Clinical Diabetes and Endocrinology最新文献

Background: There are scant data relating to prognostic biomarkers for chronic kidney disease (CKD) complicating type 1 diabetes. The aim of this study was to assess the performance of the plasma protein biomarker-based PromarkerD test developed and validated for predicting renal decline in type 2 diabetes in the context of type 1 diabetes.

Methods: The baseline PromarkerD test score was determined in 91 community-based individuals (mean age 46.2 years, 56.5% males) with confirmed type 1 diabetes recruited to the longitudinal observational Fremantle Diabetes Study Phase II. The performance of the PromarkerD test in predicting the risk of incident CKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m² in people without CKD at baseline) or an eGFR decline of ≥ 30% over the next four years was determined. The score can range from 0 to 100%, and is categorized as representing low (< 10%), moderate (10% to < 20%) or high (≥ 20%) risk.

Results: The area under the receiver operating characteristic curve was 0.93 (95% confidence interval 0.87-0.99) for the composite renal endpoint, indicating strong predictive accuracy. The positive and negative predictive values at moderate (10% to < 20%) and high (≥ 20%) risk PromarkerD cut-offs were 46.7-50.0% and ≥ 92.0%, respectively.

Conclusions: These preliminary data suggest that PromarkerD is at least as good a prognostic test for renal decline in type 1 as type 2 diabetes.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, characterised by its multifactorial nature and intricate interplay of genetic, hormonal, and environmental factors. As the search for reliable biomarkers intensifies, serum kisspeptin emerges as a promising candidate due to its central role in regulating the hypothalamic-pituitary-gonadal (HPG) axis. This review aims to consolidate the evolving understanding of kisspeptin as a potential PCOS biomarker, comprehensively exploring its physiological basis, diagnostic challenges in PCOS, and clinical implications. Diagnostic challenges in PCOS are addressed, underscoring the limitations of current criteria and the need for objective and standardised biomarkers. Kisspeptin's introduction as a potential biomarker brings forth both promises and challenges in terms of its diagnostic utility. The review recognises the importance of standardisation in research methodologies and emphasises the exploration of genetic polymorphisms to enhance kisspeptin's robustness as a diagnostic tool.

Background: Obesity is rising globally. Normal weight obesity (NWO) and normal weight central obesity (NWCO) despite normal BMI pose added metabolic risks. Limited data on these phenotypes among Indian doctors merits investigation. The present study aimed to assess the prevalence of overall obesity, NWO, NWCO, and their associations with cardiometabolic risks among doctors in Gujarat, India.

Methods: It's a Cross-sectional study among 490 doctors aged 20-60 years at a tertiary hospital. Anthropometry, blood pressure, fasting glucose, and lipids were assessed. NWO was defined as a BMI of 18.5-24.9 kg/m2 with a high body fat percentage. NWCO as normal BMI and increased waist circumference. Body composition was assessed using an Omron body composition analyzer.

Results: The prevalence of overall obesity was 101 (20%), NWO 239 (48.7%), and NWCO 210 (42.8%). Mean BMI, blood pressure, glucose, and LDL increased from normal weight to NWO/NWCO groups (p < 0.05). NWO and NWCO had significantly higher odds of hypertension, dyslipidemia, and high fasting blood sugar compared to non-obese after adjusting for confounders.

Conclusion: The high burden of overall obesity, NWO, and NWCO among doctors highlights the need for lifestyle interventions to mitigate long-term cardiometabolic disease risk.

Background: Ceramides have recently been identified as novel biomarkers associated with diabetes mellitus (DM) and major adverse cardiac and cerebrovascular events (MACCE). This study aims to explore their utility in diagnosing microvascular disease.

Methods: This study prospectively enrolled 309 patients from 2018 to 2020 into three groups: healthy controls (Group 1, N = 51), DM patients without acute myocardial infarction (AMI) (Group 2, N = 150), and DM patients with AMI (Group 3, N = 108). We assessed outcomes using stress perfusion cardiac magnetic resonance (CMR) imaging for coronary microvascular disease (CMD) (Outcome 1), retinography for retinal microvascular disease (RMD) (Outcome 2), both CMD and RMD (Outcome 3), and absence of microvascular disease (w/o MD) (outcome 4). We evaluated the classification performance of ceramides using receiver operating characteristic (ROC) analysis and multiple logistic regression. 11-ceramide panel previously identified by our research group as related to macrovascular disease were used.

