- Endocrine, Diabetes and Metabolism Fellowship, Medical College of Pennsylvania, 1988-1990
- Nutrition Fellowship, Hospital of the University of Pennsylvania, 1987-1988
- Internal Medicine Residency, Reading Hospital and Medical Center, 1983-1986
- M.D., University of Pennsylvania School of Medicine, 1982
- B.A., Brown University, 1976
The purpose of our research is to design screening tests and early interventions to decrease the impact of the diabetes and heart disease epidemic that is now occurring in African descent populations worldwide.
Diabetes and heart disease are reaching epidemic proportions in people of African descent. To reverse this trend and improve longevity and quality of life, clarity on the causes of cardiometabolic disease in people of African descent and improved screening is essential. Diabetes and heart disease result from the combined effects of insulin resistance andrelative beta- cell failure. The earliest etiological and epidemiological studies were done in populations of white European descent such as Framingham Heart Study, the Nurse’s Health Study and the Physician’s Health Study. This initial work demonstrated that insulin resistance and the associated hypertriglyceridemia were the major and earliest causes of cardiometabolic disease. This research subsequently informed the development of screening tests for diabetes and heart disease. Hence, the majority of screening tests for diabetes and heart disease focus on triglyceride (TG) levels and insulin resistance. TG-based screening tests depend on the principle that elevated TG levels are an excellent marker of insulin resistance and should trigger intervention to prevent diabetes and heart disease. TG-based screening tests include the Metabolic Syndrome, the TG/HDL-Ratio, and the Hypertriglyceridemic Waist.
In the first phase of our research, we determined that TG-based screening tests failed to detect early cardiometabolic disease in African-Americans and African immigrants to the United States. The major reason for this failure is that in African descent populations, insulin resistance does not trigger hypertriglyceridemia. Thus, TG levels are not a key marker of risk. These TG-based screening tests often diagnose people of African descent as normal at a time when intervention could have delayed or prevented disease. Hence, TG-based screening tests represent a lost opportunity for early intervention and contribute to health disparities. Once we made the observation that TG-based screening tests were not optimally beneficial in African descent populations, we used metabolic testing and mathematical modeling to identify the etiology. Factors that have been uncovered so far include the following findings: African-Americans have high levels of the enzyme lipoprotein lipase, great sensitivity to insulin-induced free fatty acid suppression, and low levels ofapoC-III and visceral adipose tissue. We are also exploring whether hyperinsulinemia and the corresponding sequale of relative beta-cell failure has a greater impact than insulin resistance on the development of cardiometabolic disease and obesity in African descent populations.
Currently we are focusing on 4 areas: (1) identifying the best screening tests to detect pre-diabetes and diabetes in blacks; (2) the effect of sickle cell trait (SCT), HbC trait and G6PD deficiency on A1C’s performance of a diagnostic test for both prediabetes and diabetes; (3) the psychosocial determinants of diabetes and heart disease in African immigrants with specific attention to the effect of the stress and reason for immigration on risk for diabetes and heart disease in African immigrants; (4) the identification of waist circumference (WC) thresholds that predict risk for cardiometabolic disease in Africans.
Best screening tests to detect prediabetes and diabetes in Africans.
We have previously shown that in African immigrants, A1C had a diagnostic sensitivity for detection of abnormal glucose tolerance of only ~50%. But combining A1C with fasting glucose increased sensitivity to ~70%.
We have evaluated the diagnostic efficacy of two new nonfasting diagnostic markers of hyperglycemia, specifically glycated albumin (GA) and fructosamine. We found that glycated albumin performs better as a diagnostic test than fructosamine. In addition, we reported that the diagnostic efficacy of A1C combined with GA is ~70% this is as good as the sensitivity of A1C combined with fasting plasma glucose. The public health advantage of A1C combined with GA is that the detection of glycemic status, will not require fasting and therefore the opportunity for widespread screening for diabetes will be increased. Our next focus is identifying the African immigrants with hyperglycemia not detected by either A1C or GA and figuring out why.
An additional important and unique of our work is that we are evaluating the reproducibility of the OGTT, as well as fasting plasma glucose (FPG), A1C, GA and fructosamine in the diagnosis of hyperglycemia in African immigrants. Our preliminary results are that the results of the OGTT as a diagnostic test are very reproducible. For FPG and A1C, the diagnostic sensitivity is very low and that this low sensitivity does not improve with repeated testing. Data on the reproducibility of GA and fructosamine is pending.
