Long-standing Type 2 Diabetes Mellitus Research Articles

Noninvasive Assessment of the Severity of Liver Fibrosis in MASLD Patients with Long-Standing Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD), which have a reciprocal relationship compounded by obesity, are highly prevalent in the Middle East affecting morbidity, mortality, and healthcare costs. This study aimed to assess the severity of MASLD and liver fibrosis among adult Emirati patients with long-standing T2DM. This cross-sectional study used noninvasive methods to assess the severity of MASLD and fibrosis progression in an adult cohort of Emirati patients (N = 546) with a mean T2DM duration of 16years. Fatty liver infiltration was assessed by hepatic steatosis index (HSI), while fibrosis was assessed by the fibrosis-4 (FIB-4) index and aspartate aminotransferase/platelet ratio index (APRI). Of those, 108 patients were randomly subjected to ultrasound-based FibroScan® to assess controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). All patients had fatty liver with ~ 83% being categorized as having severe steatosis. Serum-based fibrosis biomarker panels detected significant liver fibrosis in ~ 2.5% of these patients. The APRI appeared to be more restrictive in detecting moderate fibrosis (1.5%) than the FIB-4 index (25.5%). CAP significantly correlated with the LSM, indicating that the two methods contributed to the same underlying pathophysiology. Liver steatosis was more severe in female patients, who were older and had a higher body mass index (BMI) than those with moderate or no significant fibrosis. They also had higher serum liver enzymes and were more likely to have age-related changes in kidney function. Interestingly, severity of both steatosis and fibrosis remained unaffected by age and duration of T2D except for fibrosis severity detected by FibroScan®. This study highlights the critical need for routine screening of MASLD among Emirati patients with long-standing T2DM, given the high point prevalence of severe steatosis (~ 83%), predominantly among women in this population.

Predictors of medication regimen complexity and its impact on hemoglobin a1c in type 2 diabetes patients: a retrospective analysis in ambulatory care in Makkah City.

Type 2 diabetes mellitus (T2DM) is a widespread chronic disease that poses a significant management challenge due to the complexity of the associated medication regimens, which can have a considerable impact on patient outcomes. Explore the complexity level of diabetes medications among patients with T2DM and to identify the predictors of medication regimen complexity (MRC) and its correlation with hemoglobin A1C (HbA1c) levels. Retrospective, cross-sectional study. An ambulatory care setting of a tertiary hospital in Makkah City, Saudi Arabia. Patients with T2DM referred to the diabetic clinic were identified and assessed for eligibility. The data were collected from patient electronic medical records between October 2022 and September 2023. The MRC Index was used to evaluate the complexity of the patients' medication regimens. MRC index scores and HbA1c levels. 353 records of patients with T2DM. The analysis revealed that 61.8% (n=218) of patients had high MRC, with the dosing frequency contributing significantly to their MRC (mean=3.9, SD=1.9). Having polypharmacy and longstanding T2DM were predictors of high MRC (odds ratios=4.9 and 2.6, respectively; P≤.01). Additionally, there was an inverse association between the patients' diabetes-specific MRC index scores and their glycemic control (odds ratios=0.2, P<.001). The study findings highlight the importance of considering MRC in managing T2DM. Simplifying medication regimens and optimizing medication management strategies can improve patient outcomes. Further research is needed to explore interventions to reduce MRC and enhance diabetes management in this population. Retrospective study design measuring the MRC at a diabetes-specific level.

Loss of Cldn5 -and increase in Irf7-in the hippocampus and cerebral cortex of diabetic mice at the early symptomatic stage

Analyzing changes in gene expression within specific brain regions of individuals with Type 2 Diabetes (T2DM) who do not exhibit significant cognitive deficits can yield valuable insights into the mechanisms underlying the progression towards a more severe phenotype. In this study, transcriptomic analysis of the cortex and hippocampus of mice with long-term T2DM revealed alterations in the expression of 28 genes in the cerebral cortex and 15 genes in the hippocampus. Among these genes, six displayed consistent changes in both the cortex and hippocampus: Interferon regulatory factor 7 (Irf7), Hypoxia-inducible factor 3 alpha (Hif-3α), period circadian clock 2 (Per2), xanthine dehydrogenase (Xdh), and Transforming growth factor β-stimulated clone 22/TSC22 (Tsc22d3) were upregulated, while Claudin-5 (Cldn5) was downregulated. Confirmation of these changes was achieved through RT-qPCR. At the protein level, CLDN5 and IRF7 exhibited similar alterations, with CLDN5 being downregulated and IRF7 being upregulated. In addition, the hippocampus and cortex of the T2DM mice showed decreased levels of IκBα, implying the involvement of NF-κB pathways as well. Taken together, these results suggest that the weakening of the blood-brain barrier and an abnormal inflammatory response via the Interferon 1 and NF-κB pathways underlie cognitive impairment in individuals with long-standing T2DM

