Uncontrolled Type 2 Diabetes Mellitus Research Articles

Insulin-like growth factor 1 and sex hormones for assessment of anthropometric and pubertal growth of Egyptian children and adolescents with type 1 diabetes mellitus (single center study)

BackgroundThis study aimed to assess the anthropometric measures and pubertal growth of children and adolescents with Type 1 diabetes mellitus (T1DM) and to detect risk determinants affecting these measures and their link to glycemic control.Patients and methodsTwo hundred children and adolescents were assessed using anthropometric measurements. Those with short stature were further evaluated using insulin-like growth factor 1 (IGF-1), bone age, and thyroid profile, while those with delayed puberty were evaluated using sex hormones and pituitary gonadotropins assay.ResultsWe found that 12.5% of our patients were short (height SDS < -2) and IGF-1 was less than -2 SD in 72% of them. Patients with short stature had earlier age of onset of diabetes, longer duration of diabetes, higher HbA1C and urinary albumin/creatinine ratio compared to those with normal stature (p < 0.05). Additionally, patients with delayed puberty had higher HbA1c and dyslipidemia compared to those with normal puberty (p < 0.05). The regression analysis revealed that factors associated with short stature were; age at diagnosis, HbA1C > 8.2, and albumin/creatinine ratio > 8 (p < 0.05).ConclusionChildren with uncontrolled T1DM are at risk of short stature and delayed puberty. Diabetes duration and control seem to be independent risk factors for short stature.

Abstract PO1-20-04: STX-478-101: A phase 1/2, first-in-human study of STX-478 monotherapy or in combination with fulvestrant in patients with breast cancer or other advanced solid tumors (trial in progress)

Abstract Background: The phosphoinositide 3-kinase-alpha (PI3Kα)/AKT/mTOR pathway is one of the major pathways in oncogenesis. PI3Kα alterations are especially prevalent in breast, gynecological, and head and neck squamous cell carcinomas. PI3Kα oncogenic mutations are highly enriched for kinase (H1047X) and helical (E542K, E545K) domain hotspots. The therapeutic potential of isoform-selective PI3Kα inhibition in PI3Kα-mutant cancers was established with alpelisib, which shows equipotent activity against both wild-type (WT) and mutant PI3Kα. However, alpelisib use is limited by toxicities induced by WT PI3Kα inhibition, e.g. hyperglycemia and mucositis. This suggests that mutant-selective PI3Kα inhibitors have the potential to improve efficacy while sparing WT-related toxicity. STX-478 is an investigational allosteric, mutant-selective PI3Kα inhibitor. Preclinical testing in human breast cancer xenografts bearing helical- or kinase-domain mutant PI3Kα demonstrated that STX-478 monotherapy and combinations with fulvestrant and/or CDK4/6 inhibitors provided robust efficacy without the metabolic dysfunction observed with alpelisib. Trial Design: This first-in-human, multicenter, phase 1/2 study (NCT05768139) evaluates the optimal dosing, safety, and preliminary efficacy of STX-478 as monotherapy in patients with locally-advanced or metastatic HR+/HER2− breast cancer or other solid tumor types with PI3Kα H1047X mutations, other kinase domain mutations, or helical domain mutations (Part 1), and STX-478 in combination with fulvestrant in patients with locally-advanced or metastatic HR+/HER2− breast cancer with PI3Kα H1047X or other kinase domain mutations (Part 2). Part 1 comprises 2 subparts (Table 1) to define the optimally biologically active dose (OBD) and maximum tolerated dose (MTD) in Part 1.1, and recommended phase 2 dose (RP2D) of STX-478 monotherapy in Part 1.2. At the conclusion of each dose-level in Part 1.1 (3 + 3 design), a backfill cohort will be initiated in patients with HR+/HER2− breast cancer with PI3Kα H1047X mutations or other kinase domain mutations, who will receive STX-478 at the determined safe dose. Part 2 comprises two subparts (Table 2) to define RP2D and assess the initial efficacy of STX-478 in combination with fulvestrant in patients with HR+/HER2− breast cancer expressing PI3Kα H1047X or other kinase domain mutations. Key Eligibility Criteria: Adults with a PI3Kα-mutant advanced or refractory solid tumor malignancy that is metastatic or locally advanced and unresectable, ECOG performance status score of 0–1, and no prior PI3K/AKT/mTOR inhibitor(s) use (except with prior intolerance) are eligible. Individuals with diabetes mellitus type 1 or uncontrolled diabetes mellitus type 2 are excluded. Cohort-specific eligibility criteria are provided in Tables 1 and 2. Endpoints: Efficacy, safety, pharmacokinetics, pharmacodynamics, patient-reported quality of life, and biomarkers (e.g., glucose metabolism, circulating tumor DNA) will be assessed. Trial Status: Recruitment opened April 2023 in the US and is ongoing, with potential for ex-US site expansion. Contact clinicaltrials@scorpiontx.com for additional information. Table 1. Part 1 Dose Escalation, RP2D Selection, and RP2D Expansion (STX-478 Monotherapy) Table 2. Part 2 RP2D Selection and Expansion (STX-478 + Fulvestrant Combination Therapy) Citation Format: Alberto Montero, Douglas Orr, Pamela Munster, Patricia LoRusso, Komal Jhaveri, Timothy Pluard, Ira Winer, Michael Streit, Monica Patterson, Simon Roberts, Stefani Corsi-Travali, Courtney Ewert, Dejan Juric. STX-478-101: A phase 1/2, first-in-human study of STX-478 monotherapy or in combination with fulvestrant in patients with breast cancer or other advanced solid tumors (trial in progress) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-20-04.

