Precision Subclassification of Mental Health in Diabetes: Digital Twins for Precision Mental Health to Track Subgroups

NCT07212075 | Recruiting

• 1 other identifier: HermannsNorbert2025_08_14AM
• Study Type: observational
• Target: 1,809
• Locations: 1 country
• Sites: 3

Brief Summary

Mental conditions and disorders (e.g. distress, depressive, anxiety, and eating disorders) are more prevalent in people with diabetes (PWD) and associated with reduced quality of life and impaired glycaemic outcomes. Evidence supports a complex network between psychosocial factors and glycaemic control that can be highly variable between persons. It is assumed that subgroups exist that show different trajectories of glycaemia and mental health. Belonging to a particular subgroup may be linked with a higher risk of developing mental health problems compared to others. This suggests that it is possible to treat individuals in different subgroups in a manner that optimizes their treatment and can improve health outcomes. Accurate characterisation can inform more individualized care. This calls for a more personalised approach considering the idiosyncrasies of different subgroups. Over 3 years, the investigators have established the basis of a precision mental health approach for diabetes using n-of-1 analyses. By utilizing combined ecological momentary assessment (EMA: repeated daily sampling of psychosocial factors in everyday life) and continuous glucose monitoring (CGM), intensive longitudinal data per person could be collected. This enables the analysis of individual associations between glycaemic parameters and psychosocial variables and identification of individual sources of diabetes distress in each person. The objective of the present study is to use of the n-of-1 approach to identify subgroups of PWD who share common characteristics in the associations between glucose and psychosocial variables. The identified subgroups shall be used to develop a digital twin for precision mental health in diabetes. The digital twin serves as representation of a real person, allowing to make simulations and predictions of the course of mental health and glycaemia. These predictions can inform diabetes care and lead to more precise, personalised treatment decisions. To achieve this, a longitudinal panel including over 1,400 PWD who continuously complete EMA and questionnaire surveys and measure glucose levels using CGM was developed. Over 1000 clinical interviews to diagnose mental disorders have been conducted to identify major mental health conditions and map mental outcomes. To identify subgroups and develop the digital twin, the sampling will be expanded aiming at a total of 1,809 PWD. Incidence and remission of mental disorders will be determined via repeated interviews. The complex networks between clinical, metabolic, and psychosocial data will be analysed using machine learning, leading to new insights with the potential to shape future guidelines. These results will be used by the digital twin to predict courses of glycaemic control and mental health, translating the individual evidence into direct treatment suggestions.

Conditions

Diabetes Complications; Depression - Major Depressive Disorder; Depression Anxiety Disorder; Depression Bipolar; Depression Disorders; Anxiety Disorder (Panic Disorder or GAD); Anxiety Disorder NOS; Eating Disorder Binge; Anorexia Nervosa; Bulimia Nervosa; Eating Disorder Not Otherwise Specified; Depressed Mood; Anxiety Symptoms; Disordered Eating Behaviors; Fear of Hypoglycemia; Diabetes (DM); Diabete Mellitus; Diabete Type 1; Diabete Type 2; Diabetes Distress

Keywords

Digital Twin; Precision Medicine; Precision Mental Health; Subclassification; Trajectories; Subtypes; Person-reported Outcomes (PRO); Ecological Momentary Assessment (EMA); Continuous Glucose Monitoring (CGM); People with Diabetes (PWD); Diabetes Mellitus; HbA1c; Depression; Anxiety; Eating disorder; Diabetes Distress; TwinPeaks

Outcome Measures

Primary Outcomes (13)

• Incidence of affective disorders from baseline to follow-up (per structured diagnostic interview)

  Diagnoses of affective disorders were assessed at baseline (as part of the PRO-MENTAL study) using the corresponding section of the Brief Diagnostic Interview for Mental Disorders (Mini-DIPS OA, improved version). The PRO-MENTAL cohort is followed up in the TwinPeaks study including a re-assessment of affective disorders using the Mini-DIPS OA at 2-year follow-up. Primary outcome is the 2-year incidence of affective disorders as per structured diagnostic interview.

  Baseline, 2-year Follow-up

• Incidence of anxiety disorders from baseline to follow-up (per structured diagnostic interview)

  Diagnoses of anxiety disorders were assessed at baseline (as part of the PRO-MENTAL study) using the corresponding section of the Brief Diagnostic Interview for Mental Disorders (Mini-DIPS OA, improved version). The PRO-MENTAL cohort is followed up in the TwinPeaks study including a re-assessment of anxiety disorders using the Mini-DIPS OA at 2-year follow-up. Primary outcome is the 2-year incidence of anxiety disorders as per structured diagnostic interview.

