Current Diabetes Reviews - Volume 14, Issue 2, 2018

Background: Carbonic anhydrase is a ubiquitous zinc metalloenzyme in organisms that primarily catalyzes the reversible hydration of CO2 to HCO3 - and H+. It is involved in many important physiological and pathological conditions such as electrolyte secretion and biosynthetic reaction like gluconeogenesis, lipogenesis and ureagenesis. The enzyme provides HCO3 - as a substrate for pyruvate carboxylase, the first enzyme in hepatic gluconeogenesis. The present review showed that carbonic anhydrase is the main driver of hepatic gluconeogenesis. Methods: Google scholar and Medline Embase (inception to 2015) were searched for studies on mechanism of hepatic glucose production, increased hepatic glucose production in diabetes and changes in carbonic anhydrase activity in diabetes and its treatment. Results: Many studies have linked changes in carbonic anhydrase activity with the development and progression of diabetes mellitus. Carbonic anhydrase has been shown to provide HCO3 - as substrate for the first reaction of hepatic gluconeogenesis which has also been reported to increase significantly in type 2 diabetes. Increase in carbonic anhydrase activity increases the availability of these substrates and in turn increases hepatic glucose production. Conclusion: Carbonic anhydrase can be said to be the key factor responsible for reduction of hepatic glucose production. Thus carbonic anhydrase could serve as a new therapeutic target for reducing hepatic glucose production.

Background: Prevalence of Type 2 Diabetes Mellitus (T2DM) has reached pandemic levels in the Western societies. T2DM begins with the development of peripheral insulin resistance which prior research suggests may commonly originate within the skeletal muscle. A number of mechanisms have been proposed for the development of muscle insulin resistance including those of classical glucose handling, and also other cellular derangements observed in this disease which include mitochondrial degeneration, alterations in muscle protein turnover and early evidences for dysregulation of the microRNAs. The purpose of the current review is to examine the current findings on these latter aspects of mitochondrial maintenance, protein turnover and microRNA dysregulation along with the potential implications for these derangements in the development of insulin resistance and hence T2DM. We summarize multiple evidences for the degeneration of mitochondria and known elements of the processes regulating mitochondrial quality. Subsequently, we examine current findings of the alterations in muscle protein synthesis and autophagic protein degradation in T2DM and potential feedback of these systems onto canonical insulin signaling. Finally, evidences have emerged for the dysregulation of microRNAs in muscle insulin resistance. Of note early data point to several microRNAs altered by the insulin resistant state which exhibit relations to classic insulin signaling and the other processes discussed here. Conclusion: Considering that T2DM may be initiated with muscle insulin resistance, improved understanding of the dysregulation of these metabolic parameters of skeletal muscle in the pathogenesis of T2DM may be key to developing efficacious therapeutic modalities to prevent and treat this condition.

Background: Regular exercise improves glycemic control and reduces cardiovascular risk and mortality in patients with type 2 diabetes. Continuous moderate- to high-intensity exercise has been recommended to manage type 2 diabetes; however, only approximately 30% of diabetic patients achieve the recommended levels of physical activity. The reasons for not engaging in regular exercise vary; however, one of the common reasons is lack of time. Recently, the effectiveness of shortduration interval exercise such as high-intensity interval training and interval walking has been observed. Thus, the author aimed to summarize the current knowledge and discuss recent literature regarding the effects of interval exercise therapy in type 2 diabetes. Methods: The author searched the English literature on interval training and type 2 diabetes using Pub- Med. A total of 8 studies met the criteria. Results: Interval exercise is feasible and effective in obtaining glycemic control in patients with type 2 diabetes. It may also improve body composition, insulin sensitivity, aerobic capacity, and oxidative stress more effectively than continuous exercise. Conclusion: As a novel exercise therapy, interval training appears to be effective in managing type 2 diabetes. However, the safety and efficacy of this exercise modality in patients with progressed diabetic complications or a history of cardiovascular disease and in extremely older individuals remain unknown. Additionally, there is considerable heterogeneity in exercise interventions (intensity and duration) between clinical studies. Further studies are needed.

