Worsening Of Glycemic Control Research Articles

8812 Incidence And Clinical Experience Of Immune Checkpoint Inhibitors-Induced Endocrine Side Effects Among Filipino Cancer Patients: A Single-Center Retrospective Study

Abstract Disclosure: N.B. Luna: None. E. Mendoza: None. S.A. Kho: None. Incidence And Clinical Experience Of Immune Checkpoint Inhibitors-Induced Endocrine Side Effects Among Filipino Cancer Patients: A Single-Center, Retrospective Study Immune checkpoint inhibitors (ICIs) serve as immunomodulatory antibodies, which enhance the immune system and substantially improve the prognosis for patients with advanced malignancies [1]. Referral to endocrinology have been increasing because ICIs were associated with endocrine-related adverse effects including hypothyroidism, hyperthyroidism, diabetes, hypophysitis and adrenalitis. Hence, the study aimed to retrospectively determine the local prevalence and profile of Filipino patients who developed endocrinopathies during ICI therapy at the University of Santo Tomas Hospital (USTH), Manila, Philippines from 2013-2019. A single-center retrospective study of ICI-treated cancer patients with serial biochemical and/or radiologic monitoring of endocrine adverse effects was done upon approval by the Research Ethics Committee. A total of 27 subjects were included with a median age of 60 years and male predominance. Pembrolizumab consisted 93% of the ICIs given. The incidence of thyroid dysfunction was 36% (18% overt hypothyroidism, 9% subclinical hypothyroidism, and 9% subclinical hyperthyroidism). The median time at risk for development of overt hypothyroidism is 4 weeks with median TSH level of 9.05 uIU/mL from baseline level of 3.77 uIU/mL. All patients who had baseline hypothyroidism worsened with increase from baseline levothyroxine dose by 50 to 230% in order to achieve euthyroidism (p 0.037). Serial monitoring was done every 2 weeks until euthyroidism. ICIs were temporarily put on hold in 75%. Diabetes (p 0.05), renal carcinoma (p 0.001) and dose of 200mg (p 0.42) were associated to developing overt hypothyroidism. Checking of glycemic levels was not routine among non-diabetic patients. Fifteen percent of diabetic patients had worsening of control (median HbA1c 8.5% [8-9] and 23% were newly diagnosed pre-diabetes (median fasting glucose 114mg/dL [104-120]). With the available imaging results, there were no abnormal adrenal metabolic uptake on PET scan and no evidence of hypophysitis in pituitary MRI. In conclusion, overt hypothyroidism is a common occurrence during ICI therapy (18%). Worsening occurred among all patients with hypothyroidism at baseline. New-onset pre-diabetes and worsening of glycemic control were seen in 15 and 23%, respectively. Serial clinical and biochemical monitoring is important and referral to endocrinology should be made if deemed necessary. [1] L Agrawal, A Bacal, S Jain, V Singh, N Emanuele, Ma Emanuele & F Meah (2020) Immune checkpoint inhibitors and endocrine side effects, a narrative review, Postgraduate Medicine, 132:2, 206-214, DOI: 10.1080/00325481. 2019. 1709344 Presentation: 6/1/2024

Potential Effect of Chloroquine in Modulating Hyperglycemia and PTEN Receptor Linked Dyslipidemia on Alloxan-induced Diabetic Mice

Background: Diabetes mellitus is a life-threatening disease associated with worsening of glycemic control, progressive metabolic dysfunctions and disruption of the Phosphatase and Tensin Homolog (PTEN) receptor. Purpose: To evaluate the effect of chloroquine on blood glucose level and lipid profile of alloxan-induced diabetic mice and to observe its interaction with PTEN, a negative regulator of insulin signaling pathway. Methodology: Thirty mice were used for the experiment. A group (n = 5) was kept as healthy control while the others were pre-treated with 140 mg/kg of alloxan monohydrate in distilled water. The alloxan-induced diabetic mice were randomly divided into four groups: diabetic model control group, 60 mg/kg chloroquine, 120 mg/kg chloroquine, and 10 mg/kg glibenclamide treatment groups respectively. Treatment was done once daily for seven days and the blood glucose level was investigated acutely and then daily throughout the experimental period. A molecular docking study was also conducted to evaluate the interaction of chloroquine with PTEN using PYRX software, while an automated COBAS C 311 machine was used to analyze the lipid profile after the treatment period. Results: Oral administration of chloroquine gradually and significantly lowered the raised blood glucose level in a time- and dose-dependent manner. A repeated study with 120 mg/kg of chloroquine revealed a decline in blood sugar from 221.5 ± 3.6 on day 1 to 85.5 ± 2.4 on day 7 in comparison to glibenclamide, whose sugar level was reduced to 75.5 ± 3.7 at the end of day 7. The docking study revealed a non-competitive inhibition with an inhibition score of -6.1 in comparison to metformin, which had a score of -4.4, and glibenclamide, which had a score of -9.0. This interaction resulted in a conformational change of the receptor, hence, enhancing glucose uptake and reducing the raised hyperglycemia. Treatment with chloroquine was also observed to reduce the total cholesterol and triglyceride levels from 162 in the model group to 144 and 141 to 116 mmol/L, respectively. The levels of low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein (VLDL) following treatment with chloroquine were not statistically different from the non-diabetic healthy mice. These values were very similar to those obtained with glibenclamide-treated diabetic mice. Conclusion: From the results, chloroquine possesses potent antidiabetic properties and can improve dyslipidemia imposed by hyperglycemia probably owing to its inhibition of PTEN, a negative regulator of insulin resistance.

