Gene Expression of GSK3 in Type II Diabetics Compared to Non-Diabetics (ex vivo)

Background: GSK3 is a serine/threonine kinase that is involved in the storage of glucose into glycogen through the negative regulation of glycogen synthase. Defects in GSK3 and glycogen synthase function are early stages of the development of insulin resistance, which may cause impaired glycogen synthesis in Type II diabetes. Methods: In this cross-sectional study, the gene expression level of GSK3 from Type II diabetic and non-diabetic participants was compared via real-time RT-PCR. To investigate the relationships between GSK3 expression and indicators of insulin resistance, Pearson's correlation analysis was performed. To compare the differences between GSK3 expression levels based on BMI categories, one-way ANOVA was used. Results: Gene expression of GSK3 was slightly higher in diabetic participants compared to non-diabetics, but it was statistically insignificant. Also, no significant difference was found based on BMI categories in the two groups. No significant association between GSK3 expression and indicators of insulin resistance was observed in non-diabetic participants. There was only a positive significant correlation between GSK3 expression and FBS in diabetic participants. Conclusion: These results indicate that the regulation of GSK3 may occur at the translation level, as gene expression level was unaltered between diabetic and non-diabetic participants. Also, since circulating levels of both glucose and insulin regulate GSK3 activity, tissue specificity for the expression and post-translation regulations of GSK3 may exist, which cause hyperactivation or overexpression in some target tissues in diabetes. Furthermore, it is probable that glycogen synthase activity is also regulated by non-insulin mediated mechanisms like exercise or allosteric changes, independent of GSK3 expression.

G6PC2 rs560887 Gene Variant is Associated with Fasting Blood Glucose in the Admixed Mexican Population

Background: In Mexico, type 2 diabetes prevalence is 13.7%, which has a huge impact on Mexican public health. There is an urgent need to focus on the prevention of pre-diabetes to decrease the likelihood of type 2 diabetes onset. Gene variants predisposed to increase Fasting Blood Glucose (FBG) and glycosylated hemoglobin (HbA1c) levels could be helpful for prevention purposes. This study aimed to analyze the association of the G6PC2 rs560887 variant with pre-diabetes in a Mexican-Mestizo population. Methods: A cross-sectional case-control study was performed in 960 Mexican Mestizos participants. The association of G6PC2 rs560887 with pre-diabetes was analyzed by logistic regression and with Fasting Blood Glucose (FBG) and glycosylated hemoglobin (HbA1c) by linear regression. Results: The G6PC2 rs560887 variant was significantly associated with FBG (β -1.80, p=0.03), but not with HbA1c or the presence of pre-diabetes. Conclusion: The G6PC2 rs560887 loci could be a potential early marker of type 2 diabetes.

Role of Vitamin D Receptor in Prediabetes

Background: Recent epidemiological evidence points towards the potential association of vitamin D insufficiency with adverse metabolic risk and in the pathogenesis of cancer, cardiovascular diseases, type 2 diabetes and other diseases. Vitamin D exerts its action in a variety of cell types through vitamin D receptors. No reports are available in the literature regarding vitamin D and vitamin D receptor status in prediabetics. The present study was planned to compare serum 25-hydroxy vitamin D [25(OH)D] and vitamin D receptor (VDR) protein levels in prediabetic cases and normoglycemic controls. Methods: The present study was conducted in 80 persons who were divided into two groups, Study group (n= 40) comprised of diagnosed cases of prediabetes and control group (n=40) comprised of healthy normoglycemic controls. Serum 25-hydroxy vitamin D [25(OH)D] was analyzed by radioimmunoassay (RIA). Serum vitamin D receptor (VDR) protein was analyzed by sandwich enzyme immunoassay (ELISA). Results: Serum 25(OH) vitamin D levels were significantly decreased in prediabetic cases as compared to normoglycemic controls [p<0.001]. Serum Vitamin D receptor protein levels were highly significantly decreased in prediabetic cases as compared to normoglycemic controls [p<0.00]. Serum 25(OH)D levels showed a highly significant positive correlation with serum VDR levels in both the groups [p<0.001 at both levels]. Conclusion: The findings of the present study indicate that vitamin D and VDR can serve as a possible screening marker and target for modulation of the management and alleviating the progress and complications of diabetes.

