The effects of daily dose and treatment duration of metformin on the prevalence of vitamin B12 deficiency and peripheral neuropathy in Chinese patients with type 2 diabetes mellitus: A multicenter cross-sectional study.

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.

Effectiveness of the Lilly Connected Care Program in Improving Glycemic Management Among Patients With Type 2 Diabetes in China: Retrospective Real-world Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a worldwide public health concern. Mobile health management platforms could be a potential way to achieve effective glycemic control. OBJECTIVE: This study aimed to evaluate the real-world effectiveness of the Lilly Connected Care Program (LCCP) platform in glycemic control among patients with T2DM in China. METHODS: This retrospective study included Chinese patients with T2DM (aged ≥18 years) from April 1, 2017, to January 31, 2020, for the LCCP group and from January 1, 2015, to January 31, 2020, for the non-LCCP group. Propensity score matching was used to match the LCCP and non-LCCP groups to reduce confounding, with covariates including age, sex, the duration of diabetes, baseline hemoglobin A1c (HbA1c), and the number of oral antidiabetic medication classes. HbA1c reduction over 4 months, the proportions of patients achieving an HbA1c reduction of ≥0.5% or ≥1%, and the proportions of patients reaching to target HbA1c level of ≤6.5% or <7% were compared between the LCCP and non-LCCP groups. Multivariate linear regression was used to assess factors associated with HbA1c reduction. RESULTS: A total of 923 patients were included, among whom 303 pairs of patients were well matched after propensity score matching. HbA1c reduction during the 4-month follow-up was significantly larger in the LCCP group than the non-LCCP group (mean 2.21%, SD 2.37% vs mean 1.65%, SD 2.29%; P=.003). The LCCP group had a higher proportion of patients with an HbA1c reduction of ≥1% (209/303, 69% vs 174/303, 57.4%; P=.003) and ≥0.5% (229/303, 75.6% vs 206/303, 68%; P=.04). The proportions of patients reaching the target HbA1c level of ≤6.5% were significantly different between the LCCP and non-LCCP groups (88/303, 29% vs 61/303, 20.1%; P=.01), whereas the difference in the proportions of patients reaching the target HbA1c level of <7% was not statistically significant (LCCP vs non-LCCP: 128/303, 42.2% vs 109/303, 36%; P=.11). LCCP participation and higher baseline HbA1c were associated with a larger HbA1c reduction, whereas older age, longer diabetes duration, and higher baseline dose of premixed insulin analogue were associated with a smaller HbA1c reduction. CONCLUSIONS: The LCCP mobile platform was effective in glycemic control among patients with T2DM in China in the real world.

Promise of sodium-glucose co-transporter-2 inhibitors in heart failure with mildly reduced ejection fraction.

Heart failure with mildly reduced ejection fraction (HFmrEF) is associated with comparable poor outcomes as other subtypes of heart failure and remains a medical unmet need due to the paucity of effective therapies. According to large cardiovascular (CV) outcome trials in patients with heart failure, sodium-glucose co-transporter-2 inhibitors (SGLT2is) reduce CV mortality and hospitalizations for heart failure in patients with heart failure across the spectrum of left ventricular ejection fraction (LVEF). There has been a lack of dedicated trials in HFmrEF. However, several large outcome trials in heart failure that enrolled patients with HFmrEF could provide a hint on the role of SGLT2is in this subgroup. This review focuses on CV effects of three major SGLT2is-dapagliflozin, empagliflozin, and sotagliflozin-in patients with HFmrEF. A narrative review of trials investigating the efficacy of each medication in treating heart failure with LVEF > 40% is provided with a focus on their LVEF subgroup analyses. The purpose of this review is to discuss the current state of evidence regarding the potential of SGLT2is in HFmrEF management. Current limited evidence suggests that SGLT2is might be a favourable treatment modality for patients with HFmrEF to reduce hospitalization for heart failure and CV mortality. This conclusion needs to be further supported by clear HFmrEF subgroup analysis of the existing trials. Further outcome trials involving sufficient patients with different subtypes of HFmrEF are needed to confirm and assess CV benefits of SGLT2is in HFmrEF. Possible mechanisms by which SGLT2is exert their cardioprotective effect are also described briefly.

