Lifestyle Intervention for Type 2 Diabetes in Primary Care (CREDOenAP)

Glycated hemoglobin (HbA1c): T2DM remission will be considered if HbA1c is < 6.5% after 6 months of intervention and at least 3 months without antidiabetic medication. HbA1c will be determined by blood analysis after a minimum of 8 hours of fasting

Fasting plasma glucose: T2DM remission will be considered if fasting venous plasma glucose is < 126 mg/dL after 6 months of intervention and at least 3 months without antidiabetic medication. Fasting plasma glucose will be measured by venous blood analysis after a minimum of 8 hours of fasting

Blood pressure will be measured three times after the participant has been seated at rest for 10 minutes with uncrossed legs. The mean of the last two measurements will be used for statistical analysis. Systolic and diastolic blood pressure will be reported in mmHg using a brachial cuff sphygmomanometer.

Measured in mg/dL via blood analysis.

High-density lipoprotein (HDL) cholesterol measured in mg/dL via blood analysis.

Low-density lipoprotein (LDL) cholesterol measured in mg/dL via blood analysis.

A protein involved in cholesterol transport and relevant for evaluating elevated cholesterol causes, measured in mg/dL via blood analysis.

Measured in mg/dL via blood analysis

Assessed via Doppler ultrasound of the supraaortic trunks. If plaques are present, the total plaque area will be measured in cm², and changes in plaque area will be tracked throughout the study.

Measured in kilograms (kg)

Calculated from weight and height using the formula: BMI = weight (kg) / [height (m)]².

Measured at the midpoint between the lowest rib and the iliac crest during maximal inspiration and expiration, in centimeters (cm)

Evaluated using the HOMA-IR index (Homeostasis Model Assessment of Insulin Resistance), which estimates insulin resistance and beta-cell function. Determined via blood analysis after a minimum 8-hour fast. Values above 2.5 may indicate T2D. Calculated as: [fasting insulin (μU/mL) x glucemia basal (mmol/L)] / 22.5 = [fasting insulin (μU/mL) x (Glucemia basal (mg/dL) x 0,0555)] / 22.5

Assessed using the HOMA-B index, which evaluates the function and activity of pancreatic beta cells. HOMA-B, together with HOMA-IR, helps in the diagnosis of T2D. Values between 167 and 175 are considered normal and not indicative of T2D. Values below this range suggest impaired beta-cell function, resulting in insufficient insulin production (insulinopenia).

Measures the amount of insulin in a blood sample. Insulin is a hormone produced by the pancreas. Normal values range between 5-25 U/mL. It will be measured via blood analysis after a minimum 8-hour fast.

Metabolic Syndrome Diagnosis is established if at least three of the following five criteria are present:

• Abdominal circumference: Men of European descent > 94 cm; Women of European descent > 80 cm. For other ethnicities, cut-off points are defined according to the International Diabetes Federation (IDF). (López De La Torre et al., 2010)
• Fasting glucose: > 100 mg/dL or receiving pharmacological treatment for hyperglycemia.
• Triglycerides: > 150 mg/dL or receiving lipid-lowering therapy.
• HDL cholesterol: < 40 mg/dL in men; < 50 mg/dL in women, or receiving lipid-lowering therapy.
• Blood pressure: Systolic > 130 mmHg or Diastolic > 85 mmHg, or receiving antihypertensive treatment.

Non-alcoholic fatty liver disease (NAFLD) is a condition characterized by excessive fat accumulation in the liver. Its severity can vary according to the score: < -1.455 low risk, -1.455 to 0.675 intermediate risk, > 0.675 high risk (Angulo et al., 2007; Kotronen et al., 2009).

The calculation is determined using the following formula:

-2.89 + 1.18 × Metabolic Syndrome (Yes = 1 / No = 0) + 0.45 × T2DM (Yes = 2 / No = 0) + 0.15 × Fasting Insulin (mU/L) + 0.04 × Fasting Serum AST (U/L) - 0.94 × AST/ALT ratio

The identification and quantification of fibrosis are clinically relevant since fibrosis is associated with an unfavorable clinical prognosis. An NFS > 0.676 indicates the presence of advanced fibrosis (Angulo et al., 2007; Kotronen et al., 2009). The calculation is determined using the following formula:

-1.675 + 0.037 × Age (years) + 0.094 × BMI (kg/m²) + 1.13 × IFG/diabetes (Yes = 1 / No = 0) + 0.99 × AST/ALT ratio - 0.013 × Platelets (×10⁹/L) - 0.66 × Albumin (g/dL)

Physical activity will be assessed using the International Physical Activity Questionnaire (IPAQ)

The 24-hour dietary recall questionnaire will be administered at each biweekly visit

Measured by a study-specific questionnaire

Alcohol intake will be quantified using a questionnaire combined with a standardized alcohol unit conversion calculator

Measured by a study-specific questionnaire

SF-36: This is a generic scale that provides a health status profile and is applicable both to patients and to the general population

Defined Daily Dose (DDD) by active substance: DDDs of the active substances consumed will be classified according to ATC7. Each ATC classification has a defined daily dose based on international standards, which determine the recommended maximum daily amount for the approved indication of the active substance

Episodes of hypoglycemia detected by patients through capillary blood glucose levels and/or recorded in eCAP during the intervention (plasma glucose <60 mg/dl)

Episodes of hyperglycemia recorded in eCAP during the intervention (plasma glucose >350 mg/dl accompanied by compatible symptoms such as general malaise, nausea, asthenia, among others)

Annual contacts with the healthcare system including Primary Care (physicians and nursing), Specialized Care, and Emergency Care

Emergency visits related to diabetes during the intervention period