Current Diabetes Reviews - Volume 17, Issue 1, 2021

Background: Diabetic neuropathies (DN) are the most common complications in diabetic patients, affecting about 70% of them. Patients with DN may lose sensation in certain areas of the body, facilitating the onset of foot ulcers, as well as chronic pain. This is due to the progressive degeneration of nerve fibers, demyelination, and axonopathy. Recent studies about stem cell therapies for the treatment of DN show promising potential for tissue regeneration. Results with mesenchymal stem cells derived from various organs/tissues demonstrate great therapeutic potential considering their easy obtainment, as well as their immunomodulatory and pro-regenerative effects. However, problems such as cell transplant rejection, tumor formation, transplantation safety, and effectiveness still need to be solved. Developmental biology lacks detailed insights into some aspects of cell mechanisms, like the genetic components of cell growth or differentiation. These gaps can limit a rapid advance in stem cell therapy research and put it in the future a little bit farther from the expectations that have emerged in recent media. Conclusion: In the present review, we attempt to discuss the potential of most studied types of stem cells, their application for the treatment of experimental diabetic neuropathies and associated clinical manifestations including future perspectives around these themes.

Background: China, as the largest developing country in the world, has experienced rapid economic development during the past decades. As a side effect of the rapid growth of Chinese economy, air pollution in the form of haze is harmful to human health. Introduction: China is also one of the countries with the highest prevalence of diabetes in Asia and has the largest burden of diabetes in the world. Recent evidence suggests a positive correlation between air pollution and the increased risk of diabetes. However, the association of haze with diabetes is still unclear. Methods: Based upon literature searching with PubMed, the information on haze and prevalence of diabetes in different cities or provinces of China is summarized. The possible association of haze with diabetes and the perspectives of haze research particularly in the prevention of haze in China are then discussed. Results: The exposure of long-term air pollution such as haze reduces insulin-dependent glucose uptake, leading to insulin resistance; damages beta cell function, leading to decreased insulin secretion, and promotes subcutaneous fat accumulation. Pathophysiological effects of particulate matters in diabetes through inflammation and oxidative stress were evidenced by several epidemiological and experimental studies. Conclusion: A better understanding of the incidence of diabetes caused by haze exposure may facilitate policy development in air pollution prevention and intervention design in diabetes prevention. Continuous improvement in air quality may help to reduce diabetes prevalence in China.

Different dysglycemic states precede overt type 2 diabetes. Prediabetic dysglycemia also carries an increased cardiovascular risk per se. Prediabetic dysglycemia may be divided into impaired fasting glycemia, impaired glucose tolerance and intermediate hyperglycemia. Mixed forms of these are very common. Dysglycemia develops insidiously for many years and usually produces no symptoms until very late. It is possible to prevent prediabetic dysglycemia from progressing to manifest type 2 diabetes and it can also be made to return to normoglycemia. The importance of lifestyle interventions, pharmacological treatment, surgical treatment and community efforts are discussed.

Background: Human regular insulin 500 (U-500) is 5 five times more concentrated than the traditional regular human insulin (U-100). Thus, every 1 ml of U-500 contains 500 units of insulin as opposed to 100 units/ml with most types of insulin. Methods: Review of all the relevant clinical studies related to insulin U-500 until February 12, 2020. Results: Insulin U-500 is indicated in patients with type 2 diabetes who require more than 200 units of insulin per day. Insulin U-500 has both prandial and basal actions, and can be injected as monotherapy in a convenient twice-daily regimen. Available data suggest that insulin U-500 is effective, associated with better compliance, and decreased injection pain compared with non-concentrated insulins. Its main limitations are hypoglycemia and weight gain, and the possibility of dosing errors. Conclusions: Overall, insulin U-500 is an effective and safe treatment for patients with type 2 diabetes and insulin resistance. Randomized trials are needed to compare the long-term efficacy and safety of insulin U-500 with other forms of insulin regimens.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease which leads to the destruction of pancreatic β-cells, thereby causing insufficient insulin production. Globally, around 98, 200 children and adolescents below 15 years of age and almost 128,900 subjects below 20 years of age develop T1DM annually, along with severe complications deteriorating their quality of life. In India alone, around 15,900 incident cases below 15 years have reported annually. Hence, its prevention and reversal are significant. Unlike other chronic diseases, T1DM involves the presence of various autoantigens, which can be targeted by proper immunisation. The development of reliable immuno-regulatory surrogate markers would be of great benefit. Vaccines can be one of such strategies in the journey to prevent T1DM. It would not only benefit greatly to reduce the sufferings caused due to diabetic complications but could also help to reverse T1DM, by modulating the autoantigenic immunological reactions and prevent further degradation of pancreatic β-cells. This review collates a wide range of information related to the vaccine studies conducted in animal and human models to prevent and reverse T1DM.

