Impact Of Type 2 Diabetes Mellitus Research Articles

Disrupted Phosphorylated Phosphoinositide 3-kinase in the NTS of Type 2 Diabetic Rats

The hallmark of type 2 diabetes mellitus (T2DM) is systemic insulin resistance, where insulin signaling is impaired, blood glucose is chronically elevated, and various pathophysiological processes ensue. Much is known about the cardiovascular and metabolic consequences of T2DM. However, the impact of T2DM on autonomic nervous system function remains to be fully elucidated. Increasing evidence suggests that in both human and animal models of T2DM, the exercise pressor reflex (EPR) is abnormally augmented, characterized by heightened cardiovascular and sympathetic responses to physical activity. The underlying mechanisms are still not completely understood. Our recent studies suggest that T2DM induces alterations in peripheral somatosensory nerve activity that could explain the augmented EPR function. However, it is possible that neurons within the cardiovascular control areas of the brainstem, such as the nucleus tractus solitarius (NTS), could also be impaired by this disease. In the central nervous system, insulin has been shown to hyperpolarize neurons through activation of the phosphoinositide 3-kinase (PI3K) pathway, resulting in reduced neuronal excitability. Therefore, we hypothesized that decreased insulin transport into the brain in T2DM rats, results in increased cellular excitability as evidenced by decreased activity of the PI3K pathway in the NTS. Purpose: The aim of this study was to examine alterations in brain insulin levels and the PI3K pathway in T2DM rats as compared to control rats. Methods: Control rats were fed a low fat control diet (13% fat, 67.8% carbohydrate, and 19.2% protein) for 12-16 wks, while T2DM were generated by two low dose bolus injections of i.p. streptozotocin (35mg/kg, week 1; 25mg/kg week 2) and then fed a high fat diet (42% fat, 42.8% carbohydrate, and 15.2% protein) for 12-16wks. Cerebrospinal fluid (CSF) were collected from control and T2DM rats after an overnight fast. NTS micro-punches were performed, and then total and phosphorylated PI3K protein expressions were examined by the western blot technique. Results: CSF insulin was significantly decreased in T2DM rats as compared to control rats (0.41 ± 0.19 vs 0.11 ± 0.05 (ng/mL), Control (n=14) vs T2DM (n=4), p<0.01). Total PI3K expression in the NTS did not differ between control and T2DM (1.0 ± 0.2 vs 1.1 ± 0.2 (au), Control (n=9) vs T2DM (n=9), P=0.172). However, phosphorylated PI3K expression in the NTS of T2DM was significantly decreased as compared with control animals (1.0 ± 0.2 vs 0.8 ± 0.1 (au), Control (n=9) vs T2DM (n=9), p<0.05). Conclusion: These results suggest that 1) in consistent with earlier studies, insulin transport into the brain is impaired in high fat diet/streptozotocin-induced T2DM animals, and 2) decreased phospho-PI3K signaling in the NTS of diabetic animals is associated with lower brain insulin. Taken together, these alterations may increase neuronal excitability in the NTS, thereby contributing, at least in part, to the exaggerated EPR response to exercise in this disease. Supported by NIH HL-151632 and NIH HL-151632-01S1. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact of Type 2 Diabetes Mellitus on the Prognosis of Non-Small Cell Lung Cancer

Type 2 diabetes mellitus (T2DM) is the most common metabolic disease and is characterized by sustained hyperglycemia. The impact of T2DM on the survival of lung cancer patients remains controversial. The aim of this study was to investigate the associations of type 2 diabetes with lung cancer mortality. From January 2019 to January 2020, 228 patients with non-small cell lung cancer (NSCLC) staging earlier than IIIA were included. In our study, we found that the overall survival (OS) and progression-free survival (PFS) of lung cancer patients with diabetes was longer than non-diabetes group. Diagnosed T2DM was associated with the prognosis of lung cancer after adjusting for age and covariates. The association between T2DM and OS was influenced by age, stage of cancer and cancer treatment, as well as whether taking metformin was associated with the OS of lung cancer. However, with the adjustment for age and covariates, the relation trended to lose statistical significance. T2DM is an independent prognostic factor for patients with NSCLC staging before IIIA. The patients with both NSCLC and T2DM trended to having a longer OS, possibly due to metformin.