The Association Between Vitamin D Deficiency and the Level of Fasting C Peptide Among Patients With Uncontrolled Type 2 Diabetes Mellitus: A Retrospective Cohort Study.

This study investigates the relationship between vitamin D deficiency and uncontrolled type 2 diabetes mellitus (T2DM) indicated by elevated glycosylated hemoglobin (HbA1c) levels, alongside assessing the association between fasting C peptide levels and uncontrolled T2DM, considering their roles in β-cell function and insulin secretion. The study employs a cohort design, selecting individuals diagnosed with T2DM aged 18 years or older with baseline data on vitamin D, fasting C peptide, and HbA1c. Data were collected through electronic medical records and follow-up assessments at regular intervals. Binary logistic regression analyses were conducted to explore associations between exposure variables and uncontrolled T2DM. Significant associations were observed between vitamin D and C peptide levels with uncontrolled diabetes, with coefficients of -0.097 and -0.222, respectively. Higher vitamin D and C peptide levels are linked to a decreased likelihood of uncontrolled diabetes. In conclusion, there is a potential connection between vitamin D levels, C peptide levels, and uncontrolled diabetes mellitus (HbA1C > 7%), while higher levels of both vitamin D and C peptide appeared to correlate with a decreased likelihood of uncontrolled diabetes.

The interplay between diabetes and non-alcoholic fatty liver disease: a cross-sectional study from Pakistan.

Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic deposition of fat in the liver, in the absence of other secondary causes of fat buildup. The relationship between NAFLD, including alanine aminotransferase (ALT), and glycated haemoglobin (HbA1c), is important for predicting the severity of disease and prognosis. This study aims to investigate the association of HbA1c in type 2 diabetes mellitus (T2DM) patients with NAFLD via measuring the ALT levels. This retrospective cross-sectional study enroled 130 patients with T2DM and NAFLD. The association between levels of HbA1c and ALT in patients of NAFLD with controlled and uncontrolled T2DM, respectively, was investigated. Stratification was done based on gender and diabetic control, using HbA1c levels as a marker of glycemic control. Serum ALT levels were also compared in both groups. The mean age of the participants was 50.2±5.7 years. The total participants were 130, of which 77 (59.3%) were females and 53 (40.7%) were males. The numbers of patients having uncontrolled T2DM (HbA1c>7%), and controlled T2DM (HbA1c <7%) were 78 (60%) and 52 (40%), respectively. Moreover, 46 (35.3%) females and 32 (24.7%) males had uncontrolled T2DM, and 31 (23.8%) females and 21 (16.2%) males had controlled T2DM. The mean ALT level for uncontrolled and controlled T2DM in female patients was found to be 24.6±3.4 and 13.5±2.4, respectively, (P <0.05). For male patients, it was found to be 54.0±4.9 and 29.1±5.4, respectively (P=0.008). There is a positive association between elevated HbA1c and ALT levels in T2DM patients with NAFLD.

Development and validation of a risk assessment tool for uncontrolled type 2 diabetes among patients in South Karnataka, India

IntroductionDiabetes is a chronic medical condition with severe complications mainly caused due to unhealthy lifestyles in genetically susceptible individuals. This study attempts to develop a non-invasive risk assessment tool to...

Quality of life assessment and therapeutic adherence in Mexican patients with type 2 diabetes

Abstract Background Patients with diabetes mellitus experience physical health needs, but also psychological health needs, as some studies have suggested that addressing the psychological variables associated with diabetes mellitus may improve the biochemical parameters of the disease. Objectives To assess the quality of life (QoL) and therapeutic adherence (TA) in Mexican patients with controlled and uncontrolled type 2 diabetes mellitus (T2DM), as well as related QoL sociodemographic and clinical variables. Methods 201 people with T2DM answered a battery of psychological tests to assess TA (Therapeutic Adherence Survey or TAS-15), QoL (WHOQOL-BREF-16) and disease-related quality of life (DRQoL-27), aside from an expressly designed questionnaire that gathered sociodemographic data and took information from medical records into consideration. The average age of the participants was 65.12 ± 11.617 years and 57.2% were female, who have suffered from diabetes for 13.4 years on average ± 8.088 and an average 158.84 mg/dL ± 61.913 fasting plasma glucose. Results The correlation analyses revealed that a higher perception of QoL, the lower the perception that having diabetes affected QoL (p&lt;0.01); the higher the TA, the lower the QoL (p&lt;0.01); and the higher the TA, the lower the perception that having diabetes affected QoL (p&lt;0.01). The participants with an uncontrolled T2DM exhibited a better QoL than those that manage their glucose levels (p = 0.015). The participants’ level of education had a positive effect on QoL (β = 0.163, IC 95%: 0.429─3.415, p = 0.012), whereas the DRQoL had a negative effect (β = -0.546, IC 95%: -0.127─-0.080, p = 0.001). Conclusions If the TA of patients with T2DM increases, the overall QoL as well as the DRQoL will improve. Hence, these variables must be considered as therapeutic targets in clinical practice.