Risk factors for chronic kidney disease in middle eastern patients with type 2 diabetes mellitus: A cross-sectional study using the KDIGO classification

AimsChronic kidney disease (CKD) is prevalent in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate risk factors for CKD progression across the kidney disease-Improving Global Outcomes (KDIGO)categories in a Middle Eastern population beyond hyperglycemia as emphasized by KDIGO guidelines which classifying CKD by cause and severity. MethodsThis cross-sectional study targeted 1603 patients with T2DM. Risk factors for CKD progression were determined using odds ratios (ORs) and 95 % confidence intervals (CIs). ResultsOverall, 35.5 %, 31.7 %, and 32.8 % of patients were classified as low-risk, moderate-risk, and high-/very high-/highest-risk, respectively. Several factors were associated with high/very high/highest risk categorization, including being aged >45 years (OR: 1.85, 95 % CI: 1.36–2.49; P < 0.001), male gender (OR: 1.87, 95 % CI: 1.38–2.54; P < 0.001), hypertension (OR: 3.66, 95 % CI: 2.32–5.78; P < 0.001), and T2DM duration of ≥15 years (OR: 3.2, 95 % CI: 2.27–4.5; P < 0.001). Patients with more concurrent risk factors were notably represented in the high/very high/highest risk category. ConclusionsMale patients, older patients, and those with comorbid hypertension, longstanding T2DM, and additional concurrent risk factors have a significantly higher risk of advanced CKD. Such findings should be considered when planning management approaches for patients with CKD.

A Significant Association between Type 1 Diabetes and Helicobacter pylori Infection: A Meta-Analysis Study.

Background and Objectives: Type 1 diabetes mellitus (T1DM) is a chronic and serious condition that is characterized by inadequate pancreatic-β-cells' insulin production. The connection between T1DM and Helicobacter pylori infection remains uncertain. This study aimed to conduct a systematic meta-analysis to examine the association between H. pylori infection, hemoglobin A1c levels, and the development of T1DM. Materials and Methods: The initial search identified 451 articles on the association between H. pylori infection and T1DM. Among them, 12 articles had 2797 participants who met the inclusion criteria for an advanced meta-analysis. Results: A significant association was observed between H. pylori infection and T1DM (OR 1.77, 95% CI 1.47-2.12, p < 0.0001), with heterogeneity: Tau2 = 0.47; Chi2 = 57.07, df = 11 (p < 0.0001); I2 = 81%. Subgroup analysis showed that H. pylori infection was significantly associated with a longer duration of T1DM and higher hemoglobin A1c levels (p < 0.001 for both) but not with age at T1DM diagnosis (p = 0.306). Conclusions: These findings contribute to the understanding of the association between H. pylori infection and T1DM and highlight the potential role of H. pylori in influencing the duration and glycemic control of diabetes. Therefore, pediatric patients who have longstanding T1DM and poor glycemic control should be screened for H. pylori infection.

Status of lipid control in Bangladeshi subjects with type 2 diabetes mellitus on lipid-lowering drugs: a multicenter, facility-based, cross-sectional study

BackgroundAchievement of lipid targets is crucial in patients with type 2 diabetes mellitus (T2DM) to mitigate the risk of cardiovascular diseases (CVD). Data on lipid-control status among patients with T2DM in Bangladesh are scarce. This study was conducted to determine the lipid-control status among patients with T2DM who were on lipid-lowering drugs in the country.MethodsThis cross-sectional study was conducted in the diabetes outpatient departments of several tertiary hospitals in Bangladesh from January 2022 to December 2022. Adults of both sexes diagnosed with T2DM for at least one year and were on the lipid-lowering drug(s) for a minimum of 3 months were included in the study by consecutive sampling. Patients’ data were collected by face-to-face interviews, and blood samples were collected for fasting lipid profile. The lipid target was set at < 200 mg/dL for total cholesterol (TC), < 150 mg/dL for triglyceride (TG), < 100 mg/dL for low-density lipoprotein cholesterol (LDL-C), > 40 mg/dL for high-density lipoprotein cholesterol (HDL-C), and < 160 mg/dL for non-HDL cholesterol (non-HDL-C).ResultThree thousand sixty patients (age 44.7 ± 13.3 years, female 57%) with T2DM were evaluated. Overall, almost 81% of the study subjects achieved the LDL-C target. Besides, TC, TG, HDL-C, and non-HDL-C targets were achieved by 40.8, 21.6, 66.3, and 44.1% of patients, respectively. However, all the lipid parameters were under control in only 8.8% of patients. Almost 77.6% of the patients with ischemic heart disease, 81.5% of patients with stroke, and 65% of patients with CKD had LDL levels < 70 mg/dL. Only 10.03% achieved the HbA1c target of < 7%. 7.4% of patients achieved both HbA1c < 7% and LDL < 100 mg/dL and 5% achieved both HbA1c < 7% and LDL < 70 mg/dL. Advanced age (aOR 0.97, 95% CI 0.96, 0.98, p < 0.001), longstanding T2DM (aOR 0.53, 95% CI 0.39, 0.72, p < 0.001), and non-statin therapy (aOR 0.25, 95% CI 0.16, 0.37, p < 0.001) were negatively associated with lipid control (LDL < 100 mg/dL) while using oral hypoglycemic drugs or insulin (aOR 2.01, 95% CI 1.45, 2.77, p < 0.001) and having cardiovascular comorbidity (aOR 3.92, 95% CI 3.00, 5.12, p < 0.001) were positively associated with lipid control.ConclusionThough most patients with T2DM achieved their target LDL level, the prevalence of both glycemic and overall lipid control was low in our study despite lipid-lowering therapy.

