Immunogenicity, Safety, and Efficacy of Influenza Vaccine in T2DM and T2DM with Chronic Kidney Disease.

Patients with Type 2 diabetes mellitus (T2DM) and Chronic Kidney Disease (CKD) face an increased risk of morbidity and mortality after influenza infection. Several studies have shown that the influenza vaccine effectively prevents morbidity and mortality in T2DM patients. However, there has been limited research aimed at assessing the effectiveness of the trivalent influenza vaccine in T2DM-CKD patients. This study aimed to identify Geometric Mean Titers (GMTs), seroprotection, seroconversion, safety, and efficacy. This open-label clinical trial was conducted at AMC Hospital in Bandung, West Java, Indonesia between June 2021 and July 2022. The study subjects consisted of 41 T2DM and 26 T2DM-CKD patients who were administered the trivalent influenza vaccine. There was a significant difference in the average age, with the T2DM-CKD patients being older. Median titers post-vaccination for the B/Washington virus were higher in the T2DM patients compared to the T2DM-CKD patients, and this difference was statistically significant. A majority, comprising 75.6% of the T2DM and 80.8% of the T2DM-CKD patients monitored post-influenza-vaccination, did not experience any adverse reactions. The most common reaction was the sensation of fever, with incidence rates of 12.2% in the T2DM patients and 15.4% in the T2DM-CKD patients. Furthermore, we observed that the incidence of Influenza-like Illness was highest at 7.3% in the T2DM patients and 7.7% in the T2DM-CKD patients. The trivalent influenza vaccine demonstrated equivalent safety and effectiveness in both groups.

Different doses of imeglimin for management of type 2 diabetes mellitus: a systematic review, meta-analysis, and meta-regression of randomized clinical trials.

BACKGROUND: A new medication for type 2 diabetes mellitus (T2DM) called imeglimin can target all three organs involved in the pathogenesis of DM, namely the liver, skeletal muscles, and pancreas. This research seeks to examine the most efficacious and safe dose of imeglimin for the management of T2DM. RESEARCH DESIGN AND METHODS: Using particular keywords, we searched the CENTRAL, Medline, Scopus, and ClinicalTrials.gov databases for pertinent literature. The results of continuous variables were pooled into the mean difference (MD) and dichotomous variables into odds ratio (OR) along with their 95% confidence intervals (95% CI) using fixed-effect models. RESULTS: Our pooled analysis revealed that imeglimin 1000 mg twice daily [MD -0.90% p < 0.00001] and 1500 mg twice daily [MD -0.84% p = 0.0003] as monotherapy was associated with a higher reduction in the HbA1c compared to placebo. This superiority was still maintained when given as combination therapy. Regrettably, there was an observed escalation in gastrointestinal AEs as the dosage of imeglimin was raised, despite the absence of a corresponding improvement in its efficacy in decreasing HbA1c levels. CONCLUSIONS: Our study suggests that imeglimin 1000 mg twice daily may offer the most optimum therapeutic effects for glycemic control without compromising its safety profiles.

Anti-SARS-CoV-2 Antibody Level Is Associated with a History of COVID-19 Infection and mRNA Vaccination in Patients with Diabetes.

Type 2 diabetes mellitus (T2DM) is associated with higher severity and mortality in SARS-CoV-2 infections. Vaccination has been encouraged to boost immunity and prevent these unfortunate outcomes. Few studies have evaluated antibody levels after COVID-19 vaccination in patients with T2DM. Therefore, we examined the vaccination status and anti-SARS-CoV-2 antibody levels to identify the factors that affect the antibody levels in patients with T2DM. This cross-sectional study was conducted at the Dr. Hasan Sadikin Hospital and Bandung Kiwari Hospital, Bandung, West Java, Indonesia, between October and November 2022. Adult participants with and without T2DM were tested for SARS-CoV-2 antibodies using a point-of-care quantitative immunochromatographic assay. We enrolled 289 participants: 201 participants with T2DM and 88 participants without T2DM. The T2DM participants had a lower vaccination rate compared with the non-T2DM participants. However, no significant differences in antibody levels were observed between the two groups. Higher antibody levels among the T2DM participants were associated with mRNA vaccination and a history of COVID-19 illness. The lower antibody response observed among the T2DM participants with chronic obstructive pulmonary disease suggests that such patients may need antibody level measurement and an additional booster vaccine.

