Experimental and Clinical Endocrinology & Diabetes最新文献

Aims: This study investigated brain structure in patients of type 1 diabetes with diabetic peripheral neuropathy (DPN) and type 1 diabetes with neuropathic pain and the associations to clinical, peripheral, and cognitive measurements.

Methods: Sixty individuals with type 1 diabetes and 20 healthy controls were included in the study. Nineteen individuals with type 1 diabetes and neuropathic pain, 19 with type 1 diabetes and DPN, 18 with type 1 diabetes without DPN, and 20 healthy controls were included in the brain analyses. We utilized structural brain magnetic resonance imaging to investigate total and regional gray matter volume.

Results: Significant lower gray matter volume was found in type 1 diabetes with neuropathic pain and in type 1 diabetes without DPN compared to healthy controls (p=0.024 and p=0.019, respectively). Lower insula volume was observed in all three diabetes groups (all p≤0.050). Thalamus and hippocampus volume was lower in type 1 diabetes with neuropathic pain, cerebellum volume was lower in type 1 diabetes with DPN, and somatosensory cortex volume was lower in type 1 diabetes without DPN (all p≤0.018). Attenuated memory was associated with lower gray matter volume in type 1 diabetes with DPN. No associations were found between gray matter volume and clinical/peripheral measurements.

Conclusion: We demonstrated lower gray matter volume in individuals with type 1 diabetes regardless of the presence of DPN and neuropathic pain. Hence, central gray matter alteration was not associated with peripheral alterations.

Objective: Diabetic cardiomyopathy (DCM) constitutes a primary cause of mortality in diabetic patients. Histone deacetylase (HDAC) inhibition can alleviate diabetes-associated myocardial injury. This study investigated the mechanism of HDAC1 on myocardial fibrosis (MF) in DCM.

Methods: A murine model of DCM was established by a high-fat diet and streptozotocin injection. The bodyweight, blood glucose, serum insulin, and cardiac function of mice were analyzed. Lentivirus-packaged sh-HDAC1 was injected into DCM mice and high glucose (HG)-induced cardiac fibroblasts (CFs). The pathological structure of the myocardium and the level of myocardial fibrosis were observed by histological staining. HDAC1 expression in mouse myocardial tissues and CFs was determined. Collagen I, collagen III, alpha-smooth muscle actin (α-SMA), and vimentin levels in CFs were detected, and CF proliferation was tested. HDAC activity and histone acetylation levels in tissues and cells were measured. Bone morphogenetic protein-7 (BMP-7) expression in myocardial tissues and CFs was determined. Functional rescue experiments were conducted to confirm the effects of histone acetylation and BMP-7 on myocardial fibrosis.

Results: DCM mice showed decreased bodyweight, elevated blood glucose and serum insulin, and cardiac dysfunction. Elevated HDAC1 and reduced BMP-7 expressions were detected in DCM mice and HG-induced CFs. HDAC1 repressed BMP-7 transcription through deacetylation. HDAC1 silencing alleviated MF, reduced CF proliferation and decreased collagen I, -III, α-SMA, and vimentin levels. However, reducing histone acetylation level or BMP-7 downregulation reversed the effects of HDAC1 silencing on CF fibrosis.

Conclusion: HDAC1 repressed BMP-7 transcription by enhancing histone deacetylation, thereby promoting MF and aggravating DCM.

Aims: To describe dispensation patterns of glucose-lowering drugs in newly diagnosed type 2 diabetes in Germany.

Materials and methods: Based on claims data from four statutory health insurances (German Pharmacoepidemiological Research Database,>25 million insurants), all individuals with newly diagnosed type 2 diabetes were identified. Eligible patients had a first diagnosis for type 2 diabetes between January 2012 and December 2016. We analyzed the dispensation patterns of first-line glucose-lowering therapies initiated in the year after diabetes diagnosis and patterns of second-line therapies dispensed one year after first-line treatment.

Results: A total of 356,647 individuals with newly diagnosed type 2 diabetes were included (average age [SD]: 63.5 [13.4] years; 49.3% males). Of the 31.6% of individuals who were pharmacologically treated in the year after diagnosis, metformin monotherapy was most frequently dispensed (73.1%), followed by dual therapy of metformin and dipeptidyl peptidase-4 inhibitors (DPP-4is) (6.4%), and monotherapy with DPP-4is (2.9%). From 2012 through 2016, sulfonylurea dispensations were reduced by more than 50%. Dispensations for combination therapies with DPP-4is increased up to 10.6%. Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors contributed to 2% of all treatments. After a median of 5 months, 20.0% of individuals on pharmacological therapy initiated second-line glucose-lowering treatment.

