Investigating the efficacy of baricitinib in new onset type 1 diabetes mellitus (BANDIT)-study protocol for a phase 2, randomized, placebo controlled trial.

BACKGROUND: Type 1 diabetes (T1D) places an extraordinary burden on individuals and their families, as well as on the healthcare system. Despite recent advances in glucose sensors and insulin pump technology, only a minority of patients meet their glucose targets and face the risk of both acute and long-term complications, some of which are life-threatening. The JAK-STAT pathway is critical for the immune-mediated pancreatic beta cell destruction in T1D. Our pre-clinical data show that inhibitors of JAK1/JAK2 prevent diabetes and reverse newly diagnosed diabetes in the T1D non-obese diabetic mouse model. The goal of this study is to determine if the JAK1/JAK2 inhibitor baricitinib impairs type 1 diabetes autoimmunity and preserves beta cell function. METHODS: This will be as a multicentre, two-arm, double-blind, placebo-controlled randomized trial in individuals aged 10-30 years with recent-onset T1D. Eighty-three participants will be randomized in a 2:1 ratio within 100 days of diagnosis to receive either baricitinib 4mg/day or placebo for 48 weeks and then monitored for a further 48 weeks after stopping study drug. The primary outcome is the plasma C-peptide 2h area under the curve following ingestion of a mixed meal. Secondary outcomes include HbA1c, insulin dose, continuous glucose profile and adverse events. Mechanistic assessments will characterize general and diabetes-specific immune responses. DISCUSSION: This study will determine if baricitinib slows the progressive, immune-mediated loss of beta cell function that occurs after clinical presentation of T1D. Preservation of beta cell function would be expected to improve glucose control and prevent diabetes complications, and justify additional trials of baricitinib combined with other therapies and of its use in at-risk populations to prevent T1D. TRIAL REGISTRATION: ANZCTR ACTRN12620000239965 . Registered on 26 February 2020. CLINICALTRIALS: gov NCT04774224. Registered on 01 March 2021.

Evaluation of the diagnostic performance of the creatinine-based Chronic Kidney Disease Epidemiology Collaboration equation in people with diabetes: A systematic review.

AIMS: GFR estimated with the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICr ) equation is used to screen for diabetic kidney disease and assess its severity. We systematically reviewed the process and outcome of evaluating CKD-EPICr in estimating point GFR or GFR decline over time in adults with type 1 or type 2 diabetes. METHODS: In this systematic review, MEDLINE, Embase and Cochrane Central Register of Controlled Trials were searched up to August 2019. Observational studies comparing CKD-EPICr with measured GFR (mGFR) in adults with diabetes were included. Studies on people with kidney transplant, non-diabetes related kidney disease, pregnancy, potential kidney donors, and those with critical or other systematic illnesses were excluded. Two independent reviewers extracted data from published papers and disagreements were resolved by consensus. Risk-of-bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. (PROSPERO registration number: CRD42018108776). RESULTS: From the 2820 records identified, 29 studies (14 704 participants) were included. All studies were at risk of bias. Bias (eight different forms) ranged from -26 to 35 ml min-1  1.73 m-2 ; precision (five different forms) ranged between 9 and 63 ml min-1  1.73 m-2 ; accuracy (five different forms) ranged between 16% and 96%; the correlation coefficient between CKD-EPICr and mGFR (four different forms) ranged between 0.38 and 0.86; and the reduced major axis regression slope ranged between 0.8 and 1.8. CONCLUSIONS: Qualitative synthesis of data suggested CKD-EPICr was inaccurate in estimating point GFR or GFR decline over time. Furthermore, a lack of consistency in the methods and processes of evaluating the diagnostic performance of CKD-EPICr limits reliable quantitative assessment. The equation needs to be improved in adults with diabetes.

Impact of type 2 diabetes on hospitalization and mortality in people with malignancy.