A potential role for aspirin in the prevention and treatment of cholangiocarcinoma.

Cholangiocarcinoma is the second most common primary hepatic cancer, with a rising incidence worldwide. Owing to late diagnosis and limited treatment options, the prognosis for cholangiocarcinoma remains dismal, compelling a search for new treatments. As aspirin exhibits a well-supported chemopreventive effect on common cancers, researchers have proposed using aspirin as a potential preventive and adjuvant agent for cholangiocarcinoma. In the present review of the literature, we provide a background on cholangiocarcinoma and potential mechanisms of action underlying the anticancer effect of aspirin. Although the exact mode of action remains unclear, multiple downstream effects of aspirin may interfere with cholangiocarcinogenesis, tumour growth and metastasis-including inhibiting the COX-2 pathway, preventing platelet aggregation and modulating certain proteins and signalling. This review also summarises evidence to support the chemopreventive effects of aspirin on common cancers, particularly colorectal cancer and discusses studies that report a positive outcome of aspirin in cholangiocarcinoma. Regular use of aspirin is associated with a reduced incidence of colorectal cancers as well as cholangiocarcinomas, and improved survival. Aspirin thus appears to play a role in the primary prevention and treatment of cholangiocarcinoma. However, further studies are needed to confirm these benefits and to establish a cause-and-effect relationship.

Diabetic ketoacidosis complicated by emphysematous pyelonephritis: a case report and literature review.

BACKGROUND: The management of emphysematous pyelonephritis (EPN) includes conservative medical treatment, percutaneous drainage, and surgical resection of the involved kidney. EPN with diabetic ketoacidosis(DKA) is very rare, in which the clinical management of refusing surgical drainage is inexperienced. CASE PRESENTATION: A 34-year-old woman presented with abdominal pain, chills, fever, nausea, vomiting, chest tightness, and shortness of breath. Blood test results were consistent with diabetic ketoacidosis. Urinary computed tomography scan showed multiple stones in the right kidney and lower ureter, with right hydronephrosis. Blood culture demonstrated Escherichia coli bacteremia, and EPN was diagnosed. Considering the need for a second percutaneous nephrolithotomy, the patient refused percutaneous drainage. After continuous intravenous infusion of small doses of insulin and antibiotic treatment, the ketoacidosis resolved. The patient's temperature returned to normal and abdominal pain was alleviated, and liver and kidney functions were also back to normal. After hospital discharge, the patient underwent two percutaneous nephrolithotomy in the department of urology. CONCLUSIONS: EPN with diabetic ketoacidosis should be diagnosed as soon as possible. For patients with Class 1 and Class 2 EPN with diabetic ketoacidosis and urinary tract obstruction, if surgical drainage is refused, it is particularly important to rapidly correct diabetic ketoacidosis and intravenous use of sensitive antibiotics, so as to create conditions for follow-up percutaneous nephrolithotomy.

The Role of Occupational Therapy in Secondary Prevention of Diabetes.

Diabetes mellitus is becoming a global health concern due to its prevalence and projected growth. Despite a growing number of interventions for secondary prevention of diabetes, there is a persistent poor glycemic control and poor adherence to the prescribed diabetes management regimen. In light of the tremendous costs of diabetes to both individuals and the society, it is pressing to find effective ways to improve diabetes self-management (DSM) and treatment adherence. Occupational therapists can bring values to the diabetes care team by evaluating multiple levels of influence on DSM, addressing personal and environmental barriers to well-being and DSM, and supporting patients to develop of a highly complex competences and skills to satisfactorily self-manage diabetes. This article summarizes two evidence-based, well-structured occupational therapy (OT) programs that use activity-based treatments and psychosocial strategies, respectively, to improve DSM abilities and to enhance quality of life. As the needs of adolescents with diabetes are quite different from other diabetic populations, this article also provides a summary of pediatric OT interventions that aim to facilitate autonomy and development of DSM ability among adolescents with diabetes. Evidence indicates that OT interventions can improve the quality of life and treatment adherence in patients with diabetes and hence should be continued and built on to address the increasing needs of diabetic populations.

