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Clinical Care/Education/Nutrition
Long-term changes in carbohydrate tolerance, insulin secretion and action in African-American patients with obesity and history of hyperglycemic crises
  1. Priyathama Vellanki1,
  2. Darko Stefanovski2,
  3. Isabel I Anzola1,
  4. Dawn D Smiley1,
  5. Limin Peng3,
  6. Guillermo E Umpierrez1
  1. 1Department of Medicine, Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, Georgia, USA
  2. 2Department of Clinical Studies-New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA
  3. 3Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
  1. Correspondence to Dr Priyathama Vellanki; priyathama.vellanki{at}emory.edu

Abstract

Introduction Many African-Americans (AA) with obesity with newly diagnosed diabetes presenting with diabetic ketoacidosis (DKA) or severe hyperglycemia (SH) discontinue insulin therapy and achieve near-normoglycemia remission (hemoglobin A1c (HbA1c) <7%, fasting blood glucose (FBG) <130 mg/dL) and able to be managed on oral antidiabetic agents (OAD) during follow-up. Using combined data from two randomized controlled trials, we assessed long-term carbohydrate tolerance and changes in insulin sensitivity and insulin secretion.

Research design and methods Seventy-five participants with DKA (n=33) and SH (n=42) underwent 2-hour 75 g oral glucose tolerance test (OGTT) after insulin discontinuation and every 6 months until hyperglycemia relapse (FBG ≥130 mg/dL, HbA1c >7% or two random BG ≥180 mg/dL) while treated with OAD (metformin, sitagliptin or pioglitazone) or placebo. Glucose tolerance status was defined as per the American Diabetes Association. Sensitivity index (Si) was calculated by oral minimal model, insulin secretion as the incremental area under the curve of insulin (IncreAUCi) and disposition index (DI) as Si×IncreAUCi.

Results During remission, OGTT showed normal glucose tolerance (NGT) (n=9 (12%)), prediabetes (n=34 (45%)) and diabetes (n=32 (43%)). DI and Si were higher in patients with NGT versus prediabetes versus diabetes (p<0.001), while IncreAUCi was not significantly different among NGT, prediabetes and diabetes (p=0.14). Achieving NGT status did not prolong near-normoglycemia remission. OAD treatment significantly prolonged hyperglycemia relapse-free survival (log-rank p=0.0012) compared with placebo and was associated with lower hyperglycemia relapse (HR: 0.45, 95% CI: (0.21 to 0.96), p=0.04).

Conclusions In AA patients with obesity with history of DKA and SH, near-normoglycemia remission is associated with improved insulin secretion and action with half of patients achieving NGT or prediabetes, and only half having diabetes on OGTT. NGT and prediabetes on OGTT were not associated with prolonged hyperglycemia relapse-free survival.

Trial registration number NCT01099618, NCT00426413.

  • ketoacidosis
  • insulin action
  • insulin secretion
  • antidiabetic drugs
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjdrc-2019-001062

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    Footnotes

    • PV and DS contributed equally.

    • Contributors PV conceived the study, wrote the first draft and edited the manuscript. DS performed the minimal model analysis. DDS and IIA conducted the study. LP performed data analysis. GEU conceived and performed the study. All authors critically edited the manuscript. PV is the guarantor of the work.

    • Funding PV is supported in part by K12HD085850 and K23DK113241-01A1. This work was funded by K08DK0830361 (DDS) and was supported by the National Center for Advancing Translational Sciences Award number (UL1TR002378) and 1P30DK111024-01 from the National Institutes of Health and National Research Resources. GEU is partly supported by research grants from the NIH/NATS UL1 TR002378 from the Clinical and Translational Science Award program, and 1P30DK111024-01 from NIH and National Center for Research Resources.

    • Competing interests PV has received consulting fees from Boehringer-Ingelheim and Merck. GEU has received unrestricted research support for inpatient studies (to Emory University) from Novo Nordisk, Dexcom and Sanofi. DDS has received fees for serving on the Speaker Bureau for Novo Nordisk, Merck and Sanofi. The other authors do not have any significant conflicts of interest.

    • Patient consent for publication Not required.

    • Ethics approval The Institutional Review Board at Emory University approved to report the combined results of the two randomized controlled studies (NCT01099618 and NCT00426413, www.Clinicaltrials.gov).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available on reasonable request from the PI. Please email at pvellan@emory.edu for any requests or questions.