Evaluation of Efficacy and Safety of Empagliflozin in Bangladeshi Patients with Type 2 Diabetes Mellitus (EFFISAEM Study)

Abstract Background: Empagliflozin is a relatively newer glucose-lowering drug (GLD) with many extra-glycemic benefits. To date, no study has evaluated the efficacy and safety of empagliflozin in Bangladeshi patients with type 2 diabetes mellitus (T2DM). Objectives: To assess the efficacy and safety of empagliflozin as an add-on to ongoing GLDs in Bangladeshi adults with uncontrolled T2DM. Materials and Methods: This real-world, multicenter, open-label, prospective study was carried out at 21 sites throughout Bangladesh from 1 February 2022 to 31 July 2022. Patients with T2DM who met the criteria had Empagliflozin added to their existing GLD treatment, with necessary modifications to their ongoing medication regimen. The efficacy and safety data were collected 12 weeks after empagliflozin initiation. Results: Out of 1449 subjects initiating empagliflozin, 1340 subjects [age 50.3 ± 9.0 years, male 52.5%, overweight/obese 94.4%, insulin-treated 25.7%, baseline hemoglobin A1c (Hba1c) 9.9 ± 1.4%] completed the study. At 12 weeks, the reduction in HbA1c was 1.6% (95% CI 1.5-1.6, P &lt; 0.001); 12.5% of the study subjects achieved HbA1c &lt; 7%. There were also significant (P &lt; 0.001 in all instances) reductions in fasting plasma glucose (3.0 mmol/L), plasma glucose 2 hours after breakfast (4.8 mmoL/L), body weight (1.9 kg), body mass index (0.8 kg/m2), systolic blood pressure (BP) (10 mmHg), diastolic BP (7 mmHg), insulin dose (3 U), serum creatinine (0.06 mg/dL), total cholesterol (18 mg/dL), low-density lipoprotein cholesterol (13 mg/dL), high-density lipoprotein cholesterol (1 mg/dL), and triglyceride (42 mg/dL) and an increase in estimated glomerular filtration rate (4.2 mL/min/1.73 m2) from the baseline values. 6.62% experienced adverse events (lightheadedness 2.21%, genital tract infection 0.97%, urinary tract infection 1.24%, generalized weakness 0.48%, and nocturia 0.48%). 1.1% of subjects experienced hypoglycemia, and other 0.12% reported severe hypoglycemic events. Conclusion: Empagliflozin is effective, safe, and tolerable for treating Bangladeshi patients with uncontrolled T2DM as add-on therapy in routine clinical practice with favorable effects on body weight, BP, lipid profile, and renal function.

Efficacy and Safety of IDegAsp in a Real-World Korean Population with Type 2 Diabetes Mellitus.

This study investigated the real-world efficacy and safety of insulin degludec/insulin aspart (IDegAsp) in Korean adults with type 2 diabetes mellitus (T2DM), whose insulin treatment was switched to IDegAsp. This was a multicenter, retrospective, observational study comprising two 26-week treatment periods, before and after switching to IDegAsp, respectively. Korean adults with uncontrolled T2DM treated with basal or premix insulin (±oral antidiabetic drugs) were enrolled. The primary objective was to compare the degree of glycosylated hemoglobin (HbA1c) change in each 26-week observation period. The analyses included changes in HbA1c, fasting plasma glucose (FPG), body weight, proportion of participants achieving HbA1c <7.0%, hypoglycemic events, and total daily insulin dose (ClinicalTrials.gov, number NCT04656106). In total, 196 adults (mean age, 65.95 years; mean T2DM duration, 18.99 years) were analyzed. The change in both HbA1c and FPG were significantly different between the pre-switching and the post-switching period (0.28% vs. -0.51%, P<0.001; 5.21 mg/dL vs. -23.10 mg/dL, P=0.005), respectively. After switching, the rate of achieving HbA1c <7.0% was significantly improved (5.10% at baseline vs. 11.22% with IDegAsp, P=0.012). No significant differences (before vs. after switching) were observed in body weight change, and total daily insulin dose. The rates of overall and severe hypoglycemia were similar in the two periods. In real-world clinical practice in Korea, the change of insulin regimen to IDegAsp was associated with an improvement in glycemic control without increase of hypoglycemia, supporting the use of IDegAsp for patients with T2DM uncontrolled with basal or premix insulin.

