Showing papers in "Journal of Diabetes in 2020"

Diabetes and COVID-19

Abstract: After the recognition in December 2019 of a cluster of patients with pneumonia of unknown cause in Wuhan caused by the novel coronavirus, CoV-19, China and the world have faced the extraordinary challenge of a previously unrecognized viral illness with high infectivity. Every year, millions of persons (5%-15% of the world's population) contract influenza, causing between 300 000 and 600 000 excess respiratory deaths. In China alone, recent estimates put the annual influenza-associated mortality rate at more than 88 000 persons, likely in excess of any potential outcome of coronavirus disease 2019 (COVID-19). Regardless of the potential for spread of COVID-19, as with influenza-related mortality, diabetes is an important risk factor for adverse outcome. Mortality rates among persons with diabetes in Hong Kong age 75 and over from pneumonia currently exceed mortality rates in this age group from cardiovascular disease and from cancer. Similar evidence of risk among persons with diabetes has been reported for the two earlier CoV infections, severe acute respiratory syndrome (SARS) beginning in 2002 and affecting more than 8000 persons, mainly in Asia and the Middle East respiratory syndrome (MERS) in 2012 affecting more than 2000 persons, mainly in Saudi Arabia. As MERS-CoV binds to the receptor-binding domain of human dipeptidyl peptidase IV (DPP-IV), a transgenic mouse model expressing this DPP-IV receptor on pulmonary alveolar cells has been used to study the effect of diabetes in worsening disease severity, showing an association of diabetes with greater weight loss and greater pulmonary inflammation, with macrophage infiltrates similar to those seen clinically in the disease. We acknowledge the frontline medical staff working day and night in China to rescue critical cases and protect the public health. We know that these great efforts are now and will be in the future crucial in overcoming COVID-19. Providing care to people with diabetes is an important part of the effort. The Journal of Diabetes was started more than a decade ago in a spirit of collaboration between East and West addressing the epidemiology, etiology, pathogenesis, management, complications, and prevention of diabetes. The journal is issuing a call for submission of commentaries, original articles, and case reports regarding issues with COVID-19 in patients with diabetes, as well as descriptions of basic aspects of the interrelationships between diabetes and the novel CoV. We hope in this way to support the thousands of Chinese medical workers involving themselves in the care of patients with COVID-19, and we look forward to these efforts helping our goal of eradication of the disease.

Factors leading to high morbidity and mortality of COVID-19 in patients with type 2 diabetes.

Abstract: Coronavirus disease 2019 (COVID-19) is a recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus. Diabetes (mostly type 2 diabetes mellitus, T2DM) and hyperglycemia are among the major comorbidities in patients with COVID-19 leading to poor outcomes. Reports show that patients with diabetes and COVID-19 are at an increased risk for developing severe complications including acute respiratory distress syndrome, multi-organ failure, and death. Here we explore potential mechanistic links that could explain the observed higher morbidity and mortality in this patient population. Patients with T2DM have an underlying increased level of inflammation associated with obesity and insulin resistance in addition to other comorbidities including hypertension, obesity, cardiovascular disease, dyslipidemia, and being older. We review evidence that T2DM with hyperglycemia are among factors that lead to elevated expression of angiotensin-converting enzyme 2 (ACE2) in lungs and other tissues; ACE2 is the cellular "receptor" and port of viral entry. The preexisting chronic inflammation with augmented inflammatory response to the infection and the increasing viral load leads to extreme systemic immune response ("cytokine storm") that is strongly associated with increased severity of COVID-19. Based on the available evidence, it is recommended by a panel of experts that safe but stringent control of blood glucose, blood pressure, and lipids be carried out in patients with T2DM, measures that could potentially serve to decrease the severity of COVID-19 should these patients contract the viral infection. Once the infection occurs, then attention should be directed to proper glycemic control with use of insulin and frequent monitoring of blood glucose levels.

COVID-19 and comorbidities: A role for dipeptidyl peptidase 4 (DPP4) in disease severity?

Abstract: The coronavirus disease 2019 (COVID-19) pandemic is caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to SARS-CoV and Middle East respiratory syndrome (MERS-CoV), which cause acute respiratory distress syndrome and case fatalities. COVID-19 disease severity is worse in older obese patients with comorbidities such as diabetes, hypertension, cardiovascular disease, and chronic lung disease. Cell binding and entry of betacoronaviruses is via their surface spike glycoprotein; SARS-CoV binds to the metalloprotease angiotensin-converting enzyme 2 (ACE2), MERS-CoV utilizes dipeptidyl peptidase 4 (DPP4), and recent modeling of the structure of SARS-CoV-2 spike glycoprotein predicts that it can interact with human DPP4 in addition to ACE2. DPP4 is a ubiquitous membrane-bound aminopeptidase that circulates in plasma; it is multifunctional with roles in nutrition, metabolism, and immune and endocrine systems. DPP4 activity differentially regulates glucose homeostasis and inflammation via its enzymatic activity and nonenzymatic immunomodulatory effects. The importance of DPP4 for the medical community has been highlighted by the approval of DPP4 inhibitors, or gliptins, for the treatment of type 2 diabetes mellitus. This review discusses the dysregulation of DPP4 in COVID-19 comorbid conditions; DPP4 activity is higher in older individuals and increased plasma DPP4 is a predictor of the onset of metabolic syndrome. DPP4 upregulation may be a determinant of COVID-19 disease severity, which creates interest regarding the use of gliptins in management of COVID-19. Also, knowledge of the chemistry and biology of DPP4 could be utilized to develop novel therapies to block viral entry of some betacoronaviruses, potentially including SARS-CoV-2.

