Estimated glomerular filtration rate calculated by serum creatinine lacks precision and accuracy in adults with type 2 diabetes with preserved renal function.

AIMS: We evaluated the performance of creatinine-based equations that are currently used to estimate glomerular filtration rate (GFR) in people with type 2 diabetes compared to measured GFR using gold-standard methods. METHODS: In this post-hoc analysis, 32 participants underwent repeated measurement of GFR by inulin clearance (mGFR). GFR was estimated by serum creatinine using the MDRD (eGFRMDRD) and CKD-EPI (eGFRCKD-EPI) equations four times over the course of one month. Performance was evaluated using measurements of bias (mean difference), precision (SD), and inaccuracy (proportion of eGFR that differed by >20 % of mGFR). Treatment and time effects on bias were evaluated using linear mixed effects models. RESULTS: At baseline, participants (38 % female) were age 60 ± 8 years, had diabetes duration of 9 ± 7 years, HbA1c 56 ± 9 mmol/mol (7.2 ± 0.8 %), and BMI 31.0 ± 6.2 kg/m2. Mean mGFR was 113 ± 24, mean eGFRMDRD was 93 ± 12, and mean eGFRCKD-EPI was 94 ± 9 mL/min/1.73 m2. When 128 observations (32 participants measured 4 times) were evaluated, both equations substantially underestimated mGFR. For eGFRMDRD, mean bias was -21.5 mL/min/1.73 m2, precision was 22.7 mL/min/1.73 m2, and 46 % of observations differed by >20 %. Results were similar for eGFRCKD-EPI. No time or treatment effects on bias were observed. CONCLUSIONS: In adults with type 2 diabetes and preserved renal function, eGFR equations underestimated mGFR, lacked precision and accuracy, and performance was lower at higher ranges of mGFR. Current eGFR equations by serum creatinine are inaccurate in adults with type 2 diabetes with preserved renal function, highlighting the necessity to develop new methods to measure kidney function at earlier stages of diabetic kidney disease.

The association between physical activity time and neuropathy in longstanding type 1 diabetes: A cross-sectional analysis of the Canadian study of longevity in type 1 diabetes.

AIM: Physical activity (PA) is recommended to improve glycemic control in T1D; however, the effect of PA on distal symmetric polyneuropathy (DSPN) and cardiac autonomic function in longstanding T1D is unknown. METHODS: Data from 75 participants were collected as part of the Canadian Study of Longevity in T1D. Participants completed a physical exam, medical history, extensive complications phenotyping and reported their daily PA from the preceding 12-months. Pearson and Spearman correlations were used to assess PA time and complications variables. Linear regression was used to test associations between PA time, neurological and electrophysiological measures. Univariable regression was used to indicate the change in the given independent variables associated with a 30-min increase in PA per week. RESULTS: Participants were 66 ± 8 years old with diabetes duration of 54 [52,58] years, HbA1c was 7.3 ± 0.8, 65(89%) had DSPN. Weekly PA time was 156 ± 132 min, and 35(47%) reported ≧150 min/week. Participants with DSPN reported lower PA time compared to individuals without DSPN (141 ± 124 min/week vs. 258 ± 129 min/week; p = 0.015). PA time was associated with better cooling detection threshold (r = 0.24; p = 0.043), peroneal and sural amplitude (r = 0.36; p = 0.0017, rs = 0.26; p = 0.024) and conduction velocity (rs = 0.28; p = 0.015, r = 0.23; p = 0.050). Linear regression adjusting for age and HbA1c, showed that for each 30-min of PA there was a 0.09mv higher peroneal amplitude (p = 0.032) and 0.048 ms lower peroneal F-wave latency (p = 0.022). CONCLUSION: In longstanding T1D, PA time is associated with superior large nerve fibre function in the lower limbs and some better measures of small nerve fibre function.

The complex association between pain and neuropathy.

