Current Diabetes Reviews - Volume 13, Issue 1, 2017

Introduction: Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 350 million people worldwide. Also, another one billion people in the world are pre-diabetic, who may eventually end up with full- blown diabetes. It costs around 1,200 billion USD to diagnose, treat and care for both type 1 DM (T1DM) and type 2 DM (T2DM) patients globally. The disorder is rapidly increasing out of proportion in both developed and developing countries, especially T2DM, which is associated with modern lifestyle habits such as reduced physical activity, diet, obesity and genetic factors. If left untreated, DM can lead to a number of diseases and long-term complications leading subsequently to death. Areas Covered: In this mini review, we aim to highlight a number of complications, cascades or pathways (polyol, hexosamine, protein kinase C, advanced glycation-end product) of events and cellular, sub-cellular and molecular mechanisms associated with DM-induced hyperglycaemia (HG). Conclusion: Chronic complications of DM are caused largely by HG-induced cellular and molecular impairment of neural and vascular structure and function. HG-induced oxidative stress is a major contributor in the development of long-term complications of DM. DM-induced neuropathy and angiopathy, in turn, may lead to the dysfunction of cells, tissues and organ systems.

Introduction: Waist circumference does not distinguish subcutaneous from visceral adipose tissue, which is highly associated with impaired cardiometabolic profile and type-2 diabetes mellitus (T2DM). Because of the complexity of the assessment of visceral fat with imaging techniques, easy-to-apply and low-cost anthropometric measures have been proposed. The aim of the study was to show a possible association between Lipid Accumulation Product Index (LAP Index), Deep-abdominal adiposity tissue Index (DAAT) and Visceral Adiposity Index (VAI) with metabolic profile and adipokines in obese subjects with and without T2DM, and to compare the results with the use of waist circumference isolated. Methods: In this cross-sectional study, we enrolled 101 outpatients with obesity (BMI ≥ 30 kg/m2) of which 48% with diabetes and aged 48.9 ±13.3 years. Demographic, clinical and anthropometric data were collected. Plasma C-reactive protein, interleukin-6, vascular adhesion molecule type 1 and adiponectin levels, lipid profile and fasting glucose were assessed. LAP Index, DAAT and VAI were calculated and body composition was evaluated by bioelectric impedance analyses. Continuous variables were described as mean ±standard deviation, and categorical variables as absolute numbers and percentages. Nonparametric data were log-transformed and Student’s t test, Wilcoxon-Mann-Whitney and chi-squared test, Pearson correlation and multiple linear regression were used for statistical analyses. Results: In total, 31 men and 70 women were evaluated. Individuals with T2DM showed higher LAP values and percentage of body fat and lower waist circumference and BMI values. DAAT and LAP were positively correlated with BMI, waist circumference, percentage of body fat and free fat mass. After adjustment for age, sex and total body fat, both LAP Index and VAI were associated with plasma adiponectin, LDL-cholesterol, non-HDL cholesterol and VLDL-cholesterol in obese with and without T2DM (all P values ≤ 0.02); fasting glucose remained associated with LAP in obese patients without T2DM (P= 0.01). Waist circumference only correlated with adiponectin in obese subjects without T2DM (P= 0.048). Conclusions: Our data suggest that VAI and LAP Index are good predictors of an impaired cardiometabolic setting in obesity regardless of T2DM status. Besides, we were not able to find associations with waist circumference and biochemical markers in our sample.

Background: It is well established that there is an important genetic predisposition for type 2 diabetes mellitus (T2DM). Objective: To summarise available epidemiological data regarding T2DM transmission in various populations. Method: Narrative review. Results: The estimated risk for the diagnosis of T2DM increases approximately by 2-4 times, when father, mother or both have this condition. Conversely, many T2DM patients have family members with DM. Studies have suggested that the likelihood of T2DM in the next generation is higher in the event of a diabetic mother than father. Both genetic factors, such as mitochondrial DNA mutations, and environmental components, such as intra-uterine environment, have been implicated in the higher maternal transmission of T2DM. Despite the above findings, some studies in populations with high frequency of T2DM have not corroborated the predominantly maternal transmission. Such works have shown either an excess paternal or an equal transmission of T2DM. Conclusion: It appears that potential biases in reporting family history data, especially between the various racial groups, have contributed to the controversy over the existence of excess maternal transmission of DM.