Effect of rosiglitazone on inflammatory cytokines and oxidative stress after intensive insulin therapy in patients with newly diagnosed type 2 diabetes.

OBJECTIVE: To evaluate the effect of insulin sensitizer on inflammatory cytokines and oxidative stress in patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: After intensive insulin therapy, patients with newly diagnosed T2DM were continuously treated with either insulin sensitizer or insulin for 48 weeks, and then their inflammatory cytokine and oxidative stress levels were measured. RESULTS: Tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, hypersensitive C reactive protein (hs-CRP), malondialdehyde (MDA), and 8-iso-prostaglandin F2α (8-iso-PGF2α) levels of the rosiglitazone (RSG) group and the rosiglitazone combined with metformin (RSG + metformin) group were significantly reduced after the treatments (P < 0.05). Hs-CRP, MDA, and 8-iso-PGF2α levels of the metformin group were significantly reduced after the treatments (P < 0.05). Superoxide dismutase (SOD) and total antioxidant capacity (TAC) were significantly increased after the treatments in all three groups (P < 0.05 and P < 0.01). CONCLUSION: Early application of insulin sensitizers improved inflammation and oxidative stress in patients with newly diagnosed T2DM.

Oxidative stress and adipokine levels were significantly correlated in diabetic patients with hyperglycemic crises.

BACKGROUND: To investigate the relationship between blood adipokine level and oxidative stress in diabetic patients with hyperglycemic crises before and after treatment. METHODS: We measured superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, total antioxidant capacity (TAC), and levels of 8-iso-prostaglandin F2α (8-iso-PGF2α), adiponectin, leptin, and resistin in 63 diabetic patients with hyperglycemic crises. RESULTS: Prior to treatment, patients with hyperglycemic crises had significantly lower serum SOD activity, TAC, and adiponectin and leptin levels, and higher serum levels of MDA, 8-iso-PGF2α, and resistin compared with the healthy control individuals (all at P < 0.05). After treatment, SOD, TAC, adiponectin, and leptin levels increased significantly, while MDA, 8-iso-PGF2α, and resistin levels decreased significantly (all at P < 0.05) in the patients. CONCLUSIONS: Diabetic patients with hyperglycemic crises have increased oxidative stress, which is associated with serum adipokine abnormalities; improved oxidative stress after treatment suggests that oxidative stress may serve as target and/or indicator for the treatment of hyperglycemic crises.

Leptin concentration and oxidative stress in diabetic ketoacidosis.

BACKGROUND: Diabetes is a common metabolic state during ageing, and one in five elderly individuals suffers from diabetes. However, few studies have been performed in elderly diabetic patients, and large randomized clinical trials in this population are rare. The purpose of this study was to investigate changes in serum leptin levels in elderly patients with diabetic ketoacidosis (DKA) before and after treatment and assess its relationship with oxidative stress parameters. MATERIALS AND METHODS: Serum leptin levels, plasma superoxide dismutase (SOD) activity, plasma malondialdehyde (MDA) levels, plasma total antioxidant capacity (TAC) and plasma 8-iso-prostaglandin F2α (8-iso-PGF2α ) levels were measured in elderly patients aged 81.76 ± 9.42 years with DKA before and after treatment. RESULTS: Plasma SOD activity, TAC and serum leptins before treatment were significantly lower in elderly patients with DKA compared with the control group (P < 0.05), whereas plasma MDA and 8-iso-PGF2α levels before treatment were significantly higher in elderly patients with DKA (P < 0.05). Plasma SOD activity, TAC and serum leptin levels in elderly patients with DKA were significantly elevated after treatment, whereas their plasma MDA and 8-iso-PGF2α levels were significantly reduced (P < 0.05). Leptin levels negatively correlated with plasma 8-iso-PGF2α after treatment in elderly DKA patients (r = -0.36, P < 0.05). Stepwise multiple regression analysis showed that 8-iso-PGF2α was a significant factor affecting serum leptin levels. CONCLUSIONS: Serum leptin levels in the elderly patients with DKA were significantly reduced after treatment, which was associated with oxidative stress.

