Search

AIM To examine the impact of the sodium-glucose co-transporter-2 inhibitor, empagliflozin, on plasma and urine metabolites in participants with type 1 diabetes. MATERIAL AND METHODS Participants (n = 40, 50% male, mean age 24.3 years) with type 1 diabetes and without overt evidence of diabetic kidney disease had baseline assessments performed under clamped euglycaemia and hyperglycaemia, on two consecutive days. Participants then proceeded to an 8-week, open-label treatment period with empagliflozin 25 mg/day, followed by repeat assessments under clamped euglycaemia and hyperglycaemia. Plasma and urine metabolites were first grouped into metabolic pathways using MetaboAnalyst software. Principal component analysis was performed to create a representative value for each sufficiently represented metabolic group (false discovery rate ≤ 0.1) for further analysis. RESULTS Of the plasma metabolite groups, tricarboxylic acid (TCA) cycle (P

Aim We assessed whether adding empagliflozin to closed-loop automated insulin delivery could reduce the need for carbohydrate counting in type 1 diabetes (T1D) without worsening glucose control. Materials and methods In an open-label, crossover, non-inferiority trial, 30 adult participants with T1D underwent outpatient automated insulin delivery interventions with three random sequences of prandial insulin strategy days: carbohydrate counting, simple meal announcement (no carbohydrate counting), and no meal announcement. During each sequence of prandial insulin strategies, participants were randomly assigned empagliflozin (25mg/day) or not, and crossed over to the comparator. Mean glucose for carbohydrate counting without empagliflozin (control) was compared to no meal announcement with empagliflozin (in the primary non-inferiority comparison) and simple meal announcement with empagliflozin (in the conditional primary non-inferiority comparison). Results Participants were aged 40±15 years, had 27±15 years diabetes duration, and HbA1c 7.6±0.7% (59±8 mmol/mol). The system with no meal announcement and empagliflozin was not non-inferior (and thus reasonably considered inferior) to the control arm (mean glucose 10.0±1.6 vs 8.5±1.5 mmol/L, non-inferiority p=0.94), while simple meal announcement and empagliflozin was non-inferior (8.5±1.4 mmol/L, non-inferiority p=0.003). Use of empagliflozin on the background of automated insulin delivery with carbohydrate counting was associated with lower mean glucose, corresponding to a 14% greater time in target range. While no ketoacidosis was observed, mean fasting ketones levels were higher on empagliflozin (0.22±0.18 vs 0.13±0.11 mmol/L, p Conclusions Empagliflozin added to automated insulin delivery has the potential to eliminate the need for carbohydrate counting, improves glycemic control in conjunction with carbohydrate counting but does not allow for the elimination of meal announcement. This article is protected by copyright. All rights reserved.

