People with diabetes and hypovitaminosis C fail to conserve urinary vitamin C.

Background: Hypovitaminosis C has negative health consequences. People with diabetes and hypovitaminosis C may fail to conserve vitamin C in the urine, thereby displaying evidence of inappropriate renal leak of vitamin C. This study describes the relationship between plasma and urinary vitamin C in diabetes, with a focus on the clinical characteristics of participants with renal leak. Methods: Retrospective analysis of paired, non-fasting plasma and urine vitamin C, and also clinical characteristics, from participants with either type 1 or type 2 diabetes, recruited from a secondary care diabetes clinic. Plasma vitamin C thresholds for renal leak have been defined previously as 38.1 µmol/L for men and 43.2 µmol/L for women. Results: Statistically significant differences in clinical characteristics were seen between those with; i) renal leak (N = 77) and; ii) hypovitaminosis C but no renal leak (N = 13) and; iii) normal plasma vitamin C levels (n = 34). Compared to participants with adequate plasma vitamin C levels, participants with renal leak tended to have type 2 (rather than type 1) diabetes, a lower eGFR and a higher HbA1c. Conclusion: In the diabetes population studied, renal leak of vitamin C was common. In some participants, it may have contributed to hypovitaminosis C.

Detecting dysglycaemia in compensated liver cirrhosis: Comparison of oral glucose tolerance test and glycated haemoglobin, with continuous glucose monitoring.

AIMS: Liver cirrhosis increases the risk of developing dysglycaemia (pre-diabetes and diabetes), thus people with cirrhosis should undergo regular screening for dysglycaemia. The utility of screening using the laboratory glycated haemoglobin (HbA1c ) test has been questioned in this setting. This study examines the relationship between different potential screening modalities: 75 g oral glucose tolerance test (OGTT) and HbA1c , using continuous glucose monitoring (CGM) as a comparator. METHODS: Participants ≥18 years with no known diabetes, were recruited from a gastroenterology cirrhosis surveillance register. Study measurements included a 75 g OGTT, laboratory HbA1c and two weeks of 'blinded' CGM (Freestyle Libre Pro). The possibility of intravascular haemolysis affecting HbA1c interpretation was also assessed. RESULTS: All 20 participants had compensated cirrhosis. OGTT tended to diagnose more dysglycaemia (N = 7) than did HbA1c (N = 4). Bland-Altman analysis showed laboratory and CGM-estimated HbA1c were broadly comparable, with a difference of 4mmol/mol (95% CI -3 to 12), or 0.4% (95% CI -0.3 to 1.1). Laboratory HbA1c tended to be higher than the CGM-estimated HbA1c , perhaps reflecting positive lifestyle changes in participants during their two weeks of wearing 'blinded' CGM (Hawthorne effect). In the population studied, there was no evidence that haemolysis affected interpretation of HbA1c results. CONCLUSIONS: In the setting of compensated cirrhosis, the OGTT and HbA1c remain standard screening test for diabetes, but multiple studies show the OGTT diagnoses more people with dysglycaemia than does the HbA1c . Blinded CGM in an ambulatory, real world setting provides additional insights into glycaemic excursions but cannot be used to diagnose dysglycaemia.

Urinary Amino-Terminal Pro-C-Type Natriuretic Peptide: A Novel Marker of Chronic Kidney Disease in Diabetes.

BACKGROUND: Chronic renal inflammation and fibrosis are common sequelae in diabetes mellitus (DM) and are major causes of premature mortality. Although upregulation of NPPC expression occurs in response to renal inflammation in experimental animals, nothing is known of the molecular forms of C-type natriuretic peptide (CNP) products in urine of people with DM or links with renal function. METHODS: ProCNP products in urine were characterized with HPLC and a range of antisera directed to specific epitopes of amino-terminal proCNP (NTproCNP). The 5-kDa intact peptide was quantified in spot urine samples from healthy adults and 202 participants with DM selected to provide a broad range of renal function. RESULTS: The predominant products of proCNP in urine were consistent with the 2-kDa fragment (proCNP 3-20) and a smaller peak of intact (5-kDa) fragment (proCNP 1-50, NTproCNP). No peaks consistent with bioactive forms (proCNP 82-103, 50-103) were identified. The urine NTproCNP to creatinine ratio (NCR) was more reproducible than the albumin to creatinine ratio (ACR) and strongly associated with the presence of chronic kidney disease. In models predicting independence, among 10 variables associated with renal function in DM, including plasma NTproCNP, only 3 (sex, ACR, and plasma creatinine) contributed to NCR. CONCLUSIONS: Characterization of the products of proCNP in urine confirmed the presence of NTproCNP. In spot random urine from study participants with DM, NCR is inversely associated with estimated glomerular filtration rate. In contrast to ACR, NCR reflects nonvascular factors that likely include renal inflammation and fibrosis.

