Efficacy and safety of ultra rapid lispro in the treatment of type 2 diabetes mellitus: a randomized controlled clinical trial / 中华内科杂志

Objective:To evaluate and compare the efficacy and safety of ultra-rapid lispro insulin (URLi) and humalog lispro (HL) in the treatment of type 2 diabetes mellitus.Methods:This was an international multicenter, double-blind, randomized controlled study. From May 2019 to January 2021, a total of 481 patients with type 2 diabetes mellitus, who had been using insulin for at least 90 days and had poor glycemic control, were included. These patients were recruited from 34 research centers in China, including Shanghai Jiao Tong University School of Medicine Affiliated Sixth People′s Hospital. They were assigned to either the URLi group (319 patients) or the HL group (162 patients) using stratified blocked randomization. The primary endpoint was the change in hemoglobin A 1c (HbA 1c) relative to baseline after 26 weeks of treatment. Secondary endpoints included the proportion of patients who achieved HbA 1c<7.0% and ≤6.5% after 26 weeks of treatment, 1-h postprandial glucose (1hPG) or 2-h postprandial glucose (2hPG) excursions during a mixed meal tolerance test at week 26, as well as safety parameters. Continuous variables were compared using mixed model repeated measures or analysis of covariance, and categorical variables were compared using logistic regression or Fisher′s exact test. Results:Data based on the Chinese subgroup showed that there were no statistically significant differences between the URLi and HL groups in terms of male percentage [56.1% (179/319) vs. 56.2% (91/162); P=0.990], age [(59.5±8.4) vs. (59.6±9.3) years; P=0.839] and other baseline characteristics. Regarding the change in HbA 1c relative to baseline, the URLi group was non-inferior to the HL group (-0.59%±0.05% vs. -0.66%±0.06%; P=0.312). There were no statistically significant differences between the URLi and HL groups in proportion of patients who achieved HbA 1c<7.0% [47.3% (138/292) vs. 45.2% (70/155); P=0.907] and≤6.5% [27.7% (81/292) vs. 27.7% (43/155); P=0.816]. The excursions in 1hPG [(6.20±0.21) vs. (6.90±0.25) mmol/L; P=0.001] and 2hPG [(8.10±0.27) vs. (9.30±0.31) mmol/L; P<0.001] were lower in the URLi group than the HL group, with statistically significant differences. In terms of safety, there were no statistically significant differences in the percentage of subjects who reported treatment-emergent adverse events between the URLi and HL groups [49.8% (159/319) vs. 50.0% (81/162); P=1.000]. The event rate of nocturnal hypoglycemia was lower in the URLi group than the HL group, with statistically significant differences [(0.53±0.10) vs. (0.89±0.16) events per patient -year; P=0.040]. Conclusions:With good glycemic control, URLi showed non-inferiority for HbA 1c improvement versus HL and was superior to HL for postprandial glucose excursion control. Meanwhile the rate and incidence of nocturnal hypoglycemia were lower in the URLi group than the HL group.

Management of primary adrenal lymphoma with intracranial invasion / 中华内分泌代谢杂志

Primary adrenal lymphoma (PAL) is a rare extranodular lymphoma. It is subject to misdiagnosis due to atypical clinical and imaging features. Histopathology is required to establish the diagnosis. Patients often present to the Endocrinology Department upon revelation of adrenal incidentalomas by imaging. PAL is often accompanied by invasion of other tissues and organs, with a high mortality rate and a poor prognosis. In this paper, the clinical features of a patient with primary adrenal lymphoma and intracranial invasion were summarized, and the pathogenesis, clinical manifestations, diagnosis and treatment of this disease were reviewed.

