for Journals by Title or ISSN
for Articles by Keywords
Followed Journals
Journal you Follow: 0
Sign Up to follow journals, search in your chosen journals and, optionally, receive Email Alerts when new issues of your Followed Journals are published.
Already have an account? Sign In to see the journals you follow.
Journal Cover Diabetes Care
  [SJR: 5.827]   [H-I: 284]   [463 followers]  Follow
   Full-text available via subscription Subscription journal
   ISSN (Print) 0149-5992 - ISSN (Online) 1935-5548
   Published by American Diabetes Association Homepage  [4 journals]
  • Morning Enzymatic Activity of DPP-4 Is Differentially Altered by Sleep
           Loss in Women and Men
    • Authors: Rangtell; F. H.; Schmidt, F.; Würfel, J.; Karamchedu, S.; Andersson, P.; Vogel, H.; Benedict, C.
      Keywords: Integrated Physiology-Other Hormones
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1762
      Issue No: Vol. 41, No. 2 (2018)
  • Obstructive Sleep Apnea and Diabetes Independently Add to Cardiovascular
           Risk After Coronary Revascularization
    • Authors: Koo; C. Y.; Drager, L. F.; Sethi, R.; Ho, H.-H.; Hein, T.; Jim, M.-H.; Tai, B.-C.; Zhang, J.-J.; Lee, C.-H.; on behalf of the Sleep Stent Study Investigators
      Keywords: Complications-Macrovascular-Atherosclerotic Cardiovascular Disease and Human Diabetes
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-0759
      Issue No: Vol. 41, No. 2 (2018)
  • Twin Pregnancy With Gestational Diabetes Mellitus: A Double Whammy'
    • Authors: Ooi; S.; Wong, V. W.
      Keywords: Pregnancy-Clinical/Epidemiology
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-2227
      Issue No: Vol. 41, No. 2 (2018)
  • Comment on Edelman and Polonsky. Type 2 Diabetes in the Real World: The
           Elusive Nature of Glycemic Control. Diabetes Care 2017;40:1425-1432
    • Authors: Giugliano; D.; Maiorino, M. I.; Bellastella, G.; Esposito, K.
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1826
      Issue No: Vol. 41, No. 2 (2018)
  • Response to Comment on Edelman and Polonsky. Type 2 Diabetes in the Real
           World: The Elusive Nature of Glycemic Control. Diabetes Care
    • Authors: Edelman; S. V.; Polonsky, W. H.
      Keywords: Epidemiology-Other
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dci17-0050
      Issue No: Vol. 41, No. 2 (2018)
  • Comment on Lent et al. All-Cause and Specific-Cause Mortality Risk After
           Roux-en-Y Gastric Bypass in Patients With and Without Diabetes. Diabetes
           Care 2017;40:1379-1385
    • Authors: Pontiroli; A. E.; Zakaria, A. S.
      Keywords: Obesity-Human
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1895
      Issue No: Vol. 41, No. 2 (2018)
  • Response to comment on Lent et al. All-Cause and Specific-Cause Mortality
           Risk After Roux-en-Y Gastric Bypass in Patients With and Without Diabetes.
           Diabetes Care 2017;40:1379-1385
    • Authors: Lent; M. R.; Benotti, P. N.; Wood, G. C.
      Keywords: Obesity-Human
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dci17-0055
      Issue No: Vol. 41, No. 2 (2018)
  • In This Issue of Diabetes Care
    • Pages: 207 - 208
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc18-ti02
      Issue No: Vol. 41, No. 2 (2018)
  • The National Diabetes Education Program at 20 Years: Lessons Learned and
           Plans for the Future
    • Authors: Siminerio; L. M.; Albright, A.; Fradkin, J.; Gallivan, J.; McDivitt, J.; Rodriguez, B.; Tuncer, D.; Wong, F.
      Pages: 209 - 218
      Abstract: The National Diabetes Education Program (NDEP) was established to translate findings from diabetes research studies into clinical and public health practice. Over 20 years, NDEP has built a program with partnership engagement that includes science-based resources for multiple population and stakeholder audiences. Throughout its history, NDEP has developed strategies and messages based on communication research and relied on established behavior change models from health education, communication, and social marketing. The program’s success in continuing to engage diverse partners after 20 years has led to time-proven and high-quality resources that have been sustained. Today, NDEP maintains a national repository of diabetes education tools and resources that are high quality, science- and audience-based, culturally and linguistically appropriate, and available free of charge to a wide variety of audiences. This review looks back and describes NDEP’s evolution in transforming and communicating diabetes management and type 2 diabetes prevention strategies through partnerships, campaigns, educational resources, and tools and identifies future opportunities and plans.
      Keywords: Diabetes Education
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-0976
      Issue No: Vol. 41, No. 2 (2018)
  • Mortality Reduction in EMPA-REG OUTCOME Trial: Beyond the Antidiabetes
    • Authors: Suissa S.