  Baseline, 2-year Follow-up

• Incidence of eating disorders at from baseline to follow-up (per structured diagnostic interview)

  Diagnoses of eating disorders were assessed at baseline (as part of the PRO-MENTAL study) using the corresponding section of the Brief Diagnostic Interview for Mental Disorders (Mini-DIPS OA, improved version). The PRO-MENTAL cohort is followed up in the TwinPeaks study including a re-assessment of eating disorders using the Mini-DIPS OA at 2-year follow-up. Primary outcome is the 2-year incidence of eating disorders as per structured diagnostic interview.

  Baseline, 2-year Follow-up

• Depressive symptoms: Incidence at 2-year Follow-up

  Depressive symptoms are assessed with the Patient Health Questionnaire-9 (PHQ-9) at baseline, 12 months, and 24 months. PHQ-9 sum score range: 0 - 27; higher scores indicate higher depressive symptoms; scores of 10 and above are considered as elevated depressive symptoms. The incidence of depressive symptoms at 2-year follow-up compared to baseline (for persons without depressive symptoms at baseline) is a secondary outcome.

  Baseline, 2-year Follow-up

• Depressive symptoms: Remission at 2-year Follow-up

  Depressive symptoms are assessed with the Patient Health Questionnaire-9 (PHQ-9) at baseline, 12 months, and 24 months. PHQ-9 sum score range: 0 - 27; higher scores indicate higher depressive symptoms; scores of 10 and above are considered as elevated depressive symptoms. The remission of depressive symptoms at 2-year follow-up compared to baseline (for persons with elevated depressive symptoms at baseline) is a secondary outcome.

  Baseline, 2-year Follow-up

• Anxiety symptoms: Incidence at 2-year Follow-up

  Anxiety symptoms are assessed with the Generalized Anxiety Disorders-7 (GAD-7) Questionnaire at baseline, 12 months, and 24 months. GAD-7 sum score range: 0 - 21; higher scores indicate higher anxiety symptoms; scores of 10 and above are considered as elevated anxiety symptoms. The incidence of anxiety symptoms at 2-year follow-up compared to baseline (for persons without anxiety symptoms at baseline) is a secondary outcome.

  Baseline, 2-year Follow-up

• Anxiety symptoms: Remission at 2-year Follow-up

  Anxiety symptoms are assessed with the Generalized Anxiety Disorders-7 (GAD-7) Questionnaire at baseline, 12 months, and 24 months. GAD-7 sum score range: 0 - 21; higher scores indicate higher anxiety symptoms; scores of 10 and above are considered as elevated anxiety symptoms. The remission of anxiety symptoms at 2-year follow-up compared to baseline (for persons with elevated anxiety symptoms at baseline) is a secondary outcome.

  Baseline, 2-year Follow-up

• Disordered eating behaviour: Incidence at 2-year Follow-up

  Disordered eating behaviours are assessed with the Diabetes Eating Problems Survey-Revised (DEPS-R/DEPS-10) at baseline, 12 months, and 24 months. DEPS-R sum score range: 0 - 80; higher scores indicate more diabetes-related eating problems; scores of 20 and above are considered to indicate disordered eating. The incidence of disordered eating behaviours at 2-year follow-up compared to baseline (for persons without disordered eating at baseline) is a secondary outcome.

  Baseline, 2-year Follow-up

• Disordered eating behaviour: Remission at 2-year Follow-up

  Disordered eating behaviours are assessed with the Diabetes Eating Problems Survey-Revised (DEPS-R/DEPS-10) at baseline, 12 months, and 24 months. DEPS-R sum score range: 0 - 80; higher scores indicate more diabetes-related eating problems; scores of 20 and above are considered to indicate disordered eating. The remission of disordered eating behaviours at 2-year follow-up compared to baseline (for persons with disordered eating at baseline) is a secondary outcome.

  Baseline, 2-year Follow-up

• General diabetes distress over time

  General diabetes distress is assessed with the Problem Areas in Diabetes Scale (PAID) at baseline, 6-month FU, 12-month FU, 18-month FU, and 24-month FU to detect changes in diabetes distress from baseline to 2-year FU. PAID total score range: 0 - 100; higher scores indicate higher diabetes distress; scores of 40 and above are considered to indicate elevated diabetes distress.

  Baseline, 2-year Follow-Up

• Daily diabetes distress over time

  Daily diabetes distress is assessed at baseline, 6-month FU, 12-month FU, 18-month FU, and 24-month FU over each 14 consecutive days using smartphone-based ecological momentary assessment with selected items from the Problem Areas in Diabetes Scale (PAID) adapted for daily assessment (rated on an 11-point scale from 0 - 10; higher values indicate higher mental burden) to detect changes in daily burdens from baseline to 24-month FU. A 10-item sum score ranges from 0 - 100 with higher values indicating higher daily distress.

  Baseline, 2-year Follow-Up

• Glycated hemoglobin (HbA1c) over time

  HbA1c (glycated hemoglobin), a laboratory measure of average blood glucose over the past 8 to 12 weeks, is estimated/collected at baseline, 6-month FU, 12-month FU, 18-month FU, and 24-month FU from the participants to detect changes for glycated hemoglobin from baseline to 2-year FU.