AIM: To compare the characteristics of and outcomes for people with malignancies with and without a co-diagnosis of diabetes. METHODS: Emergency department and hospital discharge data from a single centre for the period between 1 January 2015 and 31 December 2017 were used to identify people with a diagnosis of a malignancy and diabetes. Multivariate Cox regression models were used to estimate the effect of diabetes on all-cause mortality. A truncated negative binomial regression model was used to assess the impact of diabetes on length of hospital inpatient stay. Prentice-Williams-Peterson total time models were used to assess the effect of diabetes on number of emergency department re-presentations and inpatient re-admissions. RESULTS: Of 7004 people identified with malignancies, 1195 (17.1%) were also diagnosed with diabetes. A diagnosis of diabetes was associated with a greater number of inpatient re-admissions [adjusted hazard ratio 1.13 (95% CI 1.03, 1.24)], a greater number of emergency department re-presentations [adjusted hazard ratio 1.13 (95% CI 1.05, 1.22)] and longer length of stay [adjusted incidence rate ratio 1.14 (95% CI 1.04, 1.25)]. A co-diagnosis of diabetes was also associated with a 48% increased risk of all-cause mortality [adjusted hazard ratio 1.48 (95% CI 1.22-1.76)]. CONCLUSIONS: People with malignancies and diabetes had significantly more emergency department presentations, more inpatient admissions, longer length of hospital stay and higher rates of all-cause mortality compared to people with a malignancy without diabetes.

Diabetes and higher HbA1c levels are independently associated with adverse renal outcomes in inpatients following multiple hospital admissions.

OBJECTIVE: To assess the association between glycaemic status prior to the first hospital presentation with developing adverse renal outcomes overtime in patients with multiple hospital re-admissions. DESIGN: A prospective observational cohort study. PARTICIPANTS: All inpatients aged ≥54 years admitted between 2013 and 16 to a tertiary hospital. MAIN OUTCOMES: We prospectively measured HbA1c levels in all inpatients aged ≥54 years admitted between 2013 and 16. Diabetes was defined as prior documented diagnosis of diabetes and/or HbA1c ≥6.5% (47·5 mmol/L). Included patients had ≥ two admissions (at least 90 days apart), baseline estimated glomerular filtration rate (eGFR) >30 ml/min/1·73m2 and no history of renal replacement therapy. We assessed several renal outcomes: (a) 50% decline in eGFR; (b) rapid decline in renal function (eGFR decline >5 mL/min/1·73m2/year) and (c) final eGFR<30 ml/min/1·73m2. RESULTS: Of 4126 inpatients with a median follow-up of 465 days (254, 740), 26% had diabetes. The presence of diabetes was associated with higher odds of (a) 50% decline in eGFR (OR = 1·42;95% CI:1·18-1·70;p < 0·001); (b) rapid decline in renal function (OR = 1·40;95%CI:1·20-1·63;p < 0·001), and (c) reaching eGFR<30 ml/min/1.73m2 (OR = 1·25;95%CI:1·03-1·53;p < 0·05). Every 1% (11 mmol/L) increase in baseline HbA1c was associated with significantly greater odds of (a) >50% decline in eGFR (OR = 1·07;95% CI:1·01-1·4;p < 0·05) and (b) rapid decline in renal function (OR = 1·11;95% CI:1·05-1·18;p < 0·001). CONCLUSIONS: In patients with ≥two admissions, the presence of diabetes and higher HbA1c levels were strongly and independently associated with adverse renal outcomes at follow up. Such patients are at high risk of relatively rapid deterioration in renal function and a logical target for structured preventive interventions.

Systemic mastocytosis identified in two women developing fragility fractures during lactation.

Two women presenting with fragility fractures during lactation had bone mineral density (BMD) reduced more greatly than usually associated with lactation. The first woman was 29 years old with a BMD T-score of - 3.2 SD at the spine and- 2.0 SD at the femoral neck. The second woman was 35 years old with a BMD T-score of - 4.5 SD at the spine and - 2.8 SD at the femoral neck. Both women had increased cortical porosity and reduced trabecular density. Investigation identified an elevated serum tryptase, and marrow biopsy confirmed the diagnosis of mastocytosis. Lactation causes bone loss, but the occurrence of fractures in the setting of severe deficits in BMD and microstructural deterioration signals the need to consider additional causes of bone loss.

Systematic review and meta-analysis of prevalence of sarcopenia in post acute inpatient rehabilitation.

