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Showing papers in "Diabetes Care in 2020"


Journal ArticleDOI
TL;DR: In this study, obese patients had increased odds of progressing to severe COVID-19 and clinicians should pay close attention to obese patients, who should be carefully managed with prompt and aggressive treatment.
Abstract: OBJECTIVE Patients with obesity are at increased risk of exacerbations from viral respiratory infections. However, the association of obesity with the severity of coronavirus disease 2019 (COVID-19) is unclear. We examined this association using data from the only referral hospital in Shenzhen, China. RESEARCH DESIGN AND METHODS A total of 383 consecutively hospitalized patients with COVID-19 admitted from 11 January 2020 to 16 February 2020 and followed until 26 March 2020 at the Third People’s Hospital of Shenzhen were included. Underweight was defined as a BMI RESULTS Of the 383 patients, 53.1% were normal weight, 4.2% were underweight, 32.0% were overweight, and 10.7% were obese at admission. Obese patients tended to have symptoms of cough (P = 0.03) and fever (P = 0.06) compared with patients who were not obese. Compared with normal weight patients, those who were overweight had 1.84-fold odds of developing severe COVID-19 (odds ratio [OR] 1.84, 95% CI 0.99–3.43, P = 0.05), while those who were obese were at 3.40-fold odds of developing severe disease (OR 3.40, 95% CI 1.40–2.86, P = 0.007), after adjusting for age, sex, epidemiological characteristics, days from disease onset to hospitalization, presence of hypertension, diabetes, cardiovascular disease, chronic obstructive pulmonary disease, liver disease and cancer, and drug used for treatment. Additionally, after similar adjustment, men who were obese versus those who were normal weight were at increased odds of developing severe COVID-19 (OR 5.66, 95% CI 1.80–17.75, P = 0.003). CONCLUSIONS In this study, obese patients had increased odds of progressing to severe COVID-19. As the severe acute respiratory syndrome coronavirus 2 may continue to spread worldwide, clinicians should pay close attention to obese patients, who should be carefully managed with prompt and aggressive treatment.

506 citations


Journal ArticleDOI
TL;DR: C-reactive protein may help to identify patients with diabetes who are at greater risk of dying during hospitalization and whose association with glucose-lowering or blood pressure–lowering medications is linked to poor prognosis.
Abstract: OBJECTIVE Diabetes is one of the most distinct comorbidities of COVID-19. Here, we describe the clinical characteristics of and outcomes in patients with diabetes in whom COVID-19 has been confirmed or clinically diagnosed (with typical features on lung imaging and symptoms), and their association with glucose-lowering or blood pressure–lowering medications. RESEARCH DESIGN AND METHODS In this retrospective study involving 904 patients with COVID-19 (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between the group with diabetes and the group without diabetes, and between groups taking different medications. Logistic regression was used in order to explore risk factors associated with mortality or poor prognosis. RESULTS The proportion of comorbid diabetes is similar between cases of confirmed and of clinically diagnosed COVID-19. Risk factors for higher mortality of patients with diabetes and COVID-19 were older age (adjusted odds ratio [aOR] 1.09 [95% CI 1.04, 1.15] per year increase; P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24]; P = 0.043). Insulin usage (aOR 3.58 [95% CI 1.37, 9.35]; P = 0.009) was associated with poor prognosis. Clinical outcomes of those who use an ACE inhibitor (ACEI) or angiotensin II type-I receptor blocker (ARB) were comparable with those of patients who do not use ACEI/ARB among patients with diabetes and hypertension who have COVID-19. CONCLUSIONS C-reactive protein may help to identify patients with diabetes who are at greater risk of dying during hospitalization. Older patients with diabetes were prone to death related to COVID-19. Attention needs to be paid to patients with diabetes and COVID-19 who use insulin. ACEI/ARB use showed no significant impact on patients with diabetes and hypertension who have COVID-19.

323 citations


Journal ArticleDOI
TL;DR: Insulin infusion may be an effective method for achieving glycemic targets and improving outcomes in patients with COVID-19 and Cox regression analysis evidenced that patients with hyperglycemia treated with insulin infusion had a lower risk of severe disease than patients without insulin infusion.
Abstract: OBJECTIVE An important prognostic factor in any form of infection seems to be glucose control in patients with type 2 diabetes mellitus. There is no information about the effects of tight glycemic control on Covid-19 outcomes in patients with hyperglycemia. Therefore, we examined the effects of optimal glycemic control in patients with hyperglycemia affected by Covid-19. RESEARCH DESIGN AND METHODS Fifty-nine patients with Covid-19 hospitalized with moderate disease were evaluated. On the basis of admission glycemia >7.77 mmol/L, patients were divided into hyperglycemic and normoglycemic groups. Interleukin 6 (IL-6) and D-dimer levels were evaluated at admission and weekly during hospitalization. The composite end point was severe disease, admission to an intensive care unit, use of mechanical ventilation, or death. RESULTS Thirty-four (57.6%) patients were normoglycemic and 25 (42.4%) were hyperglycemic. In the hyperglycemic group, 7 (28%) and 18 (72%) patients were diagnosed with diabetes already before admission, and 10 (40%) and 15 (60%) were treated without and with insulin infusion, respectively. The mean of glycemia during hospitalization was 10.65 ± 0.84 mmol/L in the no insulin infusion group and 7.69 ± 1.85 mmol/L in the insulin infusion group. At baseline, IL-6 and D-dimer levels were significantly higher in the hyperglycemic group than in the normoglycemic group (P CONCLUSIONS Insulin infusion may be an effective method for achieving glycemic targets and improving outcomes in patients with Covid-19.

