scholarly journals Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties

2019 ◽  
Vol 8 (3) ◽  
pp. R55-R70 ◽  
Author(s):  
Ann-Kristin Picke ◽  
Graeme Campbell ◽  
Nicola Napoli ◽  
Lorenz C Hofbauer ◽  
Martina Rauner

The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide, especially as a result of our aging society, high caloric intake and sedentary lifestyle. Besides the well-known complications of T2DM on the cardiovascular system, the eyes, kidneys and nerves, bone strength is also impaired in diabetic patients. Patients with T2DM have a 40–70% increased risk for fractures, despite having a normal to increased bone mineral density, suggesting that other factors besides bone quantity must account for increased bone fragility. This review summarizes the current knowledge on the complex effects of T2DM on bone including effects on bone cells, bone material properties and other endocrine systems that subsequently affect bone, discusses the effects of T2DM medications on bone and concludes with a model identifying factors that may contribute to poor bone quality and increased bone fragility in T2DM.

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257955
Author(s):  
Praveer Sihota ◽  
Rimesh Pal ◽  
Ram Naresh Yadav ◽  
Deepak Neradi ◽  
Shailesh Karn ◽  
...  

Type 2 diabetes mellitus (T2DM) adversely affects the normal functioning, intrinsic material properties, and structural integrity of many tissues, including bone. It is well known that the clinical utility of areal bone mineral density (aBMD) is limited to assess bone strength in individuals with T2DM. Therefore, there is a need to explore new diagnostic techniques that can better assist and improve the accuracy of assessment of bone tissue quality. The present study investigated the link between bone and fingernail material/compositional properties in type 2 diabetes mellitus (T2DM). For that, femoral head and fingernail samples were obtained from twenty-five adult female patients (with/without T2DM) with fragility femoral neck fractures undergoing hemi/total hip arthroplasty. Cylindrical cores of trabecular bone were subjected to micro-CT, and lower bone volume fraction was observed in the diabetic group than the non-diabetic group due to fewer and thinner trabeculae in individuals with T2DM. The material and compositional properties of bone/fingernail were estimated using nanoindentation and Fourier Transform Infrared Spectroscopy, respectively. Both bone/fingernails in T2DM had lower reduced modulus (Er), hardness (H), lower Amide I and Amide II area ratio (protein content), higher sugar-to-matrix ratio, and relatively high carboxymethyl-lysine (CML) content compared with non-diabetic patients. Sugar-to-matrix ratio and relative CML content were strongly and positively correlated with HbA1c for both bone/fingernail. There was a positive correlation between bone and fingernail glycation content. Our findings provide evidence that the degradation pattern of bone and fingernail properties go hand-in-hand in individuals with T2DM. Hence, the fingernail compositional/material properties might serve as a non-invasive surrogate marker of bone quality in T2DM; however, further large-scale studies need to be undertaken.


2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Lamia Oulkadi ◽  
Bouchra Amine ◽  
Imane El binoune ◽  
Samira Rostom ◽  
Rachid Bahiri

Type 2 diabetes mellitus (T2DM) and osteoporosis are chronic diseases with increasing prevalence. The aim of this study was to determine the prevalence of osteoporosis and osteoporotic fracture in women with T2DM and to identify predictive factors of fracture occurrence. The prevalence of osteoporosis and fractures in postmenopausal women with T2DM was 23.1% and 16.9%, respectively. 46.2% of T2DM patients had normal bone mineral density (BMD) (P<0.01) and 58.5% of control subjects had osteopenia (P<0.01). Incidence of fracture in T2DM patients with osteopenia was significantly increased versus control subjects when stratified according the BMD (P=0.009). By stratifying T2DM patients according to fractures, factors that were significantly associated with occurrence included T2DM duration (P=0.038), use of insulin (P=0.017), and lower BMD (P=0.048). Our study suggests that there was a higher prevalence of fracture in T2DM patients compared to control subjects and a significant difference in BMD was found between the groups. We also showed that insulin use, low BMD, and long duration of T2DM are factors associated with an increased risk of bone fracture.


