Chronic kidney disease is a common complication and concomitant condition of diabetes mellitus. The treatment of patients with diabetes and chronic kidney disease, including intensive control of ...blood sugar and blood pressure, has been very similar for type 1 and type 2 diabetes patients. New therapeutic targets have shown promising results and may lead to more specific treatment options for patients with type 1 and type 2 diabetes.
Solid organ transplantation (SOT) is a life-saving procedure and an established treatment for patients with end-stage organ failure. However, transplantation is also accompanied by associated ...cardiovascular risk factors, of which post-transplant diabetes mellitus (PTDM) is one of the most important. PTDM develops in 10-20% of patients with kidney transplants and in 20-40% of patients who have undergone other SOT. PTDM increases mortality, which is best documented in patients who have received kidney and heart transplants. PTDM results from predisposing factors (similar to type 2 diabetes mellitus) but also as a result of specific post-transplant risk factors. Although PTDM has many characteristics in common with type 2 diabetes mellitus, the prevention and treatment of the two disorders are often different. Over the past 20 years, the lifespan of patients who have undergone SOT has increased, and PTDM becomes more common over the lifespan of these patients. Accordingly, PTDM becomes an important condition not only to be aware of but also to treat. This Review presents the current knowledge on PTDM in patients receiving kidney, heart, liver and lung transplants. This information is not only for transplant health providers but also for endocrinologists and others who will meet these patients in their clinics.
Background The role of prediabetes as a risk factor for hyperfiltration and albuminuria in persons who do not develop diabetes is unclear. The lack of evidence is mainly due to the difficulty of ...accurately assessing the glomerular filtration rate (GFR) in the near-normal range of GFR. We investigated whether prediabetes is an independent risk factor for glomerular hyperfiltration and high-normal urinary albumin-creatinine ratio (ACR) using measured GFR (mGFR) rather than estimated GFR. Study Design Prospective cohort study based on the Renal Iohexol Clearance Survey in Tromsø 6 (RENIS-T6) and the RENIS Follow-Up Study. Median observation time was 5.6 years. Setting & Participants A representative sample of 1,261 persons without diabetes mellitus (DM) from the general population aged 50 to 62 years. Predictor Prediabetes defined by fasting glucose and hemoglobin A1c according to levels suggested by the American Diabetes Association (preDMADA ) and the International Expert Committee of 2009 (preDMIEC ). Outcomes Change in mGFR; hyperfiltration defined as mGFR > 90th percentile adjusted for age, sex, weight, and height; and high-normal ACR (>10 mg/g) at follow-up. Measurements GFR was measured with iohexol clearance. Results Baseline fasting glucose, hemoglobin A1c , and both definitions of prediabetes were predictors of higher mGFR at follow-up and lower annual mGFR decline in multivariable-adjusted regression analyses. Participants with preDMIEC had an OR for hyperfiltration of 1.95 (95% CI, 1.20-3.17) and for high-normal ACR of 1.83 (95% CI, 1.04-3.22) at follow-up. We adjusted for cardiovascular risk factors including ambulatory blood pressure at baseline and change in use of antihypertensive medication between baseline and follow-up. Limitations Only middle-aged white patients participated. There is no consensus on how to define glomerular hyperfiltration. Conclusions Our findings imply an independent role of prediabetes in the development of glomerular hyperfiltration and albuminuria. Prediabetes might be a target for early treatment to prevent chronic kidney disease in chronic hyperglycemia.
Abstract
Both diabetes mellitus (DM) and the metabolic syndrome (MetS) are associated with autonomic neuropathy, which predisposes to cardiac events and death. Measures of heart rate variability ...(HRV) can be used to monitor the activity of the autonomic nervous system (ANS), and there are strong indications that HRV can be used to study the progression of ANS-related diabetes complications. This study aims to investigate differences in HRV in healthy, MetS and diabetic populations. Based on 7880 participants from the sixth health survey in Tromsø (Tromsø 6, 2007–2008), we found a significant negative association between the number of MetS components and HRV as estimated from short-term pulse wave signals (PRV). This decrease in PRV did not appear to be linear, instead it leveled off after the third component, with no significant difference in PRV between the MetS and DM populations. There was a significant negative association between HbA1c and PRV, showing a decrease in PRV occurring already within the normal HbA1c range. The MetS and DM populations are different from healthy controls with respect to PRV, indicating impaired ANS in both conditions. In the future, a study with assessment of PRV measurements in relation to prospective cardiovascular events seems justified.