Effects of COVID-19 lockdown on metabolic control in patients with type 2 diabetes in Sri Lanka

Introduction: The COVID-19 pandemic has led to an island-wide lockdown in Sri Lanka, leading to restrictions in daily routines. The ensuing lifestyle changes have drastically influenced the prevalence and worsening of chronic diseases like diabetes with poor metabolic control of the disease.Objectives: To evaluate the immediate impact of the lockdown on the metabolic parameters associated with diabetes control in individuals with type-2 diabetes mellitus (T2DM).Methodology: A single center cross-sectional descriptive study was conducted on 157 T2DM patients attending a diabetes clinic in the private sector. Pre- and post-lockdown data on metabolic control of the study population was collected from patient records. Patients’ perceptions of diet/exercise and access to medication/medical care during the lockdown were collected through a telephone interview.Results: Pre- and post-lockdown data of 157 male (Females 88; mean age-58.68±SD 13.44 years) patients belonging to the age group 48-72 were evaluated. Of the patients who had a HbA1c of ≤ 7% pre-lockdown, 80% had shown to maintain their HbA1c. Of the patients with HbA1c > 7% pre-lockdown, 27.9% showed a reduction of their HbA1c below 7%.The majority of the responders had no difference in their diet (69.2%) and exercise (65.4%) during the lockdown. Among those with improved HbA1c (n=101;63% of cohort), 16.9% and 13% had better diet and exercise respectively while none in worsened HbA1c group had improved diet or exercise.Conclusions: Lockdown in Sri Lanka has not been associated with worsening of glycaemic control in the studied cohort of patients with type 2 diabetes. Adherence to the recommended diet and exercise regime during lockdown is associated with better glycaemic control in patients with type 2 diabetes.

Effects of liraglutide on intrapancreatic fat deposition in patients with type 2 diabetes

Ectopic fat deposition is associated with worsening of glycemic control. This study was conducted to determine whether liraglutide reduces ectopic fat deposition, especially in pancreas, in patients with type 2 diabetes (T2D). We retrospectively recruited T2D patients who underwent abdominal unenhanced CT scans both before and after administration of liraglutide (N=13) or glimepiride (N=29). Using CT values of pancreas (P), liver (L) and spleen (S), we defined the indices of intrapancreatic and liver fat as P-S value and L-S value, respectively. Increase of each value suggests the reduction of each fat deposition. The values of HbA1c (p=0.0017) and body weight (p=0.0081) decreased, and L-S (p=0.0024) increased significantly after administration of liraglutide compared with those at baseline. Similarly, P-S tended to increase in the liraglutide group (p=0.0547) and increased significantly in the liraglutide subgroup with fatty pancreas (p=0.0303), defined as having baseline P-S less than-5. In the glimepiride group, P-S did not increase regardless of baseline P-S. Among patients with fatty pancreas, administration of liraglutide tended to be a significant factor for the change in P-S after adjustment for the change in HbA1c (p=0.1090) and the change in visceral fat area (p=0.1030). Intrapancreatic fat deposition was decreased after treatment with liraglutide, but not glimepiride, in T2D patients with fatty pancreas. Liraglutide might reduce intrapancreatic fat deposition independently of decreases in HbA1c and visceral fat volume.

Abstract 17091: ARO-APOC3, an Investigational RNAi Therapeutic, Silences APOC3 and Reduces Atherosclerosis-Associated Lipoproteins in Patients With Mixed Dyslipidemia: MUIR Study Results