316 citations


Journal ArticleDOI
TL;DR: The association between obesity and COVID-19 severity of illness among patients with laboratory-confirmed SARS-CoV-2 infection is investigated and obesity was defined as BMI ≥25 kg/m2 in this Asian population.
Abstract: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has attracted increasing worldwide attention (1). Obesity commonly aggravates the severity of respiratory diseases, but it is currently not known whether obese patients are also more likely to have greater COVID-19 severity of illness. We investigated the association between obesity and COVID-19 severity of illness among patients with laboratory-confirmed SARS-CoV-2 infection. We enrolled adult patients with COVID-19 from three hospitals in China between 17 January 2020 and 11 February 2020. Seventy-five patients were diagnosed as obese (i.e., case subjects). We randomly matched each case subject with one control subject (nonobese) by sex (1:1) and age (±5 years). The cohort thus comprised 150 patients with COVID-19. The study protocol was approved by local ethics committees of the three hospitals. The requirement for written informed consent was waived due to the retrospective and anonymous nature of the study. COVID-19 was diagnosed as a positive result by high-throughput sequencing or real-time reverse transcriptase PCR assay of oropharyngeal swab specimens. COVID-19 severity of illness was assessed during hospitalization and classified into four clinical subtypes (i.e., mild, moderate, severe, or critically ill) based on management guidelines (2). Obesity was defined as BMI ≥25 kg/m2 in this Asian population. Diabetes was determined as either history of diagnosed diabetes, …

306 citations


Journal ArticleDOI
TL;DR: COVID-19 patients with diabetes had worse outcomes compared with the sex- and age-matched patients without diabetes, and older age and comorbid hypertension independently contributed to in-hospital death of patients with Diabetes.
Abstract: OBJECTIVE Diabetes is common in COVID-19 patients and associated with unfavorable outcomes. We aimed to describe the characteristics and outcomes and to analyze the risk factors for in-hospital mortality of COVID-19 patients with diabetes. RESEARCH DESIGN AND METHODS This two-center retrospective study was performed at two tertiary hospitals in Wuhan, China. Confirmed COVID-19 patients with diabetes (N = 153) who were discharged or died from 1 January 2020 to 8 March 2020 were identified. One sex- and age-matched COVID-19 patient without diabetes was randomly selected for each patient with diabetes. Demographic, clinical, and laboratory data were abstracted. Cox proportional hazards regression analyses were performed to identify the risk factors associated with the mortality in these patients. RESULTS Of 1,561 COVID-19 patients, 153 (9.8%) had diabetes, with a median age of 64.0 (interquartile range 56.0–72.0) years. A higher proportion of intensive care unit admission (17.6% vs. 7.8%, P = 0.01) and more fatal cases (20.3% vs. 10.5%, P = 0.017) were identified in COVID-19 patients with diabetes than in the matched patients. Multivariable Cox regression analyses of these 306 patients showed that hypertension (hazard ratio [HR] 2.50, 95% CI 1.30–4.78), cardiovascular disease (HR 2.24, 95% CI 1.19–4.23), and chronic pulmonary disease (HR 2.51, 95% CI 1.07–5.90) were independently associated with in-hospital death. Diabetes (HR 1.58, 95% CI 0.84–2.99) was not statistically significantly associated with in-hospital death after adjustment. Among patients with diabetes, nonsurvivors were older (76.0 vs. 63.0 years), most were male (71.0% vs. 29.0%), and were more likely to have underlying hypertension (83.9% vs. 50.0%) and cardiovascular disease (45.2% vs. 14.8%) (all P values CONCLUSIONS COVID-19 patients with diabetes had worse outcomes compared with the sex- and age-matched patients without diabetes. Older age and comorbid hypertension independently contributed to in-hospital death of patients with diabetes.

281 citations


Journal ArticleDOI
TL;DR: In this paper, the authors report multicenter regional data from North West London (NWL) of new-onset type 1 diabetes and diabetic ketoacidosis (DKA) in children up to the age of 16 years during the peak of the COVID-19 pandemic.
Abstract: Data on new-onset type 1 diabetes during the coronavirus disease 2019 (COVID-19) pandemic, particularly in children, are limited. A recent U.S. multicenter study reported outcomes in 64 adults and children with type 1 diabetes, and confirmed or suspected COVID-19. However, only six patients presented with new-onset type 1 diabetes (1). We report multicenter regional data from North West London (NWL) of new-onset type 1 diabetes and diabetic ketoacidosis (DKA) in children up to the age of 16 years during the peak of the COVID-19 pandemic. We collected data from five inpatient units (four National Health Service [NHS] Trusts) comprising the NWL Pediatric Diabetes Network between 23 March (coinciding with the commencement of the U.K. Government lockdown) and 4 June 2020. Thirty children aged 23 months to 16.8 years presented with new-onset type 1 diabetes (Table 1). We observed an apparent increase in two units, with 10 cases each (versus typically 2 and 4 cases, respectively, for April/May combined in the previous 5 years). Rates in the other three units were similar to previous years. A high proportion of children (21/30, 70%) presented with DKA, …

255 citations


Journal ArticleDOI
TL;DR: Using lessons from other diseases and the data gathered to date, a roadmap is delineated through which the field can incorporate the endotype concept into laboratory and clinical practice and predict that such an effort will accelerate the implementation of precision medicine and has the potential for impact on the approach to translational research, trial design, and clinical management.
Abstract: The clinical diagnosis of new-onset type 1 diabetes has, for many years, been considered relatively straightforward. Recently, however, there is increasing awareness that within this single clinical phenotype exists considerable heterogeneity: disease onset spans the complete age range; genetic susceptibility is complex; rates of progression differ markedly, as does insulin secretory capacity; and complication rates, glycemic control, and therapeutic intervention efficacy vary widely. Mechanistic and immunopathological studies typically show considerable patchiness across subjects, undermining conclusions regarding disease pathways. Without better understanding, type 1 diabetes heterogeneity represents a major barrier both to deciphering pathogenesis and to the translational effort of designing, conducting, and interpreting clinical trials of disease-modifying agents. This realization comes during a period of unprecedented change in clinical medicine, with increasing emphasis on greater individualization and precision. For complex disorders such as type 1 diabetes, the option of maintaining the "single disease" approach appears untenable, as does the notion of individualizing each single patient's care, obliging us to conceptualize type 1 diabetes less in terms of phenotypes (observable characteristics) and more in terms of disease endotypes (underlying biological mechanisms). Here, we provide our view on an approach to dissect heterogeneity in type 1 diabetes. Using lessons from other diseases and the data gathered to date, we aim to delineate a roadmap through which the field can incorporate the endotype concept into laboratory and clinical practice. We predict that such an effort will accelerate the implementation of precision medicine and has the potential for impact on our approach to translational research, trial design, and clinical management.