Decreasing complexity of glucose time series derived from continuous glucose monitoring is correlated with deteriorating glucose regulation / 医学前沿

Most information used to evaluate diabetic statuses is collected at a special time-point, such as taking fasting plasma glucose test and providing a limited view of individual's health and disease risk. As a new parameter for continuously evaluating personal clinical statuses, the newly developed technique "continuous glucose monitoring" (CGM) can characterize glucose dynamics. By calculating the complexity of glucose time series index (CGI) with refined composite multi-scale entropy analysis of the CGM data, the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes (P for trend < 0.01). Furthermore, CGI was significantly associated with various parameters such as insulin sensitivity/secretion (all P < 0.01), and multiple linear stepwise regression showed that the disposition index, which reflects β-cell function after adjusting for insulin sensitivity, was the only independent factor correlated with CGI (P < 0.01). Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.

Effectiveness of quality of care for patients with type 2 diabetes in China: findings from the Shanghai Integration Model (SIM) / 医学前沿

This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai, China. A total of 173 235 patients with type 2 diabetes in 2017 were included in the analysis. Profiles of risk factors and intermediate outcomes were determined. The patients had a mean age of 66.43 ± 8.12 (standard deviation (SD)) years and a mean diabetes duration of 7.95 ± 5.53 (SD) years. The percentage of patients who achieved the target level for HbA1c (< 7.0%) was 48.6%. Patients who achieved the target levels for blood pressure (BP) < 130/80 mmHg and low-density lipoprotein-cholesterol (LDL-c) < 2.6 mmol/L reached 17.5% and 34.0%, respectively. A total of 3.8% achieved all three target levels, and the value increased to 6.8% with an adaptation of the BP target level (< 140/90 mmHg) for those over 65 years. Multivariable analysis identified the factors associated with a great likelihood of achieving all three target levels: male, young age, short diabetes duration, low body mass index, macrovascular complications, no microvascular complications, prescribed with lipid-lowering medication, and no prescription of antihypertensive medication. In conclusion, nearly 50% and one-third of the patients with diabetes met the target levels for HbA1c and LDL-c, respectively, with a low percentage achieving the BP target level. The percentage of patients who achieved all three target levels needs significant improvement.

Comparison of efficacy and safety of insulin aspart injection Rishulin and NovoRapid for treatment of diabetes: a multicenter, randomized, open-labeled, controlled trial / 中华内科杂志

Objective:To compare the efficacy and safety of Tonghua Dongbao′s insulin aspart injection (Rishulin) and NovoRapid (Novo Nordisk) in the treatment of diabetes.Methods:A 26-week, randomized, open-label, parallel-group, positive control drug and non-inferiority trial was conducted in 23 centers in China. A total of 563 diabetes with poor blood glucose control treated with insulin for at least 3 months before were included. The subjects were randomized(stratified block random method) into those receiving Rishulin or NovoRapid at a ratio of 3∶1. Both groups were combined with basal insulin (Lantus). The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to the end of 24 weeks of treatment.Results:For full analysis set, after 24 weeks of treatment, HbA1c level of Ruishulin group decreased from (8.66±1.28)% to (7.77±1.09)% ( P<0.001), and that of NovoRapid group decreased from (8.47±1.28) % to (7.65±0.97) % ( P<0.001). Treatment difference in HbA1c (NovoRapid group-Ruishulin group) was -0.061% (95% CI -0.320-0.199). HbA1c<7.0% target reacing rates were 24.26% and 21.21% ( P=0.456), and HbA1c<6.5% target reacing rates were 9.65% and 6.82% ( P=0.310) in Ruishulin group and NovoRapid group, repectively. The standard 2 hours postprandial blood glucose (2hPG) in Ruishulin group decreased from (16.23±5.22) mmol/L to (12.65±4.57) mmol/L ( P<0.001), and 2hPG in NovoRapid group decreased from (16.13±5.37) mmol/L to (11.91)±4.21) mmol/L ( P<0.001). The fingertips blood glucose at 7-point of both groups exhibited varying degrees of reduction compared with those at baseline, repectively. Positive ratios of specific antibodies were 31.68% in Ruishulin group and 36.36% in NovoRapid group ( P=0.320). Ratios of negative to positive were 7.43% and 10.61% ( P=0.360), and ratios of positive to negative were 10.40% and 7.58% ( P=0.360) in Ruishulin group and NovoRapid group, respectively. The incidence of hypoglycemia was 60.05% and 55.40% ( P=0.371), and the incidence of adverse events was 76.60% and 77.70% ( P=0.818) in Ruishulin group and NovoRapid group, respectively. Conclusions:Rishulin is not inferior to NovoRapid, and has shown good efficacy and safety. It can be an ideal choice for clinicians in patients with poor blood glucose control with insulin.

