Kwame Osei

Peripheral insulin resistance rather than beta cell dysfunction accounts for geographical differences in impaired fasting blood glucose among sub-Saharan African individuals: findings from the RODAM study

Aims/hypothesisThe aim of this study was to assess the extent to which insulin resistance and beta cell dysfunction account for differences in impaired fasting blood glucose (IFBG) levels in sub-Saharan African individuals living in different locations in Europe and Africa. We also aimed to identify determinants associated with insulin resistance and beta cell dysfunction among this population.MethodsData from the cross-sectional multicentre Research on Obesity and Diabetes among African Migrants (RODAM) study were analysed. Participants included Ghanaian individuals without diabetes, aged 18–96xa0years old, who were residing in Amsterdam (nu2009=u20091337), Berlin (nu2009=u2009502), London (nu2009=u2009961), urban Ghana (nu2009=u20091309) and rural Ghana (nu2009=u2009970). Glucose and insulin were measured in fasting venous blood samples. Anthropometrics were assessed during a physical examination. Questionnaires were used to assess demographics, physical activity, smoking status, alcohol consumption and energy intake. Insulin resistance and beta cell function were determined using homeostatic modelling (HOMA-IR and HOMA-B, respectively). Logistic regression analysis was used to study the contribution of HOMA-IR and inverse HOMA-B (beta cell dysfunction) to geographical differences in IFBG (fasting glucose 5.6–6.9xa0mmol/l). Multivariate linear regression analysis was used to identify determinants associated with HOMA-IR and inverse HOMA-B.ResultsIFBG was more common in individuals residing in urban Ghana (OR 1.41 [95% CI 1.08, 1.84]), Amsterdam (OR 3.44 [95% CI 2.69, 4.39]) and London (OR 1.58 [95% CI 1.20 2.08), but similar in individuals living in Berlin (OR 1.00 [95% CI 0.70, 1.45]), compared with those in rural Ghana (reference population). The attributable risk of IFBG per 1 SD increase in HOMA-IR was 69.3% and in inverse HOMA-B was 11.1%. After adjustment for HOMA-IR, the odds for IFBG reduced to 0.96 (95% CI 0.72, 1.27), 2.52 (95%CI 1.94, 3.26) and 1.02 (95% CI 0.78, 1.38) for individuals in Urban Ghana, Amsterdam and London compared with rural Ghana, respectively. In contrast, adjustment for inverse HOMA-B had very minor impact on the ORs of IFBG. In multivariate analyses, BMI (βu2009=u20090.17 [95% CI 0.11, 0.24]) and waist circumference (βu2009=u20090.29 [95%CI 0.22, 0.36]) were most strongly associated with higher HOMA-IR, whereas inverse HOMA-B was most strongly associated with age (βu2009=u20090.20 [95% CI 0.16, 0.23]) and excess alcohol consumption (βu2009=u20090.25 [95% CI 0.07, 0.43]).Conclusions/interpretationOur findings suggest that insulin resistance, rather than beta cell dysfunction, is more important in accounting for the geographical differences in IFBG among sub-Saharan African individuals. We also show that BMI and waist circumference are important factors in insulin resistance in this population.

Ethnic differences in glucose effectiveness and disposition index in overweight/obese African American and white women with prediabetes: A study of compensatory mechanisms

