Clinical Diabetes and Endocrinology最新文献

Background: Acute kidney injury (AKI) due to Diabetic Ketoacidosis (DKA) is rather common. Novel biomarkers to diagnose AKI are being increasingly used in different settings. The use of urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) in predicting persistent AKI in pediatric DKA cases is still not thoroughly investigated.

Methods: This was a secondary analysis of Saline versus Plasma-Lyte in Ketoacidosis (SPinK) trial data; 66 children (> 1 month-12 years) with DKA, defined by the International Society for Pediatric and Adolescent Diabetes (ISPAD), were analyzed. Children with cerebral edema, chronic kidney disease and those who received pre-referral fluids and/or insulin were excluded. uNGAL and urine NGAL-creatinine ratio (uNCR) at 0 and 24 h were measured in all. Persistent AKI was defined as a composite outcome of continuance of AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or 3 beyond 48 h from AKI onset, progression of AKI from either KDIGO stage 0 or 1 to a worse stage, need of renal replacement therapy or death.

Main outcomes: Thirty-five (53%) children had AKI at admission; 32 (91.4%) resolved within 48 h. uNGAL was significantly higher in the AKI group at admission [79.8 ± 27.2 vs 54.6 ± 22.0, p = 0.0002] and at 24 h [61.4 ± 28.3 vs 20.2 ± 14.5, p = 0.0003]. Similar trend was observed with uNCR at admission [6.7 ± 3.7 vs 4.1 ± 2.6, p = 0.002] and at 24 h [6.3 ± 2.5 vs 1.2 ± 1.0, p = 0.01]. Furthermore, uNGAL at admission showed a moderate positive linear correlation with serum creatinine. Additionally, elevated uNGAL at 0 and 24 h correlated with corresponding KDIGO stages. Admission uNGAL >88 ng/ml and uNCR of >11.3 ng/mg had a sensitivity of 66% and 67%, specificity of 76% and 95%, and Area under the receiver operating characteristic curve (AUC) of 0.78 and 0.89 respectively for predicting persistent AKI at 48 h.

Conclusions: Majority of AKI resolved with fluid therapy. While uNGAL and uNCR both correlated with serum creatinine and AKI stages, serial uNCR was a better predictor of persistent AKI than uNGAL alone. However, feasibility of routine uNGAL measurement to predict persistent AKI in DKA needs further elucidation.

Trial registration: This was a secondary analysis of the data of SPinK trial [CTRI/2018/05/014042 ( ctri.nic.in )].

Background: Gestational diabetes mellitus (GDM) is glucose intolerance first recognised during pregnancy. Both modalities and thresholds of the GDM diagnostic test, the Oral Glucose Tolerance Test (OGTT), have varied widely over time and among countries. Additionally, OGTT limitations include inconsistency, poor patient tolerability, and questionable diagnostic reliability. Many biological parameters have been reported to be modified by GDM and could potentially be used as diagnostic indicators. This study aimed to 1) systematically explore biomarkers reported in the literature as differentiating GDM from healthy pregnancies 2) screen those indicators assessed against OGTT to propose OGTT alternatives.

Main body: A systematic review of GDM diagnostic indicators was performed according to PRISMA guidelines (PROSPERO registration CRD42020145499). Inclusion criteria were full-text, comprehensible English-language articles published January 2009-January 2021, where a biomarker (from blood, ultrasound, amniotic fluid, placenta) was compared between GDM and normal glucose tolerance (NGT) women from the second trimester onward to immediately postpartum. GDM diagnostic method had to be clearly specified, and the number of patients per study higher than 30 in total or 15 per group. Results were synthesised by biomarkers.

Results: Of 13,133 studies identified in initial screening, 174 studies (135,801 participants) were included. One hundred and twenty-nine studies described blood analytes, one amniotic fluid analytes, 27 ultrasound features, 17 post-natal features. Among the biomarkers evaluated in exploratory studies, Adiponectin, AFABP, Betatrophin, CRP, Cystatin-C, Delta-Neutrophil Index, GGT, TNF-A were those demonstrating statistically and clinically significant differences in substantial cohorts of patients (> 500). Regarding biomarkers assessed versus OGTT (i.e. potential OGTT alternatives) most promising were Leptin > 48.5 ng/ml, Ficolin3/adiponectin ratio ≥ 1.06, Chemerin/FABP > 0.71, and Ultrasound Gestational Diabetes Score > 4. These all demonstrated sensitivity and specificity > 80% in adequate sample sizes (> / = 100).

