<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04453605</url>
  </required_header>
  <id_info>
    <org_study_id>AS0006</org_study_id>
    <nct_id>NCT04453605</nct_id>
  </id_info>
  <brief_title>Phenotyping Individuals With Neo-diagnosed Type 2 Diabetes at Risk for All-cause Mortality</brief_title>
  <official_title>Determining All Cause Morality and Cardiovascular Mortality Risk in Individuals With Neo-diagnosed Type 2 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pisa</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pisa</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prevalence of type 2 diabetes (T2D) is increasing worldwide over the last two decades; in&#xD;
      these patients the rate of all-cause and cardiovascular (CV) mortality is several folds&#xD;
      higher than in the general population, configuring a major public health problem. The&#xD;
      clinical phenotype is the main determinant of such high mortality risk; however, a relevant&#xD;
      role is played by the disease duration, with a significant interaction with metabolic&#xD;
      control. However, for T2D the diagnosis does not correspond to the true onset of the disease,&#xD;
      and a high lethality rate also in patients with recent onset of the disease cannot be&#xD;
      excluded. Robust evidence supports this hypothesis, showing as in subjects with new-onset&#xD;
      T2D, the mortality risk is superimposable, and even higher, than that observed in people with&#xD;
      overt and long-term T2D. In this complex scenario, it would be desirable an early&#xD;
      identification of high-risk patients, in which an accurate estimation of risk of&#xD;
      complications, coupled with appropriate and timely interventions, might help in reducing the&#xD;
      risk of encountering premature mortality. The present study was design to address this&#xD;
      specific issue.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients referring for the first time to the outpatient diabetes clinic in the department of&#xD;
      Internal Medicine between January 2008 and December 2015 and matching the inclusion criteria&#xD;
      were recruited.&#xD;
&#xD;
      Diagnosis was confirmed on the basis of the Oral Glucose Tolerance Test (OGTT) or HbA1c ≥6.5%&#xD;
      plus fasting blood glucose ≥126 mg/dl.&#xD;
&#xD;
      Anthropometric measurements were recorded, arterial pressure and vital parameters were&#xD;
      registered, and blood samples were collected for routine analyses. Complete blood count,&#xD;
      glucose, HbA1c, Serum Glutamic Oxaloacetic Transaminase (sGOT), Serum Glutamic Pyruvic&#xD;
      Transaminase (sGPT), uric acid, were determined by standard techniques. Total and HDL&#xD;
      cholesterol and triglycerides were assayed through the automated spectrophotometer, enzymatic&#xD;
      colorimetric method, COBAS INTEGRA using commercial kits (Roche Diagnostics). Serum&#xD;
      creatinine was measured by Jaffe' method, and estimated glomerular filtration rate (eGFR) was&#xD;
      calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)&#xD;
      formula.&#xD;
&#xD;
      Previous major acute CV events, including myocardial infarction, stroke, foot&#xD;
      ulcer/gangrene/amputation and coronary, carotid and lower limb revascularisation, were&#xD;
      adjudicated based on hospital discharge records.&#xD;
&#xD;
      At the end of the baseline visit, patients were treated according to the good clinical&#xD;
      practice recommended by the international guidelines, and followed a six-month or an yearly&#xD;
      calendar of follow-up visits, until death or until 31 December 2018. All-cause mortality was&#xD;
      assessed by checking the vital status of study participants on 31 December 2018; to this aim,&#xD;
      investigators interrogated the Italian Health Card database, which provides updated&#xD;
      information on all current Italian residents.&#xD;
&#xD;
      Incident major acute cardiovascular events were registered on the basis of clinical records&#xD;
      every year; retinopathy onset was assessed by fundoscopy on a yearly basis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2008</start_date>
  <completion_date type="Actual">December 31, 2018</completion_date>
  <primary_completion_date type="Actual">December 31, 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants who died during the study</measure>
    <time_frame>At 31 December 2018</time_frame>