Impact of T2DM on right ventricular systolic dysfunction and interventricular interactions in patients with essential hypertension: evaluation using CMR tissue tracking

BackgroundPrevious studies reported that there was right ventricular (RV) systolic dysfunction in patients with hypertension. The aim of this study was to evaluate the impact of type 2 diabetes mellitus (T2DM) on RV systolic dysfunction and interventricular interactions using cardiac magnetic resonance feature tracking (CMR-FT) in patients with essential hypertension.Methods and methodsEighty-five hypertensive patients without T2DM [HTN(T2DM −)], 58 patients with T2DM [HTN(T2DM +)] and 49 normal controls were included in this study. The biventricular global radial, circumferential and longitudinal peak strains (GRS, GCS, GLS, respectively) and RV regional strains at the basal-, mid- and apical-cavity, were calculated with CMR-FT and compared among controls and different patient groups. Backward stepwise multivariable linear regression analyses were used to determine the effects of T2DM and left ventricular (LV) strains on RV strains.ResultsThe biventricular GLS and RV apical longitudinal strain deteriorated significantly from controls, through HTN(T2DM-), to HTN(T2DM +) groups. RV middle longitudinal strain in patient groups were significantly reduced, and LV GRS and GCS and RV basal longitudinal strain were decreased in HTN(T2DM +) but preserved in HTN(T2DM-) group. Multivariable regression analyses adjusted for covariates demonstrated that T2DM was independently associated with LV strains (LV GRS: β = − 4.278, p = 0.004, model R2 = 0.285; GCS: β = 1.498, p = 0.006, model R2 = 0.363; GLS: β = 1.133, p = 0.007, model R2 = 0.372) and RV GLS (β = 1.454, p = 0.003, model R2 = 0.142) in hypertension. When T2DM and LV GLS were included in the multiple regression analysis, both T2DM and LV GLS (β = 0.977 and 0.362, p = 0.039 and < 0.001, model R2 = 0.224) were independently associated with RV GLS.ConclusionsT2DM exacerbates RV systolic dysfunction in patients with hypertension, which may be associated with superimposed LV dysfunction by coexisting T2DM and suggests adverse interventricular interactions.

Implications of Type 2 Diabetes Mellitus in Patients with Acute Cholangitis: A Systematic Review of Current Literature

Type 2 diabetes mellitus (T2DM) has been associated with higher rates and poorer prognosis of infections, mainly due to poor glycemic control, reduced response of T-cells and neutrophils, and impaired migration, phagocytosis, and chemotaxis of leukocytes. However, the impact of T2DM on acute cholangitis (AC) has not been assessed so far. Thus, we aimed to explore this association by means of a systematic review of the literature. This systematic review was carried out based on the recommendations stated in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed/MEDLINE, Web of Science and SCOPUS databases to identify relevant publications depicting an association between T2DM and AC from the inception of these search services up to present. We detected a total of 435 eligible records. After we applied the inclusion and exclusion criteria, a total of 14 articles were included in the present systematic review. Included manuscripts focused on the potential role of T2DM as a risk factor for the development of AC and on its contribution to a worse prognosis in AC, e.g., development of sepsis or other complications, the risk of AC recurrence and the impact on mortality. As compared to non-diabetic individuals, patients with T2DM have a higher risk of AC as a complication of choledocholithiasis or gallstone pancreatitis. Several oral hypoglycemic drugs used in the management of T2DM may also be involved in the onset of AC. Diabetic patients who suffer from AC have a higher likelihood of longer hospital stays and sepsis, as well as a higher risk of mortality and more severe forms of AC as compared to non-diabetic individuals.

Impaired spatial navigation and age-dependent hippocampal synaptic dysfunction are associated with chronic inflammatory response in db/db mice.