Type 1 diabetes mellitus (T1DM) is a chronic disease that starts early in life and often leads to micro- and macrovascular complications. The incidence of the disease is lower than that of type 2 DM and varies in different countries and ethnic groups, and the etiological and pathogenetic factors are different from T2DM. The aim of this overview is to investigate the effect of T1DM on all-cause mortality and CVD morbidity and mortality. During the last decades, the treatment of T1DM has improved the prognosis of the patients. Still, the mortality rates are higher than those of the age- and sex-matched general population. With the prolonged survival, the macrovascular complications and cardiovascular diseases (CVD) appear as major health problems in the management of patients with T1DM. The studies on the CVD morbidity and mortality in this disease group are sparse, but they reveal that T1DM is associated with at least 30% higher mortality. In comparison to healthy people, CVDs are more common in T1DM patients and they occur earlier in life. Furthermore, they are a major cause for death and impaired quality of life in T1DM patients. The correlation between diabetic control and the duration of T1DM is not always present or is insignificant. Nevertheless, the early detection of the preclinical stages of the diseases and the risk factors for their development is important; similarly, the efforts to improve glycemic and metabolic control are of paramount importance.

Introduction: The effectiveness of the treatment has long been significant in diabetes and its complications, especially in developing countries. Prolonged hospitalization and repeated surgery should be avoided due to clinical and economic reasons. Wound breakdowns or necrosis can occur after amputation procedures, and subsequently will require reamputation. This study analyzed susceptibility factors in diabetic foot patients undergoing prior high toe amputation that are thought to be related to early reamputation. Methods: We performed a retrospective analysis in 107 patients that have undergone amputation for great toe gangrene, during May 2014-April 2019. Demographic data, clinical features, laboratory results and treatment modality, were documented and statistically analyzed by simple and multiple logistic regression methods. Results: Of all 107 patients, 17 patients had to undergo early reamputation. Limited dorsiflexion, level of amputation, and sepsis condition is shown to be significantly associated with first amputation. Multiple logistic regression analysis confirmed a significant association of early reamputation with amputation or disarticulation at the level of the metatarsophalangeal joint. Conclusion: While limited ankle dorsiflexion and sepsis conditions need to be addressed comprehensively, from the surgical options point of view, we suggest ray amputation to be preferred over metatarsophalangeal joint disarticulation to prevent early reamputation.

Background: Estrogen receptor β (ERβ) plays an important role in human metabolism and some of its metabolic actions are mediated by a positive “cross-talk” with Nuclear Factor of Activated T cells (NFAT) and the key metabolic transcriptional coregulator Transcriptional Intermediary Factor 2 (TIF2). Introduction: Our study is an “in situ” morphological evaluation of the communication between ERβ, NFAT and TIF2 in morbid obesity. Potential correlations with clinicopathological parameters and with the presence of diabetes and non-alcoholic fatty liver disease (NAFLD) were also explored. The aim of the present study was to determine the role of ERβ and NFAT in the underlying pathophysiology of obesity and related comorbidities. We have investigated the expression of specific proteins using immunochemistry methodologies. Methods: Our population consists of 50 morbidly obese patients undergoing planned bariatric surgery, during which biopsies were taken from visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), skeletal muscle (SM), extramyocellular adipose tissue (EMAT) and liver and the differential protein expression was evaluated by immunohistochemistry. Results: We demonstrated an extensive intra- and inter-tissue co-expression network, which confirms the tissue-specific and integral role of each one of the investigated proteins in morbid obesity. Moreover, a beneficial role of ERβ and NFATc1 against NAFLD is implicated, whereas the distinct roles of TIF2 still remain an enigma. Conclusion: We believe that our findings will shed light on the complex underlying mechanisms and that the investigated biomarkers could represent future targets for the prevention and therapy of obesity and its comorbidities.