Sarcopenia is associated with poor function and increased risk of falls and disability. This work reports a systematic review and meta-analysis of prevalence of sarcopenia in post acute inpatient rehabilitation. Sarcopenia is found to be present in approximately 50% of rehabilitation patients and its prevalence may vary with admission diagnosis. PURPOSE: To conduct a systematic review and meta-analysis of reported prevalence of sarcopenia in post acute inpatient rehabilitation. METHODS: Systematic review conducted according to PRISMA guidelines (PROSPERO registration number CRD42016054135). Databases searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register, and CINAHL. Studies considered the following: published January 1988-February 2017. Key terms are as follows: "sarcopenia" AND "inpatient rehabilitation" OR "rehabilitation" AND/OR "prevalence". Abstracts and subsequently full studies reporting sarcopenia prevalence in adults admitted to rehabilitation reviewed irrespective of design, provided sarcopenia diagnosis included at least assessment of muscle mass. Random effect meta-analysis was conducted. Methodological quality assessment: Agency for Healthcare Research and Quality, US Department of Health and Human Services tool (MORE tool); Joanna Briggs Institute Prevalence Critical Appraisal Tool. RESULTS: Four hundred twenty-six studies identified during initial search, 399 excluded after reviewing titles and abstracts, 21 full text articles reviewed, and six studies met inclusion criteria. Patient populations: after hip fracture (five studies), general deconditioning (one study). Identified sarcopenia prevalence ranged from 0.28 to 0.69. Pooled sarcopenia prevalence obtained with random effect meta-analysis: 0.56 (95% CI 0.46-0.65), heterogeneity I2 = 92.9%. Main quality shortcomings: lack of reporting of inter- and intra-rater reliability, lack of generalizability to other rehabilitation populations. CONCLUSIONS: Original research examining sarcopenia prevalence in inpatient rehabilitation is scarce. Patient populations studied to date are not representative of general rehabilitation population with regard to both age and admission diagnoses. Sarcopenia may be present in approximately half of rehabilitation patients and its prevalence may vary with admission diagnosis.

Cross-sectional associations of albuminuria among Aboriginal and Torres Strait Islander adults: the eGFR Study.

OBJECTIVE: To describe the detailed associations of albuminuria among a contemporary cohort of Aboriginal and Torres Strait Islander people to inform strategies for chronic kidney disease prevention and management. METHODS: A cross-sectional analysis of Indigenous participants of the eGFR Study. MEASURES: Clinical, biochemical and anthropometric measures were collected (including body-circumferences, blood pressure (BP); triglycerides, HbA1c, liver function tests, creatinine; urine- microscopic-haem, albumin: creatinine ratio (ACR), prescriptions- angiotensin converting enzyme inhibitor or angiotensin receptor II antagonist (ACEI/ARB). Albuminuria and diabetes were defined by an ACR>3.0 mg/mmol, and HbA1c≥48 mmol/mol or prior history respectively. Waist: hip ratio (WHR), and estimated glomerular filtration rate (eGFR) were calculated. ACR was non-normally distributed; a logarithmic transformation was applied (in base 2), with each unit increase in log2-albuminuria representing a doubling of ACR. RESULTS: 591 participants were assessed (71% Aboriginal, 61.6% female, mean age 45.1 years, BMI 30.2 kg/m2 , WHR 0.94, eGFR 99.2 ml/min/1.73m2 ). The overall prevalence of albuminuria, diabetes, microscopic-haem and ACEI/ARB use was 41.5%, 41.5%, 17.8% and 34.7% respectively; 69.3% of adults with albuminuria and diabetes received an ACEI/ARB. Using multivariable linear regression modelling, the potentially modifiable factors independently associated with log2-albuminuria were microscopic-haem, diabetes, WHR, systolic BP, alkaline phosphatase (all positive) and eGFR (inverse). CONCLUSION: Albuminuria is associated with diabetes, central obesity and haematuria. High ACEI/ARB prescribing for adults with diabetes and albuminuria was observed. Further understanding of the links between fat deposition, haematuria and albuminuria is required.

Bilirubin concentration is positively associated with haemoglobin concentration and inversely associated with albumin to creatinine ratio among Indigenous Australians: eGFR Study.

Low serum bilirubin concentrations are reported to be strongly associated with cardio-metabolic disease, but this relationship has not been reported among Indigenous Australian people who are known to be at high risk for diabetes and chronic kidney disease (CKD). HYPOTHESIS: serum bilirubin will be negatively associated with markers of chronic disease, including CKD and anaemia among Indigenous Australians. METHOD: A cross-sectional analysis of 594 adult Aboriginal and Torres Strait Islander (TSI) people in good health or with diabetes and markers of CKD. Measures included urine albumin: creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), haemoglobin (Hb) and glycated haemoglobin (HbA1c). Diabetes was defined by medical history, medications or HbA1c≥6.5% or ≥48mmol/mol. Anaemia was defined as Hb<130g/L or <120g/L in males and females respectively. A multivariate regression analysis examining factors independently associated with log-bilirubin was performed. RESULTS: Participants mean (SD) age was 45.1 (14.5) years, and included 62.5% females, 71.7% Aboriginal, 41.1% with diabetes, 16.7% with anaemia, 41% with ACR>3mg/mmol and 18.2% with eGFR<60mL/min/1.73m2. Median bilirubin concentration was lower in females than males (6 v 8µmol/L, p<0.001) and in Aboriginal than TSI participants (6 v 9.5µmol/L, p<0.001). Six factors explained 35% of the variance of log-bilirubin; Hb and cholesterol (both positively related) and ACR, triglycerides, Aboriginal ethnicity and female gender (all inversely related). CONCLUSION: Serum bilirubin concentrations were positively associated with Hb and total cholesterol, and inversely associated with ACR. Further research to determine reasons explaining lower bilirubin concentrations among Aboriginal compared with TSI participants are needed.