Type 2 diabetes mellitus (T2DM) increases the risk of developing Alzheimer's disease (AD), which has been proposed to be driven by an abnormal neuroinflammatory response affecting cognitive function. However, the impact of T2DM on hippocampal function and synaptic integrity during aging has not been investigated. Here, we investigated the effects of aging in T2DM on AD-like pathology using the leptin receptor-deficient db/db mouse model of T2DM. Our results indicate that adult T2DM mice exhibited impaired spatial acquisition in the Morris water maze (MWM). Morphological analysis showed an age-dependent neuronal loss in the dentate gyrus. We found that astrocyte density was significantly decreased in all regions of the hippocampus in T2DM mice. Ouranalysis showed that microglial activation was increased in the CA3 and the dentate gyrus of the hippocampus in an age-dependent manner in T2DM mice. However, the expression of presynaptic marker protein (synaptophysin) and the postsynaptic marker protein [postsynaptic density protein 95 (PSD95)] was unchanged in the hippocampus of adult T2DM mice. Interestingly, synaptophysin and PSD95 expression significantly decreased in the hippocampus of aged T2DM mice, suggesting an impaired hippocampal synaptic integrity. Cytokine profiling analysis displayed a robust pro-inflammatory cytokine profile in the hippocampus of aged T2DM mice compared with the younger cohort, outlining the role of aging in exacerbating the neuroinflammatory profile in the diabetic state. Our results suggest that T2DM impairs cognitive function by promoting neuronal loss in the dentate gyrus and triggering an age-dependent deterioration in hippocampal synaptic integrity, associated with an aberrant neuroinflammatory response.

Impact of type-2 diabetes mellitus on expression of atp-sensitive potassium channel subunits in human bypass grafts

Background and Aims : Prevalence of type-2 diabetes mellitus (T2DM) among patients that require coronary artery bypass graft (CABG) surgery increased over the years. It is well knowing that diabetes has impact on endothelial function and that cause impaired vasodilation function of blood vessels. However, vasorelaxation can be, also, achieved through opening of potassium (K) channels on vascular smooth muscle. Thus, the aim of our study was to detect the differences in the expression of ATP-sensitive K (KATP) channel subunits in bypass grafts (saphenous vein, SV and internal mammary artery, IMA) obtained from patients with and without T2DM.

Clinical Interest of Serum Alpha-2 Macroglobulin, Apolipoprotein A1, and Haptoglobin in Patients with Non-Alcoholic Fatty Liver Disease, with and without Type 2 Diabetes, before or during COVID-19.

In patients with non-alcoholic fatty liver disease (NAFLD) with or without type 2 diabetes mellitus (T2DM), alpha-2 macroglobulin (A2M), apolipoprotein A1 (ApoA1), and haptoglobin are associated with the risk of liver fibrosis, inflammation (NASH), and COVID-19. We assessed if these associations were worsened by T2DM after adjustment by age, sex, obesity, and COVID-19. Three datasets were used: the “Control Population”, which enabled standardization of protein serum levels according to age and sex (N = 27,382); the “NAFLD-Biopsy” cohort for associations with liver features (N = 926); and the USA “NAFLD-Serum” cohort for protein kinetics before and during COVID-19 (N = 421,021). The impact of T2DM was assessed by comparing regression curves adjusted by age, sex, and obesity for the liver features in “NAFLD-Biopsy”, and before and during COVID-19 pandemic peaks in “NAFLD-Serum”. Patients with NAFLD without T2DM, compared with the values of controls, had increased A2M, decreased ApoA1, and increased haptoglobin serum levels. In patients with both NAFLD and T2DM, these significant mean differences were magnified, and even more during the COVID-19 pandemic in comparison with the year 2019 (all p < 0.001), with a maximum ApoA1 decrease of 0.21 g/L in women, and a maximum haptoglobin increase of 0.17 g/L in men. In conclusion, T2DM is associated with abnormal levels of A2M, ApoA1, and haptoglobin independently of NAFLD, age, sex, obesity, and COVID-19.

