The association of cardio-metabolic risk factors and history of falling in men with osteosarcopenia: a cross-sectional analysis of Bushehr Elderly Health (BEH) program

Background Osteosarcopenia, defined as sarcopenia plus osteopenia/osteoporosis, may increase the risk of fractures and affects morbidity and mortality in the older population. Falling is also common in the elderly and increases the risk of fractures and mortality. We examined the association of cardio-metabolic risk factors with a history of falling in osteosarcopenic men. Methods We used the baseline data of the Bushehr Elderly Health (BEH) program. Osteosarcopenia was defined as having both sarcopenia (reduced skeletal muscle mass plus low physical performance and/or low muscle strength) and osteopenia/osteoporosis (T-score ≤ − 1.0). Falling was defined as a self-reported history of an unintentional down on the ground during the previous year before the study. We used logistic regression analysis to estimate the adjusted odds ratio (AOR) with a 95% Confidence Interval (CI) to quantify the associations. Results All elderly men diagnosed with osteosarcopenia (n = 341), with a mean age of 73.3(±7.4) years, were included. Almost 50(14.7%) participants reported falling. Age showed a positive association with falling (AOR: 1.09, 95%CI: 1.04–1.14). An increase of 10 mmHg in systolic blood pressure(SBP), reduces the odds of falling by 26%(AOR:0.74, 95%CI:0.62–0.89), while a positive association was detected for fasting plasma glucose (FPG), as 10 mg/dl increase in the FPG, raises the chance of falling by 14%(AOR = 1.14, 95%CI:1.06,1.23). Hypertriglyceridemia was inversely associated with falling (AOR = 0.33, 95% CI: 0.12, 0.89). Conclusions Falling is a major public health problem in rapidly aging countries, especially in individuals with a higher risk of fragility fractures. Older age-raised fasting plasma glucose and low SBP are associated with falling in osteosarcopenic patients. Considering the higher risk of fracture in osteosarcopenic men, comprehensive strategies are needed to prevent fall-related injuries in this high-risk population.

Influence of Fasting Plasma Glucose Level on Admission of COVID-19 Patients: A Retrospective Study

Background. The coronavirus disease 2019 (COVID-19) is a serious global health threat and has spread dramatically worldwide. Prolonged viral shedding is associated with a more severe disease course and inflammatory reaction. Blood glucose levels were significantly associated with an increased hazard ratio (HR) for poor outcomes in COVID-19 patients. Objective. Previous studies focused primarily on the relationship between blood glucose and mortality or severe outcomes, but there were few research studies on the relationship between fasting plasma glucose (FPG) and duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA positive status. To explore the relationship between FPG levels and prolonged duration of SARS-CoV-2 viral positivity, the clinical data of COVID-19 patients were analyzed. Method. In this retrospective study, 99 cases of COVID-19 patients in Beijing Ditan Hospital were recruited, and their clinical and laboratory findings at admission were collected and analyzed. Furthermore, the risk factors for prolonged duration of SARS-CoV-2 RNA shedding were identified, and the relationship between FPG levels and the prolonged presence of SARS-CoV-2 RNA was evaluated. Result. We found that elevated FPG levels were correlated with longer duration of SARS-CoV-2 RNA positivity, classification of COVID-19, imaging changes of chest CT, inflammation-related biomarkers, and CD8+ T cell number in COVID-19 patients. In a logistic regression model, after adjusting for gender and age, COVID-19 patients with elevated FPG were more likely to had longer duration of SARS-CoV-2 RNA positivity than those with normal FPG levels (OR 3.053 [95% CI 1.343, 6.936]). Conclusion. Higher FPG levels (≥6.1 mmol/l) at admission was an independent predictor for prolonged SARS-CoV-2 shedding, regardless of a known history of diabetes. It suggests that intensive monitoring and control of blood glucose are important for all COVID-19 patients.