  Baseline, 2-year Follow-up

• Glycemic levels (CGM glucose) over time

  Automatically recorded daily glucose values are obtained from participants where continuous glucose monitoring (CGM) devices are used. Available glucose data are extracted at baseline, 6-month FU, 12-month FU, 18-month FU, and 24-month FU for each over 14 consecutive days of CGM measurement - parallel to the daily EMA - to detect changes in glucose levels from baseline to 2-year FU.

  Baseline, 2-year Follow-Up

Secondary Outcomes (6)

• Subjective health state over time

  Baseline, 2-year Follow-up

• Wellbeing over time

  Baseline, 2-year Follow-up

• General sleep quality over time

  Baseline, 2-year Follow-up

• Daily sleep quality over time

  Baseline, 2-year Follow-up

• Fear of diabetes complications over time

  Baseline, 2-year Follow-up

Study Arms (1)

Patients with Diabetes

The subgroups of patients with type 1 diabetes versus type 2 diabetes may be analysed in individual analyses

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study participants are enrolled from the population of people with diabetes treated at several specialised diabetes centres in South Germany. Including the Diabetes Clinic Mergentheim (DCM), Diabetes Practice Mergentheim, DiaMedicum Center Würzburg.

You may qualify if:

• to 80 years of age
• Diagnosis of type 1 diabetes or type 2 diabetes or other specific type of diabetes
• Diabetes duration ≥ 1 year
• Sufficient German language skills
• Informed consent

You may not qualify if:

• Inability to consent
• Significant cognitive impairment (e.g. dementia)
• Severe disorder or condition impacting the person's ability to participate in the study or likely to confound results (e.g. treated cancer, heart disease ≥ NYHA III, schizophrenia/psychotic disorder)
• Terminal illness
• Being bedridden

Sponsors & Collaborators

• Forschungsinstitut der Diabetes Akademie Mergentheim: lead

Study Sites (3)

Diabetes Clinic Mergentheim (DCM)

Bad Mergentheim, Baden-Wurttemberg, 97980, Germany

RECRUITING

MVZ Diabetespraxis Mergentheim

Bad Mergentheim, Baden-Wurttemberg, 97980, Germany

COMPLETED

MVZ DiaMedicum Würzburg

Würzburg, Baden-Wurttemberg, 97072, Germany

COMPLETED

Related Publications (19)

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• Snoek FJ, Bremmer MA, Hermanns N. Constructs of depression and distress in diabetes: time for an appraisal. Lancet Diabetes Endocrinol. 2015 Jun;3(6):450-460. doi: 10.1016/S2213-8587(15)00135-7. Epub 2015 May 17.

  PMID: 25995123 BACKGROUND

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  PMID: 32556613 BACKGROUND

• Hermanns N, Ehrmann D, Shapira A, Kulzer B, Schmitt A, Laffel L. Coordination of glucose monitoring, self-care behaviour and mental health: achieving precision monitoring in diabetes. Diabetologia. 2022 Nov;65(11):1883-1894. doi: 10.1007/s00125-022-05685-7. Epub 2022 Apr 5.

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• Ehrmann D, Priesterroth L, Schmitt A, Kulzer B, Hermanns N. Associations of Time in Range and Other Continuous Glucose Monitoring-Derived Metrics With Well-Being and Patient-Reported Outcomes: Overview and Trends. Diabetes Spectr. 2021 May;34(2):149-155. doi: 10.2337/ds20-0096. Epub 2021 May 25.

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• Ehrmann D, Schmitt A, Priesterroth L, Kulzer B, Haak T, Hermanns N. Time With Diabetes Distress and Glycemia-Specific Distress: New Patient-Reported Outcome Measures for the Psychosocial Burden of Diabetes Using Ecological Momentary Assessment in an Observational Study. Diabetes Care. 2022 Jul 7;45(7):1522-1531. doi: 10.2337/dc21-2339.

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• Ehrmann D, Hermanns N, Schmitt A, Klinker L, Haak T, Kulzer B. Perceived glucose levels matter more than CGM-based data in predicting diabetes distress in type 1 or type 2 diabetes: a precision mental health approach using n-of-1 analyses. Diabetologia. 2024 Nov;67(11):2433-2445. doi: 10.1007/s00125-024-06239-9. Epub 2024 Jul 30.

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  BACKGROUND

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  BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Complications; Bipolar Disorder; Anxiety Disorders; Panic Disorder; Generalized Anxiety Disorder; Binge-Eating Disorder; Anorexia Nervosa; Bulimia Nervosa; Consciousness Disorders; Disordered Eating Behavior; Depression; Feeding and Eating Disorders

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Behavior; Behavioral Symptoms; Signs and Symptoms, Digestive

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. / PhD

Study Record Dates

• First Submitted: October 1, 2025
• First Posted: October 8, 2025
• Study Start: January 1, 2025
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 4, 2025

Record last verified: 2025-11

Locations

DE (3)