Management of diabetes mellitus in patients with cirrhosis: An overview and joint statement

Type 2 diabetes mellitus (T2DM) is a frequent comorbidity in patients with cirrhosis that is projected to rise in prevalence due to the worldwide burden of obesity, insulin-resistance and non-alcoholic fatty liver disease. The management of T2DM in patients with cirrhosis is complex given the requirement for accurate adaptation according to the level of liver function impairment, with lack of summary of the little evidence available in the literature. Here, we summarise the data available with respect to the epidemiology and the impact of T2DM in patients with cirrhosis, as well as those on the management of T2DM in these patients. We provide guidance for the diagnosis of T2DM and the monitoring of glycaemic control in patients with cirrhosis, and for the management of nutrition and pharmacological treatments in relation to the level of liver dysfunction.

Diabetes and Bone Involvement in Primary Hyperparathyroidism: Literature Review and Our Personal Experience.

BackgroundPrimary hyperparathyroidism (PHPT) and type 2 diabetes mellitus (T2DM) are common endocrine disorders impacting on skeletal health, whose concomitant occurrence is becoming more frequent.Patients and MethodsWe searched the PubMed database from the National Library of Medicine about the relationship between T2DM and its treatment and bone manifestations of PHPT. Thereafter, we retrospectively evaluated a consecutive series of 472 PHPT patients. Among them 55 were also affected by T2DM. At the diagnosis of PHPT we compared bone turnover markers and bone densitometry between 55 patients with and 417 without T2DM and in the former group according to antidiabetic treatment.ResultsFew data are available about T2DM and PHPT bone involvement, studies about T2DM treatments and PHPT bone manifestations are lacking. Among patients with PHPT of our series, those with T2DM were older, had a lower prevalence of osteitis fibrosa cystica, higher lumbar and femoral T-scores than the remaining patients. No difference was disclosed among the diabetic patients according to ongoing antidiabetic treatment, even though modern treatments were under-represented.ConclusionsNo clinical study specifically evaluated the impact of T2DM on bone involvement in PHPT. In our experience, diabetic patients resulted more frequently “mild asymptomatic” than non-diabetic patients and showed a lower prevalence of radiological PHPT bone manifestations. The treatment of T2DM does not seem to affect the biochemical or clinical features of PHPT in our series. Further studies are needed to fully disclose the influence of T2DM and antidiabetic treatment on bone health in patients with PHPT.

Association of Type 2 Diabetes Mellitus and Glycemic Control With Intracranial Plaque Characteristics in Patients With Acute Ischemic Stroke.

Type 2 diabetes mellitus (T2DM) has shown to be associated with carotid plaque vulnerability. However, the impact of T2DM on intracranial artery atherosclerosis is not well-understood. To evaluate the association of diabetes and glycemic control with intracranial atherosclerotic plaque characteristics identified by three-dimensional contrast enhanced MR vessel wall imaging in patients after acute ischemic stroke. Prospective. Two hundred and eighty-eight symptomatic patients with acute ischemic stroke due to intracranial atherosclerotic plaque. T1 WI volume isotropic turbo spin-echo acquisition sequence at 3.0 T. Clinical profiles, blood biomarkers, the number of intracranial plaques, plaque enhanced score, and the features (location, luminal stenotic rate, intraplaque hemorrhage, length, burden, enhancement grade, and ratio) of culprit plaque (defined as the most stenotic lesion ipsilateral to the ischemic event) and nonculprit plaque were analyzed by three radiologists. Analysis of variance (ANOVA), Shapiro-Wilk normality test, Levene's test, ANOVA with Bonferroni post-hoc test, Kruskal Wallis H test with subsequent pairwise comparisons, chi-square with Bonferroni post-hoc test, generalized linear regression, Pearson correlation test, Kendall's W and intra-class correlation coefficient. Two hundred and twenty-five participants (age 60 ± 10 years, 58.7% male) with 958 intracranial plaques were included. More intracranial plaques were found in the T2DM group than the non-T2DM group (4.80 ± 2.22 vs. 3.60 ± 1.78, P < 0.05). Patients with poorly-controlled T2DM exhibited higher culprit plaque enhancement ratio than patients with well-controlled T2DM and non-T2DM (2.32 ± 0.61 vs. 1.60 ± 0.62 and 1.39 ± 0.39; respectively, P < 0.05). After adjusting for other clinical variables, T2DM was independently associated with increased intracranial plaque number (β=0.269, P < 0.05), and HbA1c level was independently associated with culprit plaque enhancement ratio (β=0.641, P < 0.05) in multivariate analysis. T2DM is associated with an increased intracranial plaque number. Higher HbA1c is associated with stronger plaque enhancement. 3D contrast enhanced MR vessel wall imaging may help better understand the association of T2DM and glycemic control with intracranial plaque. 1 TECHNICAL EFFICACY STAGE: 3.