Reductions in Intestinal Taurine-Conjugated Bile Acids and Short-Chain Fatty Acid-Producing Bacteria Might be Novel Mechanisms of Type 2 Diabetes Mellitus in Otsuka Long-Evans Tokushima Fatty Rats

Background The pathogenesis of spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats, among the best models for human type 2 diabetes mellitus (T2DM), remains poorly defined. Therefore, we investigated the dynamic changes in taurine-conjugated bile acids (T-BAs) and intestinal microbiota during T2DM development in OLETF rats. Methods OLETF rats and corresponding diabetes-resistant Long Evans Tokushima Otsuka (LETO) rats were fed a normal baseline diet. The progress of T2DM was divided into four phases, including normal glycemia-normal insulinemia (baseline), normal glycemia-hyperinsulinemia, impaired glucose tolerance, and DM. Body weight, liver function, blood lipids, fasting plasma glucose, fasting plasma insulin, fasting plasma glucagon-like peptide (GLP)-1 and GLP-2, serum and fecal T-BAs, and gut microbiota were analyzed during the entire course of T2DM development. Results There were reductions in fecal T-BAs and short-chain fatty acids (SCFAs)-producing bacteria including Phascolarctobacterium and Lactobacillus in OLETF rats compared with those in LETO rats at baseline, and low levels of fecal T-BAs and SCFAs-producing bacteria were maintained throughout the whole course of the development of T2DM among OLETF rats compared with those in corresponding age-matched LETO rats. Fecal taurine-conjugated chenodeoxycholic acid correlated positively with Phascolarctobacterium. Fecal taurine-conjugated deoxycholic acid correlated positively with Lactobacillus and fasting plasma GLP-1 and inversely with fasting plasma glucose. Conclusion The fecal BAs profiles and microbiota structure among OLETF rats were different from those of LETO rats during the entire course of T2DM development, indicating that reductions in intestinal T-BAs and specific SCFA-producing bacteria may be potential mechanisms of T2DM in OLETF rats.

Soliqua (Lixi Lan): Sustained Long Term Cost Efficacy and Safety When Used in Combination with Metformin and Glimepiride

Background: Previous studies using basal insulin documented the lowest daily dose and least hypoglycemic events when combined with Glimepiride and Metformin while attaining desirable glycemic control. However, Pivotal trials with Soliqua excluded Glimepiride as a part of therapy as well as subjects with moderate obesity (BMI > 35kg/m2). Moreover, these trials were relatively short term. Objective: Assess long term efficacy and safety of Soliqua in combination with Glimepiride and Metformin in subjects with type 2 diabetes irrespective of BMI in ‘real world’ experience. Subjects: 30 adults with type 2 diabetes, age range 32-72 years with HbA1C >7.5% while receiving therapy with 1) Glimepiride, Metformin and Basal insulin and 2) Metformin and/or DPP 4 inhibitors and/or other SUs and /or GLP1 RA and/or Basal insulin and/or prandial insulin. Type 2 diabetes was confirmed by presence of C-peptide. Subjects with history of gastroparesis, Triglycerides over 300 mg/dl and pancreatitis were excluded. Subjects with elevated liver enzymes, over 2.5 times normal and EGFR < 30 ml/min were excluded as well. Methods: All prior therapies were discontinued. All subjects were started on Glimepiride 8 mg, Metformin 1000-2000 mg and SC Soliqua was initiated prior to breakfast with daily dose 15 or 30 units as recommended. Daily dose was increased by 2 units every 3 days until AM fasting plasma glucose of 80-130 mg/dl was attained or the dose of 60 units was reached. The stable daily dose of Soliqua was continued until the time of analysis. Comparisons were conducted between body weights (kg), fasting plasma glucose (FPG) and HbA1C prior to initiation of combination therapy (pre Rx) and every 3-6 months until the time of analysis (post Rx). Results: BMI ranged between 22-67 kg/m2. Duration of diabetes was 5-25 years. Duration of therapy with the combination therapy range, 7-56 months. Subjects were divided into 2 groups according to desirable HbA1C levels as per recommendations by ADA: 1) desirable HbA1C is < 7.0%, 2) desirable HbA1C 7-8 %. Both Fasting plasma glucose (mg/dl) and HbA1C (%) declined from 167 ± 10 and 9.7 ± 0.8 to 114 ± 4 and 7.6± 0.3 at the time of analyses (post Rx) respectively in the whole cohort. In 4 (0.13 %) morbidly obese subjects, FPG and HbA1C levels declined though not achieving desirable glycemic goals despite receiving maximal daily dose, 60 units of Soliqua. All four belonged to group 1. In the remaining 17 subjects desirable glycemic levels were attained and maintained. In group 2, desirable glycemia was reached in all 9 subjects. Symptomatic hypoglycemic events confirmed by blood sugar <70 mg/dl were reported by 4 subjects, none requiring secondary assistance. No severe hypoglycemia was reported. Mean daily dose of Soliqua was lower when compared to the pivotal trials. Conclusion: Soliqua is effective and safe in the long term in all subjects irrespective of BMI when administered in combination with Glimepiride and Metformin. Moreover, lesser daily dose required to attain desirable glycemia with this oral combination may render it to be effective without attaining maximum daily dose in subjects with higher BMIs documented in pivotal trials using Metformin alone.

