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Introduction: Few prospective clinical trials have investigated the role of fasting blood glucose (FBG) and/or postprandial glucose (PPG) in assessing overall glycemic control by using different insulin regimens. In the present post hoc analysis, we assessed the contribution of FBG and/or PPG in overall glycemic control in Chinese patients under insulin treatment.Methods: CLASSIFY is a phase IV, randomized, open-label, 26-week, parallel-arm, treat-to-target, multinational, controlled study in patients with type 2 diabetes mellitus to compare the efficacy and safety of insulin lispro mix 25 (LM25) and insulin lispro mix 50 (LM50) as starter insulins. Insulin was titrated with an aim to target pre-meal blood glucose (BG) levels at > 3.9 and ≤ 6.1 mmol/L before breakfast and dinner. The primary outcome assessed was the change in HbA1c from baseline.Results: Chinese patients contributed 38.7% (N = 156) of the total population. The majority of patients were male (52.6%). The mean (SD) body mass index was 24.54 (3.04) kg/m2 and mean (SD) HbA1c was 8.54 (1.10) % at baseline. At week 26, LM50 showed a significantly greater reduction from baseline in HbA1c (− 2.03% vs − 1.55%, P < 0.001), average daily BG (− 3.21 vs − 2.34 mmol/L, P < 0.001), average post-meal BG (− 3.58 vs − 2.39 mmol/L, P < 0.001), and average prandial BG excursion (− 1.01 vs − 0.22 mmol/L, P = 0.006) than the LM25 group. The reductions in average pre-meal BG (− 2.59 vs − 2.28 mmol/L, P = 0.137) were not significantly different between the groups. The proportion of patients achieving HbA1c targets (< 7% or ≤ 6.5%) without nocturnal hypoglycemia or weight gain was greater (P < 0.05) with LM50 compared with LM25.Conclusion: LM50 achieved better overall glycemic control than LM25 as a starter insulin in Chinese patients, which may be due to greater improvement in PPG levels.Trial Registration: Clinicaltrials.gov identification number: NCT01773473.Funding: Eli Lilly and Company, Shanghai, China. [ABSTRACT FROM AUTHOR]

Background: The association between weight change during early adulthood and cardiometabolic diseases remains uncertain in Chinese population. Whether the association varies with comprehensive cardiovascular health (CVH) in midlife assessed by "Life's Essential 8" has not been characterized. We aim to examine the associations of early adulthood weight change and midlife "Life's Essential 8" CVH status with cardiometabolic outcomes in a Chinese cohort. Methods: The study participants were from the China Cardiometabolic Disease and Cancer Cohort (4 C) Study. This analysis included 72,610 middle-aged and older participants followed for a median of 3.6 years. At baseline, the participants recalled body weight at age 20 and 40 years, and we calculated change in weight and BMI between 20 and 40 years of age. Health behaviors information in "Life's Essential 8" was collected by questionnaire, and health factors were measured in the study center. During follow-up, we ascertained incident cardiovascular events based on medical records, and diagnosed incident diabetes according to the American Diabetes Association 2010 criteria. Results: 72,610 study participants were included with a mean age of 56.0 ± 8.8 years and 29% of them were males. Weight gain of more than 10 kg between 20 and 40 years of age was associated with 22% increased risk of incident cardiovascular events (HR: 1.22; 95%CI: 1.04–1.43) and 38% increased risk of diabetes (HR: 1.38; 95%CI: 1.25–1.53) compared to stable weight. Besides, the association of weight gain more than 10 kg in early adulthood with cardiometabolic risk was even stronger in those with low CVH score in midlife (HR: 2.44; 95%CI: 2.01–2.97 for incident cardiovascular events; HR: 2.20; 95%CI: 1.90–2.55 for incident diabetes) or with few ideal cardiovascular health metrics in midlife. Conclusions: Our study indicated that weight gain in early adulthood was associated with significantly increased risk of cardiometabolic diseases. And the association could be stronger in those with poor CVH profiles in midlife. These findings confirmed the significance of weight management during early adulthood and suggested that individuals who experienced substantial weight gain in early life should be encouraged to maintain good CVH status in Chinese population. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the prevalence of vitamin B12 deficiency in Chinese patients with type 2 diabetes mellitus receiving metformin treatment and to investigate the effects of metformin daily dose and treatment duration on the prevalence of vitamin B12 deficiency and peripheral neuropathy (PN). Materials and Methods: In this multicenter cross‐sectional study, 1027 Chinese patients who had been taking ≥1000 mg/day metformin for ≥1 year were enrolled using proportionate stratified random sampling based on daily dose and treatment duration. Primary measures included the prevalence of vitamin B12 deficiency (<148 pmol/L), borderline B12 deficiency (148 pmol/L‐211 pmol/L), and PN. Results: The prevalence of vitamin B12 deficiency, borderline deficiency, and PN were 2.15%, 13.66%, and 11.59%, respectively. Patients receiving ≥1500 mg/day metformin had significantly higher prevalence of borderline vitamin B12 deficiency (16.76% vs. 9.91%, p =.0015) and serum B12 ≤221 pmol/L (19.25% vs. 11.64%, p <.001) than patients receiving <1500 mg/day metformin. No difference was found in prevalence of borderline vitamin B12 deficiency (12.58% vs. 15.49%, p =.1902) and serum B12 ≤221 pmol/L (14.91% vs. 17.32%, p =.3055) between patients receiving metformin for ≥3 and <3 years. Patients with vitamin B12 deficiency had numerically higher PN prevalence (18.18% vs. 11.27%, p =.3192) than patients without it. Multiple logistic analyses revealed that HbA1c and metformin daily dose were associated with the prevalence of borderline B12 deficiency and B12 ≤221 pmol/L. Conclusions: High daily dosage (≥1500 mg/day) played an important role in metformin‐associated vitamin B12 deficiency while not contributing to the risk of PN. [ABSTRACT FROM AUTHOR]

Background The use of self-monitoring of blood glucose (SMBG) among patients with insulin-treated, type 2 diabetes (T2DM) in China is suboptimal. Herein we evaluated the effectiveness of structured SMBG for improving glycemic control and increasing the frequency of SMBG. Methods Insulin-treated (>3 months) T2DM patients aged ≥18 years with HbA1c >8.0 % (64 mmol/mol) were recruited to the study. They received SMBG materials and were advised on a structured SMBG regimen for their insulin therapy. Patients were trained to self-adjust insulin dosage according to SMBG readings and were seen by physicians at Months 3 and 6. Endpoints included changes in HbA1c, SMBG frequency, and hypoglycemia frequency. Results The study enrolled 820 patients, with mean (± SD) age 55.1 ± 9.8 years, body mass index 24.9 ± 3.6 kg/m2, HbA1c 9.7 ± 1.6 % (83 mmol/mol), and diabetes duration 9.8 ± 7.1 years, with median insulin therapy of 30.3 (3.0-274.1) months, from 19 Chinese clinics. By Month 3, 99.9 % of patients performed daily SMBG. At Months 3 and 6, HbA1c had decreased from baseline (−1.81 % and −1.73 %, respective; P < 0.0001 for both), with reduced hypoglycemia. In addition, 36.2 % and 39.9 % of patients achieved HbA1c <7.0 % (53 mmol/mol) at Months 3 and 6, respectively. The largest HbA1c improvements were for patients with a shorter duration of diabetes and insulin therapy. Conclusions A structured SMBG regimen, with training on interpretation of and responses to SMBG readings, increased SMBG frequency and improved HbA1c and the management of insulin-treated T2DM. [ABSTRACT FROM AUTHOR]

Background: Gestational hyperglycemia increases the risk of diabetes in later life. However, the risk of future cardiovascular diseases (CVD) related to gestational hyperglycemia remains inconclusive. The purpose of this study was to investigate the impact of gestational hyperglycemia on the subsequent risk of CVD and its modifying factors among elderly Chinese women. Methods: We conducted a case‐control study of elderly women from the baseline survey of Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. Women with gestational hyperglycemia (n = 82), and controls matched by age and study site (n = 410) were included. Information on CVD, including reported coronary heart disease, stroke, or myocardial infarction, was collected through an interviewer‐assisted questionnaire. Results: Women with gestational hyperglycemia were more likely to develop diabetes (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.50‐4.18) and CVD (OR, 1.98; 95% CI, 1.05‐3.74). Even without progressing to type 2 diabetes, gestational