OBJECTIVEnPrediabetes, a major precursor of type 2 diabetes, varies among ethnic populations. Therefore, we compared the pathophysiologic mechanisms of prediabetes in overweight/obese African American (AA) and White American (WA) women.nnnSUBJECTS AND METHODSnWe recruited 95 women (67 AA, 28 WA) with prediabetes. Standard OGTT and FSIVGTT were performed in each subject. Insulin sensitivity (Si), glucose effectiveness (Sg), beta cell function (acute insulin response to glucose (AIRg) and disposition index (DI: Si×AIRg) were calculated using Bergmans Minmod.nnnRESULTSnMean BMI was greater in AA vs WA with prediabetes (38.3±8.2vs 34.6±8.5kg/m2, p=0.05). Mean fasting serum glucose, and insulin levels were lower in AA vs WA. Similarly, mean peak serum glucose levels were lower while peak insulin levels were higher at 30 and 60minutes in AA vs WA. In contrast, mean fasting and peak serum c-peptide levels at 60 and 90minutes were significantly lower in AA vs WA. Mean AIRg was higher but not significantly different in AA vs WA (633±520.92 vs 414.8±246.8, p=0.193). Although, Si (2.93±3.25vs 44 2.50±1.76 (×10-4×min-1 [μU/ml]-1), p=0.448) was not different, DI was significantly higher in AA vs WA (1381±1126 vs 901.9±477.1, p=0.01). In addition, mean Sg was significantly higher in AAvs WA (2.51±1.17 vs 1.97±0.723 (×10-2/min), p=0.02).nnnCONCLUSIONSnWe found that in overweight/obese prediabetic AA and WA women with similar Si, the mean Sg and DI were significantly higher in AA. We conclude that the pathophysiologic mechanisms of prediabetes differ in the overweight/obese AA and WA women.

Racial Disparities in the Pathogenesis of Type 2 Diabetes and its Subtypes in the African Diaspora: A New Paradigm.

The global epidemic of diabetes has extended to the developing countries including Sub-Sahara Africa. In this context, blacks with type 2 diabetes in the African Diaspora continue to manifest 1.5–2 times higher prevalent rates than in their white counterparts. Previous studies have demonstrated that blacks with and without type 2 diabetes have alterations in hepatic and peripheral insulin sensitivity, beta-cell function, and hepatic insulin clearance as well as hepatic glucose dysregulation when compared to whites. In addition, non-diabetic blacks in the African Diaspora manifest multiple metabolic mediators that predict type 2 diabetes and its subtypes. These pathogenic modifiers include differences in subclinical inflammation, oxidative stress burden, and adipocytokines in blacks in the African Diaspora prior to clinical diagnosis. Consequently, blacks in the African Diaspora manifest subtypes of type 2 diabetes, including ketosis-prone diabetes and J type diabetes. Given the diversity of type 2 diabetes in blacks in the African Diaspora, we hypothesize that blacks manifest multiple early pathogenic defects prior to the diagnosis of type 2 diabetes and its subtypes. These metabolic alterations have strong genetic component, which appears to play pivotal and primary role in the pathogenesis of type 2 diabetes and its subtypes in blacks in the African Diaspora. However, environmental factors must also be considered as major contributors to the higher prevalence of type 2 diabetes and its subtypes in blacks in the African Diaspora. These multiple alterations should be targets for early prevention of type 2 diabetes in blacks in the African Diaspora.

James R. Gavin III, MD, PhD—A Humble and Remarkable Trailblazer, Scientist, Advocate, Mentor, and Educator for Diabetes

James Raphael Gavin III, MD, PhD, represents the quintessential scientist, educator, trailblazer, and type of leader most people aspire to become. The breadth and depth of his contributions to the scientific and medical community in the area of diabetes are unparalleled, while his passion has pushed him to unprecedented heights in American medicine. His original research as a young investigator at the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health (NIH) has greatly contributed to our understanding of insulin receptor binding and function. This factor advanced the understanding of the mechanism of insulin resistance and the role of hyperinsulinemia in obesity and type 2 diabetes. These observations have become the pathophysiologic hallmarks of both diseases.nnJames R. Gavin III was born 23 November 1945 in Mobile, Alabama, the fourth of James R. Gavin II and Bessie Smoke Gavin’s seven children. Gavin’s father worked for the shipbuilding company in Mobile doing welding and sandblasting, and he eventually became a self-made chemist.nnAs a child Gavin played sports and “went to church a lot.” Because he was a precocious child and easily bored with kindergarten, he started public school at an early age, attending segregated public schools (in Mobile). “[I] had the most fantastic teachers and educational experience at all levels, including opportunities to pursue a number of extracurricular activities,” said Gavin. One particular highlight was meeting Rev. Dr. Martin Luther King Jr. As a high school freshman, he was selected to give the Gettysburg Address at the annual Emancipation Proclamation celebration in Mobile, where Dr. King was the keynote speaker. Gavin said, “I sat mesmerized behind him as he spoke for almost 90 minutes in spellbinding fashion, without a single note! I will always remember that event and always cherish that he leaned over …

