The significant interaction between age and diabetes mellitus for colorectal cancer: Evidence from NHANES data 1999–2016

BackgroundDiabetes mellitus has been associated with elevated risk of colorectal cancer (CRC), although interaction between age and DM is unclear. We examined the relationship among DM, CRC and age.Methods22,580 subjects aged ≥18 years were identified from the National Health and Nutrition Examination Survey (NHANES) database collected between 1999–2016. To account for the complex, stratified, multistage probability sampling design in NHANES, SASv9.4 Procedure Survey Methodology was applied. Univariate analysis compared individual baseline characteristics between subjects with and without DM. Multivariate logistic regression model assessed association between DM and CRC, in which the model included factors with p < 0.05 in univariate analysis as covariates.ResultsUnivariate analysis showed significant differences in age (p < 0.0001), race (p < 0.0001), smoking (p = 0.0023) and body mass index (p < 0.0001) between No-DM and DM. Multivariate analysis revealed significant interaction between age and DM (p = 0.0004). Subjects with DM aged 18–65 were more likely to experience CRC (OR = 4.47, 95%CI = (1.33–15.07); p = 0.0157) compared to those without DM. Subjects with DM aged >65 were not at increased risk for CRC (OR = 0.83, 95%CI = (0.43–1.59); p = 0.5665) compared to those without DM.ConclusionsAge, DM, and interaction between age and DM are risk factors for CRC. Individuals with DM aged 18–65 years have a higher CRC risk.     

Differences in skeletal and non-skeletal factors in a diverse sample of men with and without type 2 diabetes mellitus

AimsPatients with type 2 diabetes mellitus (T2DM) have increased fracture risk yet higher bone mineral density (BMD), but data are inconsistent in men. We compared skeletal and non-skeletal (e.g., muscle mass, strength) factors in men with/without T2DM.MethodsCross-sectional study of 1137 Boston men 30–79 years in the Boston Area Community Health/Bone Survey. Diabetes status was self-reported, and BMD and body composition were measured by DXA, and grip strength by hand dynamometer. Physical function was assessed by walking speed and chair stands. Multivariable linear regressions examined associations of T2DM with skeletal/non-skeletal factors.ResultsMean age was 48 years. The population was 24.6% Black, 13.0% Hispanic, and 62.4% White. Prevalence of T2DM was 12.5%; average disease duration was 7.4 years. While subjects with T2DM did not differ in skeletal factors (e.g., BMD), they had significantly lower appendicular lean mass [mean difference (MD) = − 1.04 kg; standard error (SE) = 0.50; p = 0.04], arms lean mass (MD = − 0.42 kg; SE = 0.15; p = 0.006) and grip strength (MD = − 3.02 kg; SE = 1.25; p = 0.025) after adjustment for age, race/ethnicity, and BMI.ConclusionsMen with T2DM have lower muscle mass and strength, but similar BMD, compared to their non-diabetic counterparts. These differences in non-skeletal factors might explain, at least in part, the higher incidence of falls and fractures observed in T2DM patients.     

Bone mineral density in patients with systemic sclerosis and its association with hand involvement

Aim of the workThe aim of the present study is to assess bone mineral density (BMD) in systemic sclerosis (SSc) patients and to determine associated factors.Patients and methodsSixty-five female SSc patients (mean age 39.5 ± 13.5 years, disease duration 7.3 ± 5.9 years), and forty age- and sex- matched controls were included. Forty-seven patients had limited SSc and 18 had diffuse type. Patients were subjected to clinical and functional assessment. BMD was quantified at the distal radius, femoral neck and lumbar spine (L2–4) by dual energy X-ray absorptiometry.ResultsSSc patients had a higher frequency of osteoporosis at the distal radius and osteopenia at the lumbar spine (p = 0.001 and 0.002, respectively), but the BMD at the femoral neck was not significantly different from the control group. Patients with osteoporosis at the distal radius had a significantly higher frequency of hand deformities (p < 0.05) and higher functional scores reflecting more disability than patients without (p = 0.01), while patients with osteoporosis at the lumbar spine were significantly older (p < 0.001) and had a longer disease duration than those without (p = 0.001). No associations were found between menopausal status, SSc subtype, skin score, internal organ affection and osteoporosis at the three skeletal sites.ConclusionPatients with SSc have lower bone mineral density than controls at the distal radius and lumbar spine. Osteoporosis at the distal radius is associated with the presence of hand deformity and functional disability, while osteoporosis at the lumbar spine is associated with older age and longer disease duration.     