Conclusions: Data from German statutory health insurances (2012 to 2016) showed that most individuals with newly diagnosed type 2 diabetes were dispensed metformin monotherapy in line with diabetes care guidelines. A substantial decrease in the use of sulfonylureas was observed after the introduction of DPP-4i and GLP-1 receptor agonists.

During the COVID-19 pandemic, there were increased concerns about glycemic control in patients with diabetes. Therefore, we aimed to assess changes in diabetes management during the COVID-19 lockdown for patients with type 1 or type 2 diabetes mellitus (T1DM, T2DM) in Germany. We included data from 24,623 patients (age>18 years) with T1DM (N=6,975) or T2DM (N=17,648) with documented data in 2019 and 2020 from the multicenter Diabetes-Prospective Follow-up registry (DPV). We conducted a groupwise comparison of identical patients in 2019 and 2020 for different time periods of pandemia. Pairwise differences of continuous parameters of treatment modalities and metabolic outcome between 2019 and 2020 were adjusted for seasonality, age, and diabetes duration. We presented these outcomes as adjusted medians with 95% confidence intervals. Rates were compared using negative-binomial models, dichotomous outcomes were compared using logistic models. Models were additionally adjusted for age and diabetes duration. These outcomes were presented as least-square means with 95% confidence intervals, p-values of<.05 were considered significant.In participants with T1DM, CGI (combined glucose indicator) increased only by 0.11-0.12% in all time periods of 2020 compared to 2019 (all p<0.001) while BMI decreased slightly by -(0.09-0.10) kg/m² (p<0.0001). In participants with T2DM, HbA1c increased by 0.12%, while BMI decreased slightly by -(0.05-0.06) kg/m² (p<0.0001).During the COVID-19 lockdown period, patients with T1DM and T2DM experienced only clinically insignificant changes in glucose control or body weight. Despite lockdown restrictions, patients were able to maintain metabolic control.

Aims: The Virtual Diabetes Outpatient Clinic for Children and Adolescents (VIDIKI) study was a 6-month quasi-randomized, multicentre study followed by an extension phase to evaluate the effects of monthly video consultations in addition to regular care. A health economic analysis was conducted to assess the direct costs.

Methods: The cost data of 240 study participants (1-16 years of age) with type 1 diabetes who were already using a continuous glucose monitoring system were collected in the first 6 months of the study. The intervention group (IG) received monthly video consultations plus regular care, and the waiting control group (WG) received only regular care. Cost data were collected for a comparable anonymized group of children from the participating health insurance companies during the 6-month period before the study started (aggregated data group [AG]).

Results: Cost data were analysed for the AG (N=840) 6 months before study initiation and those for the study participants (N=225/240). Hospital treatment was the highest cost category in the AG. There was a cost shift and cost increase in the IG and WG, whereby diabetes supplies were the highest cost category. The mean direct diabetes-associated 6-month costs were € 4,702 (IG) and € 4,936 (WG).

Conclusion: The cost development within the cost collection period over two years possibly reflects the switch to higher-priced medical supplies. Video consultation as an add-on service resulted in a small but nonsignificant reduction in the overall costs.

FAM3A is a recently identified mitochondrial protein that stimulates pancreatic-duodenal homeobox 1 (PDX1) and insulin expressions by promoting ATP release in islet β cells. In this study, the role of intracellular ATP in FAM3A-induced PDX1 expression in pancreatic β cells was further examined. Acute FAM3A inhibition using siRNA transfection in mouse pancreatic islets significantly reduced PDX1 expression, impaired insulin secretion, and caused glucose intolerance in normal mice. In vitro, FAM3A overexpression elevated both intracellular and extracellular ATP contents and promoted PDX1 expression and insulin secretion. FAM3A-induced increase in cellular calcium (Ca²⁺) levels, PDX1 expression, and insulin secretion, while these were significantly repressed by inhibitors of P2 receptors or the L-type Ca²⁺ channels. FAM3A-induced PDX1 expression was abolished by a calmodulin inhibitor. Likewise, FAM3A-induced β-cell proliferation was also inhibited by a P2 receptor inhibitor and an L-type Ca²⁺ channels inhibitor. Both intracellular and extracellular ATP contributed to FAM3A-induced PDX1 expression, insulin secretion, and proliferation of pancreatic β cells.

