Metagenomic analysis reveals crosstalk between gut microbiota and glucose-lowering drugs targeting the gastrointestinal tract in Chinese patients with type 2 diabetes: a 6 month, two-arm randomised trial.

AIMS/HYPOTHESIS: The use of oral glucose-lowering drugs, particularly those designed to target the gut ecosystem, is often observed in association with altered gut microbial composition or functional capacity in individuals with type 2 diabetes. The gut microbiota, in turn, plays crucial roles in the modulation of drug efficacy. We aimed to assess the impacts of acarbose and vildagliptin on human gut microbiota and the relationships between pre-treatment gut microbiota and therapeutic responses. METHODS: This was a randomised, open-labelled, two-arm trial in treatment-naive type 2 diabetes patients conducted in Beijing between December 2016 and December 2017. One hundred participants with overweight/obesity and newly diagnosed type 2 diabetes were recruited from the Pinggu Hospital and randomly assigned to the acarbose (n=50) or vildagliptin (n=50) group using sealed envelopes. The treatment period was 6 months. Blood, faecal samples and visceral fat data from computed tomography images were collected before and after treatments to measure therapeutic outcomes and gut microbiota. Metagenomic datasets from a previous type 2 diabetes cohort receiving acarbose or glipizide for 3 months were downloaded and processed. Statistical analyses were applied to identify the treatment-related changes in clinical variables, gut microbiota and associations. RESULTS: Ninety-two participants were analysed. After 6 months of acarbose (n=44) or vildagliptin (n=48) monotherapy, both groups achieved significant reductions in HbA1c (from 60 to 46 mmol/mol [from 7.65% to 6.40%] in the acarbose group and from 59 to 44 mmol/mol [from 7.55% to 6.20%] in the vildagliptin group) and visceral fat areas (all adjusted p values for pre-post comparisons <0.05). Both arms showed drug-specific and shared changes in relative abundances of multiple gut microbial species and pathways, especially the common reductions in Bacteroidetes species. Three months and 6 months of acarbose-induced changes in microbial composition were highly similar in type 2 diabetes patients from the two independent studies. Vildagliptin treatment significantly enhanced fasting active glucagon-like peptide-1 (GLP-1) levels. Baseline gut microbiota, rather than baseline GLP-1 levels, were strongly associated with GLP-1 response to vildagliptin, and to a lesser extent with GLP-1 response to acarbose. CONCLUSIONS/INTERPRETATION: This study reveals common microbial responses in type 2 diabetes patients treated with two glucose-lowering drugs targeting the gut differently and acceptable performance of baseline gut microbiota in classifying individuals with different GLP-1 responses to vildagliptin. Our findings highlight bidirectional interactions between gut microbiota and glucose-lowering drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02999841 FUNDING: National Key Research and Development Project: 2016YFC1304901.

Relationship between periodontal status and dyslipidemia in patients with type 2 diabetic nephropathy and chronic periodontitis: A cross-sectional study.

OBJECTIVE: The aim of this study was to investigate the association between periodontitis and total serum cholesterol level in patients with type 2 diabetic nephropathy (T2DN). BACKGROUND: Periodontitis is now recognized as the sixth complication of diabetes and can also affect other complications of diabetes, including nephropathy and coronary artery diseases. Studies have considered dyslipidemia as a risk factor for exacerbation of periodontitis. METHODS: A total of 119 T2DN patients with chronic periodontitis were included in this observational study. Participants were stratified into the Normal (serum total cholesterol <5.17 mmol/L, n = 89) and the Dyslipidemia groups (serum total cholesterol ≥5.17 mmol/L, n = 30). Participants completed a validated questionnaire that collected information on oral hygiene behaviors and knowledge of oral health and underwent a clinical oral examination. The number of remaining teeth, probing depth (PD), clinical attachment level (CAL), and bleeding index (BI) was recorded. Physical examination and laboratory tests (fasting plasma glucose, serum glycosylated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglyceride, and high-sensitivity C-reactive protein levels) were performed. RESULTS: Means of CAL and BI were significantly higher in the Dyslipidemia group compared with the Normal group. In the Dyslipidemia group, PD and percent of sites with PD ≥4 mm were positively correlated with urinary albumin/creatinine ratios; PD and percent of sites with PD ≥4 and PD ≥5 mm were positively correlated with HbA1c level; a number of remaining teeth were negatively correlated with serum LDL-C level. After adjusting for age, gender, body mass index, smoking, FPG, and serum HbA1c and triglyceride levels, BI was found to be positively associated with dyslipidemia in T2DN patients with periodontitis. CONCLUSION: T2DN patients with chronic periodontitis had a 2.355-fold higher risk of developing dyslipidemia, implying an important relationship between periodontitis and blood lipid control among T2DN patients.