Background: Despite the availability of potent LDL-C-lowering therapies, patients with mixed dyslipidemia (MD) remain at high risk of cardiovascular (CV) disease due to residual risk from triglyceride (TG)-rich atherogenic lipoproteins (TRLs), ie, remnant cholesterol and/or VLDL-C. Inhibition of APOC3 has emerged as a promising therapeutic strategy for reducing this residual CV risk. Aim: We report interim results through Week 24 from MUIR, an ongoing, randomized, placebo-controlled, Phase 2b study (NCT04998201) evaluating the effects of ARO-APOC3 in patients with MD (fasting TGs 150 to 499 mg/dL and either LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL). Methods: Eligible subjects (n=353) were randomized 3:1 to receive either subcutaneous injections of 10, 25, or 50 mg ARO-APOC3 or matched placebo on Day 1 and at Week 12 or 50 mg ARO-APOC3 on Day 1 and Week 24. Subjects were on a stable diet and optimal lipid-lowering therapies. The primary endpoint was the percent change from baseline in fasting TGs at Week 24. Statistically significant differences were determined using mixed model repeat measures analysis. Results: At Week 24, when dosed on Day 1 and Week 12, ARO-APOC3 significantly decreased APOC3 in a dose-dependent manner up to 80% (p<0.0001). Least squares (LS) mean TGs were significantly reduced by 52 to 64% (p<0.0001). Least squares (LS) mean atherogenic lipoproteins were reduced by up to 27% for non-HDL-C, 19% for apolipoprotein B, and 55% for remnant cholesterol. LS mean HDL-C was increased by up to 51%. The most frequent adverse events were COVID-19 infection, worsening of glycemic control, and upper respiratory infection. Conclusions: By silencing APOC3 expression, ARO-APOC3 significantly reduced circulating TGs and atherogenic TRLs in patients with MD. The effect of ARO-APOC3 on CV relative risk reduction will be evaluated in an upcoming outcomes trial.

328-OR: Effect of Unblinded vs. Blinded Dexcom G6 CGM Wear in Outpatients with Type 2 Diabetes—Real-World Data

Recent studies have demonstrated the value of CGM in optimizing Type 2 diabetes (T2D) management. There is an interesting debate in the literature examining the value of unblinded vs blinded wear of CGM, which is especially relevant in T2D management. We sought to understand the glycemic effects of transitioning from unblinded to blinded CGM wear in a small cohort of T2D outpatients from a community hospital. Participants (n=46) wore unblinded Dexcom G6 sensors for 90 days. After a 90-day washout period, they wore blinded G6 sensors for 10 days. They then completed surveys regarding device acceptability and behavioral changes attributable to CGM wear. Paired t-tests were used to compare unblinded vs. blinded intervals. Median (IQR) age was 59 (54-63) years and 72% were CGM naïve. Median (IQR) baseline A1C was 7.4% (6.7-8.5). Twenty-one participants completed the program in full. The post-washout mean TIR was 15 percentage points lower than during rt-CGM use (Table), attributable to more time in hyperglycemia. Most participants reported that CGM was helpful in making dietary decisions. In adults with T2D, discontinuation of CGM is associated with worsening of glycemic control. Ongoing access to CGM data is likely necessary to maintain good control in T2D. Further research with large and diverse T2D samples is needed to understand how CGM impacts patient behavior and how to sustain long-term improvements. Disclosure C.Hicks: Employee; Dexcom, Inc. H.Singh: Employee; Tandem Diabetes Care, Inc., Dexcom, Inc. T.Zhou: Employee; Pfizer Inc. S.Menon: Employee; Dexcom, Inc. M.A.Crawford: Employee; Dexcom, Inc. D.R.Cherñavvsky: None. D.Raterman: None. N.Smith: None. M.Tressler: Employee; Dexcom, Inc. J.Welsh: Employee; Dexcom, Inc. Funding Dexcom, Inc.

ODP264 An Unusual Etiology of Hypothyroidism and New-Onset Insulin-Dependent Diabetes: A Rare Side Effect of Opdivo

