PERL Continuous Glucose Monitoring (CGM) Study
Condition: Diabetic Nephropathies
MeSH terms: Diabetic Nephropathies
Study type: Observational

Summary: 
      Seven-point capillary profiles have shown that mean glucose correlates with both diabetic
      retinopathy and nephropathy risk. However, there remains great controversy as to whether the
      degree of variability around mean glucose may also contribute to these microvascular
      complications. The PERL trial (NCT02017171), testing whether treatment with allopurinol can
      slow down kidney function loss in type 1 diabetes, provides a unique opportunity to assess
      the role of glycemic variability in the progression of diabetic kidney disease in individuals
      who already have mild to moderate kidney disease. By applying Continuous Glucose Monitoring
      (CGM) in the PERL Study population, the investigators will be able to better understand how
      metrics of glycemia (mean, time above and below range, and various measures of variability)
      are associated with renal outcomes in the PERL population as a whole, but also in important
      subgroups (e.g., albuminuric vs. normoalbuminuric subjects with ongoing GFR decline,
      allopurinol vs. placebo arms). The nvestigators also aim to obtain precise information on the
      range of blood glucose corresponding to any given HbA1c value in this population since
      previous studies generally excluded patients with renal disease.
    

Detailed description: 
      Participants who consent to the study will have an Abbott Freestyle Libre Pro sensor placed
      on the back of their upper arm at their first PERL visit after this ancillary study has begun
      and at all subsequent PERL Visits. The sensor will be continuously worn by participants for
      14 days. At the end of the 14 days, the sensor will be removed and mailed by the participant
      to the Coordinating center. Since subjects are at various stages of the PERL protocol, the
      number of remaining visits at which the CGM will be applied will vary among subjects.

      STUDY AIMS

        1. To assess the effect of glycemic variability, as measured by the coefficient of
           variation of CGM glucose (CV, the ratio of standard deviation and the mean of CGM
           glucose values), on the PERL renal functional endpoint (iohexol GFR at the end of
           study).

        2. To assess the effect of other glycemic parameters measured by CGM (mean glucose, % time
           70-180 mg/dL, % time below 54 mg/dL, % time below 70 mg/dL, % time above 180 mg/dL, %
           time above 250 mg/dL, mean amplitude of glucose excursions [MAGE], low blood glucose
           index [LBGI], high blood glucose index [HBGI]) on the PERL renal functional endpoint.

        3. To assess the relationship between CGM-measured glycemic parameters and HbA1c at various
           levels of renal function.

        4. To compare the effects of CGM metrics on the PERL renal endpoint and the corresponding
           effect of HbA1c.

        5. To assess the effect of allopurinol treatment on all of the different glycemic metrics
           including HbA1c, CV, etc. and on their association with the PERL renal endpoint.
    

Intervention name(s): Mean blood glucose; Blood glucose CV; % time 70-180 mg/dL; % time below 54 mg/dL; % time above 180 mg/dL; % time above 250 mg/dL; MAGE (Mean amplitude of glucose excursions); LBGI (Low Blood Glucose Index); HBGI (High Blood Glucose Index); Allopurinol; Placebo
Intervention type(s): Other; Other; Other; Other; Other; Other; Other; Other; Other; Drug; Drug
Intervention description(s): Mean of blood glucose values measures by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Coefficient of variation of blood glucose values measures by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Percent of time with blood glucose in the 70-180 mg/dL range as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Percent of time with blood glucose below 54 mg/dL as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Percent of time with blood glucose above 180 mg/dL as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Percent of time with blood glucose above 250 mg/dL as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Mean amplitude of glucose excursions as measured by continuous glucose monitoring as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Low blood glucose index as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; High blood glucose index as measured by continuous glucose monitoring from week 80 to week 164 of the PERL trial.; Oral allopurinol tablets administered in the PERL Clinical Trial; Oral placebo tablets administered in the PERL Clinical Trial
Intervention MeSH terms: Allopurinol
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Participants of the PERL Clinical Trial