Correlation of the plasma levels of soluble RAGE and endogenous secretory RAGE with oxidative stress in pre-diabetic patients.

BACKGROUND: Soluble RAGE (sRAGE), endogenous secretory RAGE (esRAGE) and oxidative stress played important roles in the pathogenesis of diabetes and its complications. The changes in sRAGE and esRAGE during pre-diabetes were indefinite. METHODS: Patients were divided into NGT, pre-diabetes (pre-DM), and newly diagnosed diabetes mellitus (DM) groups according to blood glucose levels. The levels of sRAGE, esRAGE, 8-isoprostaglandin F2α (8-iso-PGF2α), superoxide dismutase (SOD) activity, total antioxidant capacity (TAOC), malondialdehyde (MDA), and other related indicators were then assessed. RESULTS: sRAGE and esRAGE in the pre-DM and DM groups were significantly lower than in the NGT group (p<0.05). In the pre-DM group, sRAGE was positively correlated with esRAGE (r=0.382, P=0.007), and negatively correlated with homeostasis model assessment-estimated insulin resistance (HOMA-IR), MDA, and 8-iso-PGF2α (r=-0.314, -0.313, and -0.34, P=0.028, 0.028, and 0.016, respectively). The concentration of esRAGE was positively correlated with sRAGE and TAOC (r=0.382 and 0.598, and P=0.007, <0.001), and negatively correlated with MDA (r=-0.397, P=0.005). CONCLUSIONS: Changes in sRAGE, esRAGE, and oxidative stress occurred in pre-diabetic patients. sRAGE and esRAGE might play an essential role in the balance between oxidative stress and antioxidant defense. THE SIGNIFICANT FINDINGS OF THE STUDY: Changes in sRAGE, esRAGE, and oxidative stress occurred in pre-diabetic patients. THIS STUDY ADDS: sRAGE, esRAGE, and oxidative stress are altered early during pre-diabetes. sRAGE and esRAGE may have played different roles in the balance between oxidative stress and the antioxidant defense.

The association of oxidative stress and pro-inflammatory cytokines in diabetic patients with hyperglycemic crisis.

AIMS: To investigate the relationship between oxidative stress and serum levels of pro-inflammatory cytokines in diabetic patients with hyperglycemic crisis. METHODS: Seventy-three patients presenting to hospital with diabetic ketoacidosis or non-ketotic hyperglycemia were studied. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, total antioxidant capacity (TAC), 8-iso-prostaglandin F2α (8-iso-prostaglandinF2α, 8-iso-PGF2α), tumor necrosis factor receptor-I (TNF-RI), interleukin -1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were measured in all patients. The patients were then given an intravenous infusion of insulin 0.1U • kg-1 • h-1, as well as fluids, symptomatic therapy and parenteral and intravenous nutrition. RESULTS CONCLUSION: Patients with hyperglycemic crises have significantly increased oxidative stress and dysregulated serum pro-inflammatory cytokines that can be effectively treated by intensive insulin therapy.

Impact of sociodemographic and diabetes-related factors on the presence and severity of depression in immigrant chinese Australian people with diabetes.