BACKGROUND: Several studies of patients with polyneuropathy failed to show differences between patients with and without pain. In the current study, we aimed to explore the association between neuropathic symptoms, mainly pain, and polyneuropathy characteristics. METHODS: A prospective cross-sectional study recruiting 151 patients with non-diabetic polyneuropathy was performed between November 2016 and May 2017. A total of 38 patients with chronic inflammatory demyelinating neuropathy were excluded. Patients underwent clinical, electrophysiological and functional assessments of their polyneuropathy. Polyneuropathy characteristics were compared depending on the presence and severity of neuropathic symptoms. RESULTS: The presence and the severity of weakness were associated with a more severe neuropathy as measured by clinical, electrophysiological and functional assessments, while the presence of pain was associated with higher sural amplitudes, and the severity of pain showed a curvilinear association with neuropathy severity. CONCLUSIONS: Our study shows a novel finding of a curvilinear association between pain and polyneuropathy severity.

The Prevalence of Autoimmune Diseases in Longstanding Diabetes: Results from the Canadian Study of Longevity in Adults with Type 1 Diabetes.

OBJECTIVE: We aimed to determine the prevalence of autoimmune diseases (e.g. thyroid disease, celiac disease, etc) in Canadians with longstanding type 1 diabetes (T1D) and to explore sex-specific differences and the association with complications. METHODS: Cross-sectional data were analyzed in an exploratory secondary analysis from the Canadian Study of Longevity in Type 1 Diabetes, a nationwide registry of people with T1D of at least 50 years' duration. In total, 374 participants provided self-reported questionnaire data and physician-reported laboratory results. Student's t-test, the Wilcoxon rank-sum test, the χ2 test and logistic regression were used to identify associations with autoimmune diseases. RESULTS: The 374 participants had a median T1D duration of 53 years (interquartile range, 51 to 58) and a median age of onset of 11 years (6 to 16), and 57.1% were females. Females had a greater prevalence of autoimmune diseases (60.6% vs 34.4%, p<0.001). Thyroid disease was most prevalent (41%, 153/374), especially in females (51.6% vs 26.9%), and the prevalence of 1 or more autoimmune disease was 49.3% (184/374). Autoimmune disease was associated with lower odds of cardiovascular disease (CVD)-odds ratio [OR] 0.61, 95% confidence interval [CI] 0.37 to 1.00 for thyroid autoimmune disease and OR 0.34 (95% CI 0.12 to 0.93) for nonthyroid autoimmune disease, both compared to those without autoimmune disease (p=0.033). Autoimmune diseases were not associated with the presence of nephropathy, neuropathy or retinopathy. CONCLUSIONS: Lifetime risk of autoimmune disease in longstanding T1D approaches 50%, is greater in females and is driven by thyroid disease. The probability of diabetes complications, such as CVD, was lower in those with autoimmune disease, which was driven mostly by nonthyroid autoimmune diseases.

Vasopressin associated with renal vascular resistance in adults with longstanding type 1 diabetes with and without diabetic kidney disease.

OBJECTIVE: Arginine vasopressin (AVP) and its surrogate, copeptin, have been implicated in diabetic kidney disease (DKD) pathogenesis, which develops in a subset of people with longstanding type 1 diabetes, but not in others (DKD Resistors). We hypothesized that patients with DKD would exhibit higher copeptin concentrations vs. DKD Resistors. METHODS: Participants with type 1 diabetes (n = 62, duration ≥50 years) were stratified into 42 DKD Resistors and 20 with DKD (eGFR ≤60 mL/min/1.73m2 or ≥30 mg/day urine albumin), and age/sex-matched controls (HC, n = 74) were included. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were calculated by inulin and p-aminohippurate clearance before and after angiotensin II (ang II) infusion. Renal vascular resistance (RVR) was calculated as mean arterial pressure/renal blood flow. Plasma copeptin, renin, aldosterone, neutrophil gelatinase-associated lipocalin (NGAL), and urea concentrations were measured, along with 24-h urine volume. RESULTS: DKD resistors had lower copeptin (95% CI: 4.0 [3.4-4.8] pmol/l) compared to DKD (5.8 [4.5-7.6] pmol/l, p = 0.02) and HC (4.8 [4.1-5.5] pmol/l, p = 0.01) adjusting for age, sex and HbA1c. In type 1 diabetes, higher copeptin correlated with lower GFR (r: -0.32, p = 0.01) and higher renin concentration (r: 0.40, p = 0.002) after multivariable adjustments. These relationships were not evident in HC. Copeptin inversely associated with RVR change following exogenous ang II only in participants with type 1 diabetes (ß ±â€¯SE: -6.9 ±â€¯3.4, p = 0.04). CONCLUSIONS: In longstanding type 1 diabetes, copeptin was associated with intrarenal renin-angiotensin-aldosterone system (RAAS) activation and renal hemodynamic function, suggesting interplay between AVP and RAAS in DKD pathogenesis.