Faecalibacterium prausnitzii‐derived microbial anti‐inflammatory molecule regulates intestinal integrity in diabetes mellitus mice via modulating tight junction protein expression

Abstract: Background Impaired intestinal barrier structure and function have been validated as an important pathogenic process in type 2 diabetes mellitus (T2DM). Gut dysbiosis is thought to be the critical factor in diabetic intestinal pathogenesis. As the most abundant commensal bacteria, Faecalibacterium prausnitzii (F. prausnitzii) play important roles in gut homeostasis. The microbial anti-inflammatory molecule (MAM), an F. prausnitzii metabolite, has anti-inflammatory potential in inflammatory bowel disease (IBD). Thus, we aimed to explore the function and mechanism of MAM on the diabetic intestinal epithelium. Methods 16S high-throughput sequencing was used to analyze the gut microbiota of db/db mice (T2DM mouse model). We transfected a FLAG-tagged MAM plasmid into human colonic cells to explore the protein-protein interactions and observe cell monolayer permeability. For in vivo experiments, db/db mice were supplemented with recombinant His-tagged MAM protein from E. coli BL21 (DE3). Results The abundance of F. prausnitzii was downregulated in the gut microbiota of db/db mice. Immunoprecipitation (IP) and mass spectroscopy (MS) analyses revealed that MAM potentially interacts with proteins in the tight junction pathway, including zona occludens 1 (ZO-1). FLAG-tagged MAM plasmid transfection stabilized the cell permeability and increased ZO-1 expression in NCM460, Caco2, and HT-29 cells. The db/db mice supplemented with recombinant His-tagged MAM protein showed restored intestinal barrier function and elevated ZO-1 expression. Conclusions Our study shows that MAM from F. prausnitzii can restore the intestinal barrier structure and function in DM conditions via the regulation of the tight junction pathway and ZO-1 expression.

Atherosclerosis: Pathophysiology of insulin resistance, hyperglycemia, hyperlipidemia, and inflammation

Abstract: Atherosclerotic cardiovascular disease (CVD) is on course to surpass infectious diseases as the leading cause of morbidity and mortality worldwide. Multiple risk factors are responsible for this trend including the increasing average life expectancy and reducing rates of communicable diseases in addition to potentially modifiable risk factors, such as tobacco use, hypertension, hyperlipidemia, and diabetes mellitus. The development of atherosclerosis is driven by multiple factors including hypertension, dyslipidemia, inflammation, insulin resistance, and hyperglycemia. While many techniques are available to accurately measure atherosclerosis (coronary artery calcium scanning, CT angiography, intravascular ultrasound), understanding the pathophysiology of the disease may help drive discovery to ultimately prevent the disease.

Diabetes mellitus association with coronavirus disease 2019 (COVID-19) severity and mortality: A pooled analysis.

Abstract: Highlights There are ~ 2-fold increased odds of severe coronavirus disease 2019 (COVID-19) and a ~ 2-fold increased risk of odds of mortality in patients with history of diabetes mellitus compared to those without diabetes mellitus. Patients with a history of diabetes mellitus should be closely monitored if they get infected with COVID-19. Results of meta-analysis showing association of diabetes mellitus with severity (Panel A) of disease and mortality (Panel B) in coronavirus disease 2019 (COVID-19) patients.

Identification of stress-related microRNA biomarkers in type 2 diabetes mellitus: A systematic review and meta-analysis.

Abstract: Background Many studies have investigated microRNAs (miRNAs) in the detection of type 2 diabetes mellitus (T2DM). Herein, the dysregulated direction of stress-related miRNAs used as biomarkers of T2DM are summarized and analyzed. Methods PubMed, EMBASE, ISI Web of Science, and three Chinese databases were searched for case-control miRNA profiling studies about T2DM. A meta-analysis under a random effect was performed. Subgroup analysis was conducted based on different tissues and species. Sensitivity analysis was conducted to confirm the robustness among studies. The effect size was pooled using ln odds ratios (ORs), 95% confidence intervals (95% CIs), and P-values. Results The present meta-analysis included 39 case-control studies with a total of 494 miRNAs. Only 33 miRNAs were reported in three or more studies and, of these, 18 were inconsistent in their direction of dysregulation. Two significantly dysregulated miRNAs (let-7 g and miR-155) were identified in the meta-analysis. Four miRNAs (miR-142-3p, miR-155, miR-21, and miR-34c-5p) were dysregulated in patients with T2DM, whereas five miRNAs (miR-146a, miR-199a-3p, miR-200b, miR-29b and miR-30e) were dysregulated in animal models of diabetes. In addition, two dysregulated miRNAs (miR-146a and miR-21) were highly cornea specific and heart specific. In sensitivity analysis, only miR-155 was still significantly dysregulated after removing studies with small sample sizes. Conclusions The present meta-analysis revealed that 16 stress-related miRNAs were significantly dysregulated in T2DM. MiR-148b, miR-223, miR-130a, miR-19a, miR-26b and miR-27b were selected as potential circulating biomarkers of T2DM. In addition, miR-146a and miR-21 were identified as potential tissue biomarkers of T2DM.

Dietary preferences and diabetic risk in China: A large-scale nationwide Internet data-based study.

