Liraglutide Improves Glycemic and Blood Pressure Control and Ameliorates Progression of Left Ventricular Hypertrophy in Patients with Type 2 Diabetes Mellitus on Peritoneal Dialysis

Diabetes mellitus (DM) is a multifactorial disease associated with cardiovascular complications. Patients undergoing peritoneal dialysis also experience an increased incidence of cardiovascular disease. To prevent progression of cardiovascular complications in DM patients, glycemic control is important. In this study, we examined the efficacy and safety of the glucagon‐like peptide analog liraglutide for treating type 2 diabetes patients undergoing peritoneal dialysis. Sixteen type 2 diabetes patients on peritoneal dialysis were enrolled. Before liraglutide initiation, 11 patients were on insulin therapy, three were on oral antidiabetic agents, and two were on diet therapy. Of the 16 patients, 12 had switched to liraglutide because of severe hypoglycemia and four because of hyperglycemia. Echocardiography was performed at baseline and 12 months after liraglutide initiation. Hemoglobin A1c, glycosylated albumin, and fasting/postprandial glucose levels gradually decreased after liraglutide initiation. After 6 and 12 months of treatment, postprandial glucose levels showed a significant difference from baseline. Moreover, the mean daily glucose level and glycemic fluctuations decreased. Systolic blood pressure upon waking also decreased. In addition, after 12 months, left ventricular mass index (LVMI) decreased and left ventricular ejection fraction increased. Changes in LVMI positively correlated with morning systolic blood pressure and fasting glucose levels. One patient restarted insulin because of anorexia but severe hypoglycemia was not observed. These findings suggest that liraglutide therapy in type 2 diabetes patients undergoing peritoneal dialysis is safe and effective for decreasing glucose levels, glycemic fluctuations, and blood pressure, apart from improving left ventricular function.     

Glycemic Control in Diabetic Dialysis Patients and the Burnt-Out Diabetes Phenomenon

Diabetes mellitus (DM) is the most common cause of end-stage kidney disease and a major risk of morbidity and mortality. It is not clear whether medical management of DM has any significant beneficial effect on clinical outcomes at the end-stage of diabetic nephropathy with full-blown micro- and macro-angiopathic complications. Both loss of kidney function and dialysis treatment interfere with glucose homeostasis and confound glycemic control. Given the unique nature of uremic milieu and dialysis therapy related alterations, there have been some debates about reliance on the conventional measures of glycemic control, in particular the clinical relevance of hemoglobin A1c and its recommended target range of <7 % in diabetic dialysis patients. Moreover, a so-called burnt-out diabetes phenomenon has been described, in that many diabetic dialysis patients experience frequent hypoglycemic episodes prompting cessation of their anti-diabetic therapies transiently or even permanently. By reviewing the recent literature we argue that the use of A1c for management of diabetic dialysis patients should be encouraged if appropriate target ranges specific for these patients (e.g. 6 to 8 %) are used. We also argue that "burnt-out diabetes" is a true biologic phenomenon and highly prevalent in dialysis patients with established history and end-stage diabetic nephropathy and explore the role of protein-energy wasting to this end. Similarly, the J- or U-shaped associations between A1c or blood glucose concentrations and mortality are likely biologically plausible phenomena that should be taken into consideration in the management of diabetic dialysis patients to avoid hypoglycemia and its fatal consequences in diabetic dialysis patients.     