Baseline omega-3 level is associated with nerve regeneration following 12-months of omega-3 nutrition therapy in patients with type 1 diabetes.

AIM: Omega-3 (n-3) polyunsaturated fatty-acids are essential for the development and maintenance of nerve function, but the relationship of plasma n-3 to the presence of diabetic distal-symmetric-polyneuropathy (DSP) and the effect of n-3 therapy on plasma levels and small nerve fibre morphology in T1D are unknown. METHODS: Participants with T1D (n = 40, 53% female, aged (mean ±â€¯SD) 48 ±â€¯14 years, BMI 28.1 ±â€¯5.8 kg/m2, diabetes duration 27 ±â€¯18 years), 23 of whom had DSP, took seal-oil (10 mL/day; 750 mg eicosapentaenoic acid (EPA), 560 mg docosapentaenoic acid (DPAn-3), and 1020 mg docosahexaenoic acid (DHA)) for 12-months in a single-arm open-label study. The improvement in corneal nerve fibre length (CNFL) (primary outcome) was previously reported. In this secondary analysis, plasma n-3s were measured at baseline, 4, 8 and 12-months. RESULTS: At baseline, participants with DSP had lower DHA than those without (1.73 ±â€¯0.89 vs. 2.27 ±â€¯0.70%, p = 0.049). Twelve-months seal-oil therapy increased mean plasma EPA by 185%, DPA by 29%, DHA by 79% (p < 0.001) and CNFL by 29% (p = 0.001). Change in CNFL was positively associated with higher baseline total n-3 (Spearman's correlation coefficient r = 0.41, p = 0.013), DPA (r = 0.33, p = 0.047) and DHA (r = 0.42, p = 0.012). CONCLUSION: In conclusion, low plasma DHA was associated with prevalent DSP, n-3 therapy increased blood n-3 levels and higher baseline n-3s were associated with greater nerve regeneration.

High fractional excretion of glycation adducts is associated with subsequent early decline in renal function in type 1 diabetes.

Increased protein glycation, oxidation and nitration is linked to the development of diabetic nephropathy. We reported levels of serum protein glycation, oxidation and nitration and related hydrolysis products, glycation, oxidation and nitration free adducts in patients with type 1 diabetes (T1DM) during onset of microalbuminuria (MA) from the First Joslin Kidney Study, a prospective case-control study of patients with T1DM with and without early decline in GFR. Herein we report urinary excretion of the latter analytes and related fractional excretion values, exploring the link to MA and early decline in GFR. We recruited patients with T1DM and normoalbuminuria (NA) (n = 30) or new onset MA with and without early GFR decline (n = 22 and 33, respectively) for this study. We determined urinary protein glycation, oxidation and nitration free adducts by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry (LC-MS/MS) and deduced fractional excretion using reported plasma levels and urinary and plasma creatinine estimates. We found urinary excretion of pentosidine was increased ca. twofold in patients with MA, compared to normoalbuminuria (0.0442 vs 0.0103 nmol/mg creatinine, P < 0.0001), and increased ca. threefold in patients with early decline in GFR, compared to patients with stable GFR (0.0561 vs 0.0176 nmol/mg creatinine, P < 0.01). Urinary excretion of all other analytes was unchanged between the study groups. Remarkably, fractional excretions of 6 lysine and arginine-derived glycation free adducts were higher in patients with early decline in GFR, compared to those with stable GFR. Impaired tubular reuptake of glycation free adducts by lysine and arginine transporter proteins in patients with early GFR decline is likely involved. We conclude that higher fractional excretions of glycation adducts are potential biomarkers for early GFR decline in T1DM and MA. Measurement of these analytes could provide the basis for identifying patients at risk of early decline in renal function to target and intensify renoprotective treatment.

Superiority of sonographic evaluation of contracted versus relaxed muscle thickness in motor neuron diseases.

