Clinical trial NCT02311244: The Sapienza University Mortality and Morbidity Events Rate (SUMMER) Study in Diabetes
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type 2 Diabetes Mellitus
Keywords: All-cause mortality
Cardiovascular mortality
Myocardial infarction
Stroke
Dialysis
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
Collaborators: name: Campus Bio-Medico University
name: Ospedale Sandro Pertini, Roma
name: Azienda Ospedaliera San Camillo Forlanini
name: University of Cagliari
name: Casa Sollievo della Sofferenza IRCCS
First posted: 2014-12-08
Enrollment: 5139
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Secondary care outpatients clinic

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

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.

Eligibility criteria: Inclusion Criteria:

Type 2 diabetes mellitus

Exclusion Criteria:

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

Primary outcomes:
measure: Number of all-cause deaths
timeFrame: 5 years
Secondary outcomes:
measure: Number of cardiovascular deaths
timeFrame: 5 years
measure: Number of subjects with myocardial infarction
timeFrame: 5 years
measure: Number of subjects with stroke
timeFrame: 5 years
measure: Number of subjects entering dialysis
timeFrame: 5 years
Other outcomes:
Locations:
city: Rome
country: Italy
facility: University of Roma La Sapienza
state: RM
Study officials:
affiliation: University of Roma La Sapienza
name: Vincenzo Trischitta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Roma La Sapienza
name: Giuseppe Pugliese, MD, PhD
role: STUDY_DIRECTOR
References:
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citation: 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.
citation: 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.