Interventional Radiology Approaches for Managing Postpancreatic Transplant Complications and Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder characterized by the destruction of insulin-secreting beta cells in the pancreas, resulting in metabolic disturbances and long-term complications. While subcutaneous insulin remains the primary approach for achieving normoglycemia, pancreatic transplantation has emerged as an effective intervention for long-standing T1DM, providing insulin independence and normalized glycosylated hemoglobin levels. However, complications associated with pancreatic transplantation are frequent, necessitating thorough evaluation using diverse imaging modalities. This manuscript presents an overview of vascular complications encountered with pancreatic transplantation, including vascular complications such as arterial and venous graft thrombosis, vessel stenosis, pseudoaneurysm, arterio-enteric fistula, and arteriovenous malformations (AVM). Additionally, the manuscript discusses other associated complications such as pancreatitis, pseudocyst formation, fistulas, pseudo-thrombosis of the iliac vein, post-transplantation lymphoproliferative disorder, and fluid collections. The integration of various imaging modalities plays a crucial role in diagnosing and managing these complications, with interventional radiologists assuming a vital role in employing image-guided procedures. Moreover, the manuscript explores pancreatic islet cell transplantation as a promising cellular-based therapy for T1DM, offering stable long-term glycemic control and decreased reliance on exogenous insulin in a significant proportion of recipients. This minimally invasive procedure involves the image-guided transcatheter infusion of islet cells obtained from deceased donors into the recipient's liver. The importance of interventional radiologists in managing complications related to pancreatic transplantation is underscored, with endovascular or image-guided approaches being utilized to address the diverse spectrum of encountered complications. Furthermore, the potential of islet cell transplantation as a minimally invasive alternative to traditional pancreatic transplantation is emphasized, as it offers the prospect of alleviating many associated complications.

1345-P: Proinsulin–to–C-Peptide Ratio Is Associated with the Time above the Target Glucose Range and the Duration of Type 2 Diabetes

Background: The proinsulin-to-C-peptide (PI:C) ratio is thought to be an index of pancreatic β-cell dysfunction, and in subjects with prediabetes and type 2 diabetes (T2DM), abnormally high PI:C ratios have been identified. In the present study, we investigated the relationships of the duration of diabetes and glucose variability in subjects with T2DM with the PI:C ratio. Methods: We performed a prospective observational study of 272 Japanese outpatients with T2DM who underwent blinded professional continuous glucose monitoring (CGM) and fasting blood sample collection. Their fasting PI:C ratio and CGM-related indices were calculated. After placing all the participants into four groups on the basis of quartile (Q) of diabetes duration (Q1 &amp;lt;8 years, Q2 8-13 years, Q3 14-21 years, Q4 ≥22 years), the characteristics associated with PI:C ratio were identified. All of the statistical tests were two-sided and P&amp;lt;0.05 was considered to indicate statistical significance. Results: The mean age of the cohort was 68.0 years, their mean HbA1c 7.1%, and their mean body mass index (BMI) 24.9 kg/m2. High PI:C ratio was associated with a short duration of diabetes (P&amp;lt;0.001). In each group, there was a positive correlation between PI:C ratio and the time above the target glucose range (TAR; &amp;gt;180 mg/dL) in Q1, Q2, and Q3. The closest correlation between PI:C ratio and TAR was found for Q1 but there was no significant correlation for Q4 (Q1: ρ=0.38, P=0.003; Q2: ρ=0.28, P=0.019; Q3: ρ=0.24, P=0.045; Q4: ρ=0.03, P=0.811). Conclusions: We have shown that the PI:C ratio was positively associated with TAR in subjects with a short duration of T2DM. Given that insufficient pancreatic β-cell function and hyperglycemia is closely related, the PI:C ratio may play a role as the index of pancreatic β-cell dysfunction in subjects with a short duration of T2DM, but not in those with long-standing T2DM. Disclosure A.Miya: None. A.Nakamura: Research Support; Abbott Japan Co., Ltd., Boehringer Ingelheim Japan, Inc., Daiichi Sankyo, Taisho Pharmaceutical Holdings Co., Ltd., Teijin Pharma Limited, Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation. H.Nomoto: Speaker's Bureau; Novo Nordisk, Sumitomo Pharma, Co., Ltd. H.Kameda: None. T.Atsumi: Speaker's Bureau; Eli Lilly Japan K.K., Kowa Company, Ltd. Funding Japan Society for the Promotion of Science (22K17766)

The Prevalence of Advanced Liver Fibrosis Among Patients With Type 2 Diabetes Mellitus: A Single-Centre Experience in Penang, Malaysia.