Duret hemorrhage after lumbar drainage.

Lumbar drainage (LD) is considered as a simple and effective procedure for the treatment of intracerebral hemorrhage with ventricular involvement. However, cerebrospinal fluid overdrainage and hypovolemia due to LD could induce severe fatal complications, which include transtentorial herniation and infratentorial hemorrhage. Here, we describe a 63-year-old man with transtentorial herniations and Duret hemorrhage attributable to LD after the operation of thalamic hematoma removal. This is probably the first reported case of severe complications of LD. Thus, complications related to transtentorial herniations and Duret hemorrhage should be kept in mind while performing LD.

The impact of ferritin on the disassociation of HbA1c and mean plasma glucose.

OBJECTIVE: To explore the impact of ferritin level on the disassociation of glycated hemoglobin A1c (HbA1c) and mean plasma glucose (MPG). RESEACH DESIGN AND METHODS: We used a 2012-2013 cross-sectional survey conducted in Pinggu district, Beijing including 3095 Chinese participants aged 25-75 years. We categorized their glycemic status by interviewing for diagnosed diabetes and by measuring HbA1c, fasting plasma glucose (FPG), and 2-hours post-load plasma glucose (2-hours PPG). We fitted a multivariable regression model to explore the impact of ferritin on the association of HbA1c or glycated albumin (GA) and mean plasma glucose. RESULTS: A total of 5.65% of participants were diagnosed as diabetes using HbA1c criteria, and 9.79% using oral glucose tolerance test criteria. Compared with males, females had significantly lower hemoglobin levels (159.82 ± 11.56 vs 135.93 ± 12.62) and lower ferritin levels (113.00 [68.55, 185.50] vs 33.40 [12.40, 70.13]). Linear regression analysis performed in different groups classified by different diagnose criterion indicated that the correlation between MPG and HbA1c differs in different tertiles of ferritin (lowest vs middle vs highest: R2 = 0.507 vs 0.645 vs 0.687 in female; R2 = 0.415 vs 0.715 vs 0.615 in male), and the association between MPG and HbA1c diminished in the lowest tertile of ferritin. CONCLUSIONS: Ferritin level might affect the association between glucose and HbA1c, which should be taken into account when using HbA1c as a diagnosis criterion for diabetes and prediabetes.

Search for clinical predictors of good glycemic control in patients starting or intensifying oral hypoglycemic pharmacological therapy: A multicenter prospective cohort study.

AIMS: Our aim was to search for clinical predictors of good glycemic control in patients starting or intensifying oral hypoglycemic pharmacological therapy. METHODS: A multicenter, prospective cohort of 499 diabetic subjects was enrolled in this study: patients with newly diagnosed diabetes (NDM group) or poor glycemic control with oral antidiabetic drugs (OADs) (PDM group). All subjects then started or intensified OADs therapy and followed up for 91 days. Glycemic control was determined according to HbA1c at day 91 with HbA1c <7% considered good. RESULTS: The proportions of patients with good glycemic control after follow up for 91 days were 66.9% and 34.8% in NDM group and PDM group respectively. Logistic regression analysis showed that the change in GA at 28 days was the only predictor of good glycemic control in NDM patients (OR = 1.630, 95% CI 1.300-2.044, P < 0.001). In PDM patients, changes in GA at 28 days, CPI, baseline HbA1c, diabetic duration, and BMI were all independent predictors of good glycemic control (All P < 0.05). CONCLUSIONS: GA decline is a good predictor of future success in newly diagnosed patients. In patients intensifying therapy, beside GA decline, other individualized clinical characteristics should also be considered.