Correlation between synovial vascular endothelial growth factor,clinical, functional and radiological manifestations in knee osteoarthritis

Aim of the workTo correlate between synovial vascular endothelial growth factor (VEGF), clinical, functional and radiological findings in knee osteoarthritis (KOA) patients.Patients and methodsTwenty patients with primary KOA were clinically examined and the modified Ritchie articular index (RAI) recorded. The knees were examined and knee pain evaluated by the visual analog scale (VAS) and tenderness by the knee subscale of the RAI. The Western Ontario Mc Master scale (WOMAC) was recorded and the Kellgren–Lawrence grading used to assess radiographic severity. The synovial level of VEGF was assessed using ELISA.ResultsThe mean age was 56.15 ± 7.77 years and body mass index 28.1 ± 4.04. All patients had knee effusion; 40% were bilateral and 60% unilateral. The mean duration of knee pain was 3.01 ± 1.43 years; duration of morning stiffness was 15.75 ± 3.72 min. The mean WOMAC was 44.22 ± 11.46 and modified RAI 5.45 ± 2.94. The mean knee subscale of RAI was 2.9 ± 1.16 and VAS for knee pain 5.7 ± 2.92. The mean synovial VEGF level was 693.71 ± 314.63 pg/ml. There was a significant increase in the synovial VEGF compared to the reference value (p = 0.0001). There was a significant correlation between the synovial VEGF and patients’ age (p = 0.04), knee pain duration (p = 0.025), morning stiffness (p < 0.0001), modified RAI (p = 0.0001), knee subscale of RAI (p < 0.0001), VAS for knee pain (p < 0.0001) and WOMAC (p = 0.0001). There was a significant negative correlation between synovial VEGF and muscle strength grading (p = 0.0001) and a significant correlation with the radiological assessment (p = 0.0001).ConclusionSynovial VEGF significantly correlated with clinical manifestations, functional impact, as well as radiological changes of KOA.     

Assessment of right ventricular function by myocardial performance index in diabetic patients

BackgroundAssessment of right ventricular (RV) function remains difficult because of the RV complex shape. Data regarding RV performance in patients with diabetes are incomplete The aim of this study was to assess the feasibility of pulsed wave tissue Doppler imaging and myocardial performance index (MPI) for the assessment of right ventricular function in diabetic patients without coronary artery disease.MethodsThe study included 20 diabetic patients, 20 diabetic hypertensive and 20 gender and age matched healthy subjects underwent standard echocardiography with tissue Doppler imaging (TDI) to assess RV function. Patients with myocardial ischemia, impaired left ventricular systolic function, valvular heart disease or other diseases which could alter the right ventricular performance were excluded.ResultsMyocardial performance index was significantly higher in diabetes compared to control group (0.41 ± 0.05 versus 0.27 ± 0.04, p = 0.001). Peak myocardial systolic velocity (Sa), early diastolic myocardial velocity (Ea), and late diastolic myocardial velocity (Aa) were significantly lower in patients with diabetes mellitus (DM) compared to the control group (p = 0.0001). Isovolumetric relaxation time (IVRT) was significantly higher in DM group compared to control group (p = 0.003). MPI was significantly higher in diabetic hypertensive group versus DM alone group (0.46 ± 0.050 versus 0.41 ± 0.05, p = 0.01). There was no correlation between MPI and blood glucose level and duration of diabetes.ConclusionMyocardial performance index is a useful noninvasive tool for the detection of early right ventricular systolic and diastolic dysfunction in diabetic patients, regardless of coexisting hypertension.     

