Background:Multiple published quantitative systematic reviews have reported on adverse events associated with the use of sodium glucose co-transporter 2 (SGLT-2) inhibitors in patients with type 2 ...

https://journals.sagepub.com/doi/pdf/10.1177/2042098621989134

Adverse events associated with sodium glucose co-transporter 2 inhibitors: an overview of quantitative systematic reviews.

Oxidative stress (OS) is implicated in postmenopausal osteoporosis (PO). Results show an imbalance between antioxidative and oxidative markers in PO. Thus, monitoring of OS-related biomarkers and keeping balance between reactive oxygen species and antioxidant system are beneficial to the diagnosis and prognosis of PO. Oxidative stress (OS) has been implicated in postmenopausal osteoporosis (PO). However, the relations between OS-related markers and PO are controversial. This study aimed to quantitatively and comprehensively assess the roles of OS-related biomarkers in PO. Relevant articles were retrieved from electronic databases. All OS-associated biomarkers with at least 2 independent study outcomes were meta-analyzed. The pooled standardized mean differences (SMD) with its 95% confidence intervals (CI) were presented. A total of 36 studies involving 16 OS-related biomarkers were investigated. The overall results showed that total oxidant status (TOS), superoxide dismutase (SOD), hydroperoxides (HY), paraoxonase (PON1), nitric oxide (NO), and homocysteine (Hcy) were not statistically different between the PO and control groups, whereas significantly increased levels of oxidative stress index (OSI), malondialdehyde (MDA), advanced oxidation protein products (AOPP), and vitamin B12, along with decreased total antioxidant status (TAS), total antioxidant power (TAP), catalase (CAT), glutathione peroxidase (GPx), uric acid (UA), and folate, were detected in the PO group. Subgroup analysis based on biological samples displayed significantly elevated NO in erythrocyte and Hcy in serum, along with decreased SOD in serum. Monitoring of certain OS-related biomarkers might be beneficial to the diagnosis and prognosis of PO.

Correlation of oxidative stress-related biomarkers with postmenopausal osteoporosis: a systematic review and meta-analysis

Timed up-and-go test is a useful predictor of fracture incidence

Background Since the discovery of insulin, it was the only drug available for the treatment of diabetes until the development of sulfonylureas and biguanides 50 years later. But even with the availability of oral glucose-lowering drugs, insulin supplementation was often needed to achieve good glucose control in type 2 diabetes. Insulin NPH became the basal insulin therapy of choice and adding NPH to metformin and/or sulfonylureas became the standard of care until basal insulin analogs were developed and new glucose-lowering drugs became available. Areas of uncertainty The advantages in cost-benefit of insulin analogs and their combination with new glucose-lowering drugs are still a matter of debate. There is no general agreement on how to avoid inertia by prescribing insulin therapy in type 2 diabetes when really needed, as reflected by the diversity of recommendations in the current clinical practice guidelines. Data sources When necessary for this review, a systematic search of the evidence was done in PubMed and Cochrane databases. Therapeutic advances Adding new oral glucose-lowering drugs to insulin such as DPP-4 inhibitors lead to a modest HbA1c reduction without weight gain and no increase in hypoglycemia. When SGLT-2 inhibitors are added instead, there is a slightly higher HbA1c reduction, but with body weight and blood pressure reduction. The downside is the increase in genital tract infections. GLP-1 receptor agonists have become the best alternative when basal insulin fails, particularly using fixed ratio combinations. Rapid-acting insulins via the inhaled route may also become an alternative for insulin supplementation and/or intensification. "Smart insulins" are under investigation and may become available for clinical use in the near future. Conclusions Aggressive weight loss strategies together with the new glucose-lowering drugs which do not cause hypoglycemia nor weight gain should limit the number of patients with type 2 diabetes needing insulin. Nevertheless, because of therapeutic inertia and the progressive nature of the disease, many need at least a basal insulin supplementation and insulin analogs are the best choice as they become more affordable. Fixed ratio combinations with GLP1 receptor agonists are a good choice for intensification of insulin therapy.

Insulin Therapy in Type 2 Diabetes.

Objectives Uric acid has been found to be potentially protective in bone metabolism We investigated the relationship between serum uric acid (sUA) and lumbar bone mineral density (BMD) among 4156 participants aged 60 years and over from the National Health and Nutrition Examination Survey (NHANES) Methods To estimate the association between sUA and lumbar BMD, multivariate logistic regression analyses were conducted Fitted smoothing curves and generalized additive models were also performed Results We found sUA positively correlated with lumbar BMD after adjusting for other confounders On subgroup analyses, stratified by sex and race/ethnicity, the positive correlation of sUA with lumbar BMD remained in both men and women, as well as in whites and Mexican Americans, but not in blacks In blacks, the association of sUA with lumbar BMD was an inverted U-shaped curve (inflection point: 75 mg/dL) Conclusions Our study revealed a positive relationship between sUA and lumbar BMD among most old adults This association followed an inverted U-shaped curve among blacks

/pdf/the-association-between-serum-uric-acid-and-bone-mineral-8l02tu5ffl.pdf

The Association between Serum Uric Acid and Bone Mineral Density in Older Adults.