Background: Diabetic eye disease is the most common cause of blindness worldwide in the population under 65 years of age. The prevalence of sight-threatening diabetic eye disease continues to rise rapidly, resulting in an increasing burden on health systems worldwide. This highlights the need to develop new tools to help in the screening, diagnosis and management of diabetic eye disease. Purpose: This review aims to provide a brief overview of the current standard in care for diabetic eye disease, before providing an up to date overview of newer imaging modalities, with potential application in the management of diabetic eye care. Methods: A literature search for the terms “enhanced depth imaging OCT”, “swept source OCT”, “retinal oximetry”, “OCT angiography”, “fundus autofluorescence” with the term “diabetes” was performed using the pubmed and google scholar databases. Only articles published within the last two years were selected for use in this article. Discussion: There has been a rapid increase in the available imaging techniques used to manage diabetic eye disease. To date there has been variable use of these next generation imaging techniques. A greater understanding of how phenotypic findings link to the risk of sight loss is required before there is more widespread adoption by mainstream diabetic eye services.

Background: Recent interest has emerged regarding the effects of Very Low Calorie Diet (VLCD) in people with type 2 diabetes (T2D). We therefore performed a systematic review to investigate the effects of VLCD on HbA1c, weight and cardiovascular risk profile outcomes as well as its safety and tolerability among people with T2D. Methods: We conducted searches of Cochrane Database of Systematic Reviews, Centre for reviews and Dissemination databases, Medline, Embase, Pubmed, Web of Science, Web of Knowledge and Turning Research into Practice (TRIP) as well as ongoing trial resources. We included all studies involving VLCD and diabetes published until December 2013. Outcome measures include weight, HbA1c, fasting glucose, fasting insulin, lipid profile, blood pressure, safety and drop out rates. Results: 17 studies were included in the systematic review. Duration of VLCD duration ranged from 5 days to 6 months and duration of follow up ranged from 8 days to 5 years. The age range was 14 years to 59 years of age. Mean weight loss was 13.2kg, ranging from 4.1 to 24kg. Mean Hba1c reduction was 1.4% (ranging between 0.1 to 3.1% reduction across different studies). Three studies reported a significant reduction in the daily doses of insulin. All studies which reported cardiovascular risk profile showed a significant decrease in total cholesterol, systolic and diastolic blood pressure post VLCD. Apart from two studies, all of the other studies showed that the decrease in blood pressure and total cholesterol was not only present immediately post VLCD, but it was also maintained at follow up. However it is important to note that the follow up periods did differ between studies. Overall, drop out rates ranged from 4.7% to 33% and appeared to be lower during the active intervention phase compared with during the follow-up period. No major adverse event was reported apart from one study which recorded a non-fatal myocardial infarction. Conclusion: This review demonstrated that VLCD in people with T2D was associated with significant weight loss, reduction in blood glucose profile and improvement in cardiovascular risk profile, high tolerability and good safety outcomes. Studies were heterogeneous and longer term outcomes data post VLCD is still required.

Background: Serum CA19-9 level is a sensitive marker for pancreatic tissue damage; however, its correlation factors are still unclear in diabetic patients. This study was aimed to investigate the correlation factors of serum CA 19-9 levels in these patients. Methods and Results: Based on their serum CA19-9 levels, 412 diabetic patients (57 type 1 and 355 type 2) were divided into the negative group (432 cases, CA19-9 < 37 U /ml) and the positive group (31 cases, CA19-9 ≥ 37 U /ml). The two groups were compared with age, sex, duration of diabetic history, hemoglobin A1c, blood lipid, fasting C-peptide level, and area under the curve C-peptide. The difference was significant between 2 groups in age, hemoglobin A1c, total cholesterol, highdensity lipoprotein cholesterol, fasting C-peptide level, and area under the curve C-peptide (P < 0.05). A multivariate linear regression model found that the type of diabetes, hemoglobin A1c, area under the curve C-peptide, and high-density lipoprotein cholesterol are the independent contributors to CA19-9 levels. Conclusion: The results indicated that CA19-9 levels in patients with diabetes mellitus were related to not only age and sex but also diabetic type, hemoglobin A1c, lipid metabolism, and pancreatic beta cell function.