188 citations


Journal ArticleDOI
TL;DR: It is suggested that diabetes and related traits may increase ACE2 expression, which may influence susceptibility to infection (or more severe infection), however, none of these findings withstood rigorous multiple testing corrections.
Abstract: OBJECTIVE COVID-19 has become a major public health problem. There is good evidence that ACE2 is a receptor for SARS-CoV-2, and high expression of ACE2 may increase susceptibility to infection. We aimed to explore risk factors affecting susceptibility to infection and prioritize drug repositioning candidates, based on Mendelian randomization (MR) studies on ACE2 lung expression. RESEARCH DESIGN AND METHODS We conducted a phenome-wide MR study to prioritize diseases/traits and blood proteins causally linked to ACE2 lung expression in GTEx. We also explored drug candidates whose targets overlapped with the top-ranked proteins in MR, as these drugs may alter ACE2 expression and may be clinically relevant. RESULTS The most consistent finding was tentative evidence of an association between diabetes-related traits and increased ACE2 expression. Based on one of the largest genome-wide association studies on type 2 diabetes mellitus (T2DM) to date (N = 898,130), T2DM was causally linked to raised ACE2 expression (P = 2.91E−03; MR-IVW). Significant associations (at nominal level; P CONCLUSIONS Our analysis suggested that diabetes and related traits may increase ACE2 expression, which may influence susceptibility to infection (or more severe infection). However, none of these findings withstood rigorous multiple testing corrections (at false discovery rate

187 citations


Journal ArticleDOI
TL;DR: In this multicenter, case-control, retrospective, observational study of patients with type 2 diabetes admitted to the hospital for COVID-19, sitagliptin treatment at the time of hospitalization was associated with reduced mortality and improved clinical outcomes as compared with standard-of-care treatment.
Abstract: OBJECTIVE Poor outcomes have been reported in patients with type 2 diabetes and coronavirus disease 2019 (COVID-19); thus, it is mandatory to explore novel therapeutic approaches for this population. RESEARCH DESIGN AND METHODS In a multicenter, case-control, retrospective, observational study, sitagliptin, an oral and highly selective dipeptidyl peptidase 4 inhibitor, was added to standard of care (e.g., insulin administration) at the time of hospitalization in patients with type 2 diabetes who were hospitalized with COVID-19. Every center also recruited at a 1:1 ratio untreated control subjects matched for age and sex. All patients had pneumonia and exhibited oxygen saturation RESULTS Of the 338 consecutive patients with type 2 diabetes and COVID-19 admitted in Northern Italy hospitals included in this study, 169 were on sitagliptin, while 169 were on standard of care. Treatment with sitagliptin at the time of hospitalization was associated with reduced mortality (18% vs. 37% of deceased patients; hazard ratio 0.44 [95% CI 0.29–0.66]; P = 0.0001), with an improvement in clinical outcomes (60% vs. 38% of improved patients; P = 0.0001) and with a greater number of hospital discharges (120 vs. 89 of discharged patients; P = 0.0008) compared with patients receiving standard of care, respectively. CONCLUSIONS In this multicenter, case-control, retrospective, observational study of patients with type 2 diabetes admitted to the hospital for COVID-19, sitagliptin treatment at the time of hospitalization was associated with reduced mortality and improved clinical outcomes as compared with standard-of-care treatment. The effects of sitagliptin in patients with type 2 diabetes and COVID-19 should be confirmed in an ongoing randomized, placebo-controlled trial.

175 citations


Journal ArticleDOI
TL;DR: The COVID-19 pandemic might have altered diabetes presentation and DKA severity, and Preparing for any “second wave” requires strategies to educate and reassure parents about timely emergency department attendance for non–CO VID-19 symptoms.
Abstract: OBJECTIVE To evaluate whether the diagnosis of pediatric type 1 diabetes or its acute complications changed during the early phase of the coronavirus disease 2019 (COVID-19) pandemic in Italy. RESEARCH DESIGN AND METHODS This was a cross-sectional, Web-based survey of all Italian pediatric diabetes centers to collect diabetes, diabetic ketoacidosis (DKA), and COVID-19 data in patients presenting with new-onset or established type 1 diabetes between 20 February and 14 April in 2019 and 2020. RESULTS Fifty-three of 68 centers (77.9%) responded. There was a 23% reduction in new diabetes cases in 2020 compared with 2019. Among those newly diagnosed patient who presented in a state of DKA, the proportion with severe DKA was 44.3% in 2020 vs. 36.1% in 2019 (P = 0.03). There were no differences in acute complications. Eight patients with asymptomatic or mild COVID-19 had laboratory-confirmed severe acute respiratory syndrome coronavirus 2. CONCLUSIONS The COVID-19 pandemic might have altered diabetes presentation and DKA severity. Preparing for any “second wave” requires strategies to educate and reassure parents about timely emergency department attendance for non–COVID-19 symptoms.

