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Prediction of microalbuminuria from proteinuria in chronic kidney disease due to non-diabetic lifestyle-related diseases: comparison with diabetes.
Ogi, M, Seto, T, Wakabayashi, Y
Clinical and experimental nephrology. 2021;(7):727-750
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Abstract
BACKGROUND To suppress increases in kidney failure and cardiovascular disease due to lifestyle-related diseases other than diabetes, early intervention is desirable. We examined whether microalbuminuria could be predicted from proteinuria. METHODS The participants consisted of adults who exhibited a urinary protein-to-creatinine ratio (uPCR) of < 0.5 g/gCr and an eGFR of ≥ 15 ml/min/1.73 m2 in their spot urine at their first examination for lifestyle-related disease. Urine was tested three times for each case, with microalbuminuria defined as a urinary albumin-to-creatinine ratio (uACR) of 30-299 mg/gCr, at least twice on three measurements. Youden's Index was used as an index of the cut-off value (CO) according to the ROC curve. RESULTS A single uPCR was useful for differentiating normoalbuminuria and micro- and macroalbuminuria in patients with non-diabetic lifestyle-related diseases. Regarding the GFR categories, the CO of the second uPCR was 0.09 g/gCr (AUC 0.89, sensitivity 0.76, specificity 0.89) in G1-4 (n = 197) and 0.07 g/gCr (AUC 0.92, sensitivity 0.85, specificity 0.88) in G1-3a (n = 125). Using the sum of two or three uPCR measurements was more useful than a single uPCR for differentiating microalbuminuria in non-diabetic lifestyle disease [CO, 0.16 g/gCr (AUC 0.91, sensitivity 0.85, specificity 0.87) and 0.23 g/gCr (AUC 0.92, sensitivity 0.88, specificity 0.84), respectively]. CONCLUSION Microalbuminuria in Japanese individuals with non-diabetic lifestyle-related diseases can be predicted from the uPCR, wherein the CO of the uPCR that differentiates normoalbuminuria and micro- and macroalbuminuria was 0.07 g/gCr for G1-3a, while that in G3b-4 was 0.09 g/gCr.
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Efficacy and Safety of Tradipitant in Patients With Diabetic and Idiopathic Gastroparesis in a Randomized, Placebo-Controlled Trial.
Carlin, JL, Lieberman, VR, Dahal, A, Keefe, MS, Xiao, C, Birznieks, G, Abell, TL, Lembo, A, Parkman, HP, Polymeropoulos, MH
Gastroenterology. 2021;(1):76-87.e4
Abstract
BACKGROUND & AIMS Treatments are needed for gastroparesis; antagonists of tachykinin receptor 1 (TACR1, also called NK1R) can reduce symptoms of nausea and vomiting. We investigated the safety and efficacy of tradipitant, an antagonist of NK1R, in patients with idiopathic or diabetic gastroparesis. METHODS We performed a double-blind trial of 152 adults with gastroparesis at 47 sites in the United States from November 2016 through December 2018. Participants were randomly assigned to groups given oral tradipitant 85 mg (n = 77) or placebo (n = 75) twice daily for 4 weeks. Symptoms were assessed by a daily symptom dairy, Gastroparesis Cardinal Symptom Index scores, and other patient-reported questionnaires. The primary outcome from the intent-to-treat analysis was change from baseline to week 4 in average nausea severity, measured by the Gastroparesis Core Symptom Daily Diary. RESULTS Patients receiving tradipitant had a significant decrease in nausea score (reduction of 1.2) at week 4 compared with placebo (reduction of 0.7) (P = .0099) and a significant increase in of nausea-free days at week 4 (28.8% increase on tradipitant vs 15.0% on placebo; P = .0160). Patients with nausea and vomiting at baseline (n = 101) had an even greater decrease in nausea in when given tradipitant (reduction of 1.4) compared with those given placebo (reduction of 0.4) (P < .0001), as well as an increase in nausea-free days at week 4 (32.3% improvement on tradipitant vs 7.6% on placebo; P = .0003). The average nausea score was 1 or less at week 4 in 32.9% of patients given tradipitant compared with 11.8% of patients given placebo (P = .0013). A greater than 1-point improvement in Gastroparesis Cardinal Symptom Index score was observed in 46.6% of patients given tradipitant compared with 23.5% of patients given placebo (P = .0053). CONCLUSIONS Tradipitant resulted in statistically and clinically meaningful improvements in nausea and reduced vomiting, compared with placebo, in patients with idiopathic or diabetic gastroparesis. ClinicalTrials.gov, Number: NCT02970968.
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The Effect of Far-Infrared Therapy on the Peritoneal Expression of Glucose Degradation Products in Diabetic Patients on Peritoneal Dialysis.