Asymmetric changes in circulating insulin levels after an increase compared with a reduction in insulin pump basal rate in people with Type 1 diabetes.

AIMS: To investigate circulating insulin profiles after a clinically relevant insulin pump basal rate increase vs a reduction, and the associated glucose responses. METHODS: A cohort of 12 adults with Type 1 diabetes undertook this two-stage university hospital study using Accu-Chek pumps (Roche Diagnostics, Mannheim, Germany) and insulin aspart. An insulin basal rate change of 0.2 unit/h (increase in first stage, reduction in second stage) was implemented at ~09:30 h, after a single overnight basal rate (without bolus insulin), while fasting participants rested. Frequent venous samples for the assessment of plasma free insulin, glucose and cortisol were collected from 60 min before until 300 min after rate change. The primary outcome was time to steady-state insulin. RESULTS: The 0.2-unit/h rate change represented a mean ± sd alteration of 23 ± 6%. After the rate increase, the median (interquartile range) times to 80% and 90% steady-state insulin were 170 (45) min and 197 (87) min, respectively. By contrast, after rate reduction, 80% steady-state insulin was not achieved. After the rate increase, mean ± se insulin levels increased by 4.3 ± 3.1%, 12.0 ± 2.9% and 25.6 ± 2.6% at 60, 120 and 300 min, respectively (with no significant difference until 180 min). After the rate reduction, insulin decreased by 8.3 ± 3.0% at 300 min (with no significant difference until 300 min). After rate reduction, glucose levels paradoxically declined by 17.4 ± 3.7% after 300 min; cortisol levels also fell during observation (P = 0.0003). CONCLUSIONS: The time to circulating insulin change after a 0.2-unit/h basal rate change was substantial, and was greater after a reduction than after an increase. Counter-regulatory hormone circadian variation may affect glycaemia when implementing minor changes at low basal rates. Both direction of basal rate change, and time of day, warrant consideration when anticipating the clinical effects of basal rate changes.

Associations of serum adiponectin with markers of cardio-metabolic disease risk in Indigenous Australian adults with good health, diabetes and chronic kidney disease.

The higher serum adiponectin concentrations observed in females are often attributed to differences in adiposity or sex hormones. There is little data describing adiponectin in Indigenous Australians, and no studies examining its association with cardio-metabolic disease risk markers and chronic kidney disease (CKD). AIM: To describe the relationship of serum adiponectin with cardio-metabolic disease risk markers and kidney function in a community-based sample of Indigenous Australian adults, with particular reference to sex-specific differences. METHODS: A cross-sectional analysis of a community-based volunteer sample of 548 Indigenous Australian adults (62% female), stratified into five cardio-metabolic risk groups ranging from good health (strata-1) to high cardio-metabolic risk and low measured glomerular filtration rate (mGFR, <60ml/min/1.73m2) (strata-5). We examined serum adiponectin concentrations with cardio-metabolic risk markers, albuminuria and mGFR. RESULTS: Indigenous Australian females had a lower than expected adiponectin concentration (3.5µg/ml), which was higher than males in strata 1-4 (as in other populations), but not in strata-5 (mGFR<60, p=0.19), and higher leptin: adiponectin ratio than other populations (7.8ng/µg - strata-1, healthy females; 12.2ng/µg - strata-3, females with diabetes and mGFR≥90). Female-gender, HDL-cholesterol (positive), mGFR and waist: hip ratio (WHR) (inverse) were independently associated with log-adiponectin when mGFR≥60; when mGFR<60, female-gender was associated with 0.27 units lower log-adiponectin. CONCLUSION: Female-gender was not associated with higher adiponectin concentrations in Indigenous Australians with mGFR<60ml/min/1.73m2. High WHR was frequent in both genders, and inversely associated with adiponectin. Longitudinal studies are needed to examine relationships of serum adiponectin, obesity and cardiovascular disease events in Indigenous Australians.