The coexistence of depression with diabetes significantly increases the likelihood of developing complications. This study aimed to describe the presence and severity of depression in immigrant Chinese Australian people with diabetes and explore its relationship to sociodemographic and diabetes-related factors. This study found that approximately one-fifth of immigrant Chinese Australian people with diabetes had symptoms consistent with moderate to severe depression and that individuals who are socially isolated and have more complex treatment and complications of diabetes are particularly at risk.

The relationship between oxidative stress and the levels of serum circulating adhesion molecules in patients with hyperglycemia crises.

OBJECTIVE: To investigate the relationship between oxidative stress and the levels of serum circulating adhesion molecules in patients with hyperglycemia crises. METHODS: A total of 73 patients with diabetic ketoacidosis and nonketotic hyperglycemia were treated on a low-dose insulin protocol using intravenous infusion of insulin with the established rate of 0.1U·kg(-1)·h(-1). The patients received intravenous fluids and nutrition orally and intravenously. The levels of serum ICAM-1, E-selectin, and 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)); the activities of superoxide dismutase (SOD); the total antioxidant capacity (TAC) and the contents of malondialdehyde (MDA) in 68 patients with hyperglycemia crisis on admission and after insulin therapy with resolution of hyperglycemia and ketoacidosis (72 h after resolution) were measured. Another 33 healthy individuals served as normal controls. RESULTS: The activities of SOD and TAC at admission were lower in patients with hyperglycemia crisis than in normal controls, and the levels of MDA, 8-iso-PGF(2α), ICAM-1 and E-selectin were higher in patients with hyperglycemia crisis than in normal controls (all p<0.05). The activities of SOD and TAC in patients at resolution were significantly lower than in patients at admission and were significantly higher than in controls (p<0.05). The levels of MDA, 8-iso-PGF(2α), ICAM-1 and E-selectin in patients at resolution were markedly lower than in patients at admission (all p<0.05) and were significantly higher than in normal controls (p<0.05). There was a significant positive correlation between ICAM-1 and SOD (r=0.32, p<0.05) and between E-selectin and MDA (r=0.30, p<0.05) in patients at admission, and the level of E-selectin was positively correlated with MDA and 8-iso-PGF(2α) in patients at resolution (r=0.33, 0.36, p<0.05). In stepwise regression analysis, MDA and 8-iso-PGF(2α) showed a significant association with E-selectin, and 8-iso-PGF(2α) showed a significant association with ICAM-1. CONCLUSION: The oxidative stress and the levels of serum circulating adhesion molecules are significantly changed in patients with hyperglycemia crisis. Intensive insulin therapy can attenuate the abnormity of oxidative stress and the levels of serum circulating adhesion molecules in patients with hyperglycemia crisis.

Correlation between glucose fluctuations and carotid intima-media thickness in type 2 diabetes.

AIMS: To evaluate the relationship between blood glucose fluctuations and carotid atherosclerosis (AS) in type 2 diabetic patients. METHODS: A case-control study included 36 patients with type 2 diabetes and 10 controls. According to the levels of carotid intima-media thickness (CIMT), 36 diabetic patients were classified into two groups, the diabetes mellitus without atherosclerosis (DM-AS, n=20) and diabetes mellitus with atherosclerosis (DM+AS, n=16). The glucose excursions were assessed by the following parameters obtained from continuous glucose monitoring system for 72h: the mean blood glucose (MBG) and its standard deviation (SD), the area under the ROC curve when the blood glucose was higher than 7.8mmol/L (AUC7.8), the mean amplitude of glycemic excursion (MAGE), the mean of daily differences (MODD), and the largest amplitude of glycemic excursion (LAGE). RESULTS: The levels of MBG, SD, MAGE, LAGE, and AUC7.8 were gradually increased with the progression of atherosclerosis (P<0.05). The Spearman's correlation analysis showed that the CIMT was correlated to the age (R=0.58, P<0.001), the duration (R=0.50, P<0.001), the MAGE (R=0.34, P=0.021), and the LAGE (R=0.31, P=0.035). CONCLUSION: These results suggest that glucose fluctuations may accelerate atherogenesis in older type 2 diabetic patients who had a longer duration.