Pathogenic mechanisms of prediabetes in obese vs. very obese African American women: Implications for diabetes prevention

BACKGROUNDnThe influence of obesity on the development of prediabetes among African American women (AAW) remains uncertain. Thus, we investigated whether the pathogenic mechanisms of prediabetes differ in obese (OB, BMI<35xa0kg/m2) and very obese (VOB, BMI>35xa0kg/m2) AAW.nnnSUBJECTS/METHODSnWe recruited 26-OB and 41-VOB, AAW with prediabetes, mean age (46.3xa0±xa010.3 years), A1C (5.9xa0±xa00.4%) and BMI (38.3xa0±xa08.2xa0kg/m2). OGTT and FSIVGT were performed in each subject. Body composition (% body fat) was measured using DEXA. Si, Sg acute insulin response to glucose (AIRg) and disposition index (DI) were calculated using minimal model method.nnnRESULTSnMean BMI (32.6xa0±xa01.9 vs. 42.8xa0±xa05.5xa0kg/m2) and %body fat (44.7xa0±xa02.0 vs. 49.6xa0±xa02.2%) were significantly (pxa0=xa00.0001) lower in OB vs VOB. Mean fasting and post-glucose challenge, (glucose, insulin, c-peptide) levels were significantly (pxa0=xa00.03-0.0001) lower in OB vs VOB. Mean Si and Sg was not different. Mean AIRg tended to be higher (808xa0±xa0776 vs. 535xa0±xa0443 (x min [uU/L] -1), pxa0=xa00.106) whereas DI was greater (1999xa0±xa01408 vs. 1511xa0±xa01033, (×10-2 x min-1), pxa0=xa00.01) in OB vs VOB subjects.nnnCONCLUSIONnWe found that OB and VOB AAW had similar Si and Sg, but VOB showed attenuated AIRg and DI. These parameters should be considered when developing primary prevention programs in AAW with prediabetes.

Effects of diet-induced weight loss on the cardiometabolic markers in obese African American and white women with prediabetes

Objective: The objective was to investigate the effects of a 6 month diet-induced weight loss (DIWL) on glucose homeostasis, cardiometabolic variables, and high density lipoproteins (HDL) associated functionality paraoxonase1 (PON1) enzyme in overweight/obese African American (AA) and White American (WA) women, with prediabetes. Methods: We recruited 108 obese women (67 AA and 41 WA) with prediabetes hemoglobin A 1 C (HbA 1 C; 5.7-6.4%). Metabolic studies, fasting cardiometabolic markers (lipids/lipoproteins, inflammatory markers), and PON1 were performed at 0, 3, and 6 months. Insulin sensitivity (Si), glucose effectiveness (Sg), acute insulin response to glucose (AIRg), and disposition index (DI) were obtained (Bergmans Minmod). The DIWL program consists of approximately 1200 kcal/day for 6 months. Results: The mean body mass index was greater in AA than WA (38 ± 8 vs. 34 ± 8 kg/m 2 ). DIWL resulted in a mean 7.5% and 10.3% (8kg vs. 10.3 kg) weight loss in AA versus WA. Mean fasting and 2 h serum glucose, insulin, and c-peptide levels decreased significantly during 3 and 6 versus 0 month. The mean Si, Sg, AIRg, and DI did not improve in either AA or WA. DIWL had no significant effect on the cardiometabolic markers or PON1 in the present study. Conclusions: We found ethnic differences in the magnitude of the weight loss. However, modest weight loss had no impact on the glucose homeostasis, cardiovascular markers, and HDL functionality in prediabetic AA and WA women.