Abstract Introduction Nivolumab, a monoclonal antibody targeting programmed cell death 1 receptor, is prescribed for many advanced cancers like malignant melanoma, non-small cell lung cancer, renal cell carcinoma (RCC), etc. with increased use of this medication, the incidence of immune-related side effects is also on the rise. A combined medication side effect of new-onset diabetes and hypothyroidism associated with Nivolumab use is rare. We present a case of Nivolumab-induced hypothyroidism with new-onset insulin-dependent diabetes. Case presentation A 59-year-male with a past medical history of right RCC status post nephrectomy, non-ischemic cardiomyopathy with an ejection fraction of 25-30% on goal-directed therapy/implantable cardioverter-defibrillator, hypertension, hyperlipidemia, and chronic kidney disease stage 3 who presented to the emergency department with complaints of chest pain at rest. The pain was 5/10 in severity and non-radiating. It was relieved by sublingual nitroglycerine en route to the hospital. It was associated with fatigue, nausea, polyuria, and polyphagia. He denied any history of pre-diabetes/diabetes or thyroid disease. Of note, about six months prior to this admission, he was placed on nivolumab for his RCC. Vitals were BP 121/83, RR 20, HR 85, T 97.8°F, and 97% oxygen saturation on room air. The cardiopulmonary exam was unremarkable. An electrocardiogram showed sinus rhythm with normal rate and no ST/T wave changes. Troponin level was 0. 01 ng/mL (normal:: <0. 04 ng/mL) Chest x-ray revealed no acute pathology. Labs showed glucose of 1090 mg/dL (normal:: 70-100 mg/dL) and thyroid-stimulating hormone (TSH) of >50,000 IU/L (normal:: 0.3-4.2 IU/L). Urinalysis was positive for ketones; 20 mg/dL (normal:: negative). Venous blood revealed a pH level of 7.344. An acute coronary syndrome was ruled out, and he was admitted for management of hyperosmolar hyperglycemic state (HHS) and hypothyroidism. Due to a low level of C-peptide: <0.5 ng/mL (normal:: 1.1-4.4 ng/mL) and high TSH, a new-onset insulin-dependent autoimmune diabetes and hypothyroidism induced as a side effect of nivolumab was suspected. Nivolumab was discontinued from his medication regimen. Endocrinology was consulted for the management of HHS and hypothyroidism. Insulin drip and levothyroxine were started, and he was transferred to the intensive care unit for close monitoring. Thereafter, his metabolic derangements improved with the resolution of hyperglycemia and electrolyte disturbances. On discharge, his symptoms improved and he was advised to stop taking nivolumab. Discussion Nivolumab has been reported in the literature to cause worsening of glycemic control and is also rarely reported as a cause of insulin-dependent diabetes due to autoimmune effects. Its effects on the thyroid are usually reported as transient thyrotoxic period which either resolves to euthyroid or rarely hypothyroidism which is what happened with our patient. Recognizing the side effects of Nivolumab and periodic monitoring can help earlier diagnosis and management with better outcomes. Presentation: No date and time listed

Long-Term Adverse Effect of Liver Stiffness on Glycaemic Control in Type 2 Diabetic Patients with Nonalcoholic Fatty Liver Disease: A Pilot Study.

Currently, there are limited data regarding the long-term effect of liver stiffness on glycaemic control in patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). We prospectively followed an outpatient sample of 61 consecutive postmenopausal women with T2DM and NAFLD who had baseline data on liver ultrasonography and Fibroscan®-assessed liver stiffness measurement (LSM) in 2017 and who underwent follow-up in 2022. Haemoglobin A1c (HbA1c) was measured both at baseline and follow-up. At baseline, 52 patients had NAFLD (hepatic steatosis) alone, and 9 had NAFLD with coexisting clinically significant fibrosis (defined as LSM ≥ 7 kPa on Fibroscan®). At follow-up, 16 patients had a worsening of glycaemic control (arbitrarily defined as HbA1c increase ≥ 0.5% from baseline). The prevalence of NAFLD and coexisting clinically significant fibrosis at baseline was at least three times greater among patients who developed worse glycaemic control at follow-up, compared with those who did not (31.3% vs. 8.9%; p = 0.030). In logistic regression analysis, the presence of NAFLD and clinically significant fibrosis was associated with an approximately 4.5-fold increased likelihood of developing worse glycaemic control at follow-up (odds ratio 4.66, 95% confidence interval 1.07–20.3; p = 0.041), even after adjustment for baseline confounding factors, such as age, body mass index, haemoglobin A1c (or HOMA-estimated insulin resistance) and use of some glucose-lowering agents that may positively affect NAFLD and liver fibrosis. In conclusion, our results suggest that the presence of Fibroscan®-assessed significant fibrosis was associated with a higher risk of developing worse glycaemic control in postmenopausal women with T2DM and NAFLD.

Post-transplant Diabetes Mellitus: What Physicians Need to Know.

Post-transplant diabetes mellitus (PTDM) is a common problem among solid organ transplant recipients contributing to morbidity and affecting patient as well as graft survival adversely. It can occur at any period following transplantation, but maximum incidence is observed in the first few months, with a second peak after a few years after transplantation. The pathogenesis is complex and poorly understood, however, it is associated with both dysfunctional beta-cells and insulin resistance. Both nonpharmacologic and antidiabetic therapies are important for adequate glycemic control. This point of view article provides a short review on PTDM in solid organ transplantation (SOT) recipients from a general physician's perspective.

P142 Fracture risk in diabetes: to FRAX or not to FRAX?