Conclusions: Numerous biomarkers may differentiate GDM from normoglycaemic pregnancy. Given the limitations of the OGTT and the lack of a gold standard for GDM diagnosis, advanced phase studies are needed to triangulate the most promising biomarkers. Further studies are also recommended to assess the sensitivity and specificity of promising biomarkers not yet assessed against OGTT.

Trial registration: PROSPERO registration number CRD42020145499.

Aim: Patients with lipodystrophy are at high risk for chronic complications of diabetes. Recently, we have reported 18 diabetic foot ulcer episodes in 9 subjects with lipodystrophy. This current study aims to determine risk factors associated with foot ulcer development in this rare disease population.

Methods: Ninety metreleptin naïve patients with diabetes registered in our national lipodystrophy database were included in this observational retrospective cohort study (9 with and 81 without foot ulcers).

Results: Patients with lipodystrophy developing foot ulcers had longer diabetes duration (p = 0.007), longer time since lipodystrophy diagnosis (p = 0.008), and higher HbA1c levels (p = 0.041). Insulin use was more prevalent (p = 0.003). The time from diagnosis of diabetes to first foot ulcer was shorter for patients with generalized lipodystrophy compared to partial lipodystrophy (p = 0.036). Retinopathy (p < 0.001), neuropathy (p < 0.001), peripheral artery disease (p = 0.001), and kidney failure (p = 0.003) were more commonly detected in patients with foot ulcers. Patients with foot ulcers tended to have lower leptin levels (p = 0.052). Multiple logistic regression estimated significant associations between foot ulcers and generalized lipodystrophy (OR: 40.81, 95% CI: 3.31-503.93, p = 0.004), long-term diabetes (≥ 15 years; OR: 27.07, 95% CI: 2.97-246.39, p = 0.003), and decreased eGFR (OR: 13.35, 95% CI: 1.96-90.67, p = 0.008).

Conclusions: Our study identified several clinical factors associated with foot ulceration among patients with lipodystrophy and diabetes. Preventive measures and effective treatment of metabolic consequences of lipodystrophy are essential to prevent the occurrence of foot ulcers in these high-risk individuals.

Background: There is conflicting evidence regarding an association between gonadotropin releasing hormone analogue (GnRHa) therapy and polycystic ovary syndrome (PCOS). This study aimed to compare the prevalence of endocrine disorders, primarily PCOS, between women who had been treated with GnRHa for central precocious puberty (CPP) and those who were not treated.

Methods: This was a retrospective cohort study, including women diagnosed with central precocious puberty between 1989 and 2011 in a university affiliated tertiary medical center. Data collected included demographic data, medical background, clinical presentation at diagnosis and duration of treatment (zero for non-treated). Gynecologic and endocrine long-term outcomes were compared by treatment group.

Results: Fifty-one women were included in the study, 27/51 had been treated with gonadotropin releasing hormone analogue (GnRHa). Overall prevalence of PCOS was 19.6%. No statistically significant difference in prevalence of PCOS was demonstrated between the treated and non-treated groups. Similarly, overall prevalence of either clinical or laboratory hyper-androgenism, was 29.4% and 33.3%, for the treatment and non-treatment groups respectively (p = non-significant).

Conclusions: GnRHa treatment for precocious puberty is not associated with increased risk of polycystic ovary syndrome.

Background: The study characterizes safety, tolerability, pharmacokinetic and pharmacodynamic profiles of single rising doses of the 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD1) inhibitor BI 187004 in healthy men with overweight or obesity.

Methods: This was a randomized, double-blind, parallel group, placebo-controlled study with administration of 2.5-360 mg BI 187004 or placebo once daily as single dose in 72 healthy male volunteers with overweight or obesity. Assessments included 11beta-HSD1 inhibition in the liver (assessed indirectly by urinary tetrahydrocortisol/tetrahydrocortisone ratio) and in subcutaneous adipose tissue ex vivo and determination of hypothalamus-pituitary-adrenal axis hormones.