Collection tubes containing citrate stabiliser over-estimate plasma glucose, when compared to other samples undergoing immediate plasma separation.

OBJECTIVES: Blood collection tubes containing citrate lower pH, thereby inhibiting glycolysis. When compared to other additives, they introduce an over-estimation in measured glucose. This study explored this over-estimation across a range of glucose values. Blood samples collected into lithium-heparin tubes then cooled prior to immediate refrigerated plasma separation, were used as the primary comparator. DESIGN AND METHODS: Venous blood from individuals with and without diabetes was collected into tubes containing lithium-heparin, or fluoride, or fluoride-citrate (Terumo™ Venosafe). Plasma was separated at time intervals of zero, 2 and 24h. Preparation of the 'time zero' lithium-heparin and fluoride samples was optimised by processing these samples under cooled conditions. The remaining samples were prepared at room temperature. Plasma was analysed in the routine clinical laboratory using the hexokinase method. RESULTS: Median plasma glucose for the 50 participants was 7.1mmol/L (range 3.1-21.5). At 'time zero', fluoride-citrate glucose was 0.37mmol/L (95% CI 0.26-0.48) higher than lithium-heparin glucose and 0.29mmol/L (95% CI 0.21-0.36) higher than glucose from fluoride tubes. Following delayed plasma separation at 24h, glucose loss from the lithium heparin tubes averaged 0.2mmol·L-1·hr-1. In contrast, the fluoride-citrate tubes showed minimal glucose loss over 24h. CONCLUSIONS: Acid stabilises glycolysis but causes an over-estimation in glucose, across a range of plasma glucose values, when compared to blood collected into conventional tubes under cooled conditions. The magnitude of the over-estimation seen with the fluoride-citrate tubes is unlikely to be due solely to the differential glucose stabilisation rates of acid, compared to cooling.

Plasma glucose measurement in diabetes: impact and implications of variations in sample collection procedures with a focus on the first hour after sample collection.

BACKGROUND: Previous studies of participants with plasma glucose concentrations at or near the glucose reference range demonstrate glucose loss following delayed separation and extraction of plasma from the cellular components of blood, of ≤7% per hour. We aimed to assess pre-analytical glucose loss in diabetic subjects, focusing on the first hour after sample collection. METHODS: Venous blood was collected from diabetes clinic attendees, into a series of lithium heparin PST™ (plasma separator tube) and fluoride oxalate Vacutainers™. Baseline (reference) plasma glucose measurements were undertaken on samples prepared under refrigerated conditions. The remaining samples underwent a series of controlled pre-analytical delays in sample preparation, at room temperature. Plasma glucose was measured using the hexokinase method. RESULTS: Median baseline glucose (mmol/L) for the 62 participants was 10.6 (range 3.4-31.1). Using lithium heparin PST™ tubes, mean glucose loss (95% CI) was 0.16 (0.09-0.23) after 30 min delay in plasma preparation and 0.28 (0.21-0.34) after 60 min delay. Glucose loss was independent of both baseline glucose and also individual cellular count. Fluoride failed to inhibit glucose loss within the first hour after sample collection. Immediate plasma centrifugation of PST™ tubes, followed by delayed plasma extraction (median delay 92 min), produced a mean glucose loss of 0.02 mmol/L (-0.05-0.09). CONCLUSIONS: Samples collected into lithium heparin PST™ tubes show pre-analytical glucose loss at 1 h that is independent of baseline glucose and cellular count. Furthermore, immediate plasma separation using these tubes attenuates glucose loss across a wide range of glucose concentrations.

A glucose meter evaluation co-designed with both health professional and consumer input.

Health consumer's input into assessment of medical device safety is traditionally given either as part of study outcome (trial participants) or during post marketing surveillance. Direct consumer input into the methodological design of device assessment is less common. We discuss the difference in requirements for assessment of a measuring device from the consumer and clinician perspectives, using the example of hand held glucose meters. Around 80,000 New Zealanders with diabetes recently changed their glucose meter system, to enable ongoing access to PHARMAC subsidised meters and strips. Consumers were most interested in a direct comparison of their 'old' meter system (Accu-Chek Performa) with their 'new' meter system (CareSens brand, including the CareSens N POP), rather than comparisons against a laboratory standard. This direct comparison of meter/strip systems showed that the CareSens N POP meter read around 0.6 mmol/L higher than the Performa system. Whilst this difference is unlikely to result in major errors in clinical decision making such as major insulin dosing errors, this information is nevertheless of interest to consumers who switched meters so that they could maintain access to PHARMAC subsidised meters and strips. We recommend that when practical, the consumer perspective be incorporated into study design related to medical device assessment.