Comparative efficacy and safety of two insulin aspart formulations (Rapilin and NovoRapid) when combined with metformin, for patients with diabetes mellitus: a multicenter, randomized, open-label, controlled clinical trial.

OBJECTIVE: This phase 3 confirmatory diabetes mellitus treatment study compared the safety and efficacy of Rapilin and NovoRapid insulin asparts in combination with metformin. METHODS: This 24-week, open-label, randomized, active-controlled, noninferiority phase 3 confirmatory study conducted across centers in China aimed to enroll patients with type 2 diabetes mellitus and blood sugar glucose inadequately controlled by oral antidiabetic drugs. Randomized patients received subcutaneous mealtime Rapilin or NovoRapid (3:1) injections, with metformin. The primary objectives were to demonstrate noninferiority (margin of 0.4%) in HbA1c change from baseline and compare safety profiles of Rapilin versus NovoRapid after 24 weeks. Secondary outcomes included 2-h postprandial plasma glucose (PPG), fasting plasma glucose (FPG), and patients achieving HbA1c <7.0% and ≤6.5%. RESULTS: 590 patients with type 2 diabetes mellitus were randomized to Rapilin (n = 441) and NovoRapid (n = 149) groups. After 24 weeks, the mean HbA1c change from baseline was -2.20% (Rapilin) and -2.32% (NovoRapid); the estimated treatment difference based on least-square means was 0.04% (95% CI: -0.17, 0.26), meeting the noninferiority criteria for Rapilin versus NovoRapid. Comparable improvements were reported for mean 2-hour PPG (6.14 and 6.29 mmol/L), FPG (2.02 and 1.70 mmol/L), and patients with HbA1c <7.0% (52.6% and 51.0%) and ≤6.5% (34.2% and 30.9%), in the Rapilin and NovoRapid groups, respectively, with no significant safety or immunogenicity outcome differences. CONCLUSIONS: Rapilin demonstrated non-inferior glycemic control, and matching safety and immunogenicity to NovoRapid in patients with type 2 diabetes mellitus also receiving metformin over 24 weeks. TRIAL REGISTRATION: ChiCTR20003129041.

Adiponectin and Thyroid Cancer: Insight into the Association between Adiponectin and Obesity.

In recent decades, the incidence and diagnosis of thyroid cancer have risen dramatically, and thyroid cancer has now become the most common endocrine cancer in the world. The onset of thyroid cancer is insidious, and its progression is slow and difficult to detect. Therefore, early prevention and treatment have important strategic significance. Moreover, an in-depth exploration of the pathogenesis of thyroid cancer is key to early prevention and treatment. Substantial evidence supports obesity as an independent risk factor for thyroid cancer. Adipose tissue dysfunction in the obese state is accompanied by dysregulation of a variety of adipocytokines. Adiponectin (APN) is one of the most pivotal adipocytokines, and its connection with obesity and obesity-related disease has gradually become a hot topic in research. Recently, the association between APN and thyroid cancer has received increasing attention. The purpose of this review is to systematically review previous studies, give prominence to APN, focus on the relationship between APN, obesity and thyroid cancer, and uncover the underlying pathogenic mechanisms.

Subject-driven titration of biphasic insulin aspart 30 twice daily is non-inferior to investigator-driven titration in Chinese patients with type 2 diabetes inadequately controlled with premixed human insulin: A randomized, open-label, parallel-group, multicenter trial.

AIMS/INTRODUCTION: The present study was to compare the efficacy and safety of subject-driven and investigator-driven titration of biphasic insulin aspart 30 (BIAsp 30) twice daily (BID). MATERIALS AND METHODS: In this 20-week, randomized, open-label, two-group parallel, multicenter trial, Chinese patients with type 2 diabetes inadequately controlled by premixed/self-mixed human insulin were randomized 1:1 to subject-driven or investigator-driven titration of BIAsp 30 BID, in combination with metformin and/or α-glucosidase inhibitors. Dose adjustment was decided by patients in the subject-driven group after training, and by investigators in the investigator-driven group. RESULTS: Eligible adults (n = 344) were randomized in the study. The estimated glycated hemoglobin (HbA1c) reduction was 14.5 mmol/mol (1.33%) in the subject-driven group and 14.3 mmol/mol (1.31%) in the investigator-driven group. Non-inferiority of subject-titration vs investigator-titration in reducing HbA1c was confirmed, with estimated treatment difference -0.26 mmol/mol (95% confidence interval -2.05, 1.53) (-0.02%, 95% confidence interval -0.19, 0.14). Fasting plasma glucose, postprandial glucose increment and self-measured plasma glucose were improved in both groups without statistically significant differences. One severe hypoglycemic event was experienced by one subject in each group. A similar rate of nocturnal hypoglycemia (events/patient-year) was reported in the subject-driven (1.10) and investigator-driven (1.32) groups. There were 64.5 and 58.1% patients achieving HbA1c <53.0 mmol/mol (7.0%), and 51.2 and 45.9% patients achieving the HbA1c target without confirmed hypoglycemia throughout the trial in the subject-driven and investigator-driven groups, respectively. CONCLUSIONS: Subject-titration of BIAsp 30 BID was as efficacious and well-tolerated as investigator-titration. The present study supported patients to self-titrate BIAsp 30 BID under physicians' supervision.