Glucose Control Has an Impact on Cerebral Blood Flow Alterations in Chronic Tinnitus Patients.

PurposeBoth tinnitus and type 2 diabetes mellitus (T2DM) are linked with cognitive decline and brain dysfunction. This study used arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) to examine the abnormal cerebral blood flow (CBF) patterns existed in tinnitus patients and potential relationships between the abnormal CBF and cognitive performance. The impact of T2DM on CBF alterations in tinnitus patients was further explored.MethodsSixty tinnitus patients and 40 non-tinnitus subjects were recruited. CBF images were collected and analyzed using ASL perfusion fMRI. Brain regions with CBF alterations between tinnitus patients and non-tinnitus controls were identified by one-way analysis of variance. Interaction effects between tinnitus and T2DM for CBF changes were also selected. Then, correlation analyses were calculated to specify the link between CBF changes and cognitive performance and between CBF changes and diabetic characteristics.ResultsTinnitus patients showed decreased CBF, primarily in the auditory area and default mode network (DMN), compared with non-tinnitus controls. Decreased CBF in these regions was correlated with executive function and attention. The interaction effect between tinnitus and T2DM was significant in the right medial prefrontal gyrus. Additionally, CBF in the right medial prefrontal gyrus was correlated with tinnitus distress and cognitive performance. In tinnitus patients, Hemoglobin A1c was associated with CBF in the right medial prefrontal gyrus.ConclusionTinnitus affects brain perfusion in the auditory area and DMN. T2DM and uncontrolled glucose levels may aggravate a CBF decrease in tinnitus patients. These new findings implied that tinnitus patients may benefit from blood glucose control in terms of their cognitive function and tinnitus distress.

Human Leukocyte Antigen-DR Deficiency and Immunosuppression-Related End-Organ Failure in SARS-CoV2 Infection.

Human Leukocyte Antigen-DR Deficiency and Immunosuppression-Related End-Organ Failure in SARS-CoV2 Infection.

Sensory Neuron Sensitization By Pkc-induced Trpv1 Phosphorylation In Type 2 Diabetic Rats

Skeletal muscle reflex-induced increases in blood pressure are exaggerated during exercise in type 2 diabetes mellitus (T2DM). We previously demonstrated that skeletal muscle afferent discharge in response to capsaicin, a transient receptor potential cation channel subfamily V member 1 (TRPV1) agonist, is heightened in T2DM likely contributing to the potentiated pressor response. However, the underlying mechanisms remain unclear. Evidence suggests that the high glucose levels in T2DM sensitize sensory neurons through the receptor for advanced glycation end products (RAGE)/protein kinase C (PKC) pathway in dorsal root ganglia (DRG). Moreover, early-stage diabetes associated with TRPV1 overactivity is mediated through PKC. Therefore, it was hypothesized that the augmentation in muscle afferent discharge in T2DM previously reported is due to the phosphorylation of TRPV1 via an overactive RAGE/PKC pathway. PURPOSE: To investigate 1) the impact of T2DM on plasma levels of advanced glycation end products (AGE) and high-mobility group box-protein 1 (HMGB-1), both RAGE ligands, and 2) the impact of T2DM on the RAGE/PKC pathway including the phosphorylation of TRPV1 in DRG subserving skeletal muscle afferents. METHODS: For 14-16 weeks, Sprague-Dawley rats were given either a normal diet (control) or a high fat diet in combination with a low dose (35 mg/kg) of streptozotocin (T2DM). Plasma insulin, HMGB1 and AGE were determined using ELISA. RAGE, phosphorylated PKC and TRPV1 protein levels were quantified in DRG by western blotting. RESULTS: After overnight fasting, T2DM rats exhibited hyperglycemia (95±6 vs. 156±18 mg/dL, P<0.05) and hyperinsulinemia (1.6±0.2 vs. 4.1±0.4 ng/mL, P<0.05). HMGB1, AGE and RAGE did not differ between groups. Phosphorylated PKC (1.0±0.1 vs. 1.2±0.2 arb unit, P=0.08) and TRPV1 (1.0±0.3 vs. 1.3±0.4 arb unit, P=0.08) levels in DRG tended to be greater in T2DM than control. CONCLUSIONS: These findings suggest that phosphorylated TRPV1 may be increased by PKC overactivity in DRG of T2DM but acts independently of RAGE. Importantly, these changes may mediate the sensitization of skeletal muscle afferents facilitating the exaggerated pressor response to exercise characteristic of T2DM. Supported by Lawson & Rogers Lacy Research Fund and SHP Interdisciplinary Research Grant Program.