Low-carbohydrate diets lead to greater weight loss and better glucose homeostasis than exercise: a randomized clinical trial / 医学前沿

Lifestyle interventions, including dietary adjustments and exercise, are important for obesity management. This study enrolled adults with overweight or obesity to explore whether either low-carbohydrate diet (LCD) or exercise is more effective in metabolism improvement. Forty-five eligible subjects were randomly divided into an LCD group (n = 22) and an exercise group (EX, n = 23). The subjects either adopted LCD (carbohydrate intake < 50 g/day) or performed moderate-to-vigorous exercise (⩾ 30 min/day) for 3 weeks. After the interventions, LCD led to a larger weight loss than EX ( - 3.56 ± 0.37 kg vs. - 1.24 ± 0.39 kg, P < 0.001), as well as a larger reduction in fat mass ( - 2.10 ± 0.18 kg vs. - 1.25 ± 0.24 kg, P = 0.007) and waist circumference ( - 5.25 ± 0.52 cm vs. - 3.45 ± 0.38 cm, P = 0.008). Both interventions reduced visceral and subcutaneous fat and improved liver steatosis and insulin resistance. Triglycerides decreased in both two groups, whereas low-density lipoprotein cholesterol increased in the LCD group but decreased in the EX group. Various glycemic parameters, including serum glycated albumin, mean sensor glucose, coefficient of variability (CV), and largest amplitude of glycemic excursions, substantially declined in the LCD group. Only CV slightly decreased after exercise. This pilot study suggested that the effects of LCD and exercise are similar in alleviating liver steatosis and insulin resistance. Compared with exercise, LCD might be more efficient for weight loss and glucose homeostasis in people with obesity.

Metabolic surgery reduces increased urinary mitochondrial DNA copy number in obese patients / 中华内分泌代谢杂志

At present, obesity has become an independent risk factor for chronic kidney disease through its direct or indirect effects. Urine mitochondrial DNA (mtDNA) is a new marker of mitochondrial damage in various kidney diseases, but the differences in urinary mtDNA between obese patients and healthy subjects and the effect of obesity intervention on urinary mtDNA copy number are unknown. In January 2019, " The Journal of Clinical Endocrinology & Metabolism" published an article " Bariatric surgery reduces elevated urinary mitochondrial DNA copy number in obese patients" [Lee H, Oh S, Yang W, et al. J Clin Endocrinol Metab, 2019, 104(6): 2257-2266], with the permission of the original journal, we translate the article into Chinses. This article studied the difference of urinary mtDNA levels between obese patients and healthy subjects and the changes of urinary mtDNA after metabolic surgery intervention. The results revealed that obesity was associated with the increase of urinary nicotinamide adenine dinucleotide dehydrogenase subunit 1 (mtND-1) copy number, and urinary mtDNA copy number was elevated in obese patients. Metabolic surgery reduced urinary mtND-1 copy number in obese patients. This study shows that metabolic surgery can alleviate mitochondrial damage in kidney cells in obese patients.

