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Biochemistry and Biophysics Reports Sep 2024Roux-en-Y gastric bypass (RYGB) is an effective treatment for obesity, resulting in long-term weight loss and rapid remission of type 2 diabetes mellitus. Improved...
BACKGROUND
Roux-en-Y gastric bypass (RYGB) is an effective treatment for obesity, resulting in long-term weight loss and rapid remission of type 2 diabetes mellitus. Improved glucagon-like peptide 1 (GLP-1) levels is one factor that contributes to the positive effects. Prior to RYGB, GLP-1 response is blunted which can be attributed to intestinal ketogenesis. Intestinal produced ketone bodies inhibit GLP-1 secretion in enteroendocrine cells via an unidentified G-protein coupled receptors (GPCRs). A possible class of GPCRs through which ketone bodies may reach are the free fatty acid receptors (FFARs) located at the basolateral membrane of enteroendocrine cells.
AIM
To evaluate FFAR3 expression in enteroendocrine cells of the small intestine under different circumstances, such as diet and bariatric surgery, as well as explore the link between ketone bodies and GLP-1 secretion.
MATERIALS AND METHODS
FFAR3 and enteroendocrine cell expression was analyzed using Western blot and immunohistochemistry in biopsies from healthy volunteers, obese patients undergoing RYGB and mice. GLUTag cells were used to study GLP-1 secretion and FFAR3 signaling pathways.
RESULTS
The expression of FFAR3 is markedly influenced by diet, especially high fat diet, which increased FFAR3 protein expression. Lack of substrate such as free fatty acids in the alimentary limb after RYGB, downregulate FFAR3 expression. The number of enteroendocrine cells was affected by diet in the normal weight individuals but not in the subjects with obesity. In GLUTag cells, we show that the ketone bodies exert its blocking effect on GLP-1 secretion via the FFAR3, and the Gα signaling pathway.
CONCLUSION
Our findings that ketone bodies via FFAR3 inhibits GLP-1 secretion bring important insight into the pathophysiology of T2D. This highlights the role of FFAR3 as a possible target for future anti-diabetic drugs and treatments.
PubMed: 38910871
DOI: 10.1016/j.bbrep.2024.101749 -
Proceedings (Baylor University. Medical... 2024This study aimed to describe the effect of the pandemic on epidemiologic trends and disparities in outcomes for patients hospitalized with acute hyperglycemic...
OBJECTIVE
This study aimed to describe the effect of the pandemic on epidemiologic trends and disparities in outcomes for patients hospitalized with acute hyperglycemic complications (AHC).
METHODS
This was a retrospective study of the National Inpatient Sample (NIS) database from 2016 to 2020. The population included adults hospitalized with AHCs as a principal diagnosis using the Clinical Classifications Software Refined code.
RESULTS
There was a decrease in the AHC hospitalization rate per 100,000 admissions for type 1 diabetes (T1D) during the pandemic (577 vs 600). However, there was an increase for type 2 diabetes (T2D) (117 vs 125). The mean age during the pandemic versus prepandemic was 34.8 ± 14.1 vs 34.7 ± 14.2 ( 0.41) and 59.1 ± 14.4 vs 58.8 ± 14.7 ( 0.51) for T1D and T2D, respectively. No statistically significant difference was observed in mortality in T1D (0.20 vs 0.23; 0.42) or T2D (1.1 vs 0.8; 0.09). There was no difference in mortality after stratifying results by gender, race, median household income, or hospital region. During the pandemic, COVID-19 was the principal diagnosis in 5.5% of those with AHC in T1D and 9.1% in those with AHC in T2D.
CONCLUSION
The pandemic had a significant impact on the hospitalization rate for both T1D and T2D.
PubMed: 38910828
DOI: 10.1080/08998280.2024.2346391 -
Proceedings (Baylor University. Medical... 2024Nutritional recommendations for patients with type 2 diabetes mellitus (T2DM) and hypertension assume high food security. However, food insecurity is estimated to affect...