Chang, CN, Niu, CY, Tan, AC, Chan, CH, Chen, CF, Chen, TH, Li, SY, Chen, YT, Chen, FY, Liu, WS, et al
International journal of molecular sciences. 2021;(7)
Abstract
Peritoneal dialysis (PD) is a treatment modality for end-stage renal disease (ESRD) patients. Dextrose is a common osmotic agent used in PD solutions and its absorption may exacerbate diabetes mellitus, a common complication of ESRD. PD solutions also contain glucose degradation products (GDPs) that may lead to encapsulating peritoneal sclerosis (EPS), a severe complication of PD. A previous study showed that far-infrared (FIR) therapy improved a patient's gastrointestinal symptoms due to EPS. Due to limited literature on the matter, this study aims to investigate dialysate GDPs and peritoneal function in diabetic patients on PD. Thirty-one PD patients were enrolled and underwent 40 min of FIR therapy twice daily for six months. We demonstrated the effect of FIR therapy on the following: (1) decrease of methylglyoxal (p = 0.02), furfural (p = 0.005), and 5-hydroxymethylfurfural (p = 0.03), (2) increase of D/D0 glucose ratio (p = 0.03), and (3) decrease of potassium levels (p = 0.008) in both DM and non-DM patients, as well as (4) maintenance and increase of peritoneal Kt/V in DM and non-DM patients, respectively (p = 0.03). FIR therapy is a non-invasive intervention that can decrease dialysate GDPs in PD patients by improving peritoneal transport rate and solute removal clearance, while also maintaining dialysis adequacy.
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Collagen methionine sulfoxide and glucuronidine/LW-1 are markers of coronary artery disease in long-term survivors with type 1 diabetes. The Dialong study.
Holte, KB, Svanteson, M, Hanssen, KF, Sveen, KA, Seljeflot, I, Solheim, S, Sell, DR, Monnier, VM, Berg, TJ
PloS one. 2020;(5):e0233174
Abstract
OBJECTIVES Type 1 diabetes is a risk factor for coronary heart disease. The underlying mechanism behind the accelerated atherosclerosis formation is not fully understood but may be related to the formation of oxidation products and advanced glycation end-products (AGEs). We aimed to examine the associations between the collagen oxidation product methionine sulfoxide; the collagen AGEs methylglyoxal hydroimidazolone (MG-H1), glucosepane, pentosidine, glucuronidine/LW-1; and serum receptors for AGE (RAGE) with measures of coronary artery disease in patients with long-term type 1 diabetes. METHODS In this cross-sectional study, 99 participants with type 1 diabetes of ≥ 45-year duration and 63 controls without diabetes had either established coronary heart disease (CHD) or underwent Computed Tomography Coronary Angiography (CTCA) measuring total, calcified and soft/mixed plaque volume. Skin collagen methionine sulfoxide and AGEs were measured by liquid chromatography-mass spectrometry and serum sRAGE/esRAGE by ELISA. RESULTS In the diabetes group, low levels of methionine sulfoxide (adjusted for age, sex and mean HbA1c) were associated with normal coronary arteries, OR 0.48 (95% CI 0.27-0.88). Glucuronidine/LW-1 was associated with established CHD, OR 2.0 (1.16-3.49). MG-H1 and glucuronidine/LW-1 correlated with calcified plaque volume (r = 0.23-0.28, p<0.05), while pentosidine correlated with soft/mixed plaque volume (r = 0.29, p = 0.008), also in the adjusted analysis. CONCLUSIONS Low levels of collagen-bound methionine sulfoxide were associated with normal coronary arteries while glucuronidine/LW-1 was positively associated with established CHD in long-term type 1 diabetes, suggesting a role for metabolic and oxidative stress in the formation of atherosclerosis in diabetes.
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Adverse risk factor trends limit gains in coronary heart disease mortality in Barbados: 1990-2012.