Skin autofluorescence of advanced glycation end-products relates to new cardiovascular events in type 2 diabetes: A longitudinal observational study

BackgroundCardiovascular disease is frequent in type 2 diabetes mellitus (T2DM). We investigated the relationship between skin autofluorescence (SAF) of advanced glycation end-products and later cardiovascular events (CVEs) in patients with T2DM. Research design and methodsWe conducted a retrospective analysis of 504 patients hospitalized for uncontrolled and/or complicated T2DM between 2009 and 2017. SAF was measured using an AGE-Reader. Participants were followed up from admission to December 2020, for the onset of a CVE (myocardial infarction, stroke, revascularization procedures or cardiovascular death). The relationship between SAF and CVE was analyzed by multivariable Cox regression. Log-rank curves were used to compare CVE-free survival in patients whose SAF at admission was above versus below the whole-population median. The analysis was repeated in subjects without/with macroangiopathy (defined as myocardial infarction, stroke, peripheral revascularization) at baseline. FindingsDuring 54 months of follow-up, 69 (13.7%) patients had a CVE. Baseline SAF was significantly higher in patients with T2DM who later experienced a CVE (2.89 ± 0.70 arbitrary units versus 2.64 ± 0.62 in others, P = 0.002). This relationship was significant after adjusting for age, sex, conventional risk factors (diabetes duration, HbA1c, arterial hypertension, dyslipidemia, smoking, body mass index), vascular complications, C-reactive protein, and treatments for diabetes. The CVE-free survival curves differed between subjects whose SAF was above the whole-population median (log-rank: P = 0.002) and those whose SAF was above the macroangiopathy-free sub-population median (log-rank: P = 0.016). ConclusionSAF of advanced glycation end-products was related to a higher incidence of later CVE in patients with T2DM.

A Hybrid Model of In-Person and Telemedicine Diabetes Education and Care for Management of Patients with Uncontrolled Type 2 Diabetes Mellitus: Findings and Implications from a Multicenter Prospective Study.

Patients with uncontrolled type 2 diabetes mellitus (T2DM) require close follow-up, support, and education to achieve glycemic control, especially during the initiation or intensification of insulin therapy and self-care management. This study aimed to describe and evaluate the impact of implementing a hybrid model of in-person and telemedicine care and education on glycemic control for patients with uncontrolled T2DM (hemoglobin A1c [HbA1c] ≥9%) during the coronavirus disease pandemic. This prospective multicenter-cohort pre-/post-intervention study was conducted on patients with uncontrolled T2DM. This study included three chronic illness centers affiliated with the Family and Community Medicine Department at Prince Sultan Military Medical City in Riyadh, Saudi Arabia. A hybrid model of in-person (onsite) and telemedicine care and education was developed. This involved implementing initial in-person care at the physicians' clinic and initial in-person education at the diabetes education clinic, followed by telemedicine services of tele-follow-ups, support, and education for an average 4-month follow-up period. Of the enrolled 181 patients, more than half of the participants were women (n = 103, 56.9%). The mean age of participants (standard deviation) was 58.64 ± 11.23 years and the mean duration of diabetes mellitus was 13.80 ± 8.55 years. The majority of the patients (n = 144; 79.6%) were on insulin therapy. Overall, in all three centers, the hybrid model had significantly reduced HbA1c from 10.47 ± 1.23% to 7.87 ± 1.59% (mean difference of reduction 2.59% [95% confidence interval (CI) = 2.34-2.85%], p < 0.001). At the level of each center, HbA1c was reduced significantly with mean differences of 3.17% (95% CI = 2.81-3.53%), 2.49% (95% CI = 1.92-3.06%), and 2.16% (95% CI = 1.76-2.57%) at centers A, B, and C, respectively (all p < 0.001). The findings showed that the hybrid model of in-person and telemedicine care and education effectively managed uncontrolled T2DM. Consequently, the role of telemedicine in diabetes management could be further expanded as part of routine diabetes care in primary settings to achieve better glycemic control and minimize nonessential in-person visits when appropriate.

Association of Microalbuminuria with Glycemic Status Among Patients with Diabetes Mellitus

Objectives: To evaluate the association between micro-albuminuria and glycemic status among type 2 diabetic patients in Hyderabad, Sindh.&#x0D; Methods: Cross Sectional study was conducted at the Medical unit of Isra University, Hyderabad from January 2019 to June 2020. All the patients aged between 30 and 50 years, of either genders, with both good controlled as well as uncontrolled diabetes mellitus type II admitted in the medicine ward were included. All the participants were divided into two groups according to their glycemic level. The Group I comprised of patients with poor glycemic control that is HbA1c &gt;7% while Group II comprises of patients with good glycemic control that is HbA1c&lt;7%.&#x0D; Results: Majority (56.4%) of participants in the study were Male while most (31.0%) them belongs to age group 41-45 years. The mean age of all patients was 42.3 ± 4.1 years. The mean HbA1c level in group 1(poorly controlled) and 2 (good control) participants was 8.04± 0.97% and 5.87 ± 0.44%. There was a statistically significant association (p&lt;0.05) between poorly controlled glycemic status and micro-albuminuria.&#x0D; Conclusion: Micro-albuminuria is significantly associated with the poor glycemic status among type 2 diabetic patients.