      Pages: 219 - 223
      Abstract: Two recent large-scale cardiovascular outcome trials, a now common tool in assessing the safety of pharmacological treatments for type 2 diabetes, reported significant reductions in all-cause mortality. In EMPA-REG OUTCOME [BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients], patients who received the SGLT2 inhibitor empagliflozin had a notable reduction of 9.2 deaths per 1,000 per year, while LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results—A Long Term Evaluation) found that the patients receiving the GLP-1 receptor agonist liraglutide had a reduction of 3.7 deaths per 1,000 per year. The hypotheses to explain the sizable mortality reduction in EMPA-REG OUTCOME have mainly focused on the potential cardiovascular mechanisms of empagliflozin, but none considered its expected antidiabetes effects. I estimated the portion of the reduction in mortality observed in EMPA-REG OUTCOME expected to be a result of its antidiabetes effects, as measured by glycemic control and the need for additional antidiabetes medication, and contrasted it with LEADER. With use of the mean 0.45% reduction in HbA1c with empagliflozin compared with placebo in EMPA-REG OUTCOME, the rate reduction of 9.2 deaths per 1,000 per year would be expected to be at most 4.5 deaths per 1,000 per year, leaving 4.7 deaths per 1,000 per year otherwise explained. On the other hand, LEADER’s rate reduction of 3.7 deaths per 1,000 per year with liraglutide would be expected to be 3.5 by virtue of its effect on HbA1c, leaving 0.2 deaths per 1,000 per year explained otherwise. Similar results were found using the need for additional antidiabetes treatment during follow-up to measure the antidiabetes impact. In conclusion, the expected antidiabetes effects of empagliflozin and liraglutide on the reduction in mortality are important. However, empagliflozin appears to have significant additional effects on survival, possibly due to specific cardiovascular mechanisms, which merit further investigation.
      Keywords: Epidemiology-Cardiovascular Disease
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1059
      Issue No: Vol. 41, No. 2 (2018)
  • Teasing Diabetes Apart, One Locus at a Time
    • Authors: Leslie; R. D.; Grant, S. F. A.
      Pages: 224 - 226
      Keywords: Genetics-Type 1 Diabetes
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dci17-0046
      Issue No: Vol. 41, No. 2 (2018)
  • Discovery, Knowledge, and Action--Diabetes in Pregnancy Across the
           Translational Spectrum: The 2016 Norbert Freinkel Award Lecture
    • Authors: McIntyre H. D.
      Pages: 227 - 232
      Abstract: The Norbert Freinkel Award is given in memory of Norbert Freinkel, a dedicated and insightful investigator and gifted writer, to honor a researcher who has made outstanding contributions, including scientific publications and presentations, to the understanding and treatment of diabetes in pregnancy. H. David McIntyre, MD, FRACP, Director of Obstetric Medicine at Mater Health Services and Head of the Mater Clinical Unit at The University of Queensland in Brisbane, Australia, received the prestigious award at the American Diabetes Association's 76th Scientific Sessions, 10–14 June 2016, in New Orleans, LA. He presented the Norbert Freinkel Award Lecture, "Discovery, Knowledge, and Action—Diabetes in Pregnancy Across the Translational Spectrum," on Saturday, 11 June 2016.
      Keywords: Diabetes Education
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dci17-0056
      Issue No: Vol. 41, No. 2 (2018)
  • Diabetes in Youth--Looking Backwards to Inform the Future: Kelly West
           Award Lecture 2017
    • Authors: Dabelea D.
      Pages: 233 - 240
      Abstract: The Kelly West Award for Outstanding Achievement in Epidemiology is presented in honor of the memory of Kelly M. West, widely regarded as the "father of diabetes epidemiology." Harry Keen described West as characterized by "generosity of spirit, deeply human and humorous, deliberate of address, modest, conciliatory and untiringly persevering. Few people have done so much to change the landscape of diabetes" (1). The award and lecture recognize a leading epidemiologist in the field of diabetes. Dana Dabelea, MD, PhD, received this award at the American Diabetes Association’s 77th Scientific Sessions, 9–13 June 2017, in San Diego, CA. She presented the Kelly West Award Lecture, "Diabetes in Youth—Looking Backwards to Inform the Future," on Sunday, 11 June 2017.
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dci17-0031
      Issue No: Vol. 41, No. 2 (2018)
  • The Role of Diabetes Care and Its Contributions to the Field of Diabetes:
           A Profile in Progress
    • Authors: Reynolds; L.; Genuth, S. M.
      Pages: 241 - 249
      Keywords: Health Care Delivery-Economics, Profiles in Progress
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dci17-0021
      Issue No: Vol. 41, No. 2 (2018)
  • Five-Year Cost-effectiveness of the Multidisciplinary Risk Assessment and
           Management Programme-Diabetes Mellitus (RAMP-DM)
    • Authors: Jiao; F. F.; Fung, C. S. C.; Wan, E. Y. F.; Chan, A. K. C.; McGhee, S. M.; Kwok, R. L. P.; Lam, C. L. K.
      Pages: 250 - 257
      Abstract: OBJECTIVETo estimate the cost-effectiveness of the multidisciplinary Risk Assessment and Management Programme–Diabetes Mellitus (RAMP-DM) in primary care patients with type 2 diabetes in comparison with usual primary care in a cohort with 5 years’ follow-up.RESEARCH DESIGN AND METHODSWe conducted a prospective cohort study among 17,140 propensity score–matched participants in RAMP-DM and those under usual primary care. The effectiveness measures were cumulative incidences of complications and all-cause mortality over 5 years. In a bottom-up approach, we estimated the program costs of RAMP-DM and health service utilization from the public health service provider’s perspective. The RAMP-DM program costs included the setup costs, ongoing intervention costs, and central administrative costs. We calculated the incremental cost-effectiveness ratio by dividing the incremental costs by the incremental effectiveness of the RAMP-DM group compared with those of the usual-care group.RESULTSThere were significantly lower cumulative incidences of individual on any complications (15.34% vs. 28.65%, P < 0.001) and all-cause mortality (7.96% vs. 21.35%, P < 0.001) in the RAMP-DM group compared with the usual-care group. The mean program cost of RAMP-DM was 157 U.S. dollars (range 66–209) per participant over 5 years. The costs of health service utilization among participants in RAMP-DM group was 7,451 USD less than that of the usual-care group, resulting in a net savings of 7,294 USD per individual.CONCLUSIONSRAMP-DM added to usual primary care was a cost-saving intervention in managing diabetes in patients over 5 years. These findings support the integration of RAMP-DM as part of routine primary care for all patients with diabetes.