BACKGROUND
Nutritional recommendations for patients with type 2 diabetes mellitus (T2DM) and hypertension assume high food security. However, food insecurity is estimated to affect 10% of the US population and more so patients at our student-run free clinic (SRFC). The aims of the study were to (1) assess food security in patients with a diagnosis of T2DM, hypertension, or both and (2) examine the relationship between food security and glycated hemoglobin (HbA1C) or blood pressure at an SRFC.
METHODS
Eligible participants completed a 10-item food security questionnaire and an item addressing perceived barriers. Most recent HbA1C and blood pressure measurements were gathered. Comparisons were made using univariate or multivariate linear regression analysis.
RESULTS
Results from 79 participants showed that 25.3% experienced high food security, 29.1% had marginal food security, 13.9% had low food security, and 30.4% had very low food security. No statistically significant association was found between food security category and HbA1C or blood pressure. However, we did find that approximately 73% of patients experienced some degree of food insecurity.
CONCLUSIONS
Patients at our SRFC are ethnically and racially diverse, most have a high school education or less, and most have food insecurity. No association between food security category and HbA1C or blood pressure control was found. Providers should consider the degree of food insecurity and incorporate a culturally sensitive approach when making nutritional recommendations.
PubMed: 38910821
DOI: 10.1080/08998280.2024.2333231 -
Cureus May 2024Current guidelines recommend shifting physician-led care (PLC) for type 2 diabetes mellitus (T2DM) to more effective multidisciplinary health care (MHC). However, few...
BACKGROUND
Current guidelines recommend shifting physician-led care (PLC) for type 2 diabetes mellitus (T2DM) to more effective multidisciplinary health care (MHC). However, few researchers have studied its real-life implementation in Saudi Arabia. Therefore, we aimed to assess the implementation and compare the outcomes of an MDC diabetes management program (DMP) among T2DM patients to a PLC at a general hospital after one year of follow-up in a real-world practice setting.
METHODS
We conducted this comparative patient files review study by analyzing medical records of all T2DM patients at two private care centers. Both were compared for their effectiveness in achieving two outcomes: the glycated hemoglobin (HbA1c) <7% and low-density lipoprotein-cholesterol (LDL-c) <70 mg/dl at the end of the first year. Additionally, we assessed the implementation of the DMP.
RESULTS
Eight hundred thirty-four medical records were reviewed, 537 from DMP, and 279 from the PLC center. The personal health coordination was almost complete (97.8%) in the DMP, but the implementation was incomplete regarding nutrition (65.7%), dental exam (64.8%), and foot care (58.3%). Both care groups were matched for age (p = 0.056), gender (p = 0.085), duration of diabetes (p = 0.217), and basal glycemic control (p = 0.171). The DMP showed a significant net decrease in HbA1c (-0.5 [IQR 1.47%] vs -0.2 [IQR 3.05%], p = 0.0001) and LDL-c (-10 [IQR 50] vs -5 [IQR 60.5] mg/dl, p = 0.004) compared to PLC. A higher percentage of patients achieved glycemic control in the DMP than in the PLC (49.4% vs 38.7%, p = 0.038). However, both programs demonstrated similar outcomes in lipid control (28.7% vs. 30%, p = 0.695).
CONCLUSION
Despite some gaps in implementation, one year of DMP showed better glycemic control among T2DM patients compared to PLC. Both programs were comparable in terms of lipid control. Further studies identifying the gaps in care implementation could improve sustainability, future replication, and generalizability of similar programs to other healthcare systems in Saudi Arabia.
PubMed: 38910761
DOI: 10.7759/cureus.60979 -
Cureus May 2024Introduction Diabetic foot complications leading to limb amputations pose a global health concern. Platelet-rich plasma (PRP) gel has emerged as a promising method for...