A comparative study of efficacy and safety of glimepiride versus gliclazide as an add on to metformin in Type 2 diabetes mellitus at a tertiary care hospital

Background: Type 2 diabetes mellitus (T2DM) is a chronic disorder with progressive pancreatic β-cell dysfunction and insulin resistance. Hyperglycemia associated with uncontrolled T2DM leads to various diabetes-related complications. Although metformin is the most preferred first-line drug, 5–10% of patients per year subsequently fail to achieve target HbA1c levels, subsequently requiring combination therapy. While efficacy and cost favor the use of sulfonylureas, hypoglycemic episodes limit its use. Newer generation sulfonylureas such as glimepiride and gliclazide are presumed to have lower incidence of hypoglycemia. Aims and Objectives: The aim of the study was to assess the efficacy and safety of glimepiride versus gliclazide as an add-on to metformin in T2DM. Materials and Methods: A total of 60 patients with T2DM (HbA1c 7.0–10.0%, on metformin monotherapy) were recruited and randomized into two groups of 30 cases each. Group A received glimepiride 2 mg as add-on to metformin 1500 mg and Group B received gliclazide 80 mg as add-on to metformin 1500 mg. HbA1c, lipid profile, body mass index, and total blood count were assessed at baseline and at the end 12 weeks of treatment. Fasting blood sugar (FBS) and post prandial blood sugar (PPBS) were assessed at the end of 4, 8, and 12 weeks and adverse events were assessed throughout the study period. Results: There was a significant decrease in HbA1c, FBS, and PPBS scores from baseline to the end of 12 weeks in both groups (P &lt; 0.001), but the difference was not statistically significant between the two groups (P &gt; 0.05). A significant decrease in lipid levels was observed in both groups except for high-density lipoprotein, low-density lipoprotein in the metformin + gliclazide group. The treatment was well tolerated in both groups, with the most common adverse events being nausea, diarrhea, and epigastric pain. Conclusion: Glimepiride and gliclazide are both equally effective as an add-on to metformin in improving glycaemic indices and are well tolerated in the management of uncontrolled T2DM.

Population Study Insights Linked to Genetic Variants (rs16890979 and rs206833) and Type 2 Diabetes Control in Northern Jordan

Abstract Background: The relationships between uric acid levels, specific single nucleotide polymorphisms (SNPs) in genes linked to uric acid metabolism [xanthine dehydrogenase (XDH) and Solute carrier family 2 member 9 (SLC2A9) genes], and control of HbA1c levels in type 2 diabetes mellitus (T2DM) within the Jordanian population were determined. Methods: A total of 184 T2DM patients who received care in the Endocrine Clinic at KAUH in Northern Jordan were enrolled in this study. These patients were classified into controlled and uncontrolled T2DM groups based on the HbA1c test results. Genotyping of two SNPs from the SLC2A9 gene and one SNP related to the XDH gene was performed using the tetra ARMS PCR method. Uric acid concentrations were measured using enzymatic colorimetric reagents. Results: The study revealed no significant correlation between uric acid levels and T2DM control. However, statistically significant correlations (P&lt;0.05) were detected between the AA genotype at the rs206833 variant related to the XDH gene and reduced control over T2DM, as well as the CT genotype at the rs16890979 variant in the SLC2A9 gene. Notably, the rs206833 variant had an association between allele frequency level with T2DM regulation. Conclusion: Genetic variants (rs16890979 and rs206833) may influence T2DM control and could be associated with an elevated risk of impaired glucose homeostasis in patients with diabetes.

Evaluating the Clinical Effectiveness and Safety of Semaglutide in Individuals with Uncontrolled Type2 Diabetes. Real-World Evidence from Saudi Arabia: The Observational, Multicenter, 15-Month EVOLUTION Study.