Background: Diabetes is a growing epidemic that is affecting Hispanics in high rates. Introduction: Although Hispanics use the internet for health-related informational and educational purposes, there is a lack of information available in the Spanish-language. Methods: A review was conducted to examine the literature on internet-based, Spanish-language, diabetes focused information. One search was conducted using three different databases (i.e. CINAHL, MEDLINE, and PubMed). The search used the keywords diabetes, internet, and Spanish, and was based on published articles from January 1, 2005 to June 30, 2016. Results: Of the 46 articles reviewed, one was a duplicate, and 41 were eliminated. These findings show a lack of data and research on Spanish-language, internet-based diabetes informational and educational sites. Conclusion: Qualitative and quantitative studies are needed to develop and examine Spanish-language diabetes internet sites and the health-related impact they have on Hispanics who prefer Spanishlanguage sites.

Introduction: Diabetic nephropathy is characterized by hypertension, progressive albuminuria, glomerulosclerosis and declines in glomerular filtration rate leading to end stage renal disease. Although the pathogenesis of diabetic nephropathy is not fully understood, current treatment of the patients with diabetic nephropathy is mainly based upon the control of hyperglycaemia and management of blood pressures. Background: Several drugs, which are originally developed for hypertension therapy, have been adopted for stabilization of renal function in diabetic nephropathy. In this review, we first discussed the relationships between diabetic nephropathy and hypertension particularly in the renin-angiotensinaldosterone system. We then summarized chemical structures, pharmacological characteristics and clinical studies of the common drugs used for treatment of diabetic nephropathy, while these drugs have effects against hypertension. Conclusion: This review may provide the constructive information for further drug development in diabetic nephropathy.

Background: Diabetic Nephropathy (DN), a serious and prevalent complication of diabetes, has been rapidly raising worldwide. Vaspin, as an adipokine with anti-diabetic effects, is predominantly released from visceral adipose tissue. Moreover, vaspin has the stimulatory effect on nitric oxide (NO) bioavailability through the activation of NO synthase. Objective: The aim of the present study was to investigate the serum levels of vaspin and their correlation with NO metabolite in diabetic patients with normal renal function and renal insufficiency. Methods: Volunteers patients with non-nephropathy Type 2 Diabetic Mellitus (T2DM) as control (n=40, age= 56.95±6.11 years) and patients with diabetic nephropathy (DN) (n=40, age=57.85±5.63 years) as case group were enrolled in this study, and serum samples were collected for the measurement of vaspin levels by ELISA technique. Also, serum levels of NO metabolites were calorimetrically assessed. Results: We found that vaspin levels significantly decreased in diabetic patients with nephropathic condition as compared with diabetic patients with normal renal function (p <0.04). In addition, serum levels of NO metabolites were significantly higher in diabetic patients with nephropathy in comparison with non-nephropathic diabetics (p<0.001). When patients with DN were studied, vaspin levels positively correlated with NO metabolites and Homeostasis model assessment of insulin resistance (HOMA-IR) levels. Conclusion: This study showed that low serum vaspin levels may be a risk factor for nephropathy in type II diabetic patients and increased levels of NO may be a defensive mechanism in the DN.

Background: Cotton-wool spots also referred as soft exudates are the early signs of complications in the eye fundus of the patients suffering from diabetic retinopathy. Early detection of exudates helps in the diagnosis of the disease and provides better medical attention. Methods: In this paper, an automated system for the detection of soft exudates has been suggested. The system has been developed by the combination of different techniques like Scale Invariant Feature Transform (SIFT), Visual Dictionaries, K-means clustering and Support Vector Machine (SVM). Results: The performance of the system is evaluated on a publically available dataset and AUC of 94.59% is achieved with the highest accuracy obtained is 94.59%. The experiments are also performed after mixing three datasets and AUC of 92.61% is observed with 91.94% accuracy. Conclusion: The proposed system is easy to implement and can be used by medical experts both online and offline for referral of Cotton-wool spots in large populations. The system shows promising performance.