    <description>The number of participants who died during the study was assessed by checking the vital status of study participants on 31 December 2018; to this aim, we interrogated the Italian Health Card database, which provides updated information on all current Italian residents.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of cardiovascular disease</measure>
    <time_frame>At 31 December 2018</time_frame>
    <description>Incident major acute cardiovascular events were registered on the basis of clinical records every year</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of microvascular complication</measure>
    <time_frame>At 31 December 2018</time_frame>
    <description>Retinopathy onset was assessed by fundoscopy on a yearly basis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of renal function through study completion (an average of 5 year)</measure>
    <time_frame>From baseline until the end of observation or the date of death from any cause, whichever came first, assessed up to 60 months.</time_frame>
    <description>Serum creatinine was measured by Jaffe' method and expressed by mg/dl. It was used to calculate eGFR according to the CKD-EPI formula.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of blood glucose through study completion (an average of 5 year)</measure>
    <time_frame>From baseline until the end of observation or the date of death from any cause, whichever came first, assessed up to 60 months.</time_frame>
    <description>Blood glucose was expressed in mg/dl and was determined by standard techniques.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of HbA1c through study completion (an average of 5 year)</measure>
    <time_frame>From baseline until the end of observation or the date of death from any cause, whichever came first, assessed up to 60 months.</time_frame>
    <description>HbA1c was expressed as percentage or mmol/l and was determined by standard techniques.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">300</enrollment>
  <condition>Type 2 Diabetes</condition>
  <condition>Vascular Diseases</condition>
  <condition>Cardiac Disease</condition>
  <arm_group>
    <arm_group_label>Patients with neo-diagnosed type 2 diabetes</arm_group_label>
    <description>Patients referring for the first time to the outpatient diabetes clinic in the department of Internal Medicine between January 2008 and December 2015 and matching the inclusion criteria.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>standard treatments</intervention_name>
    <description>patients were treated according to the good clinical practice recommended by the international guidelines, and followed a six-month or an yearly calendar of follow-up visits</description>
    <arm_group_label>Patients with neo-diagnosed type 2 diabetes</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients referring for the first time to the outpatient diabetes clinic in the department&#xD;
        of Internal Medicine between January 2008 and December 2015 and matching the inclusion&#xD;
        criteria.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age ≥30 years&#xD;
&#xD;
          -  personal history of known T2D lasting not more than six months&#xD;
&#xD;
          -  diagnosis confirmed on the basis of the OGTT or HbA1c ≥6.5% plus fasting blood glucose&#xD;
             ≥126 mg/dl&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  longstanding disease duration&#xD;
&#xD;
          -  type 1 diabetes&#xD;
&#xD;
          -  diabetes secondary to steroid therapy&#xD;
&#xD;
          -  active cancer&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anna Solini, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pisa</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pisa</name>
      <address>
        <city>Pisa</city>
        <zip>56125</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract. 2011 Dec;94(3):311-21. doi: 10.1016/j.diabres.2011.10.029. Epub 2011 Nov 12.</citation>
    <PMID>22079683</PMID>
  </reference>
  <reference>
    <citation>Tancredi M, Rosengren A, Svensson AM, Kosiborod M, Pivodic A, Gudbjornsdottir S, Wedel H, Clements M, Dahlqvist S, Lind M. Excess Mortality among Persons with Type 2 Diabetes. N Engl J Med. 2015 Oct 29;373(18):1720-32. doi: 10.1056/NEJMoa1504347.</citation>
    <PMID>26510021</PMID>
  </reference>
  <reference>