PONI and its association with oxidative stress in type I and type II diabetes mellitus

ObjectiveParaoxonase (PON) is an antioxidant enzyme linked with cardiovascular disease (CVD), diabetes as it prevents LDL oxidation. The relation of PON with the other established risk factor of diabetic complications has not been looked into.Research design and methods370 subjects were included in the study. Dividing into four group, i.e. group I included type II DM (n = 220), group II was age matched control (n = 100), group III were type I DM (n = 25) and group IV (n = 25) were age matched control group. The protocol of the study was approved by the ethical committee of the institute. SOD, GSH, PON (paraoxonase and arylesterase activity), GHb, and MDA were estimated.ResultsA highly significant decrease in paraoxonase and arylesterase activity was seen in the type II DM (p < 0.0001) while in type I DM both the activity was not significant (p > 0.05). Paraoxonase and arylesterase activity of PONI showed a negative significant correlated with MDA (r = ?0.51, p < 0.0001 and r = ?0.23, p < 0.001) in type II DM but was not correlated in type I DM. The GHb and MDA levels were significantly increased (p < 0.0001) while the levels of SOD and GSH have been decreased in type I and type II DM.ConclusionPONI is definitely associated with development of the complications of diabetes. This may be due to the role of it as an antioxidant. As it also show a negative correlation with MDA like the other antioxidants studied.     

Parental brevity linked to cardiometabolic risk in diabetic descendants

BackgroundNon-diabetic offspring from long-lived parents benefit from lowered CV risk. No study investigated the effects of parental lifespan on their progeny when offspring have T2DM. This study assessed CV and metabolic features of T2DM offspring according to parental lifespan.Patients & Methods558 T2DM patients were questioned on parental longevity (paternal and/or maternal lifespan ≥ 80 years); mean age 66 (11) years; male:female 66:34; divided into 6 groups: long-lived father [LLF] (n = 143); short-lived father [SLF] (n = 262); long-lived mother [LLM] (n = 229); short-lived mother [SLM] (n = 176); long-lived father and long-lived mother [LLF & LLM] (n = 82); and short-lived father and/or short-lived mother [SLF &/or SLM] (n = 323).ResultsAge was similar in [LLF & LLM] and [SLF &/or SLM]. Diabetes duration was longer in [SLF &/or SLM] (p 0.0073). Body composition, hypertension, hepatic steatosis and metabolic syndrome (MetS) were similar in both groups, [SLF &/or SLM] having a higher MetS score: 3.79 (1.12) vs. 3.48 (1.12) (p 0.0257). Fasting insulinemia was higher in [SLF &/or SLM] (p 0.0001), who were more insulin resistant (+ 10%: p 0.0440). HbA_1c was higher (+ 0.36%) in [SLF &/or SLM] (p 0.0138). LDL-C; non-HDL-C; and apoB100 were similar in both groups, whereas HDL-C and apoA-I were higher in [LLF & LLM] (p 0.0233 and p 0.0179). Prevalence and severity of atherogenic dyslipidemia were raised in [SLF &/or SLM], by 53% (prevalence) and 13% (log[TG]/HDL-C) (p 0.0172 and p 0.0067).ConclusionBilateral reductions in parental longevity are linked to unfavorable cardiometabolic phenotype in T2DM descendants, with worsened insulin resistance and atherogenic dyslipidemia among 1st-degree offspring.     

Relationship between achieved personalized glycaemic targets and monitoring of clinical events in elderly diabetic patients