AIMS/INTRODUCTION In the present meta-analysis, we aimed to determine the effects of sodium-glucose cotransporter 2 inhibitor (SGLT-2i) in addition to insulin therapy on cardiovascular risk factors in type 2 diabetes patients. MATERIALS AND METHODS Randomized controlled trials were identified by searching the PubMed, Embase and Cochrane Library databases published before September 2017. The intervention group received SGLT-2i as add-on treatment to insulin therapy, and the control group received placebos in addition to insulin. We assessed pooled data, including weighted mean differences and 95% confidence intervals (CIs) using a random-effects model. RESULTS A total of 10 randomized controlled trials (n = 5,159) were eligible. The weighted mean differences for systolic blood pressure and diastolic blood pressure were -3.17 mmHg (95% CI -4.53, -1.80, I2 = 0%) and -1.60 mmHg (95% CI -2.52, -0.69, I2 = 0%) in the intervention groups. Glycosylated hemoglobin, fasting plasma glucose, postprandial glucose and daily insulin were also lower in the intervention groups, with relative weighted mean differences of -0.49% (95% CI -0.71, -0.28%, I2 = 92%), -1.10 mmol/L (95% CI -1.69, -0.51 mmol/L, I2 = 84%), -3.63 mmol/L (95% CI -4.36, -2.89, I2 = 0%) and -5.42 IU/day (95% CI -8.12, -2.72, I2 = 93%). The transformations of uric acid and bodyweight were -26.16 μmol/L (95% CI -42.14, -10.17, I2 = 80%) and -2.13 kg (95% CI -2.66, -1.60, I2 = 83%). The relative risk of hypoglycemia was 1.09 (95% CI 1.02, 1.17, P < 0.01). The relative risks of urinary tract and genital infection were 1.29 (95% CI 1.03, 1.62, P = 0.03) and 5.25 (95% CI 3.55, 7.74, P < 0.01). CONCLUSIONS The results showed that in the intervention group, greater reductions were achieved for blood pressure, glucose control, uric acid and bodyweight. This treatment regimen might therefore provide beneficial effects on the occurrence and development of cardiovascular events.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jdi.12876

Effects of sodium-glucose cotransporter 2 inhibitors in addition to insulin therapy on cardiovascular risk factors in type 2 diabetes patients: A meta-analysis of randomized controlled trials

Aims Previous evidence has demonstrated an increased fracture risk among the population with type 2 diabetes mellitus (T2DM). This study investigated the prevalence of bone fractures in elderly subjects (with and without type 2 diabetes) and identified any fracture risk factors, especially the risk factors for common known fractures in particular diabetic populations. Methods This cross-sectional study was conducted with community-dwelling people over 60 years old in nine communities from the city of Shenyang, which is the capital of Northeast China's Liaoning Province. A total of 3430 elderly adults (2201 females, mean ± standard deviation age 68.16 ± 6.1 years; 1229 males, 69.16 ± 6.7 years) were included. Our study measured the heel bone mineral density (BMD) and used the timed "up and go" (TUG) test and other indicators. In addition, we performed logistic regression analysis to explore the risk factors for fractures in the general population and the diabetic population and to analyze the differences. Results The results revealed that a total of 201 elderly persons (5.8%), with an average age of 70.05 ± 6.54 years, suffered from a history of fragility fractures, which affected more females (74.6%) than males (p = 0.001). The prevalence of fractures in the T2DM population was 7.3%, which was much higher than the 5.2% in non-T2DM population (p = 0.001). The prevalence of fractures in the T2DM population was 7.3%, which was much higher than the 5.2% in non-T2DM population (p = 0.001). The prevalence of fractures in the T2DM population was 7.3%, which was much higher than the 5.2% in non-T2DM population (p = 0.001). The prevalence of fractures in the T2DM population was 7.3%, which was much higher than the 5.2% in non-T2DM population (T-score≤-2.5 (OR 1.750) were independent risk factors for fragility fractures in the non-T2DM population, but they were not risk factors in the T2DM population. Conclusions This study found that low BMD and slow TUG time were independent risk factors for fractures in non-T2DM patients, while no associations were found in the T2DM population. Patients with T2DM have a higher risk for fractures even when they have sufficient BMD and a short TUG time. TUG and BMD underestimated the risk for fractures in the T2DM population.