A Significance Assessment of Diabetes Diagnostic Biomarkers Using Machine Learning

Diabetes can be diagnosed by either Fasting Plasma Glucose or Hemoglobin A1c. The aim of our study was to explore the differences between the two criteria through the development of a machine learning based diabetes diagnostic algorithm and analysing the predictive contribution of each input biomarker. Our study concludes that fasting insulin is predictive of diabetes defined by FPG, but not by HbA1c. Besides, 28 other fasting blood biomarkers were not significant predictors of diabetes.

Dapagliflozin, metformin, monotherapy or both in patients with metabolic syndrome

The present study evaluated the effects of dapagliflozin, a SGLT2 inhibitor, or dapagliflozin plus metformin versus metformin monotherapy in patients with metabolic syndrome. This study included patients who admitted in Jiangxi Provincial People’s Hospital from January 1, 2017 to December 31, 2019 and were diagnosed with metabolic syndrome. A total of 248 participants were randomly assigned to divide into three groups: dapagliflozin group; metformin group; dapagliflozin in combined with metformin group. Dapagliflozin group and metformin group were associated with similar improvements in components of metabolic syndrome. Relative to dapagliflozin or metformin monotherapy, dapagliflozin combined with metformin provided greater improvements in components of metabolic syndrome. So did HOMA-IR scores, fasting plasma insulin and inflammatory indicators (hsCRP, PMN/HDL-C and Monocytes/HDL-C). Dapagliflozin improved all components of metabolic syndrome in patients with metabolic syndrome. Furthermore, dapagliflozin combined with metformin showed more meaningful improvements in any of components of metabolic syndrome than dapagliflozin or metformin monotherapy.

Plasma FGF-21 and Sclerostin Levels, Glycemia, Adiposity and Insulin Sensitivity in Normoglycemic Black and White Adults