168 citations


Journal ArticleDOI
TL;DR: These first-ever global estimates suggest that DRLECs are a large and growing contributor to the disability burden worldwide and disproportionately affect males and middle- to older-aged populations, and should facilitate policy makers worldwide to target strategies at populations disproportionately affected byDRLECs.
Abstract: OBJECTIVE: No study has reported global disability burden estimates for individual diabetes-related lower-extremity complications (DRLECs). The Global Burden of Disease (GBD) study presents a robust opportunity to address this gap. RESEARCH DESIGN AND METHODS: GBD 2016 data, including prevalence and years lived with disability (YLDs), for the DRLECs of diabetic neuropathy, foot ulcer, and amputation with and without prosthesis were used. The GBD estimated prevalence using data from systematic reviews and DisMod-MR 2.1, a Bayesian meta-regression tool. YLDs were estimated as the product of prevalence estimates and disability weights for each DRLEC. We reported global and sex-, age-, region-, and country-specific estimates for each DRLEC for 1990 and 2016. RESULTS: In 2016, an estimated 131 million people (1.8% of the global population) had DRLECs. An estimated 16.8 million YLDs (2.1% global YLDs) were caused by DRLECs, including 12.9 million (95% uncertainty interval 8.30–18.8) from neuropathy only, 2.5 million (1.7–3.6) from foot ulcers, 1.1 million (0.7–1.4) from amputation without prosthesis, and 0.4 million (0.3–0.5) from amputation with prosthesis. Age-standardized YLD rates of all DRLECs increased by between 14.6% and 31.0% from 1990 estimates. Male-to-female YLD ratios ranged from 0.96 for neuropathy only to 1.93 for foot ulcers. The 50- to 69-year-old age-group accounted for 47.8% of all YLDs from DRLECs. CONCLUSIONS: These first-ever global estimates suggest that DRLECs are a large and growing contributor to the disability burden worldwide and disproportionately affect males and middle- to older-aged populations. These findings should facilitate policy makers worldwide to target strategies at populations disproportionately affected by DRLECs.

Journal ArticleDOI
TL;DR: EMPA effectively reduces hepatic fat in patients with T2D with excellent glycemic control and short known disease duration, and Interestingly, EMPA also decreases circulating uric acid and raises adiponectin levels despite unchanged insulin sensitivity.
Abstract: OBJECTIVE To evaluate whether the sodium–glucose cotransporter 2 inhibitor empagliflozin (EMPA) reduces liver fat content (LFC) in recent-onset and metabolically well-controlled type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Patients with T2D (n = 84) (HbA1c 6.6 ± 0.5% [49 ± 10 mmol/mol], known disease duration 39 ± 27 months) were randomly assigned to 24 weeks of treatment with 25 mg daily EMPA or placebo. The primary end point was the difference of the change in LFC as measured with magnetic resonance methods from 0 (baseline) to 24 weeks between groups. Tissue-specific insulin sensitivity (secondary outcome) was assessed by two-step clamps using an isotope dilution technique. Exploratory analysis comprised circulating surrogate markers of insulin sensitivity and liver function. Statistical comparison was done by ANCOVA adjusted for respective baseline values, age, sex, and BMI. RESULTS EMPA treatment resulted in a placebo-corrected absolute of −1.8% (95% CI −3.4, −0.2%; P = 0.02) and relative change in LFC of −22% (−36, −7%; P = 0.009) from baseline to end of treatment, corresponding to a 2.3-fold greater reduction. Weight loss occurred only with EMPA (placebo-corrected change −2.5 kg [−3.7, −1.4 kg]; P CONCLUSIONS EMPA effectively reduces hepatic fat in patients with T2D with excellent glycemic control and short known disease duration. Interestingly, EMPA also decreases circulating uric acid and raises adiponectin levels despite unchanged insulin sensitivity. EMPA could therefore contribute to the early treatment of nonalcoholic fatty liver disease in T2D.

Journal ArticleDOI
TL;DR: This Consensus Report describes a foundation for precision diabetes medicine, while highlighting what remains to be done to realize its potential, to provide a roadmap for precision medicine in diabetes that helps improve the quality of life for all those with diabetes.
Abstract: The convergence of advances in medical science, human biology, data science, and technology has enabled the generation of new insights into the phenotype known as "diabetes." Increased knowledge of this condition has emerged from populations around the world, illuminating the differences in how diabetes presents, its variable prevalence, and how best practice in treatment varies between populations. In parallel, focus has been placed on the development of tools for the application of precision medicine to numerous conditions. This Consensus Report presents the American Diabetes Association (ADA) Precision Medicine in Diabetes Initiative in partnership with the European Association for the Study of Diabetes (EASD), including its mission, the current state of the field, and prospects for the future. Expert opinions are presented on areas of precision diagnostics and precision therapeutics (including prevention and treatment), and key barriers to and opportunities for implementation of precision diabetes medicine, with better care and outcomes around the globe, are highlighted. Cases where precision diagnosis is already feasible and effective (i.e., monogenic forms of diabetes) are presented, while the major hurdles to the global implementation of precision diagnosis of complex forms of diabetes are discussed. The situation is similar for precision therapeutics, in which the appropriate therapy will often change over time owing to the manner in which diabetes evolves within individual patients. This Consensus Report describes a foundation for precision diabetes medicine, while highlighting what remains to be done to realize its potential. This, combined with a subsequent, detailed evidence-based review (due 2022), will provide a roadmap for precision medicine in diabetes that helps improve the quality of life for all those with diabetes.

Journal ArticleDOI
TL;DR: In this article, the clinical impact of four treatment strategies in adults with Type 1 diabetes (T1D): real-time continuous glucose monitoring (rtCGM) with multiple daily insulin injections (RTCGM+MDI), rtCGM with continuous subcutaneous insulin infusion (RTCGM+CSII), self-monitoring of blood glucose with MDI (SMBG+, MDI), and SMBG with CSII (SBMG+, CSII).
Abstract: OBJECTIVE This study assessed the clinical impact of four treatment strategies in adults with type 1 diabetes (T1D): real-time continuous glucose monitoring (rtCGM) with multiple daily insulin injections (rtCGM+MDI), rtCGM with continuous subcutaneous insulin infusion (rtCGM+CSII), self-monitoring of blood glucose with MDI (SMBG+MDI), and SMBG with CSII (SMBG+CSII). RESEARCH DESIGN AND METHODS This 3-year, nonrandomized, prospective, real-world, clinical trial followed 94 participants with T1D (rtCGM+MDI, n = 22; rtCGM+CSII, n = 26; SMBG+MDI, n = 21; SMBG+CSII, n = 25). The main end points were changes in A1C, time in range (70–180 mg/dL [3.9–10 mmol/L]), time below range ( RESULTS At 3 years, the rtCGM groups (rtCGM+MDI and rtCGM+CSII) had significantly lower A1C (7.0% [53 mmol/mol], P = 0.0002, and 6.9% [52 mmol/mol], P CONCLUSIONS rtCGM was superior to SMBG in reducing A1C, hypoglycemia, and other end points in individuals with T1D regardless of their insulin delivery method. rtCGM+MDI can be considered an equivalent but lower-cost alternative to sensor-augmented insulin pump therapy and superior to treatment with SMBG+MDI or SMBG+CSII therapy.

