Type 1 diabetes induced by immune checkpoint inhibitors / 中华医学杂志(英文版)

With the increasing use of immune checkpoint inhibitors (ICI) including anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) in cancers, ICI-induced type 1 diabetes has been reported throughout the world. In this review, we aim to summarize the characteristics of this disease and discuss the mechanism of it. As an immune-related adverse event, type 1 diabetes developed after the administration of anti-PD-1 or anti-PD-ligand 1 (PD-L1) in the combination with or without anti-CTLA-4. It usually presented with acute onset, and 62.1% of the reported cases had diabetic ketoacidosis. Only a third of them had positive autoantibodies associated with type 1 diabetes. Susceptible HLA genotypes might be associated. T-cell-stimulation by blocking of the interaction of PD-1 and PD-L1 in pancreatic β cells was the main mechanism involved in the pathology. Insulin was the only effective treatment of ICI-induced type 1 diabetes. In conclusions, ICI-induced type 1 diabetes is a potentially life-threating adverse event after the immunotherapy of cancers. Screening and early recognition is important. Further investigation of the mechanism may help to better understand the pathology of type 1 diabetes.

Comparison of Placebo Effect between Asian and Caucasian Type 2 Diabetic Patients: A Meta-Analysis / 中华医学杂志(英文版)

<p><b>Background</b>Placebo was defined as any therapy that is used for its nonspecific psychological and physiologic effect but has no specific pharmacologic impact on the condition being treated. Besides medication therapies, studies have found that the optimal dietary approach as well as physical activity and education are useful to control hyperglycemia in patients with type 2 diabetes (T2DM). The aim of this study was to evaluate the placebo effects of antidiabetic therapies in Asian and Caucasian T2DM patients and make a comparison between the two ethnicities.</p><p><b>Methods</b>A search using the MEDLINE database, EMBASE, and Cochrane Database was performed, from when recording began until December 2016. The main concepts searched in English were sulfonylurea (SU); alpha glucosidase inhibitors (AGI); metformin (MET); thiazolidinediones (TZD); dipeptidyl peptidase-4 inhibitors (DPP-4i); sodium-glucose cotransporter 2 inhibitors (SGLT2i); glucagon-like peptide-1 receptor agonist (GLP-1RA); type 2 diabetes (T2DM); placebo controlled; and randomized controlled trials. Using the Cochrane instrument, we evaluated the adequacy of randomization, allocation concealment procedures, and blinding.</p><p><b>Results</b>This study included 63 studies with a total of 7096 Asian patients involved and 262 studies with a total of 27,477 Caucasian patients involved. In Caucasian population, the use of placebo led to significant reductions of glycosylated hemoglobin (HbA1c), -0.683% (P = 0.008) in SU monotherapy treatment, -0.193% (P = 0.001) in DPP-4i treatment, and -0.230% (P < 0.001) in SGLT2i treatment, respectively. In Asian population, the use of placebo resulted in significant decreases of HbA1c, -0.162% (P = 0.012) in DPP-4i treatment and -0.269% (P = 0.028) in GLP-1RA add-on therapy, respectively. The placebo also significantly reduced body weight. In Caucasian population, placebo use resulted in 0.833 kg (P = 0.006) weight loss by SU treatment and 0.953 kg (P = 0.006) weight loss by GLP-1RA treatment. In Asian population, the placebo led to a weight change of 0.612 kg (P < 0.001) by GLP-1RA analog treatment. The changes of HbA1c and weight due to the placebo effect in other treatments were not significant in both Asian and Caucasian population. Comparisons of the placebo effect on HbA1c change and weight change in each treatment group indicated that no significant difference was found between Asian and Caucasian population.</p><p><b>Conclusions</b>The overall differences of the placebo effect on HbA1c changes as well as on body weight changes were not significant between Asian and Caucasian T2DM patients. The placebo effect on HbA1c changes and weight changes was not associated with baseline age, gender, baseline body mass index, baseline HbA1c, duration of diabetes, or study duration.</p>