Glycemic Control and Extended Hemodialysis Survival in Patients with Diabetes Mellitus: Comparative Results of Traditional and Time-Dependent Cox Model Analyses

Background and objectives: The benefits and risks of aggressive glycemic control in diabetes mellitus complicated by end-stage kidney failure remain uncertain but have importance because of the large patient population with inferior overall prognosis. Recent large observational studies with differing methodologies reached somewhat contrasting conclusions regarding the association of hemoglobin A1c with survival in diabetic chronic hemodialysis patients.Design, setting, participants, & measurements: This study supplements the authors'' previous analysis (which found no correlation) by extending the follow-up period to 3 years and using time-dependent survival models with repeated measures. Among 24,875 nationally distributed study patients, 94.5% had type 2 diabetes, allowing additional analysis in the subset with type 1 diabetes. Data were collected at baseline and every quarter to a maximum of 3 years'' follow-up.Results: Adjusted standard and time-dependent Cox models indicated that only extremes of glycemia were associated with inferior survival. There was no effect modification by serum albumin levels, a marker of protein nutrition status, and no trend associated with random glucose measurements in a post hoc analysis. In type 1 diabetic patients, upper extreme hemoglobin A1c values indicated lower survival risk.Conclusions: Sustained extremes of glycemia were only variably and weakly associated with decreased survival in this population. In the absence of randomized, controlled trials, these results suggest that aggressive glycemic control cannot be routinely recommended for all diabetic hemodialysis patients on the basis of reducing mortality risk. Physicians are encouraged to individualize glycemic targets based on potential risks and benefits in diabetic ESRD patients.Suboptimal glycemic control is a major determinant of mortality worldwide (1). Specifically, elevated hemoglobin A1c (HgbA1c) is an independent risk factor for coronary heart disease in persons with diabetes (2,3). Recently, three large randomized trials have indicated that intensive glucose lowering in patients with type 2 diabetes mellitus (who comprise 95% of diabetic ESRD patients in the United States) did not reduce the risks of cardiovascular disease, the most common source of ESRD mortality (4–7). Although diabetic ESRD patients continue to comprise approximately half of all precedent patients in the United States and substantial portions elsewhere (8), very few diabetic chronic kidney disease (CKD) patients have been evaluated in trials for which the results provided evidence for the benefit of aggressive glucose control (9,10). Furthermore, the objectives of glycemic management in this population remain uncertain (11). Although the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines for diabetes and CKD support standard HgbA1c targets in patients with advanced kidney disease (12), the glycemic control targets were devised for patients without advanced CKD. Support for universal targets for glycemic control in those with renal insufficiency was lacking (because of insufficient evidence), even in recent guidelines, such as those developed by the American College of Physicians (13) and the Department of Veterans Affairs (14).We previously reported findings from a large national ESRD database that survival curves in diabetic patients grouped by HgbA1c levels did not differ statistically, and that there was no correlation between HgbA1c levels and 12-month mortality risk singly or when adjusted for case-mix and laboratory variables (15). However, those results were not independently confirmed by a similar-sized retrospective database analysis that indicated that higher HgbA1c was associated with increased death risk in diabetic ESRD patients (16). In addition to contrasting results, the two studies had significant methodological differences, with the latter study using a longer follow-up period, time-dependent survival models (i.e., with repeated measures), and adjustments for certain surrogates of malnutrition and inflammation.In light of these unresolved differences, this report attempts to build on our previous analysis by providing standardized time-independent (Cox) and time-dependent models. It extends patient follow-up to a maximum of 3 years and, for the first time, provides a separate analysis of the subgroup of patients with type 1 diabetes mellitus. Finally, it includes an analysis stratified by serum albumin levels, the most common marker of protein nutrition status.     

Association of Hemoglobin and Survival in Peritoneal Dialysis Patients

Summary

Background and objectives

Interventional trials and some observational studies show target hemoglobin >13 g/dl to be associated with higher mortality in erythropoiesis-stimulating agent–treated (ESA-treated) hemodialysis patients; data for peritoneal dialysis (PD) patients are limited.

Design, setting, participants, & measurements

We tested our hypothesis that higher and lower achieved hemoglobin levels are associated with increased mortality in 9269 ESA-treated PD patients from all DaVita dialysis clinics during the time period July 2001 through June 2006 followed through June 2007 using a time-dependent analysis.