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1149
      Issue No: Vol. 41, No. 2 (2018)
  • Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in
           Subjects With Type 2 Diabetes (SUSTAIN 3): A 56-Week, Open-Label,
           Randomized Clinical Trial
    • Authors: Ahmann; A. J.; Capehorn, M.; Charpentier, G.; Dotta, F.; Henkel, E.; Lingvay, I.; Holst, A. G.; Annett, M. P.; Aroda, V. R.
      Pages: 258 - 266
      Abstract: OBJECTIVETo compare the efficacy and safety of once-weekly semaglutide 1.0 mg s.c. with exenatide extended release (ER) 2.0 mg s.c. in subjects with type 2 diabetes.RESEARCH DESIGN AND METHODSIn this phase 3a, open-label, parallel-group, randomized controlled trial, 813 subjects with type 2 diabetes taking oral antidiabetic drugs were randomized (1:1) to semaglutide 1.0 mg or exenatide ER 2.0 mg for 56 weeks. The primary end point was change from baseline in HbA1c at week 56.RESULTSMean HbA1c (8.3% [67.7 mmol/mol] at baseline) was reduced by 1.5% (16.8 mmol/mol) with semaglutide and 0.9% (10.0 mmol/mol) with exenatide ER (estimated treatment difference vs. exenatide ER [ETD] –0.62% [95% CI –0.80, –0.44] [–6.78 mmol/mol (95% CI –8.70, –4.86)]; P < 0.0001 for noninferiority and superiority). Mean body weight (95.8 kg at baseline) was reduced by 5.6 kg with semaglutide and 1.9 kg with exenatide ER (ETD –3.78 kg [95% CI –4.58, –2.98]; P < 0.0001). Significantly more subjects treated with semaglutide (67%) achieved HbA1c
      Keywords: Clinical Therapeutics/New Technology-Non-Insulin Injectables
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-0417
      Issue No: Vol. 41, No. 2 (2018)
  • Predictors of Quality of Life and Other Patient-Reported Outcomes in the
           PANORAMA Multinational Study of People With Type 2 Diabetes
    • Authors: Bradley; C.; Eschwege, E.; de Pablos-Velasco, P.; Parhofer, K. G.; Simon, D.; Vandenberghe, H.; Gönder-Frederick, L.
      Pages: 267 - 276
      Abstract: OBJECTIVEPANORAMA, a nine-country cross-sectional type 2 diabetes study, investigated factors associated with quality of life (QoL), health status, and other patient-reported outcome measures (PROMs).RESEARCH DESIGN AND METHODSPatients were randomly or consecutively selected from primary/secondary care. PROMs included the Audit of Diabetes-Dependent Quality of Life (ADDQoL) (generic QoL item and average weighted impact [AWI] scores), Diabetes Treatment Satisfaction Questionnaire (DTSQ) (patient- and physician-completed), Hypoglycemia Fear Survey-II worry subscale, and the EuroQoL–5 Dimension visual analog scale (EQ-VAS) measuring patient-reported health. Multivariable linear regression analyses determined predictors of each PROM including patient characteristics, physician-reported adherence, complications, and glycosylated hemoglobin.RESULTSIn 5,813 patients, mean PROM scores indicated that generic QoL approximated "good" (0.93); perceived impact of diabetes on QoL was negative (AWI –1.69). Treatment satisfaction exceeded physicians’ estimates (patient-reported: 29.76; physician-estimated: 27.75), but so did patients’ perceived frequency of hypo-/hyperglycemia. Worry about hypoglycemia (13.27) was apparent. Intensifying treatments to three oral agents or insulin regimens predicted worse QoL (AWI P < 0.01). Insulin alone use predicted worse QoL (generic P < 0.02; AWI P < 0.001) and hypoglycemia worry (P < 0.007). No treatment had significant associations with EQ-VAS health status.CONCLUSIONSPredictors for different PROMs differed markedly and provided insights for understanding and improving these important outcomes. Intensive treatment regimens had significant negative associations with all PROMs, except the EQ-VAS health status measure. The findings demonstrate the importance of measuring QoL alongside health status and other patient-reported outcomes when evaluating diabetes treatments with a view to protecting QoL and facilitating adherence and long-term glycemic control.
      Keywords: Psychosocial, Behavioral Medicine
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc16-2655
      Issue No: Vol. 41, No. 2 (2018)
  • Interaction of Dietary and Genetic Factors Influencing Body Iron Status
           and Risk of Type 2 Diabetes Within the EPIC-InterAct Study
    • Authors: Meidtner; K.; Podmore, C.; Kröger, J.; van der Schouw, Y. T.; Bendinelli, B.; Agnoli, C.; Arriola, L.; Barricarte, A.; Boeing, H.; Cross, A. J.; Dow, C.; Ekblom, K.; Fagherazzi, G.; Franks, P. W.; Gunter, M. J.; Huerta, J. M.; Jakszyn, P.; Jenab, M.; Katzke, V. A.; Key, T. J.; Khaw, K. T.; Kühn, T.; Kyro, C.; Mancini, F. R.; Melander, O.; Nilsson, P. M.; Overvad, K.; Palli, D.; Panico, S.; Quiros, J. R.; Rodriguez-Barranco, M.; Sacerdote, C.; Sluijs, I.; Stepien, M.; Tjonneland, A.; Tumino, R.; Forouhi, N. G.; Sharp, S. J.; Langenberg, C.; Schulze, M. B.; Riboli, E.; Wareham, N. J.