Plantar Pressure Changes and Correlating Risk Factors in Chinese Patients with Type 2 Diabetes: Preliminary 2-year Results of a Prospective Study.

BACKGROUND: Plantar pressure serves as a key factor for predicting ulceration in the feet of diabetes patients. We designed this study to analyze plantar pressure changes and correlating risk factors in Chinese patients with type 2 diabetes. METHODS: We recruited 65 patients with type 2 diabetes. They were invited to participate in the second wave 2 years later. The patients completed identical examinations at the baseline point and 2 years later. We obtained maximum force, maximum pressure, impulse, pressure-time integral, and loading rate values from 10 foot regions. We collected data on six history-based variables, six anthropometric variables, and four metabolic variables of the patients. RESULTS: Over the course of the study, significant plantar pressure increases in some forefoot portions were identified (P < 0.05), especially in the second to forth metatarsal heads. Decreases in heel impulse and pressure-time integral levels were also found (P < 0.05). Plantar pressure parameters increased with body mass index (BMI) levels. Hemoglobin A1c (HbA1c) changes were positively correlated with maximum force (ß = 0.364, P = 0.001) and maximum pressure (ß = 0.366, P = 0.002) changes in the first metatarsal head. Cholesterol changes were positively correlated with impulse changes in the lateral portion of the heel (ß = 0.179, P = 0.072) and pressure-time integral changes in the second metatarsal head (ß = 0.236, P = 0.020). Ankle-brachial index (ABI) changes were positively correlated with maximum force changes in the first metatarsal head (ß = 0.137, P = 0.048). Neuropathy symptom score (NSS) and common peroneal nerve sensory nerve conduction velocity (SCV) changes were positively correlated with some plantar pressure changes. In addition, plantar pressure changes had a correlation with the appearance of infections, blisters (ß = 0.244, P = 0.014), and calluses over the course of the study. CONCLUSIONS: We should pay attention to the BMI, HbA1c, cholesterol, ABI, SCV, and NSS changes in the process of preventing high plantar pressure and ulceration. Some associated precautions may be taken with the appearance of infections, blisters, and calluses.

[The predictive factors of good glycaemic control in Chinese patients receiving biphasic insulin as part 30: a subgroup analyses from the A1 chieve study].

OBJECTIVE: To identify the baseline factors associated with achievement of glycosylated haemoglobin A1c (HbA1c) < 7.0% in Chinese patients receiving biphasic insulin as part 30 (BIAsp 30), who were previously inadequately controlled with oral anti-diabetic drugs (OADs). METHODS: A1 chieve was a multinational, prospective, open-label, 24-week non-interventional study in patients with type 2 diabetes initiating insulin analogues in 28 countries. The patients were enrolled to take BIAsp 30 according to physician's clinical judgments, who was also responsible for the treatment regimen and dosage adjustment. Primary safety endpoints were the incidence of serious drug adverse reactions (SADRs) including serious hypoglycaemia. Major efficacy endpoints were change in HbA1c, fasting plasma glucose (FPG), 2h post-prandial plasma glucose (2 hPG) from baseline. Relationships between baseline predictive baseline factors and achievement of HbA1c < 7.0% after treatment were examined using multivariate analysis. RESULTS: In China, 4 100 patients initiated BIAsp 30 [54.2% males, age (56.2 ± 13.6) years]. No SADRs were reported. Mean HbA1c was reduced from (9.3 ± 2.1)% to (7.0 ± 1.0)%; FPG was reduced from (10.2 ± 3.3) mmol/L to (6.8 ± 1.3) mmol/L. Changes in 2 hPG after breakfast, lunch and dinner were (-5.6 ± 4.7), (-4.9 ± 4.3) and (-4.2 ± 4.1) mmol/L, respectively (all P < 0.001). The proportion of patients achieving HbA1c < 7.0% increased from 9.7% at baseline to 54.2% at week 24. Multivariate analysis revealed a negative relationship between baseline HbA1c, FPG, 2 hPG and HbA1c < 7.0% after treatment. CONCLUSIONS: In the Chinese subgroup of the A1 chieve study, lower baseline HbA1c, FPG, 2 hPG were predictive factors for achieving HbA1c < 7.0% after 24-week treatment of BIAsp 30, indicating that the earlier initiation of BIAsp 30 in patients poorly controlled with OADs, the more helpful for them to achieve treatment target.