Results

Lower hemoglobin was associated with significantly higher all-cause mortality in ESA-treated PD patients: with hemoglobin of 11.0 to <12.0 g/dl as reference, the time-dependent adjusted death hazard ratios for hemoglobin levels of 10.0 to <11.0, 9.0 to <10.0, and ≤9.0 g/dl were 1.12 (1.00 to 1.24), 1.30 (1.12 to 1.50), and 1.38 (1.14 to 1.67), respectively. The time-dependent adjusted hazard ratios for cardiovascular death with hemoglobin levels of 10.0 to <11.0, 9.0 to <10.0, and ≤9.0 g/dl were 1.11 (0.93 to 1.32), 1.37 (1.09 to 1.72), and 1.12 (0.79 to 1.57), respectively. The same trend for association of lower hemoglobin level with higher mortality was seen in African-American and non–African American men and women. In contrast, there was no association between higher achieved hemoglobin and all-cause or cardiovascular mortality in ESA-treated PD patients.

Conclusions

Lower, but not higher, achieved hemoglobin is associated with higher mortality in ESA-treated PD patients. Randomized controlled trials are needed to examine the target hemoglobin level with lowest mortality in PD patients.     

Use of Insulin to Improve Glycemic Control in Diabetes Mellitus

BACKGROUND: The restoration of normoglycemia ensures the control of diabetic symptoms and reduction in microangiopathic complications in type 1 and type 2 diabetes. However, there is no conclusive evidence that intensive glycemic control alone will prevent macrovascular disease, the commonest cause of morbidity and mortality in type 2 diabetes. As atherosclerosis is an inflammatory condition, it is relevant that the two common insulin resistant states of obesity and type 2 diabetes have significant inflammatory processes, which promote atherosclerosis. It is also relevant that glucose has been shown to have profound effects on the endothelial cell, the leukocyte and the platelet. These effects include the induction of acute oxidative and inflammatory stress and a prothrombotic and pro-apoptotic effect following glucose intake. In contrast insulin has been shown to exert several biological effects at physiologically relevant concentrations, in relation to the endothelial cell, the platelet and leucocyte function, which may be cardioprotective and potentially anti-atherosclerotic. CONCLUSION: These findings are of great interest as it is possible that the prevention of macrovascular complications in type 2 diabetes may require the use of those glucose lowering drugs which have additional anti-inflammatory effects in addition to the control of comorbid conditions (hypertension and dyslipidemia) associated with this disease. Results of future clinical trials are awaited to confirm the benefits of this approach in the primary and secondary prevention of macrovascular complications in type 2 diabetes.     

Linking Glycemic Control and Executive Function in Rural Older Adults with Diabetes Mellitus

OBJECTIVES: To examine the association between glycemic control and the executive functioning domain of cognition and to identify risk factors for inadequate glycemic control that may explain this relationship. DESIGN: Cross‐sectional study. SETTING: In‐person interviews conducted in participants' homes. PARTICIPANTS: Ninety‐five rural older African Americans, American Indians, and whites with diabetes mellitus (DM) from three counties in south‐central North Carolina. MEASUREMENTS: Participants underwent uniform evaluations. Glycemic control was measured using a validated method, and executive function was assessed using a previously established set of measures and scoring procedure. Information pertaining to medication for treatment of DM, knowledge of DM, and DM self‐care behaviors were obtained. RESULTS: In linear regression models adjusting for sex, age, education, ethnicity, duration of DM, and depressive symptoms, executive function was significantly associated with glycemic control. A 1‐point higher executive function score was associated with a 0.47 lower glycosylated hemoglobin value (P=.01). The association between glycemic control and executive function became nonsignificant (P=.08) when controlling for several glycemic control risk factors, including use of DM medication and DM knowledge. CONCLUSION: These results suggest that poor glycemic control is associated with impairments in performance on composite measures of executive function and that modifiable risk factors for glycemic control such as use of DM medication and DM knowledge may explain this relationship.     