      Pages: 277 - 285
      Abstract: OBJECTIVEMeat intake has been consistently shown to be positively associated with incident type 2 diabetes. Part of that association may be mediated by body iron status, which is influenced by genetic factors. We aimed to test for interactions of genetic and dietary factors influencing body iron status in relation to the risk of incident type 2 diabetes.RESEARCH DESIGN AND METHODSThe case-cohort comprised 9,347 case subjects and 12,301 subcohort participants from eight European countries. Single nucleotide polymorphisms (SNPs) were selected from genome-wide association studies on iron status biomarkers and candidate gene studies. A ferritin-related gene score was constructed. Multiplicative and additive interactions of heme iron and SNPs as well as the gene score were evaluated using Cox proportional hazards regression.RESULTSHigher heme iron intake (per 1 SD) was associated with higher ferritin levels (β = 0.113 [95% CI 0.082; 0.144]), but not with transferrin (–0.019 [–0.043; 0.006]) or transferrin saturation (0.016 [–0.006; 0.037]). Five SNPs located in four genes (rs1799945 [HFE H63D], rs1800562 [HFE C282Y], rs236918 [PCK7], rs744653 [SLC40A1], and rs855791 [TMPRSS6 V736A]) were associated with ferritin. We did not detect an interaction of heme iron and the gene score on the risk of diabetes in the overall study population (Padd = 0.16, Pmult = 0.21) but did detect a trend toward a negative interaction in men (Padd = 0.04, Pmult = 0.03).CONCLUSIONSWe found no convincing evidence that the interplay of dietary and genetic factors related to body iron status associates with type 2 diabetes risk above the level expected from the sum or product of the two individual exposures.
      Keywords: Epidemiology-Nutrition
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1080
      Issue No: Vol. 41, No. 2 (2018)
  • Incretin-Based Therapies and the Short-term Risk of Pancreatic Cancer:
           Results From Two Retrospective Cohort Studies
    • Authors: Boniol; M.; Franchi, M.; Bota, M.; Leclercq, A.; Guillaume, J.; van Damme, N.; Corrao, G.; Autier, P.; Boyle, P.
      Pages: 286 - 292
      Abstract: OBJECTIVEConcerns have been raised about a possible increased risk of pancreatic cancer associated with incretin-based therapies. We examined the risk of pancreatic cancer among patients with diabetes prescribed incretin drugs.RESEARCH DESIGN AND METHODSWith the use of public health insurance databases of Belgium and the Lombardy Region, Italy, we created two retrospective cohorts that included adult patients who were first prescribed an incretin drug or another noninsulin antidiabetic drug (NIAD) from 1 July 2008 to 31 December 2013 in Belgium and from 1 January 2008 to 31 December 2012 in the Lombardy Region. The risk of pancreatic cancer was evaluated by multivariate-adjusted Cox models that included time-dependent variables. Adjusted hazard ratios (aHRs) from Belgium and Italy were pooled by using fixed-effects meta-analyses.RESULTSThe cohorts included 525,733 patients with diabetes treated with NIADs and 33,292 with incretin drugs. Results in both cohorts were similar. Eighty-five and 1,589 subjects who developed pancreatic cancer were registered among the incretin and NIAD new users, respectively, which represented an aHR of pancreatic cancer of 2.14 (95% CI 1.71–2.67) among those prescribed an incretin compared with an NIAD. The aHR with a drug use lag exposure of 6 months was 1.69 (1.24–2.32). The aHR decreased from 3.35 (2.32–4.84) in the first 3 months after the first incretin prescription to 2.12 (1.22–3.66) in months 3–5.9, 1.95 (1.20–3.16) in months 6–11.9, and 1.69 (1.12–2.55) after 12 months. Among those prescribed an NIAD, pancreatic cancer occurred mostly within the year after the first prescription. The risk of pancreatic cancer among patients subsequently prescribed insulin was 6.89 (6.05–7.85).CONCLUSIONSThe recent prescription of incretin therapy is associated with an increased risk of pancreatic cancer. The reason for such an increase is likely the consequence of an occult pancreatic cancer that provokes or aggravates diabetes. Studies are warranted for assessing the risk of pancreatic cancer associated with long-term use of incretin drugs.
      Keywords: Epidemiology-Other
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-0280
      Issue No: Vol. 41, No. 2 (2018)
  • Declining Rates of Hospitalization for Selected Cardiovascular Disease
           Conditions Among Adults Aged>=35 Years With Diagnosed Diabetes, U.S.,
    • Authors: Burrows; N. R.; Li, Y.; Gregg, E. W.; Geiss, L. S.
      Pages: 293 - 302
      Abstract: OBJECTIVEReductions in heart attack and stroke hospitalizations are well documented in the U.S. population with diabetes. We extended trend analyses to other cardiovascular disease (CVD) conditions, including stroke by type, and used four additional years of data.RESEARCH DESIGN AND METHODSUsing 1998–2014 National (Nationwide) Inpatient Sample (NIS) data, we estimated the number of discharges having acute coronary syndrome (ACS) (ICD-9 codes 410–411), cardiac dysrhythmia (427), heart failure (428), hemorrhagic stroke (430–432), or ischemic stroke (433.x1, 434, and 436) as first-listed diagnosis and diabetes (250) as secondary diagnosis. Hospitalization rates for adults aged ≥35 years were calculated using estimates from the population with and the population without diabetes from the National Health Interview Survey (NHIS) and age-adjusted to the 2000 U.S. standard population. Joinpoint regression was used to analyze trends and calculate an average annual percentage change (AAPC) with 95% confidence limits (CLs).RESULTSFrom 1998 to 2014, in the population with diabetes, age-adjusted hospitalization rates declined significantly for ACS (AAPC –4.6% per year [95% CL –5.3, –3.8]), cardiac dysrhythmia (–0.7% [–1.1, –0.2]), heart failure (–3.6% [–4.6, –2.7]), hemorrhagic stroke (–1.1% [–1.4, –0.7]), and ischemic stroke (–2.9% [–3.9, –1.8]). In the population without diabetes, rates also declined significantly for these conditions, with the exception of dysrhythmia. By 2014, rates in the population with diabetes population remained two to four times as high as those for the population without diabetes, with the largest difference in heart failure rates.CONCLUSIONSCVD hospitalization rates declined significantly in both the population with diabetes and the population without diabetes. This may be due to several factors, including new or more aggressive treatments and reductions in CVD risk factors and CVD incidence.