The effect of diabetes mellitus on COVID-19 mortality among patients in a tertiary-level hospital in Bandung, Indonesia.

Immune system dysregulation in people with diabetes mellitus (DM) increases the risk of acquiring severe infection. We compared the clinical characteristics and laboratory parameters of coronavirus disease 2019 (COVID-19) patients with and without DM and estimated the effect of DM on mortality among COVID-19 patients. A retrospective cohort study collecting patients' demographic, clinical characteristics, laboratory parameters and treatment outcomes from medical records was conducted in a hospital in Bandung City from March to December 2020. Univariable and multivariable logistic regression was performed to determine the association between DM and death. A total of 664 COVID-19 patients with positive real-time reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 were included in this study, of whom 147 were with DM. Half of DM patients presented HbA1c ≥10%. DM patients were more likely to present with comorbidities and severe to critical conditions at admission (P <0.001). Laboratory parameters such as neutrophil-lymphocyte count ratio, C-reactive protein, D-dimer, ferritin, and lactate dehydrogenase were higher in the DM group. In the univariate analysis, variables associated with death were COVID-19 severity at baseline, neurologic disease, DM, age ≥60 years, hypertension, cardiovascular disease, and chronic kidney disease. DM remained associated with death (aOR 1.82; 95% CI 1.13-2.93) after adjustment with sex, age, hypertension, cardiovascular disease, and chronic kidney disease. In conclusion, COVID-19 patients with DM are more likely to present with a very high HbA1c, comorbidities, and severe-critical illness. Chronic inflammation in DM patients may be aggravated by the disruption of immune response caused by COVID-19, leading to worse laboratory results and poor outcomes.

The association between metabolic dysfunction-associated fatty liver disease and chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The term metabolic dysfunction-associated fatty liver disease (MAFLD) has been established to better define patients with fatty liver disease who also present with metabolic dysfunction. However, the association between MAFLD and chronic-kidney disease (CKD) remains elusive. METHODS: . We conducted systematic literature searching across multiple databases-PubMed, EMBASE, Cochrane library, and Google Scholar up until June 9th, 2022. The main exposure was the diagnosis of MAFLD and nonalcoholic fatty liver disease (NAFLD) regardless of the diagnostic modalities being used. The outcome of interest was the prevalence or the incidence of CKD. RESULTS: There were 355,886 subjects from 11 included studies with the period of follow up of 4.6-6.5 years. Meta-analysis of cross-sectional studies showed that MAFLD was associated with a higher prevalent CKD (OR 1.50, 95%CI [1.02-2.23]; test for overall effect Z = 2.04, p = 0.04; I2 = 97.7%, p < 0.001) and incident CKD (adjusted HR 1.35, 95%CI [1.18-1.52]; test for overall effect Z = 15.47, p < 0.001; I2 = 84.6%, p < 0.001) and did not vary between age, sex, comorbidities, study region, and follow-up duration. No difference in CKD prevalence was found between MAFLD and NAFLD patients. Significant liver fibrosis, but not steatosis in was associated with greater odds of developing CKD. More severe MAFLD was also associated with higher odds of developing CKD. CONCLUSION: This present meta-analysis using a large population indicates a significant association between MAFLD and the prevalence and incidence of CKD.

Pre-admission use of sodium glucose transporter-2 inhibitor (SGLT-2i) may significantly improves Covid-19 outcomes in patients with diabetes: A systematic review, meta-analysis, and meta-regression.

AIMS: This study aims to examine the effectiveness of using sodium glucose transporter-2 inhibitor (SGLT-2i) before hospital admission on Covid-19 outcomes in diabetic patients. METHODS: A literature search was conducted using specific keywords until October 24th, 2022 on 4 databases: Medline, Scopus, Cochrane Library, and ClinicalTrials.gov. All articles regarding SGLT-2i in diabetic patients with Covid-19 were included in the study. Outcomes in this study were calculated using random-effect models to generate pooled odds ratio (OR) with 95% confidence intervals (CI). RESULTS: A total of 17 studies were included in the analysis. Our meta-analysis showed that pre-admission use of SGLT-2i was associated with reduced mortality (OR 0.69; 95 %CI: 0.56 - 0.87, p = 0.001, I2 = 91 %) and severity of Covid-19 (OR 0.88; 95 %CI: 0.80 - 0.97, p = 0.008, I2 = 13 %). This benefit of SGLT-2i on Covid-19 mortality was not significantly affected by patient's factors such as age (p = 0.2335), sex (p = 0.2742), hypertension (p = 0.2165), heart failure (p = 0.1616), HbA1c levels (p = 0.4924), metformin use (p = 0.6617), duration of diabetes (p = 0.7233), and BMI (p = 0.1797). CONCLUSIONS: This study suggests that SGLT-2i as glucose lowering treatment in patients with diabetes has a positive effect on Covid-19 outcomes, therefore can be considered as an antidiabetic drug of choice, especially during the Covid-19 pandemic. Short Title: SGLT-2i in diabetes and Covid-19. REGISTRATION DETAILS: CRD42022369784.