Physical activity (PA) is recommended for patients with diabetes to improve glycemic control. In prediabetes and T2D there is a causal relationship between PA and peripheral nerve health; however, the effect of PA on nerve structure and function in longstanding T1D is unclear. We aimed to determine the relationship between PA and small nerve fiber morphology, large nerve fiber function and cardiac autonomic function in this population. Data from 75 participants was collected as part of the Canadian Study of Longevity in T1D. Participants completed a physical exam, medical history and neuropathy assessment including nerve conduction studies (NCS), corneal confocal microscopy measurement of corneal nerve fiber length (CNFL) and assessment of heart rate variability. Participants also reported their daily PA from the preceding 12-months. There were 41(55%) female participants, mean ± SD age was 66 ± 8 years, median duration of diabetes was 54 [52,58] years, BMI was 26.6 ± 3.8, HbA1c of 7.3 ± 0.8. 65(89%) participants met the criteria for diagnosis of diabetic neuropathy. The weekly mean PA time was 156 ± 132 min and 35(47%) reported ≧150 minutes/week. PA time was associated with a greater cooling detection threshold (r=0.24; p=0.043), higher 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). Vibration perception threshold at the toe was inversely associated with PA (r=-0.31; p=0.025), whereas there was no association at the finger. There was no association between PA time and heart rate variability (r=-0.040; p=0.74) or CNFL (r=0.23; p=0.055). Linear regression for NCS, adjusting for age and A1c, showed that for each 30 min of PA there was an 0.09 mv higher peroneal amplitude (p=0.032) and 0.048 ms lower peroneal F-wave latency (p=0.022). In individuals with longstanding T1D, PA is associated with substantially better large nerve fiber function in the lower limbs and some better measures of small nerve fiber function. Disclosure E. J. H. Lewis: Board Member; Self; Nutarniq Corp, Board Member; Spouse/Partner; Nutarniq Corp, Research Support; Self; Canadian Institutes of Health Research. B. A. Perkins: Advisory Panel; Self; Abbott Diabetes, Boehringer Ingelheim International GmbH, Insulet Corporation, Novo Nordisk Canada Inc., Other Relationship; Self; Abbott Diabetes, Medtronic, Novo Nordisk Canada Inc. L. Lovblom: None. S. O. Lanctot: None. D. Scarr: None. N. Cardinez: None. A. Weisman: None. M. H. Brent: Advisory Panel; Self; Novartis Pharmaceuticals Canada Inc., Roche Canada, Research Support; Self; Bayer AG, Novartis Pharmaceuticals Canada Inc. V. Bril: Advisory Panel; Self; Akcea Therapeutics, Alnylam Pharmaceuticals, Inc., CSL Behring, Sanofi Genzyme, Consultant; Self; Janssen Research & Development, LLC, Research Support; Self; Takeda Canada. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Scientific Affairs, LLC., Lilly Diabetes, Merck & Co., Inc., Mitsubishi-Tanabe, Maze Inc, Prometic, Novo Nordisk, Sanofi. Funding JDRF (17-2013-312)

We aimed to assess whether adding Empa to the artificial pancreas can alleviate the burden of carbohydrate counting without degrading glucose control. We conducted a randomized, open-label, crossover, non-inferiority trial in 30 adults with T1D (age 40±15 years, A1c 7.6±0.7%). Each participant used the artificial pancreas on 5 non-consecutive days at home (9-14 hours/day) with: Empa 25mg and (i) carbohydrate counting, (ii) simple meal announcements (pressing a button, no carbohydrate counting), and (iii) no meal announcements (fully automated), and with: no Empa and (iv) carbohydrate counting (control arm) and (v) simple meal announcements. The fully automated artificial pancreas with Empa was inferior to the artificial pancreas with carbohydrate counting without Empa (mean glucose 10.0±1.6 vs. 8.5±1.5 mmol/L, p Disclosure A. Haidar: Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc., Eli Lilly and Company. J. Yale: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Board Member; Self; Diagnos. Research Support; Self; Bayer Inc., Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Medtronic, Novo Nordisk A/S, Sanofi. L. Lovblom: None. N. Cardinez: None. A. Orszag: None. C.M. Falappa: None. N. Gouchie-Provencher: None. A. El Fathi: None. D. Eldelekli: None. D. Scarr: None. B.A. Perkins: Consultant; Self; Abbott, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Other Relationship; Self; Medtronic. Funding Diabetes Canada

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.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.Participants were 66 ± 8 years old with diabetes duration of 54 [52,58] years, HbAIn 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.

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.

OBJECTIVE Type 1 diabetes carries a significant risk for cardiovascular mortality, but it is unclear how atherosclerosis associates with microvascular complications. We aimed to determine the relationships between atherosclerotic burden and neuropathy, retinopathy, and diabetic kidney disease (DKD) in adults with a ≥50-year history of type 1 diabetes. RESEARCH DESIGN AND METHODS Adults with type 1 diabetes (n = 69) underwent coronary artery calcification (CAC) volume scoring by wide-volume computerized tomography. Microvascular complications were graded as follows: neuropathy by clinical assessment, electrophysiology, vibration and cooling detection thresholds, heart rate variability, and corneal confocal microscopy; retinopathy by ultra–wide-field retinal imaging; and DKD by renal hemodynamic function measured by inulin and para-aminohippurate clearance at baseline and after intravenous infusion of angiotensin II. The cohort was dichotomized to high (≥300 Agatston units [AU]) or low ( RESULTS CAC scores were higher in participants with type 1 diabetes (median Agatston score 1,000 [interquartile range = 222, 2,373] AU vs. 1 [0.75] AU in comparators, P < 0.001). In participants with type 1 diabetes, high CAC scores associated with markers of neuropathy and retinopathy, but not with DKD, or renal hemodynamic function at baseline or in response to angiotensin II. CONCLUSIONS The presence of high CAC in adults with longstanding type 1 diabetes was associated with large nerve fiber neuropathy and retinopathy but not with renal hemodynamic function, suggesting that neuropathy, retinopathy, and macrovascular calcification share common risk factors.