Type 2 diabetes mellitus (T2DM) is an important risk factor for Non-alcoholic fatty liver disease (NAFLD). It worsens the course of NAFLD. We investigated the prevalence of advanced liver fibrosis among patients with T2DM. Our secondary objectives were to describe patient demographics, to explore associated clinical factors, and to compare FIB-4 Index and liver stiffness measurement (LSM). This was a cross-sectional study on 258 patients with T2DM duration of at least 10 years. Transient elastography (FibroScan®) was performed on all subjects. Advanced liver fibrosis was diagnosed based on LSM results. The FIB-4 index formula was used. The prevalence of advanced liver fibrosis was 22.1%. Associated factors were body mass index (BMI), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), triglyceride (TG) and high-density lipoprotein (HDL) cholesterol. Independent factors were BMI and GGT (p=0.003 and p<0.001). FIB-4 index has 30.0% sensitivity, 85.0% specificity, 38.7% positive predictive value, and 79.4% negative predictive value in detecting advanced liver fibrosis by LSM criteria. Our study confirmed the high prevalence of advanced liver fibrosis among patients with long-standing T2DM. This study suggests the benefit of advanced liver fibrosis screening in patients with a minimum of 10 years of T2DM, especially those with high BMI and GGT.

Digestive, anorectal, and urogenital functions in patients with type 2 diabetes mellitus, impaired glucose tolerance and normal glucose tolerance: Association with autonomic neuropathy.

Gastrointestinal disorders including constipation and fecal incontinence are common in type 2 diabetes and may derive from diabetic autonomous neuropathy, severe intestinal bacterial overgrowth, or a dysfunctional anorectal sphincter. The present study aims to characterize the correlation between these conditions. Patients with type 2 diabetes, prediabetes and normal glucose tolerance were included. Anorectal function was assessed with high-resolution anorectal manometry. Patients were screened for autonomous neuropathy by measuring olfactory, sweat, and erectile dysfunction as well as heart rate variability. Constipation and fecal (in-)continence were evaluated using validated questionnaires. Breath tests were used to assess severe intestinal bacterial overgrowth. We included 59 participants (32 (54.2%) type 2 diabetes, 9 (15.3%) prediabetes and 18 (30.5%) normal glucose tolerance). Presence of autonomous neuropathy, severe bacterial overgrowth and symptoms of constipation and incontinence was comparable. HbA1c was correlated with an increased anorectal resting sphincter pressure (r = 0.31, P = 0.019) and constipation symptoms (r = 0.30, P = 0.031). In patients with long- standing diagnosis of type 2 diabetes significantly higher values for maximum anorectal resting pressure (∆ = +27.81 ± 7.84 mmHg, P = 0.0015) and baseline pressure (∆ = 20.50 ± 9.74 mmHg, P = 0.046) were found compared with normal glucose tolerance, but not with prediabetes. Long-standing type 2 diabetes increases anorectal sphincter activity, and constipation symptoms are associated with higher HbA1c levels. The lack of an association of symptoms with autonomous neuropathy suggests glucotoxicity as the primary mechanism.

Evaluation of urodynamic pattern in short and long-standing diabetic patients

To address the pattern of urodynamic findings in diabetic patients with lower urinary tract symptoms (LUTS), comparing short-standing and long-standing type 2 diabetes mellitus (T2DM). A prospective study was conducted on 50 patients presenting with LUTS and a concurrent diagnosis of T2DM, between February 2016 and May 2018. Patients were classified and evaluated according to the duration of diabetes into two groups: short-standing DM (< 15 years, n = 31), and long-standing DM (≥ 15 years, n = 19) groups. The impact of LUTS and quality of life were assessed in female patients using ICIQ-FLUTS and male patients using ICIQ-MLUTS. A total of 50 patients were included in the study. The mean duration of T2DM was 10 ± 0.7 years. The mean age was 56.3 ± 1.2 years, and the mean HbA1c was 7.5 ± 1.2%. Urodynamic evaluation detected significantly higher detrusor overactivity (DO) and increased bladder sensation with the short-standing DM group (35.5 vs. 15.8%, p = 0.01 and 32.3 vs. 5.3%, p = 0.01, respectively). Comparatively, weak, or absent detrusor contractility were more frequent in patients with long-standing DM (52% and 26% respectively p = 0.01). As expected, overflow incontinence and straining during voiding were significantly higher in the long-standing DM group (p = 0.04 and p = 0.03, respectively). Surprisingly, there was no significant correlation between patients presenting with urgency in their voiding diary (subjective) and urodynamic detection of DO (p = 0.07). There are different patterns in urodynamic characterizations of T2DM. Patients with short-standing DM present more commonly with storage symptoms and detrusor overactivity on urodynamics. Contrastingly, patients with long-standing DM present more frequently with voiding symptoms and detrusor underactivity on urodynamics. Thus, screening for an underactive bladder is advisable in patients with long-standing T2DM.