Cardiovascular outcomes with antihypertensive therapy in type 2 diabetes: an analysis of intervention trials.

In studies of antihypertensive therapy, relative cardiovascular (CV) risk reduction is largely independent of attained systolic blood pressure (SBP). How this translates to absolute risk reduction (ARR) in diabetes is not clear. We have compared 5-year CV outcomes in 10 studies of intensive versus moderate or active versus placebo therapy in subjects with type 2 diabetes and attained SBP < or ⩾ 140 mm Hg. Attained SBP ⩾ 140 mm Hg occurred in five early studies (HOT n = 1001, UKPDS n = 1148, SHEP n = 583, SYSTEUR n = 422, MICRO_HOPE n = 3377) and attained SBP<140 mm Hg occurred in five recent studies (ABCD-NT n = 480, ADVANCE n = 11,140 INVEST n = 4266, ACCORD n = 4733, ROADMAP n= 4447). In each study, ARR was calculated from group mean data and expressed as % change in CV events over 5 years per 10 mm Hg decrease in attained SBP. In studies with attained SBP ⩾ 140 mm Hg, ARR was 13 ± 2.6% per 10 mm Hg, and the number needed to treat (NNT) to prevent one event in 5 years was 8. In studies with attained SBP < 140 mm Hg, ARR was 1.6 ± 1 .9% per 10 mm Hg (P = 0.0007), and NNT was 68. The present analysis indicates that CV outcomes reach a plateau after attaining SBP of 140 mm Hg in patients with type 2 diabetes.

Combining cutaneous silent periods with quantitative sudomotor axon reflex testing in the assessment of diabetic small fiber neuropathy.

OBJECTIVE: Routine electrophysiological testing is often normal in the evaluation of painful diabetic neuropathy, as it is unable to detect dysfunction of thinly myelinated (Aδ) and unmyelinated (C) small fibers. Although cutaneous silent periods (CSP) and quantitative sudomotor axon reflex testing (QSART) respectively evaluate these fiber types in the extremities, these two tests have yet to be assessed together. METHODS: 26 patients with a clinical diagnosis of small fiber neuropathy (SFN) and 26 age-matched controls were assessed. Nine patients had Type I diabetes, nine had Type II diabetes, and eight had impaired glucose tolerance. The CSP onset latency and duration were recorded in each extremity. QSART was performed on the right side. RESULTS: 58% (15/26) of patients had abnormal sweat volumes obtained from QSART, while 50% (13/26) of patients had abnormal CSP responses. Combining these two tests increased the sensitivity of testing to 77% (20/26). Abnormalities were seen equally across all patient groups. CONCLUSIONS: Combining CSP with QSART significantly increases the sensitivity of testing when assessing patients with SFN related to diabetes, or prediabetes. SIGNIFICANCE: For clinically suspected SFN, it is preferable to test more than one small fiber type, as each possess different structural and functional properties and may be heterogeneously affected between patients.

The impact of hyperfiltration on the diabetic kidney.

More than two decades ago, hyperfiltration (HF) in diabetes was postulated to be a maladaptive response observed early in the course of diabetic kidney disease (DKD), which may eventually predispose to irreversible damage to nephrons and development of progressive renal disease. Despite this, the potential mechanisms leading to renal HF in diabetes are not fully understood, although several hypotheses have been proposed, including alterations in glomerular haemodynamic function and tubulo-glomerular feedback. Furthermore, the role of HF as a causative factor in renal disease progression is still unclear and warrants further prospective longer-term studies. Although HF has been entrenched as the first stage in the classic albuminuric pathway to end-stage renal disease in DKD, and HF has been shown to predict the progression of albuminuria in many, but not all studies, the concept that HF predisposes to the development of chronic kidney disease (CKD) stage 3, that is, glomerular filtration rate (GFR) decline to<60mL/min/1.73m(2), remains to be proved. Further long-term studies of GFR gradients therefore are required to establish whether HF ultimately leads to decreased kidney function, after adjustment for glycaemic control and other confounders. Whether reversal of HF with therapeutic agents is protective against reducing the risk of development of albuminuria and renal impairment is also worth investigating in prospective randomized trials.

Performance of formulas for estimating glomerular filtration rate in Indigenous Australians with and without Type 2 diabetes: the eGFR Study.

