First Author: E L Los
All Authors: Los EL, Deen PM, Robben JH
Journal Title: Journal of neuroendocrinology
Abstract: According to the body's need, water is reabsorbed from the pro-urine that is formed by ultrafiltration in the kidney. This process is regulated by the antidiuretic hormone arginine-vasopressin (AVP), which binds to its type 2 receptor (V2R) in the kidney. Mutations in the gene encoding the V2R often lead to the X-linked inheritable form of nephrogenic diabetes insipidus (NDI), a disorder in which patients are unable to concentrate their urine despite the presence of AVP. Many of these mutations are missense mutations that do not interfere with the intrinsic functionality of V2R, but cause its retention in the endoplasmic reticulum (ER), making it unavailable for AVP binding. Because the current treatments for NDI relieve its symptoms to some extent, but do not cure the disorder, cell-permeable antagonists (pharmacological chaperones) have been successfully used to stabilise the mutant receptors and restore their plasma membrane localisation. Recently, cell-permeable agonists also were shown to rescue ER-retained V2R mutants, leading to increased cAMP levels and translocation of aquaporin-2 to the apical membrane. This makes V2R-specific cell-permeable agonists very promising therapeutics for NDI as a result of misfolded V2R receptors.
Evaluate the Effect of Education Interventions in the Prevention of Diabetic Foot Ulcers through Knowledge of the Disease and Self-Care Practices in Saudi Arabia
Authors: Miyoshi S, Morita T, Kadoi Y, Goto F
Abstract: We sought to examine what factors, including cerebrovascular carbon dioxide (CO(2)) reactivity, are related to a decrease in internal jugular venous oxygen saturation (SjvO(2)) during normothermic cardiopulmonary bypass (CPB) in patients with diabetes mellitus.Twenty-three diabetic patients scheduled to undergo elective coronary artery bypass grafting were studied. As a control, 27 age-matched control patients without diabetes mellitus were also examined. After the induction of anesthesia, a fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to continuously monitor SjvO(2). Arterial and jugular venous blood gases were measured during CPB. The cerebrovascular CO(2) reactivity was measured after the induction of anesthesia and before the start of surgery using a 2.5-MHz pulsed transcranial Doppler probe.The SjvO(2) values in the diabetic group were lower than those in the control group at the initiation of CPB and at 20, 40, and 60 min after the start of CPB. The values for pre- and post-CO(2) reactivity in the control group did not significantly differ (pre-CPB: 4.8% +/- 2.3% mmHg(-1); post-CPB: 5.9% +/- 4.4% mmHg(-1)). In contrast, the values for CO(2) reactivity were lower post CPB than pre-CPB in the diabetic group (Pre-CPB: 6.3% +/- 2.9% mmHg(-1); post-CPB: 4.7% +/- 2.6% mmHg(-1); P < 0.05). In the diabetic group, glycosylated hemoglobin A1c (HbA1c) is considered to be a factor related to a decrease in SjvO(2) during CPB.Cerebrovascular CO(2) reactivity in diabetic patients decreased after the cessation of CPB but not in the control patients. In addition, HbA1c is also thought to be a factor related to a decrease in SjvO(2) in diabetic patients.
Authors: Tamemoto H, Ikoma A, Saitoh T, Ishikawa SE, Kawakami M
Abstract: Type 2 diabetes patients insufficiently controlled with sulfonylurea (SU) are commonly treated by switching to twice-daily premix insulin replacing SU. The efficacy of glargine (GL) added on to SU compared with the premix therapy has not been analyzed in Japan.The open-label two-arm study was conducted in 30 type 2 diabetes patients poorly controlled [hemoglobin A(1c) (HbA(1c)) >7.5%] with SU with or without other oral hypoglycemic agents (OHAs). The GL group injected once-daily GL in addition to the OHAs. The aspart 70/30 (70/30) group discontinued SU among the OHAs and injected twice-daily 70/30. Patients were recommended either method in a block random method, and if twice-daily 70/30 was rejected, once-daily GL was selected only at the first time. The insulin dose was titrated to achieve a target fasting plasma glucose of <120 mg/dL and/or HbA(1c) of <7%.Nineteen of 20 patients treated with GL and 11 of 14 patients treated with 70/30 completed the 6-month study. Mean HbA(1c) improved from 8.45% to 7.5% in the GL group and from 9.13% to 7.93% in the 70/30 group. The mean HbA(1c) decrease during 6 months was -0.95% in the GL group and -1.20% in the 70/30 group (P = 0.49). Mean insulin doses at 6 months were 12.0 units/day for the GL group and 26.7 units/day for the 70/30 group. Both therapies were well tolerated without severe hypoglycemia.Once-daily GL injection added on to OHAs was equally safe and effective compared with twice-daily injection of aspart 70/30 premix replacing SU in type 2 patients insufficiently controlled with OHAs.
