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.

Association of serum creatinine levels and risk of type 2 diabetes mellitus in Korea: a case control study

Background Reduced skeletal muscle has been suggested as a potential risk factor for type 2 diabetes mellitus (T2DM). Serum creatinine is the primary metabolite of creatine in skeletal muscle. Therefore, low serum creatinine levels may be associated with an increased risk of T2DM. We aimed to evaluate the association between serum creatinine levels and the risk of T2DM in Korea. Methods We analyzed a total of 264,832 nondiabetic adults older than 40 years of age who had undergone a national health examination at least once from 2009 to 2015 in the Korean National Health Insurance Service Cohort. Hazard ratios for T2DM were calculated. Results In men, serum creatinine levels and the risk for T2DM showed an inverse J-shaped association. This association was confirmed after adjustment for age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting plasma glucose. In women, there was a trend that serum creatinine levels were inversely associated with the risk of T2DM among those with serum creatinine below 1.1 mg/dl. However, serum creatinine levels were not significantly associated with the risk of T2DM after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose. Conclusions Reduced levels of serum creatinine were significantly associated with an increased risk of T2DM in men with creatinine below 1.20 mg/dl. There was a trend that decreased levels of serum creatinine were associated with an increased risk of T2DM among women with serum creatinine below 1.1 mg/dl, although this result was not statistically significant.

Hyperglycemia Is Not Associated With Higher Volumetric BMD in a Chinese Health Check-up Cohort

Background and PurposeType 2 diabetes mellitus patients have an increased fracture risk despite having higher areal bone mineral density (aBMD) measured by DXA. This apparent paradox might be explained by the overestimation of BMD by DXA due to the higher fat mass in type 2 diabetes mellitus patients. Volumetric BMD (vBMD) as assessed by quantitative CT (QCT) is not influenced by fat mass. We assessed the association of vBMD and fasting plasma glucose in a large cohort of Chinese subjects and compared the vBMD in healthy and diabetic subjects. In addition, we compared the relation between aBMD, vBMD, glucose and fat mass in a subset of this cohort.Materials and Methods10309 participants from the China Biobank project underwent QCT based on chest low dose CT to compute vBMD of L1 and L2 vertebrae and FPG measurements between 2018 and 2019. Among them, 1037 subjects also had spine DXA scans. Data was analyzed using linear regression models.ResultsIn the total cohort (5889 men and 4420 women, mean age 53 years, range 30-96), there was no significant association between vBMD and FPG after adjustment for age (women: p=0.774; men: p=0.149). 291 women and 606 men fitted the diagnostic criteria of diabetes. Both women and men with diabetes had lower vBMD compared to non-diabetic subjects, but this became non-significant after adjusting for age in the total cohort (women: p=0.817; men: p=0.288) and after propensity score matching based on age (women: p=0.678; men: p=0.135). In the DXA subcohort, aBMD was significantly higher in men with diabetes after adjusting for age and this difference disappeared after further adjusting for total fat area (p=0.064).ConclusionWe did not find any effect of fasting plasma glucose or diabetes on the volumetric BMD measured with QCT after adjustment for age. Therefore, vBMD measured with QCT might be a more reliable measurement to diagnose osteoporosis and assess fracture risk than aBMD measured with DXA in diabetic patients.

Антропометричні, біохімічні та актиграфічні характеристики популяційного зразка випадково відібраних дорослих сільських мешканців України, у яких раніше не було встановлено діагнозу «цукровий діабет»