We evaluated the performance of creatinine-based estimating equations for glomerular filtration rate (GFR) in adults with type 2 diabetes without nephropathy compared to measured GFR by gold-standard inulin clearance methods. mGFR was performed 4 times over the course of a 1 month treatment period in the context of a small randomized placebo-controlled trial measuring the intrarenal hemodynamics function responses to the dipeptidyl peptidase 4 inhibitor sitagliptin. Thirty-two adults with type 2 diabetes (randomized 1:1 to placebo or sitagliptin) completed the trial, and all participants underwent mGFR by inulin clearance and GFR estimated by serum creatinine using the MDRD (eGFRMDRD) and CKD-EPI (eGFRCKD-EPI). Performance of eGFR equations was evaluated using measurements of bias (mean difference), precision (standard deviations [SD]), and inaccuracy (defined as the proportion of eGFR that differed by >20% of mGFR). The effects of treatment and time on bias were evaluated using linear mixed effects models. Mean±SD age, diabetes duration, HbA1c, and BMI was 60±8 years, 9±7 years, 7.2±0.8%, and 31.0±6.2 kg/m2, respectively, and 12(38%) participants were female. At baseline, mean mGFR was 113±24, mean eGFRMDRD was 93±12, and mean eGFRCKD-EPI was 94±9, all in mL/min/1.73m2. When all 128 observations (32 participants measured 4 times) were evaluated, both equations substantially underestimated mGFR. For the eGFRMDRD, mean bias was -21.5 mL/min/1.73m2, precision was 22.7 mL/min/1.73m2, and 46% of observations differed by more than 20%. Results were similar for eGFRCKD-EPI. No time or treatment effects on bias were observed. In adults with type 2 diabetes, eGFR equations underestimated mGFR, lacked precision and accuracy, and had lower performance at higher ranges of mGFR. More accurate measures of kidney function may improve clinical decision-making in adults with type 2 diabetes. Disclosure J.A. Lovshin: Other Relationship; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi, Merck Sharp & Dohme Corp.. Other Relationship; Self; Novo Nordisk Inc.. L. Lovblom: None. P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. Y. Lytvyn: None. H. Rajasekeran: None. D. Scarr: None. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc. D. Cherney: Consultant; Self; AbbVie Inc.. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company. Consultant; Self; Sanofi. Other Relationship; Self; Merck & Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Self; Janssen Pharmaceuticals, Inc..