Effect of Treatment with Direct Acting Antiviral on Glycemic Control in Patients with Diabetes Mellitus and Chronic Hepatitis C

Introduction and aim. The effect of the new direct acting antiviral drugs (DAAs) for chronic hepatitis C (HCV) on glycemic control is unknown.Materials and methods. We conducted a retrospective cohort study of patients who were treated for chronic HCV with direct-acting antiviral medications at a single academic institution between May 2013 and April 2016. Univariate analysis was performed comparing subjects pre- and post-treatment.Results. One hundred seventy-five consecutive adult patients were treated for chronic HCV and met enrollment criteria. The majority (80.8%) were genotype 1 and overall cohort sustained virologic response at week 12 (SVR12) was 97.8%. Thirty-one (18.5%) had diabetes mellitus (DM); twenty-six had pre- and post-treatment HbA1c values. Of these, 76.9% were male and 61.5% had cirrhosis. Ninety-six percent were prescribed sofosbuvir-based therapy and all but one (96.8%) achieved SVR12. Three patients were started on treatment despite meeting the definition for poorly controlled DM (HbA1c > 9 mg/dL). There was no significant difference when comparing pre-treatment (7.36 mg/dL, 95% CI 6.55-8.16) to post-treatment HbA1c (7.11 mg/dL, 95% CI 6.34-7.88, p = 0.268). Thirty-one percent of subjects required dose escalation or the initiation of insulin based therapy during treatment.Discussion. Although chronic HCV is associated with exacerbation of insulin resistance, our results showed HbA1c to be unaffected by eradication of chronic HCV with DAA in diabetic patients with and without cirrhosis. Paradoxically, almost 1/3 of patients required escalation of anti-diabetic therapy during treatment. Long-term studies are warranted to understand the relationship between HCV viral eradication and insulin metabolism.     

Helicobacter pylori Prevalence in Diabetes Mellitus Patients with Dyspeptic Symptoms and its Relationship to Glycemic Control and Late Complications

Background There are contradictory reports on Helicobacter pylori prevalence and its relationship to late complications of diabetes mellitus (DM). The aim of this study was to determine the prevalence of H. pylori infection in type 2 DM patients and to evaluate the relationship between H. pylori infection and the glycemic control, late complications. Material and Method A total of 141 type 2 DM patients and 142 nondiabetic subjects with upper gastrointestinal symptoms were enrolled in the study. All patients underwent upper gastrointestinal endoscopy with biopsy specimens obtained from gastric antrum and corpus. H. pylori status was evaluated in each patient by both the rapid urease test and histopathological examination. Plasma glucose, HbA1c, microalbuminuria in 24 h collected urine, electroneuromyography, and fundoscopic examinations were performed in all subjects. Results The prevalence of H. pylori infection was 61.7% and 58.5%, respectively, among type 2 diabetic patients and nondiabetic controls and was not statistically significant (P = 0.577). The duration of diabetes, fasting blood glucose and haemoglobin A1c levels, nephropathy and retinopathy prevalence did not differ significantly between the two groups (diabetics versus nondiabetics). There was no late complication in 60.3% of the type 2 diabetic patients as compared to at least one late complication in the remainders. A statistically significant correlation was found between H. pylori infection and the presence of neuropathy (P = 0.021). Conclusions The prevalence of H. pylori infection did not differ significantly between the diabetic patients and nondiabetic controls. Interestingly, diabetics with H. pylori infection had a higher incidence of neuropathy, although there was no association between the duration and regulation of diabetes, retinopathy, nephropathy and H. pylori status.     

Diabetes Mellitus, Glycemic Control, and Risk of Atrial Fibrillation

BACKGROUND  

Diabetes may be an independent risk factor for atrial fibrillation. However, results from prior studies are in conflict, and no study has examined diabetes duration or glycemic control.     