Effect of SCT, HbC trait and G6PD deficiency on the diagnostic efficacy of A1C
As the “A” in “A1C” stands for hemoglobin A, hemoglobinopathies such as sickle cell trait (SCT) and HbC trait have levels of HbA which are lower than normal by 25 to 50%. Therefore in the presence of either SCT or HeA1C might not correctly reflect glycemia. While there is some published data, much of it conflicting on the effect of SCT on A1C as a diagnostic test, there is no published data on the effect of HbC trait. This is because most studies either exclude people with HbC trait or combine them with SCT. Therefore, the separate effect of HbC trait on A1C is not known. In our study we have 14 people with HbC trait, 50 percent of whom had either prediabetes or diabetes. In this small sample the diagnostic sensitivity of A1C was 0% and the specificity was 100%. We need to continue to recruit, discover HbC trait on electrophoresis and evaluate. If this finding holds, it will be important in areas of the world where the prevalence of both diabetes and HbC trait are high to have diagnostic alternatives to A1C.
G6PD Deficiency was recognized by genetic studies to be associated with low A1C levels even in the presence of hyperglycemia. This finding needs to be tested clinically. Therefore we sought permission to test this and even though the number of African immigrants who have been evaluated to date are few (n=24), this appears to be true. Consecutive testing of African immigrants who have G6PD deficiency should yield the answer.
Psychosocial determinants of diabetes and heart disease in African immigrants
We have demonstrated that the reason for immigration affects biologic stress measured by allostatic load. When reasons for immigration were associated with keeping the family intact, the allostatic load was much lower than when the reason for immigration was work, study or asylum/refugee.
Going forward, we are evaluating the degree to which biologic stress related to reason for immigration translates into increased risk for both obesity and diabetes.
Identification of WC thresholds which predict insulin resistance in Africans
Risk for cardiometabolic disease is closely linked to insulin resistance and visceral adipose tissue (VAT) volume. Waist circumference is a proxy for VAT. We have previously shown that at every level of WC, Africans have a higher VAT volume. Therefore, the WC thresholds derived in populations of African Americans cannot be assumed to valid in Africans and primary studies of Africans are necessary. We are obtaining CT scans to measure VAT and OGTT to determine to both insulin resistance and glucose tolerance status, we found that the WC which predicted insulin resistance in African immigrant men was 91 cm and in African immigrant women 96 cm. We were able to conduct this study because we have access through collaboration with the Radiology Department at the Clinical Center to CT scans with special windows to measure adipose tissue. This work was just accepted in August 2018 for publication in the British Medical Journal-Global Health. We are now proceeding to validation studies.
Overall, there is great public health significance to our work with African descent populations. This work should lead to results that convert undiagnosed diabetes into diagnosed diabetes and better prevention of diabetes and its complications including cardiovascular disease in African descent populations worldwide.
Applying our Research
My research will improve cardiometabolic health through better screening and early intervention.
Need for Further Study
We need to explore and identify universal screening tests for diabetes and heart disease.
- Hepatic and Extrahepatic Insulin Clearance Are Differentially Regulated: Results From a Novel Model-Based Analysis of Intravenous Glucose Tolerance Data.
- Polidori DC, Bergman RN, Chung ST, Sumner AE.
- Diabetes (2016 Jun) 65:1556-64. Abstract/Full Text
- Stress Measured by Allostatic Load Score Varies by Reason for Immigration: The Africans in America Study.
- Utumatwishima JN, Baker RL Jr, Bingham BA, Chung ST, Berrigan D, Sumner AE.
- J Racial Ethn Health Disparities (2018 Apr) 5:279-286. Abstract/Full Text
Research in Plain Language
The specific goal of this research program is the identification of screening tests that are effective in detecting individuals of African descent who are at high risk for developing diabetes. Screening tests which work well create the opportunity to intervene when both disease prevention and minimization of complications can be optimized. Due to the magnitude and multiplicity of racial and ethnic differences, the Section on Ethnicity and Health is a major advocate for evaluating screening tests in the populations in which they are going to applied. The African descent populations with whom the Section is currently working include: African Americans, African immigrants to the United States and Africans living in sub-Saharan Africa.