Risk factors correlated with plantar pressure in Chinese patients with type 2 diabetes.

BACKGROUND: Plantar pressure is a key factor for predicting ulceration in the foot of a diabetes patient. SUBJECTS AND METHODS: We recruited a group of 100 Chinese patients with type 2 diabetes and an age-, sex-, weight-, and height-matched group of 100 Chinese subjects without diabetes. We obtained plantar pressure data using a Footscan(®) gait system (RsScan International, Olen, Belgium) when the subjects with and without diabetes walked barefoot across a sensor platform. We recorded the maximum force, maximum pressure, impulse, pressure-time integral, and loading rate from 10 regions of the foot. We collected the data of 11 history-based variables, 10 anthropometric variables, and three metabolic variables regarding the clinical characteristics of the diabetes patients. RESULTS: Weight was identified as a determining factor for high plantar pressure. Height, the Neuropathy Symptom Score (NSS), and ankle-brachial index (ABI) were correlated positively with plantar pressure measurements, respectively. The sex, history of ulcer and callus, intima-media membrane of the lower limb blood vessels, and fasting blood glucose (FBG) could also explain a portion of the variability of the plantar pressure measurements. However, the correlations were low or weak. CONCLUSIONS: High plantar pressure in diabetes patients could be predicted, in part, based on weight, height, NSS, ABI, sex, history of ulcer and callus, intima-media membrane of the lower limb blood vessels, and FBG. Therefore, interventions should be taken specifically before high plantar pressure emerges.

[Association of visceral adiposity with urinary albumin excretion in type 2 diabetics].

OBJECTIVE: To decipher the association of visceral adiposity (VA) with 24-hour urinary albumin excretion (24 h-UAE) in type 2 diabetics. METHODS: We collected the clinical data, VA, subcutaneous adiposity (SA), 24 h-UAE, blood lipids, fasting blood glucose, glycosylated hemoglobin, insulin and tumor necrosis factor (TNF)-α of type 2 diabetic inpatients at our hospital. According to the quartile of VA, the subjects were divided into 4 groups. And their profiles were compared with regards to the level of 24 h-UAE and the incidence of heavy proteinuria. And their relative intensities and the linear relationship of VA and lg (24 h-UAE) were analyzed. RESULTS: lg (24 h-UAE) of groups C and D was larger than that of groups A and B. With the rising level of VA, the prevalence of heavy proteinuria increased. A moderate correlation existed between VA and lg (24 h-UAE) (r = 0.51). lg (24 h-UAE) increased 0.26 units as VA expanded 100 cm(2), i.e. 0.15 units after relative factor adjusting. After gender and triglyceride adjusting, the odds ratio of heavy albuminuria in group C was 2.75 versus that in group A. And the OR was 3.87 in group D. CONCLUSION: Expansion of VA is a risk factor for an elevated risk of 24 h-UAE. With the expansion of VA, the prevalence of heavy albuminuria increases.

[Differences in risk factors of diabetic foot in the patients in South and North China].