Introduction Diabetic foot complications leading to limb amputations pose a global health concern. Platelet-rich plasma (PRP) gel has emerged as a promising method for ulcer healing, leveraging the growth factors provided by autologous PRP to enhance tissue healing. Therefore, we aimed to assess the frequency of the success of PRP therapy in the treatment of non-healing diabetic foot ulcers. Methods This quasi-experimental study, conducted in Lahore, Pakistan, from April 2021 to October 2022, enrolled 80 eligible individuals with non-responsive diabetic foot ulcers using a consecutive sampling technique. Inclusion criteria involved patients of both genders, aged 45-75 years, with unhealed diabetic foot ulcers, and exclusion criteria considered factors such as recurrent ulcers at the same site, smoking, and immunosuppressive or anticoagulant drug therapy. Baseline demographic details, ulcer measurements using a scale, and AutoCAD (Autodesk, Inc., San Francisco, California, United States)-assisted quantification of ulcer base were recorded. Autologous PRP injections were administered following strict aseptic protocols, with dressing changes and assessments performed at specified intervals over four weeks. Treatment success, defined as >90% healing after four weeks, was the primary outcome. Data analysis utilized IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States), employing post-stratification chi-square and t-tests where appropriate for significant differences. Results The mean age of the patients was 60.40 ± 9.72 years, the mean duration of diabetes was 9.48 ± 2.21 years, and the mean ulcer duration was 11.41 ± 1.63 months. The treatment success rate was 63.7%. Age, gender, and disease duration showed no significant impact on treatment success. However, patients with a normal BMI and shorter ulcer duration exhibited a significantly higher success rate (p <0.001 and p = 0.002, respectively). Conclusions This study reaffirms the efficacy of PRP in treating non-healing diabetic foot ulcers, aligning with previous research. Despite a slightly lower success rate compared to literature reports, PRP remains a promising agent for managing diabetic foot ulcers.
PubMed: 38910752
DOI: 10.7759/cureus.60934 -
Cureus May 2024Introduction Primary hyperparathyroidism (PHPT) has undergone a considerable change from being symptomatic to asymptomatic. This is the first large study from North...
Introduction Primary hyperparathyroidism (PHPT) has undergone a considerable change from being symptomatic to asymptomatic. This is the first large study from North India to study the clinical and biochemical features and surgical outcomes in the present era. Study design This is a cross-sectional study that was conducted in the Department of Endocrinology (SKIMS) from February 2021 to December 2022, in which 103 patients diagnosed with PHPT were included. Evaluation included measurement of total calcium, phosphorus, alkaline phosphate, intact parathyroid hormone, 25-hydroxy vitamin, 24-hour urinary calcium, radiological survey of hands and skull, Dual Energy X-ray absorptiometry, and ultrasonography (USG) of the abdomen. USG neck and technetium-99m sestamibi scans were used for preoperative localization; however, in cases of discordance between these investigations or suspicions of multi-glandular disease, four-dimensional computerized tomography of the neck was used. Patients were subjected to surgery according to the guidelines and monitored post-surgery for complications like hypocalcemia and hungry bone syndrome and to document the cure. Results The mean age of patients was 42.8±14.73 years, with a female-to-male ratio of 4.4:1. The mean eGFR of patients was 99.1±30.87 ml/min, with 55 (53.4%) of them having renal disease. Osteoporosis and fractures were present in 41 (39.8%) and 5 (4.8%) patients, respectively. Cholelithiasis and pancreatitis were present in 25 (24.3%) and 5 (4.9%) patients, respectively. Hypertension (HTN) and diabetes mellitus (DM) were the commonest comorbidities, which were present in 34 (33.1%) and 15 (14.5%) patients, respectively. Mean preoperative levels of calcium, phosphorus (PO4), alkaline phosphate (ALP), intact parathyroid hormone (iPTH), 25(OH)vitamin D, and 24-hour urinary calcium were 12.1 mg/dl, 2.35 mg/dl, 210.2 U/L, 332.9 pg/ml, 25.7 ng/ml, and 452.1 mg/day, respectively. The most common type was right inferior parathyroid adenoma, present in 45 cases (43.7%), followed by left inferior parathyroid adenoma in 31 cases (30.1%). A total of 75 patients (72.8%) underwent minimally invasive parathyroidectomy, with 68 patients (90.7%) achieving a biochemical cure. The mean adenoma weight was 3.19±2.25 g. There was no statistically significant correlation (r) between preoperative biochemical parameters and adenoma weight. Conclusion Despite improvements in imaging and the easy availability of immunoassays for early diagnosis, renal disease continued to be the most common presentation, followed by skeletal involvement in our population. In developing countries like India, any patient presenting with nephrolithiasis or nephrocalcinosis, low bone mass, or fragility fractures should be evaluated for PHPT.