Authors: Isobe S, Yamada T, Sato K, Katagiri T, Ohyama H, Hayashi M, Yoshikawa D, Ishii H, Murohara T
Abstract: Diabetes mellitus (DM) and high fasting glucose levels are reportedly risk factors for contrast-induced nephropathy after invasive coronary angiography in patients with renal dysfunction. Cystatin C (CyC) is a sensitive marker for detecting early impairment of renal function. Using CyC, we investigated whether DM would be a risk for worsening renal function after coronary computed tomography angiography (CCTA) in patients with preserved renal function.Two hundred twenty-eight patients scheduled for CCTA were enrolled. The serum CyC at preprocedure and 1 day after procedure, urinary microalbumin at preprocedure, and oral fluid volume for 24 hours after procedure were measured. The percentage changes in CyC from preprocedure to 1 day after procedure (%CyC) were also calculated.Ninety-eight patients had DM. The %CyC and urinary microalbumin were significantly greater in DM patients than in non-DM patients. The percentage of patients showing a %CyC of 10% or greater was significantly greater in DM patients than in non-DM patients (27% vs 8%, P < 0.01). Using multivariate regression analysis, oral fluid volume and urinary microalbumin were independent predictors for a %CyC of 10% or greater in DM patients (? = -?0.428 [P < 0.0001] and ? = 0.464 [P < 0.0001], respectively).Diabetes mellitus is a risk factor for worsening changes in renal function after CCTA, even in patients with preserved renal function. In particular, elevated microalbuminuria and low oral fluid intake are high-risk factors for renal functional deterioration.
Authors: Patel YR, Kirkman MS, Considine RV, Hannon TS, Mather KJ
Abstract: The anti-diabetic agent acarbose reduces postprandial glucose excursions. We have evaluated the effect of randomized treatment with acarbose on the progression of carotid intima-media thickness (IMT) in early diabetes.The Early Diabetes Intervention Program was a randomized trial of acarbose versus placebo in 219 participants with early diabetes characterized by glucose values over 11.1 mmol/L 2 h after a 75 g oral glucose load and a mean HbA1c of 6.3%. IMT was measured at baseline and yearly. Follow-up was discontinued if participants progressed to the study glucose endpoints; IMT readings were available for a median of 2 years, with 72 subjects followed for 5 years.Progressive increases in IMT were seen in both treatment groups, but progression was reduced in participants randomized to acarbose (p = 0.047). In age, sex and smoking-adjusted analyses, IMT progression was associated with greater fasting and oral glucose tolerance test-excursion glucose, fasting insulin, cholesterol and glycated low-density lipoprotein concentrations. IMT progression was reduced with study-related changes in weight, insulin and non-esterified fatty acids; these features were more strongly associated with reduced IMT progression than acarbose treatment. Despite strong associations of baseline glycemia with IMT progression, study-related changes in glucose were not important determinants of IMT progression.Acarbose can delay progression of carotid intima-media thickness in early diabetes defined by an oral glucose tolerance test. Glucose, weight, insulin and lipids contributed to risk of progression but reductions in glycemia were not major determinants of reduced rate of IMT progression. Vascular benefits of acarbose may be independent of its glycemic effects.