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 insulin pump basal requirements. Thirty-three participants from two insulin pump studies were analyzed. Twenty were obtained from a methodologically-ideal semi-automated 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 validation set). Prevalence was determined for the total cohort and the individual trials using the standard definition of an increase in insulin exceeding 20% and lasting 90 minutes or more. Among cases, time of onset and percent change in the magnitude of basal delivery was determined. Seventeen of the 33 (52%) participants experienced the dawn phenomenon [11 of 20 (55%) in the derivation set, 6 of 13 (46%) in the validation set]. Time of onset was 3:00 am [IQR; 3:00, 4:15 am] in the derivation set and 3:00 am [3:00, 4:00 am] in the validation set. The magnitude of the dawn phenomenon was a 58.1% [28.8, 110.6%] increase in insulin requirements in the derivation set and 65.5% [45.6%, 87.4%] in the validation set. The dawn phenomenon occurs in approximately half of patients with type 1 diabetes, when present it has predictable timing of onset (generally 3am), and has substantial but highly variable magnitude. These findings imply that optimization of glycemic control requires clinical emphasis on fasted overnight basal insulin assessment. Disclosure I. Ostrovski: None. L. Lovblom: None. D. Scarr: None. A. Weisman: None. A. Orszag: None. E. D'Aoust: None. A. Haidar: Consultant; Self; Eli Lilly and Company. Research Support; Self; AgaMatrix, Medtronic MiniMed, Inc. R. Rabasa-Lhoret: Consultant; Self; Abbott, Amgen Inc.. Other Relationship; Self; Animas Corporation. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Diabetes Canada, Canadian Institutes of Health Research. Other Relationship; Self; Eli Lilly and Company. Consultant; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; JDRF. Consultant; Self; Medtronic. Other Relationship; Self; Merck & Co., Inc., Novo Nordisk Inc., Sanofi-Aventis. Advisory Panel; Self; Sanofi US. Research Support; Self; National Institutes of Health, Cystic Fibrosis Canada, Société Francophone du Diabéte. L. Legault: Advisory Panel; Self; Insulet Corporation. Research Support; Self; Merck & Co., Inc., Sanofi. Advisory Panel; Self; Medtronic. Other Relationship; Self; Eli Lilly and Company. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc..

Neuropathy and neuropathic pain are common complications in T1D. We aimed to determine if sex-specific differences in the prevalence of neuropathic pain and neuropathy exist in patients with longstanding T1D. In Phase 1 of the study, 361 Canadians with ≥50 years of T1D completed questionnaires which included subjective assessment for neuropathy defined by Michigan Neuropathy Screening Instrument Questionnaire score ≥3, termed NEUROPATHYMNSI-Q. In Phase 2 of the study, we studied a sub-cohort of 75 diabetes participants and 75 age- and sex-matched nondiabetic controls who completed objective neurological examinations which included assessment of abnormal nerve conduction studies (NCS) for neuropathy, termed NEUROPATHYNCS. In the Phase 1 cohort, more females than males reported neuropathic pain [87(42%) vs. 41(27%); p=0.003)], but the presence of neuropathy (NEUROPATHYMNSI-Q) did not differ by sex [87(42%) females vs. 66(43%) males, p=0.82], and thus neuropathic pain was independent of the presence of neuropathy [adjusted OR for neuropathic pain in females compared to males, 2.7 (1.4-5.0; p=0.002)]. In the Phase 2 participants, neuropathic pain was similar between the sexes (29% females vs. 21% males, p=0.43) while NEUROPATHYNCS was less prevalent among females (83% females vs. 97% males, p=0.05). Though not statistically significant, in a combined analysis of Phase 2 participants adjusted for NEUROPATHYNCS, females had a tendency to a higher adjusted OR for neuropathic pain compared to males [OR 2.0 (95% CI 0.8-4.7), p=0.11]. In conclusion, in patients with longstanding TID, neuropathic pain appears to be greater among females compared to males independent of the presence of neuropathy. Further research using larger datasets with objective neuropathy measures are required to further confirm and address these sex-specific differences. Disclosure N. Cardinez: None. L. Lovblom: None. J. Bai: None. A. Abraham: None. E.J. Lewis: Employee; Self; Nutarniq Corp. D. Scarr: None. J.A. Lovshin: Other Relationship; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi, Merck Sharp & Dohme Corp.. Other Relationship; Self; Novo Nordisk Inc.. Y. Lytvyn: None. G. Boulet: Advisory Panel; Self; Medtronic, Sanofi, Novo Nordisk Inc.. Other Relationship; Self; Janssen Global Services, LLC., Abbott. M. Farooqi: None. A. Orszag: None. A. Weisman: None. H.A. Keenan: Research Support; Self; Sanofi. Employee; Self; Sanofi Genzyme. M.H. Brent: Research Support; Self; Novartis Canada. Advisory Panel; Self; Novartis Canada. Research Support; Self; Bayer Canada. Advisory Panel; Self; Bayer Canada, Allergan Canada. Research Support; Self; Roche Canada. N. Paul: None. V. Bril: Consultant; Self; Alexion Pharmaceuticals, Inc.. Research Support; Self; CSL Behring, Grifols. Advisory Panel; Self; CSL Behring. Consultant; Self; Grifols. Research Support; Self; Shire. Advisory Panel; Self; Pfizer Inc. D. Cherney: Consultant; Self; AbbVie Inc.. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company. Consultant; Self; Sanofi. Other Relationship; Self; Merck & Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Self; Janssen Pharmaceuticals, Inc. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc..