Abstract Background/Aims Diabetes mellitus is associated with decreased bone strength as well as increased fracture risk. The risk of fragility fracture increases with an increase in the duration of diabetes and worsening of glycemic control. However, this increased fracture risk often goes unidentified. Identifying patients at risk of fracture is fundamental in helping to prevent fractures. WHO FRAX (fracture risk assessment) tool computing the 10-year probability of hip fracture or a major osteoporotic fracture helps ascertain fracture risk. In Type 2 Diabetes Mellitus (T2DM), the diagnosis of osteoporosis by dual-energy X-ray absorptiometry (DXA) and the FRAX are only partially useful in assessing fracture risk. Our aims were: 1. To identify the fracture risk in patients with diabetes and 2. To assess the impact of adding diabetes as a risk factor in the calculation of FRAX score. Methods One hundred patients above the age of 50 years with duration of diabetes above a year who attended the diabetes clinic from December 2020 to June 2021 were included. Data was collected on demographics (age, sex, ethnicity), diabetes-related factors (the type, duration, complications and medications) and clinical risk factors for osteoporotic fracture (parental fracture, previous fracture, smoking, alcohol intake) from patient interviews and the FRAX score was calculated. FRAX tool was modified for diabetes by adding either 10 years of age or Rheumatoid arthritis as risk factor. Results Mean age of our cohort of patients was 67 years and their mean BMI was 33 kg/sq m. Duration of diabetes was over 5 years in 95% of the patients. T2DM was seen in 82% and Type 1 Diabetes mellitus (T1DM) in 18%. The mean HbA1c was 8.4%. Unadjusted mean FRAX score for a major osteoporotic fracture was 8.9% and hip fracture 2.3%. High risk of future fracture was seen in 4% of the patients and intermediate risk in 23% and low risk in 73%. Four patients had Rheumatoid arthritis and 21 had previous fragility fractures. Modifying the FRAX tool by adding 10 years to age moved 15% more patients to the intermediate-risk category needing DXA and 5% more to the high-risk category needing osteoporosis treatment. However, adding Rheumatoid arthritis changed 20% more patients to the intermediate-risk category needing DXA and 7% more to the high-risk category needing osteoporosis treatment. Conclusion Modifying FRAX tool in patients with diabetes mellitus will enable more patients to have a DXA scan and to receive osteoporosis treatment and the strategy using rheumatoid arthritis as a risk factor identified more patients than adding 10 years of age. Disclosure M. Mathew: None. S. Dwivedi: None. H. Buch: None. S. Venkatachalam: None.

Impact of Successful HCV Eradication on Glycemic Control in Chronic HCV Patients with Type II Diabetes Mellitus

Introduction: Chronic HCV infection has been implicated as a risk factor for new onset diabetes mellitus type II and worsening of glycemic control in patients with already established Diabetes due to defined molecular mechanisms. The impact of successful HCV eradication with direct-acting antiviral agents (DAAs) on glycemic control in HCV patients with concomitant Diabetes mellitus is being assessed by several studies but still unclear due to scarce data in literature, which specifically address this aspect of DAAs. Objective: To study the impact of successful HCV eradication with DAAs based regimes on glycemic control in a cohort of Chronic HCV patients with concomitant Type II Diabetes Mellitus. Materials and Methods Study design: Descriptive Case series Study place: Department of Gastroenterology, Lahore General Hospital, Lahore. Duration: Six months i.e. 15-2-2021 to 15-8-2021 Data collection procedure: 110 patients, who fulfill the inclusion, were enrolled in the study.All patients of Hepatitis C received DAAs in the form of Oral Sofosbuvir 400 mg and Oral Daclatasvir 60 mg daily for 12 weeks without Ribavirin. Only Child Pugh class A and class B patients were included. Before starting treatment glycosylated haemoglobin (HbA1c) and Viral load by HCV RNA polymerase chain reaction was also checked. All the patients were followed at the end of treatment i.e. at 12 weeks( from the baseline ) and then three months after treatment (at 24 weeks), for viral load testing by HCV RNA polymerase chain reaction and HbA1c levels. Results: In this study 91% patients achieved sustained virological response and 83% of the patients achieved improved glycemic control after successful HCV eradication. Age (23-33: 16.5%, 34-44: 40.7%, 44-54: 29.7% p-value=0.728) and gender (Male: 39.6% & Female: 60.4%, p-value=0.142) have no significant association with glycemic control of patients. Conclusion: Based on the findings of this study, it can be concluded that oral DAAs can help improving the glucose levels and glycemic control significantly in HCV patients with concomitant Type II diabetes mellitus and successful HCV eradication can prevent the long term complications of diabetes and may need dose reduction for insulin therapy in these patients Keywords: Glycemic control, dual-acting antiviral agents, chronic hepatitis C virus infection, Diabetes Mellitus

Impact of the COVID-19 Pandemic on Glycemic Control and Blood Pressure Control in Patients with Diabetes in Japan.