To Tell or Not to Tell: Disclosure and Self-Management among Adults with Early-Onset Type 2 Diabetes: A Qualitative Study

Background: Adults with early-onset Type 2 Diabetes Mellitus (T2DM) are an emerging high-risk population who may experience social challenges related to diabetes management. Objective: To explore the disclosure of T2DM and how disclosure affects diabetes self-management and the psychosocial adjustment to life with diabetes among adults with early-onset T2DM. Methods: A qualitative study was conducted using Systematic Text Condensation (STC). Data was derived from semi-structured interviews with 15 individuals with T2DM ≤ 46 years (10 women and 5 men) recruited from diverse settings using purposeful sampling. Results: Most informants disclosed their diabetes to a close relative shortly after receiving the diagnosis. This led to immediate emotional support and overall positive disclosure experiences. However, informants often hesitated to disclose their condition to others due to shame, fear of negative judgement or social exclusion. Over time, the majority of informants became more open about their condition, which often resulted in emotional and practical self-management support. Those most reluctant to disclosing their diabetes struggled with shame and negative diabetes-related emotions, which had negative effects on their diabetes self-management. Conclusion: Disclosure of T2DM seemed important for the social, emotional and practical management of diabetes among adults with early-onset T2DM. The disclosure was most often accompanied by feelings of shame and fear of condemnation. Professional guidance to support disclosure and interventions to address stigma may improve well-being and diabetes self-management in this population.

Assessment of Cardiovascular Disease Risk among Qatari Patients with Type 2 Diabetes Mellitus, Attending Primary Health Care Centers, 2014

Background: The accumulated knowledge on the development of cardiovascular disease in diabetic patients due to clustering and synergistic interaction of multiple risk factors leads to the establishment of cardiovascular disease 10-year risk prediction tools. The management of patients based on their total risk prediction is an effective way to reduce disease burden. The behavior of such tools varies based on population and their risk profile. Objective: To estimate the total 10-year cardiovascular disease risk using General Framingham Risk Prediction Score and World Health Organization /International Society for Hypertension (WHO/ISH) Risk Prediction Chart on Qatari diabetic patients. Methods: Cross-sectional design was used. A total of 532 Qatari diabetic patients attending primary healthcare were enrolled. Data were collected using an interview administered questionnaire, anthropometric & blood pressure measurement, and medical records. The total 10-year cardiovascular disease risk was assessed using the WHO/ISH risk prediction chart and Framingham score. Results: The former categorized (81.6%) of participants as low risk and only (3.8%) as in high and very high risk. While the later categorized (12.2%) of participants as low risk and (57.6%) as in high and very high risk. No agreement between both tools in assessment of cardiovascular disease risk (κ = - 0.019, p-value = 0.216). All risk factors used by both tools illustrated a statistically significant relation with risk categories, except ‘anti-hypertensive medications intake’ in the Framingham score. Conclusion: Encouraging assessment of patients based on total risk rather than single risk factor and further study of total risk prediction can help to establish a national tool for Qatar.

Markers of Oxidative Stress and Inflammation in only Diabetic and Obese Ghanaian Populations: The RODAM Study

Background: The RODAM study has established a link between peripheral insulin resistance and varying fasting blood glucose levels among Ghanaian populations. However, associations of oxidative stress and inflammation with type 2 Diabetes Mellitus (T2DM) and obesity is yet to be assessed in this population. Objective: This study determined the association of inflammatory and oxidative stress markers in T2DM and obesity among Ghanaian migrants in Europe and non-migrants in Ghana. Methods: Socio-demographic and anthropometric variables were collected from 5350 participants of 25-70 years and stratified into migrant Ghanaians (n= 2921), urban (n=1411) and rural Ghanaians (n=1018). C-Reactive Protein (CRP), Uric Acid (UA) and ferritin were quantified and associations drawn between these markers and the metabolic disorders using logistic regression. Results: Overall mean ages (years) were highest for migrant Ghanaians [46.59, 95%CI (46.24, 46.93)] compared to rural [46.49 (45.72, 47.26)] and urban [45.24 (44.65, 45.83)]. CRP was associated with obesity and T2DM respectively in urban [OR=1.531, 95%CI (1.407, 1.666): OR=1.354, 95% CI (1.195, 1.535)] and migrant Ghanaians [OR=1.552, 95% CI (1.449, 1.662): OR=1.405, 95%CI (1.234, 1.600)]. Similarly, ferritin was positively associated (p<0.05) with T2DM in migrant [OR=1.312, 95% CI (1.058, 1.626)], urban [OR=1.972, 95% CI (1.510, 2.575)] and rural Ghanaians [OR=1.240, 95%CI (1.020, 1.507)]. Conclusion: CRP and ferritin are associated with T2DM in Ghanaian populations at varying magnitudes. Moreover, indulgence in lifestyles that elevate inflammation and oxidative stress has the potential to increase risk of T2DM and obesity among Ghanaian populations.