    <citation>Gregg EW, Zhuo X, Cheng YJ, Albright AL, Narayan KM, Thompson TJ. Trends in lifetime risk and years of life lost due to diabetes in the USA, 1985-2011: a modelling study. Lancet Diabetes Endocrinol. 2014 Nov;2(11):867-74. doi: 10.1016/S2213-8587(14)70161-5. Epub 2014 Aug 12.</citation>
    <PMID>25128274</PMID>
  </reference>
  <reference>
    <citation>Ghouse J, Isaksen JL, Skov MW, Lind B, Svendsen JH, Kanters JK, Olesen MS, Holst AG, Nielsen JB. Effect of diabetes duration on the relationship between glycaemic control and risk of death in older adults with type 2 diabetes. Diabetes Obes Metab. 2020 Feb;22(2):231-242. doi: 10.1111/dom.13891. Epub 2019 Nov 18.</citation>
    <PMID>31596048</PMID>
  </reference>
  <reference>
    <citation>Gimeno Orna JA, Blasco Lamarca Y, Campos Gutierrez B, Molinero Herguedas E, Lou Arnal LM. [Morbidity and mortality cardiovascular risk in dependence of type 2 diabetes duration]. Clin Investig Arterioscler. 2014 May-Jun;26(3):122-30. doi: 10.1016/j.arteri.2013.11.010. Epub 2014 Jan 23. Spanish.</citation>
    <PMID>24461345</PMID>
  </reference>
  <reference>
    <citation>Herrington WG, Alegre-Diaz J, Wade R, Gnatiuc L, Ramirez-Reyes R, Hill M, Solano-Sanchez M, Baigent C, Lewington S, Collins R, Tapia-Conyer R, Peto R, Kuri-Morales P, Emberson JR. Effect of diabetes duration and glycaemic control on 14-year cause-specific mortality in Mexican adults: a blood-based prospective cohort study. Lancet Diabetes Endocrinol. 2018 Jun;6(6):455-463. doi: 10.1016/S2213-8587(18)30050-0. Epub 2018 Mar 19.</citation>
    <PMID>29567074</PMID>
  </reference>
  <reference>
    <citation>Huo L, Magliano DJ, Ranciere F, Harding JL, Nanayakkara N, Shaw JE, Carstensen B. Impact of age at diagnosis and duration of type 2 diabetes on mortality in Australia 1997-2011. Diabetologia. 2018 May;61(5):1055-1063. doi: 10.1007/s00125-018-4544-z. Epub 2018 Feb 22.</citation>
    <PMID>29473119</PMID>
  </reference>
  <reference>
    <citation>Huang Y, Cai X, Mai W, Li M, Hu Y. Association between prediabetes and risk of cardiovascular disease and all cause mortality: systematic review and meta-analysis. BMJ. 2016 Nov 23;355:i5953. doi: 10.1136/bmj.i5953.</citation>
    <PMID>27881363</PMID>
  </reference>
  <reference>
    <citation>Smith NL, Barzilay JI, Kronmal R, Lumley T, Enquobahrie D, Psaty BM. New-onset diabetes and risk of all-cause and cardiovascular mortality: the Cardiovascular Health Study. Diabetes Care. 2006 Sep;29(9):2012-7. doi: 10.2337/dc06-0574.</citation>
    <PMID>16936145</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 7, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>June 29, 2020</last_update_submitted>
  <last_update_submitted_qc>June 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pisa</investigator_affiliation>
    <investigator_full_name>Anna Solini</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>neo-diagnosed type 2 diabetes</keyword>
  <keyword>all-cause mortality</keyword>
  <keyword>cardiovascular mortality</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vascular Diseases</mesh_term>
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04453605
org study id: AS0006
nct id: NCT04453605
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Prevalence of type 2 diabetes (T2D) is increasing worldwide over the last two decades; in
      these patients the rate of all-cause and cardiovascular (CV) mortality is several folds
      higher than in the general population, configuring a major public health problem. The
      clinical phenotype is the main determinant of such high mortality risk; however, a relevant
      role is played by the disease duration, with a significant interaction with metabolic
      control. However, for T2D the diagnosis does not correspond to the true onset of the disease,
      and a high lethality rate also in patients with recent onset of the disease cannot be
      excluded. Robust evidence supports this hypothesis, showing as in subjects with new-onset
      T2D, the mortality risk is superimposable, and even higher, than that observed in people with
      overt and long-term T2D. In this complex scenario, it would be desirable an early
      identification of high-risk patients, in which an accurate estimation of risk of
      complications, coupled with appropriate and timely interventions, might help in reducing the
      risk of encountering premature mortality. The present study was design to address this
      specific issue.