Author(s):  
NITHYA K ◽  
ANGELINE T ◽  
PRISCILLA AS ◽  
ASIRVATHAM AJ

Objective: Glutamate carboxypeptidase II (GCPII), reduced folate carrier 1 (RFC1), and methionine synthase (MTR) genes involved in the folate metabolic pathway may play a key role in the pathogenesis of diabetes and its complications. The present study aimed to investigate the prevalence of genetic polymorphisms of GCPII C1561T, RFC1 A80G, and MTR A2756G in individuals with type 2 diabetes mellitus (T2DM) among South Indians. Methods: The study subjects consisted of 100 healthy individuals and 200 patients with T2DM. Genetic polymorphisms (GCPII C1561T, RFCI A80G, and MTR A2756G) in the folate metabolic pathway were analyzed by polymerase chain reaction-restriction fragment length polymorphism method. Statistical analysis was performed to test the level of significance. Results: With regard to GCPII C1561T and MTR A2756G gene polymorphisms, significant differences were not found when diabetic patients (with and without complications) and controls were compared according to different statistical models (dominant, recessive, and overdominant) p>0.05. A case–control genetic association analysis of RFC1 A80G gene polymorphism has shown that there was 3.7-fold increased risk for patients without complications and 4.9-fold increased risk for diabetic patients with complications. Conclusions: Our findings suggest that the GCPII C1561T and MTR A2756G gene polymorphisms were not significantly associated with diabetes and its complications. Whereas, the RFCI A80G gene polymorphism involved in folate metabolism confers increased risk for diabetes and its complications in South Indian population.


2021 ◽  
Vol 24 (1) ◽  
pp. 4-9
Author(s):  
D. A. Lebedev ◽  
N. V. Timkina ◽  
T. L. Karonova ◽  
A. T. Andreeva ◽  
M. A. Kokina ◽  
...  

Background: Sodium glucose co-transporter type 2 inhibitors (iSGLT2) are antihyperglycemic drugs approved for the treatment of type 2 diabetes mellitus (T2DM). Clinical trials with these drugs have shown evidence of an increased risk of fractures and an effect on phosphorus, vitamin D and parathyroid hormone (PTH) levels.Aim: The aim of this study was to investigate the effect of the most selective iSGLT2 empagliflozin on the calcium and phosphorus metabolism in patients with T2DM and preserved kidney function.Materials and methods: Thirty-nine T2DM patients were received empagliflozin 10 mg in addition to their antihyperglycemic drugs for 12 weeks. Before starting treatment, a dual-energy X-ray absorptiometry (DXA) with an assessment of the trabecular bone score (TBS) was performed. The concentration of phosphorus (P), total (tCa) and ionized calcium (Ca++), fibroblast growth factor 23 (FGF-23), 25(OH)D and PTH were assessed.Results: According to the DXA results, only 2 patients had osteoporosis, 10 (25.6%) patients had bone mineral density (BMD) values below 1.35 g /cm2 on the TCI scale. Treatment with empagliflozin for 12 weeks was lead to significant increase in FGF-23. Compared to the baseline level, there were no statistically significant differences in the concentrations of P, oCa, Ca++, PTH and 25(OH)D after 12 weeks of treatment. The level of FGF-23 did not correlate with the level of glomerular filtration rate either before or after treatment (r = 0.31, p = 0.27 and r = 0.39, p = 0.55, respectively). In addition, baseline BMD adjusted for TBS and baseline 25(OH)D did not correlate with Ca, F, FGF-23, and PTH concentrations (p>0.05).Conclusion: Thus, empagliflozin has increased the level of FGF-23 without significant changes in the concentration of phosphorus, calcium, 25 (OH) D, and PTH after 12 weeks of treatment in patients with T2DM and preserved renal function. The obtained data confirmed the necessity to assess the TBS in patients with T2DM, because it’s provide additional information on the quality of bone tissue.


2021 ◽  
Vol 17 (4) ◽  
pp. 322-328
Author(s):  
A.V. Кovalchuk ◽  
О.В. Zinych ◽  
V.V. Korpachev ◽  
N.M. Кushnareva ◽  
О.В. Prybyla ◽  
...  