AimRecent guidelines for the management of type 2 diabetes (T2DM) in the elderly recommend adjusting the therapeutic target (HbA_1c) according to the patient's health. Our study aimed to explore the association between achieving the recommended personalized HbA_1c target and the occurrence of major clinical events under real-life conditions.MethodsThe T2DM S.AGES cohort was a prospective multicentre study into which 213 general practitioners recruited 983 non-institutionalized T2DM patients aged > 65 years. The recommended personalized HbA_1c targets were < 7%, < 8% and < 9% for healthy, ill and very ill patients, respectively. Major clinical events (death from any cause, major vascular events and/or hospitalization) were recorded during the 3-year follow-up. Mixed-effects logistic regression models were used for the analyses.ResultsOf the 747 patients analyzed at baseline, 551 (76.8%) were at their recommended personalized HbA_1c target. During follow-up, 391 patients (52.3%) experienced a major clinical event. Of the patients who did not achieve their personalized HbA_1c target (compared with those who did), the risk (OR) of a major clinical event was 0.95 (95% CI: 0.69–1.31; P = 0.76). The risk of death, major vascular event and hospitalization were 0.88 (95% CI: 0.40–1.94; P = 0.75), 1.14 (95% CI: 0.7–1.83; P = 0.59) and 0.84 (95% CI: 0.60–1.18; P = 0.32), respectively.ConclusionOver a 3-year follow-up period, our results showed no difference in risk of a major clinical event among patients, regardless of whether or not they achieved their personalized recommended HbA_1c target. These results need to be confirmed before implementing a more permissive strategy for treating T2DM in elderly patients.     

Sleep duration is a significant predictor of cardiac autonomic neuropathy in type 2 diabetes mellitus

AimTo investigate the association between sleep quality outcomes and measures of cardiac autonomic function and to assess the predictive ability of sleep quality outcomes for cardiac autonomic neuropathy (CAN) in type 2 diabetes mellitus (T2DM).MethodsFifty patients with T2DM (age, 51.3 ± 7.01 years; glycemic control, 8.4 ± 1.65%) completed the study. Patients were diagnosed for CAN using the standard clinical autonomic test battery and were also assessed for heart rate variability (HRV) under resting conditions. Sleep quality was examined using the Pittsburg Sleep Quality Index (PSQI).ResultsSleep duration, sleep onset latency, sleep efficiency, daytime dysfunction and global PSQI score showed significant correlations with measures of cardiac autonomic control (p < 0.05). At an optimal cut-off of ≤ 5.83 h (area under the curve: 0.76, p = 0.0003; sensitivity: 50%; specificity: 94.4%), sleep duration predicted occurrence of CAN (odds ratio, confidence interval: 0.18, 0.04–0.70; p = 0.01) in T2DM after adjusting for various clinical confounders.ConclusionFindings of the present study suggest that subjective sleep outcomes such as sleep duration, sleep onset latency, sleep efficiency, daytime dysfunction and overall sleep quality are associated with the indices of cardiac autonomic function in T2DM. Moreover, short sleep duration may be considered a predictor in the occurrence of CAN in these patients. Considering the role of sleep in the pathophysiology of CAN, sleep should be routinely examined in patients with T2DM and appropriate therapeutic interventions should be implemented particularly in case of reduced sleep duration.     

Association of HbA1c with emotion regulation,intolerance of uncertainty,and purpose in life in type 2 diabetes mellitus

BackgroundThe extant literature lacks breadth on psychological variables associated with health outcome for type 2 diabetes mellitus (T2DM). This investigation extends the scope of psychological information by reporting on previously unpublished factors.ObjectiveTo investigate if intolerance of uncertainty, emotion regulation, or purpose in life differentiate T2DM adults with sustained high HbA_1c (HH) vs. sustained acceptable HbA_1c (AH).Subjects and methodsCross-sectional observational study. Adult patients with diagnosed T2DM meeting inclusionary criteria for AH, HH, or a nondiabetic reference group (NDR) were randomly selected and invited to participate. Patients who consented and participated resulted in a final sample of 312 subgrouped as follows: HH (n = 108); AH (n = 98); and NDR (n = 106). Data sources included a survey, self-report questionnaires, and electronic medical record (EMR).ResultsHH individuals with T2DM reported lower purpose in life satisfaction (p = 0.005) compared to the NDR group. The effect size for this finding is in the small-to-medium range using Cohen's guidelines for estimating clinical relevance. The HH–AH comparison on purpose in life was nonsignificant. The emotion regulation and intolerance of uncertainty comparisons across the three groups were not significant.ConclusionsThe present study determined that lower purpose in life satisfaction is associated with higher HbA_1c. In a T2DM patient with sustained high HbA_1c, the primary care clinician is encouraged to consider screening for purpose in life satisfaction by asking a single question such as “Do the things you do in your life seem important and worthwhile?” The patient's response will assist the clinician in determining if meaning or purpose in life distress may be interferring with diabetes self-care. If this is the case, the clinician can shift the conversation to the value of behavioral and emotional health counseling.     