Efficacy and safety of avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone: a multicenter, randomized, controlled trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>At present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone.</p><p><b>METHODS</b>This study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment.</p><p><b>RESULTS</b>At week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 μU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 μU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups.</p><p><b>CONCLUSIONS</b>Compared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated.</p><p><b>REGISTRATION NUMBER</b>ChiCTR-TRC-13003776.</p>

Efficacy and safety of insulin treatment in type 2 diabetes using a new index called glucose safety control index / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To recommend an index named glucose safety control index (GSCI) to evaluate the efficacy and safety for insulin regimens.</p><p><b>DATA SOURCES</b>We searched databases for primary studies published in English. The main search concepts were type 2 diabetes, insulin treatment, premixed insulin, premixed insulin analogs, basal inuslin, basal inuslin analogs, bolus insulin, bolus insulin analogs, safety and efficacy.</p><p><b>STUDY SELECTION</b>Studies were eligible for inclusion if they met all of the following criteria: (1) type 2 diabetic patients aged >18 years were included; (2) random control studies with at least 12 weeks of follow-up; (3) different insulin regimens were evaluated.</p><p><b>RESULTS</b>When long-acting basal insulin therapy compared with neutral protamine Hagedorn (NPH) insulin therapy, the proportion of GSCI%A1c ratio more than 1 was 100%, the proportion of GSCIΔA1c ratio more than 1 was 94.44%. When premixed insulin therapy compared with oral hypoglycemic agents plus basal insulin therapy, the proportion of GSCI%A1c ratio more than 1 was 45.5%, the proportion of GSCIΔA1c ratio more than 1 was 38.9%. When premixed insulin therapy compared with oral hypoglycemic agents, the proportion of GSCI%A1c ratio less than 1 was 100%, the proportion of GSCIΔA1c ratio more than 1 was 50%. When premixed insulin therapy compared with basal-bolus insulin therapy, the proportion of GSCI%A1c ratio more than 1 was 37.5%, the proportion of GSCIΔA1c ratio more than 1 was 50%.</p><p><b>CONCLUSION</b>According to the GSCI ratio, long-acting basal insulin therapy tended to be superior to NPH therapy, oral hypoglycemic agents plus basal insulin therapy tended to be superior to premixed insulin therapy, noninsulin antidiabetic agents and premixed insulin therapy was comparable, and basal-bolus insulin therapy tended to be superior to premixed insulin therapy in type 2 diabetes.</p>

High-normal serum uric acid is associated with albuminuria and impaired glomerular filtration rate in Chinese type 2 diabetic patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recently, some studies had shown that elevated serum uric acid (SUA) itself may increase the risk for development of renal disease in patients with diabetes. This study aimed to explore whether SUA was a predictor of microalbuminuria and impaired renal function in type 2 diabetes in Chinese patients.</p><p><b>METHODS</b>This cross-sectional study included 2108 type 2 diabetic patients. Kidney function was estimated using the simplified modification of diet in renal disease (MDRD) equation to obtain estimated glomerular filtration rate. The urine samples were obtained for measuring the albumin-to-creatinine ratio (ACR).</p><p><b>RESULTS</b>According to the ACR level, these patients were divided into two groups, normal ACR (NA) and non-normal ACR (non-NA). Both SUA and creatinine were significantly higher in the non-NA group than those in the NA group ((318.89 ± 107.52) vs. (283.44 ± 88.64) µmol/L, and (95.08 ± 53.24) vs. (79.63 ± 18.20) µmol/L, respectively). Logistic regression analysis showed that diabetic duration, systolic blood pressure, creatinine and SUA were the independent predictors of albuminuria. Furthermore, to identify the factors associated with renal function, these patients were divided into two groups according to the MDRD level (MDRD < 90 or MDRD ≥ 90). Both SUA and creatinine were significantly higher in the lower MDRD group than those in the higher MDRD group ((301.90 ± 96.46) vs. (264.07 ± 84.74) µmol/L, and (89.10 ± 31.00) vs. (66.37 ± 11.15) µmol/L, respectively). Logistic regression analysis showed that only age and SUA were the independent predictors of MDRD.</p><p><b>CONCLUSION</b>High-normal SUA was associated with albuminuria and impaired glomerular filtration rate in Chinese type 2 diabetic patients.</p>