Patients referring for the first time to the outpatient diabetes clinic in the department of
      Internal Medicine between January 2008 and December 2015 and matching the inclusion criteria
      were recruited.

      Diagnosis was confirmed on the basis of the Oral Glucose Tolerance Test (OGTT) or HbA1c ≥6.5%
      plus fasting blood glucose ≥126 mg/dl.

      Anthropometric measurements were recorded, arterial pressure and vital parameters were
      registered, and blood samples were collected for routine analyses. Complete blood count,
      glucose, HbA1c, Serum Glutamic Oxaloacetic Transaminase (sGOT), Serum Glutamic Pyruvic
      Transaminase (sGPT), uric acid, were determined by standard techniques. Total and HDL
      cholesterol and triglycerides were assayed through the automated spectrophotometer, enzymatic
      colorimetric method, COBAS INTEGRA using commercial kits (Roche Diagnostics). Serum
      creatinine was measured by Jaffe' method, and estimated glomerular filtration rate (eGFR) was
      calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      formula.

      Previous major acute CV events, including myocardial infarction, stroke, foot
      ulcer/gangrene/amputation and coronary, carotid and lower limb revascularisation, were
      adjudicated based on hospital discharge records.

      At the end of the baseline visit, patients were treated according to the good clinical
      practice recommended by the international guidelines, and followed a six-month or an yearly
      calendar of follow-up visits, until death or until 31 December 2018. All-cause mortality was
      assessed by checking the vital status of study participants on 31 December 2018; to this aim,
      investigators interrogated the Italian Health Card database, which provides updated
      information on all current Italian residents.

      Incident major acute cardiovascular events were registered on the basis of clinical records
      every year; retinopathy onset was assessed by fundoscopy on a yearly basis.
observational model: Cohort
time perspective: Prospective
measure: Number of participants who died during the study
time frame: At 31 December 2018
description: The number of participants who died during the study was assessed by checking the vital status of study participants on 31 December 2018; to this aim, we interrogated the Italian Health Card database, which provides updated information on all current Italian residents.
measure: Incidence of cardiovascular disease
time frame: At 31 December 2018
description: Incident major acute cardiovascular events were registered on the basis of clinical records every year
measure: Incidence of microvascular complication
time frame: At 31 December 2018
description: Retinopathy onset was assessed by fundoscopy on a yearly basis.
measure: Change of renal function through study completion (an average of 5 year)
time frame: From baseline until the end of observation or the date of death from any cause, whichever came first, assessed up to 60 months.
description: Serum creatinine was measured by Jaffe' method and expressed by mg/dl. It was used to calculate eGFR according to the CKD-EPI formula.
measure: Change of blood glucose through study completion (an average of 5 year)
time frame: From baseline until the end of observation or the date of death from any cause, whichever came first, assessed up to 60 months.
description: Blood glucose was expressed in mg/dl and was determined by standard techniques.
measure: Change of HbA1c through study completion (an average of 5 year)
time frame: From baseline until the end of observation or the date of death from any cause, whichever came first, assessed up to 60 months.
description: HbA1c was expressed as percentage or mmol/l and was determined by standard techniques.
arm group label: Patients with neo-diagnosed type 2 diabetes
description: Patients referring for the first time to the outpatient diabetes clinic in the department of Internal Medicine between January 2008 and December 2015 and matching the inclusion criteria.
intervention type: Other
intervention name: standard treatments
description: patients were treated according to the good clinical practice recommended by the international guidelines, and followed a six-month or an yearly calendar of follow-up visits
arm group label: Patients with neo-diagnosed type 2 diabetes
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 30 Years
maximum age: 85 Years
healthy volunteers: No
last name: Anna Solini, MD, PhD
role: Principal Investigator
affiliation: University of Pisa
facility: 
country: Italy
citation: Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract. 2011 Dec;94(3):311-21. doi: 10.1016/j.diabres.2011.10.029. Epub 2011 Nov 12.