OBJECTIVE: To investigate the differences on the diabetic foot problems and its risk factors in south and north of China. METHODS: Patients with foot problems were surveyed from January 1 to December 31, 2004 in 14 teaching hospitals located in different cities in China, including demographic data, present and past history of the foot problems and peripheral artery disease (PAD), the classification of the foot ulcers based on the Wagner' system, control of the hyperglycemia and lipids disorder, medical cost in hospital and the diabetic complications. All the patients were divided into two groups due to their geographical data, south and north. RESULTS: There were 285 and 349 patients for the group south and group north. No significant differences were found for duration of diabetes or foot problems, fasting or post-meal glucose, total cholesterol, triglycerides, HDL-C, and the numbers of patients with smoke, hypertension, nephropathy or neuropathy between the two groups. There were significant differences for the age (70 yrs vs 66 yrs), percentage of the patients with average person income with over RMB 1000 per month (57.7% vs 45.6%), coronary heart disease (42.6% vs 61.0%) and retinopathy (35.7% vs 49.5%), HbA1c (7.90% vs 8.80 %), LDL-C (2.75 mmol/L vs 2.98 mmol/L), WBC (6.70 x 10(9) vs 7.40 x 10(9)/L), HCT (0.37 vs 0.38), creatinine (87 micromol/L vs 76 micromol/L) and uric acid (333 mmol/L vs 271 mmol/L), and amputation rate (2.6% vs 9.7%) between south and north groups. Logistic analysis showed that severity of the foot problems was associated with ABI and WBC in south group, and with ABI, PLT and HCT in north group. CONCLUSION: Diabetic foot problems were more severe, with more risk factors and with more medical cost in north patients.

[A multicenter survey on the diabetic foot and its neuropathy in China].

OBJECTIVE: To investigate the characteristics of diabetic foot with neuropathy and its related factors. METHODS: 530 out- and in-patients in 14 grade A class 3 comprehensive hospitals in China with foot problems were surveyed. 337 of the 500 patients (63.58%) suffered from neuropathy, 172 (32.45%) with diabetic foot with simple neuropathy and 165 (31.13%) with simple neuropathy combined with peripheral artery disease (PAD). 193 of the 500 patients (36.42%) suffered from peripheral artery disease (PAD). 77.7% of ulcer were caused by physical factors. Questionnaire survey was conducted to collect the demographic data, present and past history, history of the hyperglycemia and lipid disorders, classification and phases of the foot ulcers based on Wagner' system and Texas system, characteristics of neuropathy and other diabetic complications, and relative risk factors. Detailed physical examination was performed, including 10 g nylon filament sensation examination. RESULTS: The duration of diabetic foot of the patients with simple neuropathy was 3 (1, 60) months, significantly shorter than that of the diabetic foot patients with PAD [5 (1, 96) months, P < 0.001]. The Wagner degree of ulcer was related to the duration of diabetes, economic income, foot deformity, nerve reflection, diapason vibration sensation of foot, sensation point of 10 g nylon filament, ankle/brachial index (ABI), foot artery pulse, fasting blood sugar (FBS) and glycated hemoglobin (HbA1c). Stepwise regression analysis revealed that ABI of left posterior tibial artery, vibration detection threshold and economic income were the most significant influencing factors of the degree of ulcer. CONCLUSION: Neuropathy ulcer is common in diabetic foot patients. The prognosis of healing in diabetic foot with neuropathy is prior to that of diabetic foot with PAD. The neuropathy and PAD of foot influence each other and aggravate the condition of diabetic foot. The examinations of diapason vibration sensation of foot, sensation point of 10 g nylon filament, and Achilles tendon reflex are simple and practical, and are worth recommending.

[The medical cost of diabetic patients with foot problems due to peripheral artery disease].

OBJECTIVE: To investigate the medical cost of diabetic patients with foot problems and peripheral artery disease. METHODS: Type 2 diabetic patients with foot problems admitted into the endocrinology departments of 14 teaching hospitals from Jan. 1 to Dec. 31, 2004 were surveyed for their type and phase of foot ulcers, diabetic complications, medical cost and general personal characteristics. RESULTS: The average medical cost of the hospitalization of these patients was RMB yen 14,906 +/- 7072 (about US $ 1640 +/- 873); medication and examination cost was separately 56% and 19% of the total cost. There was obviously higher medical cost for these patients with longer diabetes duration of over 20 years and with the occupation of laborer and retired worker. Patients with kidney disease had significantly higher medical cost than those without (RMB yen 11 690.7 vs yen 9493.0; P = 0.0013), even if the hospital stay was nearly the same (21 days vs 20 days). The medical cost increase with the severity of diabetic foot problems based on the classification of Wagner System or Texas System. Patients with infection, ischemic foot and gangrene foot stayed in the hospitals longer and had much higher medical cost. CONCLUSION: The medical cost is higher for diabetic patients with foot problems and is related with the presence of complicating kidney disease, infection and ischemia as well as the severity of foot ulcers.