Association of type 2 diabetes mellitus and antidiabetic medication with risk of prostate cancer: a population-based case-control study

BackgroundProstate cancer (PCa) and type 2 diabetes mellitus (T2DM) are prevalent conditions that often occur concomitantly. However, many aspects of the impact of T2DM, particularly the duration of T2DM and antidiabetic medications, on PCa risk are poorly understood.MethodsTo assess the association of duration of T2DM and antidiabetic medication with PCa risk, we designed a matched case-control study, including 31,415 men with PCa and 154,812 PCa-free men in Prostate Cancer data Base Sweden (PCBaSe) 4.1.ResultsOverall, a decreased risk of PCa was observed for men with T2DM (odds ratio (OR): 0.81, 95% confidence interval (CI): 0.78–0.84), as compared to men without T2DM. The decreased risk of PCa was consistently showed across duration of T2DM. With respect to use of antidiabetic drugs, this inverse association with duration was also found for all medications types, as compared to men without T2DM, including insulin, metformin and sulphonylurea (SU) (e.g. 3- < 5 yr insulin OR:0.69, 95%CI:0.60–0.80; 3- < 5 yr metformin OR: 0.82, 95%CI: 0.74–0.91; 3- < 5 yr SU OR: 0.72, 95%CI: 0.62–0.83). When stratifying by PCa risk categories, this decreased risk was most evident for diagnosis of low and intermediate-risk PCa (low-risk OR: 0.65, 95%CI: 0.66–0.70, intermediate-risk OR: 0.80, 95%CI: 0.75–0.85).ConclusionsThe study showed an inverse association between pre-existing T2DM and PCa across different durations of T2DM and all types of T2DM medication received. This inverse association was most evident for low- and intermediate-risk PCa, suggesting that whilst T2DM and its medication may protect some men from developing PCa, the relationship warrants further study.

Impact of diabetes mellitus on left ventricular longitudinal function of patients with non-ischemic dilated cardiomyopathy

BackgroundLeft ventricular (LV) longitudinal dysfunction has been identified in type 2 diabetes mellitus (T2DM) patients with preserved LV ejection fraction (LVEF). However, the impact of T2DM on LV longitudinal function or the association of LV longitudinal function with outcome for dilated cardiomyopathy (DCM) remains unclear.MethodsWe retrospectively studied 206 patients with non-ischemic DCM, mean age of 59 ± 17 years and LVEF of 31 ± 8% (all < 45%). All patients underwent a standard echocardiographic examination, and LV longitudinal function was assessed in terms of global longitudinal strain (GLS). Long-term outcomes were assessed, with a median follow-up period of 6.2 years, as primary endpoints of death from or hospitalization for deteriorating heart failure.ResultsGLS of DCM patients with T2DM (n = 55) was significantly lower than that in DCM patients without T2DM (n = 151) in spite of similar conventional LV function (7.0 ± 2.0% vs. 7.8 ± 2.2%, p = 0.03). Kaplan–Meier curves indicated that long-term outcomes for DCM patients without T2DM were better than for those with T2DM (log-rank p = 0.001). Subdividing the two groups into four with by using the median value of GLS (7.9%) showed long-term outcome was worst for DCM patients with T2DM and low GLS. Cox proportional hazards analyses demonstrated an independent association of T2DM, GLS and left atrial volume index with long-term outcome. Moreover, multiple regression analysis for the association of GLS showed that T2DM was the independent determinant parameter for GLS as well as for LVEF and left atrial volume index.ConclusionManagement of DCM patients with T2DM may be improved by using GLS guidance.