Background: Self Monitoring of Blood Glucose (SMBG) is a useful adjunct to lifestyle modification and medications for optimal management of type 2 Diabetes Mellitus (DM). This study was aimed at evaluating the practice, cost and associations of SMBG in subjects with type 2 DM in Enugu, Nigeria. Methods: In a cross-sectional survey conducted at the diabetes clinic in three hospitals, 366 type 2 diabetic subjects aged 18-65 years were consecutively interviewed. Socio-demographic and clinical information were documented and glycated hemoglobin was performed for all the participants. Results: A total of 318 subjects with mean age of 49.0 ± 9.4 years completed the study. 304 subjects (95.6%) reported that they were aware of SMBG and 60.7% practiced SMBG at frequencies ranging from ≥ 1/day (7.9%), ≥ 1/week (26.1%) or < 1/week (26.7%). 39.3% of the respondents did not perform any SMBG. Lack of finance was the predominant reason for not performing any SMBG. The median monthly cost of performing SMBG excluding the cost of meters was N2,000 (USD 6.7) per patient, amounting to annual societal cost of N37.8 billion (USD 126 million). Significant associates of performing any SMBG were longer DM duration, previous participation in diabetes education, insulin treatment and infrequent hospitalization. Conclusion: Despite high awareness, SMBG practice is grossly inadequate and is associated with a huge economic burden that may be unsustainable in a resource-poor country like Nigeria. Measures aimed at reducing the cost of glucometers and strips, and improving diabetes education are recommended.

Background: Cytokine dysregulation plays an important role in Type 2 Diabetes Mellitus (T2DM) and Chronic Periodontitis (CP) with a commonality in pathogenic mechanisms. CP is considered the sixth complication of diabetes and may have an increased influence on systemic levels of cytokines in individuals with T2DM. Objective: This study investigated two pro-, and two presumed anti-inflammatory cytokines and their ratios in the serum of healthy individuals, in chronic periodontitis with and without T2DM with, and without CP and in CP alone aimed at evaluating the systemic inflammatory burden of a local oral infection. Methods: Eighty participants were divided equally into four groups as healthy volunteers (H) and patients having T2DM with, and without CP (T2DM+CP, and T2DM) and only CP (CP). Serum samples were collected to measure glycated hemoglobin (HbA1c), Random Blood Sugar (RBS) and also Tumor Necrosis Factor (TNF)-α, Interleukin (IL)-4, -6 - 10 were assessed using commercially available ELISA kits. Results: The cytokines were detected in all groups. Significant differences were observed between groups for all the clinical, biochemical parameters and cytokines. Cytokine levels and the ratios showed significant correlations. The ratios of the cytokines differed significantly amongst groups, were highest in T2DM+CP. Conclusion: In this study, the cytokine ratios provided a qualitative profile along with the absolute levels in T2DM with periodontitis, indicative of an intensified systemic inflammatory state.

Background: Renal dysfunction is a common complication in type 2 diabetes mellitus patients associated with oxidative damage which could be characterized by 8-iso-prostaglandin F2α and hydrogen peroxide level as oxidative stress markers. Objective: The aim of our study is to determine if there is a difference in 8-iso-prostaglandin F2α and hydrogen peroxide levels between sulfonylurea and combination of metformin-sulfonylurea in diabetic patients. We also wanted to determine if these oxidative stress markers correlate with the estimated Glomerular Filtration Rate (eGFR). Subjects and Methods: We conducted a cross-sectional study with inclusion of 55 patients with type 2 diabetes mellitus in Dr. Sitanala Tangerang Hospital, Indonesia with purposive sampling. The value of eGFR was obtained by serum creatinine levels, while the level of 8-iso-prostaglandin F2α was measured by ELISA and urinary hydrogen peroxide using FOX-1 (Ferrous Ion Oxidation Xylenol Orange 1). Results: There was no difference in 8-iso-prostaglandin F2α and hydrogen peroxide level between the two groups (p=0.088 and p=0.848). Moreover, there was no difference in eGFR values between the two groups, measured by Cockroft-Gault, MDRD, and CKD-EPI. 8-iso-prostaglandin F2α (n=55) was positively correlated with eGFR based on Cockroft-Gault (r=0.382; p=0.009), whereas urinary hydrogen peroxide (n=47) also generate significant positive correlation with eGFR based on the MDRD equation (r=0.326; p=0.021). Linear regression analysis showed that 8-iso-prostaglandin F2α is the most predictive factor and the only significant factor for eGFR in Cockroft-Gault, MDRD and also CKDEPI, even after controlled by gender, age, BMI, HbA1c, systole, and H2O2. Conclusion: The two treatments did not have any significant differences in antioxidant activity. However, an increase of urinary 8-iso-prostaglandin F2α and hydrogen peroxide which correlates with eGFR in the total sample may play a significant role in the pathophysiology of diabetic nephropathy.