Background: Diabetes mellitus (DM) and osteoarthritis (OA) are two of the most relevant and common chronic diseases affecting older people. Both DM and OA are considered metabolic diseases due to their high correlation with the capacity of the body to metabolize some nutritive substances such as glucose, fat, vitamins and also the response to oxidative molecules. Methods: We searched PubMed, Scopus, Google Scholar, and authors' bibliographies in order to extract articles regarding the relationship between DM and OA. Objective: The main purpose of this review is to investigate the molecules involved in the onset and progression of both DM and OA and the beneficial role of physical activity. Results: The main focus is on the importance of glucose metabolism and its derivatives in the pathogenesis of OA and DM. Advanced glycation end-product (AGEs), sorbitol and diacylglycerol (DAG) are glucose derivatives which promote the activation of several pathways, most of them involved in the activation of inflammatory processes. The possible link between DM and OA is represented by the inflammatory process deriving from the increased expression of pro-inflammatory cytokines. Moreover, we investigated the biological mechanisms and the clinical findings that confirm a beneficial effect of physical activity in both DM and OA. Conclusion: Thus a tailored and adapted physical activity can be used in the treatment of both diseases as a part of a correct and healthy lifestyle. For this reason we strongly suggest the scientific community to introduce mild physical activity as part of our lifestyle to prevent metabolism diseases and osteoarthritis.

The World Health Organization has ranked Saudi Arabia as having the second highest rate of diabetes in the Middle East (7^th highest in the world) with an estimated population of 7 million living with diabetes and more than 3 million with pre-diabetes. This presents a pressing public health problem. Several challenges in diabetes management need to be tackled in Saudi Arabia, including the growing prevalence (chiefly among children and young adults), micro-and macrovascular complications, lifestyle changes, late diagnosis, poor awareness and high treatment costs. Over the last two decades, the Saudi population saw an increase in the expenses in healthcare and treatment of diabetes by more than 500%. In 2014, the health care budget was 180 billion (Saudi Riyal) of which 17 billion was spent on all Saudis, with an approximate 25 billion on the entire Saudi diabetic population. This implies that the direct expense of diabetes is costing Saudi Arabia around 13.9% of the total health expenditure. Therefore, unless a comprehensive epidemic control program/ multidisciplinary approach is stringently enforced, the diabetes mellitus burden on Saudi Arabia will probably increase to very serious levels. It is crucial to implement improved health and health-related quality of life of to those with diabetes, thus minimizing the social and personal expenses for diabetes care in Saudi Arabia. In this study we discuss the significant and major threats posed by diabetes mellitus to the Saudi population and recommend essential possible solutions to delay/ prevent this formidable issue.

Non-communicable diseases (NCDs; including coronary heart disease and type 2 diabetes) are rapidly increasing in India causing nearly 5.8 million deaths per year. Primary reasons for rise in NCDs in India are nutrition and lifestyle transitions. Further, presence of higher body fat, abdominal fat, liver and pancreatic fat and lower lean mass than whites, contribute to heightened metabolic and cardiovascular risk in Asian Indians. Importantly, conversion from pre-diabetes to diabetes occurs more rapidly, and reversion to normal glucose regulation with appropriate lifestyle measures is more difficult in Asian Indians than white population. Huge number of patients with diabetes and with complications increase morbidity, mortality and pose substantial economic burden. It is difficult, though not impossible, to decrease pace of rapidly expanding juggernaut of NCDs in India. Only concerted efforts from multiple stakeholders, consistently sincere efforts and intensely focused attention from health officialdom and clear political will may help counter this increasingly difficult challenge. Finally, all prevention and management approaches should be cost-effective, pragmatic, and focused on children and underprivileged populations.

Background: There are growing evidence that indicate a relation between diabetic microangiopathy and cardiovascular disease with different mechanism. Objective: To investigate the association of diabetic retinopathy (DR) with the risk of cardiovascular disease (CVD) in type 2 diabetic patients. Methods: 180 type 2 diabetic patients who were free of CVD at baseline were enrolled. Patients were classified according to fundoscopy to no diabetic retinopathy (NDR), non proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). CVD risk at 10 years was estimated using the UK Prospective Diabetes Study risk engine and patients were classified as high risk (>20%), moderate risk (10-20%) and low risk (<10%). Results: Prevalence of DR was 30.5%. Risk of CVD was significantly higher in PDR vs NDR (18.7±10.0% vs. 11.3±8.4%, p= 0.01) .The prevalence of NPDR (32% vs. 17.8%, p=0.002) and PDR (20% vs. 4.1%, p=0.04) was more in high risk group for CVD in comparison with low risk group for CVD. After adjustment for traditional risk factor for CVD, the risk for CVD remained markedly increased in the presence of DR. Conclusion: DR is associated with estimated risk of CVD in type 2 diabetic patients.