MON-382 Bone Quality and Strength in Obese Men with Type 2 Diabetes Mellitus Are Impaired and Negatively Influenced by Adiposity

Background: Obesity and type 2 diabetes mellitus (T2DM) are both associated with normal to above average bone mineral density (BMD) but increased risk of fragility fractures. The impact of T2DM on bone mechanical and microarchitectural features in the obese population is unknown. We hypothesize that obese diabetics have lower bone quality compared to obese nondiabetic individuals. In this study, we investigated the microarchitectural features and mechanical properties of bone of obese men with and without T2DM along with the independent predictors of bone strength. Methods: Ninety-seven obese men (BMI >30) aged 35-65 years-old of which 38 had T2DM were included in the analysis. BMD and body composition were evaluated by DXA and bone microarchitecture of the tibia by high-resolution peripheral quantitative computed tomography. Bone strength was assessed by micro finite element analysis-derived parameters as failure load (f. load) and stiffness. Serum testosterone and estradiol were measured by LC-MS. Serum SHBG, osteocalcin (OCN), C-telopeptide (CTx) and sclerostin (SCL) were measured by ELISA. Results: OCN is lower in obese men with T2DM compared to those without T2DM (4.8 ± 2.8 vs 6.2 ± 2.6 ng/mL p=0.03, respectively), with also a trend for reduced CTx and SCL in the former. BMD at all sites was reduced in obese men with T2DM, but there were no differences in body composition. Obese diabetics also had lower tibial total volumetric BMD (vBMD) (p=0.04) and trabecular vBMD (p=0.01) with greater trabecular spacing (p=0.005). F. load (13.3 ± 2.1 vs 14.5 ± 2.3 kN, p= 0.02) and stiffness (24.7± 4.2 vs 27 ± 4.6 kN/mm, p=0.02) were reduced in men with T2DM relative to men without T2DM, respectively. F. load and stiffness were positively correlated with BMD at all sites, fat free mass (FFM), lean mass, free testosterone, free estradiol and SCL, but negatively correlated with % total body fat and visceral adipose tissue (VAT). FFM, BMD of the total hip, femoral neck and lumbar spine and free testosterone were significant independent predictors of bone strength in the entire group (model: R2: 65.01 p< 0.0001 for f. load and model: R2:63.21 p < 0.0001 for stiffness), whereas age and lumbar spine BMD were found to be independent predictors of bone strength in the non-diabetic group (model R2: 54.6 p< 0.0001 for both f. load and stiffness). Analysis limited to the diabetic subgroup showed that BMD at the femoral neck and total hip, % total body fat, VAT volume, SCL and free estradiol were independent predictors of bone strength (model: R2: 88.4 and p< 0.0001 for f. load and model: R2: 85.3 and p<0.0001 for stiffness). Interleukin-6 was comparable between groups. Conclusions: Obese men with T2DM have lower bone formation and impaired bone quality and strength compared to those without T2DM. In addition to BMD and gonadal hormones, adiposity is an important predictor of bone strength in obese men with T2DM.

Impact of type 2 diabetes on postoperative outcome after hip fracture: nationwide population-based study in Taiwan

SummaryThe impact of diabetes mellitus (DM) on hip fracture (HFx) is still controversial. We used nationwide population-based data in Taiwan to observe postoperative outcomes of HFx in patients with type...