Association between serum uric acid and large-nerve fiber dysfunction in type 2 diabetes: a cross-sectional study.

BACKGROUND: Large-nerve fiber dysfunction, as assessed by vibration perception threshold (VPT) predicts risks of ulceration, amputation, and mortality in diabetes. Serum uric acid (UA) is closely associated with various metabolic disorders, especially diabetes. Thus, we sought to investigate the clinical relevance of UA to large-nerve fiber dysfunction, among patients with type 2 diabetes (T2D). METHODS: Medical records of consecutive patients with T2D who were admitted to Beijing Friendship Hospital Pinggu Campus between May 2014 and December 2016 were collected. Data for the 824 eligible patients included in the final analysis were extracted using a structured form. A VPT value ≥15 in either foot was defined as abnormal. We compared the clinical characteristics between patients with abnormal VPT and those with normal VPT (VPT value <15 in both feet) in the overall population and in gender subgroups. Logistic regression analysis was performed to explore the association of abnormal VPT with UA level. One-way analysis of variance was used to compare VPT values across four UA quartiles. RESULTS: UA levels were significantly lower in T2D patients with abnormal VPT than in those with normal VPT (294.5 ±â€Š84.0 vs. 314.9 ±â€Š92.8 µmol/L, P < 0.01), especially among male patients (311.7 ±â€Š85.2 vs. 336.9 ±â€Š89.6 µmol/L, P < 0.01). From the logistic regression analysis, hyperuricemia (males >420 µmol/L; females >360 µmol/L) was associated with a reduced risk of abnormal VPT (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.39-0.91; P < 0.05). This association was robust in male patients (OR, 0.43; 95% CI, 0.24-0.76; P < 0.01) but not in female patients (OR, 0.92; 95% CI, 0.47-1.82; P = 0.816), even after adjustment for confounding factors. For the younger male subgroup (age <65 years), VPT values decreased as the UA level increased (P for trend = 0.002), but this trend was not significant in older male subgroup (age ≥65 years; P for trend = 0.400). CONCLUSIONS: Low serum UA levels showed a significant association with an increased risk of large-nerve fiber dysfunction in male patients with T2D, but not in female patients with T2D. In addition, in only the younger subgroup of male patients (<65 years), lower levels of UA also correlated with higher VPT values.

Glycated albumin is superior to glycated hemoglobin for glycemic control assessment at an early stage of diabetes treatment: A multicenter, prospective study.

AIMS: This study was to determine whether serum glycated albumin (GA) was a better indicator of glycemic control than hemoglobin A1c (HbA1c) when starting a new treatment regimen for type 2 diabetes. METHODS: Newly diagnosed type 2 diabetes patients, or patients who had poor glycemic control with oral hypoglycemic agents, were enrolled at 10 hospitals in Beijing. Serum GA, HbA1c, fasting blood glucose (FBG), and C-peptide were assayed on Days 0, 14, 28, and 91 after treatment. RESULTS: Four hundred ninety-nine patients were enrolled. Mean FBG, GA and HbA1c decreased significantly in patients at Days 14, 28, and 91. In patients with improved glycemic control, the reduction of GA and HbA1c levels was 10.5±13.3% vs. 5.1±5.4% on Day 14, 16.0±13.4% vs. 9.0±7.0% on Day 28, and 18.0±16.7% vs. 18.3±9.4% on Day 91, respectively, compared with baseline values. Changes in GA on Day 14, 28 and 91 were all closely correlated with changes in HbA1c on Day 91. Change in GA on Day 14 was correlated with treatment effectiveness evaluated by HbA1c on Day 91. CONCLUSIONS: GA may be a useful marker for assessing glycemic control at an early stage of new diabetes treatment and assist in guiding adjustments to treatment and therapy.