Efficacy and safety of tirzepatide as novel treatment for type 2 diabetes: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND AND AIMS: This study aims to explore the efficacy and safety of tirzepatide for patients with type 2 diabetes (T2D). METHODS: Using specific keywords, we comprehensively go through the potential articles on Europe PMC, Scopus, PubMed, and ClinicalTrials.gov sources until July 12th, 2022. We collected all clinical trials that compare tirzepatide 5, 10, or 15 mg once-weekly with placebo or other glucose lowering agents in adult patients with T2D. RESULTS: Nine clinical trials were included. Our pooled analysis revealed the dose-dependent superiority of tirzepatide in reducing HbA1c, ranging from -1.50% with 5 mg to -1.80% with 15 mg when compared with placebo, -0.61% with 5 mg to -0.95% with 15 mg when compared with GLP-1 receptor agonist, and -0.70% with 5 mg to 1.09% with 15 mg when compared with basal insulin. The dose-dependent superiority of tirzepatide was also seen in the bodyweight reduction effect with all comparators. These superiorities were not accompanied by increased odds of hypoglycemia, but there is an increase in gastrointestinal adverse events incidence. CONCLUSIONS: Tirzepatide has shown superiority in glycemic control and bodyweight reduction with a good safety profile in patients with T2D. Tirzepatide may become a future potential drug in the management of T2D.

Empirical Antibiotic for Diabetic Foot Infection in Indonesian Tertiary Hospital, Is It Time to Rethink the Options?

BACKGROUND: The choice of empiric antibiotics in Diabetic Foot Infection (DFI) is a key to successful therapy. Meanwhile, the management of DFI in Indonesia is  based on guideline originating from western countries which have different bacteriological patterns. Therefore, this study aimed to describe the bacterial and antibiotic susceptibility pattern on DFI which potentially contribute to better antibiotics selection guidelines. METHODS: This was a cross-sectional descriptive study conducted using consecutive sampling with DFI patients admitted in the emergency room and wards of Hasan Sadikin Hospital between February and July 2020. Tissue samples were obtained from all wounds, while antibiotic susceptibility tests were carried out on the culture results. RESULTS: A total of 65 bacterial growths were obtained from 45 enrolled patients. Gram-negative bacteria dominated with 54 growths (83.07%) including Klebsiela pneumonia 13 (20%) as the most common. Furthermore, antibiotics with good susceptible (> 80%) against Gram-negative bacteria are the carbapenemes (meropenem and ertapenem) and amikacin. The multi drug resistant bacteria were found in 18 growths (27.7%), which include ESBL, Carbapenemase producing bacteria, and MRSA. However, there were no susceptibility pattern differences between patients with ulcer duration above or below 2 months, higher grade wound (Wagner 4 and 5) and lower, as well as patients with previous or no antibiotic history. CONCLUSION: The growth of Gram-negative bacteria dominated DFI with limited susceptibility to the empirical first-line antibiotics in the known international guidelines. Therefore, there is a need to reconsider the algorithm for selecting empirical antibiotics and management of DFI which is appropriate in our current condition.

The prognostic values of thyroid disorders in predicting COVID-19 composite poor outcomes: A systematic review and meta-analysis.