Results: BI 187004 was well tolerated and safe in all tested dose groups. The incidence of drug-related adverse events was 16.7% (n = 9) for all 9 BI 187004 dose groups and 5.9% (n = 1) for placebo. All treatment groups were similar concerning kind and intensity of adverse events. No clinically relevant deviations in clinical laboratory or ECG parameters were reported. Exposure of BI 187004 increased non-proportionally over the entire dose range tested. The geometric mean apparent terminal half-life decreased from 33.5 h (5 mg) to 14.5 h (160 mg) remaining stable up to 360 mg. Renal excretion of BI 187004 was low (3-5%). Urinary tetrahydrocortisol/tetrahydrocortisone ratio decreased, indicating liver 11beta-HSD1 inhibition. Median inhibition of 11beta-HSD1 in subcutaneous adipose tissue biopsies following single dosing ranged from 86.8% (10 mg) to 99.5% (360 mg) after 10 h and from 59.4% (10 mg) to 98.6% (360 mg) after 24 h.

Conclusions: BI 187004 as single dose was safe and well tolerated and is suitable for once daily dosing. There was significant, sustained 11beta-HSD1 inhibition in liver and adipose tissue.

Trial registration: ClinicalTrials.gov, NCT01587417 , registered on 26-Apr-2012.

Aims: Diabetic ketoacidosis (DKA) is an emergency with high morbidity and mortality. This study examined patient factors associated with hospitalization for recurrent DKA.

Methods: Characteristics of 265 subjects admitted for DKA at Hennepin County Medical Center between January 2017 and January 2019 were retrospectively analyzed. Differences between subjects with a single admission versus multiple were reviewed.

Results: Forty-eight out of 265 patients had recurrent DKA. Risk factors included African American race (adjusted odds ratio (aOR) versus white non-Hispanic = 4.6, 95% CI 1.8-13, p = 0.001) or other race/ethnicity (aOR = 8.6, 2.9-28, p < 0.0001), younger age (aOR 37-52y versus 18-36y = 0.48, 0.19-1.16, p = 0.10; aOR 53-99y versus 18-36y = 0.37, 0.12-0.99, p = 0.05), type 1 diabetes mellitus (aOR = 2.4, 1.1-5.5, p = 0.04), ever homeless (aOR = 2.5, 1.1-5.4, p = 0.03), and drug abuse (aOR = 3.2, 1.3-7.8, p = 0.009). DKA cost a median of $29,981 per admission.

Conclusions: Recurrent DKA is costly, and social determinants are strong predictors of recurrence. This study highlights the need for targeted preventative care programs.

Background: Diabetic retinopathy is the most frequent complication of Diabetes Mellitus and remains the leading cause of preventable blindness. However, there are limited studies on the determinants of diabetic retinopathy in the study area as well in Ethiopia. Hence, this study aimed to assess the determinants of diabetic retinopathy among diabetic patients at Tikur Anbessa Hospital.

Methods: An institution-based unmatched case-control study design was conducted at Tikur Anbessa Hospital from May 11 to June 26, 2020. Diabetic patients who developed retinopathy within 2 years were cases in the study. Patients who were free of retinopathy were controls in this study. Data were collected using a pretested interviewer-administered questionnaire, Topcon retinal examination, and a record review. The collected data were entered into Epi Data version 3.1 software, and analyzed using SPSS version 25. Binary logistic regression analysis was used to assess the determinants of diabetic retinopathy.

Results: A total of 282 patients (142 cases and 140 controls) were included in the study. The mean age (± Standard deviation) for the cases and the controls were 50.6 (SD: ± 18.7) and 44.9 (SD: ± 17.65) respectively. Patients who had a glucometer at home (AOR = 0.048; 95% CI: 0.005-0.492), exercise adherence (AOR = 0.075; 95% CI: 0.007-0.84), diabetes duration < 5 years (AOR = 0.005; 95% CI: 0.00-0.10) and 5-10 years (AOR = 0.041; 95% CI: 0.003-0.57), health information on diabetic complications (AOR = 0.002; 95% CI: 0.00-0.042) and appointments every month (AOR = 0.004; 95% CI: 0.00-0.073) and every 3 months (AOR = 0.022; 95% CI: 0.002-0.23) were less likely to develop diabetic retinopathy. Participants who had poor glycemic control (AOR = 19.9; 95% CI: 2.34-168.69), systolic hypertension (AOR = 23.4; 95% CI: 2.56-215.36) and nephropathy (AOR = 17.85; 95% CI: 2.01-158.1), had a higher risk of developing diabetic retinopathy.