PubMed: 38910736
DOI: 10.7759/cureus.60965 -
Cureus May 2024The association of s with vasculitis remains relatively rare and poorly understood. In this report, we present a case of Methicillin-sensitive (MSSA)-associated...
The association of s with vasculitis remains relatively rare and poorly understood. In this report, we present a case of Methicillin-sensitive (MSSA)-associated leukocytoclastic vasculitis (LCV) following a surgical site infection, adding to the limited body of knowledge on this intriguing clinical entity. A 52-year-old male with a medical history significant for type 2 diabetes mellitus, hypertension, hyperlipidemia, and coronary artery disease presented with progressively worsening generalized petechial rash and migratory joint pains with associated joint swelling. The patient's symptoms began following surgical repair for a rectus abdominis incisional hernia with mesh placement that was complicated by an abdominal wall abscess at the surgical site, prompting drain placement. Cultures from the abscess aspirate revealed Methicillin-sensitive infection. A punch biopsy of the petechial lesions revealed findings consistent with leukocytoclastic vasculitis. The rash and joint pains resolved approximately one week after initiation of treatment with antibiotics and steroids. This case sheds light on the rare but clinically significant association between Methicillin-sensitive infection and leukocytoclastic vasculitis, particularly following surgical site infections. The prompt recognition and treatment of underlying MSSA infection, along with the targeted management of LCV, resulted in the resolution of symptoms in our patient. This case emphasizes the importance of a comprehensive diagnostic approach and highlights the efficacy of antibiotic therapy in mitigating MSSA-associated vasculitic manifestations.
PubMed: 38910712
DOI: 10.7759/cureus.60867 -
Cureus May 2024Introduction Type 2 diabetes mellitus (T2DM), a prevalent chronic metabolic disorder, necessitates multifaceted treatment approaches. Emerging studies highlight the...
Retrospective Observational Study on Assessing Sitagliptin and Dapagliflozin as a Fixed-Dose Combination in the Indian Population With Type 2 Diabetes Mellitus: The SIDAXA Study.
Introduction Type 2 diabetes mellitus (T2DM), a prevalent chronic metabolic disorder, necessitates multifaceted treatment approaches. Emerging studies highlight the cardiovascular advantages of sodium-glucose transport protein 2 (SGLT2) and dipeptidyl peptidase 4 (DPP-4) inhibitors in T2DM. This investigation delves into the synergistic effects of the fixed-dose combination (FDC) of sitagliptin and dapagliflozin, offering insights into its safety and efficacy for the Indian population. Methods This real-world, retrospective, observational study spanned 328 cases across 111 Indian centres, evaluating the safety, efficacy, and clinical utilization of the sitagliptin and dapagliflozin FDC in T2DM patients after obtaining ethical approval. Assessments at baseline, week four, and week 12 encompassed hemoglobin A1C (HbA1C), fasting plasma glucose (FPG), postprandial blood glucose (PPBG), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), and weight change. The statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 29.0.1.0(171) (IBM Corp., Armonk, NY, USA) with a significance level p<0.05. Results Study participants [mean age: 51.14±5.55 years, 77.74% (n=255) males, 22.26% (n=73) females] exhibited prevalent risk factors like sedentary lifestyle (n=167, 50.91%) and smoking (n=147, 44.82%). Comorbidities included hypertension (n=235, 71.65%) and dyslipidaemia (n=139, 42.38%). Metformin (n=282, 85.98%) and sulfonylurea (n=134, 40.85%) were commonly prescribed concomitant oral antidiabetic agents (OADs). FDC administration significantly reduced HbA1c by 1.05 ± 0.83% (p < 0.0001) at week 12. FPG and PPBG showed significant reductions of 22.98 ± 22.23 mg/dL (p < 0.0001), 165.50 ± 37.02 mg/dL and 40.94 ± 36.04 mg/dL (p < 0.0001) at four weeks respectively. By week 12, significant reductions were noted in SBP (14.61±13.98mmHg reduction, p-value <0.0001), DBP (7.80±8.45mmHg reduction, p-value <0.0001), and LDL-C levels (18.14±23.95 mg/dL reduction, p-value <0.0001). In patients with established cardiovascular disease, there was reduction in HbA1c levels by 1.02 ± 0.63% after 12 weeks, with FPG decreasing by 54.52 ± 32.67 mg/dL and PPBG decreasing by 88.73 ± 44.90 mg/dL. Treatment-emergent adverse events included headache, changes in micturition, genital mycotic infection, and nausea and diarrhoea which were mild, transient, and necessitated no treatment discontinuation. Conclusion The FDC of sitagliptin and dapagliflozin significantly improved glycaemic control and lipid profiles in T2DM patients, particularly those with coronary artery disease. It demonstrated a favourable safety profile in the Indian population, signifying its potential as an effective and well-tolerated therapeutic option in patients with established cardiovascular disease.