Results: Average glycated hemoglobin (HbA1c) values were 5.1% in Group 1, 8.3% in Group 2, and 7.6% in Group 3. Within the cohort, CMD was present in 59.5% of patients, RMD in 25.8%, both CMD and RMD in 18.8%, and w/o MD in 38.5%. The AUC values for the reference ceramide ratios were as follows: CMD at 0.66 (p = 0.012), RMD at 0.61 (p = 0.248), CMD & RMD at 0.64 (p = 0.282), and w/o MD at 0.67 (p = 0.010). In contrast, the AUC values using 11-ceramide panel showed significant improvement in the outcomes prediction: CMD at 0.81 (p = 0.001), RMD at 0.73 (p = 0.010), CMD & RMD at 0.73 (p = 0.04), and w/o MD at 0.83 (p = 0.010). Additionally, the plasma concentration of C14.0 was notably higher in the w/o MD group (p < 0.001).

Conclusions: Plasma ceramides serve as potential predictors for health status and microvascular disease phenotypes in diabetic patients.

Background: Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by destruction of pancreatic islet beta-cells. There is significant residual beta-cell function, measured through circulating C-peptide, present at the time of T1D diagnosis but this subsequently decreases with time. Higher residual beta-cell function at diagnosis associates with better glycaemic control and less glucose variability, and later in the disease course with less hypoglycaemia, lower glucose variability and fewer microvascular complications. There is therefore value in preserving residual beta cell function in new onset T1D Immunotherapeutic agents can protect residual beta-cell function in type 1 diabetes. However, clinical trials of such agents, whilst demonstrating C-peptide preservation in short term studies, have yet to be taken forward into routine clinical care due to concerns around safety and long-term efficacy. Here we report the case of a gentleman with newly diagnosed T1D whose glycaemic control and insulin requirement improved whilst on a five year infusion programme of infliximab, a monoclonal antibody against TNF-alpha, for colitis.

Case presentation: A 52-year-old White Caucasian man was diagnosed with T1D in August 2018. Glucose was 25.6 mmol/L, HbA1c was 98mmol/mol and GAD antibodies were strongly positive. HbA1c marginally improved to 91mmol/mol following initiation of insulin detemir 5 units at night and 1:10 g of insulin aspart (November 2018). In June 2019, he developed rectal bleeding and abdominal pain. Following colonoscopy, he was diagnosed with "indeterminate colitis" and commenced on 6-weekly infusions of 400-450 mg infliximab. Thus far, he has received 32 doses and achieved colitis remission. Following infliximab initiation there was increased frequency of mild-moderate hypoglycaemia and he was gradually weaned off and discontinued detemir in June 2020. Since then, HbA1c improved from 57mmol/mol in August 2019 to 52mmol/mol in April 2022, remaining stable at 51mmol/mol. His most recent HbA1c is 54mmol/mol in February 2024. His c-peptide was 550pmol/L in October 2022 and 442pmol/L in February 2024, suggesting well-preserved beta-cell function almost 6 years post-diagnosis.

Conclusions: Our patient's improvement in glycaemic control can be explained by immunomodulation and C peptide preservation from infliximab. With the growing focus on type 1 diabetes disease modulation and working towards an 'insulin free T1D', our findings strengthen the evidence base for the repurposing of and long-term treatment with anti-TNF-α agents to preserve beta-cell function in new onset T1D.

Background: Elevated blood glucose concentration, also known as hyperglycemia, has been identified as a significant factor influencing the prognosis of COVID-19, alongside the impact of the SARS-CoV-2 infection itself.

Methods: This research is a cross-sectional investigation that examined the relationship between COVID-19 and hyperglycemia in patients admitted to Afzalipour Hospital in Kerman, Iran, from July to September 2021. A standardized data sheet was used to capture demographic data (age, gender) and laboratory information (blood sugar, arterial blood oxygen saturation, and C-reactive protein (CRP)) upon admission.

Results: The present research evaluated a total of 300 individuals diagnosed with COVID-19, with an average age of 50.19 ± 15.55 years. Among these patients, the majority were male, accounting for 51.67% of the total. Hyperglycemia was seen in 21.67% of patients, but less than 20% had new-onset diabetes. Individuals exhibiting hyperglycemia were typical of advanced age (P < 0.001). Furthermore, there was a slight but statistically significant association between advanced age and elevated blood glucose concentration (R = 0.254, P < 0.001). Gender had no significant impact on the occurrence of hyperglycemia (P = 0.199). There was no significant association between CRP levels and blood glucose concentration (P = 0.524) or the incidence of hyperglycemia (P = 0.473). Although there was no significant disparity in blood oxygen saturation between individuals with or without hyperglycemia (P = 0.06), higher blood glucose concentration was correlated with lower blood oxygen saturation (R = -0.151, P < 0.001).

Conclusion: Considering the correlation between blood glucose concentration, advanced age, and disease severity, it is recommended to carefully screen and monitor all COVID-19 patients for hyperglycemia and new-onset diabetes. Effective management of these complications could enhance the control of patients' overall prognosis and subsequent complications.