Recent studies have demonstrated the importance of bone as an endocrine organ that produces biologically active substances, which regulate both local bone metabolism and metabolic functions throughout the body. In the process of bone remodeling (formation/destruction), the active cells secrete specific biomarkers that help detect osteometabolic dysfunction. Among bone hormones, osteocalcin plays an important role as a coordinator of bone modeling processes, energy homeostasis, metabolism of glucose, lipids and minerals. Osteocalcin is a structural protein of the bone matrix, which is synthesized by osteoblasts and enters the bloodstream in the process of bone resorption. The level of osteocalcin in the serum is used as a specific marker of bone formation. Osteocalcin promotes pancreatic β-cell proliferation and insulin secretion, and also affects the insulin sensitivity of peripheral tissues. The inverse association of glycemia with the level of osteocalcin was revealed. Patients with type 2 diabetes mellitus usually have normal or even slightly elevated bone mineral density compared to age-appropriate controls. Decreased bone quality and increased risk of fractures are associated with changes in bone microarchitecture and local humoral environment. An imbalance in osteoblast/osteoclast activity may be due to oxidative stress and the accumulation of glycosylation end products, which contributes to chronic inflammation and bone resorbtion in patients with diabetes. It is shown that the level of osteocalcin in the blood serum is significantly reduced compared to healthy controls, both in patients with type 1 diabetes mellitus and, especially, in type 2 diabetes mellitus. Given the importance of developing new approaches to the diagnosis and correction of metabolic disorders in diabetic patients, the study of the influence of bone hormones on hormonal and metabolic parameters and bone status, including the risk of fractures, remains relevant in modern diabetology.


2021 ◽  
Vol 8 ◽  
Author(s):  
Liang Ma ◽  
Shaoting Wang ◽  
Hailing Zhao ◽  
Meijie Yu ◽  
Xiangling Deng ◽  
...  

This study aimed to investigate the susceptibility of 8 polymorphisms in ApoB and PCSK9 genes to diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus. This is a case-control association study, including 575 DKD cases and 653 controls. Genotypes were determined using ligase detection reaction method, and data are analyzed using STATA software. The genotype distributions of rs1042034 and rs12720838 differed significantly between the two groups (P &lt; 0.001 and P = 0.008, respectively). After adjusting for confounding factors, the mutations of rs1042034 and rs12720838 were associated with the significantly increased risk of DKD. For instance, carriers of rs1042034 T allele (CT and TT genotypes) were 1.07 times more likely to have DKD than carriers of rs1042034 CC genotype [odds ratio (OR) = 1.07, 95% confidence interval (CI): 1.03–1.10, P &lt; 0.001]. Further, haplotype T-A-G-T in ApoB gene was overrepresented in cases (18.10%) compared with controls (12.76%) (PSimulated = 0.045), and haplotype T-A-G-T was associated with a 33% increased risk of DKD (OR = 1.33, 95% CI: 1.04, 1.70). In further haplotype-phenotype analysis, significant association was only noted for hypertension and omnibus haplotypes in ApoB gene (PSimulated = 0.001). Our findings indicate that ApoB gene is a candidate gene for DKD in Chinese patients with type 2 diabetes mellitus.


Author(s):  
S. Pavithra ◽  
S. Lavanya ◽  
P. Vaishnavi ◽  
A. Rakesh Rosario ◽  
Priyadharshini A ◽  
...  

COVID-19 is a pathogenic virus that caused a pandemic outbreak in December 2019. The impact of this virus may be severe in the patients having co-morbidities like diabetes, hypertension, Chronic Kidney Disease, cardiovascular disease, etc. Aim and Objectives: This study Aims in Assessing the impact of COVID-19 on Diabetic and Hypertensive patients as well as COVID-19 patients without any co-morbidities. Objective of this is to evaluate the association between COVID-19 and its risk factors (diabetes and hypertension) and to evaluate whether the severity of the symptoms in COVID-19 patients is due to comorbidities or past medications. Methodology: A Retrospective study was conducted in SRM Hospital (Medical Records Department) for a period of 3 Months with the study population 670 at the age group of 25, known case of Diabetes and Hypertension. Cases of Pregnant women are excluded from the study. The patients were grouped into 4 categories 1) control group (patient without any co-morbidities) 2) diabetic patients 3) Hypertensive patient 4) Diabetic+Hypertension patient and studied their prescribing pattern by collecting the past medication history. Results and Discussion: There is a significant decrease in a lymphocyte in covid-19 Type 2 diabetic patients in our study. These results suggest that different mechanism exists for hypertension and diabetes mellitus as risk factors for covid-19. It is also known that these patients have impaired immune response to many infections [30]. In our retrospective study, we collected 670 covid-19 cases. It consists of 12.5% of diabetic patients and 6.6% of hypertensive patients. This study compared COVID-19 patients without any comorbidity (neither Type 2 diabetes mellitus nor hypertension) with covid- 19 patients with comorbidities (Type 2 diabetes mellitus and hypertension). COVID-19 patients with T2DM have an increased level of D-dimer compared to non-T2DM patients. Conclusion: Diabetic and hypertensive patients affected with COVID-19 are low in our study. Out of the total study population, only 12.5% are diabetic, 6.56% are hypertensive, and 9.25% were both diabetic and hypertensive. But when comparing in terms of severity, hypertensive and diabetic patients have severe effects than the control patients. In simpler terms, not every person who has diabetes and hypertension are affected with COVID-19, but those who were affected by COVID-19 showed more severity than the patients who don't have any comorbidities