This study aimed to assess the safety and effectiveness of semaglutide, administered either by weekly subcutaneous (SC) injection or orally, in real-life practice in Saudi Arabia in individuals with type2 diabetes mellitus (T2DM). A retrospective chart review study was conducted at 18 Saudi Arabia centers. An accredited centralized institutional review board approved the study. Medical records were included for individuals of any age ≥ 18years with uncontrolled T2DM. The primary outcome measure was the laboratory glycated hemoglobin (HbA1c) level.Secondary measures included fasting blood glucose (FBG), weight, and hypoglycemia. All variables were checked after 6 and 12months of semaglutide initiation. The analysis of this study included 1223 patients with uncontrolled T2DM (HbA1c > 7%). The mean (SD) baseline HbA1c was 10.02% (1.17). HbA1c was reduced by an average of 3.02% (0.84) and 3.17% (0.84) at 6 and 12months, respectively. Results of a repeated measure analysis of variance (ANOVA) indicated significant differences in HbA1c (pvalue < 0.001). HbA1c levels at 6 and 12months were significantly lower, 7.00% (0.70) and 6.85% (0.69), than at baseline, 10.02% (1.17). About 193 patients (56.4%) of the 295 patients having HbA1c < 9% achieved HbA1c of 5.7% or less. The frequency of hypoglycemia events was 4.60 (1.10) in the 3months before semaglutide was initiated. The frequency of hypoglycemia events in the last 3months was 2.30 (0.80) events and 0.80 (0.50) events at 6-month and 12-month follow-up visits, respectively. The percent reduction in body mass index (BMI) was an average of 13.07% (1.53) and 19.89% (4.07) at 6 and 12months, respectively. Lipid profile and blood pressure were improved at 6 and 12months. Semaglutide, administered either by SC injection or orally, provided substantial glycemic and weight-loss benefits in adults with T2DM.

Trabecular Bone Score (TBS) in Individuals with Type 2 Diabetes Mellitus: An Updated Review

Bone fragility is a complication of type 2 diabetes mellitus (T2DM) that has been identified in recent decades. Trabecular bone score (TBS) appears to be more accurate than bone mineral density (BMD) in diabetic bone disease, particularly in menopausal women with T2DM, to independently capture the fracture risk. Our purpose was to provide the most recent overview on TBS-associated clinical data in T2DM. The core of this narrative review is based on original studies (PubMed-indexed journals, full-length, English articles). The sample-based analysis (n = 11, N = 4653) confirmed the use of TBS in T2DM particularly in females (females/males ratio of 1.9), with ages varying between 35 and 91 (mean 65.34) years. With concern to the study design, apart from the transversal studies, two others were prospective, while another two were case-control. These early-post-pandemic data included studies of various sample sizes, such as: males and females (N of 245, 361, 511, and 2294), only women (N of 80, 96, 104, 243, 493, and 887), and only men (N = 169). Overall, this 21-month study on published data confirmed the prior profile of BMD-TBS in T2DM, while the issue of whether checking the fracture risk is mandatory in adults with uncontrolled T2DM remains to be proven or whether, on the other hand, a reduced TBS might function as a surrogate marker of complicated/uncontrolled T2DM. The interventional approach with bisphosphonates for treating T2DM-associated osteoporosis remains a standard one (n = 2). One control study on 4 mg zoledronic acid showed after 1 year a statistically significant increase of lumbar BMD in both diabetic and non-diabetic groups (+3.6%, p = 0.01 and +6.2%, p = 0.01, respectively). Further studies will pinpoint additive benefits on glucose status of anti-osteoporotic drugs or will confirm if certain glucose-lowering regimes are supplementarily beneficial for fracture risk reduction. The novelty of this literature research: these insights showed once again that the patients with T2DM often have a lower TBS than those without diabetes or with normal glucose levels. Therefore, the decline in TBS may reflect an early stage of bone health impairment in T2DM. The novelty of the TBS as a handy, non-invasive method that proved to be an index of bone microarchitecture confirms its practicality as an easily applicable tool for assessing bone fragility in T2DM.

Alterations in the gene expression of SARS-COV-2 entry receptors and enzymes in lungs and hearts of controlled and uncontrolled diabetic mice.

The entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell is carried out by specific receptors and enzymes, including human angiotensin-converting enzyme 2 receptor (ACE2), transmembrane serine protease 2 (TMPRSS2), and cathepsin-L (CTSL). COVID-19 patients with comorbidities, such as diabetes mellitus (DM), are more prone to severe symptoms and have a higher risk of mortality. The present study aimed to investigate the impact of controlled and uncontrolled type 1 DM (T1DM) on the gene expression of mouse Ace2, Tmprss2, and Ctsl and correlate it with the pathological alterations in the lungs and the heart of DM mice. Balb/c mice were administered a single dose of 240 mg/kg streptozocin to induce T1DM. The blood glucose level was measured to confirm the induction of DM. Normalization of blood glucose levels in T1DM mice was achieved using 0.1mL/kg Mixtard® insulin therapy. The mice's lungs and hearts were harvested, and the mRNA was extracted and converted to cDNA. The gene expression of Ace2, Tmprss2, Ctsl, Cyp4a11, and Adrb1 genes, which play a role in the homeostasis of lungs and hearts, were measured using quantitative real-time polymerase chain reaction (RT-PCR). The pathological alterations in the hearts and lungs induced by T1DM were evaluated using the relative heart and lung weights, in addition to the pathohistological examination. After inducing T1DM for 14 days, we observed a significant reduction in the total weight of uncontrolled DM (UDM) mice (P<0.05). Pathohistological examination of UDM lung tissues revealed thickening of the alveolar walls with narrowing of the surface of the alveolar sacs. Additionally, we found that UDM mice exhibited downregulation of Ace2 gene expression (P< 0.05) in their lungs, while both UDM and control DM (CDM) mice showed upregulation of Ctsl gene expression in their hearts (P<0.05). Notably, Cyp4a12 gene expression was significantly downregulated (P<0.05) in UDM mice but returned to normal levels in CDM mice. We conclude from this study that T1DM downregulates Ace2 receptor and Cyp4a12 gene expression, which is correlated with the thickening of alveolar walls and narrowing of the surface of alveolar sacs in the lungs. Insulin administration for controlling T1DM ameliorated these pathological alterations. These results can help increase our understanding of the impact of controlled and uncontrolled T1DM on the lungs and may explain, at least in part, why DM patients with COVID-19 experience exacerbation of symptoms.