Abstract: Background Unhealthy diet is one of the important risk factors of diabetes, which is one of the major public health problems in China. The Internet tools provide large-scale passively collected data that show people's dietary preferences and their relationship with diabetes risk. Methods 212 341 708 individuals' dietary preference labels were created based on Internet data from online search and shopping software. Metabolic data obtained from the 2010 China Noncommunicable Disease Surveillance, which had 98 658 participants, was used to estimate the relation between dietary preferences geographical distribution and diabetes risk. Results Chinese dietary preferences had different geographical distribution, which is related to the local climate and consumption level. Fried food preference proportion distribution was significantly positively correlated with diabetes prevalence, hypertension prevalence and body mass index (BMI). Similarly, grilled food preference proportion distribution had significantly positive correlation with the prevalence of diabetes and hypertension. In contrast, spicy food preference proportion distribution was negatively correlated with diabetes prevalence. Sweet food preference proportion distribution was positively related to diabetes prevalence. Using dietary preferences data to predict regional prevalence of diabetes, hypertension and BMI, the average values of error (95% CI) between the three paired predicted and observed values were 9.8% (6.9%-12.7%), 7.5% (5.0%-10.0%) and 1.6% (1.2%-2.0%), respectively. Conclusions Fried food, grilled food, and sweet food preferences were positively related to diabetes risk whereas spicy food preference was negatively correlated with diabetes risk. Dietary preferences based on passively collected Internet data could be used to predict regional prevalence of diabetes, hypertension, and BMI and showed good value for public health monitoring.

The Jiangnan diet, a healthy diet pattern for Chinese

Abstract: Geographically, the Qinling Mountain-Huai River line divides China into two parts, Northern and Southern. Surprisingly, the line also divides the high prevalence of obesity and metabolic syndrome in Northern China from the low prevalence of Southern China. In past decades, the diet-center hypothesis has gained much support from the apparent cardiometabolic disease-protection effect of the Mediterranean diet. Questions include the following: Does the diet pattern explain the disease prevalence difference between two parts with similar genetic background? What kind of diet pattern is suitable for future national diet recommendation for Chinese, as the Mediterranean diet does for the Western countries? Here, we review the main healthy diet components, which the native inhabitants in the Yangtze River Delta region have eaten for several hundreds of years, and refer to this healthy diet as "Southern River ()-style dietary pattern" or "Jiangnan Diet."

Care for diabetes with COVID-19: Advice from China.

Abstract: The epidemic of the coronavirus disease 2019 (COVID19) has expanded from Wuhan throughout China and is being exported to a growing number of countries outside of China. The growing epidemic of COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The potential public health threat posed by COVID-19 is very high, both to China and globally. By 9 March 2020, 80 904 cases of COVID-19, including more than 3123 deaths, had been confirmed in China, mainly in Hubei province. A further 28 673 laboratory confirmed cases have been reported across 104 other countries/territories/areas. Considering the high proportion of critically ill patients with diabetes or hyperglycemia, the difficulty for treatment and high mortality rate, effective diabetes management under epidemic conditions is extremely important. In order to increase disease awareness and improve the prognosis and outcome of patients with diabetes, better understanding of the etiological associations between COVID-19 and diabetes, the clinical impact of COVID-19 on diabetes, and proposing detailed recommendations for prevention and treatment are needed.

Obstructive sleep apnea and risk of type 2 diabetes mellitus: A systematic review and dose-response meta-analysis of cohort studies.

Abstract: Background This meta-analysis was performed to quantitatively evaluate the dose-response association between obstructive sleep apnea (OSA) and risk of type 2 diabetes mellitus (T2DM). Methods PubMed, Embase, and Web of Science were searched up to 12 December 2018 for articles that assessed the OSA-T2DM association. Random effects models were used to analyze the quantitative association between OSA and risk of T2DM. Restricted cubic splines were used to model the dose-response association between apnea-hypopnea index (AHI), used to assess the severity of OSA according to events/h, and risk of T2DM. Results We included 16 cohort studies in our meta-analysis. During a median follow-up of 10.5 years (range: 3.0-22.0), 19 355 T2DM cases were reported among 338 912 study participants. The pooled relative risk of T2DM was 1.40 (95% CI, 1.32-1.48) for OSA in the binary meta-analysis and 1.08 (1.01-1.14) for each 5-event/h increase in AHI value. We found a positive linear association between OSA and T2DM risk. Conclusions Our dose-response meta-analysis revealed a linear association between OSA and T2DM.

Increasing insulin resistance predicts adverse pregnancy outcomes in women with gestational diabetes mellitus

Abstract: Background This study aimed to investigate the association between maternal insulin resistance (IR) in the late second trimester and pregnancy outcomes, as well as to identify risk factors of IR among women with gestational diabetes mellitus (GDM). Methods A retrospective study was conducted among 2647 women diagnosed with GDM. IR was evaluated using the homeostasis model assessment method for IR (HOMA-IR) in the late second trimester (between 24 and 28 weeks), and the lipid profiles were measured at the same time. Patients were divided into groups based on quartiles of HOMA-IR. The information on pregnancy outcomes and risk factors was extracted from the medical records of all participants and entered electronically. Logistic regression models were used to analyze the associations between HOMA-IR and pregnancy outcomes, as well as the associations between risk factors and HOMA-IR. Results Greater IR was associated with cesarean delivery, preterm delivery, macrosomia, and large for gestational age newborns, but only significantly associated with preterm delivery after adjustment for potential confounders (P < .001). Prepregnancy body mass index (BMI), weight gain before diagnosis of GDM, and triglycerides were significantly related with IR in the late second trimester (P < .001). Besides, the total area under the curve of the diagnostic 75-g oral glucose tolerance test and glycosylated hemoglobin A1c increased from the lowest to the highest HOMA-IR groups. Conclusions Increasing IR in the late second trimester predicts adverse pregnancy outcomes especially for preterm delivery in women with GDM. Additionally, prepregnancy BMI and weight gain before diagnosis of GDM are independent risk factors for the development of IR.