Thyroid storm is a medical emergency with a high mortality rate. Acute liver failure (ALF) and disseminated intravascular coagulation (DIC) are rarely reported with thyroid storm, and their occurrence is unrelated to the degree of free circulating thyroxine.We present the case of a 41-year-old Sri Lankan female, with a fatal case of thyroid storm. She initially presented with palpitations and heat intolerance, and subsequently developed acute liver failure with hepatic encephalopathy and coagulopathy. There was hypoglycemia and resistant lactic acidosis consequent to the liver failure. The clinical course progressed to DIC and she eventually succumbed to the illness. Treatment comprised the standard management of thyroid storm.This case report highlights the importance of bearing ALF and DIC in mind as complications of thyroid storm, outlines their pathophysiology, and uses pathophysiological mechanisms to justify, evolving extracorporeal therapeutic strategies for resistant cases.

Background: Hungry bone syndrome (HBS) is defined as prolonged hypocalcemia caused by a sudden decrease in parathyroid hormone (PTH) levels after parathyroidectomy (PTX). Multiple fractures after PTX due to HBS in an end-stage renal disease (ESRD) patient on chronic hemodialysis (HD) are challenging and rare medical conditions presented in this study.

Case presentation: A 42-year-old ESRD patient on HD 3 times a week presented to Shariati Hospital, Tehran, Iran, complaining of worsening bone pain and loss of appetite. Laboratory data revealed an intact parathyroid hormone (iPTH) concentration of 2500 pg/mL, an alkaline phosphatase (Alp) level of 4340 IU/L, a phosphorus (P) level of 9 mg/dL, and a calcium (Ca) concentration of 7.2 mg/dL. Sestamibi scintigraphy revealed parathyroid adenoma. The findings suggested tertiary hyperparathyroidism (HPT-III), and the patient was scheduled for total PTX. Approximately one month after surgery, the patient was referred due to convulsions, leg mobility problems, and worsening bone pain. There was bilateral femoral ecchymosis. The Ca concentration was 5.8 mg/dL, and radiological evaluations revealed multiple skeletal fractures. HBS after PTX was suggested for this patient. After several days of hospitalization, he suffered subcutaneous emphysema followed by rib fractures and passed away.

Conclusions: Multiple fractures after PTX due to HBS following HPT-III in ESRD patients are rare and demanding, highlighting the necessity of timely diagnosis and management of patients with HPT-III. Severe hypocalcemia following PTX can cause skeletal disorders. However, the surgical treatment of parathyroid adenomas may be more important than the risk of complications associated with bone health.

This review explores the immunomodulatory potential of Teplizumab and its impact on pancreatic β-cell function in T1D. Characterized by the autoimmune destruction of insulin-producing beta cells, T1D's management involves maintaining glycemic control through exogenous insulin. Teplizumab, a humanized monoclonal antibody targeting the CD3 antigen, has shown promise in delaying T1D onset and preserving residual β-cell function. The review employs a narrative approach, synthesizing evidence from diverse clinical trials and studies gathered through a meticulous literature search. It scrutinizes Teplizumab's mechanisms of action, including its influence on autoreactive CD8 + T cells and regulatory T cells, offering insights into its immunological pathways. The synthesis of findings from various trials demonstrates Teplizumab's efficacy in preserving C-peptide levels and reducing exogenous insulin requirements, particularly in recent-onset T1D. Considering Teplizumab's real-world implications, the paper addresses potential obstacles, including side effects, patient selection criteria, and logistical challenges. It also emphasizes exploring combination therapies and personalized treatment strategies to maximize Teplizumab's benefits. The review contributes a nuanced perspective on Teplizumab's clinical implications and future directions in T1D management, bridging theoretical understanding with practical considerations.

Aim: Type 2 diabetes is increasing in Sub-Saharan Africa, but the pathophysiology in this population is poorly investigated. In Western populations, the incretin effect is reduced in type 2 diabetes, leading to lowered insulin secretion. The aim of this study was to investigate the incretin effect in a group of Sub-Saharan Africans with type 2 diabetes.

Methods: Twenty adults diagnosed with type 2 diabetes, based on either an oral glucose tolerance test (n = 10) or on glycated hemoglobin A1c (n = 10), and 10 non-diabetic controls were included in an interventional study in Tanzania. We investigated the incretin effect as the difference between the plasma insulin area under the curve during an oral glucose tolerance test and that obtained during an intravenous glucose infusion. Differences between diabetes groups were analyzed by Kruskal-Wallis one-way analysis of variance.

Results: The incretin effect did not differ between groups (p = 0.45), and there was no difference in plasma concentrations of the incretin hormones during the OGTT.

Conclusion: A reduced incretin effect appears not to contribute to hyperglycemia in type 2 diabetes in this Tanzanian population. More research is needed to explain the diabetes phenotype often seen in Sub-Saharan Africa.

Trial registration: Clinicaltrials.gov: NCT03106480 , date of registration: 04/10/2017.