Aim Neuropathy and neuropathic pain are common complications of type 1 diabetes (T1D). We aimed to determine if sex-specific differences in neuropathic pain are present in adults with longstanding T1D. Methods Canadians with ≥50 years of T1D (n = 361) completed health history questionnaires that included assessment of neuropathy (defined by Michigan Neuropathy Screening Instrument questionnaire components ≥3; NEUROPATHYMNSI-Q) and neuropathic pain. Multivariable logistic regression was used to determine sex-differences in neuropathic pain controlling for neuropathy. Results Participants had mean age 66 ± 9 years, median diabetes duration 53[51,58] years, mean HbA1c 7.5 ± 1.0%, and 207(57%) were female. Neuropathic pain was present in 128(36%) of all participants, more prevalent among those with NEUROPATHYMNSI-Q compared to those without [96(63%) vs. 31(15%), p Conclusions We demonstrated a novel sex-specific difference in neuropathic pain in females compared to males with longstanding T1D, independent of the presence of neuropathy. Further research using more objective measures of neuropathy than the MNSI is justified to further understand this sex-specific difference.

OBJECTIVE Central adiposity is considered to be an important cardiorenal risk factor in the general population and in type 1 diabetes. We sought to determine the relationship between central adiposity and intrarenal hemodynamic function in adults with long-standing type 1 diabetes with and without diabetic nephropathy (DN). RESEARCH DESIGN AND METHODS Patients with type 1 diabetes (n = 66, duration ≥50 years) and age-/sex-matched control subjects (n = 73) were studied. The cohort was stratified into 44 DN Resistors (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73 m2 and RESULTS Whereas measures of adiposity did not associate with GFRINULIN or ERPFPAH in healthy control subjects, trunk fat mass inversely correlated with GFRINULIN (r = −0.46, P < 0.0001) and ERPFPAH (r = −0.31, P = 0.01) and positively correlated with RVR (r = 0.53, P = 0.0003) in type 1 diabetes. In analyses stratified by DN status, greater central adiposity related to lower GFRINULIN values in DN and DN Resistors, but the relationships between central adiposity and ERPFPAH and RVR were attenuated and/or reversed in patients with DN compared with DN Resistors. CONCLUSIONS The adiposity-intrarenal hemodynamic function relationship may be modified by the presence of type 1 diabetes and DN, requiring further study of the mechanisms by which adiposity influences renal hemodynamic function.

Aims/hypothesis Small cohort studies raise the hypothesis that corneal nerve abnormalities (including corneal nerve fibre length [CNFL]) are valid non-invasive imaging endpoints for diabetic sensorimotor polyneuropathy (DSP). We aimed to establish concurrent validity and diagnostic thresholds in a large cohort of participants with and without DSP. Methods Nine hundred and ninety-eight participants from five centres (516 with type 1 diabetes and 482 with type 2 diabetes) underwent CNFL quantification and clinical and electrophysiological examination. AUC and diagnostic thresholds were derived and validated in randomly selected samples using receiver operating characteristic analysis. Sensitivity analyses included latent class models to address the issue of imperfect reference standard. Results Type 1 and type 2 diabetes subcohorts had mean age of 42 ± 19 and 62 ± 10 years, diabetes duration 21 ± 15 and 12 ± 9 years and DSP prevalence of 31% and 53%, respectively. Derivation AUC for CNFL was 0.77 in type 1 diabetes (p

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 ± 0.8%. T1D females had higher LS T-scores compared to female controls (−0.3 ± 1.2 vs. −1.1 ± 1.4, p = 0.014), lower FN T-scores (−1.5 ± 1.0 vs. −1.2 ± 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.