Amino acids levels in early pregnancy predict subsequent gestational diabetes

Abstract: Background We aimed to estimate the performance of amino acids levels in predicting the risk of subsequent gestational diabetes mellitus (GDM). Methods A total of 431 women at 12 to 16 weeks of gestation in the Department of Obstetrics and Gynecology of the Second Affiliated Hospital of Soochow University were recruited. High-performance liquid chromatography electrospray tandem mass spectrometry was used to measure amino acids levels in maternal blood at 12 to 16 weeks of gestation. At 24 to 28 weeks of gestation, all participants were administered 75-g oral glucose tolerance tests for the diagnosis of GDM. Results Alanine, isoleucine, and tyrosine levels in early pregnancy were significantly different between women who developed GDM and those who remained normal glucose tolerant. Logistic regressions showed that after adjustments for age, parity, body mass index, family history of diabetes, γ-glutamyltranspeptidase, triglycerides, fasting glucose and fasting insulin levels, alanine (odds ratio [OR], 1.46; 95% CI, 1.05-2.04; P = .027), isoleucine (OR, 1.48; 95% CI, 1.12-1.96; P = .0062), and tyrosine (OR, 1.46; 95% CI, 1.07-2.03; P = .020) levels in early pregnancy were independently associated with subsequent GDM. The addition of isoleucine and tyrosine into the conventional model improved the area under curve from 0.692 to 0.737 (P = .036) and significantly increased the net reclassification improvement (+13.7%, P = .0025). Conclusions The present study suggests that elevated isoleucine, tyrosine, and alanine levels are independently and significantly associated with subsequent incidence of GDM. New models including conventional risk factors, isoleucine and tyrosine levels in early pregnancy might help physicians identify high-risk population of GDM.

The impact of type 2 diabetes and its management on the prognosis of patients with severe COVID-19.

Abstract: Background Although type 2 diabetes mellitus (T2DM) patients with coronavirus disease 2019 (COVID-19) develop a more severe condition compared to those without diabetes, the mechanisms for this are unknown. Moreover, the impact of treatment with antihyperglycemic drugs and glucocorticoids is unclear. Methods From 1584 COVID-19 patients, 364 severe/critical COVID-19 patients with clinical outcome were enrolled for the final analysis, and patients without preexisting T2DM but elevated glucose levels were excluded. Epidemiological data were obtained and clinical status evaluation carried out to assess the impact of T2DM and its management on clinical outcomes. Results Of 364 enrolled severe COVID-19 inpatients, 114 (31.3%) had a history of T2DM. Twenty-seven (23.7%) T2DM patients died, who had more severe inflammation, coagulation activation, myocardia injury, hepatic injury, and kidney injury compared with non-DM patients. In severe COVID-19 patients with T2DM, we demonstrated a higher risk of all-cause fatality with glucocorticoid treatment (adjusted hazard ratio [HR], 3.61; 95% CI, 1.14-11.46; P = .029) and severe hyperglycemia (fasting plasma glucose ≥11.1 mmol/L; adjusted HR, 11.86; 95% CI, 1.21-116.44; P = .034). Conclusions T2DM status aggravated the clinical condition of COVID-19 patients and increased their critical illness risk. Poor fasting blood glucose (≥ 11.1 mmol/L) and glucocorticoid treatment are associated with poor prognosis for T2DM patients with severe COVID-19.

Emerging trends and the clinical impact of food insecurity in patients with diabetes.

Abstract: Food insecurity is a major public health concern in the United States affecting 15 million households according to data in 2017 from the US Department of Agriculture. Food insecurity, or the inability to consistently obtain nutritious food, disproportionately affects socioeconomically disadvantaged households, as well as those with chronic diseases including diabetes mellitus (DM). This review article explores the literature over the past 10 years pertaining to the complex relationship between food insecurity, social determinants of health, and chronic disease with an emphasis on diabetes and glycemic control. Those with diabetes and food insecurity together have been shown to have worse glycemic control compared to those who are food secure, but it remains unclear exactly how food insecurity affects glycemic control. Prior interventional studies have targeted aspects of food insecurity in patients with diabetes but have reported variable outcomes with respect to improvement in glycemic control despite effectively reducing rates of food insecurity. Additionally, few data exist regarding long-term outcomes and diabetes-related complications in this population. It is likely that many factors at both the community and individual levels impact glycemic control outcomes in the setting of food insecurity. Further studies are needed to better understand these factors and to create multifaceted targets for future interventional studies aimed at improving glycemic control in this population.

Early life exposure to 1959-1961 Chinese famine exacerbates association between diabetes and cardiovascular disease.

Abstract: BACKGROUND We aimed to assess whether early life exposure to the Chinese famine (1959-1961) modifies the association between type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in adulthood. METHODS Data from 4247 adults born between 1954 and 1964 from the 2011 and 2015 China Health and Retirement Longitudinal Study (CHARLS) were analyzed. CVD in 2011 and 2015 was based on self-reported doctor's diagnosis of cardiac events (heart attack, coronary heart disease, angina, congestive heart failure, or other heart problems) and stroke. Diabetes in 2011 was defined by fasting blood glucose, HbA1C, or known diabetes. RESULTS Diabetes in 2011 was cross-sectionally associated with an increase of CVD risk in 2011 (OR 1.91, 95%CI 1.53-2.40, P < 0.001) after adjusting for age and gender. Famine exposure changed the association between diabetes and CVD in areas severely affected by famine. The odds ratios (OR) of diabetes in 2011 for CVD in 2015 were 1.24 (95%CI 0.73-2.10), 1.27 (95%CI 0.72-2.24), 2.25 (95%CI 1.29-3.91), 4.31 (95%CI 2.07-8.97) and 1.72 (95%CI 0.84-3.51) among adults in late childhood-, mid-childhood-, early childhood-, fetal-, and nonexposed cohorts in severe famine areas, respectively. CONCLUSION T2DM is associated with the risk of CVD among Chinese adults. Fetal and early childhood exposure to the Chinese famine exacerbated the associated risk.