Association Between Cognitive Function and Social Support with Glycemic Control in Adults with Diabetes Mellitus

OBJECTIVES: To examine whether cognitive impairment in adults with diabetes mellitus is associated with worse glycemic control and to assess whether level of social support for diabetes mellitus care modifies this relationship.
DESIGN: Cross-sectional analysis.
SETTING: The 2003 Health and Retirement Study (HRS) Mail Survey on Diabetes and the 2004 wave of the HRS.
PARTICIPANTS: Adults aged 50 and older with diabetes mellitus in the United States (N=1,097, mean age 69.2).
MEASUREMENTS: Glycosylated hemoglobin (HbA1c) level; cognitive function, measured with the 35-point HRS cognitive scale (HRS-cog); sociodemographic variables; duration of diabetes mellitus; depressed mood; social support for diabetes mellitus care; self-reported knowledge of diabetes mellitus; treatments for diabetes mellitus; components of the Total Illness Burden Index related to diabetes mellitus; and functional limitations.
RESULTS: In an ordered logistic regression model for the three ordinal levels of HbA1c (<7.0, 7.0–7.9, ≥8.0 mg/dL), respondents with HRS-cog scores in the lowest quartile had significantly higher HbA1c levels than those in the highest cognitive quartile (adjusted odds ratio=1.80, 95% confidence interval=1.11–2.92). A high level of social support for diabetes mellitus care modified this association; for respondents in the lowest cognitive quartile, those with high levels of support had significantly lower odds of having higher HbA1c than those with low levels of support (1.11 vs 2.87, P =.02).
CONCLUSION: Although cognitive impairment was associated with worse glycemic control, higher levels of social support for diabetes mellitus care ameliorated this negative relationship. Identifying the level of social support available to cognitively impaired adults with diabetes mellitus may help to target interventions for better glycemic control.     

Significance of Glycemic Variability in Diabetes Mellitus

The goal of diabetes treatment is to maintain good glycemic control, prevent the development and progression of diabetic complications, and ensure the same quality of life and life expectancy as healthy people. Hemoglobin A1c (HbA1c) is used as an index of glycemic control, but strict glycemic control using HbA1c as an index may lead to severe hypoglycemia and cardiovascular death. Glycemic variability (GV), such as excessive hyperglycemia and hypoglycemia, is associated with diabetic vascular complications and has been recognized as an important index of glycemic control. Here, we reviewed the definition and evaluated the clinical usefulness of GV, and its relationship with diabetic complications and therapeutic strategies to reduce GV.     

Peritoneal Protein Clearance and not Peritoneal Membrane Transport Status Predicts Survival in a Contemporary Cohort of Peritoneal Dialysis Patients