Background: Vitamin D is increasingly investigated as having a role in Type 2 Diabetes Mellitus (T2DM) and its cardiovascular and renal complications. Objective: This study aimed to investigate the association between 25-hydroxyvitamin D (25-OHD) and biomarkers of cardiovascular and renal complications, including cystatin-C. Methods: This cross-sectional study involved 117 participants with T2DM that was not complicated with cardiovascular or renal diseases except hypertension. 25-OHD was measured by electrochemiluminescence immunoassay, while cystatin-C was measured by enzyme-linked-immunosorbent-assay. Other biomarkers, including lipids, creatinine, urea and glycemic measures, were determined by the routine biochemistry assays. Results: The prevalence of vitamin D deficiency was 74.36%. There was no significant difference in cardiovascular and renal biomarkers, including glucose, HbA1c, lipids, urea, creatinine and cystatin-C between participants with adequate and deficient vitamin D (p-values<0.05). Participants with adequate vitamin D were older in age, more obese and having lower eGFR (p-values<;0.05). 25-OHD was weakly correlated with age, duration of DM, urea, creatinine and inversely correlated with eGFR (rvalues<0.32, p-values<0.05). Although creatinine and cystatin-C were directly correlated (r=0.42, pvalue<0.001), cystatin-C and 25-OHD were not correlated (p-value<0.05). Hypertensive participants were more obese, having a longer duration of DM and higher urea and cystatin-C compared to nonhypertensive participants (p-values<0.05). Binary logistic regression analysis revealed that hypertension could be predicted from increased BMI. Conclusion: 25-OHD was not found to be correlated with cardiovascular risk biomarkers, but it was correlated with renal biomarkers, including urea, creatinine and eGFR. Cystatin-C and 25-OHD were not observed to be correlated to each other, but both were correlated to renal function. Obesity was a significant predictor of hypertension.

Background: Type 2 diabetes (T2DM) has been associated with deficiencies in serum magnesium level, decreasing insulin sensitivity and glucose metabolism. Glycosylated hemoglobin (Hb1Ac) is a biomarker of glucose values within the half-life of the erythrocyte, that is, 3 months. Low circulating and intracellular magnesium levels can modify glucose metabolism and insulin sensitivity. Renal solute management is a parameter little used to estimate circulating and excreted concentrations of elements such as magnesium. Objective: The purpose of this study was to assess and associated fractional excretion of magnesium (FEMg) and serum magnesium with metabolic parameters, especially Hb1Ac percent, in a group of well characterized subjects with T2DM and non-diabetics subjects (ND). Methods: According to Hb1Ac, two groups were compared and associated with existing biochemical parameters, included Hb1Ac, fasting glucose, lipid profile, serum creatinine, serum magnesium and urinary creatinine for FEMg. Results: HbA1c levels were explained by serum magnesium in 25%. Serum magnesium levels in the ND group were higher than in the T2DM group and this was a statistically significant difference. Serum magnesium ≤1.8 is a risk factor (OD 16.1; P=0.021) for an HbA1c ≥ 6.5%. Conclusion: In this study, hypomagnesemia was a parameter strongly associated with the diagnosis and progression of T2DM, while FEMg showed no significant association.

Background: Diabetes mellitus is a serious chronic condition affecting millions of people globally. The focus of our future health care providers should not lie primarily on increasing the “quantity” of life but also on improving the Quality of Life of the patient. There is a serious lack of awareness and adherence regarding self-care for Diabetes in countries like India. Objectives: To determine the Quality of Life and self-care behavior among people living with Diabetes. Methods: A cross-sectional study was carried out among 190 of all patients diagnosed with Diabetes mellitus type II of the duration of one year and more who came to Government Wenlock Hospital, Mangalore. The Quality of Life was assessed using the WHO BREF questionnaire. Data was entered and analyzed using the Statistical Package for Social Sciences. Results: Amongst 190 participants, 151 (79.5%) of them had a good physical and psychological QOL. In a social relationship and environmental health domain, good quality of life was observed among 81.6% (n=155) and 89.5% (n=170) of study participants, respectively. It was noted that out of 190 people with Diabetes, only 24 (12.6%) participants inspected their feet daily. Conclusion: The Quality of Life was found to be good amongst the majority of the study participants. Results of the study point that the majority of the patients enjoy a good quality of life but also reinstate the importance of self-care activities for the betterment of health.