Diabetes during the COVID-19 pandemic: A global call to reconnect with patients and emphasize lifestyle changes and optimize glycemic and blood pressure control.

Abstract: Individuals with diabetes, obesity, and hypertension are at heightened risk of adverse outcome of coronavirusassociated disease 2019 (COVID-19). Data from many studies show that patients with diabetes have increased risk of admission in intensive care units and of mortality. Hypertension is highly prevalent in patients with COVID-19 and was the most common cardiovascular comorbidity in a meta-analysis, contributing to increase in mortality. Further, in a retrospective analysis of French patients with COVID-19, obesity (BMI >30 kg/ m) and severe obesity (BMI >35 kg/m) were present in 47.6% and 28.2% of cases, respectively. In this study, patients with higher BMI values were at greater risk for invasive mechanical ventilation than those who were nonobese. These data show high mortality risk in COVID-19 patients with diabetes, hypertension, and obesity. COVID-19 prevalence is likely to vary with different ethnic groups, country, socio-economic stratum, and healthcare support. Many countries or parts of countries are under “lockdown,” restricting movements of individuals. Such approaches are likely to have undesirable effects on patients with diabetes: on exercise, on diet, on obtaining adequate supplies of medicines, insulin, and glucosetesting reagent strips, and on interaction with healthcare providers (HCPs). In addition, psychological impacts of the COVID-19 pandemic including anxiety and depression affect more than half of the population. All these factors may destabilize glycemic and blood pressure control and may worsen obesity. A recent analysis from mathematical modeling in India predicts that lockdown will cause substantial increase in glycosylated hemoglobin (HbA1c) and future diabetes-related complications. Patients with diabetes having poorly controlled glycemia may in turn be at greater risk for COVID-19 complications and mortality. Patients with diabetes often have insufficient health education to modify drug/insulin dosages when it is difficult to communicate with or visit their primary HCPs, particularly in disadvantaged and marginalized populations, and in elderly without support. Increases in blood glucose or blood pressure levels with little expert help and inadequate knowledge to control them is likely to further increase psychological stress in patients. Fortunately, we have reached a threshold of use of telemedicine services, including video chats, telephone calls, and short messaging services to impart advice and guide treatment. Telemedicine studies before the COVID-19 pandemic show that these communication strategies can effectively lower HbA1c. In a 4-year follow-up of a study of nearly 1000 persons with diabetes randomized to a telemedicine self-management behavioral intervention, all-cause and diabetes-related hospitalizations were reduced by 11% and 17%, respectively, with consequent cost-savings. The call for “an immediate digital revolution to face this crisis” of COVID-19 seems eminently appropriate. DOI: 10.1111/1753-0407.13048

Antihyperglycemic properties of hydroxychloroquine in patients with diabetes: Risks and benefits at the time of COVID-19 pandemic.

Abstract: The antimalarial drug hydroxychloroquine (HCQ) has long been used as a disease-modifying antirheumatic drug for the treatment of several inflammatory rheumatic diseases. Over the last three decades, various studies have shown that HCQ also plays a role in the regulation of glucose homeostasis. Although the mechanisms of action underlying the glucose-lowering properties of HCQ are still not entirely clear, evidence suggests that this drug may exert multifaceted effects on glucose regulation, including improvement of insulin sensitivity, increase of insulin secretion, reduction of hepatic insulin clearance, and reduction of systemic inflammation. Preliminary studies have shown the safety and efficacy of HCQ (at a dose ranging from 400 to 600 mg/day) in patients with type 2 diabetes over a short-term period. In 2014, HCQ has been approved in India as an add-on hypoglycemic agent for patients with uncontrolled type 2 diabetes. However, large randomized controlled trials are needed to establish the safety and efficacy profile of HCQ in patients with type 2 diabetes over a long-term period. With regard to the COVID-19 pandemic, several medications (including HCQ) have been used as off-label drugs because of the lack of proven effective therapies. However, emerging evidence shows limited benefit from HCQ use in COVID-19 in general. The aim of this manuscript is to comprehensively summarize the current knowledge on the antihyperglycemic properties of HCQ and to critically evaluate the potential risks and benefits related to HCQ use in patients with diabetes, even in light of the current pandemic scenario.

Glycemic control in type 1 diabetes mellitus and COVID-19 lockdown: What comes after a "quarantine"?

Abstract: A stable or even improved glycemic control was found in adolescents with T1DM using hybrid closed loop system not only during COVID-19 lockdown but also in the weeks after, when daily activities slowly resumed. Although the slowing down of routine daily activities might still have an influence, we believe that the continuation of the health care professional assistance through telemedicine during lockdown might have led to a "dragging effect" in these patients also after its suspension.

The association between sleep efficiency and diabetes mellitus in community-dwelling individuals with or without sleep-disordered breathing.