The association between serum ferritin and bilirubin with glycemic control among patients with type 2 diabetes mellitus.

Previous evidence has shown an association between serum ferritin and bilirubin levels in the development of type 2 diabetes mellitus (T2DM) and glycemic control. However, the evidence is scarce in Saudi Arabia. In this study, we aimed to evaluate the association between serum ferritin and bilirubin levels with glycemic control in patients with T2DM. This was a cross-sectional study that involved 153 patients with T2DM recruited from outpatient diabetes clinics. Participants were categorized into two groups: well-controlled and uncontrolled T2DM, based on their glycemic status. We focused on comparing the iron profile and bilirubin levels between these two groups and examining the influence of antidiabetic medications on these parameters. A total of 153 patients with T2DM were included (58.2% women and 41.8% men). In both univariate and multivariate analyses, ferritin levels did not have a statistically significant association with glycemic control. However, patients with well-controlled T2DM had a significantly higher median level of total bilirubin and direct bilirubin than those with uncontrolled T2DM. Only direct bilirubin showed a statistically significant association with FBG less than 130 mg/dl and HbA1c level less than 7.0%. Ferritin level was not associated with glycemic control in patients with T2DM. On the other hand, direct bilirubin level was an independent predictor of better glycemic control. Monitoring direct bilirubin levels could aid in predicting glycemic control in T2DM and could be a potential target for developing antidiabetic medications.

SAT148 A Rare Case Of Proinsulinoma In A Patient With Type 2 Diabetes Mellitus

Abstract Disclosure: E. Tirthani: None. F. Erenler: None. Background: A proinsulinoma is a very rare neuroendocrine tumor of the pancreas, which predominantly secretes proinsulin, the precursor hormone of insulin. Even though not as potent as insulin, proinsulin in higher amounts can bind to insulin receptors and result in hypoglycemia. Most patients present with initial hypoglycemia symptoms at the time of diagnosis of the tumor. The diagnosis becomes challenging in patients with underlying type 2 diabetes mellitus (T2DM) who may initially have a spontaneous remission of diabetes, followed by hypoglycemia episodes later in the disease course. Clinical Case: A 66-year-old man presented to our clinic in October 2020 with frequent episodes of dizziness and diaphoresis, which were relieved by eating food. The patient's symptoms began in 2018, occurred during the daytime, and were exacerbated by exercise. He had a past medical history of T2DM diagnosed in 2009 (HbA1c=10%) and treated with glipizide and metformin; however, over the years, his HbA1c improved, and glipizide was discontinued. By 2018 his HbA1c was down to 5.9%, and metformin was also stopped. The patient denied any change in his weight, diet, or exercise frequency during this time course. A fingerstick blood glucose (BG) checked during one of these episodes was 51 mg/dL. An abdominal CT scan in August 2020 revealed a 12x13 mm enhancing mass within the neck of the pancreas concerning for a neuroendocrine tumor. The patient was further evaluated with a 14-day continuous glucose monitor (CGM), which showed that the patient's BG was &amp;lt;70 mg/dL 31% of the time and &amp;lt;55 mg/dL 6% of the time. Additional fasting blood work showed a proinsulin level of 191.3 pmol/L (normal ≤18 pmol/L), insulin 15.5 uIU/mL (2-25 uIU/mL), BG 103mg/dL, C-peptide 2.44 ng/mL (0.80-3.85 ng/mL) and chromogranin A 124 ng/mL (25-140 ng/mL) which suggested the diagnosis of proinsulinoma. A Gallium-DOTATATE scan showed a localized tumor within the pancreas with no metastasis. The patient underwent enucleation of the tumor in November 2020. Pathology showed a well-differentiated neuroendocrine tumor staged T1 pN0 with immunohistochemistry staining diffusely positive for chromogranin, synaptophysin, and insulin with a Ki67 index &amp;lt;3%. In January 2021, at a post-surgery follow-up visit, blood work showed HbA1c 7.1%, proinsulin 31 pmol/L, insulin 13.4 uIU/mL, C-peptide 1.6 ng/mL, BG 193 mg/dl, and chromogranin A 118 ng/mL. HbA1c continued to trend up to 8.0% in January 2022, confirming the resurgence of diabetes, and metformin and pioglitazone were started. Conclusion: Per our literature review, this is the first reported case of a proinsulinoma in a patient with T2DM. In a patient with uncontrolled T2DM, an unexpected amelioration of the disease should raise concern for insulin-secreting tumors, and further workup should be considered. A CGM can be a valuable tool to assess the severity of hypoglycemia in patients with these tumors. Presentation: Saturday, June 17, 2023