Background and objectives: Fast peritoneal membrane transport status may be due to inflammation or increased peritoneal membrane surface area. We evaluated the ability of peritoneal protein clearance (Pcl) to distinguish fast peritoneal membrane transport status as a consequence of peritoneal membrane inflammation and assess its impact on patient survival.Design, setting, participants, & measurements: Patients who initiated peritoneal dialysis at our center since January 1998 and had a baseline peritoneal equilibration test, measurement of dialysis adequacy, and 24-h dialysate Pcl were included. Demography, comorbidities, and biochemical data were prospectively collected. Follow-up was until death or the end of the period studied. Multivariate regression analysis identified factors that were associated with Pcl. A Cox proportional hazards model was used to identify factors that were associated with survival.Results: A total of 192 patients (56% men, mean age 54.3 ± 15.3; 32% with diabetes) were included. On univariate analysis, Pcl was negatively correlated with serum albumin and positively correlated with age, dialysate/plasma creatinine ratio (D/Pcr), the presence of peripheral vascular disease, and urine volume. On multivariate analysis, serum albumin, D/Pcr, urine volume, and peripheral vascular disease remained significant. Predictors of mortality were age, comorbidity grade, and Pcl but not D/Pcr.Conclusions: In this cohort, peritoneal transport status no longer predicted survival, whereas Pcl remained a predictor. Increased large-pore protein loss may reflect the severity of underlying cardiovascular disease, portending a poor prognosis for these patients.Fast peritoneal membrane transport status (fPTS) is defined by the measurement of the diffusive peritoneal transport rate for small solutes such that the dialysate-to-plasma creatinine ratio (D/Pcr) is ≥0.81 at 4 h (1). It may be present at the initiation of peritoneal dialysis (PD) but may develop with time on treatment (2,3). Studies of continuous ambulatory PD (CAPD) patients have demonstrated baseline fPTS to be an independent predictor of mortality and technique failure (4). Explanations for this association include reduced peritoneal membrane ultrafiltration capacity owing to more rapid dissipation of the glucose osmotic gradient and resultant fluid reabsorption (5). This results in extracellular fluid volume expansion and hypertension (5). Because of an association between fPTS and hypoalbuminemia, it has been postulated that fPTS may be a manifestation of local or systemic inflammation while serving as a surrogate marker for the increased mortality seen with the malnutrition, inflammation, and atherosclerosis syndrome (6). Against this explanation is emerging evidence that fPTS does not seem to be associated with reduced survival and technique failure in contemporary cohorts (7–9).To resolve this problem, it has been postulated that fPTS may have two potential etiologies: Increased vascularity of the membrane associated with an increased anatomic membrane area or the result of inflammation and vascular injury. In both instances, fPTS will be due to increased blood flow and increased effective small-pore area in contact with dialysate (10). One way to distinguish these processes, according to the three-pore model of membrane function, is to dissociate the small solute transport rate, proportional to the small-pore area, from peritoneal protein clearance (Pcl), which, depending on the protein size, will be a function of both small pores and large pores (11). Protein leak across large pores, equivalent to large-pore flow, will be determined by their relative number, which will be increased during inflammation or by increased hydrostatic pressure across the capillary (12).Heaf et al. (13) showed that patients whose membranes have increased large-pore flow (JvL) using the personal dialysis capacity (PDC) test have inferior survival; however, the membrane area parameter (A0/δx), a measure essentially equivalent to solute transport, was not included in a multivariate survival model (13). In a subsequent study, Van Biesen et al. (14) found that large-poor flow was associated with survival only when corrected for A0/δx such that a higher JvL for a given membrane area decreased survival, yet interpretation of these results is also confounded by the potential for internal mathematical coupling between JvL and A0/δx when using the PDC test, because the former is derived from the product of the pressure gradient and the ultrafiltration coefficient, LpS, and this in turn is derived from A0/δx (12). Both of these studies found a high level of correlation between small solute transport rates (either 4-h D/Pcr or A0/δx) and JvL. This might represent true biologic coupling, yet the use of shared parameters in the PDC test makes this unclear (15).Here we determined the association between patient survival and both solute transport and Pcl, measured and calculated independently, in a prospective, single-center cohort that had previously reported worse outcomes in patients with fPTS (16). We explored the relationship among peritoneal protein leak, comorbidity, and BP.     

Differential Impact of Homelessness on Glycemic Control in Veterans with Type 2 Diabetes Mellitus

BACKGROUND

Veterans with evidence of homelessness have high rates of mental health and substance abuse disorders, but chronic medical conditions such as diabetes are also prevalent.

OBJECTIVE

We aimed to determine the impact of homelessness on glycemic control in patients with type 2 diabetes mellitus.

DESIGN

Longitudinal analysis of a retrospective cohort.

SUBJECTS

A national cohort of 1,263,906 Veterans with type 2 diabetes. Subjects with evidence of homelessness were identified using a combination of diagnostic and administrative codes.

MAIN MEASURES

Odds for poor glycemic control using hemoglobin A1C (HbA1C) cutoff values of 8 % and 9 %. Homeless defined as a score based on the number of indicator variables for homelessness within a veterans chart.