Polymorphism in microRNA-196a2 contributes to the risk of cardiovascular disease in type 2 diabetes patients

AimsTo investigate the effect of the microRNA-196a2 gene polymorphism (rs11614913) on risk of cardiovascular disease in type 2 diabetes patients.MethodsWe examined 920 patients with diabetes and 834 healthy controls. All subjects were genotyped for the miRNA-196a2 SNP by polymerase chain reaction (PCR) and restriction analysis.ResultsThe genotype distribution among controls and patients was in Hardy–Weinberg equilibrium (p = 0.227 and 0.308, respectively). The frequency of the T allele was lower in patients than in controls (p = 0.044). The odds ratio 0.66 (95% CI 0.54–0.79) suggests an association of the T allele with decreased risk of T2DM. For the main purpose of the study, T2DM patients were stratified into patients with CVD and those without it. The T allele and TT genotype were significantly more frequent in patients with CVD compared to those without CVD (p = 0.013, p < 0.001, respectively). The odds ratio for the T allele in the CVD + subgroup vs. CVD − was 1.76 (1.35–2.30), p < 0.0001, mostly due to the overrepresentation of TT homozygotes. The highest risk of development of CVD was observed in the additive model for TT homozygotes (OR 3.33, 95% CI 2.05–5.42, p < 0.0001).ConclusionOur findings suggest that miRNA-196a2 T/C polymorphism (rs11614913) is associated with an increased risk of CVD in type 2 diabetes patients. This provides further insights on pathogenesis of cardiovascular disease in type 2 diabetes patients.     

Decreasing postprandial C-peptide levels over time are not associated with long-term use of sulphonylurea: An observational study

AimThe present study aimed to describe changes over 10 years in HbA_1c and beta-cell function, as assessed by postprandial C-peptide (PP-CPT) and C-peptide/glucose (PP-CPT/glucose) ratio, and to investigate whether treatment with sulphonylurea (SU) exerts a deleterious effect on beta-cell function.MethodsDuring 1997–1998, HbA_1c, PP-CPT and PP glucose were measured in 462 patients. Ten years later, 171 of the 341 patients who were still alive were followed-up.ResultsHbA_1c decreased from 7.41 to 6.96% (P = 0.002) as treatments were intensified. There was a decrease in both PP-CPT (P < 0.001) and PP-CPT/glucose ratio (P = 0.063). A multivariable-regression model was used to evaluate the effects on beta-cell function changes, using the following variables as effect modifiers: gender; age; BMI; diabetes duration; baseline PP-CPT/glucose ratio; HbA_1c; GAD-antibody class; and SU treatment (continuously, periodically, never). Baseline PP-CPT/glucose ratio was the most important variable (R² = 45%; P < 0.001) for explaining variations in beta-cell function. An increase in HbA_1c was associated with a decrease in beta-cell function, and beta-cell function remained unchanged if glycaemic control was improved. Long-term treatment with SU had no effect on long-term changes in beta-cell function (R² = 0.1%; P = 0.894).ConclusionBoth HbA_1c and beta-cell function decreased over 10 years with SU treatment, but such treatment was not associated with a pronounced decline in beta-cell function. These results, however, need to be interpreted with caution, as this was an observational study. Nevertheless, the present study findings do not support the notion that SU, as used in clinical practice, is harmful to beta-cell function.     