SAT364 A Rare Cause of Hyperandrogenism in a Premenopausal Woman

Abstract Disclosure: L. El Musa Penna: None. W. Medina-Torres: None. L.R. Sepulveda-Garcia: None. L.N. Madera Marin: None. A. Rosado-Burgos: None. M.A. Ortiz-Rivera: None. B. Torres Rivera: None. M. Alvarado: None. M. Ramirez: None. L.A. Gonzalez-Rodriguez: None. M. Marcos Martínez: None. M. Correa Rivas: None. N. Bracero, MD: None. Hyperandrogenism in premenopausal women is most commonly associated to polycystic ovarian syndrome (PCOS). Approximately 10% of females in reproductive age present with clinical and/or biochemical findings of androgen excess, such as hirsutism, acne, alopecia, oligo-amenorrhea or if hyperandrogenism is severe it can lead to extreme virilization. Androgen excess can also contribute to insulin resistance. In this case we discuss a patient with severe hyperandrogenism, extreme insulin resistance and a rare cause of androgen excess in a woman of childbearing age. 34-year-old female patient G0P0 with type 2 diabetes mellitus (T2DM) on continuous insulin infusion system (CIIS), familial partial lipodystrophy, PCOS and severe hyperandrogenism, who was referred to our clinics for management of uncontrolled T2DM. Patient was on CIIS with regular insulin U-500 using a total daily dose of 95 units. She referred amenorrhea for the past 12 years and significant progression of hirsutism, alopecia and acanthosis nigricans in the past two years. Patient had clinical findings of hyperandrogenism such as hirsutism evaluated with modified Ferriman-Gallwey scale with a score of 32, alopecia Ludwig class 3 and marked acanthosis nigricans in neck and abdomen.Pre-operative laboratories: hemoglobin (Hgb) level 15.13 g/dL, hematocrit (Ht) 44.59 %, total testosterone level 525 ng/dL (13-53 ng/dL) and DHEAS 113 ug/dL (95.8-511.7 ug/dL), suggesting an ovarian source of androgen excess. Transvaginal ovarian ultrasound showed at the posteromedial edge of right ovary a hyperechoic structure measuring 1.5 cm long x 1.0 cm AP representing a lesion of unknown etiology. After discussion with patient a decision for oophorectomy was made. Pathology report described the ovary negative for neoplasia with findings consistent with hyperthecosis. Laboratories two weeks post-operative showed significant decrease in total testosterone to 81 ng/dL and in Hgb/ Ht (12.50 g/dL and 37.8% respectively). Insulin requirement decreased and she was able to be transitioned to U-100 insulin lispro with a total daily dose of 100. Four weeks after surgery patient had her menstrual period. Ovarian hyperthecosis is a disorder where there is an increased tissue with luteinized theca cells in the ovarian stroma; these cells are ovarian interstitial cells that differentiate into steroidogenically active cells. It is most commonly observed in post-menopausal women, but it has been described in women of childbearing age presenting with worsening hirsutism, virilization and insulin resistance. Monitoring patterns and progression of androgen excess is important in premenopausal women with a diagnosis of PCOS. Severe biochemical or clinical presentation, as well as progression of hyperandrogenism should increase suspicion of additional pathological entities as it will improve patient’s quality of life with the appropriate management. Presentation Date: Saturday, June 17, 2023

A 56 Years Old Female with Uncontrolled Diabetes Mellitus Type II, Pneumonia, and Suspect With Lung Abscess: a Case Report

Background:Diabetes mellitus is a group of metabolic diseases with characteristic hyperglycemia. Proper management of DM patients is essential, and this is useful for controlling appropriate blood glucose levels. If blood glucose levels are uncontrolled, this lead to other complications in other organs, like interference with the immune system. Disruption of the immune system causes the risk of infectious diseases, such as pneumonia and lung abscess.Case Presentation:We report a female patient with a history of type 2 diabetes mellitus, complaining of dyspnea, cough with sputum, high fever, and headache. On chest examination showed left chest movement in the right lung, increased stem fremitus in all right lung fields, dullness in the right upper lung field, and amphoric sound, coarse and wet crackles heard in the right upper lung. Several supporting examinations, including laboratory and radiological examinations were carried out.Conclusion: The patient was diagnosed with uncontrolled type 2 diabetes mellitus, pneumonia, and a suspected lung abscess. The patient was given several treatments and showed clinical improvement on the fifth day of treatment.