      Keywords: Epidemiology-Cardiovascular Disease
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1259
      Issue No: Vol. 41, No. 2 (2018)
  • Reduction in Hypoglycemia With the Predictive Low-Glucose Management
           System: A Long-term Randomized Controlled Trial in Adolescents With Type 1
    • Authors: Abraham; M. B.; Nicholas, J. A.; Smith, G. J.; Fairchild, J. M.; King, B. R.; Ambler, G. R.; Cameron, F. J.; Davis, E. A.; Jones, T. W.; on behalf of the PLGM Study Group
      Pages: 303 - 310
      Abstract: OBJECTIVEShort-term studies with automated systems that suspend basal insulin when hypoglycemia is predicted have shown a reduction in hypoglycemia; however, efficacy and safety have not been established in long-term trials.RESEARCH DESIGN AND METHODSWe conducted a 6-month, multicenter, randomized controlled trial in children and adolescents with type 1 diabetes using the Medtronic MiniMed 640G pump with Suspend before low (predictive low-glucose management [PLGM]) compared with sensor-augmented pump therapy (SAPT) alone. The primary outcome was percentage time in hypoglycemia with sensor glucose (SG)
      Keywords: Clinical Therapeutics/New Technology-Insulin Delivery Systems
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1604
      Issue No: Vol. 41, No. 2 (2018)
  • TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1
    • Authors: Redondo; M. J.; Geyer, S.; Steck, A. K.; Sosenko, J.; Anderson, M.; Antinozzi, P.; Michels, A.; Wentworth, J.; Xu, P.; Pugliese, A.; the Type 1 Diabetes TrialNet Study Group
      Pages: 311 - 317
      Abstract: OBJECTIVEThe phenotypic diversity of type 1 diabetes suggests heterogeneous etiopathogenesis. We investigated the relationship of type 2 diabetes–associated transcription factor 7 like 2 (TCF7L2) single nucleotide polymorphisms (SNPs) with immunologic and metabolic characteristics at type 1 diabetes diagnosis.RESEARCH DESIGN AND METHODSWe studied TrialNet participants with newly diagnosed autoimmune type 1 diabetes with available TCF7L2 rs4506565 and rs7901695 SNP data (n = 810; median age 13.6 years; range 3.3–58.6). We modeled the influence of carrying a TCF7L2 variant (i.e., having 1 or 2 minor alleles) on the number of islet autoantibodies and oral glucose tolerance test (OGTT)–stimulated C-peptide and glucose measures at diabetes diagnosis. All analyses were adjusted for known confounders.RESULTSThe rs4506565 variant was a significant independent factor of expressing a single autoantibody, instead of multiple autoantibodies, at diagnosis (odds ratio [OR] 1.66 [95% CI 1.07, 2.57], P = 0.024). Interaction analysis demonstrated that this association was only significant in participants ≥12 years old (n = 504; OR 2.12 [1.29, 3.47], P = 0.003) but not younger ones (n = 306, P = 0.73). The rs4506565 variant was independently associated with higher C-peptide area under the curve (AUC) (P = 0.008) and lower mean glucose AUC (P = 0.0127). The results were similar for the rs7901695 SNP.CONCLUSIONSIn this cohort of individuals with new-onset type 1 diabetes, type 2 diabetes–linked TCF7L2 variants were associated with single autoantibody (among those ≥12 years old), higher C-peptide AUC, and lower glucose AUC levels during an OGTT. Thus, carriers of the TCF7L2 variant had a milder immunologic and metabolic phenotype at type 1 diabetes diagnosis, which could be partly driven by type 2 diabetes–like pathogenic mechanisms.
      Keywords: Genetics-Type 1 Diabetes
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-0961
      Issue No: Vol. 41, No. 2 (2018)
  • Comparison of {beta}-Cell Function Between Overweight/Obese Adults and
           Adolescents Across the Spectrum of Glycemia
    • Authors: Chen; M. E.; Chandramouli, A. G.; Considine, R. V.; Hannon, T. S.; Mather, K. J.
      Pages: 318 - 325
      Abstract: OBJECTIVEType 2 diabetes is a growing health problem among both adults and adolescents. To better understand the differences in the pathogenesis of diabetes between these groups, we examined differences in β-cell function along the spectrum of glucose tolerance.RESEARCH DESIGN AND METHODSWe evaluated 89 adults and 50 adolescents with normal glucose tolerance (NGT), dysglycemia, or type 2 diabetes. Oral glucose tolerance test results were used for C-peptide and insulin/glucose minimal modeling. Model-derived and direct measures of insulin secretion and insulin sensitivity were compared across glycemic stages and between age-groups at each stage.RESULTSIn adolescents with dysglycemia, there was marked insulin resistance (insulin sensitivity index: adolescents, median [interquartile range] 1.8 [1.1–2.4] x 10–4; adults, 5.0 [2.3–9.9]; P = 0.01). The nature of β-cell dysfunction across stages of dysglycemia differed between the groups. We observed higher levels of secretion among adolescents than adults (total insulin secretion: NGT, 143 [103–284] x 10–9/min adolescent vs. 106 [71–127], P = 0.001); adults showed stepwise impairments in static insulin secretion (NGT, 7.5 [4.0–10.3] x 10–9/min; dysglycemia, 5.0 [2.3–9.9]; type 2 diabetes, 0.7 [0.1–2.45]; P = 0.003), whereas adolescents showed diabetes-related impairment in dynamic secretion (NGT, 1,905 [1,630–3,913] x 10–9; dysglycemia, 2,703 [1,323–3,637]; type 2 diabetes, 1,189 [269–1,410]; P = 0.001).CONCLUSIONSAdults and adolescents differ in the underlying defects leading to dysglycemia, and in the nature of β-cell dysfunction across stages of dysglycemia. These results may suggest different approaches to diabetes prevention in youths versus adults.