Sobers, NP, Unwin, N, Samuels, TA, Capewell, S, O'Flaherty, M, Critchley, JA
PloS one. 2019;(4):e0215392
Abstract
BACKGROUND Although most countries face increasing population levels of obesity and diabetes their effect on coronary heart disease (CHD) mortality has not been often studied in small island developing states (SIDs) where obesity rates are among the highest in the world. We estimated the relative contributions of treatments and cardiovascular risk factors to the decline in CHD mortality from 1990 to 2012 in the Caribbean island, Barbados. METHODS We used the IMPACT CHD mortality model to estimate the effect of increased coverage of effective medical/surgical treatments and changes in major CHD risk factors on mortality trends in 2012 compared with 1990. We calculated deaths prevented or postponed (DPPs) for each model risk factor and treatment group. We obtained data from WHO Mortality database, population denominators from the Barbados Statistical Service stratified by 10-year age group (ages 25-34 up to 85 plus), population-based risk factor surveys, Global Burden of Disease and Barbados' national myocardial infarction registry. Monte Carlo probabilistic sensitivity analysis was performed. RESULTS In 1990 the age-standardized CHD mortality rate was 109.5 per 100,000 falling to 55.3 in 2012. Implementation of effective treatment accounted for 56% DPPs (95% (Uncertainty Interval (UI) 46%, 68%), mostly due to the introduction of treatments immediately after acute myocardial infarction (AMI) (14%) and unstable angina (14%). Overall, risk factors contributed 19% DPPs (95% UI 6% to 34%) mostly attributed to decline in cholesterol (18% DPPs, 95% UI 12%, 26%). Adverse trends in diabetes: 14% additional deaths(ADs) 95% UI 8% to 21% ADs) and BMI (2% ADs 95%UI 0 to 5% ADs) limited potential for risk factor gains. CONCLUSIONS Given the significant negative impact of obesity/diabetes on mortality in this analysis, research that explores factors affecting implementation of evidenced-based preventive strategies is needed. The fact that most of the decline in CHD mortality in Barbados was due to treatment provides an example for SIDs about the advantages of universal access to care and treatment.
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Influence of oral moisturizing jelly as a saliva substitute for the relief of xerostomia in elderly patients with hypertension and diabetes mellitus.
Dalodom, S, Lam-Ubol, A, Jeanmaneechotechai, S, Takamfoo, L, Intachai, W, Duangchada, K, Hongsachum, B, Kanjanatiwat, P, Vacharotayangul, P, Trachootham, D
Geriatric nursing (New York, N.Y.). 2016;(2):101-9
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Abstract
Dry mouth is common in elderly patients. However, the use of saliva substitute has been limited due to its inedibility. This study investigated the efficacy of oral moisturizing jelly (OMJ), a novel edible saliva substitute. A pre-post design was conducted in 118 elderly patients diagnosed with hypertension and/or diabetes mellitus. After using OMJ, signs and symptoms of dry mouth were compared with baseline data. The properties of saliva were compared between the OMJ use and non-use periods. The use of OMJ for 2 weeks significantly reduced symptoms of dry mouth, while the use for 1 month reduced the signs of xerostomia, prevented the decline of salivary pH(s) and improved buffering capacities. OMJ was equally effective in patients taking 1 to 2 and 3 to 7 medications. Furthermore, 65% of patients preferred OMJ over a commercial product. OMJ could be new edible saliva substitute for elderly patients suffering from dry mouth. Clinicaltrials.gov ID: NCT02317172.
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Type 2 diabetes mellitus is associated with increased risks of sarcopenia and pre-sarcopenia in Chinese elderly.
Wang, T, Feng, X, Zhou, J, Gong, H, Xia, S, Wei, Q, Hu, X, Tao, R, Li, L, Qian, F, et al
Scientific reports. 2016;:38937
Abstract
Sarcopenia is a condition characterized by progressive and generalized loss of skeletal muscle mass and function. In this study, we used a cross-sectional study with 1090 community-dwelling Chinese citizens aged 60 years and older to evaluate the association of type 2 diabetes mellitus (T2DM) with the risk of sarcopenia and pre-sarcopenia. Sarcopenia was defined using the Asian Working Group for Sarcopenia (AWGS) criteria that include both muscle mass and muscle function/physical activity. Pre-sarcopenia was defined as having low skeletal muscle index but with normal muscle/physical activity. The prevalence of sarcopenia and pre-sarcopenia was significantly higher in T2DM patients than in healthy controls (14.8% vs. 11.2%, p = 0.035 for sarcopenia, and 14.4% vs. 8.4%, p = 0.002 for pre-sarcopenia). In multivariate logistic regression analyses adjusting by age, gender, anti-diabetic medication, energy intake, protein intake, physical activity, and visceral fat area, we found that Chinese elderly with T2DM exhibited significantly increased risks of sarcopenia (OR = 1.37, 95% CI = 1.02-2.03) and pre-sarcopenia (OR = 1.73, 95% CI = 1.10-2.83) compared to non-diabetic individuals. This is the first study to evaluate the association of T2DM with the risks of sarcopenia and pre-sarcopenia in China. Among a group of community-dwelling Chinese elderly, T2DM was significantly associated with increased risks of sarcopenia and pre-sarcopenia.
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Association between Hyperhomocysteinemia and Thyroid Hormones in Euthyroid Diabetic Subjects.
