuss two cases and reveal a practical approach to investigating and managing patients with obesity and diabetes in the ‘real world’. Within this scope, the aetiology, associated disease burden, and pharmacological therapies for the treatment of the obese patient with type 2 diabetes are reviewed. An insight into non-surgical metabolic rehabilitation is also provided. Summary: Lifestyle, including diet, exercise, medications, as well as genetic predisposition, and rarely, endocrinopathies should be considered in the assessment of the obese patient. Investigations are not complex and include cardiometabolic and nutritional screens and an assessment for institution of graded, safe levels of exercise. In more complicated patients, referral to a multidisciplinary outpatient program may be necessary and it is not uncommon for patients to lose between 10-20% of their initial weight. Despite this, metabolic surgery may be necessary as further weight loss with long-term weight maintenance may be medically indicated. The type of surgery is tailored to the patient's medical risk and co-morbidities as well as likelihood of compliance with the required follow-up. Conclusion: It is the opinion of the authors that metabolic rehabilitation should be intensive, multidisciplinary, and have a supervised exercise program, as the gold standard of care. These suggestions are based on the clinical pearls gained over two decades of clinical experience working in one of Australia's most innovative multidisciplinary metabolic rehabilitation programs caring for patients with severe obesity.

Background: Despite its well-established health benefits, exercise imposes challenges on glucose control in individuals with type 1 diabetes due to the complex interactions between exerciseinduced effects on glucose metabolism and exogenous insulin therapy. Although clinical guidelines for exercise management in type 1 diabetes are available, implementation is challenging in daily life. The risk of exercise-induced dysglycaemia deters many people with type 1 diabetes from participating and benefitting from exercise. Rapid progress has been made in the development of closed-loop systems, also known as the artificial pancreas. The autonomous modulation of insulin delivery in a glucoseresponsive manner by closed-loop systems may be beneficial in addressing and overcoming the risk and burden of exercise-induced dysglycaemia. Methods: A summative overview of closed-loop application during exercise in type 1 diabetes is discussed, outlining current evidence and limitations, our perspectives in the field and future outlook. Results: Outcomes from clinical studies evaluating both single- and dual-hormone closed-loop during exercise are reported. Current approaches to enhance closed-loop performance during exercise are described. Conclusion: Closed-loop system has the potential to ameliorate exercise management in type 1 diabetes. Promising results have been shown, however innovative approaches are still needed to overcome inherent limitations of closed-loop performance during exercise. Future studies in larger generalizable patient population during real-life settings are still needed, to further evaluate its clinical applicability.

Background: Most of the current understanding of type 1 diabetes (T1D) etiology and pathogenesis stemmed from studies conducted in majoritarily Non-Hispanic White (NHW) populations. However, evidence is emerging that unique mechanisms of disease may contribute to the development of T1D in individuals of Hispanic ethnicity. Objective: We reviewed the currently available literature on genetic, immunologic, metabolic and clinical characteristics of T1D in Hispanic as compared with NHW individuals. Methods: We searched PubMed, Google Scholar, and authors' bibliographies to collect information from relevant articles on the influence of ethnicity on T1D etiology and pathogenesis. Results: There are significant epidemiological variation based on ethnicity, with consistently higher T1D incidence and prevalence rate in NHWs than Hispanics. The frequencies of T1D high-risk HLA haplotypes and genotypes, as well as their susceptibility or protective effects show considerable ethnic differences. There are conflicting data on immunologic factors (e.g. islet autoantibody positivity) and markers of beta-cell function (e.g., C-peptide levels), as well as in some clinical characteristics (e.g. frequencies of diabetic ketoacidosis and severe hypoglycemia), while age of onset is consistently similar between both groups. Higher prevalence of obesity, less intensive diabetes management, and poorer glycemic control were reported in Hispanics. Accordingly, ethnic disparities in clinical outcomes have been demonstrated as well. Conclusion: There are considerable differences in T1D characteristics between NHWs and Hispanics. Better insight into these ethnic differences would not only affect patient care of patients with T1D, but may also inform the design of future prediction and prevention trials.