KEY RESULTS

Veterans with evidence of homelessness had a significantly greater annual mean HbA1C?≥ 8 (32.6 % vs. 20.43 %) and HbA1C?≥ 9 (21.4 % vs. 9.9 %), tended to be younger (58 vs. 67 years), were more likely to be non-Hispanic black (39.1 %), divorced (43 %) or never married (34 %), to be urban dwelling (88.8 %), and to have comorbid substance abuse (46.7 %), depression (42.3 %), psychoses (39.7 %), liver disease (18.8 %), and fluid/electrolyte disorders (20.4 %), relative to non-homeless veterans (all p?<?0.0001). Homelessness was modeled as an ordinal variable that scored the number of times a homelessness indicator was found in the Veterans medical record. We observed a significant interaction between homelessness and race/ethnicity on the odds of poor glycemic control. Homelessness, across all racial-ethnic groups, was associated with increased odds of uncontrolled diabetes at a cut-point of 8 % and 9 % for hemoglobin A1C ; however, the magnitude of the association was greater in non-Hispanic whites [8 %, OR 1.55 (1.47;1.63)] and Hispanics [8 %, OR 2.11 (1.78;2.51)] than in non-Hispanic blacks [8 %, OR 1.22 (1.15;1.28)].

CONCLUSIONS

Homelessness is a significant risk factor for uncontrolled diabetes in Veterans, especially among non-Hispanic white and Hispanic patients. While efforts to engage homeless patients in primary care services have had some success in recent years, these data suggest that broader efforts targeting management of diabetes and other chronic medical conditions remain warranted.

     

Improved Glycemic Control and Lipid Profile in a Randomized Study of Pioglitazone Compared with Acarbose in Patients with Type 2 Diabetes Mellitus

Objective: To assess the efficacy of pioglitazone treatment in comparison with that of acarbose treatment in patients with type 2 diabetes mellitus. Participants and methods: In this randomized, parallel-group, open-label study patients were assigned to treatment with either pioglitazone (n = 129) or acarbose (n = 136). During a 1-week run-in patients commenced an individualized dietary regimen which was maintained throughout the study. Patients received the assigned study medication for 26 weeks. Serum glycosylated hemoglobin (HbA_1c) levels, insulin resistance and lipid profiles were determined at baseline and at endpoint. Results: Mean HbA_1c was reduced from 8.98 ± 1.20% to 7.82 ± 1.95% with pioglitazone treatment and from 9.03 ± 1.32% to 8.55 ± 1.96% with acarbose treatment during the 26-week study. The change from baseline to endpoint was significantly greater for pioglitazone compared with acarbose when analyzed for all patients (p < 0.001) and for those who had (p = 0.009) or had not (p < 0.001) received previous medication for diabetes mellitus. Compared with acarbose, pioglitazone produced a significantly greater decrease in fasting glucose, insulin and insulin resistance (p < 0.001 for each). Triglycerides were decreased by 71.1 ± 184.1 mg/dl with pioglitazone compared with 38.1 ± 171.3 mg/dl with acarbose (p = 0.001 for difference between groups). High density lipoprotein (HDL)-cholesterol level was increased by 7.8 ± 10.2 mg/dl with pioglitazone compared with a decrease of 0.8 ± 24.1 mg/dl with acarbose (p < 0.001). While serum low density lipoprotein (LDL)-cholesterol levels remained unchanged with both treatment regimens, the decrease from baseline in very low density lipoprotein (VLDL)-cholesterol was significantly greater with pioglitazone than with acarbose (p < 0.04). Pioglitazone decreased systolic blood pressure by 5.6 ± 17.7mm Hg compared with a 0.4 ± 18.4mm Hg increase during acarbose treatment (p < 0.001). Pioglitazone caused a significantly greater decrease compared with acarbose in serum levels of γ-glutamyl aminotransferase (p < 0.001) and alanine aminotransferase (p = 0.004). Conclusions: Six months of pioglitazone treatment decreased insulin resistance and improved glycemic control to a significantly greater extent than acarbose treatment. Pioglitazone was also associated with a significantly improved lipid profile, suggesting a reduction in risk of coronary heart disease.     