hyperglycemia was associated with an increased risk of CVD (OR, 2.88; 95% CI, 1.18‐7.00). However, subgroup analysis indicated that compared with those without gestational hyperglycemia or hypertension, women with both gestational hyperglycemia and hypertension had higher risk of CVD (OR, 3.98; 95% CI, 1.65‐9.58), whereas the risk estimate did not significantly change in women with gestational hyperglycemia alone (OR, 2.15; 95% CI, 0.71‐6.57). Stratified analysis indicated that among those with overweight/obesity, inactive physical activity, or unhealthy dietary habits, gestational hyperglycemia increased the risk of CVD. Conclusions: In elderly Chinese women, gestational hyperglycemia was associated with an increased risk of CVD in later life. This association was independent of the progression to diabetes and might be modified by lifestyle factors and hypertension. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes is increasingly diagnosed at a younger age worldwide and in China. Limited data are available regarding the association between age at diabetes diagnosis and risks of albuminuria. This study sought to examine the independent effect of age at diagnosis of type 2 diabetes on the risk of albuminuria. Methods: We used data from a nationwide multicenter study with 207 961 participants in mainland China. Age, sex, and study site were matched for 31 366 screen‐detected type 2 diabetes cases and 31 366 normal controls. Age, sex, study site, and diabetes duration were matched for 7490 self‐reported type 2 diabetes cases and 7490 normal controls. Risks of having albuminuria in matched type 2 diabetes vs controls were examined using multivariable logistic regression analysis in strata of age at diabetes diagnosis. Results: Although the absolute rate of albuminuria is higher in older adults, the odds ratio of albuminuria in type 2 diabetes vs matched controls decreased with increasing age at diagnosis. For participants with diabetes diagnosed at an age of <50, 50 to 59, 60 to 69, or ≥70 years, the multivariable adjusted risk of albuminuria increased by 81%, 60%, 45%, and 33% for screen‐detected diabetes, and 135%, 121%, 90%, and 58% for self‐reported diabetes compared with their normal controls, respectively. Conclusions: A younger age at diagnosis of type 2 diabetes is associated with a more significantly elevated risk of albuminuria than an older age at diagnosis in Chinese adults. [ABSTRACT FROM AUTHOR]

Objective: Comprehensive assessment of serum bile acids (BAs) aberrations before diabetes onset remains inconclusive. We examined the association of serum BA profile and coregulation with the risk of developing type 2 diabetes mellitus (T2DM) among normoglycemic Chinese adults.Research Design and Methods: We tested 23 serum BA species in subjects with incident diabetes (n = 1,707) and control subjects (n = 1,707) matched by propensity score (including age, sex, BMI, and fasting glucose) from the China Cardiometabolic Disease and Cancer Cohort (4C) Study, which was composed of 54,807 normoglycemic Chinese adults with a median follow-up of 3.03 years. Multivariable-adjusted odds ratios (ORs) for associations of BAs with T2DM were estimated using conditional logistic regression.Results: In multivariable-adjusted logistic regression analysis, per SD increment of unconjugated primary and secondary BAs were inversely associated with incident diabetes, with an OR (95% CI) of 0.89 (0.83-0.96) for cholic acid, 0.90 (0.84-0.97) for chenodeoxycholic acid, and 0.90 (0.83-0.96) for deoxycholic acid (P < 0.05 and false discovery rate <0.05). On the other hand, conjugated primary BAs (glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, and sulfated glycochenodeoxycholic acid) and secondary BA (tauroursodeoxycholic acid) were positively related with incident diabetes, with ORs ranging from 1.11 to 1.19 (95% CIs ranging between 1.05 and 1.28). In a fully adjusted model additionally adjusted for liver enzymes, HDL cholesterol, diet, 2-h postload glucose, HOMA-insulin resistance, and waist circumference, the risk estimates were similar. Differential correlation network analysis revealed that perturbations in intraclass (i.e., primary and secondary) and interclass (i.e., unconjugated and conjugated) BA coregulation preexisted before diabetes onset.Conclusions: These findings reveal novel changes in BAs exist before incident T2DM and support a potential role of BA metabolism in the pathogenesis of diabetes. [ABSTRACT FROM AUTHOR]