Objective In this study, we investigated whether and how the COVID-19 pandemic affected glycemic control and blood pressure (BP) control in patients with diabetes mellitus (DM). Methods DM patients whose HbA1c level was measured regularly before and after the declaration of a state of emergency were included in this study. Some patients were given questionnaires about changes in their lifestyle to determine the factors affecting glycemic control and BP control. Results The median HbA1c level of the 804 patients increased significantly from 6.8% before the state of emergency to 7.1% and 7.0% during and after the state of emergency, respectively. This was in contrast to the decrease one year earlier due to seasonal variations. In the 176 patients who responded to the questionnaire, the HbA1c level also increased significantly during and after the state of emergency. The worsening of glycemic control was more pronounced in the group that had achieved HbA1c of <7% before the state of emergency than in those with higher values. Unlike the rise in HbA1c, the BP did not rise during the state of emergency but did rise significantly afterwards. There was no marked decrease in HbA1c or BP after the state of emergency, even in patients who responded that they were much more careful with their diet, ate less, or exercised more. Conclusions The COVID-19 pandemic worsened glycemic control and BP control, even in patients who perceived no marked change in their diet or exercise, suggesting that more active lifestyle guidance is necessary for good treatment of DM patients.

Four-year changes in central fatness, risk of diabetes, and metabolic control in older adults: a cohort study with mediation analysis.

Background/AimsOlder adults are vulnerable to central obesity, while the association of changes in central fatness with risk of diabetes and metabolic control has not been investigated among this particular population. This study was aimed to address these issues.MethodsA total of 1,815 adults aged ≥ 60 years without diabetes at baseline were followed for 4 years. Incident diabetes was ascertained based on plasma glucose, hemoglobin A1c, medical history, and/or the use of anti-diabetic drugs. Central fatness was assessed by waist circumference (WC), waist-height ratio (WHtR), and body roundness index (BRI). Logistic regression analyses were used to assess the association of changes in central fatness with risk of diabetes, along with dose-response and mediation analyses.ResultsDuring the 4-year follow-up, 177 participants developed diabetes. The risk of diabetes was increased by 42%, 41%, and 40% per 1 standard deviation increases in WC, WHtR, and BRI, respectively, in multivariable-adjusted models (all p < 0.01). Moreover, these relationships were all linearly-shaped (all pnonlinearity ≥ 0.11). Increases in WC, WHtR, and BRI correlated with increases in hemoglobin A1c, triglycerides-and-glucose index, triglycerides, white blood cell, and C-reactive protein (all p ≤ 0.04). Yet only changes in hemoglobin A1c and triglycerides-and-glucose index were identified as the possible mediators for risk of diabetes, with their mediating effect being about 35% and 21%, respectively.ConclusionsIncreases in central fatness were related to elevated risk of diabetes, and this association might be partly explained by the worsening of glycemic control and insulin resistance in older adults.

26-LB: Glycemic Control in People with Type 1 Diabetes Mellitus after the First Portuguese COVID-19–Related State of Emergency

Introduction: The first Portuguese COVID-19-related state of emergency (SE) extended between March and May 2020. The relevance of achieving the glycemic target for the person with type 1 Diabetes Mellitus (T1DM) is deepened in these circumstances, given the forced changes in daily routine. Objective: To determine the influence of work activity (WA) on glycemic control (GC) of adults with T1DM after the first SE. Material and methods: A retrospective cohort study was designed to enroll adults with ≥2 years from T1DM diagnosis. Cases of pregnancy/hospitalizations in 2019/2020, factors that affect interpretation of glycated hemoglobin (HbA1c) and/or SARS-CoV-2 infections were excluded. The participants were stratified into groups of WA after the SE: g1 (telework/lay-off/students), g2 (retired/unemployed) and g3 (WA without lockdown). HbA1c were obtained from 4 periods: t3 (4/1-6/1/2020); t4 (7/1-9/1/2020); t1 and t2 (homologous periods of 2019). Differences in HbA1c were calculated in both years and compared to each other in the same group and between groups in the same year. Hypoglycemia and insulin regimens (insulin pump and multiple injections daily) were analyzed in intragroup (t3 vs. t4) and intergroup (t3 and t4) comparisons. Results: Two hundred and seven participants were included [106 (51.2%) men; median age of 35 (25;47) years]: 144 (69.6%) in g1, 44 (21.3%) in g2 and 19 (9.2%) in g3. HbA1c increased significantly between t4 and t3 (vs. t2 and t1) in g1 (p=0.001), but not in g2 (p=0.077) and g3 (p=0.744). In 2020, HbA1c raised significantly in the analysis "g1 vs. g3" (p=0.004), but not in "g1 vs. g2" (p=0.213) and "g2 vs. g3" (p=0.083). No differences were reported in 2019, along with all the comparisons involving hypoglycemia and insulin regimens. Conclusions: This study found an overall worsening of GC in participants who returned to higher levels of activity after a total lockdown. This is probably explained by the time spent on T1DM self-care during the lockdown. Disclosure D. Ramalho: None. S. Correia: None. L. Almeida: None. H. Alves: None. G. Rocha: None. M. Ferreira: None. M. J. Oliveira: None.