Zhang, Y, Wang, Q, Li, Q, Lu, P
BioMed research international. 2015;:196379
Abstract
OBJECTIVES The concept now emerging is that higher thyroid-stimulating hormone (TSH) and lower thyroid hormone levels within the euthyroid range may adversely affect atherosclerosis. The present study aimed to investigate the potential associations between thyroid parameters and hyperhomocysteinaemia in a cohort of euthyroid diabetic subjects. MATERIAL AND METHODS Two hundred and seventy-three euthyroid diabetic subjects (167 males and 106 females) were consecutively recruited in this cross-sectional study. Clinical and biomedical data was collected. RESULTS TSH level was higher in females than males. Compared to normal-homocysteine group, hyperhomocysteinaemia group was more likely to be elderly, males, with longer diabetes history, and with lower diastolic blood pressure. Free thyroxine (FT4) level was lower in hyperhomocysteinaemia group than in normal-homocysteine group; however, it was not statistically significant. Adjusted for age, sex, body mass index, duration of diabetes, blood pressure, fasting glucose, total cholesterol, and triglyceride in logistic regression analyses, hyperhomocysteinaemia was significantly correlated with FT4 (P = 0.021). No significant association was found with TSH or free triiodothyronine. When analyzed in subjects with TSH < 2.5 uIU/mL separately, we got similar results. CONCLUSIONS In conclusion, we identified a relation between hyperhomocysteinemia and FT4 in a group of euthyroid diabetic patients.
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The durability of sitagliptin in elderly patients with type 2 diabetes.
Hsieh, CJ, Shen, FC
Clinical interventions in aging. 2014;:1905-11
Abstract
AIM: To evaluate the durability of sitagliptin and to assess changes in clinical chronic complications following sitagliptin monotherapy for 48 months in elderly patients with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS We enrolled 76 drug-naïve patients (40 women and 36 men; mean age: 71.3±11.7 years) with T2DM who received 25-100 mg of sitagliptin therapy from an outpatient clinic. The observational period for each patient was >48 months, beginning at the time sitagliptin therapy was initiated. The following were measured or performed at the beginning of each year: body mass index; serum total cholesterol, low-density lipoprotein, high-density lipoprotein; triglyceride levels; creatinine (Cr) levels; urine albumin and urine Cr; nonmydriatic fundusgraphy; and semiquantified neuropathy. The fasting plasma glucose and glycated hemoglobin (HbA1c) was measured every 3-6 months. RESULTS The change in HbA1c was significantly reduced after 6 months of therapy (7.1%±0.8% to 6.3%±0.2%). No changes in fasting plasma glucose, Cr, serum total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, body mass index, and microvascular complications were apparent. Using repeated measures to test the sequential changes in HbA1c from month 6 to month 48, the test of within-subjects effect was not significant (P=0.34). CONCLUSION Sitagliptin has a durable effect and stabilizes microvascular complication progression in elderly patients. This study can provide useful data for clinicians and health care professionals using sitagliptin monotherapy in the treatment of elderly patients with T2DM.
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[Effects of intensive insulin therapy after an acute myocardial infarction in patients with type 2 diabetes: results of the DIGAMI-2 trial].
Scheen, AJ, Radermecker, RP, Philips, JC
Revue medicale de Liege. 2004;(9):534-9
Abstract
The results of DIGAMI-2 (<>) trial were presented at the 40th scientific congress of the European Association for the Study of Diabetes (EASD) in Munich on September 6, 2004. The main objective of this multicentre international trial was to confirm the positive results of the first DIGAMI trial published in 1995--1997. This pilot trial demonstrated that insulin-glucose infusion followed by a subcutaneous multidose insulin regimen reduces total mortality after 1 and 3 years in diabetic patients with acute myocardial infarction. DIGAMI-2, by comparing three groups of subjects receiving various interventions, aimed at determining the relative benefit resulting from the insulin-glucose infusion in the acute phase and that attributable to long-term intensive insulin therapy in a similar population of type 2 diabetic patients. No significant difference was observed between the three groups as far as total mortality and cardiovascular morbidity were concerned. These negative results may be explained by the absence of significant difference in blood glucose control between the three groups, by the fact that glycaemic targets were not reached in the intensive group and, last but not least, by a better management of other risk factors, allowing already markedly reduced cardiovascular morbidity and mortality in the reference group treated with conventional antidiabetic therapy. In conclusion, DIGAMI-2 argues for a multidisciplinary management of diabetic patients to reach strict glycaemic targets with an intensive insulin scheme and confirms the remarkable advances in cardiovascular protection thanks to an optimised global pharmacological approach combined with modern revascularisation procedures.