Type 2 diabetes coincides with insulinoma: One case report and literature review / 中华内分泌代谢杂志

Insulinoma is a rare neuroendocrine tumor originating from pancreatic beta cells, which clinically manifests Whipple′ s triad and recurrent hypoglycemia. Insulinoma in a patient with type 2 diabetes mellitus is even a more rarely encountered case. In clinical practice, hypoglycemia in patients with diabetes is often considered to be associated with oral hypoglycemic agents, but insulinoma, as a possible etiology, is usually neglected. This article reported a case of a patient with type 2 diabetes mellitus, before the diagnosis of which she had experienced recurrent hypoglycemia for about 14 years. Hypoglycemia symptoms with hyperinsulinemia kept existing even after the withdrawal of antidiabetic agents. The pancreatic imaging and postoperative histopathology supported the diagnosis of insulinoma. After surgery, plasma glucose level of the patient increased and diabetes treatments continued. The co-existence of insulinoma and type 2 diabetes mellitus in this case may be attributed to the insulin resistance induced by chronic hyperinsulinemia due to insulinoma.

Type 2 diabetes coincides with insulinoma:One case report and literature review / 中华内分泌代谢杂志

Insulinoma is a rare neuroendocrine tumor originating from pancreatic beta cells, which clinically manifests Whipple' s triad and recurrent hypoglycemia. Insulinoma in a patient with type 2 diabetes mellitus is even a more rarely encountered case. In clinical practice, hypoglycemia in patients with diabetes is often considered to be associated with oral hypoglycemic agents, but insulinoma, as a possible etiology, is usually neglected. This article reported a case of a patient with type 2 diabetes mellitus, before the diagnosis of which she had experienced recurrent hypoglycemia for about 14 years. Hypoglycemia symptoms with hyperinsulinemia kept existing even after the withdrawal of antidiabetic agents. The pancreatic imaging and postoperative histopathology supported the diagnosis of insulinoma. After surgery, plasma glucose level of the patient increased and diabetes treatments continued. The co-existence of insulinoma and type 2 diabetes mellitus in this case may be attributed to the insulin resistance induced by chronic hyperinsulinemia due to insulinoma.

Osteocalcin-mediated crosstalk between bone and cardiovascular diseases / 中华内分泌代谢杂志

Bone is newly recognized as an endocrine organ. Osteocalcin, secreted by osteoblasts and osteocytes, serves as a biochemical marker for bone metabolism;in addition, it also participates in metabolisms of energy, glucose, and lipid. Recent studies have revealed the associations of osteocalcin with vascular calcification, atherosclerosis, and cardiovascular events. This review summarized the current evidences, as well as the research findings of our team on the potential role of osteocalcin in cardiovascular diseases to provide some new insights for the prevention and treatment of metabolic diseases.

Approach to the patient with hot nodules in hypothyroidism with Hashimoto' s thyroiditis: diagnosis and treatment / 中华内分泌代谢杂志

Hashimoto's thyroiditis( HT) is known as the most common cause of hypothyroidism. It has been noted that solitary or dominant cold nodules are common (50％ of the cases) in patients with HT while hot nodules are much less common. Chronic stimulation by TSH contributed to the increased ability of the nodular tissue to concentrate isotopes. Herein, we present in detail a patient who has HT with two hot nodules in hypothyroidism and the outcome of two-year follow-up, in order to call attention to the diagnosis and treatment of Hashimoto's thyroiditis.

Clinical application of continuous glucose monitoring / 中华内分泌代谢杂志

Continuous glucose monitoring (CGM), an emerging technology for glucose monitoring, is able to reflect blood glucose level with a glucose sensor that monitors the glucose concentration in the subcutaneous tissue. Providing the continuous and comprehensive glycemic information, CGM shows unique advantages in the assessment of blood glucose fluctuations. CGM offers an effective supplement to the traditional monitoring approaches, which is of great significance in the study of the individualized treatment for patients and the research of the pathogenesis of diabetes mellitus.

Pay attention to the epidemiological characteristics of diabetes mellitus and improve its prevention and management / 中华内分泌代谢杂志

Epidemiological studies are important methods to discover the characteristics of diabetes mellitus,which are also helpful in improving the effectiveness of prevention and management of the diseases.Continuous improvement in the design and implementation of epidemiological studies itself would have great significance.