The Impact of Peri-Implantitis on Systemic Diseases and Conditions: A Review of the Literature.

While periodontitis has been proven to have an impact on systemic conditions, such as cardiovascular diseases, pregnancy complications, or poor glycemic control in diabetic patients, the influence of peri-implantitis on systemic health has not been adequately explored in the literature as yet. The existing evidence suggests that peri-implant lesions lead to more intense inflammatory response than periodontitis. Given the analogies between periodontal diseases and peri-implantitis, the aim of the present paper was to review the scientific evidence about the potential correlation between peri-implantitis and systemic diseases and conditions. Two clinical trials on animals reported that experimental peri-implantitis determined an alteration in hematological and biological parameters. One human study explored the risk indicators for cardiovascular diseases and found that patients with peri-implantitis had significantly higher levels of triglyceride, uric acid, and white blood cells and lower levels of vitamin D. It was described in the literature that periodontitis affects cardiovascular health through a number of mechanisms, including the increase in systemic mediators of inflammation, which also has a role in the worsening of glycemic control in diabetic patients. Similarly, peri-implantitis may influence the systemic status through inflammatory cytokines such as IL-1, IL-6, and IL-10 and matrix metalloproteinases. One microbiological mechanism, based on the systemic dissemination of periodontal bacteria, has been hypothesized for cardiovascular diseases and pregnancy complications. Again, it is plausible that the same could occur in peri-implantitis. In conclusion, only few studies explored the systemic impact of peri-implantitis. Although changes in hematological parameters, biochemical parameters, and inflammatory markers have been reported in peri-implantitis, further studies are needed to investigate this correlation.

COVID-19 Associated Rhino-orbito-cerebral Mucormycosis: Clinical Profile and Imaging Spectrum

Introduction: Rhino-orbito-cerebral mucormycosis is a fatal disease caused by saprophytic fungi seen almost exclusively in diabetic and immunocompromised patients. Aim: To describe various imaging findings of mucormycosis, and to emphasise the importance of imaging in its diagnosis and management. Materials and Methods: A retrospective, observational, single centre study was done including patients with clinical and microbiological evidence of rhino-orbito-cerebral mucormycosis, who had a history of Coronavirus Disease 2019 (COVID-19) infection and had undergone Computed Tomography (CT) and/ or Magnetic Resonance Imaging (MRI) scan of the head, orbit, and paranasal sinuses during the period of one month from 1st-31st May 2021. The clinical and imaging data of 67 such cases were interpreted and analysed by two radiologists. Results: The study included 67 patients out of which 44 were male and 23 were female, and the average age of patients was 49±13 years. During their treatment for COVID-19, 55 (82.08%) patients had a history of hospitalisation and administration of supplemental oxygen, all 67 (100%) patients had taken broad spectrum antibiotics, 56 (83.58%) patients had taken steroids, 20 (29.85%) patients previously had a history of diabetes with worsening of glycaemic control during COVID-19 infection, and 47 (70.15%) patients were diagnosed with new onset hyperglycaemia. On imaging i.e., on CT and/or MRI with or without contrast, the infection was found to primarily affect the sino-nasal region. There was unilateral or bilateral involvement of single or multiple paranasal sinuses in all 67 patients with involvement of nasal cavity in 42 patients. Maxillary sinus was the most common and consistently involved sinus seen in all 67 patients, followed by ethmoid sinus seen in 54 patients. Additionally, 56 patients had extra-sinus disease with spread along vessels, nerves, or via bone erosion. CT showed soft tissue thickening, oedema, and fat stranding with or without bone erosion as the predominant finding in involved areas, while MRI showed Short Tau Inversion Recovery (STIR) hyperintense soft tissue thickening and postcontrast enhancement as the main finding. Conclusion: There is a complex interplay of various COVID-19 infection and treatment related factors that are responsible for increased susceptibility to mucormycosis infection. Imaging plays an important role in aiding the diagnosis, determining the extent and spread of infection, guiding the extent of the surgical intervention, and determining the prognosis of these patients. The contrast enhanced MRI along with plain CT should be the preferred choice of imaging.

Psychological adaptive difficulties and their management during COVID-19 pandemic in people with diabetes mellitus

Background and aimsPeople with diabetes have multiple psychosocial issues related to diabetes and its complications and this may be exacerbated during the COVID-19 pandemic. MethodsWe reviewed the psychological adaptative difficulties in people with diabetes especially during natural disasters including the prevailing COVID-19 pandemic. ResultsThere are significant concerns regarding worsening of glycemic control, unavailability of appropriate medicines, inaccessibility to health care or acquiring SARS- CoV-2 infection and subsequent poorer outcomes during the COVID-19 pandemic. Although there are some guidance documents for managing diabetes and associated complications during COVID-19 pandemic but very few address the psychological issues in people with diabetes. We discuss the psychological adaptive difficulties and an approach to address the psychosocial concerns in people with diabetes during the COVID-19 pandemic. ConclusionsPeople with diabetes have significant diabetes distress and psychological adaptive difficulties that is aggravated by the COVID-19 pandemic. An integrated multidisciplinary approach is needed to manage the prevailing psychological issues amongst people with diabetes during the COVID-19 pandemic.