Incidence and risk factors of delirium in patients after cardiac surgery: Modifiable and non-modifiable factors

BackgroundPost cardiac surgery delirium is a severe complication. This study tried to evaluate the early postoperative delirium risk factors and to identify which of them can be modified in order to optimize perioperative management.MethodsIt is a prospective observational study. 250 consecutive cardiac surgery patients took part in the study. Cardiac surgery, the anesthetic regiment and the postoperative management were standardized. The incidence and the risk factors of the postoperative delirium were analyzed by univariate and multivariate analysis. Delirium was assessed with screening scale – The Confusion Assessment Method for the intensive care unit every 12 h postoperatively.ResultsDelirium developed in 52 patients (20.8%). Univariate analysis of the variables confirmed that older age (p = 0.0001), the higher EuroSCORE II value (p = 0.0001), longer CPB time (p = 0.0001), longer ACC time (p = 0.0001), and the sufentanil dose (p = 0.010) were strongly independently associated with postoperative delirium. The benzodiazepine administration was shown to be an intermediate predictor for developing postoperative delirium (p = 0.055).ConclusionsAdvanced age, higher EuroSCORE II value, longer CPB and ACC times, and higher sufentanil doses during anesthesia were all predictors for the development of postoperative delirium. The only modifiable risk factor was the use of larger doses of sufentanil which is related with the duration of the operation. New preventive strategies and use of reduced dose of sufentanil intraoperatively, or the use of different opioid should be studied and applied in order to reduce the incidence of the postoperative delirium.     

Changes in liver stiffness using acoustic radiation force impulse imaging in patients with obstructive cholestasis and cholangitis

BackgroundAcoustic radiation force impulse imaging is used to assess stages of liver fibrosis. The aim of our study was to evaluate liver stiffness changes in patients with biliary obstruction with or without sclerosing cholangitis after biliary drainage.MethodsA total of 71 patients were enrolled in this prospective study (cohort N = 51, control group N = 20); 51 patients with obstructive cholestasis, indicated for endoscopic retrograde cholangiography, received stiffness measurement by acoustic radiation force impulse imaging before and 1–2 days after endoscopic retrograde cholangiography. Seventeen patients with obstructive cholestasis had primary or secondary sclerosing cholangitis. Forty one patients had a follow-up acoustic radiation force impulse imaging measurement after 3.0 ± 9.31 weeks.ResultsIn all patients with obstructive cholestasis, stiffness decreased significantly after biliary drainage (p < 0.001). The main decrease was observed within 2 days after endoscopic retrograde cholangiography (1.92–1.57 m/s, p < 0.001) and correlated with the decrease of bilirubin and alkaline phosphatase (p = 0.04 and p = 0.002, respectively). In patients with sclerosing cholangitis, the initial decrease of stiffness after biliary drainage was weaker than in those without (2.1–1.85 m/s vs. 1.81–1.43 m/s, p = 0.016).ConclusionAcoustic radiation force impulse imaging elastography shows that liver stiffness is increased by biliary obstruction, and decreases after endoscopic retrograde cholangiography irrespective of the aetiology. In patients with sclerosing cholangitis the reduction in stiffness after biliary drainage is impaired.     

The association between ectopic fat in the pancreas and subclinical atherosclerosis in type 2 diabetes

AimsEvidence that pancreatic fat accumulation has a role in obesity, metabolic syndrome and type 2 diabetes mellitus (DM) is emerging. However, data on the influence of pancreatic steatosis on subclinical atherosclerosis are lacking.MethodsWe examined 198 patients with type 2 DM. Pancreatic computed tomography (CT) attenuations were assessed using CT imaging. Obesity was defined as BMI ≥ 25 kg/m² according to the Asian-specific BMI cut-offs. We defined pancreatic steatosis as pancreatic attenuations below median levels.ResultsThe pancreatic attenuations was significantly correlated with age (r = −0.302, p < 0.001), visceral fat area (r = −0.194, p = 0.006) and vascular stiffness (r = −0.242, p = 0.001). In the non-obese group (BMI < 25 kg/m²), pancreatic steatosis was associated with a higher prevalence of carotid artery plaque and vascular stiffness. In the non-obese group, patients with pancreatic steatosis, compared with those without, had an odds ratio (OR) of 3.1 (95% CI 1.2–8.1) for carotid atherosclerosis, after adjusting for age, gender and BMI. However, significant associations between pancreatic steatosis and atherosclerosis were not found in the obese group.ConclusionEctopic fat in the pancreas is strongly associated with carotid atherosclerosis in non-obese subjects with type 2 DM. This finding highlights the importance of pancreatic fat deposits related to a higher risk of cardiovascular disease, especially in non-obese subjects.     