Recent progress in research of adipocyte fatty acid binding protein and atherosclerosis / 中华内分泌代谢杂志

Adipocyte fatty acid binding protein (AFABP) is a member of fatty acid binding protein superfamily.Studies in the relationship between AFABP and atherosclerosis may provide new ideas for its pathogenesis.This review summarised a concise and general overview of AFABP' s role in atherosclerosis and atherosclerosis-related disease.

Control of long-term complications and secular management after metabolic surgery / 中国糖尿病杂志

Metabolic surgery has brought new hope for obese T2DM patients. Control of long‐term complications and integrated management after metabolic surgery are important for patients to obtain a long‐term benefit. Cooperation of multidisciplinary teams plays an indispensable role in this systemic work.

Recent progress in metabonomics with regard to hypoglycemic drugs / 中华内分泌代谢杂志

Metabonomics is an emerging platform for technology.It provides a new method in study of drugs.This article summarized evidences derived from recent metabonomics studies regarding hypoglycemic drugs.We collected all proofs of body metabolite profiling in assessing drugs and exploring their potential mechanisms.An outlook of metabonomics for future research into hypoglycemic drugs was also postulated.

Approach to the patient with Graves' disease and concomitant subacute thyroiditis: diagnosis and treatment / 中华内分泌代谢杂志

Subacute thyroiditis can cause destruction of thyroid follicles and subsequent transient thyrotoxicosis.In cases of simultaneous occurrences of subacute thyroiditis and Graves' disease,the former may be missed and thus may further exacerbate thyrotoxicosis.Herein,we report in detail a case with abrupt onset of thyrotoxic heart disease when taking anti-thyroid medications,in order to call attention to the diagnosis and treatment of concomitant Graves' disease and subacute thyroiditis.

Study of metabolic syndrome prevalence and its risk factors of patients with type 2 diabetes in special care unit / 中国综合临床

Objective To investigate the prevalence and risk factors of metabolic syndrome (MS) in patients with type 2 diabetes in special care unit.Methods Two thousand three hunrded and sixty patients with type 2 diabetes were selected as our subject in The Sixth People's Hospital Affiliated to Shanghai Jiaotong University from Jan.2010 to Jul.2012.Among these patients,462 patients from special care unit were served as special care group and 1 898 patients from endocrinology ward were assigned to control group.The disease history information was recorded and physical examination and biochemical tests,including blood lipids,blood pressure,fasting glucose,glycosylated hemoglobin,serum insulin,C peptide were measured.Results (1) In special care group,there were 335 male (72.5％) and the prevalence of smoking,alcohol drinking and the proportion of the high income people were 40.5％,24.9％,76.6％ respectively,higher than that of control group (56.6％,24.6％,10.7％,12.7％ ;x2 =32.1,16.9,12.3,32.8 ;P ＜ 0.01).The body mess index (BMI),levels of waist circumference,alanine aminotransferase (ALT),gamma glutamyhransferase (γ-GT),triglyceride (TG),serum uric acid and fasting C peptide in special care group were ((25.6 ± 3.7) kg/m2,(91.0 ± 9.5) cm,(27.8 ±19.7) U/L,(34.1 ±26.3) U/L,(2.35 ±2.31) mmol/L,(333.7 ±85.5) μmol/L,(2.11 ±1.04) μg/L) higher than those of control group ((24.8 ± 3.5) kg/m2,(89.1 ± 10.3) cm,(23.0 ± 16.1) U/L,(29.2 ±23.2) U/L,(1.82 ±1.64) mmol/L,(317.1 ±85.2) μ mol/L,(1.74 ± 1.05) μg/L;F =11.44,6.90,16.65,8.35,18.23,7.34,21.21 ; P ＜ 0.01).The age,duration of diabetes,systolic blood pressure,level of serum high-density lipoprotein-cholesterol (HDL-C),and glycosylated hemoglobin were ((52.9 ± 11.1) years,5 (2,10) years,(126.7 ± 15.2) mmHg,(1.02 ± 0.32) mmol/L,(8.44 ± 1.99) ％) lower than those of control group((60.4 ± 12.2) years,7 (2,12) years,(131.9 ± 17.3) mmHg,(1.10 ± 0.32) mmol/L,(9.16 ±2.32)％;F =79.41,12.71,18.93,12.78,18.52; P ＜ 0.01); (2) The rate of overweight/obesity,dyslipidemia and MS prevalence rates in special care group were 55.6％,68.4％,60.2％,significantly higher than the control group(46.1％,52.9％,50.6％ ;x2 =7.59,18.76,7.18,P ＜ 0.01).While the prevalence of hypertension in special care group was significantly lower than control group(39.6％ vs 50.7％,x2 =10.15,P =0.01).There was on significant difference between male and female in term of the prevalence of the MS in the special care group(61.2％ vs 57.5％,x2 =0.01,P =0.92).According to age,patients in special care group were divided into three groups and that were ＜45 years group,45-59 years group and ≥60 years group.With the increase of age group of female,the prevalence of MS was increasing(33.3％,48.0％,74.1％ ;x2 =4.43,P =0.04).Among the male patients,there was no significant different was seen among three groups (58.8％,62.5％,55.6％ ;x2 =0.05,P =0.87).(3) Multiple Logistic regression analysis showed that the independent risk factors of MS in special care group including age(OR =1.071,95％ CI(1.027-1.117),P =0.01),BMI (OR =1.391,95％ CI(1.112-1.739) ; P =0.013),waist circumference (OR =1.126,95％ CI(1.039-1.222) ; P =0.004),TG (OR =1.747,95 ％ CI(1.124-2.717) ; P =0.013) and diastolic blood pressure (OR =1.111,95％CI(1.045-1.180);P =0.001).HDL-C(OR=0.048,95％CI(0.005-0.464) ;P =0.009) were protective factors of MS in special care group.Conclusion Approximately 3/5 patients with diabetes in special care unit got MS.The factors including age,BMI,waist circumference,diastolic blood pressure,TG,HDL-C were related to MS occurrence.

