The Sapienza University Mortality and Morbidity Events Rate (SUMMER) Study in Diabetes (SUMMER)

The Sapienza University Mortality and Morbidity Events Rate (SUMMER) Study in Diabetes: Identification of New Molecular Promoters of Mortality and Morbidity in Patients With Type 2 Diabetes Mellitus

This observational study is aimed at identifying new molecular promoters of mortality (and morbidity) in patients with type 2 diabetes mellitus (T2DM).

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus

Detailed Description

Background Mortality rate of diabetic patients is about twice as much that of non-diabetic individuals of similar age; this makes diabetes a leading risk factor for mortality, especially of cardiovascular origin, which accounts for 2.9 million global events yearly. Such scenario is expected to further deteriorate, given that the prevalence of type 2 diabetes mellitus (T2DM), by far the most common form of diabetes comprising more than 90% of all diabetic individuals, is increasing worldwide. Predicting such devastating event is, therefore, urgently needed in order to target aggressive prevention strategies in high risk T2DM patients.

Aims This observational study is aimed at identifying new molecular promoters of all-cause mortality in patients with T2DM.

Secondary endpoints are to identify in these individuals molecular markers of

• cardiovascular mortality;
• myocardial infarction;
• stroke;
• dialysis.

Other pre-specified endpoints are to assess in these subjects:

• LADA;
• severe hypoglycemic episodes;
• revascularization procedures;
• hospitalization for heart failure;
• other co-morbidities (cancer - at follow-up only, liver disease, chronic obstructive pulmonary disease, autoimmune and endocrine disorders, other - non-diabetic - renal diseases, fractures, cognitive impairment).

Patients A total of 5,000 patients with T2DM of both sexes will be recruited. Measures The following parameters will be recorded as exposure variables at baseline.

• Age, BMI, waist circumference, systolic and diastolic pressure;
• Lifestyle habits, including diet, physical activity (both by validated questionnaires) and smoking.
• Menopausal state (for women).
• Family history of diabetes (3 consecutive generations).
• Family history of cardiovascular disease (first degree relatives).
• Diabetes duration.
• Severe (requiring assistance) hypoglycemic episodes (per year).
• Myocardial infarction, stroke, ulcer/gangrene/amputation, coronary and peripheral revascularization, hospitalization for heart failure, dialysis (at follow-up only).
• Glucose, HbA1c, creatinine, uric acid, total and HDL cholesterol, triglycerides, high sensitive C reactive protein, testosterone, Vitamin D, uric acid levels, white blood cells counting, urinary albumin creatinine ratio (ACR)
• Current glucose-, lipid-, blood pressure-lowering and anti-platelet or anti-coagulant treatment.
• Other relevant treatments (steroids, NSAIDs, immunomodulators, androgens, estrogens, anti-fracturative therapy).
• Main co-morbidities (cancer, chronic liver disease, chronic obstructive pulmonary disease, autoimmune and endocrine disorders, other - non-diabetic - renal diseases, fractures, cognitive impairment).

The following parameters will be assessed at baseline only:

• GADAs (by a radiobinding assay using in vitro translated [35S] methionine-labelled GAD65) and IA-2 antibodies (by radioimmunoprecipitation assays) to identify subjects with LADA.
• Genomic (common and rare variants in genes of interest according to a pathway-centric approach by means of Affymetrix platforms), transcriptomic (differential levels of mRNA by GeneChip Human Gene 1.0 ST Array from Affymetrix) and metabolomic by a combination of ultra-pressure liquid chromatography and gas chromatography coupled to mass spectrometry) analysis.

Measurements of testosterone, Vitamin D, GADAs and IA-2 antibodies as well as gnomic, transcriptomic and metabolomic analysis will be centralized.

Time schedule Recruitment of patients will last approximately 3 years. The enrolled patients will be followed for at least 5 years with yearly visits and telephone calls or consultation of death records in case of drop-out for unknown reasons.