PubMed: 38910691
DOI: 10.7759/cureus.60815 -
Cureus May 2024Heart disease remains a prominent global health concern, with cardiovascular disease (CVD) standing as a leading cause of death worldwide. Preventing heart disease not... (Review)
Review
Heart disease remains a prominent global health concern, with cardiovascular disease (CVD) standing as a leading cause of death worldwide. Preventing heart disease not only decreases the risk of premature death but also mitigates complications like heart attacks, strokes, and arrhythmias, thereby enhancing overall health and quality of life. The economic burden of heart disease treatment highlights the importance of implementing preventive measures, such as lifestyle changes and early interventions, which can alleviate healthcare costs. These strategies, targeting risk factors like hypertension (HTN), diabetes mellitus (DM), dyslipidemia, and obesity, not only prevent heart disease but also reduce the risk of other health issues. Herein, this review covers various preventive measures, including dietary interventions, exercise, controlling HTN, DM, cholesterol, and weight, smoking cessation, and pharmacological interventions. By critically analyzing the guidelines and leveraging robust data alongside variations in recommendations, this review aims to elucidate effective primary prevention strategies for CVD.
PubMed: 38910676
DOI: 10.7759/cureus.60877 -
Cureus May 2024Destructive thyroiditis and secondary adrenal insufficiency are major endocrinological immune-related adverse events of immune checkpoint inhibitors (ICIs). However, the...
Destructive thyroiditis and secondary adrenal insufficiency are major endocrinological immune-related adverse events of immune checkpoint inhibitors (ICIs). However, the timing at which each event occurs most frequently after drug administration varies, and cases where multiple events occur simultaneously are rare. We encountered a patient who concurrently suffered from thyrotoxicosis and adrenal insufficiency. An 80-year-old woman with a history of type 2 diabetes mellitus (DM) was diagnosed with stage IVA squamous cell carcinoma of the lungs. Treatment with a combination of nivolumab and ipilimumab was initiated. Although she tested positive for thyroglobulin antibody and transient subclinical hyperthyroidism was observed after two courses, treatment with ICIs was continued. Four months later, treatment was discontinued due to drug-induced lung disease. One month after the last administration, the patient became unconscious and was admitted to another hospital, diagnosed with diabetic ketoacidosis, urinary tract infection, and sepsis. After acute-phase treatment, she was transferred to our hospital due to persistent fever and tachycardia. Thyrotoxicosis and adrenal insufficiency were observed, with high levels of free thyroxine, low thyroid-stimulating hormone (TSH), and cortisol levels. Treatment with extracellular fluids, potassium iodide, beta-blockers, and hydrocortisone was initiated, and the patient's condition improved. No other pituitary hormone deficiencies were observed. She was diagnosed with painless thyroiditis and secondary adrenal insufficiency based on the positive thyroglobulin antibody, negative TSH receptor antibody, decreased Doppler flow in thyroid ultrasonography, low adrenocorticotrophic hormone (ACTH), and low response of ACTH and cortisol to corticotropin-releasing hormone loading test. MRI revealed no abnormalities. We report a case of thyrotoxicosis and secondary adrenal insufficiency five months after the first administration of nivolumab and ipilimumab. Careful follow-up and early detection of endocrine disorders are critical in patients treated with a combination of ICIs.
PubMed: 38910605
DOI: 10.7759/cureus.60850