Effects of active and passive smoking on chronic kidney disease in patients with type 2 diabetes mellitus / 中华内科杂志

Objective This study aimed to assess the effects of active and passive smoking on chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM).Methods Seven hundred and five patients with T2DM were recruited in the study and were divided into three groups based on smoking status as active smokers,passive smokers and non-smokers.Twenty-four hour urinary albumin excretion (24hUAE) was measured,and estimate glomerular filtration rate (eGFR) was calculated with age and blood creatinine levels.Results (1) The proportion of CKD in T2DM in the present study was 31.63％ (223/705) with 28.6％ (22/77),30.0％ (15/50) and 29.6％ (73/247) for non-smokers,passive smokers and active smokers in men,and 29.9％ (40/134),35.9％ (66/184) and 7/13 for non-smokers,passive smokers and active smokers in women,respectively.In comparison with non-smokers,a higher risk of CKD was found in both passive and active smokers (OR =1.07 and OR =1.05 in men ; OR =1.31 and OR =2.74 in women,respectively).(2) Compared with non-smokers,passive smokers had a significant higher risk for albuminuria in women (OR =2.02,P =0.016).(3) After adjusting for gender,age,duration of T2DM,BMI,systolic blood pressure,glycosylated hemoglobin A1C and lipids,there was a significant decrease in eGFR between active and never smokers (P =0.018)or passive smokers (P =0.000) in women.No differences could be found in eGFR between each smoking statues in men.Conclusions Smoking exposure alone confers a high risk for CKD in patients with T2DM.Our results highlight an importance in implementation of a smoke-free environment for patients with T2DM.

Approach to the patient with acute suppurative thyroiditis: diagnosis and treatment / 中华内分泌代谢杂志

Acute suppurative thyroiditis (AST) is a rare non-specific infectious disease of thyroid gland.The signs and symptoms of AST may mimic those of a variety of noninfectious inflammatory conditions or other anterior neck infectious diseases.AST is a progressive disease and is also potentially life threatening if devoid of prompt diagnosis and proper treatment.Herein,we report a case in order to call attention to the diagnosis and treatment of AST.