Hyperuricemia leads to insulin resistance, whereas insulin resistance decreases renal excretion of uric acid, both mechanisms link elevated serum uric acid with metabolic syndrome. The aim of this study is to evaluate the probability for the development of metabolic syndrome in low-income young adults with hyperuricaemia. Methods: We evaluated 103 patients less than 40 years of age, from a low-income population, and without history of cardiovascular disease, in all of them the presence of metabolic syndrome was assessed in accordance with the International Diabetes Federation criteria. In all patients, fasting serum uric acid levels were measured; hyperuricaemia was defined as serum uric acid values > 6.5 mg/dl in men and > 5.1 mg/dl in women. Statistical analysis was performed with odds ratio. Results: 83 of our patients (80.5%) suffered metabolic syndrome, the odds ratio for the presence of metabolic syndrome in patients with hyperuricaemia was 5.1 (p=0.002, I.C 1.8- 14.5). When patients were evaluated by gender a significantly association between hyperuricaemia and metabolic syndrome was found in women (odds ratio 3.6, p=0.048, C.I. 1.0-12.9), and men (odds ratio 10.2, p= 0.015, IC 1.5-13.2). When uric acid was correlated with the components of metabolic syndrome, we only found a positive correlation with waist circumference (r=0.483). Conclusion: Our results showed a significant association between hyperuricemia and metabolic syndrome in low-income young adults in Mexico. DR is associated with estimated risk of CVD in type 2 diabetic patients.

Background: In recent studies, we have incorporated bile acid and polyelectrolytes into pancreatic β-cell microcapsules and examined their cell viability and microcapsule morphology using various encapsulating methods. Objective: This study aimed to incorporate 3 colloids; ultrasonic gel (USG; 1%), polystyrenic sulphate (PSS; 0.1%) and polyallylamine (PAA; 3%) and ursodeoxycholic acid (UDCA; 4%) with the polymer sodium alginate (SA; 1.2%) and the copolymer poly-L-ornithine (PLO; 1%), and using a refined vibrational jet-flow microencapsulating method, test the microcapsule properties, and cell viability without or with UDCA. Method: The pancreatic β-cells NIT-1 were encapsulated using concentric nozzles and a refined method using voltage > 600 mv and frequency of 1750 Hz with syringe flow of 1.5 ml/min (core) and formulation solution of 2.1 ml/min, with a mixture of SA, PLO, USG, PSS and PAA without UDCA (control) or with UDCA (test). Both formulations and microcapsules were examined for surface composition and thermal and chemical biocompatibilities. The microencapsulated cells were examined for bioenergetics and production of inflammatory biomarkers. UDCA distribution within the microcapsules was also examined. Results: Using our method, viability remained low after the addition of PSS, PAA and USG, while the incorporation of UDCA enhanced cell viability, and thermal stability was maintained. Conclusion: Our refined microencapsulating method, when incorporating polystyrenic sulphate, polyallylamine, the gel and UDCA at 0.1:3:1:4 ratio respectively, produced stable microcapsules suggesting potential applications in cell microencapsulation and diabetes treatment.

Background: Depression and anxiety can potentially influence treatment results of diabetic complications. Objective: Of our study was to explore: (1) prevalence of these disorders in patients with diabetic foot ulcers (DFU); (2) possible risk factors of depression and anxiety; (3) possible links between ulcer treatment results and depression/anxiety status. Methods: 285 outpatients with diabetes and foot or leg ulcers were tested for depression and anxiety with self-report scales: CES-D and the anxiety subscale from HADS. Ulcer treatment results, incidence of new ulcers and number of hospital admissions were assessed after 1.5 years of follow-up. Results: Depression was detected in 110 patients (39%), anxiety in 103 (36%). Females had depression and anxiety more often than males (48% and 46% vs. 27% and 25% respectively). A combined score based on diabetes duration, insulin treatment, history of myocardial infarction, history of foot ulcers and recent foot surgery was higher in patients with than without depression (3.0 vs. 2.0, p=0.02). Every of these or other potential risk factors alone was not associated with depression or anxiety. Patients with depression did not demonstrate poorer prognosis except higher mortality in subgroup of severely depressed patients without ulcer history. For anxiety we got similar results as its presence strongly correlated with depression. Conclusion: The overall prevalence of depression and anxiety in DFU patients is compatible with other diabetic populations. Various parameters of ulcer severity and duration did not influence the probability of depression and anxiety occurrence. Depression in general was not associated with poorer ulcer treatment results.