Author(s):  
Jeung-Hee Kim ◽  
Weon-Young Lee ◽  
Song Soo Lim ◽  
Young Taek Kim ◽  
Yeon-Pyo Hong

Previous studies have analyzed the impact of diabetes mellitus on labor market participation by men and women, but gender difference between type 2 diabetes mellitus (T2DM) and employment has not been the focus. This study aims to explore gender differences between T2DM and employment status. Data from the Korea Health Panel Study, 2013–2015 were analyzed by distinguishingT2DM and non-diabetes (N = 11,216). The empirical model was established and the generalized two-stage least squares (2SLS) was estimated, controlling for endogeneity. A family history of diabetes, as an instrumental variable, was related to an individual’s genetic predisposition to develop diabetes. The estimated results for the 2SLS showed the interaction effects between T2DM and employment. T2DM had a statistically significant and negative effect on employment for women only. The comparison with non-diabetes showed that women with T2DM had a lower probability of employment by 51.9% (p < 0.05). Exposing gender bias in employment suggests that healthcare policies and disease management programs for diabetic patients should adopt gender-specific remedies.


2017 ◽  
Vol 42 (12) ◽  
pp. 1316-1321 ◽  
Author(s):  
Kaiping Gao ◽  
Yongcheng Ren ◽  
Jinjin Wang ◽  
Zichen Liu ◽  
Jianna Li ◽  
...  

The impact of gene-environment interaction on diabetes remains largely unknown. We aimed to investigate if interaction between glucose metabolizing genes and lifestyle factors is associated with type 2 diabetes mellitus (T2DM). Interactions between genotypes of 4 glucose metabolizing genes (MTNR1B, KCNQ1, KLF14, and GCKR) and lifestyle factors were estimated in 722 T2DM patients and 759 controls, using multiple logistic regression. No significant associations with T2DM were detected for the single nucleotide polymorphisms of MTNR1B, KLF14 and GCKR. However, rs151290 (KCNQ1) polymorphisms were found to be associated with risk of T2DM. Compared with AA, the odds ratios (ORs) of AC or CC genotypes for developing T2DM were 1.545 (P = 0.0489) and 1.603 (P = 0.0383), respectively. In stratified analyses, the associations were stronger in smokers with CC than smokers with AA (OR = 3.668, P = 0.013); drinkers with AC (OR = 5.518, P = 0.036), CC (OR = 8.691, P = 0.0095), and AC+CC (OR = 6.764, P = 0.016) than drinkers with AA. Compared with nondrinkers with AA, drinkers who carry AC and CC had 12.072-fold (P = 0.0007) and 8.147-fold (P = 0.0052) higher risk of developing T2DM. In conclusions, rs151290 (KCNQ1) polymorphisms are associated with increased risk of T2DM, alone and especially in interaction with smoking and alcohol.


Author(s):  
P. S. Singh ◽  
Sudhir K. Yadav ◽  
Himanshu Sharma ◽  
Manoj Kumar

Cardiovascular disease is the leading cause of morbidity and mortality among patients with type 2 diabetes mellitus (DM). There is twofold increased risk of cardiovascular (CV) mortality among diabetic patients as compared with nondiabetic patients. The glycemic efficacy of anti-diabetic drugs does not necessarily provide cardiovascular safety. Since 2008, US Food and Drug Administration has recommended that new drugs for type 2 DM should undergo clinical trials to demonstrate cardiovascular safety in addition to glycemic benefit. In 2012, European medicine agencies issued a similar recommendation. In this review, we have tried to examine the cardiovascular safety of oral antidiabetic agents in major published trials. Metformin remains the initial drug of choice in type2 DM till date. The sulfonylureas, one of oldest oral anti-diabetic drugs, have adverse cardiovascular events and are gradually being out classed by other second line drugs. The glitazones have been found to have adverse outcome in heart failure. The incretin based drugs have been found to have cardiovascular safety in various trials in recent past and their performances have been reassuring. There is lack of enough cardiovascular outcome data for meglitinides and glucosidase inhibitors. Various current trials have found sodium glucose cotransporter-2 inhibitors to have a potential for cardiovascular benefit. Careful selection of drug therapy with special attention for cardiovascular risk is important in selection and optimization of diabetic therapy.


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