The stomach in diabetes: an assistant or an opponent?

The results of experimental and clinical studies indicate that in patients with diabetes, the stomach is often the cause of various dyspeptic symptoms, and the impaired gastric emptying may be accompanied by a worsening of glycemic control. The use of drugs that acts as endogenous incretins, inhibits gastric emptying and improves glycemic control. Different methods of bariatric surgery in patients with obesity and type 2 diabetes reduce food intake and body weight, and their effect on glycemic control precedes weight loss and does not correlate with the degree of weight loss. Currently, the mechanisms responsible for improving glycemic control after bariatric surgery are intensively studied, such as increasing the level of circulating incretins stimulated by the release of nutrients in the intestine and contributing to weight loss regardless of glycemic control. It was concluded that the stomach should be considered not only as a negative, but also as a positive modifying factor, the effect of which can improve the results of treatment and prolonged management of patients with type 2 diabetes

Association between proprotein convertase subtilisin/kexin 9 (PCSK9) and lipoprotein subclasses in children with type 1 diabetes mellitus: Effects of glycemic control

Background and aimsDyslipidemia in type 1 diabetes mellitus (T1DM) is characterised by altered distributions of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses. Recent studies suggested that proprotein convertase subtilisin/kexin 9 (PCSK9) may contribute to the development of dyslipidemia in T1DM. In this cross-sectional study, we investigated the association between PCSK9 and lipoprotein subclasses in young T1DM patients, with respect to glycemic control. MethodsPlasma PCSK9 and lipoprotein subclasses were determined in 207 patients with T1DM (106 boys and 101 girls), aged 13.9 ± 3.0 years and treated by intensive insulin therapy. ResultsPlasma PCSK9 levels significantly increased with worsening of glycemic control (p < 0.001). T1DM patients with poor glucoregulation had the highest proportion of small, dense LDL (sdLDL) and smaller HDL particles, as well. PCSK9 was positively associated with markers of glucose homeostasis and serum lipid parameters only in patients with suboptimal/poor glucoregulation. In well-controlled T1DM, plasma PCSK9 level was inversely associated with a relative proportion of sdLDL particles (p < 0.01) and this association remained significant in multivariate analysis. In T1DM patients with suboptimal/poor glycemic control, PCSK9 was positively associated with the proportion of the smallest HDL3c particles (p < 0.001), but negatively with HDL size (p < 0.05). ConclusionsThe extent of achieved metabolic control modifies the association between PCSK9 and lipoprotein subclasses in T1DM. Further investigations are needed to reveal whether the observed effects of glycemic control on PCSK9 and sdLDL levels have causal consequences on CVD risk in young patients with T1DM.

AVALIAÇÃO DE NÍVEIS SÉRICOS DE TSH EM PACIENTES DIABÉTICOS TIPO 2

A associação entre o diabetes tipo 1 e doenças tireoidianas autoimunes é bem descrita na literatura, estando claramente indicado o rastreio de tireoidopatias em diabéticos tipo 1, mesmo que em indivíduos assintomáticos. Não obstante, a presença de distúrbios tireoidianos está associado a piora do controle glicêmico em diabéticos, bem como aumento da prevalência e gravidade das complicações da doença. A correlação entre o diabetes tipo 2 e distúrbios tireoidianos não está clara, baseando-se em resultados conflitantes de estudos clínicos. Dados de custo-eficácia e estudos longitudinais são escassos na literatura. Desta forma, a necessidade de rastreio de doença tireoidiana nessa população permanece indefinida. Este estudo transversal avaliou 120 participantes assintomáticos (60 diabéticos tipo 2 e 60 não diabéticos), sem distúrbio tireoidiano conhecido, através da dosagem sérica de TSH. Não foram observadas diferença estatística dos níveis plasmáticos de TSH entre os grupos (p= 0,29), embora uma significativa parcela de indivíduos diabéticos assintomáticos tenha apresentado anormalidades do TSH (8,33 %). Baseando-se em estudos de desfechos clínicos, a pesquisa de anormalidades do TSH em diabéticos tipo 2 poderia apresentar benefícios, tendo em vista a influência desta anormalidade no perfil glicídico e nas complicações do diabetes, bem como sua detecção em parcela significativa de indivíduos diabéticos assintomáticos. Palavras-chave: TSH, tireoidopatia diabetes tipo 2.