Conclusions: Patients who had a glucometer at home, exercise adherence, diabetes duration < 10 years, health information on diabetic complications, and frequent follow-up had a preventive role. However, poor glycemic control, systolic hypertension, and nephropathy increase the risk of diabetic retinopathy. A concerted effort should be made to improve the health status of patients with Diabetes Mellitus, with particular emphasis on lifestyle modification practices to prevent diabetic retinopathy.

Background: Hyperglycemia is the most common side-effect of phosphatidylinositol 3-kinase (PI3K) inhibitors that are approved for the treatment of some advanced or metastatic breast cancers. This side-effect is likely due to the central role of PI3K in insulin signalling. Here we report the use of a sodium-glucose cotransporter 2 (SGLT2) inhibitor to manage severe hyperglycemia.

Case presentation: We describe a 74-year-old woman who developed severe uncontrolled hyperglycemia after commencing alpelisib, a new oral PI3K inhibitor indicated for a metastatic breast cancer, despite taking oral anti-diabetic drugs, metformin and vildagliptin, combined with intravenous insulin infusion of up to 250 units/day. The introduction of the SGLT2 inhibitor dapagliflozin rapidly improved blood glucose with a drastic reduction in insulin dosage, from 250 to 12 units/day, and without significant side-effects.

Conclusions: We report the successful management of hyperglycemia induced by alpelisib using a SGLT2 inhibitor without the need to discontinue effective cancer treatment.

Introduction: The relationship between H. pylori infection and obesity development has remained controversial among various studies. The aim of this study was to clarify the pooled effect of H. pylori infection on the development of obesity and vice versa.

Methods: We searched international databases including Medline (PubMed), Web of sciences, Scopus, EMBASE, Cochrane, Ovid, and CINHAL to retrieve all case-control studies reporting the effect of H. pylori on obesity and vice versa, which had been published in English between January 1990 and June 2019. The quality of included studies was assessed by the Modified Newcastle-Ottawa Scale for Case-Control studies. The logarithm of the odds ratio (OR) and its standard error was used for the meta-analysis.

Results: Eight case-control studies with 25,519 participants were included for qualitative and quantitative analyses. The pooled analysis showed that obese participants had a higher risk of H. pylori infection than lean participants with an odds ratio of 1.46 (95%CI: 1.26, 1.68). Also, the pooled analysis revealed that participants infected by H. pylori had a higher risk of obesity than non-infected participants with an odds ratio of 1.01 (95%CI: 1.01, 1.02).

Conclusion: The results of this meta-analysis showed that there was a positive correlation between the risk of H. pylori infection and the prevalence of obesity development. Thus, H. pylori positive patients were more likely to be obese, and obese individuals had higher risks of H. pylori infection.

Background: Central Diabetes Insipidus (CDI) results from decreased production of antidiuretic hormone (ADH) leading to an inability to concentrate urine. CDI is treated with desmopressin (DDAVP). Rarely reported in the literature, opioids and non-steroidal anti-inflammatories (NSAIDs) can induce hyponatremia in individuals treated for CDI.

Case presentation: A 10-year-old boy with septo-optic dysplasia and CDI was treated with DDAVP 1.6 mg orally TID maintaining normal sodium levels. Post admission for a femur fracture, he was discharged on ibuprofen and hydromorphone. Sodium was 136 mmol/l two days before discharge. He returned to the ED after having a seizure at home. He was euvolemic and mildly lethargic. Sodium was low at 108 mmol/l. DDAVP and hydromorphone were held and he was fluid restricted, but the sodium remained low. Sodium began to rise when Ibuprofen was stopped. Intermittent small doses of DDAVP were given to facilitate gradual correction of hyponatremia. At discharge, sodium had normalized.

Conclusion: Hyponatremia has occasionally been described as a side effect of opioids and rarely of NSAIDs in patients with CDI. Stimulation of the thirst centre may play a role with opioids while a decrease in urine output may be the mechanism with NSAIDs.