De Novo Fibrinogen A Alpha Chain Amyloidosis in a Kidney Transplant Patient: Case Report and Literature Review

Rationale: De Novo transplant amyloidosis denotes the condition when a patient develops amyloidosis after transplantation but had not been diagnosed with the disease prior to transplantation. The incidence of de novo amyloidosis in kidney transplants is rare, but few published case reports have described the occurrence of de novo Amyloid A protein (AA) and Light Chain (AL) amyloidosis. However, de novo hereditary fibrinogen A alpha chain (AFib) has not been previously reported. Patient Presentation: We present a 72-year-old man, a kidney transplant recipient, who developed progressive rise in his creatinine about 3 years after transplantation. He has long-standing diabetes mellitus type 2, obesity, and hypertension, so he did not have a kidney biopsy of his native kidneys prior to transplantation. Diagnosis: A kidney transplant biopsy was done that showed amyloidosis. Mass spectrophotometry confirmed it as AFib amyloidosis. Genetic testing of the patient revealed that he has fibrinogen A alpha gene (FGA) point mutation with a p.E545V variant. Interventions: Cardiac evaluation showed normal transthoracic echocardiogram. Cardiac magnetic resonance imaging (MRI) showed no involvement by amyloidosis. A peripheral nerve biopsy showed diabetic neuropathy. Thus, the kidney was the only organ involved by the disease. The kidney transplant was managed conservatively with blood pressure and diabetes control in addition to his usual immunosuppression regimen which was not altered. He is being treated with diuretics, angiotensin receptor inhibitors, and sodium glucose transport 2 inhibitors. Outcomes: Kidney transplant function exhibited only slow progression over 18 months since the diagnosis was confirmed. This slow progression is likely because the p.E545V point mutation variant is less aggressive than other gene deletion mutations and because our patient was judged to have been diagnosed early in the course of his disease. Teaching Points: In this case report, we illustrate the findings and testing that confirmed the diagnosis of AFib amyloidosis. We summarize the clinical aspects, outcomes of the disease, and treatment options. We believe this case report is interesting because it is the first reported case of AFib amyloidosis in a kidney transplant recipient who was not known to have the disease prior to kidney transplantation.

ODP181 Diabetes Mellitus and Advanced Liver Fibrosis – is Cirrhosis Reversible and Who Should We Screen?

Abstract Recent evidence shows an association between type 2 diabetes mellitus (T2DM) and liver steatosis, fibrosis, and hepatocellular carcinoma. Studies suggest that improved glycemic control, weight loss, and GLP-1 agonists may halt progression and even improve non-alcoholic fatty liver disease (NAFLD); however, little is known about the extent of improvement these factors have on liver fibrosis. ADA guidelines suggest only patients with T2DM or pre-DM and elevated liver enzymes (or fatty liver on ultrasound) should be evaluated for NAFLD and fibrosis. Three patients ages 65-71 with long-standing T2DM, HLD, obesity, and no history of liver disease or current alcohol use were followed in our diabetic clinic and referred for screening for liver steatosis and fibrosis. The transient elastography method (fibroscan) was used to determine the degree of liver fibrosis. On initial fibroscans, all three patients were found to have F4 scores consistent with liver cirrhosis. The first patient is a 71-year-old male with T2DM (BMI 37.5kg/m 2), treated with semaglutide, empagliflozin, glipizide, and insulin. Over two years, he experienced a 4-lb weight loss and improvement in HbA1c(7.8% to 7.1%). Repeat fibroscan after two years showed improved fibrosis score – F3 (11.6 kPa to 10.2 kPa), consistent with moderate fibrosis. The second patient is a 69-year-old female with T2DM (BMI 37.3kg/m 2) and transient mild LFT abnormalities, found to have cirrhosis on fibroscan – F4 score. She was managed with semaglutide, empagliflozin, metformin, and insulin; weight decreased 9-lbs over two years and HbA1c improved(10.8% to 7.8%). Repeat fibroscan showed improvement in fibrosis score to F2 (15.1 kPa to 8.9 kPa), and her LFT abnormalities resolved. The third patient is a 65-year-old male with T2DM (BMI 35kg/m 2). His initial fibroscan showed cirrhotic liver – F4 score. He was maintained on empagliflozin and dulaglutide- then switched to semaglutide. He experienced a 10-lb weight loss during this time and had a stable HbA1c(6.6%). Repeat fibroscan after one year showed improvement to F0-F1(11.3 kPa to 6.1 kPa) consistent with little to no liver scarring. These cases highlight two important factors: 1) ADA liver screening guidelines should be expanded to include obesity and dyslipidemia; and 2) advanced liver fibrosis in patients with diabetes is, to some degree, reversible. Not all of the patients initially met standard ADA screening criteria, mostly without elevated liver enzymes and no prior abnormal liver imaging. Yet, all were diabetic and obese with dyslipidemia, which are independent risk factors for NAFLD. Additionally, patients with improved glycemic control on GLP-1 treatment as well as some weight loss have promising results on repeat fibroscan. These findings may improve screening and management of diabetes-related liver disease. Further studies are needed to investigate to what extent GLP-1 agonists alone or in combination with glycemic control and weight loss contribute to these improvements. Presentation: No date and time listed