Authors: George A Bray
Abstract: Metformin produced weight loss and delayed or prevented diabetes in the Diabetes Prevention Program (DPP). We examined its long-term safety and tolerability along with weight loss, and change in waist circumference during the DPP and its long-term follow-up.The randomized double-blind clinical trial of metformin or placebo followed by a 7-8-year open-label extension and analysis of adverse events, tolerability, and the effect of adherence on change in weight and waist circumference.No significant safety issues were identified. Gastrointestinal symptoms were more common in metformin than placebo participants and declined over time. During the DPP, average hemoglobin and hematocrit levels were slightly lower in the metformin group than in the placebo group. Decreases in hemoglobin and hematocrit in the metformin group occurred during the first year following randomization, with no further changes observed over time. During the DPP, metformin participants had reduced body weight and waist circumference compared with placebo (weight by 2.06 ± 5.65% vs. 0.02 ± 5.52%, P < 0.001, and waist circumference by 2.13 ± 7.06 cm vs. 0.79 ± 6.54 cm, P < 0.001 in metformin vs. placebo, respectively). The magnitude of weight loss during the 2-year double-blind period was directly related to adherence (P < 0.001). Throughout the unblinded follow-up, weight loss remained significantly greater in the metformin group than in the placebo group (2.0 vs. 0.2%, P < 0.001), and this was related to the degree of continuing metformin adherence (P < 0.001).Metformin used for diabetes prevention is safe and well tolerated. Weight loss is related to adherence to metformin and is durable for at least 10 years of treatment.
Authors: Nguyen HT, Kirk JK, Arcury TA, Ip EH, Grzywacz JG, Saldana SJ, Bell RA, Quandt SA
Abstract: Cognitive impairment is common in older adults with diabetes, yet it is unclear to what extent cognitive function is associated with health literacy. We hypothesized that cognitive function, independent of education, is associated with health literacy.The sample included 537 African American, American Indian, and White men and women 60 years or older. Measures of cognitive function included the Mini-Mental State Examination (MMSE), Verbal Fluency, Brief Attention, and Digit Span Backward tests. Health literacy was assessed using the S-TOFHLA.Cognitive function was associated with health literacy, independent of education and other important confounders. Every unit increase in the MMSE, Digit Span Backward, Verbal Fluency or Brief Attention was associated with a 20% (p<.001), 34% (p<.001), 5% (p<.01), and 16% (p<.01) increase in the odds of having adequate health literacy, respectively.These results suggest that cognitive function is associated with health literacy in older adults with diabetes. Because poor cognitive function may undermine health literacy, efforts to target older adults on improving health literacy should consider cognitive function as a risk factor.
Authors: Brown J, Grzeskowiak L, Williamson K, Downie MR, Crowther CA
Abstract: Gestational diabetes mellitus (GDM) is associated with short- and long-term complications for the mother and her infant. Women who are unable to maintain their blood glucose concentration within pre-specified treatment targets with diet and lifestyle interventions will require anti-diabetic pharmacological therapies. This review explores the safety and effectiveness of insulin compared with oral anti-diabetic pharmacological therapies, non-pharmacological interventions and insulin regimens.To evaluate the effects of insulin in treating women with gestational diabetes.We searched Pregnancy and Childbirth's Trials Register (1 May 2017), ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (1 May 2017) and reference lists of retrieved studies.We included randomised controlled trials (including those published in abstract form) comparing:a) insulin with an oral anti-diabetic pharmacological therapy;b) with a non-pharmacological intervention;c) different insulin analogues;d) different insulin regimens for treating women with diagnosed with GDM.We excluded quasi-randomised and trials including women with pre-existing type 1 or type 2 diabetes. Cross-over trials were not eligible for inclusion.Two review authors independently assessed study eligibility, risk of bias, and extracted data. Data were checked for accuracy.We included 53 relevant studies (103 publications), reporting data for 7381 women. Forty-six of these studies reported data for 6435 infants but our analyses were based on fewer number of studies/participants.Overall, the risk of bias was unclear; 40 of the 53 included trials were not blinded. Overall, the quality of the evidence ranged from moderate to very low quality. The primary reasons for downgrading evidence were imprecision, risk of bias and inconsistency. We report the results for our maternal and infant GRADE outcomes for the main comparison. Insulin versus oral anti-diabetic pharmacological