Ketosis Prone Diabetes in African-Americans

NCT00426413 | Completed DMC

• 3 other identifiers: IRB00024857GCRC 1703897-2003
• Study Type: observational
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Over 50% of obese African-Americans (AA) presenting with newly diagnosed, severe hyperglycemia and/or unprovoked diabetic ketoacidosis (DKA) display clinical, metabolic, and immunogenetic features of type 2 diabetes. Prior studies indicate that these patients a) have markedly decreased insulin secretion and impaired insulin action at presentation, b) absent or low prevalence of beta-cell autoantibodies and c) are able to discontinue aggressive insulin therapy in \~70% of cases within 3 months of follow-up. These patients have been referred to as having ketosis-prone type 2 diabetes (KPDM). Most patients with KPDM, however, experience a hyperglycemic relapse within a year of insulin discontinuation. Consequently, patients with "KPDM" are an ideal model to follow throughout their clinical course. The specific aims of this proposal are to 1) identify clinical, metabolic, and immunogenetic markers that alone, or in combination, are predictive of short- and long-term near-normoglycemic remission and 2) determine whether pioglitazone or sitagliptin therapy will delay an insulin-deficient relapse once insulin is discontinued. The Principal Investigator hypothesizes that measures of beta-cell function at presentation, alone or in combination with measures of insulin sensitivity, will correlate with the ability of a patient to achieve and remain in near-normoglycemic remission. She also hypothesizes that intervention compared to placebo will preserve beta-cell function, improve insulin sensitivity, and prevent an insulin-deficient relapse. This prospective, cohort study with a RCT arm would better characterize the natural history of KPDM, facilitate the direction of long-term therapy, and likely decrease the recurrence of DKA which is associated with increased mortality and morbidity.

Conditions

Ketosis Prone Diabetes; Diabetic Ketoacidosis; Severe Hyperglycemia

Keywords

ketosis-prone diabetes; diabetic ketoacidosis; obesity; insulin dependence; mechanisms

Study Arms (3)

1

Obese AA subjects with DKA or severe hyperglycemia

Drug: pioglitazone

2

obese nondiabetic subjects, age 19-65.

3

Any subjects with recurrent DKA. Recurrent DKA is defined as more than one admission to Grady Memorial Hospital.

Interventions

pioglitazone DRUG

Obese AA subjects with DKA or severe hyperglycemia that are able to discontinue insulin at 12 weeks or less will be randomized (blinded fashion) to receive either placebo or pioglitazone qd. The subjects will be followed while in the study arm and beta-cell function will be assessed using OGTT at set intervals.

Also known as: Actos (pioglitazone)

1

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

36 Obese AA subjects with DKA or severe hyperglycemia and 8 obese nondiabetic subjects, age 19-65.

You may qualify if:

• Obese AA subjects with DKA or severe hyperglycemia and 8 obese nondiabetic subjects, age 19-65. All studies will be performed in the GCRC at Grady Memorial Hospital.
• Subjects with a BMI ≥ 28 kg/m2 will be included.
• Diagnostic criteria for DKA will include:
• a plasma glucose \> 250 mg/dl,
• a venous pH \< 7.30,
• a serum bicarbonate \< 18 mEq/l, and
• high serum ketones.
• Obese hyperglycemic patients will have:
• a blood glucose on admission \> 400 mg/dl,
• a serum bicarbonate \> 18 mEq/l, and
• negative ketones.

You may not qualify if:

• Patients with significant medical or surgical illness, including but not limited to myocardial ischemia, congestive heart failure, chronic renal insufficiency, liver failure, and infectious processes;
• Patients with recognized endocrine disorders, such as hypercortisolism, acromegaly, or hyperthyroidism;
• Bleeding disorders, or abnormalities in coagulation studies;
• Pregnancy.

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Related Publications (1)

• Vellanki P, Stefanovski D, Anzola II, Smiley DD, Peng L, Umpierrez GE. Long-term changes in carbohydrate tolerance, insulin secretion and action in African-American patients with obesity and history of hyperglycemic crises. BMJ Open Diabetes Res Care. 2020 May;8(1):e001062. doi: 10.1136/bmjdrc-2019-001062.

  PMID: 32475838 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

The study has IRB approval for blood sample collection for future DNA analyses and HLA typing.

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Hyperglycemia; Obesity

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Ketosis; Acidosis; Acid-Base Imbalance; Diabetes Complications; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Dawn D Smiley, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 22, 2007
• First Posted: January 24, 2007
• Study Start: May 1, 2007
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: November 13, 2013

Record last verified: 2013-11

Locations

US (1)