S2740 Incidentally Discovered Cryptogenic Cirrhosis in a Patient With Untreated Celiac Disease

Introduction: Celiac disease is an autoimmune enteropathy that affects around 1% of the general population and primarily manifests its effects on the small bowel. However, the systemic nature of this condition, especially regarding the liver, has been gaining some recognition in the literature. Mild liver disease is common, but few cases progress to cirrhotic liver disease. In this case report, cryptogenic cirrhosis was incidentally discovered in a patient with a long history of untreated celiac disease with no evidence of any other underlying cause for the cirrhosis. Case Description/Methods: A 78-year-old male with past medical history of longstanding celiac disease, atrial fibrillation, CHF, T2DM, CKD III, and thoracic aortic aneurysm underwent a CT scan for thoracic aortic aneurysm surveillance. Incidentally, on CT scan, a 1.2 cm enhancing focus in left hepatic lobe, cirrhotic liver morphology, and sclerosing mesenteritis were discovered. Initial lab work-up was remarkable for an elevated alkaline phosphatase of 171 and initial tissue transglutaminase (TTG) was >100. Confirmatory ultrasound showed a liver with heterogeneous echotexture, 1.2cm cyst on the left hepatic lobe, and patent main portal vein. Further laboratory workup showed negative anti-smooth muscle antibody, negative antimitochondrial antibody, negative liver kidney microsomal antibody, and alpha-fetoprotein < 2. Patient reported a history of constipation but denied any other gastrointestinal symptoms, including abdominal pain, hematochezia, diarrhea, nausea, or vomiting. Patient had a remote history of alcohol use, with only occasional recreational use at presentation. The patient had never followed a gluten-free diet. (Figure) Discussion: Celiac disease is now thought to be a systemic condition, with up to 30% of patients displaying extraintestinal manifestations. Multiple studies have shown an increased incidence of celiac disease in patients with cirrhosis, and that cessation of gluten can improve not only the small bowel, but also liver function. This suggests that there is utility in monitoring liver function in patients with celiac disease and screening patients with cirrhosis for celiac disease on initial workup. It is also important to inform patients of these connections, as compliance with a gluten-free diet may prevent the progression of the enteropathy and protect its systemic targets.Figure 1.: Sagittal View of Cirrhotic Liver Morphology on Right Upper Quadrant Ultrasound.

Brain Structure Among Middle-aged and Older Adults With Long-standing Type 1 Diabetes in the DCCT/EDIC Study.

Individuals with type 1 diabetes mellitus (T1DM) are living to ages when neuropathological changes are increasingly evident. We hypothesized that middle-aged and older adults with long-standing T1DM will show abnormal brain structure in comparison with control subjects without diabetes. MRI was used to compare brain structure among 416 T1DM participants in the Epidemiology of Diabetes Interventions and Complications (EDIC) study with that of 99 demographically similar control subjects without diabetes at 26 U.S. and Canadian sites. Assessments included total brain (TBV) (primary outcome), gray matter (GMV), white matter (WMV), ventricle, and white matter hyperintensity (WMH) volumes and total white matter mean fractional anisotropy (FA). Biomedical assessments included HbA1c and lipid levels, blood pressure, and cognitive assessments of memory and psychomotor and mental efficiency (PME). Among EDIC participants, HbA1c, severe hypoglycemia history, and vascular complications were measured longitudinally. Mean age of EDIC participants and control subjects was 60 years. T1DM participants showed significantly smaller TBV (least squares mean ± SE 1,206 ± 1.7 vs. 1,229 ± 3.5 cm3, P < 0.0001), GMV, and WMV and greater ventricle and WMH volumes but no differences in total white matter mean FA versus control subjects. Structural MRI measures in T1DM were equivalent to those of control subjects who were 4-9 years older. Lower PME scores were associated with altered brain structure on all MRI measures in T1DM participants. Middle-aged and older adults with T1DM showed brain volume loss and increased vascular injury in comparison with control subjects without diabetes, equivalent to 4-9 years of brain aging.