[The relationship between serum level of leptin and oxidative stress in patients with hyperglycemia crisis].

OBJECTIVE: To investigate the relationship between the levels of serum leptin and oxidative stress in patients with hyperglycemia crisis. METHODS: A total of 96 patients with diabetic ketoacidosis (DKA) and nonketotic hyperglycemia (NKH) were treated on a low-dose insulin protocol using intravenous infusion of insulin with the established rate of 0.1 Uxkg(-1)xh(-1), with the patients on intravenous fluids and receiving nutrition by mouth and vein. The levels of serum leptin, 8-iso-prostaglandin F(2 alpha) (8-iso-PGF(2 alpha)), the activities of superoxide dismutase (SOD), total antioxidant capacity (TAC) and the contents of malondialdehyde (MDA) in 96 patients with hyperglycemia crisis on admission and after insulin therapy with resolution of hyperglycemia and ketoacidosis (72 hours) were measured. Another 35 healthy individuals served as normal control. RESULTS: The activities of SOD, TAC and the levels of leptin before treatment were lower in patients with hyperglycemia crisis than in normal controls, and the levels of MDA and 8-iso-PGF(2 alpha) were more markedly elevated than those in normal controls (all P<0.05). The activities of SOD, TAC and the levels of leptin in patients after treatment were significantly higher than those in patients before treatment, and the levels of MDA and 8-iso-PGF(2 alpha) were significantly lower than those in patients on admission (all P<0.05). There was significant positive correlation between leptin and MDA in patients before treatment (r=0.38, P<0.05), and the level of leptin was negatively correlated with MDA and 8-iso-PGF(2 alpha) in patients after treatment (r(1)=-0.35, r(2)=-0.37, both P<0.05). In stepwise regression analysis, MDA and 8-iso-PGF(2 alpha) showed a significant association with leptin. CONCLUSION: The levels of leptin are significantly lowered in patients with hyperglycemia crisis. Oxidative stress may participate in determining the leptin level in hyperglycemia crisis.

[Circulating levels of oxidative stress and adipocytokines in obese subjects].

AIM: To investigate the relationship between adipocytokines levels and oxidative stress in obese males. METHODS: The levels of 8-iso-prostaglandinF2alpha(8-iso-PGF2alpha), superoxide dismutase (SOD), malondialdehyde (MDA), adiponectin, leptin, restistin, TNF-receptors 1(TNF-R1), Interleukin-1beta(IL-1beta) and Interleukin-6(IL-6) were measured in obese men and normal controls. RESULTS: The levels of 8-iso-PGF(2alpha), MDA, leptin, TNF-R1, IL-1beta and IL-6 was significantly higher than that normal controls (P<0.05, P<0.01). The levels of adiponectin and the activity of SOD decreased significantly in obese men.There was no significant difference in the restistin between obese men and normal controls. There was significantly positive correlation between 8-iso-PGF(2alpha) and body mass index (BMI) (r=0.54, P<0.05) in obese. A significantly negative correlation was found between 8-iso-PGF(2alpha) and adiponectin (r=-0.56, P<0.05) in obese subjects. The levels of leptin was negative correlated with body fat content(%)(r=-0.53, P<0.05) in obese subjects. A significant negative correlation was observed between the levels of adiponectin and LDL(r=-0.54, P<0.05), IL-6 (r=-0.41, P<0.05). In a multiple regression analysis model, the levels of adiponectin and IL-6 were the main determinants of the oxidative stress in obese men. CONCLUSION: Changed concentration of adipocytokines was found in obese men. There are significantly correlation with between oxidative stress and adipocytokines.