Table 1

Estimated marginal means and mean changes in metabolic, liver-related and non-invasive markers at baseline and after 1 year of the CCI and UC interventions

Baseline1 yearChange
VariablesMean±SEP valueMean±SEP valueMean difference±SEP value
Full cohort (CCI, n=262 and UC, n=87)
Non-invasive biomarker
 NAFLD-LFS*†0.449.8×10-9
   CCI3.26±0.211.30±0.19−1.95±0.223.3×10−16
   UC3.25±0.383.71±0.350.47±0.410.26
   CCI versus UC0.01±0.44−2.41±0.41
 NAFLD fibrosis score*0.314.3×10-8
   CCI−0.32±0.06−0.97±0.07−0.65±0.066.5×10−22
   UC−0.45±0.11−0.19±0.120.26±0.110.02
   CCI versus UC0.13±0.13−0.78±0.14
Liver-related tests
 Albumin (g/dL)*0.840.02
   CCI4.43±0.024.51±0.020.08±0.024.7×10−6
   UC4.42±0.044.42±0.03−0.01±0.030.87
   CCI versus UC0.01±0.040.09±0.04
 Platelet (× 109)*0.760.06
   CCI250.52±3.86227.60±3.69−22.92±2.281.6×10−20
   UC252.96±6.91241.87±6.53−11.09±3.880.005
   CCI versus UC−2.44±8.03−14.27±7.62
Abnormal ALT cohort (CCI: n=153 and UC: n=38)
Non-invasive biomarker
 NAFLD-LFS‡†0.462.7×10-6
  CCI3.96±0.281.46±0.26−2.50±0.301.5×10-13
  UC4.44±0.584.53±0.570.09±0.660.9
  CCI versus UC−0.48±0.65−3.06±0.63
 NAFLD fibrosis score‡0.330.0002
   CCI−0.43±0.08−1.14±0.09−0.71±0.087.5×10−15
   UC−0.62±0.17−0.35±0.180.26±0.170.12
   CCI versus UC0.19±0.19−0.79±0.20
Metabolic parameters
 HbA1c (%)‡0.083.4×10−8
   CCI7.50±0.106.16±0.10−1.35±0.113.6×10−25
   UC7.10±0.217.32±0.180.22±0.230.33
   CCI versus UC0.41±0.23−1.16±0.20
 Fasting glucose (mg/dL)‡0.070.02
   CCI158.34±4.42124.05±3.94−34.29±5.102.4×10−10
   UC139.79±9.15152.13±8.0812.34±10.370.24
   CCI versus UC18.55±10.19−28.09±9.05
 Fasting insulin (m/UL)‡†0.620.002
   CCI30.16±1.7518.01±1.56−12.15±1.783.0×10−10
   UC32.15±3.6330.01±3.41−2.14±3.820.58
   CCI versus UC−1.99±4.04−12.00±3.77
 HOMA-IR‡
   CCI9.57±0.605.18±0.70−4.38±0.788.7×10−8
   UC11.51±1.1813.73±1.432.22±1.560.16
   CCI versus UC−1.95±1.330.14−8.56±1.603.7×10−7
 Triglycerides (mg/dL)‡§0.120.0001
   CCI197.54±8.74162.59±15.85−34.95±17.352.7×10−9
   UC232.18±24.87267.29±47.9035.11±51.340.62
   CCI versus UC−34.64±21.50−104.70±39.84
 Cholesterol (mg/dL)‡0.730.17
   CCI181.58±3.35197.13±4.4615.55±4.050.0001
   UC178.91±7.02182.69±9.513.78±8.680.66
   CCI versus UC2.67±7.8214.44±10.53
 HDL cholesterol (mg/dL)‡0.051.8×10−7
   CCI41.67±1.1050.18±1.308.51±1.159.2×10−12
   UC36.60±2.3033.45±2.77−3.15±2.460.2
   CCI versus UC5.07±2.5616.73±3.07
 LDL cholesterol (mg/dL)‡0.750.002
   CCI100.31±2.85117.16±3.4216.86±3.268.7×10−7
   UC98.12±6.2390.22±7.87−7.90±7.560.3
   CCI versus UC2.19±6.8826.94±8.60
Liver-related tests
 ALT (U/L)‡†0.763.5×10−6
   CCI37.00±1.2423.55±1.32−13.44±1.592.7×10−14
   UC37.86±2.5638.04±2.680.18±3.230.96
   CCI versus UC−0.86±2.86−14.49±3.01
 AST (U/L)‡†0.81.1×10−5
   CCI27.11±0.9719.77±0.83−7.34±1.008.9×10−12
   UC27.69±2.0328.55±1.730.86±2.090.68
   CCI versus UC−0.59±2.26−8.78±1.93
 ALP (U/L)‡0.220.0005
   CCI74.07±2.0064.53±2.02−9.55±1.332.5×10−11
   UC79.79±4.1681.02±4.181.23±2.680.65
   CCI versus UC−5.72±4.64−16.49±4.67
 Albumin (g/dL)‡0.640.11
   CCI4.50±0.024.56±0.020.06±0.020.004
   UC4.52±0.054.48±0.05−0.04±0.050.35
   CCI versus UC−0.02±0.050.08±0.05
 Platelet (×109)‡0.870.21
   CCI247.45±5.21225.87±5.06−21.57±3.119.8×10−11
   UC249.46±10.84240.78±10.48−8.69±6.300.17
   CCI versus UC−2.02±12.09−14.90±11.71
Kidney function tests
 Creatinine (mg/dL)‡0.390.71
   CCI0.86±0.020.82±0.01−0.05±0.010.0005
   UC0.83±0.030.83±0.03−0.01±0.030.85
   CCI versus UC0.03±0.03−0.01±0.03
 eGFR (CKD-EPI)‡0.720.43
   CCI81.53±0.9083.32±0.881.79±0.750.02
   UC82.26±1.8681.72±1.81−0.54±1.530.72
   CCI versus UC−0.73±2.081.60±2.03
Other parameters
 CRP (mg/dL)‡†0.038.2×10−6
   CCI6.85±0.504.51±0.50−2.34±0.482.4×10−6
   UC9.41±1.039.84±1.040.43±0.970.66
   CCI versus UC−2.56±1.15−5.33±1.16
 BHB (mmol/L)‡†0.50.002
   CCI0.17±0.010.26±0.020.09±0.027.3×10−5
   UC0.15±0.030.12±0.04−0.03±0.040.45
   CCI versus UC0.02±0.030.14±0.04
  • Unless otherwise noted, estimates reported were obtained from linear mixed-effects models that provide marginal means and mean changes, adjusting for baseline age, gender, race, diabetes duration, body mass index and insulin use.