395-P: BeAM Value and Glycemia Assessed by Continuous Glucose Monitoring among Participants with Type 2 Diabetes and Chronic Kidney Disease

Introduction: The difference between bedtime and morning glucose levels (BeAM value) is a clinically relevant measure that can guide clinicians regarding insulin titrations. As chronic kidney disease (CKD) develops, changes in insulin sensitivity and kinetics and limitations to available medications may contribute to over-basalization, insufficient prandial control, and large BeAM. We hypothesized that CKD and less time in range (TIR) derived from continuous glucose monitoring (CGM) are associated with large BeAM in T2DM. Methods: This was a prospective observational cohort study of 1people with T2DM treated with insulin or sulfonylurea, 81 participants with CKD (eGFR &amp;lt;60 mL/min/1.73 m2) , and 24 controls with eGFR ≥60 frequency matched on age, duration of diabetes, HbA1c, and glucose-lowering medications. Each participant wore a CGM for two 6-day periods. BeAM was calculated as the difference between mean bedtime sensor glucose values and mean morning sensor values, with large BeAM defined as ≥30 mg/dL glucose drop from bedtime to morning. Results: Participants had a mean age of 68 years, diabetes duration years and HbA1c 7.7%. CKD and controls had a mean eGFR 38 and 83 mL/min/1.73 m2 respectively. Median (IQR) BeAM was 29 (9-52) mg/dL for participants with CKD and (-4-31) mg/dL for controls (p = 0.11) . Forty participants with CKD (49%) and 7 controls (29%) had a large BeAM. Those with a large BeAM had less TIR (58 v 68%) , higher HbA1c (8.0 vs. 7.5%) , and higher glucose management indicator (GMI, 7.5 vs. 7.2%) compared to those with BeAM &amp;lt;30 mg/dL (each p&amp;lt;0.05, adjusting for age, sex, and race) . Coefficient of variation, diabetes duration, and insulin dose (total or basal) did not correlate with BeAM. Conclusions: Large BeAM was common among participants with long-standing T2DM and CKD and was associated with less TIR and higher GMI. These data suggest that there is opportunity for improvement in daytime and prandial diabetes management among patients with CKD. Disclosure L.Mayeda: None. L.Zelnick: None. S.Trikudanathan: Research Support; Bionic pancreas, Bionic pancreas , Insulet Corporation, Insulet Corporation. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. I.De boer: Advisory Panel; AstraZeneca, Bayer AG, Cyclerion Therapeutics, Inc., George Clinical, Goldfinch Bio, Inc., Other Relationship; American Society of Nephrology, Research Support; Dexcom, Inc. Funding American Diabetes Association (4-15-CKD-20) ; National Institute of Diabetes and Digestive and Kidney Diseases (R01DK088762, R01087726)

Restrictive Pulmonary Disease in Diabetes Mellitus Type II Patients.

BackgroundThe present study aimed to evaluate the proportion of restrictive pulmonary disease in individuals with diabetes mellitus type II patients.MethodologyA cross-sectional study was performed at Liaquat University of Medical & Health Sciences between May 2020 and June 2021. All individuals aged between 40 and 65 years, irrespective of gender were included in the study. While those individuals with known obstructive lung diseases, blood disorders, or malignancy were excluded. Spirometry, total lung capacity (TLC), and carbon monoxide diffusing capacity (DLCO) measurements were conducted to obtain a pattern of restrictive disease in patients. Patients were divided into three main groups; i) prediabetes, ii) newly diagnosed cases of diabetes, iii) longstanding diabetes mellitus type II, and iv) control group. The parameters like the patients’ age, sex, medication, history of smoking, and cardiac diseases, among other demographics were recorded. The data collected was recorded on a predesigned proforma.ResultsThe majority of the newly diagnosed cases, as well as long-standing diseases, were elderly males (p=0.014 and p<0.0001). Dyspnea was significantly correlated with longstanding diabetes mellitus type II as indicated by a higher mean score of 0.65 ± 0.10 (p=0.006). Smoking did not significantly correlate with diabetes mellitus type II. In patients with longstanding diabetes, 27 (14.4%) had a modified Medical Research Council (mMRC) score of greater than two while none of the controls had severe breathlessness. Reduced forced vital capacity (FVC) was detected in 16.0% of patients with longstanding diabetes and 12.8% in patients with newly diagnosed disease. Similar results were obtained for total lung capacity (TLC) and diffusing capacity (DLCO) (p=0.003 and p=0.02).ConclusionDiabetes mellitus type II is significantly associated with restrictive lung disease in patients as indicated by a high number of patients with longstanding diabetes in our study who were found to have restrictive lung disease and severe dyspnea. Screening for lung dysfunction could aid in optimum management of this debilitating disease.