BACKGROUND AND AIMS: In this meta-analysis, we aimed to evaluate the prognostic properties of thyroid disorder during admission on poor prognosis and factors that may influence the relationship in patients with COVID-19. METHODS: A systematic literature search of PubMed, EBSCO, and CENTRAL was conducted from inception to August 27, 2021. The main exposure was unspecified and specified thyroid disorders-hypothyroidism or hypothyroidism. The outcome of interest was the COVID-19 composite poor outcome that comprises of severity, mortality, ICU admission, and hospitalization. RESULTS: There were 24,734 patients from 20 studies. Meta-analysis showed that thyroid disorder was associated with composite poor outcome (OR 2.87 (95% CI 2.04-4.04), p < 0.001; I2 = 62.4%, p < 0.001). Meta regression showed that age (p = 0.047) and hypertension (p = 0.01), but not gender (p = 0.15), DM (p = 0.10), CAD/CVD (p = 0.38), obesity (p = 0.84), and COPD (p = 0.07) affected the association. Subgroup analysis showed that thyroid disorder increased risk of severe COVID-19 (OR 5.13 (95% CI 3.22-8.17), p < 0.05; I2 = 0%, p = 0.70) and mortality (OR 2.78 (95%CI 1.31-5.90), p < 0.05; I2 = 80%, p < 0.01). Pooled diagnostic analysis of thyroid disorder yielded a sensitivity of 0.22 (0.13-0.35), specificity of 0.92 (0.87-0.95), and AUC of 0.72. The probability of poor outcome was 38% in patients with thyroid disorder and 15% in patients without thyroid abnormality. CONCLUSION: On-admission thyroid disorder was associated with poor prognosis in COVID-19 patients.

Antibody response following SARS-CoV-2 vaccination among patients with type 2 diabetes mellitus: A systematic review.

BACKGROUND AND AIM: DM patients' antibody response after the COVID-19 vaccine is still unknown amid the COVID-19 vaccination rollout. This study aimed to explore the SARS-CoV-2 antibody response or seropositivity among DM patients following the COVID-19 vaccine administration. METHODS: We performed a systematic review of the literature consisting of observational or cross-sectional studies, which reported the antibody serology or seropositivity among DM patients by following the PRISMA 2020 guidelines. RESULTS: Eight studies with a total of 64468 patients were identified, and 5156 (7.9%) of them had diabetes. Most studies showed that antibody response and seropositivity in DM patients were lower than healthy population after one until four weeks following full COVID-19 vaccination dose. CONCLUSION: The antibody response and seropositivity after the COVID-19 vaccine in DM patients were lower than in healthy subjects. Therefore, DM patients are expected to receive vaccines according to the dose and schedule appropriately and might be prioritized to receive vaccine boosters.

The Prognostic Properties of Thyroid Disorders, Hypothyroidism, and Hyperthyroidism in Predicting COVID-19 Poor Outcomes: A Systematic Review and Diagnostic Meta-analysis.

Purpose: The relationship between thyroid metabolism and coronavirus disease 2019 (COVID-19) inflammation has been extensively investigated. This meta-analysis aimed to evaluate the prognostic properties of unspecified thyroid disorders, hypothyroidism and hyperthyroidism for predicting poor COVID-19 outcomes. Methods: We conducted systematic literature searching through multiple databases-PubMed, EBSCO and CENTRAL up until 27 September 2021. The main exposure was unspecified thyroid disorders, hypothyroidism or hypothyroidism on-admission status. The outcome of interest was the COVID-19 composite poor outcome that comprises severity, mortality, ICU admission and hospitalisation. Results: There were 24517 patients from 20 studies. Meta-analysis showed that thyroid disorder, regardless of its type, was associated with COVID-19 poor outcome (OR 2.92 (95% CI 2.09 - 4.08), P < 0.001; I2 = 71%, P < 0.001). Unspecified thyroid disorder has a sensitivity of 0.17 (0.08-0.33), specificity of 0.94 (0.88-0.97) and Area Under Curve (AUC) of 0.66. Hypothyroidism has a sensitivity of 0.24 (0.12-0.42), specificity of 0.92 (0.87-0.96) and AUC of 0.77. Hyperthyroidism has a sensitivity of 0.05 (0.02-0.11), specificity of 0.98 (0.88-1.00) and AUC of 0.36. In this pooled analysis, the posttest probability of unspecified thyroid disease, hypothyroidism and hyperthyroidism were 42%, 27% and 8% for poor outcomes, respectively. Conclusion: Thyroid disorders are associated with poor COVID-19 prognosis.

Validation of the Indonesian Version of the Asian Diabetes Quality of Life Questionnaire.