Journal ArticleDOI
TL;DR: Higher tirzepatide doses significantly decreased NASH-related biomarkers and increased adiponectin in patients with type 2 diabetes mellitus (T2DM).
Abstract: OBJECTIVE To determine the effect of tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptors, on biomarkers of nonalcoholic steatohepatitis (NASH) and fibrosis in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS Patients with T2DM received either once weekly tirzepatide (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks. Changes from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), keratin-18 (K-18), procollagen III (Pro-C3), and adiponectin were analyzed in a modified intention-to-treat population. RESULTS Significant (P CONCLUSIONS In post hoc analyses, higher tirzepatide doses significantly decreased NASH-related biomarkers and increased adiponectin in patients with T2DM.

Journal ArticleDOI
TL;DR: Nationwide unrestricted reimbursement of isCGM in people with type 1 diabetes treated in specialist diabetes centers results in higher treatment satisfaction, less severe hypoglycemia, and less work absenteeism, while maintaining quality of life and HbA1c.
Abstract: OBJECTIVE In 2016, nationwide reimbursement of intermittently scanned continuous glucose monitoring (isCGM) for people living with type 1 diabetes treated in specialist diabetes centers was introduced in Belgium. We undertook a 12-month prospective observational multicenter real-world study to investigate impact of isCGM on quality of life and glycemic control. RESEARCH DESIGN AND METHODS Between July 2016 and July 2018, 1,913 adults with type 1 diabetes were consecutively recruited in three specialist diabetes centers. Demographic, metabolic, and quality of life data were collected at baseline, 6 months, and 12 months of standardized clinical follow-up. The primary end point was evolution of quality of life from baseline to 12 months. Secondary outcome measures were, among others, change in HbA1c, time spent in different glycemic ranges, occurrence of acute diabetes complications, and work absenteeism. RESULTS General and diabetes-specific quality of life was high at baseline and remained stable, whereas treatment satisfaction improved (P CONCLUSIONS Nationwide unrestricted reimbursement of isCGM in people with type 1 diabetes treated in specialist diabetes centers results in higher treatment satisfaction, less severe hypoglycemia, and less work absenteeism, while maintaining quality of life and HbA1c.

Journal ArticleDOI
TL;DR: There is a high potential for COVID-19 to exacerbate existing health disparities, and research and practice guidelines need to take this into account.
Abstract: Evidence relating to the impact of COVID-19 in people with diabetes (PWD) is limited but continuing to emerge. PWD appear to be at increased risk of more severe COVID-19 infection, though evidence quantifying the risk is highly uncertain. The extent to which clinical and demographic factors moderate this relationship is unclear, though signals are emerging that link higher BMI and higher HbA1c to worse outcomes in PWD with COVID-19. As well as posing direct immediate risks to PWD, COVID-19 also risks contributing to worse diabetes outcomes due to disruptions caused by the pandemic, including stress and changes to routine care, diet, and physical activity. Countries have used various strategies to support PWD during this pandemic. There is a high potential for COVID-19 to exacerbate existing health disparities, and research and practice guidelines need to take this into account. Evidence on the management of long-term conditions during national emergencies suggests various ways to mitigate the risks presented by these events.

Journal ArticleDOI
TL;DR: Diabetes selfmanagement education and support (DSMES) as mentioned in this paper addresses the comprehensive blend of clinical, educational, psychosocial, and behavioral aspects of care needed for daily self-management and provides the foundation to help all people with diabetes navigate their daily self care with confidence and improved outcomes.
Abstract: Diabetes is a complex and challenging disease that requires daily self-management decisions made by the person with diabetes. Diabetes self-management education and support (DSMES) addresses the comprehensive blend of clinical, educational, psychosocial, and behavioral aspects of care needed for daily self-management and provides the foundation to help all people with diabetes navigate their daily self-care with confidence and improved outcomes (1,2). The prevalence of diagnosed diabetes is projected to increase in the U.S. from 22.3 million (9.1% of the total population) in 2014, to 39.7 million (13%) in 2030, and to 60.6 million (17%) in 2060 (3). Approximately 90–95% of those with diabetes have type 2 diabetes (4). Diabetes is an expensive disease, and the medical costs of health care alone for a person with diabetes are 2.3 times more than for a person without diabetes (5). Confounding the diabetes epidemic and high costs, therapeutic targets are not being met (6). There is a lack of improvement in reaching clinical target goals since 2005 despite advancements in medication and technology treatment modalities. Indeed, between 2010 and 2016 improved outcomes stalled or reversed (6). The goals of this Consensus Report are to improve clinical care and education services, to improve the health of individuals and populations, and to reduce diabetes-associated per capita health care costs (1,7). This article is specifically directed toward health care providers (physicians, nurse practitioners, physician assistants [PAs]), referred to herein as providers, as it outlines the benefits of DSMES, defines four critical times to provide and modify DSMES (see Fig. 1), proposes how to locate DSMES-related resources, and discusses potential solutions to access and utilization barriers. This report provides guidance to others as well: health systems and organizations can use this report to anticipate and address the needs of persons with …