Clinical significance of UbA52 level in the urine of patients with type 2 diabetes mellitus and diabetic kidney disease

BackgroundUbiquitin-52 amino acid fusion protein (UbA52) is an important factor in the pathogenesis of diabetic kidney disease (DKD) and has been suggested a potential marker in the disease. However, whether upregulation of UbA52 marks early kidney injury in T2DM mellitus (T2DM) patients remains unclear. In this study, we examine the diagnostic value of UbA52 as a biomarker in predicting early diabetic kidney disease (DKD) in T2DM patients.MethodsWe used two-step ELISA to test UbA52 level in urine of 3 defined patient groups. Samples from T2DM patients without albuminuria or diabetic retinopathy (DM-WNP; n = 30), T2DM patients with albuminuria and diabetic retinopathy, excluding other renal diseases clinically (DM-NP; n = 30) and healthy controls (n = 30) were analyzed. Spearman's correlation analysis and multiple linear regression model were used to analyze the correlation of urinary UbA52 level with laboratory results regarding kidney function. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of UbA52 in predicting T2DM and early DKD.ResultsUrinary UbA52 level in DM-NP group was 1.75 times and 2.71 times higher than in DN-WNP (p = 0.004) and normal control group (p < 0.001), respectively. The level of urinary UbA52 correlated significantly with serum creatinine (r = 0.468, p < 0.001), GFR (r = −0.300, p = 0.004) and proteinuria (r = 0.484, p < 0.001). Multiple linear regression analysis showed that proteinuria level was independently associated with urinary UbA52 level (β = 0.833, p < 0.001). The area under the ROC of urinary UbA52 in diagnosing T2DM and DKD was 0.751 and 0.755, respectively.ConclusionThe level of urinary UbA52 increased significantly in T2DM patients with DKD. The level of proteinuria is independently associated with urinary UbA52 level. Urinary UbA52 could serve as an early marker in the diagnosis of DKD.ClinicalTrials.gov Identifier: NCT02204280.     

An exploratory trial of basal and prandial insulin initiation and titration for type 2 diabetes in primary care with adjunct retrospective continuous glucose monitoring: INITIATION study

AimsTo evaluate basal and prandial insulin initiation and titration in people with type 2 diabetes mellitus (T2DM) in primary care and to explore the feasibility of retrospective-continuous glucose monitoring (r-CGM) in guiding insulin dosing. The new model of care features General Practitioners (GPs) and Practice Nurses (PNs) working in an expanded role, with Credentialed Diabetes Educator – Registered Nurse (CDE-RN) support.MethodsInsulin-naïve T2DM patients (HbA1c >7.5% [>58 mmol/mol] despite maximal oral therapy) from 22 general practices in Victoria, Australia commenced insulin glargine, with glulisine added as required. Each was randomised to receive r-CGM or self-monitoring of blood glucose (SMBG). Glycaemic control (HbA1c) was benchmarked against specialist ambulatory patients referred for insulin initiation.ResultsNinety-two patients mean age (range) 59 (28–77) years; 40% female; mean (SD) diabetes duration 10.5 (6.1) years participated. HbA1c decreased from (median (IQR)) 9.9 (8.8, 11.2)%; 85 (73, 99) mmol/mol to 7.3 (6.9, 7.8)%; 56 (52, 62) mmol/mol at 24 weeks (p < 0.0001). Comparing r-CGM (n = 46) with SMBG (n = 42), there were no differences in major hypoglycaemia (p = 0.17) or ΔHbA1c (p = 0.31). More r-CGM than SMBG participants commenced glulisine (26/48 vs. 7/44; p < 0.001). Results were comparable to 82 benchmark patients, with similar low rates of major hypoglycaemia (2/89 vs. 0/82; p = 0.17) and less loss to follow up in the INITIATION group (3/92 vs. 14/82; p = 0.002).ConclusionsInsulin initiation and titration for T2DM patients in primary care was safe and improved HbA1c with low rates of major hypoglycaemia. CDE-RNs were effective in a new consultant role. r-CGM use in primary care was feasible and enhanced post-prandial hyperglycaemia recognition.Trial registration ACTRN12610000797077.     