      Keywords: Integrated Physiology-Insulin Secretion In Vivo
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1373
      Issue No: Vol. 41, No. 2 (2018)
  • Revisiting the Relationships Between Measures of Glycemic Control and
           Hypoglycemia in Continuous Glucose Monitoring Data Sets
    • Authors: Gimenez; M.; Tannen, A. J.; Reddy, M.; Moscardo, V.; Conget, I.; Oliver, N.
      Pages: 326 - 332
      Abstract: OBJECTIVEThe Diabetes Control and Complications Trial (DCCT) identified an inverse relationship between HbA1c and severe hypoglycemia. We investigated the relationship between hypoglycemia and HbA1c in a large type 1 diabetes cohort on multiple daily injection or insulin pump therapy using blinded continuous glucose monitoring (CGM) data. The impact of real-time CGM on these relationships and how these relationships differ with biochemical definitions of hypoglycemia have also been assessed.RESEARCH DESIGN AND METHODSCGM data were obtained from the JDRF CGM randomized control trial. Baseline blinded CGM data were used to assess time in hypoglycemia in all individuals. End point data from the CGM intervention group were used to assess the impact of CGM. Percentage of time spent below 3.9, 3.3, 3.0, and 2.8 mmol/L were calculated and quadratic regression plots drawn. Relationships were analyzed visually, and ANOVA was used to assess relationships between glycemia and time below threshold.RESULTSJ-shaped relationships were observed for all biochemical hypoglycemia thresholds, with the lowest hypoglycemia risk occurring at HbA1c values between 8.1 and 8.6% (65–70 mmol/mol). The use of an average of 5 days/week of CGM flattened the relationships for 3.3, 3.0, and 2.8 mmol/L, and ANOVA confirmed the loss of relationship for the 3.3 mmol/L threshold using CGM.CONCLUSIONSThe relationship between hypoglycemia and HbA1c in a population with type 1 diabetes is J-shaped. Lower HbA1c values are still associated with increased hypoglycemia risk, although the magnitude of risk depends on biochemical threshold. Real-time CGM may reduce the percentage time spent in hypoglycemia, changing the relationship between HbA1c and hypoglycemia.
      Keywords: Complications-Hypoglycemia
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1597
      Issue No: Vol. 41, No. 2 (2018)
  • Efficacy and Safety of ITCA 650, a Novel Drug-Device GLP-1 Receptor
           Agonist, in Type 2 Diabetes Uncontrolled With Oral Antidiabetes Drugs: The
           FREEDOM-1 Trial
    • Authors: Rosenstock; J.; Buse, J. B.; Azeem, R.; Prabhakar, P.; Kjems, L.; Huang, H.; Baron, M. A.
      Pages: 333 - 340
      Abstract: OBJECTIVEITCA 650 (exenatide in osmotic mini-pump) continuously delivers exenatide subcutaneously for 3–6 months. Two doses of ITCA 650 were compared with placebo in patients with uncontrolled type 2 diabetes.RESEARCH DESIGN AND METHODSThis 39-week, phase 3, double-blind, placebo-controlled trial randomized 460 patients aged 18–80 years with glycated hemoglobin (HbA1c) 7.5–10% [58–86 mmol/mol] 1:1:1 to placebo, ITCA 650 40 μg/day, or ITCA 650 60 μg/day. Primary end point was change in HbA1c at 39 weeks.RESULTSLeast squares (LS) mean change from baseline HbA1c was –1.1% [–12.2 mmol/mol] and –1.2% [–13.2 mmol/mol] for ITCA 650 40 and 60 μg/day, respectively (P < 0.001 vs. placebo –0.1% [–1.3 mmol/mol]). In a prespecified analysis, greater HbA1c reductions occurred in patients not receiving sulfonylureas (SUs) versus those receiving SUs (–1.7% vs. –1.2% [–18.6 and –13.1 mmol/mol]). At week 39, HbA1c
      Keywords: Clinical Therapeutics/New Technology-Non-Insulin Injectables
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1306
      Issue No: Vol. 41, No. 2 (2018)
  • Cardiovascular Disease, Cancer, and Mortality Among People With Type 2
           Diabetes and Alcoholic or Nonalcoholic Fatty Liver Disease Hospital
    • Authors: Wild; S. H.; Walker, J. J.; Morling, J. R.; McAllister, D. A.; Colhoun, H. M.; Farran, B.; McGurnaghan, S.; McCrimmon, R.; Read, S. H.; Sattar, N.; Byrne, C. D.; on behalf of the Scottish Diabetes Research Network Epidemiology Group
      Pages: 341 - 347
      Abstract: OBJECTIVETo describe associations between alcoholic liver disease (ALD) or nonalcoholic fatty liver disease (NAFLD) hospital admission and cardiovascular disease (CVD), cancer, and mortality in people with type 2 diabetes mellitus (T2DM).RESEARCH DESIGN AND METHODSWe performed a retrospective cohort study by using linked population-based routine data from diabetes registry, hospital, cancer, and death records for people aged 40–89 years diagnosed with T2DM in Scotland between 2004 and 2013 who had one or more hospital admission records. Liver disease and outcomes were identified by using ICD-9 and ICD-10 codes. We estimated hazard ratios (HRs) from Cox proportional hazards regression models, adjusting for key risk factors.RESULTSA total of 134,368 people with T2DM (1,707 with ALD and 1,452 with NAFLD) were studied, with a mean follow-up of 4.3 years for CVD and 4.7 years for mortality. Among those with ALD, NAFLD, or without liver disease hospital records 378, 320, and 21,873 CVD events; 268, 176, and 15,101 cancers; and 724, 221, and 16,203 deaths were reported, respectively. For ALD and NAFLD, respectively, adjusted HRs (95% CIs) compared with the group with no record of liver disease were 1.59 (1.43, 1.76) and 1.70 (1.52, 1.90) for CVD, 40.3 (28.8, 56.5) and 19.12 (11.71, 31.2) for hepatocellular carcinoma (HCC), 1.28 (1.12, 1.47) and 1.10 (0.94, 1.29) for non-HCC cancer, and 4.86 (4.50, 5.24) and 1.60 (1.40, 1.83) for all-cause mortality.CONCLUSIONSHospital records of ALD or NAFLD are associated to varying degrees with an increased risk of CVD, cancer, and mortality among people with T2DM.