Pancreas transplant alone (PTA) recipients are more affected by pancreas graft thrombosis, and graft loss compared to simultaneous pancreas-kidney (SPK) recipients. The pathophysiology is unknown, ...but an increased immune response has been suggested in the PTA recipients. In this observational study, we compared perioperative thromboinflammation between PTA (n=32) and SPK (n=35) recipients, and between PTA recipients with (n=14) versus without (n=18) early graft thrombosis.
We measured C-reactive protein (CRP), plasma markers of activated coagulation and complement, and cytokines preoperatively and daily during the first postoperative week.
Preoperatively, coagulation and complement activation markers were comparable between PTA and SPK recipients, while cytokine concentrations were higher in SPK recipients (TNF, IL-8, IP-10, MCP-1, MIP-1α; all
<0.05). On the first postoperative day, PTA recipients had higher coagulation activation, measured as thrombin-antithrombin complex (TAT), than SPK recipients (
=0.008). In the first postoperative week, PTA recipients showed higher relative cytokine release (IL-6, IL-8, G-CSF, IP-10, MCP-1, and MIP-1α; all
<0.05) while SPK recipients showed higher absolute cytokine concentrations (TNF, IL-1ra, IL-8, MIP-1α, and IL-4; all
<0.05). PTA and SPK recipients showed similar terminal complement complex (TCC, sC5b-9) activation. On the first postoperative day, TCC (OR 1.2 95% CI 1.0-1.5 for 0.1 CAU/ml increase,
=0.02) and CRP (OR 1.2 95% CI 1.0-1.3 for 10 mg/L increase,
=0.04) were associated with an increased risk of early graft thrombosis. TCC was specific for graft thrombosis, while CRP increased with several complications. PTA recipients with compared to those without graft thrombosis had higher TCC pre- (
=0.04) and postoperatively (
=0.03).
The relative increase in postoperative thromboinflammatory response was more pronounced in PTA recipients. Complement activation was associated with an increased risk of graft thrombosis. This study indicates that innate immune activation rather than elevated levels may affect early postoperative pancreas graft thrombosis.
https://clinicaltrials.gov/ct2/show/NCT01957696, identifier NCT01957696.
Despite advances in immunosuppression and surgical technique, pancreas transplantation is encumbered with a high rate of complication and graft losses. Particularly, venous graft thrombi occur ...relatively frequently and are rarely detected before the transplant is irreversibly damaged.
To detect complications early, when the grafts are potentially salvageable, we placed microdialysis catheters anteriorly and posteriorly to the graft in a cohort of 34 consecutive patients. Glucose, lactate, pyruvate, and glycerol were measured at the bedside every 1-2 hours.
Nine patients with graft venous thrombosis had significant lactate and lactate-to-pyruvate-ratio increases without concomitant rise in blood glucose or clinical symptoms. The median lactate in these patients was significantly higher in both catheters compared to non-events (n = 15). Out of the nine thrombi, four grafts underwent successful angiographic extraction, one did not require intervention and four grafts were irreversibly damaged and explanted. Four patients with enteric anastomosis leakages had significantly higher glycerol measurements compared to non-events. As with the venous thrombi, lactate and lactate-to-pyruvate ratio were also increased in six patients with graft surrounding hematomas.
Bedside monitoring with microdialysis catheters is a promising surveillance modality of pancreatic grafts, but differentiating between the various pathologies proves challenging.
Abstract
Background
A scoping review from 2021 identified a lack of studies on the incidence, prevention and management of hypoglycaemia in home-dwelling older people with diabetes. The aim of this ...study was to investigate the frequency and duration of hypoglycaemic episodes measured by continuous glucose monitoring (CGM) in older people with diabetes who received home care and who were treated with glucose-lowering medications, and to compare the frequency and duration of hypoglycaemic episodes between subgroups of the study population according to demographic and clinical variables.
Methods
This was an observational study investigating the occurrence of hypoglycaemia in people with diabetes aged ≥ 65 years. Data were collected using blinded continuous glucose monitoring (CGM, iPro2) for 5 consecutive days. Frequency and duration of hypoglycaemic episodes were assessed using a sensor glucose cut-off value of 3.9 mmol/L. A blood sample for measurement of HbA1c and creatinine-based eGFR (CKD-EPI) was obtained during the monitoring period. Demographic and clinical data were collected from electronic patient records.
Results
Fifty-six individuals were enrolled (median age 82 years and 52% were men). Of the 36 participants who were treated with insulin, 33% had at least one hypoglycaemic episode during the five-day period. Among 18 participants who neither used insulin nor sulfonylurea, but other glucose-lowering medications, 44% had at least one hypoglycaemicepisode. Of those with hypoglycaemic episodes, 86% lived alone. The median duration of the hypoglycaemia was 1 h and 25 min, ranging from 15 min to 8 h and 50 min.