Coronary artery disease in pre and postmenopausal women. The influence of type 2 diabetes mellitus

Postmenopausal women have higher severity of coronary heart disease (CHD) than premenopausal women and type 2 diabetes mellitus (T2DM) is an independent risk factor. To assess the severity of CHD in pre and postmenopausal patients undergoing coronary angiography and the impact of T2DM in both groups. A coronary angiography was performed to 707 women due to suspected CHD during 2013 and 2014. Of these, 579 were older than 55 years and were considered as postmenopausal. Factors such as hypertension, obesity, smoking, creatinine and T2DM were registered. The severity of CHD in coronary angiography was evaluated according to the number of vessels with more than 50% stenosis. Compared to their postmenopausal counterparts, premenopausal women had less frequency of T2DM (31% and 42% p < 0.033), hypertension (52 and 78%, p < 0.001) and alteration of renal function (11 vs. 39%, p < 0.001). Absence of coronary lesions was found in 44 and 32% of premenopausal and postmenopausal women, respectively (p < 0.01). Premenopausal women with T2DM had a higher frequency of multi-vessel disease than those without the disease (25 and 4.5%, p < 0.001). The frequency of multi-vessel disease was higher in postmenopausal than premenopausal women (24 and 11%, p < 0.01). Hypertension, T2DM and renal involvement were associated with a higher frequency multiple vessel disease. The severity of CHD is higher in postmenopausal women and T2DM is associated with the disease.

Impact of Type-2 Diabetes Mellitus on the Outcomes of Catheter Ablation of Atrial Fibrillation (European Observational Multicentre Study)

Type-2 diabetes mellitus (DM) is associated with an increased risk of atrial fibrillation (AF). It is unclear whether DM is a risk factor for arrhythmia recurrence following catheter ablation of AF. We performed a nonrandomised, observational study in 7 high-volume European centres. A total of 2,504 patients who underwent catheter ablation of AF were included, and procedural outcomes were compared among patients with or without DM. Patients with DM (234) accounted for 9.3% of the sample, and were significantly older, had a higher BMI and suffered more frequently from persistent AF. Arrhythmia relapses at 12 months after AF ablation occurred more frequently in the DM group (32.0% vs 25.3%, p = 0.031). After adjusting for type of AF (i.e., paroxysmal vs persistent), during a median follow-up of 17 ± 16 months, atrial arrhythmia free-survival was lower in the diabetics with persistent AF (log-rank p = 0.003), and comparable for paroxysmal AF (log-rank p = 0.554). These results were confirmed in a propensity-matched analysis, and DM was also an independent predictor of AF recurrence on the multivariate analysis (hazard ratio 1.39; 95% confidence interval 95%1.07 to 1.88; p = 0.016). There was no significant difference in the rate of periprocedural complications among DM and non-DM patients (3.8% vs 6.3%, p = 0.128). Efficacy and safety of cryoballoon ablation were comparable to radiofrequency ablation in both DM and no-DM groups. In conclusion, catheter ablation of AF appears to be safe in patients with DM. However, DM is associated with higher rate of atrial arrhythmia relapse, particularly for patients with persistent AF.

The relationship between pancreatic cancer and type 2 diabetes: cause and consequence.

Pancreatic cancer (PC) is a devastating and lethal malignant disease and it is well known that there is a complex bidirectional relationship between PC and type 2 diabetes mellitus (T2DM). In order to more deeply summarize the relationship between them, this article summarizes the epidemiological data on the relationship between PC and T2DM in the past 5 years, and further explains the mechanism of interaction between them. Meanwhile, it also summed up the effects of drug therapy for T2DM on PC and the impact of T2DM on surgical resection of PC. Epidemiological studies clearly indicate that the risk of PC is increased in patients with T2DM. But increasing epidemiological data points out that PC also acts as a cause of T2DM and new-onset T2DM is sign and consequence of PC. Insulin resistance, hyperinsulinemia, hyperglycemia, and chronic inflammation are the mechanisms of T2DM-Associated PC. Metformin decreases the risk of PC, while insulin therapy increases the risk of PC. Besides, studies have shown that T2DM decreases the survival in patients with PC resection.