      Keywords: Epidemiology-Diabetes Complications
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1590
      Issue No: Vol. 41, No. 2 (2018)
  • Modulation of GLP-1 Levels by a Genetic Variant That Regulates the
           Cardiovascular Effects of Intensive Glycemic Control in ACCORD
    • Authors: Shah; H. S.; Morieri, M. L.; Marcovina, S. M.; Sigal, R. J.; Gerstein, H. C.; Wagner, M. J.; Motsinger-Reif, A. A.; Buse, J. B.; Kraft, P.; Mychaleckyj, J. C.; Doria, A.
      Pages: 348 - 355
      Abstract: OBJECTIVEA genome-wide association study in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial identified two markers (rs57922 and rs9299870) that were significantly associated with cardiovascular mortality during intensive glycemic control and could potentially be used, when combined into a genetic risk score (GRS), to identify patients with diabetes likely to derive benefit from intensive control rather than harm. The aim of this study was to gain insights into the pathways involved in the modulatory effect of these variants.RESEARCH DESIGN AND METHODSFasting levels of 65 biomarkers were measured at baseline and at 12 months of follow-up in the ACCORD-Memory in Diabetes (ACCORD-MIND) MRI substudy (n = 562). Using linear regression models, we tested the association of the GRS with baseline and 12-month biomarker levels, and with their difference (), among white subjects, with genotype data (n = 351) stratified by intervention arm.RESULTSA significant association was observed between GRS and GLP-1 (glucagon-like peptide 1, active) in the intensive arm (P = 3 x 10–4). This effect was driven by rs57922 (P = 5 x 10–4). C/C homozygotes, who had been found to derive cardiovascular benefits from intensive treatment, showed a 22% increase in GLP-1 levels during follow-up. By contrast, T/T homozygotes, who had been found to experience increased cardiac mortality with intensive treatment, showed a 28% reduction in GLP-1 levels. No association between GLP-1 and GRS or rs57922 was observed in the standard treatment arm.CONCLUSIONSDifferences in GLP-1 axis activation may mediate the modulatory effect of variant rs57922 on the cardiovascular response to intensive glycemic control. These findings highlight the importance of GLP-1 as a cardioprotective factor.
      Keywords: Complications-Macrovascular-Atherosclerotic Cardiovascular Disease and Human Diabetes
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1638
      Issue No: Vol. 41, No. 2 (2018)
  • How Does Empagliflozin Reduce Cardiovascular Mortality' Insights From
           a Mediation Analysis of the EMPA-REG OUTCOME Trial
    • Authors: Inzucchi; S. E.; Zinman, B.; Fitchett, D.; Wanner, C.; Ferrannini, E.; Schumacher, M.; Schmoor, C.; Ohneberg, K.; Johansen, O. E.; George, J. T.; Hantel, S.; Bluhmki, E.; Lachin, J. M.
      Pages: 356 - 363
      Abstract: OBJECTIVEIn the BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) trial involving 7,020 patients with type 2 diabetes and established cardiovascular (CV) disease, empagliflozin given in addition to standard of care reduced the risk of CV death by 38% versus placebo (hazard ratio [HR] 0.62 [95% CI 0.49, 0.77]). This exploratory mediation analysis assesses the extent to which treatment group differences in covariates during the trial contributed to CV death risk reduction with empagliflozin.RESEARCH DESIGN AND METHODSEffects of potential mediators, identified post hoc, on the HR for CV death with empagliflozin versus placebo were analyzed by Cox regression models, with treatment group adjusted for the baseline value of the variable and its change from baseline or updated mean (i.e., considering all prior values), each as a time-dependent covariate. HRs were compared with a model without adjustment for covariates. Multivariable analyses also were performed.RESULTSChanges in hematocrit and hemoglobin mediated 51.8% and 48.9%, respectively, of the effect of empagliflozin versus placebo on the risk of CV death on the basis of changes from baseline, with similar results in analyses on the basis of updated means. Smaller mediation effects (maximum 29.3%) were observed for uric acid, fasting plasma glucose, and HbA1c. In multivariable models, which incorporated effects of empagliflozin on hematocrit, fasting glucose, uric acid, and urine albumin:creatinine ratio, the combined changes from baseline provided 85.2% mediation, whereas updated mean analyses provided 94.6% mediation of the effect of empagliflozin on CV death.CONCLUSIONSIn this exploratory analysis from the EMPA-REG OUTCOME trial, changes in markers of plasma volume were the most important mediators of the reduction in risk of CV death with empagliflozin versus placebo.