OBJECTIVE: To compare the correlations of relaxed and contracted limb muscle thickness with clinical scales in patients with amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). METHODS: Patients with ALS and SMA were prospectively recruited from December 2018 to November 2019. All patients underwent clinical assessment and sonographic muscle thickness measurement of eight relaxed muscles (biceps brachii, abductor pollicis brevis (APB), first dorsal interosseous, abductor digiti minimi, quadriceps, tibialis anterior, extensor digitorum brevis, and abductor hallucis brevis), and four contracted muscles (biceps brachii, APB, quadriceps, and tibialis anterior). RESULTS: 91 patients with ALS and 31 patients with SMA were recruited. Contracted muscle thickness compared to relaxed muscle showed higher reliability and similar or better correlations with muscle strength and clinical scales, especially in ALS patients with hyperreflexia. Strong to very strong correlations with clinical scales were observed with multivariate analysis of relaxed and contracted muscle thickness (0.64-0.87). CONCLUSIONS: Sonographic evaluation of contracted muscle thickness is an objective measure that correlates with disease burden. It is feasible, quick, valid and reliable, and may be superior to evaluation of relaxed muscles. SIGNIFICANCE: Sonographic evaluation of contracted muscle thickness is superior to evaluation of relaxed muscles.

Rapid Corneal Nerve Fiber Loss: A Marker of Diabetic Neuropathy Onset and Progression.

OBJECTIVE: Corneal nerve fiber length (CNFL) represents a biomarker for diabetic distal symmetric polyneuropathy (DSP). We aimed to determine the reference distribution of annual CNFL change, the prevalence of abnormal change in diabetes, and its associated clinical variables. RESEARCH DESIGN AND METHODS: We examined 590 participants with diabetes (399 with type 1 diabetes [T1D] and 191 with type 2 diabetes [T2D]) and 204 control patients without diabetes with at least 1 year of follow-up and classified them according to rapid corneal nerve fiber loss (RCNFL) if CNFL change was below the 5th percentile of the control patients without diabetes. RESULTS: Control patients without diabetes were 37.9 ± 19.8 years old, had median follow-up of three visits over 3.0 years, and mean annual change in CNFL was -0.1% (90% CI -5.9% to 5.0%). RCNFL was defined by values exceeding the 5th percentile of 6% loss. Participants with T1D were 39.9 ± 18.7 years old, had median follow-up of three visits over 4.4 years, and mean annual change in CNFL was -0.8% (90% CI -14.0% to 9.9%). Participants with T2D were 60.4 ± 8.2 years old, had median follow-up of three visits over 5.3 years, and mean annual change in CNFL was -0.2% (90% CI -14.1% to 14.3%). RCNFL prevalence was 17% overall and was similar by diabetes type (64 T1D [16.0%], 37 T2D [19.4%], P = 0.31). RNCFL was more common in those with baseline DSP (47% vs. 30% in those without baseline DSP, P = 0.001), which was associated with lower peroneal conduction velocity but not with baseline HbA1c or its change over follow-up. CONCLUSIONS: An abnormally rapid loss of CNFL of 6% per year or more occurs in 17% of diabetes patients. RCNFL may identify patients at highest risk for the development and progression of DSP.

The utility of a single simple question in the evaluation of patients with nondiabetic polyneuropathy.

INTRODUCTION: A single and simple question, namely "What percentage of normal (PoNL) do you feel regarding your disease?" is feasible and valid in myasthenia gravis. In this study, we aimed to determine the validity of this question in patients with nondiabetic polyneuropathy. METHODS: Clinical, electrophysiological, and functional and disability assessments were performed in 151 patients with nondiabetic polyneuropathy. One hundred forty patient answers were recorded for the PoNL question, and these were included in the current study. RESULTS: The PoNL correlated moderately with functional and disability scales. DISCUSSION: "What PoNL do you feel?" is a simple, quick, and valid question, which correlates moderately with functional and disability scales in nondiabetic polyneuropathy, and it may be incorporated in polyneuropathy assessment.

Quantitative sonographic evaluation of muscle thickness and fasciculation prevalence in healthy subjects.