therapyFor the mother, insulin was associated with an increased risk for hypertensive disorders of pregnancy (not defined) compared to oral anti-diabetic pharmacological therapy (risk ratio (RR) 1.89, 95% confidence interval (CI) 1.14 to 3.12; four studies, 1214 women; moderate-quality evidence). There was no clear evidence of a difference between those who had been treated with insulin and those who had been treated with an oral anti-diabetic pharmacological therapy for the risk of pre-eclampsia (RR 1.14, 95% CI 0.86 to 1.52; 10 studies, 2060 women; moderate-quality evidence); the risk of birth by caesarean section (RR 1.03, 95% CI 0.93 to 1.14; 17 studies, 1988 women; moderate-quality evidence); or the risk of developing type 2 diabetes (metformin only) (RR 1.39, 95% CI 0.80 to 2.44; two studies, 754 women; moderate-quality evidence). The risk of undergoing induction of labour for those treated with insulin compared with oral anti-diabetic pharmacological therapy may possibly be increased, although the evidence was not clear (average RR 1.30, 95% CI 0.96 to 1.75; three studies, 348 women; I² = 32%; moderate-quality of evidence). There was no clear evidence of difference in postnatal weight retention between women treated with insulin and those treated with oral anti-diabetic pharmacological therapy (metformin) at six to eight weeks postpartum (MD -1.60 kg, 95% CI -6.34 to 3.14; one study, 167 women; low-quality evidence) or one year postpartum (MD -3.70, 95% CI -8.50 to 1.10; one study, 176 women; low-quality evidence). The outcomes of perineal trauma/tearing or postnatal depression were not reported in the included studies.For the infant, there was no evidence of a clear difference between those whose mothers had been treated with insulin and those treated with oral anti-diabetic pharmacological therapies for the risk of being born large-for-gestational age (average RR 1.01, 95% CI 0.76 to 1.35; 13 studies, 2352 infants; moderate-quality evidence); the risk of perinatal (fetal and neonatal death) mortality (RR 0.85; 95% CI 0.29 to 2.49; 10 studies, 1463 infants; low-quality evidence);, for the risk of death or serious morbidity composite (RR 1.03, 95% CI 0.84 to 1.26; two studies, 760 infants; moderate-quality evidence); the risk of neonatal hypoglycaemia (average RR 1.14, 95% CI 0.85 to 1.52; 24 studies, 3892 infants; low-quality evidence); neonatal adiposity at birth (% fat mass) (mean difference (MD) 1.6%, 95% CI -3.77 to 0.57; one study, 82 infants; moderate-quality evidence); neonatal adiposity at birth (skinfold sum/mm) (MD 0.8 mm, 95% CI -2.33 to 0.73; random-effects; one study, 82 infants; very low-quality evidence); or childhood adiposity (total percentage fat mass) (MD 0.5%; 95% CI -0.49 to 1.49; one study, 318 children; low-quality evidence). Low-quality evidence also found no clear differences between groups for rates of neurosensory disabilities in later childhood: hearing impairment (RR 0.31, 95% CI 0.01 to 7.49; one study, 93 children), visual impairment (RR 0.31, 95% CI 0.03 to 2.90; one study, 93 children), or any mild developmental delay (RR 1.07, 95% CI 0.33 to 3.44; one study, 93 children). Later infant mortality, and childhood diabetes were not reported as outcomes in the included studies.We also looked at comparisons for regular human insulin versus other insulin analogues, insulin versus diet/standard care, insulin versus exercise and comparisons of insulin regimens, however there was ins
Authors: Downes K, Marcovecchio ML, Clarke P, Cooper JD, Ferreira RC, Howson JM, Jolley J, Nutland S, Stevens HE, Walker NM, Wallace C, Dunger DB, Todd JA
Abstract: Type 1 diabetes is a common autoimmune disease that has genetic and environmental determinants. Variations within the IL2 and IL2RA (also known as CD25) gene regions are associated with disease risk, and variation in expression or function of these proteins is likely to be causal. We aimed to investigate if circulating concentrations of the soluble form of CD25, sCD25, an established marker of immune activation and inflammation, were increased in individuals with type 1 diabetes and if this was associated with the concentration of C-peptide, a measure of insulin production that reflects the degree of autoimmune destruction of the insulin-producing beta cells.We used immunoassays to measure sCD25 and C-peptide in peripheral blood plasma from patient and control samples.We identified that sCD25 was increased in patients with type 1 diabetes compared with controls and replicated this result in an independent set of 86 adult patient and 80 age-matched control samples (p?=?1.17?×?10(-3)). In 230 patients under 20 years of age, with median duration-of-disease of 6.1 years, concentrations of sCD25 were negatively associated with C-peptide concentrations (p?=?4.8?×?10(-3)).The 25% increase in sCD25 in patients, alongside the inverse association between sCD25 and C-peptide, probably reflect the adverse effects of an on-going, actively autoimmune and inflammatory immune system on beta cell function in patients.