BACKGROUND: quality of life has been identified as the goal of therapy especially in patient with chronic disease such as type 2 diabetes mellitus. Quality of life measurement requires an instrument that was specifically developed in accordance with socio-cultural background of the measured population. The aim of this study was to adapt Asian Diabetes Quality of Life Questionnaire so it can be used in Indonesia as valid and reliable tool. METHODS: Asian Diabetes Quality of Life Questionnaire was translated and adapted by group of experts, then validity and reliability tests were conducted on type 2 diabetes mellitus patients at Dr. Hasan Sadikin General Hospital, Bandung. Construct validity was analyzed using correlation test between score of each item and total score. Reliability was measured using test-retest method and internal consistency represented in Cronbach's alpha score. RESULTS: validity test showed significant correlation (p-value ≤0.05) between score of each item and total score across all domains with moderate to very strong correlation (r: 0.496-0.956). Reliability test using test-retest method showed no significant difference between Test I and II results (p-value >0.05) with very strong correlation (r: 0.830-0.975) and internal consistency yielded Cronbach's alpha scores of  ≥ 0.07 for all domains. CONCLUSION: Indonesian version of Asian DQOL is a valid and reliable tool to measure quality of life of type 2 diabetes mellitus patients.

Cost-Effectiveness Analysis of Type 2 Diabetes Mellitus (T2DM) Treatment in Patients with Complications of Kidney and Peripheral Vascular Diseases in Indonesia.

Type 2 diabetes mellitus (T2DM) is a chronic disease with high-cost treatment. This study aimed to analyze the cost-effectiveness of T2DM treatment in hospitalized patients with complications of kidney and peripheral vascular disease (PVD) in Indonesia by focusing on patients of Health Social Security Agency (BPJS Kesehatan). An observational study was applied by collecting data retrospectively from patients' medical record at the biggest public hospital in West Java Province, Indonesia. Two perspectives of payer and healthcare provider were applied to estimate the treatment cost. We considered following inclusion criteria: (i) Hospitalized T2DM patients without complication, with complications of kidney and PVD during 2014-2017; (ii) member of BPJS Kesehatan; (iii) >18 years old patients; and (iv) patients with complete medical record data. The results showed that the majority patients were female (56.72%), 45-64 years old (69.40%), and had a length of stay at 4-10 days (54.48%). The greatest contributions in the total treatment cost were found to be hospital room, medical services and medicines for the treatment of T2DM without complications, with complications of kidney and PVD, respectively. From the perspective of payer, the incremental cost-effectiveness ratios (ICERs) of T2DM treatment with complications of kidney and PVD would be IDR 215,723 and IDR 234,591 per 1 mg/dL blood glucose reduction, respectively. From the perspective of healthcare provider, the ICERs of T2DM treatment with complications of kidney and PVD would be IDR 166,289 and IDR 681,853 per 1 mg/dL blood glucose reduction in both perspectives (1 US$ = IDR 13,451). In a comparison with T2DM without complication, reducing 1 mg/dL blood glucose in T2DM treatment with complication of PVD would require higher cost than in T2DM treatment with complication of kidney from both perspectives.

In-hospital use of statins is associated with a reduced risk of mortality in coronavirus-2019 (COVID-19): systematic review and meta-analysis.

BACKGROUND AND AIMS: The idea of treating COVID-19 with statins is biologically plausible, although it is still controversial. The systematic review and meta-analysis aimed to address the association between the use of statins and risk of mortality in patients with COVID-19. METHODS: Several electronic databases, including PubMed, SCOPUS, EuropePMC, and the Cochrane Central Register of Controlled Trials, with relevant keywords up to 11 November 2020, were used to perform a systematic literature search. This study included research papers containing samples of adult COVID-19 patients who had data on statin use and recorded mortality as their outcome of interest. Risk estimates of mortality in statin users versus non-statin users were pooled across studies using inverse-variance weighted DerSimonian-Laird random-effect models. RESULTS: Thirteen studies with a total of 52,122 patients were included in the final qualitative and quantitative analysis. Eight studies reported in-hospital use of statins; meanwhile, the remaining studies reported pre-admission use of statins. In-hospital use of statin was associated with a reduced risk of mortality (RR 0.54, 95% CI 0.50-0.58, p < 0.00001; I2: 0%, p = 0.87), while pre-admission use of statin was not associated with mortality (RR 1.18, 95% CI 0.79-1.77, p = 0.415; I2: 68.6%, p = 0.013). The funnel plot for the association between the use of statins and mortality were asymmetrical. CONCLUSION: This meta-analysis showed that in-hospital use of statins was associated with a reduced risk of mortality in patients with COVID-19.

The effect of a structured clinical algorithm on glycemic control in patients with combined tuberculosis and diabetes in Indonesia: A randomized trial.