Impact of Self-monitoring of Blood Glucose on Glycaemic Control in Type 2 Diabetic Nigerians who Reside in Lagos

Background: Self-Monitoring of Blood Glucose (SMBG) is a vital constituent of diabetes care. The aim of this study was to document the practice, determinants and effects of SMBG in our setting. Methods: A cross-sectional study was carried out on 249 adult type 2 diabetic subjects who attended the diabetes clinic of the Lagos State University Teaching Hospital Ikeja. The statistical analysis was done with independent t-test and logistic regression. A P-value of less than 0.05 was taken as significant. Results: The age of the study subjects ranged from 28 years to 87 years. The mean + S.D age is 62 + 11 years. The mean + S.D BMI of the study subjects is 27.79 + 4.73 Kgm2. 159 (64%) of the patients practised SMBG while 90 (36%) patients did not. Twenty-two (14%) of the patients have been practising SMBG for less than 12 months, 71 (46%) patients for 12 - 36 months, while 60 (39%) of them for more than 36 months. 36 (23%) of the patients did SMBG daily, 58 (37%) patients twice weekly, 48 (30%) patients weekly, 11 (7%) patients monthly, 5 (3%) patients did it for unspecified time period while 1 (1%) patient was unable to report the time period. SMBG practice was associated with better short term glycemic control P= < 0.001, OR= 0.399 and 95% CI 0.229-0.693. Predictors of SMBG were male sex, higher socioeconomic status and insulin therapy. More male patients (72.7%) practice SMBG compared to female patients (59.9%) p-value 0.051. The detection of chronic complications of DM was comparable between those who practice SMBG and those who do not. Conclusion: SMBG practice is significantly associated with better short term glycaemic control.

Hypoglycemia among Insulin-treated Patients with Diabetes: Egypt Cohort of IO HAT Study

Objectives: The study aims to assess the real-world incidence of hypoglycemia in patients with Type 1 Diabetes Mellitus (T1DM) or Type 2 Diabetes Mellitus (T2DM) in Egypt cohort of the International Operations Hypoglycemia Assessment Tool (IO HAT) study. Methods: This is a non-interventional study to estimate hypoglycemia in eligible patients with T1DM or T2DM, aged ≥18 years and treated with insulin for >12 months, who have completed self-assessment questionnaires to record demography, treatment information, and hypoglycemia during the 6-month/4-week retrospective and 4-week prospective periods. Data on hypoglycemia for this sub-analysis were collected from DM patients of Egyptian cohort who were recruited in IO HAT study across 36 sites in Egypt between 22 Nov 2014 and 15 Apr 2015. Results: Percentage of patients who reported at least one hypoglycemic event in the prospective period was any: T1DM: 96.3% (95% confidence interval [CI]: 89.6%, 99.2%) and T2DM: 93.1% (95% CI: 89.8%, 95.6%) and severe: T1DM: 67.5% (95% CI: 56.1%, 77.6%) and T2DM: 64.2% (95% CI: 58.7%, 69.4%). An estimated rate of any and severe hypoglycemia in the prospective period was 63.3 (95% CI: 57.2, 69.9) events per patient year (PPY) and 28.9 (95% CI: 24.8, 33.4) events PPY, respectively, for patients with T1DM and 32.0 (95% CI: 29.8, 34.3) events PPY and 15.5 (95% CI: 14.0, 17.1) events PPY, respectively, for patients with T2DM. Hypoglycemic rate was independent of glycated hemoglobin levels. Conclusion: The self-reported hypoglycemia data from Egypt confirms that hypoglycemia is under-reported. The high impact of hypoglycemia on the Egyptian DM patients and healthcare system warrants patient education to prevent hypoglycemia.

Type 2 Diabetes Treatment and Drug Development Study

The causality and etio-pathologic risks for patients with Type 2 Diabetes (T2DM) are important areas in modern medicine. Disease complications are largely unpredictable in patients with T2DM. In the future, we welcome therapeutics of both cutting-edge and traditional for anti-diabetic treatments and management with higher efficiency and less cost. Expanding medical knowledge, behavior/life-style notification in healthcare, modern genetic/bioinformatics diagnostic promotion, clinical developments (Traditional Chinese Medicine and personalized medicine) and new drug developments - including candidate drug targets should be implemented in the future. These efforts might be useful avenues for updating anti-diabetic therapeutics globally. This article aims at introducing this information for T2DM treatment boosts.

Type 2 Diabetes Study, Introduction and Perspective

Background:The prevalence of Type 2 Diabetes Mellitus (T2DM) continues to rise globally. The T2DM prevalence is not only in developing countries, but also in developed countries now. Correspondingly, the therapeutics of T2DM calls for a change (higher efficiency) due to growing number of patients and increasing economic burdens globally. Entering into this millennium, both piecemeal pathways (idea driven) and exponential growth of human genomic study are developing quickly. Genetypic-phenotypic translation, modern diagnostics, pharmacology, drug developments, traditional Chinese medicine, personalized medicine and so on are promising disciplines for this change. The clinical anti-diabetic therapeutics, pathogenesis, drug development pipelines are especially highlighted.Conclusion:In summary, a general landscape and principle of T2DM is provided.