AIMS: It has been proposed that the Chronic Kidney Disease Epidemiology Collaboration formula estimates glomerular filtration rate more accurately than the Modification of Diet in Renal Disease formula. With the very high incidence of diabetes and end-stage kidney disease in Indigenous Australians, accurate estimation of glomerular filtration rate is vital in early detection of kidney disease. We aimed to assess the performance of the Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease and Cockcroft-Gault formulas in Indigenous Australians with and without diabetes. METHODS: Indigenous Australians with (n = 224) or without (n = 340) Type 2 diabetes had a reference glomerular filtration rate measure using plasma disappearance of iohexol (measured glomerular filtration rate) over 4 h. Serum creatinine was measured by an enzymatic method. Performance was assessed by bias (measured glomerular filtration rate - estimated glomerular filtration rate) and accuracy (percentage of estimated glomerular filtration rate within 30% of measured glomerular filtration rate). RESULTS: The median measured glomerular filtration rate (interquartile range) in participants with or without diabetes was 97 (68-119) and 108 (90-122) ml min(-1)  1.73 m(-2) , respectively. The Chronic Kidney Disease Epidemiology Collaboration formula had smaller bias and greater accuracy than the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall, for participants both with and without diabetes. However, for estimated glomerular filtration rate > 90 ml min(-1)  1.73 m(-2) , the Chronic Kidney Disease Epidemiology Collaboration formula had greater bias in participants with diabetes, underestimating measured glomerular filtration rate by 7.4 vs. 1.0 ml min(-1)  1.73 m(-2) in those without diabetes. The Chronic Kidney Disease Epidemiology Collaboration formula was less accurate across the whole range of estimated glomerular filtration rates in participants with vs. those without diabetes (87.1% vs. 93.3%). CONCLUSIONS: The Chronic Kidney Disease Epidemiology Collaboration formula outperforms the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall in Indigenous Australians with and without diabetes. However, the Chronic Kidney Disease Epidemiology Collaboration formula has greater bias in people with diabetes compared with those without diabetes, especially in those with normal renal function.

New approaches for the evaluation of renal vascular function in diabetes.

In this issue of Diabetologia, two new approaches are described for the assessment of intra-renal blood flow in people with diabetes. The first approach used the technique of dynamic assessment of the resistance index (RI) in the renal interlobar arteries before and after administration of sublingual glyceryl trinitrate, and the second used MRI to assess total renal blood flow in relation to mean arterial pressure, thereby enabling direct measurement of overall renal RI. The results of the first study raise the possibility that dynamic evaluation of the intra-renal RI could be used as an early detector of vascular alterations in type 2 diabetes, before the onset of microalbuminuria. The results of the second study suggest that decreases in renal blood flow in people with longstanding type 1 diabetes reflect intra-renal vascular stiffening and raise the possibility that in microalbuminuric patients it may also reflect increased intraglomerular pressure.

High sodium and low potassium intake in patients with Type 2 diabetes.

AIMS: To document dietary sodium and potassium intake and adherence to the Australian National Heart Foundation (NHF) guidelines in patients with Type 2 diabetes mellitus attending an Australian tertiary referral and university teaching hospital. METHODS: In a longitudinal study, 24h urinary sodium (uNa), potassium (uK), creatinine (uCr), urea (uUrea) and glucose (uGlu) excretions, urine volume (uVol) and body mass index were recorded in 122 regular attenders over an 8 year period (2001-2008; mean of 1.9 samples/patient/year). In a cross-sectional study, the same measurements were recorded in patients providing urine samples in the month of June from 2001 to 2009 (782 patients, averaging 87/year). RESULTS: In the longitudinal study, uNa (mmol/24 h) was 170 ± 53 (mean ± SD) in males and 142 ± 51 in females, whereas uK (mmol/24 h) was 75 ± 22 in males and 62 ± 18 in females. Once adjusted for insensible losses, only 3% of males and 14% of females met the NHF dietary sodium intake guidelines, and 14% of males and 3% of female patients met the NHF dietary potassium guidelines. Body mass index, uUrea, uVol and uGlu were independent predictors of uNa (adjusted r(2) =0.57, P<0.0001). The mean intra-individual coefficient of variation of the corrected uNa was 21 ± 1%. The cross-sectional study confirmed these findings, and no temporal trends were observed. There was no correlation with glycated haemoglobin to suggest natriuresis with hyperglycaemia. CONCLUSIONS: Most patients with Type 2 diabetes mellitus do not meet NHF sodium or potassium intake guidelines. A diet high in sodium and low in potassium may contribute to the development of hypertension and to resistance to blood-pressure-lowering therapies.