AIMS: Diabetes mellitus (DM) is associated with worse tuberculosis (TB) treatment outcomes, especially among those with poor glycemic control. We examined whether a structured clinical algorithm could improve glycemic control in TB patients with DM. METHODS: In an open label randomized trial, TB-DM patients were randomized to scheduled counselling, glucose monitoring, and adjustment of medication using a structured clinical algorithm (intervention arm) or routine DM management (control arm), with glycated hemoglobin (HbA1c) at month 6 as the primary end point. RESULTS: We randomized 150 pulmonary TB-DM patients (92% culture positive, 51.3% male, mean age 53 years). Baseline mean HbA1c was 11.0% in the intervention arm (n = 76) and 11.6% in the control arm (n = 74). At 6 months, HbA1c had decreased more in the intervention arm compared with the control arm (a difference of 1.82% HbA1c, 95% CI 0.82-2.83, p < 0.001). Five patients were hospitalized in the intervention arm and seven in the control arm. There was more hypoglycemia (35.0% vs 11.8%; p = 0.002) in the intervention arm. Two deaths occurred in the intervention arm, one due to cardiorespiratory failure and one because of suspected septic shock and multiorgan failure. CONCLUSION: Regular monitoring and algorithmic adjustment of DM treatment led to improved glycemic control.

The Association Between Chronic Kidney Disease and New Onset Renal Replacement Therapy on the Outcome of COVID-19 Patients: A Meta-analysis.

OBJECTIVE: The aim of the study was to evaluate the association between chronic kidney disease (CKD) and new onset renal replacement therapy (RRT) with the outcome of Coronavirus Disease 2019 (COVID-19) in patients. METHODOLOGY: A systematic literature search from several databases was performed on studies that assessed CKD, use of RRT, and the outcome of COVID-19. The composite of poor outcome consisted of mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care, and use of mechanical ventilator. RESULTS: Nineteen studies with a total of 7216 patients were included. CKD was associated with increased composite poor outcome (RR 2.63 [1.33, 5.17], P = .03; I 2 = 51%, P = .01) and its subgroup, consisting of mortality (RR 3.47 [1.36, 8.86], P = .009; I 2 = 14%, P = .32) and severe COVID-19 (RR 2.89 [0.98, 8.46], P = .05; I 2 = 57%, P = .04). RRT was associated with increased composite poor outcome (RR 18.04 [4.44, 73.25], P < .001; I 2 = 87%, P < .001), including mortality (RR 26.02 [5.01, 135.13], P < .001; I 2 = 60%, P = .06), severe COVID-19 (RR 12.95 [1.93, 86.82], P = .008; I 2 = 81%, P < .001), intensive care (IC) (RR 14.22 [1.76, 114.62], P < .01; I 2 = 0%, P < .98), and use of mechanical ventilator (RR 34.39 [4.63, 255.51], P < .0005). CONCLUSION: CKD and new-onset RRT were associated with poor outcome in patients with COVID-19.

The use of renin angiotensin system inhibitor on mortality in patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

BACKGROUND: and Aims; To investigate the association between use of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB) and outcomes of hypertensive COVID-19 patients, a systematic review and meta-analysis were performed. METHODS: We systematically searched PubMed, EuropePMC, ProQuest, and Cochrane Central Databases using the terms "(COVID-19 OR SARS-CoV-2) AND (angiotensin converting enzyme OR angiotensin receptor blocker)". The primary and second outcomes were mortality (non-survivor) and severe COVID-19, respectively. RESULTS: Totally, 7410 patients were included from 15 studies. Pooled analysis showed that the use of ACEI/ARB was not associated with mortality (OR 0.73 [0.38, 1.40], p = 0.34; I2: 81%) and severity (OR 1.03 [0.73, 1.45], p = 0.87; I2: 65%). Pooled adjusted OR showed no risk/benefit associated with ACEI/ARB use in terms of mortality (OR 0.83 [0.54, 1.27], p = 0.38; I2: 0%). Subgroup analysis showed that the use of ARB was associated with reduced mortality (OR 0.51 [0.29, 0.90], p = 0.02; I2: 22%) but not ACEI subgroup (OR 0.68 [0.39, 1.17], p = 0.16; I2: 0%). Meta-regression showed that the association between ACEI/ARB use and mortality in patients with COVID-19 do not varies by gender (p = 0.104). GRADE showed a very low certainty of evidence for effect of ACEI/ARB on mortality and severity. The certainty of evidence was very low for both ACEI and ARB subgroups. CONCLUSION: Administration of a renin angiotensin system (RAS) inhibitor, was not associated with increased mortality or severity of COVID-19 in patients with hypertension. Specifically, ARB and not ACEI use, was associated with lower mortality.