Association between serum uric acid and different states of glucose metabolism and glomerular filtration rate / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recently, it has been suggested that the serum uric acid (SUA) level decreased in diabetic patients. The aim of this study was to explore the association between SUA level and different state of glucose metabolism and glomerular filtration rate (GFR) reflected by the simplified Modification of Diet in Renal Disease (MDRD) equation and to test the hypothesis that high MDRD is one of the determinants of SUA level.</p><p><b>METHODS</b>This cross-sectional study included 2373 subjects in Beijing who underwent a 75 g oral glucose tolerance test (OGTT) for screening of diabetes. According to the states of glucose metabolism, they were divided into normal glucose tolerance, impaired glucose regulation and diabetes.</p><p><b>RESULTS</b>Multiple stepwise linear regression analysis showed that adjusted by gender, SUA was positively correlated with body mass index (BMI), waist/hippo ratio, systolic blood pressure (SBP) and triglyceride, meanwhile negatively correlated with age, hemoglobin A1c, fasting insulin and MDRD. There was an increasing trend in SUA concentration and a decreasing trend in MDRD when the levels of fasting plasma glucose (FPG) increased from low to high up to the FPG level of 8.0 mmol/L; thereafter, the SUA concentration started to decrease with further increases in FPG levels, and the MDRD started to increase with further increases in FPG levels.</p><p><b>CONCLUSION</b>This study confirmed the previous finding that SUA decreased in diabetes and provided the supporting evidence that the increased MDRD might contribute to the fall of SUA.</p>

Risk factors of diabetic retinopathy in type 2 diabetic patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Advances in treatment have greatly reduced the risk of blindness from this disease, but because diabetes is so common, diabetic retinopathy remains an important problem. The purpose of this study is to investigate the risk factors of diabetic retinopathy (DR) in Chinese type 2 diabetic patients.</p><p><b>METHODS</b>Totally 746 type 2 diabetic patients were selected for biochemical and clinical characteristics test and examined by the retina-camera for diabetic retinopathy and the average age was 55.9 years old.</p><p><b>RESULTS</b>A total of 526 patients was classified as non-DR, 159 patients as non-proliferative-DR and 61 patients as proliferative-DR. Duration of diabetes [(66.09 +/- 72.51) months vs (143.71 +/- 93.27) months vs (174.30 +/- 81.91) months, P = 0.00], systolic blood pressure [(131.95 +/- 47.20) mmHg vs (138.71 +/- 21.36) mmHg vs (147.58 +/- 24.10) mmHg, P = 0.01], urine albumin [(32.79 +/- 122.29) mg/L vs (190.96 +/- 455.65) mg/L vs (362.00 +/- 552.51) mg/L, P = 0.00], glycated hemoglobin (HbA1c) [(8.68 +/- 2.26)% vs (9.42 +/- 1.84)% vs (9.42 +/- 1.96)%, P = 0.04], C-reactive protein (CRP) [(3.19 +/- 7.37) mg/L vs (6.36 +/- 23.59) mg/L vs (3.02 +/- 4.34) mg/L, P = 0.03], high-density lipoprotein cholesterol (HDL-C) [(1.23 +/- 0.37) mmol/L vs (1.33 +/- 0.35) mmol/L vs (1.24 +/- 0.33) mmol/L, P = 0.01], uric acid (UA) [(288.51 +/- 90.85) mmol/L vs (300.29 +/- 101.98) mmol/L vs (337.57 +/- 115.09) mmol/L, P = 0.00], creatinine (CREA) [(84.22 +/- 16.31) micromol/L vs (89.35 +/- 27.45) micromol/L vs (103.28 +/- 48.64) micromol/L, P = 0.00], blood urine nitrogen (BUN) [(5.62 +/- 1.62) mmol/L vs (6.55 +/- 2.74) mmol/L vs (8.11 +/- 3.60) mmol/L, P = 0.00] were statistically different among the three groups. Logistic regression analysis showed that diabetic duration and urine albumin were two independent risk factors of DR (the OR values were 1.010 and 1.003 respectively).</p><p><b>CONCLUSIONS</b>Diabetic duration and urine albumin are two independent risk factors of diabetic retinopathy in elderly type 2 diabetic patients.</p>