Journal ArticleDOI
TL;DR: Hyperglycemia is an independent factor associated with severe prognosis in people hospitalized for COVID-19 and remained an independent predictor upon multiple adjustments.
Abstract: OBJECTIVE To explore whether at-admission hyperglycemia is associated with worse outcomes in patients hospitalized for coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS Hospitalized COVID-19 patients (N = 271) were subdivided based on at-admission glycemic status: 1) glucose levels RESULTS Neutrophils were higher and lymphocytes and PaO2/FiO2 lower in HG than in DM and NG patients. DM and HG patients had higher D-dimer and worse inflammatory profile. Mortality was greater in HG (39.4% vs. 16.8%; unadjusted hazard ratio [HR] 2.20, 95% CI 1.27–3.81, P = 0.005) than in NG (16.8%) and marginally so in DM (28.6%; 1.73, 0.92–3.25, P = 0.086) patients. Upon multiple adjustments, only HG remained an independent predictor (HR 1.80, 95% CI 1.03–3.15, P = 0.04). After stratification by quintile of glucose levels, mortality was higher in quintile 4 (Q4) (3.57, 1.46–8.76, P = 0.005) and marginally in Q5 (29.6%) (2.32, 0.91–5.96, P = 0.079) vs. Q1. CONCLUSIONS Hyperglycemia is an independent factor associated with severe prognosis in people hospitalized for COVID-19.

Journal ArticleDOI
TL;DR: CGM improves glycemic control by expanding TIR and decreasing TBR, TAR, and glucose variability in both type 1 and type 2 diabetes.
Abstract: BACKGROUND Continuous glucose monitoring (CGM) provides important information to aid in achieving glycemic targets in people with diabetes. PURPOSE We performed a meta-analysis of randomized controlled trials (RCTs) comparing CGM with usual care for parameters of glycemic control in both type 1 and type 2 diabetes. DATA SOURCES Many electronic databases were searched for articles published from inception until 30 June 2019. STUDY SELECTION We selected RCTs that assessed both changes in HbA1c and time in target range (TIR), together with time below range (TBR), time above range (TAR), and glucose variability expressed as coefficient of variation (CV). DATA EXTRACTION Data were extracted from each trial by two investigators. DATA SYNTHESIS All results were analyzed by a random effects model to calculate the weighted mean difference (WMD) with the 95% CI. We identified 15 RCTs, lasting 12–36 weeks and involving 2,461 patients. Compared with the usual care (overall data), CGM was associated with modest reduction in HbA1c (WMD −0.17%, 95% CI −0.29 to −0.06, I2 = 96.2%), increase in TIR (WMD 70.74 min, 95% CI 46.73–94.76, I2 = 66.3%), and lower TAR, TBR, and CV, with heterogeneity between studies. The increase in TIR was significant and robust independently of diabetes type, method of insulin delivery, and reason for CGM use. In preplanned subgroup analyses, real-time CGM led to the higher improvement in mean HbA1c (WMD −0.23%, 95% CI −0.36 to −0.10, P LIMITATIONS Heterogeneity was high for most of the study outcomes; all studies were sponsored by industry, had short duration, and used an open-label design. CONCLUSIONS CGM improves glycemic control by expanding TIR and decreasing TBR, TAR, and glucose variability in both type 1 and type 2 diabetes.

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TL;DR: The “thrifty fuel hypothesis”, which proposes that enhanced ketone bodies formation might possibly provide an efficient fuel that could boost the energy state of organs under stress, is proposed to explain the cardiorenal benefits of SGLT2 inhibitors.
Abstract: There is compelling evidence that sodium–glucose cotransporter 2 (SGLT2) inhibitors exert cardioprotective and renoprotective effects that are far greater than expected based on their effects on glycemia or glycosuria. In large-scale randomized controlled trials, SGLT2 inhibitors reduce the risk of hospitalizations for heart failure by ∼30% and often decrease the risk of cardiovascular death (1). This benefit is particularly striking in patients who have the most marked impairment of systolic function prior to treatment. In parallel, SGLT2 inhibitors also reduce the risk of end-stage renal events, including the occurrence of renal death and the need for dialysis or renal transplantation by ∼30% (2). This benefit is seen even when glomerular filtration rates are sufficiently low to abolish the glycosuric effect of these drugs. These cardiorenal benefits cannot be explained by an action of SGLT2 inhibitors to lower blood glucose, since similar effects are not seen with antidiabetes drugs that have greater antihyperglycemic actions. Additionally, they cannot be ascribed to a natriuretic action, since these drugs exert only a modest effect on plasma volume or on circulating natriuretic peptides (3). In 2016, two articles published in Diabetes Care proposed the “thrifty fuel hypothesis” to explain the cardiorenal benefits of SGLT2 inhibitors. Ferrannini et al. (4) and Mudaliar et al. (5) postulated that the action of SGLT2 inhibitors to promote ketogenesis might account for their favorable effects on the heart and kidney because enhanced ketone bodies formation might possibly provide an efficient fuel that could boost the energy state of organs under stress. However, type 2 diabetes represents a state of nutrient overabundance and not energy deprivation, as is evidenced by the enhancement of molecular pathways that promote both energy retention (e.g., through SGLT2 upregulation) and energy storage (6,7). In fact, the stressed heart already preferentially utilizes ketone bodies, …