Objective: Jordan has a high prevalence of painful diabetic peripheral neuropathy (PDPN), leg complications, and amputations due to diabetes. This study evaluated the effect of educational programs on pain management, self-efficacy behaviors, and quality of life (QoL) among adult patients with PDPN.

Methods: The randomized controlled trial study was conducted at the Jordanian Ministry of Health hospitals between October 2019 - March 2020. Seventy-two adult patients with PDPN were randomized to an experimental group of 36 patients who attended an educational program and a control group who followed routine diabetic care in the study setting. The data were collected using a socio-demographic and diabetes clinical/laboratory data form, the numeric rating scale (NRS), diabetes self-efficacy scale (DSES), and the quality-of-life questionnaire (EQ-5D). The intervention program consisted of four educational sessions at weekly intervals. Pre-test and post-test evaluations were conducted.

Results: After the educational intervention, the mean scores of the NRS (p=0.020), DSES (p<0.001), and EQ-5D (p<0.001) in the experimental group improved significantly improved compared to those in the control group. Additionally, while there were no significant correlations between the three study outcomes in the pre-test stage, correlations were observed to be significant after the educational intervention.

Conclusion: This study shows that the design and implementation of educational intervention combined with routine diabetic care facilitate effective pain management, self-efficacy behaviors, and QoL of patients with PDPN. The health care providers are recommended to use the educational programs for such patients at various levels of services in both health centers and diabetes clinics.

Background: The association between type 2 diabetes mellitus (T2DM) and advanced stages of non-alcoholic fatty liver disease is well known. Some studies indicate a relevant prevalence also in type 1 diabetes mellitus (T1DM), but so far there is only limited data.

Objective: To determine the prevalence of non-alcoholic fatty liver disease (NAFLD)-related liver fibrosis in individuals with T1DM and compare to those with type 2 diabetes.

Methods: Diabetic patients from a single diabetes care centre were screened for liver fibrosis by sonographic shear wave elastography (SWE). In addition, all patients received laboratory evaluation including non-alcoholic fatty liver fibrosis score and Fibrosis-4 Index.

Results: Three hundred and forty patients were included in the study, of these, 310 received SWE. Overall 254 patients (93 with type 1 and 161 with type 2 diabetes) had reliable measurements and were included in the final analysis. In patients with type 1 diabetes, the prevalence of NAFLD-related liver fibrosis was 16-21%, depending on the method of detection. Significant liver fibrosis was observed in 30-46% of patients with type 2 diabetes.

Conclusions: Our data revealed an unexpectedly high prevalence of NAFLD-related liver fibrosis in patients with type 1 diabetes. To our knowledge, this is one of the first studies using SWE to diagnose advanced NAFLD in type 1 diabetes in a non-preselected cohort. Considering the findings of our study, regular screening for hepatic complications must be recommended for all diabetic patients, even for those with type 1 diabetes.

Aim: To investigate the alterations in the plantar fascia (PF), intrinsic muscles, and tendons in the feet of patients at high risk for developing diabetic foot.

Methods: The healthy feet of 22 patients with type 2 diabetes, who had developed diabetic foot ulcers on a single foot without any pathology on the contralateral extremity, and those of 22 healthy volunteers were evaluated by magnetic resonance imaging. The volume of the Achilles tendon (AT), the surface area of the PF, the thickness of AT, flexor hallucis longus, flexor digitorum longus, tibialis posterior, and peroneus longus tendons, irregularity in the PF, and edema of intrinsic foot muscles were examined.

Results: Nineteen patients (86%) had irregularity in the PF, whereas none of the healthy controls had any (p<0.001). Intrinsic muscle edema was more common in the group with diabetes (p=0.006). The volume of AT and the surface area of PF were decreased in patients with peripheral arterial disease (PAD) (p<0.05). Patients with diabetes mellitus but without PAD had a larger surface area of PF than that of controls (p<0.05). There were no differences in the volume of AT, the surface area of the PF, and other tendon thickness between the groups.

Conclusion: Irregularity in the PF and muscle edema may indicate a high risk for the diabetic foot. The presence of PAD may lead to regression in the structure of AT and PF.