      Keywords: Clinical Therapeutics/New Technology-Oral Agents
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1096
      Issue No: Vol. 41, No. 2 (2018)
  • Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors and
           Incident Type 2 Diabetes: A Systematic Review and Meta-analysis With Over
           96,000 Patient-Years
    • Authors: de Carvalho; L. S. F.; Campos, A. M.; Sposito, A. C.
      Pages: 364 - 367
      Abstract: OBJECTIVELike mutations with loss of function in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene, inhibitors of PCSK9 (PCSK9i) may potentially favor the manifestation of diabetes.RESEARCH DESIGN AND METHODSA meta-analysis of phase 2/3 randomized clinical trials (RCTs) assessed PCSK9i versus placebo in the primary hypercholesterolemia setting. Statins and ezetimibe were used in 98.4% of these studies and balanced between PCSK9i and placebo. We calculated relative risks (RRs) and 95% CIs using random- and fixed-effect models.RESULTSWe included 68,123 participants (20 RCTs) with median follow-up of 78 weeks. PCSK9i increased fasting blood glucose (weighted mean difference 1.88 mg/dL [95% CI 0.91–2.68]; I2 = 0%; P < 0.001) and HbA1c (0.032% [0.011–0.050]; I2 = 15.5%; P < 0.001) when compared with placebo. This effect was not sufficient to increase incidence of diabetes (RR 1.04 [0.96–1.13]; I2 = 0%; P = 0.427). Exploratory meta-regression analyses indicated an association between the increased risk of diabetes and the potency (P = 0.029) and duration (P = 0.026) of PCSK9i treatment.CONCLUSIONSIn the short term, PCSK9i therapy favors a small but significant increase in plasma glycemia and HbA1c.
      Keywords: Epidemiology-Diabetes Complications
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1464
      Issue No: Vol. 41, No. 2 (2018)
  • Increased Liver Fatty Acid Uptake Is Partly Reversed and Liver Fat Content
           Normalized After Bariatric Surgery
    • Authors: Immonen; H.; Hannukainen, J. C.; Kudomi, N.; Pihlajamäki, J.; Saunavaara, V.; Laine, J.; Salminen, P.; Lehtimäki, T.; Pham, T.; Iozzo, P.; Nuutila, P.
      Pages: 368 - 371
      Abstract: OBJECTIVEChanges in liver fatty acid metabolism are important in understanding the mechanisms of diabetes remission and metabolic changes after bariatric surgery.RESEARCH DESIGN AND METHODSLiver fatty acid uptake (LFU), blood flow, and fat content (LFC) were measured in 25 obese subjects before bariatric surgery and 6 months after using positron emission tomography/computed tomography and MRS; 14 lean individuals served as the control subjects.RESULTSThe increased LFU in obese subjects was associated with body adiposity. LFU was reduced postoperatively but was still high compared with the control subjects. LFC was normalized. Liver blood flow (per unit volume) was higher in obese subjects than in the control subjects at baseline and was further increased postoperatively; however, the total organ blood flow was unchanged as the liver volume decreased.CONCLUSIONSThe findings suggest that in a postoperative state, intrahepatic fatty acids are not stored in the liver but are used for oxidation to provide energy. Changes in perfusion may contribute to improved liver metabolism postoperatively.
      Keywords: Integrated Physiology-Liver
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-0738
      Issue No: Vol. 41, No. 2 (2018)
  • Nonalcoholic Fatty Liver Disease and Risk of Incident Type 2 Diabetes: A
    • Authors: Mantovani; A.; Byrne, C. D.; Bonora, E.; Targher, G.
      Pages: 372 - 382
      Abstract: OBJECTIVESeveral studies have explored the impact of nonalcoholic fatty liver disease (NAFLD) on risk of incident type 2 diabetes. However, the extent to which NAFLD may confer risk of incident diabetes remains uncertain. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident diabetes.RESEARCH DESIGN AND METHODSWe collected data using PubMed, Scopus, and Web of Science from January 2000 to July 2017. We included only large (n ≥500) observational studies with a follow-up duration of at least 1 year in which NAFLD was diagnosed on imaging methods. Eligible studies were selected according to predefined keywords and clinical outcomes. Data from selected studies were extracted, and meta-analysis was performed using random-effects modeling.RESULTSA total of 19 observational studies with 296,439 individuals (30.1% with NAFLD) and nearly 16,000 cases of incident diabetes over a median of 5 years were included in the final analysis. Patients with NAFLD had a greater risk of incident diabetes than those without NAFLD (random-effects hazard ratio [HR] 2.22, 95% CI 1.84–2.60; I2 = 79.2%). Patients with more "severe" NAFLD were also more likely to develop incident diabetes; this risk increased across the ultrasonographic scores of steatosis (n = 3 studies), but it appeared to be even greater among NAFLD patients with advanced high NAFLD fibrosis score (n = 1 study; random-effects HR 4.74, 95% CI 3.54–5.94). Sensitivity analyses did not alter these findings. Funnel plot and Egger test did not reveal significant publication bias. Study limitations included high heterogeneity, varying degrees of confounder adjustment across individual studies, and lack of studies using liver biopsy.CONCLUSIONSNAFLD is significantly associated with a twofold increased risk of incident diabetes. However, the observational design of the eligible studies does not allow for proving causality.
      Keywords: Epidemiology-Clinical-Diagnosis and Screening
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc17-1902
      Issue No: Vol. 41, No. 2 (2018)
  • Issues and Events
    • Pages: 383 - 383
      PubDate: 2018-01-22T12:00:29-08:00
      DOI: 10.2337/dc18-ie02
      Issue No: Vol. 41, No. 2 (2018)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
Home (Search)
Subjects A-Z
Publishers A-Z
Your IP address:
About JournalTOCs
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-