Abstract: BACKGROUND Sleeping habits have been reported to be associated with diabetes mellitus. This study aimed to explore the relationship of sleep efficiency with diabetes mellitus in individuals with or without sleep-disordered breathing based on polysomnography records. METHODS We enrolled participants from the Sleep Heart Health Study. Objective indicators of sleep characteristics including sleep efficiency, sleep latency, slow-wave sleep, wake after sleep onset, and total arousal index were monitored via in-home polysomnography. Sleep efficiency was divided into grade 1 (≥85%), grade 2 (80%-84.9%), and grade 3 (<80%). Multivariate logistic regression models were utilized to investigate the association between sleep quality and diabetes mellitus. RESULTS The present study comprised 4737 participants with a mean age of 63.6 ± 11.0 years. The prevalence of diabetes mellitus was higher in those with grade 3 sleep efficiency than that in those with grade 1 and grade 2 sleep efficiency in participants with (10.9% vs 8.5% vs 8.3%, respectively; P =.134) or without (9.5% vs 5.6% vs 3.5%, respectively; P <.001) sleep-disordered breathing. After adjusting for potential confounding factors, sleep efficiency <80% was associated with the prevalence of diabetes mellitus only in participants without sleep-disordered breathing (odds ratio, 1.894; 95% confidence interval, 1.187-3.022, P =.007). CONCLUSION Poor sleep efficiency is associated with diabetes mellitus in those without sleep-disordered breathing. Therefore, the relationship between sleep efficiency and diabetes mellitus is worth further investigation.

Randomized controlled trial comparing hydroxychloroquine with pioglitazone as third‐line agents in type 2 diabetic patients failing metformin plus a sulfonylurea: A pilot study

Abstract: Funding information National Center for Advancing Translational Sciences, Grant/Award Number: UCLA CTSI UL1TR000124; National Institute of General Medical Sciences, Grant/Award Number: SC3GM113767; National Institute on Minority Health and Health Disparities, Grant/Award Number: U54 MD007598 Highlights • The anti-inflammatory agent, hydroxychloroquine, improved glycemic control in type 2 diabetes patients when used as a third-line agent added to metformin and a sulfonylurea. • In comparison to pioglitazone, hydroxychloroquine lowered hemoglobin A1c levels less effectively and did not improve insulin sensitivity, but also did not cause any weight gain, hypoglycemia, or pedal edema. • In this small, proof-of-concept study, hydroxychloroquine was well tolerated and may be an alternative treatment choice in combination with other agents.

Metabolic syndrome and semen quality in adult population

Abstract: BACKGROUND Male obesity is suggested to impact negatively on male fertility and semen quality in numerous studies. However, previous literatures regarding health effects of the metabolic syndrome (MetS) on semen quality are rare and inconsistent. The aim of this study is to investigate the relationship between MetS and sperm parameters in a Taiwanese reproductive-age male population. METHODS A total of 8395 men who attended a private medical screening program in Taiwan from 2010 to 2016 were included in this cross-sectional study. Semen analysis was assessed in accordance with the WHO guidelines and included sperm concentration, total motility, progressive motility, and morphology. MetS was defined by the modified National Cholesterol Education Program Third Adult Treatment Panel (NCEP ATP III) criteria with the Asian cutoff for waist circumference (WC). The associations between MetS and semen analysis were examined by multivariable linear regressions. RESULTS After fully adjusting for pertinent covariables, MetS was significantly associated with a reduced percentage of sperm normal morphology. Blood pressure, WC, and serum glucose had a significantly negative association with sperm normal morphology. Individuals with an increased number of MetS components had a closer association with reduced sperm progressive motility and the percentage of normal morphology. CONCLUSION MetS and its components exhibited deleterious effects on semen quality among reproductive-age men. Further studies are warranted to explore these pathophysiologic relationship and underlying mechanisms.

Therapeutic approaches for latent autoimmune diabetes in adults: One size does not fit all

Abstract: Recent advances in the understanding of latent autoimmune diabetes in adults (LADA) pathophysiology make it increasingly evident that people with LADA comprise a heterogenous group of patients. This makes the establishment of a standard treatment algorithm challenging. On top of its glucose-lowering action, insulin may exert anti-inflammatory effects, rendering it an attractive therapeutic choice for a type of diabetes in which autoinflammation and beta cell insufficiency play major pathogenetic roles. However, there is growing evidence that other antidiabetic drugs, such as metformin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and thiazolidinediones, might have a role in optimizing glycemic control and preserving beta cell function in individuals with LADA, either alone or in combination with insulin. Although most of these drugs have been routinely used in the daily clinical setting for years, large prospective randomized trials are needed to assess whether they are capable of delaying progression to insulin dependence as well as their effects on diabetic complications. The aim of the present review is to discuss the current state and future perspectives of LADA therapy, emphasizing the need for individualized and patient-centered therapeutic approaches.

Home-based training strategy to maintain muscle function in older adults with diabetes during COVID-19 confinement.

Abstract: On 11 March 12020, the World Health Organization (WHO) declared a global pandemic caused by a new virus of the family Coronaviridae that later was denominated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Like others in the coronavirus family, this virus causes various clinical manifestations under the term coronavirus disease 2019 (COVID-19), including respiratory symptoms that vary from the common cold to severe pneumonia with respiratory distress syndrome, septic shock, and multiorgan failure. Since the beginning of the epidemic nearly 2 million cases have been detected worldwide and numbers are rapidly increasing (1 934 583, updated data 14 April 2020). Governments in many countries have adopted strategies proposed by Chinese experts and supported by the WHO to contain the virus, which may lead to movement restrictions for most of their citizens. Potential negative health effects of isolation need to be addressed. Studies have shown that prolonged confinement (eg, in submariners) can result in loss of muscle strength in 2 months and that only 7 days of bed rest are needed to impair insulin sensitivity and exercise capacity in healthy young men. The joint effort of the world scientific community is generating a large amount of information that is rapidly modified with new evidence, most of it regarding interventions to treat and control COVID-19. However, there is a lack of information available about strategies to maintain health while confined during this pandemic, especially in at-risk populations like older adults and people suffering from type 2 diabetes (DM2) and respiratory and cardiovascular diseases. In addition, those individuals recovering from COVID-19 can be expected to have even greater loss of muscle strength. Maintaining muscle mass and its principal functions (strength, power, and endurance) is particularly critical in diabetic older adults undergoing a situation of home confinement. Physical activity has been shown to be a very effective strategy in the prevention and treatment of DM2, with similar benefits from both endurance and strength training on insulin sensitivity and glycemic control, increased fitness levels, and decreased risk of disability. Moreover, strength training focusing on performing the concentric phase of the movement as fast as possible has been shown to improve physical performance in DM2 frail older people. The Supplement provides a simple, well-structured multicomponent training program that older DM2 adults could follow at home. The exercise protocol has been developed to maintain muscle mass, strength, and therefore glycemic control and functional ability. Other important aspects like mobility, flexibility, and balance are also included. In general, this training program is suitable for older adults without severe mobility and/or balance limitations, as well as other medical Received: 4 April 2020 Revised: 20 April 2020 Accepted: 5 May 2020