Класичні «польові» епідеміологічні дослідження щодо факторів ризику розвитку цукрового діабету (ЦД) та серцево-судинної патології все ще рідкісні в Україні, через що оцінка поширеності ЦД 2-го типу (ЦД2) базується на екстраполяції з іноземних досліджень. Об’єктивні методи вимірювання фізичної активності (ФА), яку вважають одним із головних чинників профілактики ЦД2, в Україні мало відомі. Зокрема не з’ясовано, наскільки поширеним є серед дорослого населення України виконання рекомендацій Всесвітньої організації охорони здоров’я (ВООЗ) щодо мінімальної кількості помірної фізичної активності (150 хв/тиждень). Залишається недостатньо дослідженим питання про зв’язок композиції тіла та характеристик, що впливають на ризик розвитку ЦД2. Матеріал і методи. Наше дослідження представляє аналіз біохімічних, антропометричних та актиграфічних характеристик 50 рандомізовано відібраних сільських мешканців Київської області України (16 чоловіків із медіанним віком 63,5 року, 34 жінки з медіанним віком 58,0 року), у яких раніше не було діагностовано ЦД2. Після отриманої інформованої згоди всім досліджуваним проведено оральний тест толерантності до глюкози (ОТТГ) за методом ВООЗ (1999). Вимірювали рівні глюкози плазми крові натщесерце (fasting plasma glucose, FPG), глюкози плазми через 2 год після стандартного навантаження (2 hours plasma glucose, 2hPG), тригліцеридів (ТГ), холестерину ліпопротеїнів високої щільності (ХСЛВЩ), глікованого гемоглобіну (glycated hemoglobin, HbA1c), індекс маси тіла (ІМТ), окружність шиї (ОШ), окружність талії (ОТ) та окружність стегон (ОС). Визначили показники композиції тіла за допомогою методу біоелектричного імпедансу: пропорцію жиру тіла (body fat, %) та загальної води тіла (total body water, %). Актиграфічні вимірювання було проведено шляхом акселерометрії за допомогою програмного забезпечення ActiGraph. Моніторинг ФА відбувався протягом 7 днів за такими показниками: середня кількість метаболічних еквівалентів (metabolic equivalents, MET’s), частка ФА помірної інтенсивності за весь час носіння та записування акселерометра (moderate physical activity, ModPA, %) і показник помірної ФА — кількість хв/тиждень, накопичених у періодах тривалістю не менше 10 хв (ModPA, хв/тиждень). Статистичну обробку результатів проведено за пакетом MedStat. Результати. Серед досліджених осіб за даними ОТТГ та вимірювання HbA1c ЦД виявлено в 4 осіб (8%). Порушена глікемія натщесерце (impaired fasting glucose, IFG) за критеріями Американської діабетичної асоціації (АДА) (FPG: 5,6-6,9 ммоль/л) виявлена у 21 особи, а за критеріями ВООЗ (FPG: 6,1-6,9 ммоль/л) — у 7 осіб. IFG незалежно від застосованого критерію не виявляє зв’язку з рівнем ФА. Порушена толерантність до глюкози (impaired glucose tolerance, IGT: 2hPG 7,8-11,0 ммоль/л) виявлена в 5 осіб. За рівнем глікемії, HbA1c та ліпідів не виявлено зв’язку з ФА. Жінки не відрізнялися від чоловіків за віком, мали більший ІМТ (35,08±5,53 проти 27,43±4,98, р<0,001) і більшу частку жиру тіла (45,8±5,7% проти 26,3±5,5%, р<0,001). Водночас, показники ФА у чоловіків і жінок не відрізнялися, були дуже низькими й мали помірну негативну кореляцію з віком (р<0,05). Результати наведені як середнє арифметичне та стандартне відхилення (M±SD). Лише в одного чоловіка та двох жінок було досягнуто рекомендований рівень помірної ФА (150 хв/тиждень). Серед осіб з IGT кількість ФА виявилась меншою: MET’s — 1,22±0,07 проти 1,32±0,19, р=0,023; помірна ФА — 6,95±2,3% проти 10,41±6,43%, р=0,020. Висновки. Виявлена поширеність раніше не діагностованого ЦД2 близька до результатів наших попередніх досліджень та сучасних оцінок поширеності ЦД2 серед дорослого населення у світі. Рівень ФА, оціненої об’єктивним методом актиграфії, виявився нижчим у групі осіб з IGT. Подальші дослідження зможуть прояснити питання профілактичної ефективності ФА в різних групах ризику ЦД2.

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.

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.