• Study Type: Observational
• Enrollment (Actual): 5139

Contacts and Locations

• Study Contact: Name: Vincenzo Trischitta, MD; Phone Number: +390644160534; Email: vincenzo.trischitta@uniroma1.it
• Study Contact Backup: Name: Giuseppe Pugliese, MD, PhD; Phone Number: +390633775440; Email: giuseppe.pugliese@uniroma1.it

Study Locations

• Italy
  • RM
    • Rome, RM, Italy, 00161
      • University of Roma La Sapienza

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Secondary care outpatients clinic

Description

Inclusion Criteria:

Type 2 diabetes mellitus

Exclusion Criteria:

• Severe psychiatric illnesses
• End-stage renal disease and dialysis
• Cirrhosis
• Any active cancer

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of all-cause deaths	Number of participants who die for all causes and time of occurrence of such events	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of cardiovascular deaths	Number of participants who die for cardiovascular causes and time of occurrence of such events	5 years
Number of subjects with myocardial infarction	Number of participants who develop myocardial infarction and time of occurrence of such events	5 years
Number of subjects with stroke	Number of participants who develop stroke and time of occurrence of such events	5 years
Number of subjects entering dialysis	Number of participants who enter dialysis and time of occurrence of such events	5 years

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza
• Collaborators: University of Cagliari; Campus Bio-Medico University; Azienda Ospedaliera San Camillo Forlanini; Casa Sollievo della Sofferenza IRCCS; Ospedale Sandro Pertini, Roma
• Investigators: Principal Investigator: Vincenzo Trischitta, MD, University of Roma La Sapienza; Study Director: Giuseppe Pugliese, MD, PhD, University of Roma La Sapienza

Publications and helpful links

General Publications

• Rao Kondapally Seshasai S, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, Sarwar N, Whincup PH, Mukamal KJ, Gillum RF, Holme I, Njolstad I, Fletcher A, Nilsson P, Lewington S, Collins R, Gudnason V, Thompson SG, Sattar N, Selvin E, Hu FB, Danesh J; Emerging Risk Factors Collaboration. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011 Mar 3;364(9):829-841. doi: 10.1056/NEJMoa1008862. Erratum In: N Engl J Med. 2011 Mar 31;364(13):1281.
• Roglic G, Unwin N, Bennett PH, Mathers C, Tuomilehto J, Nag S, Connolly V, King H. The burden of mortality attributable to diabetes: realistic estimates for the year 2000. Diabetes Care. 2005 Sep;28(9):2130-5. doi: 10.2337/diacare.28.9.2130.
• De Cosmo S, Copetti M, Lamacchia O, Fontana A, Massa M, Morini E, Pacilli A, Fariello S, Palena A, Rauseo A, Viti R, Di Paola R, Menzaghi C, Cignarelli M, Pellegrini F, Trischitta V. Development and validation of a predicting model of all-cause mortality in patients with type 2 diabetes. Diabetes Care. 2013 Sep;36(9):2830-5. doi: 10.2337/dc12-1906. Epub 2013 May 1.
• Hong Kong Diabetes Registry; Yang X, So WY, Tong PC, Ma RC, Kong AP, Lam CW, Ho CS, Cockram CS, Ko GT, Chow CC, Wong VC, Chan JC. Development and validation of an all-cause mortality risk score in type 2 diabetes. Arch Intern Med. 2008 Mar 10;168(5):451-7. doi: 10.1001/archinte.168.5.451.
• Wells BJ, Jain A, Arrigain S, Yu C, Rosenkrans WA Jr, Kattan MW. Predicting 6-year mortality risk in patients with type 2 diabetes. Diabetes Care. 2008 Dec;31(12):2301-6. doi: 10.2337/dc08-1047. Epub 2008 Sep 22.
• McEwen LN, Karter AJ, Waitzfelder BE, Crosson JC, Marrero DG, Mangione CM, Herman WH. Predictors of mortality over 8 years in type 2 diabetic patients: Translating Research Into Action for Diabetes (TRIAD). Diabetes Care. 2012 Jun;35(6):1301-9. doi: 10.2337/dc11-2281. Epub 2012 Mar 19.
• Barchetta I, Capoccia D, Baroni MG, Buzzetti R, Cavallo MG, De Cosmo S, Leonetti F, Leotta S, Morano S, Morviducci L, Prudente S, Pugliese G, Trischitta V; SUMMER Study in Diabetes Group. The "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes": Study protocol. Nutr Metab Cardiovasc Dis. 2016 Feb;26(2):103-8. doi: 10.1016/j.numecd.2015.09.009. Epub 2015 Oct 9.

Helpful Links

• Study webpage

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: November 24, 2014
• First Submitted That Met QC Criteria: December 4, 2014
• First Posted (Estimate): December 8, 2014

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 11, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Stroke; Myocardial infarction; Dialysis; All-cause mortality; Cardiovascular mortality
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: URomLS-01-2014