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TL;DR: A joint review of the current landscape of available diabetes digital health technology and practices of regulatory authorities and organizations found that, across the U.S. and Europe, mobile apps intended to manage health and wellness are largely unregulated unless they meet the definition of medical devices for therapeutic and/or diagnostic purposes.
Abstract: Digital health technology, especially digital and health applications ("apps"), have been developing rapidly to help people manage their diabetes. Numerous health-related apps provided on smartphones and other wireless devices are available to support people with diabetes who need to adopt either lifestyle interventions or medication adjustments in response to glucose-monitoring data. However, regulations and guidelines have not caught up with the burgeoning field to standardize how mobile health apps are reviewed and monitored for patient safety and clinical validity. The available evidence on the safety and effectiveness of mobile health apps, especially for diabetes, remains limited. The European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) have therefore conducted a joint review of the current landscape of available diabetes digital health technology (only stand-alone diabetes apps, as opposed to those that are integral to a regulated medical device, such as insulin pumps, continuous glucose monitoring systems, and automated insulin delivery systems) and practices of regulatory authorities and organizations. We found that, across the U.S. and Europe, mobile apps intended to manage health and wellness are largely unregulated unless they meet the definition of medical devices for therapeutic and/or diagnostic purposes. International organizations, including the International Medical Device Regulators Forum and the World Health Organization, have made strides in classifying different types of digital health technology and integrating digital health technology into the field of medical devices. As the diabetes digital health field continues to develop and become more fully integrated into everyday life, we wish to ensure that it is based on the best evidence for safety and efficacy. As a result, we bring to light several issues that the diabetes community, including regulatory authorities, policy makers, professional organizations, researchers, people with diabetes, and health care professionals, needs to address to ensure that diabetes health technology can meet its full potential. These issues range from inadequate evidence on app accuracy and clinical validity to lack of training provision, poor interoperability and standardization, and insufficient data security. We conclude with a series of recommended actions to resolve some of these shortcomings.

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TL;DR: The incorrect figure legend was printed for Figure 2.
Abstract: The incorrect figure legend was printed for Figure 2. The first sentence of the legend should read as …

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TL;DR: Over the past few months, coronavirus disease 2019 (COVID-19) and subsequent social distancing have affected biological, psychological, economic, and social aspects of life.
Abstract: Psychological stress is a known general health risk potentially increasing the risk of type 1 diabetes. Consistent with this hypothesis, there were reports of a higher incidence of type 1 diabetes after other stressful catastrophic events, e.g., the Chernobyl incident in 1986 or the Los Angeles earthquake in 1994 (1,2). Over the past few months, coronavirus disease 2019 (COVID-19) and subsequent social distancing have affected biological, psychological, economic, and social aspects of life. Social distancing during the lockdown could be perceived as a stressful situation for children and adolescents, who could not attend kindergarten or school and were unable to pursue hobbies like sports or meeting friends. Perceived stress caused by feelings of isolation may have increased the risk of type 1 diabetes (3). Since type 1 diabetes is also associated with viral infections (4), explaining, for example, the higher type 1 diabetes incidence during winter months, COVID-19 infection may have caused an increase of type 1 diabetes manifestations by affecting immune regulation or by directly damaging pancreatic β-cells (5 …

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TL;DR: Plasma glucose levels at admission and antidiabetes drugs may influence the survival of COVID-19 patients affected by type 2 diabetes, and the use of dipeptidyl peptidase 4 inhibitors was significantly and independently associated with a lower risk of mortality.
Abstract: OBJECTIVE Diabetes may unfavorably influence the outcome of coronavirus disease 19 (COVID-19), but the determinants of this effect are still poorly understood. In this monocentric study, we aimed at evaluating the impact of type 2 diabetes, comorbidities, plasma glucose levels, and antidiabetes medications on the survival of COVID-19 patients. RESEARCH DESIGN AND METHODS This was a case series involving 387 COVID-19 patients admitted to a single center in the region of Lombardy, the epicenter of the severe acute respiratory syndrome coronavirus 2 pandemic in Italy, between 20 February and 9 April 2020. Medical history, pharmacological treatments, laboratory findings, and clinical outcomes of patients without diabetes and patients with type 2 diabetes were compared. Cox proportional hazards analysis was applied to investigate risk factors associated with mortality. RESULTS Our samples included 90 patients (23.3%) with type 2 diabetes, who displayed double the mortality rate of subjects without diabetes (42.3% vs. 21.7%, P CONCLUSIONS Plasma glucose levels at admission and antidiabetes drugs may influence the survival of COVID-19 patients affected by type 2 diabetes.

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TL;DR: This model predicts significant clinical and economic burden due to NASH with T2DM over the next 20 years, and this burden may be greater since it assumed conservative inputs for the model and did not increase costs or the incidence of T2 DM over time.
Abstract: OBJECTIVE Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) and is strongly associated with type 2 diabetes mellitus (T2DM). Patients with both T2DM and NASH have increased risk for adverse clinical outcomes, leading to higher risk for mortality and morbidity. We built a Markov model with 1-year cycles and 20-year horizon to estimate the economic burden of NASH with T2DM in the U.S. RESEARCH DESIGN AND METHODS Cohort size was determined by population size, prevalence of T2DM, and prevalence and incidence of NASH in 2017. The model includes 10 health states—NAFL, NASH fibrosis stages F0 through F3, compensated and decompensated cirrhosis, hepatocellular carcinoma, 1 year post–liver transplant, and post–liver transplant—as well as liver-related, cardiovascular, and background mortality. Transition probabilities were calculated from meta-analyses and literature. Annual costs for NASH and T2DM were taken from literature and billing codes. RESULTS We estimated that there were 18.2 million people in the U.S. living with T2DM and NAFLD, of which 6.4 million had NASH. Twenty-year costs for NAFLD in these patients were $55.8 billion. Over the next 20 years, NASH with T2DM will account for 65,000 transplants, 1.37 million cardiovascular-related deaths, and 812,000 liver-related deaths. CONCLUSIONS This model predicts significant clinical and economic burden due to NASH with T2DM over the next 20 years. In fact, this burden may be greater since we assumed conservative inputs for our model and did not increase costs or the incidence of T2DM over time. It is highly likely that interventions reducing morbidity and mortality in NASH patients with T2DM could potentially reduce this projected clinical and economic burden.