Background: Cardiovascular disease is the leading cause of death in patients with type 2 diabetes. Objective: To assess the impact of glucagon-like peptide-1 receptor agonist (GLP1RA) therapy, compared to placebo, on clinically relevant outcomes including all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalizations for heart failure, in patients with type 2 diabetes. Methods: EMBASE, MEDLINE, and CENTRAL were searched (inception to September 2016) for randomized, double-blind, placebo-controlled trials of at least one year in duration that compared any GLP1RA to placebo in patients with type 2 diabetes. Both authors independently completed the literature search, data extraction, and risk of bias assessment. For each outcome, a Risk Ratio (RR) and 95% Confidence Interval (CI) were calculated using a Mantel-Haenszel random effects model. Results: Eight trials (three albiglutide, two lixisenatide, two liraglutide, one semaglutide) consisting of 21,135 patients were included. Most patients had, or were at high risk for, cardiovascular disease. Follow- up ranged from 1-3.8 years. Trials contributing the majority of data were deemed to have a low risk of bias. The risk of all-cause mortality was lowered by 11% in patients receiving a GLP1RA (RR 0.89, 95% CI 0.81-0.99). There was no statistically significant difference between groups with respect to cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalizations for heart failure. Conclusion: GLP1RA therapy when compared to placebo reduced all-cause mortality in high cardiovascular risk patients with type 2 diabetes. They did not impact cardiovascular mortality, nonfatal MI, nonfatal stroke, or heart failure hospitalizations.

Background: Androgen Deficiency in Aging Male (ADAM) questionnaire is increasingly popular for the evaluation of testosterone deficiency (TD) in Sub-Saharan African men with type 2 diabetes mellitus (T2DM). However, its reliability in this population is unknown. Objective: To evaluate the reliability of the ADAM questionnaire for the clinical detection of testosterone deficiency in Sub-Saharan African men with T2DM. Methods: Total testosterone < 8nmol/L was used as gold standard for diagnosis of TD in a crosssectional survey of 200 males with T2DM aged 30-69 years. Participants also completed the Saint Louis University ADAM questionnaire whereby TD was diagnosed by a “yes” answer to question 1 (reduced libido) or 7 (erectile dysfunction) or any other three questions. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy of the ADAM tool were computed. Results: The mean age of the participants was 58.0 ± 8.8 years. 142 subjects (71.0%) had TD based on the ADAM questionnaire. However, TD was biochemically confirmed in 59 subjects (29.5%). ADAM questionnaire rendered sensitivity of 88.1%, specificity of 44.7%, PPV of 50.0%, NPV of 85.7% and accuracy of 61.4%. Low libido alone had better specificity (75.5%) and accuracy (73.2%) than the entire questionnaire. Conclusion: Despite an impressive sensitivity, the low specificity and overall accuracy of the ADAM questionnaire makes it unreliable for the detection of AD in Sub-Saharan African men with type 2 DM. However, presence of a sustained low libido appears to be a reliable pointer to underlying testosterone deficiency requiring biochemical confirmation.

Background: Recent studies have shown an inverse relationship between diabetes and prostate- specific antigen (PSA) levels. Objective: This study aimed to evaluate the PSA levels in the serum of diabetic and non-diabetic Moroccan males. Methods: In a cross-sectional study, four hundred and seventy diabetic and 869 non-diabetic males were screened from January 2015 to April 2016 at Pasteur institute of Morocco. Hemoglobin A1c and Fasting Blood Glucose were measured using high performance liquid chromatography and dry chemistry, respectively. We used a chemiluminescent microparticle immunoassay technology to evaluate the levels of Serum PSA and testosterone. Results: Overall, the PSA levels revealed no significant difference between diabetic and non-diabetic males (1.31 ± 0.04ng/mL vs.1.36 ± 0.03ng/mL, p = 0.380, respectively). The PSA levels increased with age both in non-diabetics and diabetics. Moreover, in diabetic subjects, the PSA levels were less age dependent (p =0.002) than in non-diabetic (p < 0.0001). The stratified analysis showed that the PSA was significantly lower in diabetic than in non-diabetic subjects aged between 50-59 years (p= 0.0004). Furthermore, no significant testosterone concentrations were observed in the subjects with or without diabetes (p= 0.904). Conclusion: Our results show that the PSA levels are age-dependant in diabetic and non-diabetic males but the PSA levels are affected by diabetes status only in the group aged between 50-59 years.