  • This maximum likelihood-based approach uses all available repeated data, resulting in an intent-to-treat analysis.

  • Multiple comparisons were adjusted for Bonferroni corrections (P<0.0025).

  • However, because transformed numbers are difficult to interpret, non-transformed and unadjusted means, mean changes, and standard errors for participants who completed the study visit were computed and provided in the table.

  • *Full sample analysis.

  • †Variable was positively skewed and after removing the top 1% of values, skew and kurtosis values fell within acceptable ranges. Analyses were conducted on data excluding the top 1% of values for each variable, although due to the maximum likelihood approach all cases were still included in the analyses.

  • ‡Subgroup analysis of participants with abnormal ALT at baseline. Abnormal ALT refers to >19 U/L for women and 30 U/L for men.

  • §Variable was positively skewed and a natural log transformation was performed. The linear mixed-effects model analysis including covariates was conducted on the transformed variable and significance values provided are from the transformed analysis.

  • ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BHB, beta-hydroxybutyrate; CCI, continuous care intervention; CKD-EPI, chronic kidney disease-epidemiological collaboration equation; CRP, C reactive protein; eGFR, estimated glomerular filtration rates; HbA1c, glycosylated haemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein; LFS, liver fat score; NAFLD, non-alcoholic fatty liver disease; UC, usual care.