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TL;DR: Performance of noninvasive clinical models/scores and plasma biomarkers for the diagnosis of NASH or advanced fibrosis was suboptimal in patients with type 2 diabetes mellitus (T2DM).
Abstract: OBJECTIVE The 2019 Standards of Medical Care in Diabetes suggested that patients with nonalcoholic fatty liver disease (NAFLD) should be evaluated for liver fibrosis. However, the performance of noninvasive clinical models/scores and plasma biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) and advanced fibrosis has not been carefully assessed in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS In this cross-sectional study, patients (n = 213) had a liver MRS, and those with a diagnosis of NAFLD underwent a percutaneous liver biopsy. Several noninvasive clinical models/scores and plasma biomarkers were measured to identify NASH and advanced fibrosis (NASH: alanine aminotransferase [ALT], cytokeratin-18, NashTest 2, HAIR, BARD, and OWLiver; advanced fibrosis: AST, fragments of propeptide of type III procollagen [PRO-C3], FIB-4, APRI, NAFLD fibrosis score, and FibroTest). RESULTS None of the noninvasive tools assessed for the diagnosis of NASH in patients with T2DM had an optimum performance (all areas under the curve [AUCs] CONCLUSIONS Performance of noninvasive clinical models/scores and plasma biomarkers for the diagnosis of NASH or advanced fibrosis was suboptimal in patients with T2DM. Combination of multiple tests may provide an alternative to minimize the need of liver biopsies to detect fibrosis in these patients.

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TL;DR: This study investigated patient attributes and clinical outcomes in people with COVID-19–like symptoms for whom testing was unavailable or results were pending, and was the first U.S.-based multicenter study that addresses these questions in a population with type 1 diabetes.
Abstract: The Centers for Disease Control and Prevention states that individuals with diabetes are at higher risk for severe illness with coronavirus disease 2019 (COVID-19) and poorer health outcomes (1). Research suggests the underlying reason for an increased risk of COVID-19 complications in individuals with diabetes may be poor glycemic control or hyperglycemia (2). Information on clinical outcomes for patients with type 1 diabetes who have confirmed cases of COVID-19 is limited. To our knowledge, this is the first U.S.-based multicenter study that addresses these questions in a population with type 1 diabetes. This study aimed to examine patient characteristics and adverse outcomes among patients with type 1 diabetes with confirmed COVID-19. As a secondary objective, we investigated patient attributes and clinical outcomes in people with COVID-19–like symptoms for whom testing was unavailable or results were pending. The T1D Exchange Quality Improvement Collaborative (T1DX-QI) (3) is conducting this study in collaboration with an additional 49 endocrinology clinics (a total of 64 U.S. sites). The study was approved as exempt by a central review …

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TL;DR: It is shown that the use of FSL was associated with significantly improved glycemic control and hypoglycemia awareness and a reduction in hospital admissions and a significant reduction in paramedic callouts and hospital admissions due to hypoglyCEmia and hyperglycemia/diabetic ketoacidosis.
Abstract: OBJECTIVE The FreeStyle Libre (FSL) flash glucose-monitoring device was made available on the U.K. National Health Service (NHS) drug tariff in 2017. This study aims to explore the U.K. real-world experience of FSL and the impact on glycemic control, hypoglycemia, diabetes-related distress, and hospital admissions. RESEARCH DESIGN AND METHODS Clinicians from 102 NHS hospitals in the U.K. submitted FSL user data, collected during routine clinical care, to a secure web-based tool held within the NHS N3 network. The t and Mann-Whitney U tests were used to compare the baseline and follow-up HbA1c and other baseline demographic characteristics. Linear regression analysis was used to identify predictors of change in HbA1c following the use of FSL. Within-person variations of HbA1c were calculated using . RESULTS Data were available for 10,370 FSL users (97% with type 1 diabetes), age 38.0 (±18.8) years, 51% female, diabetes duration 16.0 (±49.9) years, and BMI of 25.2 (±16.5) kg/m2 (mean [±SD]). FSL users demonstrated a −5.2 mmol/mol change in HbA1c, reducing from 67.5 (±20.9) mmol/mol (8.3%) at baseline to 62.3 (±18.5) mmol/mol (7.8%) after 7.5 (interquartile range 3.4–7.8) months of follow-up (n = 3,182) (P 8.5%), reducing from 85.5 (±16.1) mmol/mol (10%) to 73.1 (±15.8) mmol/mol (8.8%) (P CONCLUSIONS We show that the use of FSL was associated with significantly improved glycemic control and hypoglycemia awareness and a reduction in hospital admissions.

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TL;DR: Daily vitamin D supplementation to maintain a serum 25(OH)D level ≥100 nmol/L is a promising approach to reducing the risk of diabetes in adults with prediabetes.
Abstract: OBJECTIVE Postrandomization biases may influence the estimate of efficacy of supplemental vitamin D in diabetes prevention trials. In the Vitamin D and Type 2 Diabetes (D2d) study, repeated measures of serum 25-hydroxyvitamin D [25(OH)D] level provided an opportunity to test whether intratrial vitamin D exposure affected diabetes risk and whether the effect was modified by trial assignment (vitamin D vs. placebo). RESEARCH DESIGN AND METHODS The D2d study compared the effect of daily supplementation with 100 μg (4,000 units) of vitamin D3 versus placebo on new-onset diabetes in adults with prediabetes. Intratrial vitamin D exposure was calculated as the cumulative rolling mean of annual serum 25(OH)D measurements. Hazard ratios for diabetes among participants who had intratrial 25(OH)D levels of RESULTS There was an interaction of trial assignment with intratrial 25(OH)D level in predicting diabetes risk (interaction P = 0.018). The hazard ratio for diabetes for an increase of 25 nmol/L in intratrial 25(OH)D level was 0.75 (95% CI 0.68–0.82) among those assigned to vitamin D and 0.90 (0.80–1.02) among those assigned to placebo. The hazard ratios for diabetes among participants treated with vitamin D who maintained intratrial 25(OH)D levels of 100–124 and ≥125 nmol/L were 0.48 (0.29–0.80) and 0.29 (0.17–0.50), respectively, compared with those who maintained a level of 50–74 nmol/L. CONCLUSIONS Daily vitamin D supplementation to maintain a serum 25(OH)D level ≥100 nmol/L is a promising approach to reducing the risk of diabetes in adults with prediabetes.