Conclusion
This study identified an unacceptably high number of unknown hypoglycaemic episodes among older home-dwelling people with diabetes receiving home care, even among those not using insulin or sulfonylurea. The study provides essential knowledge that can serve as a foundation to improve the treatment and care for this vulnerable patient group. The routines for glucose monitoring and other prevention tasks need to be considered more comprehensively, also, among those treated with glucose-lowering medications other than insulin.
Graft thrombosis is the main cause of early graft loss following pancreas transplantation, and is more frequent in pancreas transplant alone (PTA) compared with simultaneous pancreas-kidney (SPK) ...recipients. Ischemia-reperfusion injury during transplantation triggers a local thromboinflammatory response. We aimed to evaluate local graft inflammation and its potential association with early graft thrombosis.
In this observational study, we monitored 67 pancreas-transplanted patients using microdialysis catheters placed on the pancreatic surface during the first postoperative week. We analyzed 6 cytokines, interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-8, interferon gamma-induced protein 10 (IP-10), macrophage inflammatory protein 1β (MIP-1β), IL-10, and the complement activation product complement activation product 5a (C5a) in microdialysis fluid. We compared the dynamic courses between patients with pancreas graft thrombosis and patients without early complications (event-free) and between PTA and SPK recipients. Levels of the local inflammatory markers, and plasma markers C-reactive protein, pancreas amylase, and lipase were evaluated on the day of thrombosis diagnosis compared with the first week in event-free patients.
IL-10 and C5a were not detectable. Patients with no early complications (n = 34) demonstrated high IL-1ra, IL-6, IL-8, IP-10, and MIP-1β concentrations immediately after surgery, which decreased to steady low levels during the first 2 postoperative days (PODs). Patients with early graft thrombosis (n = 17) demonstrated elevated IL-6 (
= 0.003) concentrations from POD 1 and elevated IL-8 (
= 0.027) concentrations from POD 2 and throughout the first postoperative week compared with patients without complications. IL-6 (
< 0.001) and IL-8 (
= 0.003) were higher on the day of thrombosis diagnosis compared with patients without early complications. No differences between PTA (n = 35) and SPK (n = 32) recipients were detected.
Local pancreas graft inflammation was increased in patients experiencing graft thrombosis, with elevated postoperative IL-6 and IL-8 concentrations, but did not differ between PTA and SPK recipients. Investigating the relationship between the local cytokine response and the formation of graft thrombosis warrants further research.
Health‐related quality of life (HRQOL) is reduced in Fabry disease (FD) and associated with clinical disease manifestations, but few have used Fabry‐specific severity scores to study how disease ...burden interferes with quality of life. We investigated how the Fabry DS3, consisting of four somatic domains and one patient‐reported item, associates with HRQOL, while also evaluating fatigue, pain and psychological distress as possible predictors. Thirty‐six adults with FD completed the Short‐form Health Survey (SF‐36), the hospital anxiety and depression scale (HADS), the brief pain inventory (BPI) and reported fatigue on a visual analog scale. Clinical data were collected from the last multidisciplinary hospital visit. Using correlation and hierarchical linear regression analyses, we examined associations between demographic, clinical and self‐reported predictors and the SF‐36 physical (PCS) and mental (MCS) component summary scores. Males scored lower than the general population in all SF‐36 domains (P < .05). General health and social functioning were reduced in females. Before including self‐reported symptom scores, DS3 showed associations with PCS (P = .009). Our fully adjusted model explained 66% of the variation in PCS, where education (P = .040) and fatigue (P = .002) retained significance. With HADS depression score (P = .001) as the sole significant factor, our regression model explained 56% of the variation in MCS. The DS3 score has implications for HRQOL in FD. Low education and fatigue represent major barriers to physical well‐being, while depression strongly influences mental quality of life. Fatigue should be recognized as an important endpoint in future FD trials. Increased efforts to diagnose and treat affective disorders are warranted.
As many as 10% to 20% of patients undergoing kidney transplantation develop post-transplant diabetes mellitus, which is associated with increased mortality. Even borderline changes in glucose ...metabolism, so-called prediabetes, may involve a similar risk. A recent study by Porrini et al. showed for the first time that such changes in glucose metabolism are in fact associated with future cardiovascular disease and death in kidney-transplanted patients. This commentary discusses the relevance and clinical implications of these new findings.
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