Similar Survival on Automated Peritoneal Dialysis and Continuous Ambulatory Peritoneal Dialysis in a Large Prospective Cohort

Background and objectives: Automated peritoneal dialysis (APD) is increasingly used in comparison with continuous ambulatory peritoneal dialysis (CAPD). Although APD is expected to improve survival, convincing evidence of major advantages is lacking. The objective was to investigate whether overall mortality and technique failure of incident dialysis patients treated with APD are different from those treated with CAPD.Design, setting, participants, & measurements: Patients on APD or CAPD at 3 mo after start of dialysis were selected from a prospective multicenter cohort study in incident dialysis patients (NECOSAD). Overall mortality was studied with an intention-to-treat design; the event was death. Technique failure was studied with an as-treated design; the event was a switch of dialysis modality. Hazard ratios (HRs) were calculated with a follow-up of 5 yr. The HRs were adjusted for gender, age, primary kidney disease, comorbidity, residual GFR, urine production and plasma albumin at 3 mo after inclusion.Results: Eighty-seven APD and 562 CAPD patients were included. In the intention-to-treat analysis 154 CAPD and 21 APD patients died. The crude HR for overall mortality was 0.98 (95% CI: 0.62–1.54), the adjusted HR was 1.09. In the as-treated analysis 238 CAPD and 34 APD patients switched therapy, whereas 91 CAPD and 7 APD patients died. The crude HR for technique failure was 0.92 (95% CI: 0.64–1.31) and did not change after adjustment.Conclusions: No difference was found in overall mortality and technique failure for APD compared with CAPD in incident dialysis patients.Automated peritoneal dialysis (APD) is increasingly used in comparison with continuous ambulatory peritoneal dialysis (CAPD). Although APD has been expected to improve survival, convincing evidence of major advantages is lacking. In addition APD has potential disadvantages compared with CAPD like a possible faster decline in residual renal function (1–3), less sodium removal (3–6) and more peritoneal protein loss (6). Furthermore, APD is more expensive than CAPD. Two observational studies reported better overall and technique survival on APD (7,8). However, other studies could not demonstrate a benefit for APD in terms of survival (5,9).Three randomized controlled trials comparing APD to CAPD have been published (10–12). The number of patients was relatively small: the largest study comprised 50 patients in the largest group (11). These were reviewed in 2006 (13,14), and no significant differences in survival were found.Comparison of the published studies about this subject is complicated because the indications for APD differ between countries and nephrologists. At the same time, the uncertainty in the literature about the expected benefit of APD probably contributes to these differences in indications. The comparison is also complicated by the different patient selections in the studies; some included prevalent and incident APD patients (9), others included incident patients for PD (7,8) or incident dialysis patients (5,9). The definition of APD differs between the studies as well. Large prospective observational cohorts in incident dialysis patients are required to gain more insight into survival on APD compared with CAPD.The Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) is a large prospective, multicenter cohort study of end-stage renal disease (ESRD) patients starting on dialysis treatment. We used the NECOSAD database to investigate whether overall mortality and technique failure of incident dialysis patients treated with APD are different from those of patients treated with CAPD.     

Alcohol Ingestion and Glycaemic Control in Patients with Insulin-dependent Diabetes Mellitus

It is widely accepted that alcohol consumption by patients with insulin-dependent (Type 1) diabetes mellitus is associated with an increased risk of hypoglycaemia. This association has been the subject of few studies, however, and there is not much evidence to support advice currently given to patients. Available information suggests that moderate alcohol consumption by healthy, fed subjects does not cause acute hyper- or hypoglycaemia although there may be a delayed risk of hypoglycaemia the morning after evening alcohol intake. Alcohol can lead to potentially hazardous hypoglycaemia in fasted individuals or in those dependent upon alcohol and has been associated with hypoglycaemic unawareness. © 1997 by John Wiley & Sons, Ltd.