Reduced risk of hypoglycemia with once-daily glargine versus twice-daily NPH and number needed to harm with NPH to demonstrate the risk of one additional hypoglycemic event in type 2 diabetes: Evidence from a long-term controlled trial

AimsThis analysis evaluated HbA_1c-adjusted hypoglycemia risk with glargine versus neutral protamine Hagedorn (NPH) over a 5-year study in patients with Type 2 diabetes mellitus (T2DM). Clinical significance was assessed using number needed to harm (NNH) to demonstrate the risk of one additional patient experiencing at least one hypoglycemic event.MethodsIndividual patient-level data for symptomatic documented hypoglycemia and HbA_1c values from a 5-year randomized study comparing once-daily glargine (n = 513) with twice-daily NPH (n = 504) were analyzed. Symptomatic hypoglycemia was categorized according to concurrent self-monitoring blood glucose levels and need for assistance. Hypoglycemic events per patient-year as a function of HbA_1c were fitted by negative binomial regression using treatment and HbA_1c at endpoint as independent variables. An estimate of NNH was derived from logistic regression models.ResultsThe cumulative number of symptomatic hypoglycemia events was consistently lower with glargine compared with NPH over 5 years. Compared with twice-daily NPH, once-daily glargine treatment resulted in significantly lower adjusted odds ratios (OR) for all daytime hypoglycemia (OR 0.74; p = 0.030) and any severe event (OR 0.64; p = 0.035), representing a 26% and 36% reduction in the odds of daytime and severe hypoglycemia, respectively. Our model predicts that, if 25 patients were treated with NPH instead of glargine, then one additional patient would experience at least one severe hypoglycemic event.ConclusionsThis analysis of long-term insulin treatment confirms findings from short-term studies and demonstrates that glargine provides sustained, clinically meaningful reductions in risk of hypoglycemia compared with NPH in patients with T2DM.     

Is there a relationship between hypomagnesemia and proton-pump inhibitors in patients on chronic hemodialysis?

AimWe investigated the association among long-term proton-pump inhibitors (PPIs) use with serum magnesium (Mg) levels in chronic hemodialysis (HD) patients, as well as possible association among PPI use and increased risk of cardiovascular (CVD) morbidity in HD patients.MethodsOf 418 HD patients that were screened for inclusion, 136 were excluded due to incomplete medical data, duration of renal replacement therapy (RRT) for less than 12 months, use of Mg-based-phosphate binders or other Mg-based medications or either to presence of chronic increased GI losses. Among 282 patients included in the study, 170 patients were on PPIs.ResultsSerum Mg levels were significantly lower among PPI users vs. non-users (0.94 ± 0.2 vs. 1.03 ± 0.2 mmol/L; p < 0.0001). The median duration of PPI use was 27 ± 9.6 months (range from 12 to 108) and it was not significantly associated with Mg levels (r = 0.116; p = 0.167). Additionally, residual renal function didn't show a significant correlation with Mg concentration (r = − 0.102; p = NS) in both groups of patients. The use of PPIs was an independent and strong predictor of low Mg concentrations even in multivariate analysis (OR 3.05; 95% CI 1.2498–7.4594, p = 0.01). On the other hand, the daily dose of PPIs was not associated with low Mg levels. PPI users had a higher rate of adverse CVD events during the 1 year of follow-up in comparison to non-PPI users but that difference wasn't statistically significant (17.6% vs. 10.7%; p = 0.110).ConclusionWe have found a significant association between PPI use and lower serum Mg levels in chronic HD patients.