Authors: Kullberg CE, Abrahamsson M, Arnqvist HJ, Finnström K, Ludvigsson J,
Abstract: The VISS study (Vascular complications in South-east Sweden) investigates prevalence and incidence of vascular complications in a population with Type 1 diabetes, from a well-defined geographical area and followed from diagnosis with HbA1c measurement.The study population comprised all 440 patients with Type 1 diabetes onset before the age of 36 years, onset during 1983-1987, and at the time of onset living within the counties of Jönköping, Kalmar or Ostergötland. Retinopathy was examined with fundus photography 1994-1995, and classified according to a modified Airlie House protocol.Fundus photographs from 390 patients were evaluated. In 277 (71%) patients no retinopathy was seen. The prevalence of retinopathy increased from 11% among patients < 5 years old at diabetes onset, to 48% among those 15-19 years old at diabetes onset, and then decreased to 30% for patients 30-35 years old at diabetes onset (P for chi2 for linear trend for all ages 0.017, for age at onset 0-19 years P = 0.0003), without corresponding differences in duration or HbA1c between patients with different onset age. Patients with HbA1c in the highest quartile (> 8.3% HbA1c) had a relative risk of 2.4 (95% confidence interval (CI) 1.7-3.2) of having any retinopathy compared with patients with lower HbA1c, and a relative risk of 7.1 (95% CI 3.0-16.7) of having other forms of retinopathy than microaneurysms.In patients with diabetes duration of 6-13 years, the prevalence of retinopathy is clearly related to glycaemic control. Furthermore, the risk of retinopathy varies with different age at onset, independently of differences in duration or glycaemic control.
Authors: Slabaugh SL, Curtis BH, Clore G, Fu H, Schuster DP
Abstract: The objective of this study was to apply quantile regression (QR) methodology to a population from a large representative health insurance plan with known skewed healthcare utilization attributes, co-morbidities, and costs in order to identify predictors of increased healthcare costs. Further, this study provides comparison of the results to those obtained using ordinary least squares (OLS) regression methodology.Members diagnosed with Type 2 Diabetes and with 24 months of continuous enrollment were included. Baseline patient demographic, clinical, consumer/behavioural, and cost characteristics were quantified. Quantile regression was used to model the relationship between the baseline characteristics and total healthcare costs during the follow-up 12 month period.The sample included 83,705 patients (mean age = 70.6 years, 48% male) residing primarily in the southern US (78.1%); 81.2% of subjects were on oral-only anti-diabetic therapy. Co-morbid conditions included nephropathy (43.5%), peripheral artery disease (26.4%), and retinopathy (18.0%). Variables with the strongest relationship with costs during the follow-up period included outpatient visits, ER visits, inpatient visits, and Diabetes Complications Severity Index score during the baseline period. In the top cost quantiles, each additional glycohemoglobin (HbA1c) test was associated with cost savings ($1400 in the 98th percentile). Stage 4 and Stage 5 chronic kidney disease were associated with an incremental cost increase of $33,131 and $106,975 relative to Stage 1 or no CKD in the 98th percentile ($US).These results demonstrate that QR provides additional insight compared to traditional OLS regression modeling, and may be more useful for informing resource allocation to patients most likely to benefit from interventions. This study highlights that the impact of clinical and demographic characteristics on the economic burden of the disease vary across the continuum of healthcare costs. Understanding factors that drive costs on an individual patient level provide important insights that will help in ameliorating the clinical, humanistic, and economic burden of diabetes.