BACKGROUND: In the current study, we aimed to determine normative values for muscle thickness and fasciculation prevalence in healthy subjects. METHODS: We performed a prospective study from October to December 2018 in 65 healthy subjects. All subjects underwent quantitative sonographic evaluation of muscle thickness and fasciculation prevalence in the following 8 muscles: Biceps brachii, abductor pollicis brevis, first dorsal interosseous, abductor digiti minimi, quadriceps, tibialis anterior, extensor digitorum brevis, and abductor hallucis brevis. RESULTS: Subject ages ranged from 21 to 82 years, with 63% women. Normative values for muscle thickness were determined using the fifth percentile. Multivariate regression analysis showed that sex, age, body mass index, and hand dominance affected muscle thickness. Fasciculations were observed frequently only in distal muscles. CONCLUSIONS: Normal values for muscle thickness were determined, and may enhance neuromuscular ultrasound sensitivity and serve as a basis for future studies. Larger series are needed to confirm these values.

Analysis of Prevalence, Magnitude and Timing of the Dawn Phenomenon in Adults and Adolescents With Type 1 Diabetes: Descriptive Analysis of 2 Insulin Pump Trials.

OBJECTIVES: To better understand the dawn phenomenon in type 1 diabetes, we sought to determine its prevalence, timing and magnitude in studies specifically designed to assess basal insulin requirements in patients using insulin pumps. METHODS: Thirty-three participants from 2 sensor-augmented insulin pump studies were analyzed. Twenty participants were obtained from a methodologically ideal semiautomated basal analysis trial in which basal rates were determined from repeated fasting tests (the derivation set) and 13 from an artificial pancreas trial in which duration of fasting was variable (the "confirmation" set). Prevalence was determined for the total cohort and for individual trials using the standard definition of an increase in insulin exceeding 20% and lasting ≥90 minutes. Among cases, time of onset and percent change in the magnitude of basal delivery were determined. RESULTS: Seventeen participants (52%) experienced the dawn phenomenon (11 of 20 [55%] in the derivation set and 6 of 13 [46%] in the confirmation set). Time of onset was 3 AM (interquartile range [IQR], 3 to 4:15 AM) in the derivation set and 3 AM (IQR, 3 to 4 AM) in the confirmation set. The magnitude of the dawn phenomenon was a 58.1% (IQR, 28.8% to 110.6%) increase in insulin requirements in the derivation set and 65.5% (IQR, 45.6% to 87.4%) in the confirmation set. CONCLUSIONS: The dawn phenomenon occurs in approximately half of patients with type 1 diabetes; when present, it has predictable timing of onset (generally 3 AM) and a substantial, but highly variable, magnitude. These findings imply that optimization of glycemic control requires clinical emphasis on fasted overnight basal insulin assessment.

Sex differences in neuropathy & neuropathic pain: A brief report from the Phase 2 Canadian Study of Longevity in Type 1 Diabetes.

To evaluate previous results from a questionnaire-based study, we studied objective neuropathy measures to determine sex differences in the prevalence of neuropathy and neuropathic pain in longstanding type 1 diabetes. Despite better neuropathy measures in females compared to males, we confirmed a trend towards higher neuropathic pain in females.

European Federation of Neurological Societies cutoff values significantly reduce creatine kinase sensitivity for diagnosing neuromuscular disorders.

INTRODUCTION: Elevated creatine kinase (CK) level was redefined by the European Federation of Neurological Societies)EFNS(as 1.5 times the upper limit of normal. In the current study we sought to determine the sensitivity and specificity of CK testing for the diagnosis of neuromuscular disorders. METHODS: Demographics and CK levels were retrospectively extracted from an electronic database for 234 patients with neuromuscular disorders. Sensitivity, specificity, and likelihood ratios and the area under curve were determined for each diagnosis and different cutoff CK values. RESULTS: Using the EFNS cutoff values significantly reduced CK test sensitivity. Creatine kinase values >1000 IU/L showed a high likelihood (11.04) for myopathies and a low likelihood for polyneuropathies (0). DISCUSSION: European Federation of Neurological Societies cutoff values significantly reduce CK sensitivity for diagnosing neuromuscular disorders. While low CK values cannot exclude a neuromuscular disease, values >1000 IU/L are associated with a high likelihood of myopathy.

Muscle thickness measured by ultrasound is reduced in neuromuscular disorders and correlates with clinical and electrophysiological findings.