Insulin resistance is associated with urinary albumin-creatinine ratio in normal weight individuals with hypertension and diabetes: The REACTION study.

Abstract: BACKGROUND The relationship between albuminuria and insulin resistance (IR) has not been clarified in previous studies. This study was conducted to examine whether IR is associated with albuminuria in subjects with diverse blood pressure and glycometabolism statuses. METHODS This study included 34 136 participants whose data were drawn from a cross-sectional survey named the 2011 REACTION study. The participants were divided into six groups. The urinary albumin-creatinine ratio (UACR) and glomerular filtration rate (GFR) were used as markers of chronic kidney disease (CKD). Variance tests and logistic regression models were performed for homeostatic model assessment of insulin resistance (HOMA-IR) in relation to UACR and eGFR. RESULTS First, UACR levels and HOMA-IR exhibited a positive correlation among participants (P < 0.05), and a negative correlation existed between GFR and HOMA-IR (P < 0.05). Second, in the hypertension with diabetes group, in individuals whose body mass index (BMI) was 18.5-24.0 kg/m2 , age was 50-60 years old, low density lipoprotein cholesterol (LDL-C) was 2.6-3.4 mmol/L or high density lipoprotein cholesterol (HDL-C) was 0.9-1.55 mmol/L, HOMA-IR was positively associated with UACR (P < 0.05). However, there was a negative correlation between GFR and HOMA-IR in the hypertension with diabetes group in individuals whose BMI was 18.5-24.0 kg/m2 or whose age was over 65 years old (P < 0.05). CONCLUSIONS In the context of different blood pressure and glycometabolism statuses, the positive correlation between UACR levels and HOMA-IR was affected by BMI, age, LDL-C, HDL-C, and GFR. In patients with hypertension and diabetes, the early detection and intervention of IR and related risk factors in patients with normal BMI may reduce the occurrence of microalbuminuria and delay the progression of CKD.

Current situation of clinical islet transplantation from allogeneic toward xenogeneic

Abstract: Currently, type 1 diabetes requires lifelong insulin injection and careful blood glucose control to prevent secondary complications, but islet transplantation could make a type 1 diabetic patient insulin independent. On the other hand, islet transplantation needs human donors and donor shortage is the most serious issue. To alleviate the donor shortage, non-heart-beating and living donors were used; in addition, the efficacy of islet isolation and transplantation has been improved. However, the donor shortage issue will not be solved as long as human donors are the only source. To solve the donor shortage issue, islet xenotransplantation using porcine islets was initiated in 1994. Islet xenotransplantation has a potential to cure many type 1 diabetic patients, although there is the risk of developing serious or novel infection. Therefore, the World Health Organization has been interested in xenotransplantation, and the International Xenotransplantation Association (IXA) has published consensus statements to initiate xenogeneic islet transplantation. Clinical islet xenotransplantation was conducted under the official regulation, and safety and efficacy data have been accumulated. Currently an efficient method to overcome xenorejection is an important research target. In addition to traditional immunosuppressive drugs and immune isolation methods, the gene modification with CRISPR and blastocyst complementation have been investigated with promising outcomes. Once the xenorejection issue is overcome, islet xenotransplantation should become a curative treatment for type 1 diabetic patients. HIGHLIGHTS: Allogeneic islet transplantation has been developed for unstable type 1 diabetic patients to stabilize the blood glucose levels and prevent hypoglycemia, and donor shortage is the most serious issue. To alleviate the donor shortage issue, non-heart-beating donor and living donors were used and to solve the donor shortage issue porcine islets have been used for islet transplantation. Recent new technologies including CRISPR and blastocyst complementation should improve the efficacy of islet xenotransplantation.

Dose-response associations between serum creatinine and type 2 diabetes mellitus risk: A Chinese cohort study and meta-analysis of cohort studies

Abstract: Background This study aims to investigate the association between serum creatinine and risk of type 2 diabetes mellitus (T2DM) based on a cohort analysis and meta-analysis of cohort studies. Methods We enrolled 41 439 participants aged ≥18 years without T2DM at baseline, who had ≥2 health examinations based on an ongoing prospective cohort in Beijing. Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% CIs. For the meta-analysis, cohort studies reporting risk estimates for the serum creatinine-T2DM association were included. A random-effects model was used to calculate summary relative risks (RRs) and restricted cubic splines to model the dose-response association. Results During a mean follow-up of 3.54 years, 1867 developed T2DM. Low serum creatinine was associated with increased risk of T2DM; adjusted HRs (95% CIs) across sex-specific quartiles were 1.45 (1.24, 1.71), 1.19 (1.02, 1.39), 1.07 (0.92, 1.24), and 1.00 (reference). The association was significant for both sexes and individuals with overweight or obesity. In the meta-analysis of six cohort studies (including the current study) involving 115 767 participants and 5370 T2DM events, the pooled RR was 1.61 (95% CI 1.35, 1.92), comparing the lowest with the highest category of serum creatinine. We found a linear association between serum creatinine and T2DM risk (Pnonlinearity = .082) and an increased risk of T2DM with each 0.1-mg/dL decrease in serum creatinine (RR = 1.07; 95% CI 1.04, 1.09). Conclusions The cohort study and meta-analysis provide further evidence supporting the negative association between serum creatinine and T2DM risk in a linear dose-response pattern.