/pdf/assessment-of-risk-factors-for-fractures-in-patients-with-3dho06k0u3.pdf

Assessment of Risk Factors for Fractures in Patients with Type 2 Diabetes over 60 Years Old: A Cross-Sectional Study from Northeast China.

Background and objective: Oxidative stress has been demonstrated to be a mechanism that leads to bone mass reduction, and according to many studies, serum uric acid (UA) is a strong endogenous antioxidant that can protect bone mineral density (BMD). To date, there have been no large-scale, cross-sectional studies based on the population in northeast China to assess the relationship between serum UA and BMD. Therefore, we examined the association between serum UA and BMD among a Chinese population older than 60 years old in northeast China. Methods: This research was a cross-sectional study of 3465 Chinese individuals over 60 years old in nine communities from the city of Shenyang, which is the capital of northeast China's Liaoning Province. Participants were stratified into three groups by serum UA or BMD levels, and then Pearson's correlation analysis and multiple regression analysis were used to study the relationship between serum UA and BMD. Results: We found that participants with higher serum UA levels had significantly greater BMD and T-values compared to those of participants with lower serum UA levels. After adjusting for confounding factors, Pearson's correlation analysis and multiple regression analysis showed that higher serum UA levels remained associated with higher BMD levels (P<0.05). In different models, the prevalence of osteoporosis (OP) among participants with higher serum UA levels was reduced by 23% to 26% (P<0.05) compared to that in individuals with lower serum UA levels. In addition, serum UA levels were negatively correlated with estimated glomerular filtration rate (eGFR) and positively correlated with 25-hydroxy vitamin D3 [25-(OH)D3] (P<0.05). Conclusion: We concluded that higher serum UA levels are associated with greater BMD, and serum UA might have a protective effect on bone metabolism due to its antioxidant properties.

/pdf/specific-higher-levels-of-serum-uric-acid-might-have-a-s8jmz6cinu.pdf

Specific higher levels of serum uric acid might have a protective effect on bone mineral density within a Chinese population over 60 years old: a cross-sectional study from northeast China.

BACKGROUND Serum uric acid (SUA) and alanine aminotransferase (ALT) levels are increased in patients with metabolic syndrome. This study aimed to investigate the association between the combined levels of SUA and ALT and the risk of metabolic syndrome in residents ≥60 years of age in Northeastern China. MATERIAL AND METHODS A population study included nine communities in Shenyang, Northeast China, and 3,998 participants (1,434 men and 2,564 women) who were ≥60 years old. SUA and ALT measurements (levels 1-3) and clinical parameters were recorded. Metabolic syndrome was diagnosed according to the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). The association between the combined SUA and ALT levels and metabolic syndrome was determined by multivariate logistic regression analysis in tertiles that included Groups 1-9. RESULTS The prevalence of metabolic syndrome was 43.2% (men), and 61.9% (women), and the prevalence and odds ratio (OR) values increased with increasing SUA and ALT levels. The OR values of metabolic syndrome in the ALT Groups 2-3 were 1.329 (95% CI, 1.137-1.554) and 2.362 (95% CI, 2.006-2.781), and in the SUA Groups 2-3 the OR values were 1.718 (95% CI, 1.466-2.015) and 2.743 (95% CI, 2.310-3.256). The OR of the combined increase in SUA and ALT and metabolic syndrome in Groups 1-9 ranged from 1.494-5.889 (all, p<0.05). CONCLUSIONS Increased combined SUA and ALT was more significantly associated with metabolic syndrome than an increase in SUA or ALT alone.

/pdf/measurement-of-the-combined-levels-of-serum-uric-acid-and-1duy3a4ygo.pdf

Measurement of the Combined Levels of Serum Uric Acid and Alanine Aminotransferase and the Risk of Metabolic Syndrome in a Population Aged 60 Years or More in Northeastern China.

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Effects of sodium-glucose cotransporter 2 inhibitors in addition to insulin therapy on cardiovascular risk factors in type 2 diabetes patients: A meta-analysis of randomized controlled trials

Assessment of Risk Factors for Fractures in Patients with Type 2 Diabetes over 60 Years Old: A Cross-Sectional Study from Northeast China.

Specific higher levels of serum uric acid might have a protective effect on bone mineral density within a Chinese population over 60 years old: a cross-sectional study from northeast China.

Measurement of the Combined Levels of Serum Uric Acid and Alanine Aminotransferase and the Risk of Metabolic Syndrome in a Population Aged 60 Years or More in Northeastern China.