INTRODUCTION: Nerve imaging has a limited role in axonal and muscle fiber loss. In this study, we sought to explore the utility of standardized muscle ultrasound (US) assessment in these clinical scenarios. METHODS: We performed a prospective study from March to August 2018 of patients attending the neuromuscular clinic. All patients underwent clinical evaluation and standardized muscle thickness measurement by US in seven muscles. RESULTS: The study cohort consisted of 114 participants, including patients with polyneuropathy, motor neuron disease, and myopathy. The smallest distal muscle thickness was found in patients with polyneuropathy, while the smallest proximal muscle thickness was found in patients with myopathy. Muscle thickness was strongly correlated with muscle strength (r 2 = 0.62), electrophysiological findings (r 2 : 0.44-0.55), and disability score (r 2 = 0.53). DISCUSSION: Standardized muscle thickness measured by US shows diagnostic usefulness in a spectrum of neuromuscular disorders and correlates with clinical and electrophysiological findings.

Baseline Decrement in Patients with Mild Myasthenia Gravis Predicts Immunomodulation Treatment.

To explore whether higher degrees of electrophysiological abnormalities are associated with a more frequent exposure to a more aggressive treatment regimen, we performed a retrospective chart review of patients attending the neuromuscular clinic from June 2012 to December 2015 and included 87 patients. We compared treatment regimens during the follow-up period between patients with high and low jitter and decrement. Myasthenia gravis patients with high jitter or decrement at baseline were more frequently treated with intravenous immunoglobulins (IVIG) and/or plasma exchange (PLEX) during the follow-up period. In patients with mild disease, IVIG or PLEX treatment was associated with high decrement.

La diminution initiale du potentiel moteur de patients atteints de myasthénie grave peut permettre de prédire le type d'immuno-modulation thérapeutique prodiguée. Afin d'explorer dans quelle mesure des niveaux plus élevés d'anomalies électro-physiologiques peuvent être associés à une exposition davantage fréquente à des régimes de traitement plus vigoureux, nous avons effectué un examen rétrospectif des dossiers de patients, 87 au total, s'étant présentés à une clinique neuromusculaire de juin 2012 à décembre 2015. Nous avons alors comparé les régimes de traitement des patients montrant de basses mesures de gigue (jitter) et une faible diminution d'amplitude du potentiel d'action au cours de leur période de suivi avec les régimes de traitement d'autres patients pour qui ces mesures étaient élevées. Les patients atteints de myasthénie grave (MG) dont les mesures de gigue et la diminution d'amplitude du potentiel d'action étaient initialement élevées ont été plus fréquemment traités, lors d'un suivi, avec des immunoglobulines intraveineuses et/ou des échanges plasmatiques. Chez les patients atteints de la forme bénigne de cette maladie, ces deux traitements ont été associés à une diminution d'amplitude du potentiel d'action plus élevée.

Estimating GFR by Serum Creatinine, Cystatin C, and ß2-Microglobulin in Older Adults: Results From the Canadian Study of Longevity in Type 1 Diabetes.

INTRODUCTION: Glomerular filtration rate (GFR) is routinely used for clinical assessment of kidney function. However, the accuracy of estimating equations in older adults is uncertain. METHODS: In 66 adults with ≥50 years type 1 diabetes (T1D) duration and 73 nondiabetic controls from age/sex-matched subgroups (65 ± 8 years old and 77[55%] were women) we evaluated the performance of estimated GFR (eGFR) by creatinine (Modification of Diet and Renal Disease [MDRD], Chronic Kidney Disease-Epidemiology [CKD-EPI]cr), cystatin C (CKD-EPIcys, CKD-EPIcr-cys), and ß2-microglobulin (ß2M) compared with measured GFR by inulin clearance (mGFR). Performance was evaluated using metrics of bias (mean difference), precision (SD), and accuracy (proportion of eGFR that differed by >20% of mGFR). RESULTS: Mean mGFR was 104 ± 18 ml/min per 1.73 m2 (range: 70-154 ml/min per 1.73 m2) and was not different between T1D and controls (103 ± 17 vs. 105 ± 19 ml/min per 1.73 m2, P = 0.39). All equations significantly underestimated mGFR (bias: -15 to -30 ml/min per 1.73 m2, P < 0.001 for all comparisons) except for ß2M, which had bias of 1.9 ml/min per 1.73 m2 (P = 0.61). Bias was greatest in cystatin C-based equations. Precision was lowest for ß2M (SD: 43.5 ml/min per 1.73 m2, P < 0.001 for each comparison). Accuracy was lowest for CKD-EPIcysC (69.1%, P < 0.001 for each comparison). Cystatin C-based equations demonstrated greater bias and lower accuracy in older age subgroups (<60, 60-69, ≥70 years). All equations demonstrated greater bias across higher ranges of mGFR (60-89, 90-119, ≥120 ml/min per 1.73 m2). Results were similar between T1D and controls except that ß2M had lower performance in T1D. CONCLUSION: Better estimates of GFR in older adults are needed for research and clinical practice, as this subgroup of the population has an amplified risk for the development of chronic kidney disease (CKD) that requires accurate GFR estimation methods.