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates cholesterol metabolism by targeting the low-density lipoprotein receptor. Recent studies have shown that circulating PCSK9 is associated with glucose homeostasis and insulin resistance. The aim of this study was to examine the association of circulating PCSK9 levels and risk for the development of type 2 diabetes in individuals with prediabetes. Methods: A population-based prospective study was conducted among 4205 Chinese subjects with prediabetes (average age 56.1 ± 7.5 years). Incident type 2 diabetes was diagnosed according to 2010 American Diabetes Association criteria. Circulating PCSK9 levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA). The association of circulating PCSK9 levels with the risk of incident type 2 diabetes was assessed by Cox regression analysis. Results: During a median follow-up period of 3.1 years, 568 subjects developed type 2 diabetes. Baseline circulating PCSK9 levels were significantly higher in female subjects developing incident type 2 diabetes than in those not developing incident type 2 diabetes (p < 0.001). In female subjects, the risk of incident type 2 diabetes was significantly higher in the highest PCSK9 quartile group (hazard ratio 2.16; 95% confidence interval 1.16–4.04) than in the lowest quartile group after adjustments for age, body mass index, waist circumference, C-reactive protein, γ-glutamyltransferase, triglycerides, low-density lipoprotein cholesterol, systolic blood pressure, and homeostatic model assessment of insulin resistance score. No significant association was observed between PCSK9 and incident type 2 diabetes in male subjects. Conclusion: Elevated circulating PCSK9 levels are associated with an increased incidence of type 2 diabetes in female subjects with prediabetes. [ABSTRACT FROM AUTHOR]

Background: Recent study showed that individuals with type 2 diabetes have a high risk of developing colorectal cancer (CRC), in which Receptor for Advanced Glycation End Products (RAGE) plays a pivotal role. We conducted a cross-sectional study to examine the relationships of circulating sRAGE, CRC and other clinical factors in type2 diabetes patients. Methods: A total of 150 type 2 diabetes patients aged 50 years and older were enrolled, including 50 patients with CRC and 100 patients without CRC. We measured Serum levels of sRAGE and interleukin-6(IL-6) using an enzyme-linked immunosorbent assay (ELISA). In addition, other clinical parameters were also measured during hospitalization. Results: Type 2 diabetes patients with CRC had higher triglyceride, total cholesterol, IL-6, and circulating sRAGE levels and lower use of medicines than type 2 diabetes patients without CRC. Circulating sRAGE was associated with an increased risk for CRC (OR = 2.289 for each SD increase in sRAGE, 95% CI = 1.037–5.051; P = 0.04) among Type 2 diabetes patients after adjustment for confounders. Furthermore, circulating sRAGE levels among type 2 diabetes patients were positively correlated with triglyceride (r = 0.377, P < 0.001), total cholesterol (r = 0.491, P < 0.001), and low-density lipoprotein cholesterol (LDL-c)(r = 0.330, P < 0.001) levels; the homeostatic model assessment for insulin resistance(HOMA-IR)score (r = 0.194, P = 0.017); and fasting serum insulin (r = 0.167, P = 0.041) and IL-6 (r = 0.311, P < 0.001) concentrations. Conclusions: Our results suggested that circulating sRAGE is independently risk factor for CRC, and also closely related to inflammation, dyslipidemia in type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Objective: We investigated the relationship between fasting serum fructose levels and the risk of incident type 2 diabetes in a prospective Chinese cohort.Research Design and Methods: Among 949 community-based participants aged ≥40 years without diabetes at baseline, fasting serum fructose levels were measured using liquid chromatography-tandem mass spectrometry. The participants were followed up for the occurrence of diabetes. Cox regression models were performed to analyze the effect of fasting serum fructose levels on risk of incident diabetes.Results: During a median of 3.5 years' follow-up, 179 of 949 (18.9%) participants developed type 2 diabetes. Elevated fasting serum