Adjunct Therapies in Treatment of Type 1 Diabetes

Abstract: In spite of developments with novel insulin preparations, novel modes of insulin delivery with insulin infusion pumps, and the facility of continuous glucose monitoring, only 20% of patients with type 1 diabetes are under adequate control The need for innovation is clear, and, therefore, the use of adjunct therapies with other pharmacological agents currently in use for type 2 diabetes, has been tried Currently, pramlintide is the only agent licensed for use in this condition in addition to insulin Global trials have been conducted with liraglutide, a glucagon-like peptide 1 receptor agonist (GLP-1RA), dapagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, and sotagliflozin, an inhibitor of both SGLT1 and SGLT2 transporters While dapagliflozin and sotagliflozin have now been licensed for clinical use in this condition in Europe and Japan, they have hitherto not been licensed in the United States due to a small increase in the risk of diabetic ketoacidosis However, these agents reduce glycosylated hemoglobin (HbA1c) by 04%, reduce glycemic oscillations, and do not increase the risk of hypoglycemia Liraglutide, on the other hand, induced a smaller reduction in HbA1c and thus was not considered for a license However, further trials are currently being conducted with a combination of semaglutide, the most potent GLP-1RA, and dapagliflozin to determine whether this approach would yield better outcomes

Liver adenomatosis in patients with hepatocyte nuclear factor-1 alpha maturity onset diabetes of the young (HNF1A-MODY): Clinical, radiological and pathological characteristics in a French series

Abstract: Background Liver adenomatosis (LA) is a rare disease resulting from biallelic inactivation of the hepatocyte nuclear factor-1 alpha (HNF1A) gene, which induces the proliferation of adenoma cells in liver parenchyma. Liver adenomatosis has only been documented in case reports from patients carrying a HNF1A germline mutation. We have evaluated the frequency of LA among a large cohort of patients with HNF1A-maturity onset diabetes of the young (MODY), previously termed "MODY3," and herein describe its clinical, radiological, and pathological characteristics. Methods In all, 137 HNF1A-MODY subjects from 74 families were screened by liver ultrasonography in 13 centers, and 15 additional cases of LA were later included in the series. Liver adenomatosis was confirmed by liver computed tomography, magnetic resonance imaging (MRI), and/or histopathology. Results Among 137 carriers of an HNF1A mutation, 9 patients (6.5%) from seven families were diagnosed with LA. Diabetes mellitus was present in 87.5% of patients with LA. In 25% of patients, LA was diagnosed due to intra-abdominal or intratumoral bleeding. Liver biochemistry was near normal in all patients. Liver imaging showed adenomas of various sizes and numbers. On MRI, most nodules had the radiological characteristics of steatotic adenomas. Histopathological confirmation of LA was available in 13 cases, and these adenomas were mostly steatotic. Surgery was initially performed in 37.5% of patients, and liver disease progression was observed in 30%. No disease progression was observed in 14 pregnancies. Conclusions The frequency of LA in a cohort of screened HNF1A-MODY patients and the high incidence of LA progression and/or hemorrhage warrants systematic screening for liver adenomatosis in HNF1A-MODY families.

Assessing different anthropometric indices and their optimal cutoffs for prediction of type 2 diabetes and impaired fasting glucose in Asians: The Jinchang Cohort Study.

Abstract: Background To study the association between anthropometric measurements and the risk of diabetes and impaired fasting glucose (IFG) and compare body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) to determine the best indicator and its optimal cutoffs for predicting type 2 diabetes and IFG. Methods A Chinese prospective (2011-2019) cohort named the Jingchang cohort that included 48 001 participants was studied. Using Cox proportional hazard models, hazard ratios (HRs) for incident type 2 diabetes or IFG per 1 SD change in BMI, WC, and WHtR were calculated. Area under the curve (AUC) was compared to identify the best anthropometric variable and its optimal cutoff for predicting diabetes. Results The association of BMI, WC, and WHtR with type 2 diabetes or IFG risk was positive in the univariate and multivariable-adjusted Cox proportional hazard models. Of all three indexes, the AUC of BMI was largest and that of WC was smallest. The derived cutoff values for BMI, WC, and WHtR were 24.6 kg/m2 , 89.5 cm, and 0.52 in men and 23.4 kg/m2 , 76.5 cm, and 0.47 in women for predicting diabetes, respectively. The derived cutoff values for BMI, WC, and WHtR were 23.4 kg/m2 , 87.5 cm, and 0.50 in men and 22.5 kg/m2 , 76.5 cm, and 0.47 in women for predicting IFG, respectively. [Correction added on 14 April 2020, after first online publication: '0' has been deleted from 'WC,0' in the first sentence.]. Conclusions Our derived cutoff points were lower than the values specified in the most current Asian diabetes guidelines. We recommend a cutoff point for BMI in Asians of 23 kg/m2 and for WC a cutoff point of 89 cm in men and 77 cm in women to define high-risk groups for type 2 diabetes; screening should be considered for these populations.