Elevated plasma cyclic guanosine monophosphate may explain greater efferent arteriolar tone in adults with longstanding type 1 diabetes: A brief report.

Cyclic guanosine monophosphate (cGMP) influences intrarenal hemodynamics in animal models, but the relationship between cGMP and renal function in adults with type 1 diabetes (T1D) remains unclear. In this study, plasma cGMP correlated with efferent arteriolar resistance, effective renal plasma flow, and renal vascular resistance in adults with T1D.

Bone mineral density in patients with longstanding type 1 diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes.

AIM: It is currently unclear if longstanding type 1 diabetes (T1D) affects bone mineral density (BMD). METHODS: BMD measured by dual-energy X-ray absorptiometry and history of fragility fracture was determined in 75 T1D participants with ≥50 years of diabetes duration and 75 age- and sex-matched non-diabetic controls. BMD T-scores were determined for the lumbar spine (LS), total hip (TH) and femoral neck (FN). RESULTS: T1D participants had median diabetes duration of 54 [52, 58] years, 41 (55%) were females, and mean A1c was 7.3 ±â€¯0.8%. T1D females had higher LS T-scores compared to female controls (-0.3 ±â€¯1.2 vs. -1.1 ±â€¯1.4, p = 0.014), lower FN T-scores (-1.5 ±â€¯1.0 vs. -1.2 ±â€¯0.9, p = 0.042) and more fragility fractures (7 (17%) vs. 1 (2%), p = 0.021). In T1D, higher A1c was associated with higher adjusted odds of fragility fracture (p = 0.006). T1D males and controls showed no difference in BMD or fractures. CONCLUSIONS: There were no substantial differences in T-score between T1D and matched controls; however, T1D females showed higher BMD at the LS and possibly paradoxically higher fragility fractures compared to matched controls. These findings suggest that lower T-scores may not be associated with a history of fragility fracture in females with longstanding T1D and that other factors should be investigated.

Uric Acid Levels Correlate with Sensory Nerve Function in Healthy Subjects.

BACKGROUND: High levels of uric acid (UA) are associated with various peripheral neuropathies. Furthermore, uric acid levels have been found to correlate with both the clinical and electrophysiological severity of diabetic sensorimotor polyneuropathy, mainly with sensory functions. OBJECTIVES: To determine whether higher UA levels are associated negatively with nerve function in healthy subjects. METHODS: A total of 126 healthy subjects recruited prospectively for another study were included. We extracted demographic data, body mass index (BMI), blood pressure, Toronto Clinical Neuropathy Score (TCNS), electrophysiological findings, vibration perception thresholds (VPT), and laboratory test results including UA, hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), and lipid levels. RESULTS: The mean age of the cohort was 56 ± 17 years with 56% females. Males had higher UA values compared with females. Univariate beta regression coefficient analysis between UA levels and demographic, clinical, electrophysiological, and laboratory findings showed significant positive correlations with male gender, components of the metabolic syndrome, and with VPT, while an inverse correlation was found with electrophysiological sensory parameters. A multivariate regression model showed positive correlations only with BMI, finger VPT, and triglycerides. CONCLUSION: Higher UA levels correlate with lower sensory nerve function in healthy subjects, expanding the evidence of possible negative influence of UA on peripheral nerves, although a causative role has not yet established.