Is subcutaneous insulin administration adequate for the management of hyperglycemic crisis in COVID-19?

There is a desperate need to explore different insulin administration strategies, particularly in coronavirus disease 2019 (COVID-19) patients with hyperglycemic crisis. Noteworthily, diabetes mellitus (DM) and poorly controlled blood glucose increase the risk of mortality and severity of COVID-19. Intravenous (IV) insulin administration with hourly monitoring of blood glucose is the ideal approach in managing patients with hyperglycemic crisis, but it is not judicious to be applied in developing countries where shortage of personal protective equipment (PPE) is a major issue. Furthermore, increasing the probability of "already greater risks" for doctors or other healthcare workers contracting COVID-19 seems inappropriate. Thus, an alternative administration strategy and more moderate glucose monitoring to reduce the contact exposure of healthcare workers with COVID-19 patients, by ensuring appropriate blood glucose levels, needs to be performed in this critical pandemic era. Subcutaneous (SC) rapid-acting insulin analog administration could presumably be a solution to this contentious issue.

Impaired glucose tolerance among adolescents with low birth weight history: The Tanjungsari Cohort Study in Indonesia.

BACKGROUND AND OBJECTIVES: Diabetes prevalence has been increasing overtime in Indonesia along with its complications and morbidities. Diabetes prevention program is still a challenge. Previous study concluded poor intrauterine nutritional status, low birth weight (LBW), and nutrition status early in life were risk factors for impaired glucose tolerance (IGT) or type 2 diabetes mellitus in adulthood. This study aimed to evaluate the association between both LBW and intrauterine growth restriction (IUGR) with IGT in adolescents. METHODS AND STUDY DESIGN: Total of 536 subjects from Tanjungsari Cohort Study were included in this study. Subjects were in their early adolescence age (12-14 years). Anthropometric data were collected and IGT was determined by using 2- hour postprandial plasma glucose level, then it was assessed based on their birth weight and intrauterine nutritional status. RESULTS: Subjects with LBW history were shorter, had lower body weight and body mass index (p<0.05, respectively). The proportion of IGT is significantly higher among subject with LBW (RR 1.692 [1.079- 2.653]). There was no difference on proportion of IGT among subjects with IUGR compared with subjects who were not IUGR or born preterm (p=0.286). Multiple regression analysis showed the effect of LBW remain independent after adjusted with sex and socioeconomic variables (RR 1.650 [1.054-2.584]). CONCLUSIONS: Significant association was found between LBW and IGT in comparison to those who were born with normal birth weight. Hence, diabetes should be prevented as early as possible, even since in the pregnancy.

Utility of Precision Medicine in the Management of Diabetes: Expert Opinion from an International Panel.

AIM: The primary objective of this review is to develop a practice-based expert group opinion on the role of precision medicine with a specific focus on sulfonylureas (SUs) in diabetes management. BACKGROUND: The clinical etiology, presentation and complications of diabetes vary from one patient to another, making the management of the disease challenging. The pre-eminent feature of diabetes mellitus (DM) are chronically elevated blood glucose concentrations; however, in clinical practice, the exclusion of autoimmunity, pregnancy, pancreatic disease or injury and rare genetic forms of diabetes is crucial. Within this framework, precision medicine provides unique insights into the risk factors and natural history of DM. Precision medicine goes beyond genomics and encompasses patient-centered care, molecular technologies and data sharing. Precision medicine has evolved in the field of diabetology. It has helped improve the efficacy of SUs, a class of drugs, which have been effectively used in the management of diabetes mellitus for decades, and it has enabled the expansion of SUs use in diabetes patients with genetic mutations. REVIEW RESULTS: After due discussions, the expert group analyzed studies that focused on the use of SUs in diabetes patients with genomic variations and rare mutations. The expert group opined that SUs are important glucose-lowering drugs and that precision medicine helps in improving the efficacy of SUs by matching them to those patients who will benefit most. CONCLUSION: Precision medicine opens new vistas for the effective use of SUs in unexpected patient populations, such as those with genetic mutations.