Muscle strength, an independent determinant of glycemic control in older adults with long-standing type 2 diabetes: a prospective cohort study

BackgroundAlthough the proportion of older patients with type 2 diabetes mellitus (T2DM) has increased, few studies have reported the factors affecting glucose levels in older patients with long-standing T2DM. This study assessed the determinants of glycemic control in older adults with T2DM of a duration of ≥10 years, including muscle mass, muscle quality, and β-cell function.MethodsThis was a prospective study of older patients aged ≥60 years with a T2DM duration of ≥10 years. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index, handgrip strength (HGS), and body composition through bioelectrical impedance analysis were assessed. The primary outcome was a composite of: (i) increment of glycated hemoglobin (HbA1c) from the baseline ≥0.6% and (ii) HbA1c ≥ 9% at any time point during the follow-up period. To find the predicting determinants of the outcome, we performed the Cox proportional hazard analysis.ResultsAmong 100 patients (mean age, 64.0 ± 8.6 years; median duration of diabetes, 20 [interquartile range (IQR), 17–23] years; median HbA1c at baseline, 7.1 [IQR, 6.7–7.4] %), the primary outcome was observed in 40 (40.0%) patients during 4.0 (IQR 2.3–5.0) years of follow-up. A Cox proportional hazards model adjusted for age, sex, baseline HbA1c, obesity, duration of DM and anti-diabetic medication at baseline showed that low HGS and insulin resistance at the baseline were independent determinants of the primary outcome (hazard ratio [HR] = 2.23 [95% confidence interval (CI), 1.06–4.72] and 2.39 [95% CI, 1.18–4.83], respectively). Sex stratification confirmed that HGS and muscle mass were independent determinants of the primary outcome only in women (HR per quartile, 0.58 [95% CI, 0.37–0.93] and 0.46 [95% CI, 0.25–0.85], respectively). `.ConclusionsLow HGS and insulin resistance were independent risk factors for aggravated glycemic control among older patients with long standing T2DM.

The Non-Significant Benefit of BCG Vaccination for the Treatment of Iranian Patients with Type 1 Diabetes up to 48 Weeks: A Controversial Result.

Background:There has been considerable interest in target immunotherapy in patients with diabetes. This study was designed to identify the effect of BCG vaccination in the treatment of Iranian patients with longstanding diabetes mellitus type 1. Methods: After approval of the cross-sectional study protocol by the ethics committee under number IRCT2017042919940N2, a total of 19 Iranian volunteers with diabetes mellitus type 1 completed this 48-month study. These patients received three 0.1 ml intradermal injections of BCG vaccination in weeks 0, 4 and 24. The serum level of glucose, HgbA1C and c-peptide was measured before and serially after the interventions. Insulin requirements were recorded for each patient in different weeks as the mean and standard deviation. Results: This study showed a decrease in the blood sugar level of 171.15±75.54 mg/dL in baseline to 133.77±76.97 mg/dL in 12 weeks after the first dose of BCG vaccination in these patients. There was no significant change in the mean± SD of serum blood sugar, HgbA1C and c-peptide after BCG vaccination in the baseline and week 48. Conclusion: Our results showed that small doses of BCG vaccination were not effective in long-term treatment of Iranian patients with diabetes mellitus type 1 up to 48 weeks.

Serum zonulin levels in type 2 diabetes patients with diabetic kidney disease.

Recent data have shown that diabetic kidney disease (DKD) is associated with abnormal gut microbiota composition. Zonulin is a physiological tight junction modulator and an intestinal permeability marker. In this study we aimed to investigate serum levels of zonulin and interleukin 6 (IL-6) in patients with type 2 diabetes mellitus (T2DM) and different levels of albuminuria. Ninety patients with T2DM and 30 healthy controls (HC) aged between 18 and 65 years were enrolled in the study. T2DM patients were divided into three groups as patients with normoalbuminuria (n = 30), microalbuminuria (n = 30), and macroalbuminuria (n = 30). Serum zonulin and IL-6 levels were measured by ELISA method. There was no significant difference between groups in terms of age, gender, serum ALT, LDL-C, HDL-C, and zonulin levels (p > 0.05). Significant differences between groups were present for the duration of diabetes (p < 0.001), body mass index (p < 0.001), fasting blood glucose (p < 0.001), creatinine (p < 0.001), uric acid (p = 0.037), triglyceride (p = 0.003), total cholesterol (p < 0.001), glycated haemoglobin (p < 0.001), and IL-6 (p < 0.001) levels. IL-6 levels were significantly increased in the microalbuminuria and macroalbuminuria groups compared to the HC group, but no significant difference was determined between the HC and normoalbuminuria group. In patients with diabetic kidney disease, a significant positive correlation was found between zonulin with IL-6 and proteinuria (rho = 0.296, p = 0.008; rho = 0.190, p < 0.047, respectively). The serum IL-6 level was positively correlated with microalbuminuria and proteinuria (rho = 0.451, p < 0.001; rho = 0.425, p < 0.001, respectively). We suggest that the serum zonulin level is not a promising biomarker to assess the severity of DKD in patients with long-standing T2DM.