Introduction: Insulin resistance may develop with Type 1 diabetes. Insulin resistance is currently recognized by the estimated glucose disposal rate. Serum fetuin has been accused as a risk factor for metabolic syndrome. Aim: To determine the relationship between the serum fetuin and insulin resistance in Type 1 diabetes subjects and the effect of short-term Metformin therapy on this relationship. Methods: 40 T1DM male ≥ 18 years of age were screened for insulin resistance (defined using estimated glucose disposal rate). 20 subjects (Group I) were insulin resistant with a mean estimated glucose disposal rate of (7.15±0.37 mg/kg/min) while 20 subjects (Group II) were non-insulin resistant with a mean estimated glucose disposal rate of (9.08±0.42 mg/kg/min). Fasting blood sugar, 2 hours-post prandial blood sugar, HbA1c%, C-peptide, lipid profile, highly sensitive-C reactive protein, and serum fetuin were assessed. Group I were given 1gm Metformin twice daily for 3 months as an add-on to their insulin regimen. All anthropometric and laboratory parameters were reassessed at the end of the 3 months. Results: Group I had a higher age, BMI and waist/hip ratio, FBS, PPBS, HbA1c%, TC, LDL-C, TG, Hs-CRP and serum fetuin (ρ ≤ 0.001), and a lower C-peptide (ρ=0.001). Fetuin showed a positive correlation with age, FBS, HbA1c%, and Hs-CRP. After Metformin therapy, FBS, PPB and HbA1c%, Hs- CRP and fetuin decreased (ρ≤0.001) while eGDR and insulin dose in units/kg increased (ρ <0.001). Correlation after Metformin therapy within Group I showed that eGDR was inversely related with FBS and PPBS and fetuin showed a positive correlation with Hs-CRP. Conclusion: Serum fetuin was elevated in insulin resistant T1DM, yet this was not associated with eGDR. Levels of fetuin-A and HsCRP decreased after Metformin therapy.

Background: Hypogonadism in male patients with diabetes mellitus is associated with older age, obesity and poor glycaemic control. The patterns of sperm count, testicular volume, sperm motility and morphology have also been reported to be abnormal in these patients, though reports are conflicting. The objectives of this study were to assess gonadal function and sperm parameters in Nigerian males with diabetes mellitus. Methods: A study sample of 150 males consisting of 108 patients and 56 age-matched controls were recruited. The ADAM questionnaire was used to obtain a clinical score for hypogonadism. Laboratory parameters measured were fasting plasma glucose, serum LH, FSH, free testosterone, total cholesterol, LDL, HDL and triglyceride. Testicular volume was measured with a Prader orchidometer. Total sperm count, sperm morphology and motility were assessed. Results: Hypogonadism was present in 38.9% of males with diabetes compared to 3.6% in controls. The patients with diabetes had significantly lower sperm count, reduced sperm motility with increased abnormal forms than the controls (p<0.001, p<0.001). Only 8.5% of the patients did not demonstrate any abnormality in testicular function. Conclusion: Poor sperm function was more common than hypogonadism and was associated with poor glycaemic control (p<0.001). Likewise, hypogonadism was significantly associated with poor glycaemic control (p<0.001).

Background: Diabetes is the third widespread after heart disease and cancer. We have investigated genetic polymorphisms in cytokine genes viz. IL-4, IL-1Ra, IL-1β, IL-18, IL-6, TNF-α, IL-10 and ADIPOQ. The aim of study was to investigate the haplotypes, gene-gene interactions and their role in determining individual susceptibility to T2DM of family members with diabetic history. Methods: Haplotype analysis of 2 SNPs each in IL-6 and adiponectin genes showing Pairwise Linkage disequilibrium (LD) was done by SHEsis software. Logistic regression was used to study various combinations of gene-gene interactions. Results: The TCGT* set of allele combination appeared to increase the disease risk upto 2 times while TATG* upto 51.4 times when four SNPs are taken together viz. IL-1β-511 C/T, IL-18-607 A/C, ADIPOQ1 +45 G/T and ADIPOQ2 +10211 T/G. Interaction of SNPs in eight genes showed one highly significant combination of alleles, TCGAGCTT* which increased the risk of T2DM upto 7.4 times while CAGAGCGT* allele combination increased the risk upto 4 times. Conclusion: During pedigree analysis in six families with four SNPs, it was interesting to note that susceptible ‘AC’ genotype of IL-18-607 A/C was frequent in diabetic individuals in almost all families. Moreover, when checked for the presence of risk haplotypes it was observed that TCGT* and TATG* sets of allele combinations were present in most of the diabetic individuals. Individuals with certain abnormal biochemical parameters but not yet diagnosed for T2DM carried the risk genotype or haplotype. This suggested that individuals carrying risk genotypes/haplotypes might be susceptible to T2DM and develop the disease in the future.