Clinical trial NCT03308773: Disease Prevention in Clinical Practice Base on Patient Specific Physiology
Official title: Physiology of Disease Prevention Observational Study in Clinical Practice
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: PreDiabetes
Insulin Resistance
Type2 Diabetes
NASH - Nonalcoholic Steatohepatitis
Diastolic Dysfunction
Dementia
Atrial Fibrillation
Cancer
Atherosclerosis
Carotid Plaque
Keywords: Prediabetes
insulin resistance
T2DM
Carotid IMT/Plaque
Lead sponsor: Pacific Coast Family Medical Group
Sponsor class: OTHER
First posted: 2017-10-13
Enrollment: 5000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Internal Medicine/Endocrinology private practice in Southern California

Brief summary: It is well known that the Type 2 diabetes and vascular disease are preceded by over ten years by metabolic dysfunction and anatomic changes that can be quantified. In order to develop effective preventive strategies and reduce the cost burden to the health care system, recognition of the earliest pathophysiology of Type 2 diabetes and vascular disease is clinically relevant. The interval retrospective evaluation of data from patient records, reflect the effectiveness of the various treatments implemented in clinical practice.

Prevalence of "prediabetes" among American adults is estimated to be \~84 million, or one out of three Americans. Over a 5-7 year period approximately one third of these prediabetic individuals will progress to type 2 diabetes. Prediabetes is a heterogenous group comprised of individuals with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and increased A1c (5.7-6.4%). Although different pathophysiologies are present in individuals with IFG and IGT, their conversion rate to overt type 2 diabetes mellitus (T2DM) is similar.

Insulin resistance is a common causal feature of many of the pathophysiologic mechanisms linking macrovascular disease and type 2 diabetes. Because hyperglycemia is the major factor responsible for the development of microvascular complications, it logically follows that prevention of progression of prediabetes to overt diabetes should retard/prevent the development of the microvascular complications. From the measurement of plasma glucose, insulin, and c-peptide levels during the oral glucose tolerance test, one can derive measures of the two core defects responsible for the development of T2DM, i.e. insulin resistance and beta cell dysfunction as well as the degree of dysglycemia.

By combining a standard medical evaluation with the evaluation of cardiovascular biomarkers, patients at intermediate risk of vascular disease can be identified. In these patients, carotid intima media thickness (IMT) and carotid plaque evaluation is offered to attempt to clarify risk.

The hypothesis of this observational study is that the characterization of the physiology and anatomy of patients at risk of developing type 2 diabetes and/or cardiovascular disease can stratify risk of developing disease and direct treatment strategies tailored to the identified physiologic defect, leading to improvements in the delay or prevention of disease.

Detailed description: It is well known that the Type 2 diabetes and vascular disease are preceded by over ten years by metabolic dysfunction and anatomic changes that can be quantified. In order to develop effective preventive strategies and reduce the cost burden to the health care system, recognition of the earliest pathophysiology of Type 2 diabetes and vascular disease is clinically relevant. In patients with risk factors for type 2 diabetes and/or vascular disease, we have quantified this dysmetabolic state using glucose tolerance testing to quantify insulin resistance and beta cell function while measuring vascular biomarkers as well as Intima-media thickness and carotid plaque to characterize cardiovascular risk. The interval retrospective evaluation of data from patient records, reflect the effectiveness of the various treatments implemented in clinical practice.

Prevalence of "prediabetes" among American adults is estimated to be \~84 million, or one out of three Americans. Over a 5-7 year period approximately one third of these prediabetic individuals will progress to type 2 diabetes. Prediabetes is a heterogenous group comprised of individuals with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and increased A1c (5.7-6.4%). Although different pathophysiologies are present in individuals with IFG and IGT, their conversion rate to overt type 2 diabetes mellitus (T2DM) is similar.

Prospective epidemiologic studies have demonstrated that \~40% of subjects who progress to T2DM over 5 years had Normal glucose tolerance (NGT) at baseline, suggesting that a large group of NGT subjects also are at increased T2DM risk. It has previously been demonstrated that a 1-hour plasma glucose concentration \>155 mg/dl identifies a subgroup of NGT subjects with high future T2DM risk.

Further, multiple studies have demonstrated that background retinopathy, microalbuminuria, and peripheral neuropathy are present in 10-20% of prediabetic individuals. Compared with normoglycemic patients, those with prediabetes were associated with a 13-30% higher risk for composite cardiovascular disease.

Insulin resistance is a common causal feature of many of the pathophysiologic mechanisms linking macrovascular disease and type 2 diabetes. Because hyperglycemia is the major factor responsible for the development of microvascular complications, it logically follows that prevention of progression of prediabetes to overt diabetes should retard/prevent the development of the microvascular complications. From the measurement of plasma glucose, insulin, and c-peptide levels during the oral glucose tolerance test, one can derive measures of the two core defects responsible for the development of T2DM, i.e. insulin resistance and beta cell dysfunction as well as the degree of dysglycemia.

The need for improvement in the identification of asymptomatic atherosclerosis is exemplified by the observation that nearly 50% of patients suffering a first myocardial infarction have either, none or only one of the standard risk factors; smoking, diabetes, hypercholesterolemia, hypertension and family history of heart disease. By combining a standard medical evaluation with the evaluation of cardiovascular biomarkers, patients at intermediate risk of vascular disease can be identified. In these patients, carotid intima media thickness and carotid plaque evaluation is offered to attempt to clarify risk.

Further associations exist between insulin resistance and other medical conditions including; fatty liver, epicardial fat, diastolic dysfunction, arrhythmia, dementia and cancer. Quantifying insulin resistance may allow advances in preventive strategies.

Following these evaluations, a discussion of the scientific literature as well as the risk, benefits and alternatives available, a personalized treatment plan is generated. Interval reassessment is carried out as part of the routine medical care of the patients in the practice.

The hypothesis of this observational study is that the characterization of the physiology and anatomy of patients at risk of developing type 2 diabetes and/or cardiovascular disease can stratify risk of developing disease and direct treatment strategies tailored to the identified physiologic defect, leading to improvements in the delay or prevention of disease.

Eligibility criteria: Inclusion Criteria:

* American Diabetic Association (ADA)/American Association of Clinical Endocrinologists (AACE) criteria for patients at risk for developing type 2 diabetes

Exclusion Criteria:

* Patients with prior treatment with medications for type 2 diabetes

Primary outcomes:
measure: Number of participants who develop type 2 diabetes based on response to oral glucose tolerance test
timeFrame: 6 months and an average of every 2 years through the study completion, approximately 20 years
measure: Time to development of type 2 diabetes
timeFrame: 6 months and an average of every 2 years through the study completion, approximately 20 years
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Providence St Josephs Health
name: John P Armato, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Armato J, DeFronzo RA, Abdul-Ghani M, Ruby R. Successful treatment of prediabetes in clinical practice: targeting insulin resistance and beta-cell dysfunction. Endocr Pract. 2012 May-Jun;18(3):342-50. doi: 10.4158/EP11194.OR.
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citation: Armato JP, DeFronzo RA, Abdul-Ghani M, Ruby RJ. Successful treatment of prediabetes in clinical practice using physiological assessment (STOP DIABETES). Lancet Diabetes Endocrinol. 2018 Oct;6(10):781-789. doi: 10.1016/S2213-8587(18)30234-1. Epub 2018 Sep 14.