Objective 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 33 participants from two sensor-augmented insulin pump studies were analyzed. Twenty participants were obtained from a methodologically-ideal semi-automated 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 the individual trials using the standard definition of an increase in insulin exceeding 20% and lasting 90 minutes or more. Among cases, time of onset and percent change in the magnitude of basal delivery were determined. Results Seventeen participants (52%) experienced the dawn phenomenon [11/20 (55%) in the derivation set and 6/13 (46%) in the confirmation set]. Time of onset was 3:00 am [IQR; 3:00, 4:15 am] in the derivation set and 3:00 am [3:00, 4:00 am] in the confirmation set. The magnitude of the dawn phenomenon was a 58.1% [28.8, 110.6%] increase in insulin requirements in the derivation set and 65.5% [45.6%, 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 3am) and has substantial but highly variable magnitude. These findings imply that optimization of glycemic control requires clinical emphasis on fasted overnight basal insulin assessment.

s / Can J Diabetes 39 (2015) 529e547 544 clinical and electrophysiological criteria. CNFL was determined by manual (CNFLManual, reference standard) and automated (CNFLAuto) protocols, and results were compared for correlation and agreement using Spearman coefficients and the method of Bland and Altman. Associations with neuropathy severity were evaluated by analysis-of-variance. Results: Participants demonstrated broad variability in clinical characteristics associated with neuropathy. The mean age, diabetes duration and HbA1C was 53.1 17.6 years, 15.9 12.6 years, and 7.4 1.6%, respectively, and 218 (47%) individuals had neuropathy. Mean CNFLManual was 15.1 4.9 mm/mm2, and mean CNFLAuto was 10.5 3.71 mm/mm2 (CNFLAuto underestimation bias, 4.58 2.65 mm/mm2 corresponding to 36.6 22.1%). Bias was similar across healthy volunteer, type 1, and type 2 diabetes subgroups. Levels of CNFLAuto and CNFLManual were both associated with neuropathy severity (ANOVA p

Objective In vivo Corneal Confocal Microscopy (IVCCM) is a validated, non-invasive test for diabetic sensorimotor polyneuropathy (DSP) detection, but its utility is limited by the image analysis time and expertise required. We aimed to determine the inter- and intra-observer reproducibility of a novel automated analysis program compared to manual analysis. Methods In a cross-sectional diagnostic study, 20 non-diabetes controls (mean age 41.4±17.3y, HbA1c 5.5±0.4%) and 26 participants with type 1 diabetes (42.8±16.9y, 8.0±1.9%) underwent two separate IVCCM examinations by one observer and a third by an independent observer. Along with nerve density and branch density, corneal nerve fibre length (CNFL) was obtained by manual analysis (CNFLMANUAL), a protocol in which images were manually selected for automated analysis (CNFLSEMI-AUTOMATED), and one in which selection and analysis were performed electronically (CNFLFULLY-AUTOMATED). Reproducibility of each protocol was determined using intraclass correlation coefficients (ICC) and, as a secondary objective, the method of Bland and Altman was used to explore agreement between protocols. Results Mean CNFLManual was 16.7±4.0, 13.9±4.2 mm/mm2 for non-diabetes controls and diabetes participants, while CNFLSemi-Automated was 10.2±3.3, 8.6±3.0 mm/mm2 and CNFLFully-Automated was 12.5±2.8, 10.9 ± 2.9 mm/mm2. Inter-observer ICC and 95% confidence intervals (95%CI) were 0.73(0.56, 0.84), 0.75(0.59, 0.85), and 0.78(0.63, 0.87), respectively (p = NS for all comparisons). Intra-observer ICC and 95%CI were 0.72(0.55, 0.83), 0.74(0.57, 0.85), and 0.84(0.73, 0.91), respectively (p