Increased circulating fibroblast growth factor (FGF)-21 and sclerostin levels have been reported in patients with type 2 diabetes (T2D). We assessed the association of FGF-21 and sclerostin with adiposity, glycemia and glucoregulatory measures in healthy subjects. We studied 20 normoglycemic Black and White offspring of parents with T2D. Assessments included OGTT, insulin sensitivity (Si-clamp), insulin secretion (HOMA-B), and body fat (DXA). Fasting plasma FGF-21 and sclerostin levels were measured with ELISAs. The participants' mean (+SD) age was 50.4 ± 5.97 yr; BMI 32.5 ± 5.86 kg/m2; fasting plasma glucose (FPG) 96.1 ± 5.21 mg/dl, and 2-hr post-load glucose (2hPG) 116 ± 5.45 mg/dl. FGF-21 levels were similar in Blacks vs. Whites (0.36 ± 0.15 ng/ml vs. 0.39 ± 0.25 ng/ml), men vs. women (0.45 ± 0.14 vs. 0.44 ± 0.07ng/ml), correlated positively with body mass index (BMI) (r=0.23, P=0.05) and waist circumference (r=0.27, P=0.04), and inversely with FPG (r= -0.26, P=0.05). Sclerostin levels also were similar in Blacks (33.5 ± 17.1 pmol/l) vs. Whites (34.2 ± 6.41 pmol/l), men vs. women (35.3 ± 9.01 pmol/l vs. 32.3 ± 15.8 pmol/l), and correlated inversely with FPG (r= - 0.11-0.44) but not adiposity measures. The correlation coefficient between Si-clamp values and FGF-21 levels was -0.31 (P=0.09) compared with 0.04 (P=0.89) for sclerostin levels. FGF-21 and sclerostin levels were not correlated with each other or HOMA-B. Among healthy Black and White subjects, plasma FGF-21 and sclerostin showed differential associations with adiposity but concordant association with FPG levels.

The Glucagon Receptor Antagonist LY2409021 has No Effect on Postprandial Glucose in Type 2 Diabetes

Objective: Type 2 diabetes (T2D) pathophysiology includes fasting and postprandial hyperglucagonemia, which has been linked to hyperglycemia via increased endogenous glucose production (EGP). We used a glucagon receptor antagonist (LY2409021) and stable isotope tracer infusions to investigate consequences of hyperglucagonemia in type 2 diabetes. Design: A double-blinded, randomized, placebo-controlled crossover study was conducted. Methods: Ten patients with T2D and ten matched non-diabetic controls underwent two liquid mixed meal tests preceded by single-dose administration of LY2409021 (100 mg) or placebo. Double-tracer technique was used to quantify EGP. Antagonist selectivity towards related incretin receptors was determined in vitro. Results: Compared to placebo, LY2409021 lowered fasting plasma glucose from 9.1 to 7.1 mmol/L in patients and from 5.6 to 5.0 mmol/L in controls (both P<0.001) by mechanisms involving reduction of EGP. Postprandial plasma glucose excursions (baseline-subtracted area under the curve) were unaffected by LY2409021 in patients and increased in controls compared to placebo. Glucagon concentrations more than doubled during glucagon receptor antagonism. The antagonist interfered with both glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptors, complicating the interpretation of the postprandial data. Conclusions: LY2409021 lowered fasting plasma glucose concentrations but did not improve postprandial glucose tolerance after a meal in patients with T2D and controls. The metabolic consequences of postprandial hyperglucagonemia are difficult to evaluate using LY2409021 because of its antagonizing effects on the incretin receptors.

Association of fasting plasma glucose change trajectory and risk of hypertension: a retrospective cohort in China

To assess the association between fasting plasma glucose (FPG) change trajectory and incident hypertension among Chinese people, this cohort study included 11,791 adults aged 18 to 80 years without hypertension at first entry and who completed at least four follow-ups between 2009 and 2016. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between FPG change trajectory and probability of hypertension. During a median follow-up of 5.10 years (total person-years 61,887.76), hypertension developed in 2177 participants. After adjusting for baseline potential confounders, the probability of hypertension increased with the increasing FPG change trajectory (adjusted OR [aOR] 1.22, 95% CI 1.07-1.40), bell-shape trajectory (aOR 1.15, 95% CI 1.02-1.30) and other-shape trajectory (aOR 1.13, 95% CI 1.02-1.25) which showed a higher variability of FPG compared to the decreasing group. In addition, the increasing FPG change trajectory was associated with a higher probability of hypertension compared with the decreasing group regardless of age and body mass index (BMI) but was only significant in males and in those with normal FPG at baseline. Our study indicates that the increasing FPG change trajectory determines the highest risk of hypertension, demonstrating the importance of maintaining low and stable levels of FPG, especially in males and in those with normal FPG.