fructose levels were associated with an increased risk of incident diabetes in a dose-response manner. After adjustment for age, sex, BMI, lipid profiles, blood pressure, liver function, smoking and drinking status, baseline glucose level, and sugar-sweetened beverage consumption, a 1-SD increased fasting fructose level was associated with a 35% (95% CI 1.08-1.67) increased risk of developing diabetes. After further adjustment for serum uric acid and estimated glomerular filtration rate, the association was partially attenuated (hazard ratio 1.33 [95% CI 1.07-1.65]). The association was similar by age, prediabetes status, BMI, and family history of diabetes but attenuated in women (P for heterogeneity = 0.037).Conclusions: Elevated fasting serum fructose levels were independently associated with increased risk of incident type 2 diabetes in a middle-aged and older Chinese population. Our data suggest that higher fasting serum fructose levels might serve as a biomarker and/or a contributor to incident diabetes. [ABSTRACT FROM AUTHOR]

Objectives. The study provided data to demonstrate the characteristics of type 2 diabetes (T2D) with ketosis in rural parts of south-west border of China in order to help health professionals with optimizing diabetic care. Methods. All hospitalized adult diabetic patients consecutively between January 2011 and July 2015 in Baoshan People’s Hospital, Yunnan province of China, were evaluated. T2D with ketosis, ordinary T2D (without ketosis), and type 1 diabetes (T1D) patients were analyzed according to the clinical and biochemical parameters and chronic complications in these subjects. Results. The prevalence of T2D with ketosis was 12% in the whole study subjects. Overweight and obese patients were predominant (49.1%) in T2D patients with ketosis. The mean HbA1c (13.3±3.1%, P=0.01), fasting plasma glucose (16.9±6 mmol/L, P<0.0001), and plasma triglyceride (4.0±4.0 mmol/L, P<0.0001) in T2D patients with ketosis were significantly higher than ordinary T2D patients without ketosis. Infections were the most common inducements in T2D patients with ketosis. Chronic complications including peripheral neuropathy (34.9%), retinopathy (12.7%), diabetic foot (18.1%), and persistent microalbuminuria (11.7%) were common in T2D patients with ketosis. Conclusions. This study indicated the poor glycemic control in diabetic patients in rural areas of south-west part of China. More efforts were urgently required to popularize public health education and improve medical quality in diabetic treatment in these regions. [ABSTRACT FROM AUTHOR]

Vaspin is a novel adipocytokine that has potential insulin-sensitizing effects. The aim of this study is to explore the role of vaspin in the progression of type 2 diabetes mellitus (T2DM) in humans through a longitudinal process. This was a 2-year follow-up study that included 132 patients with T2DM and 170 non-diabetic subjects. The serum vaspin and adiponectin levels were determined with ELISA. Anthropometric measurements, circulating glucose, hemoglobin A1c, insulin level, liver function, kidney function, and lipid profile were measured for each participant. The new onset of T2DM was counted in non-diabetic subjects and the glycemic control was analyzed in T2DM patients at follow-up. At enrollment, the serum vaspin and adiponectin levels were lower in T2DM patients compared with non-diabetic subjects. Significant positive correlation between serum vaspin and HDL-C levels (r = 0.23, P = 0.006) was observed in non-diabetic controls. The serum vaspin concentration was also significantly correlated with body mass index (BMI) (r = 0.19, P = 0.028), waist-hip ratio (WHR) (r = 0.17, P = 0.035) and homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.14, P = 0.029) in T2DM patients. In cohort analyses, it was found that lower serum vaspin [odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.10–0.87, P = 0.015] and adiponectin (OR = 0.35, 95% CI: 0.20–0.72, P = 0.015) levels at baseline were risk factors for new onset of T2DM at follow-up. The percentage of insulin treatment in T2DM patients was higher in the sub-group with lower serum vaspin level than that in the sub-group with higher vaspin level at follow-up (55.3% vs. 44.7%, P = 0.020). Our study indicates that low serum concentration of vaspin is a risk factor for the progression of T2DM. [ABSTRACT FROM AUTHOR]