PMID: 22079683
citation: Tancredi M, Rosengren A, Svensson AM, Kosiborod M, Pivodic A, Gudbjornsdottir S, Wedel H, Clements M, Dahlqvist S, Lind M. Excess Mortality among Persons with Type 2 Diabetes. N Engl J Med. 2015 Oct 29;373(18):1720-32. doi: 10.1056/NEJMoa1504347.
PMID: 26510021
citation: Gregg EW, Zhuo X, Cheng YJ, Albright AL, Narayan KM, Thompson TJ. Trends in lifetime risk and years of life lost due to diabetes in the USA, 1985-2011: a modelling study. Lancet Diabetes Endocrinol. 2014 Nov;2(11):867-74. doi: 10.1016/S2213-8587(14)70161-5. Epub 2014 Aug 12.
PMID: 25128274
citation: Ghouse J, Isaksen JL, Skov MW, Lind B, Svendsen JH, Kanters JK, Olesen MS, Holst AG, Nielsen JB. Effect of diabetes duration on the relationship between glycaemic control and risk of death in older adults with type 2 diabetes. Diabetes Obes Metab. 2020 Feb;22(2):231-242. doi: 10.1111/dom.13891. Epub 2019 Nov 18.
PMID: 31596048
citation: Gimeno Orna JA, Blasco Lamarca Y, Campos Gutierrez B, Molinero Herguedas E, Lou Arnal LM. [Morbidity and mortality cardiovascular risk in dependence of type 2 diabetes duration]. Clin Investig Arterioscler. 2014 May-Jun;26(3):122-30. doi: 10.1016/j.arteri.2013.11.010. Epub 2014 Jan 23. Spanish.
PMID: 24461345
citation: Herrington WG, Alegre-Diaz J, Wade R, Gnatiuc L, Ramirez-Reyes R, Hill M, Solano-Sanchez M, Baigent C, Lewington S, Collins R, Tapia-Conyer R, Peto R, Kuri-Morales P, Emberson JR. Effect of diabetes duration and glycaemic control on 14-year cause-specific mortality in Mexican adults: a blood-based prospective cohort study. Lancet Diabetes Endocrinol. 2018 Jun;6(6):455-463. doi: 10.1016/S2213-8587(18)30050-0. Epub 2018 Mar 19.
PMID: 29567074
citation: Huo L, Magliano DJ, Ranciere F, Harding JL, Nanayakkara N, Shaw JE, Carstensen B. Impact of age at diagnosis and duration of type 2 diabetes on mortality in Australia 1997-2011. Diabetologia. 2018 May;61(5):1055-1063. doi: 10.1007/s00125-018-4544-z. Epub 2018 Feb 22.
PMID: 29473119
citation: Huang Y, Cai X, Mai W, Li M, Hu Y. Association between prediabetes and risk of cardiovascular disease and all cause mortality: systematic review and meta-analysis. BMJ. 2016 Nov 23;355:i5953. doi: 10.1136/bmj.i5953.
PMID: 27881363
citation: Smith NL, Barzilay JI, Kronmal R, Lumley T, Enquobahrie D, Psaty BM. New-onset diabetes and risk of all-cause and cardiovascular mortality: the Cardiovascular Health Study. Diabetes Care. 2006 Sep;29(9):2012-7. doi: 10.2337/dc06-0574.
PMID: 16936145
responsible party type: Principal Investigator
investigator affiliation: University of Pisa
investigator full name: Anna Solini
investigator title: Associate Professor
mesh term: Vascular Diseases
mesh term: Heart Diseases
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
sharing ipd: No