Dr. Mandana Khalili presensts on

1. Clinical &
Translational
Factors associated with impairment of insulin secretion in HCV infection:
Sciences impact of Latino ethnicity
Institute †Sun Kim MD, Claudia Ayala MSc, Jacquelyn Maher MD, Mandana Khalili MD
Dept of Medicine and Liver Center, University of California San Francisco, San Francisco, CA; †Stanford University, Palo Alto, CA
UCSF
Introduction Methods Results Figure 2. Comparison of total integrated insulin
secretion rate (ISR-AUC) in relation to severity of
HCV is associated with type 2 diabetes and Glucose-stimulated insulin secretion rate (GS-ISR) Overall, both indices of insulin secretion as determined insulin resistance (SSPG) in Latinos versus Whites
insulin resistance. dose-response curves were determined using a by c-peptide AUC (r=0.61, p<0.001) and the total
240 min graded intravenous glucose infusion. The integrated (AUC) GS-ISR (r=0.43, p<0.001) correlated
Impairment of -cell function is a major
total integrated area under the curve (AUC) of with SSPG.
pathophysiologic mechanism of type 2 diabetes.
glucose, insulin, c-peptide, and insulin secretion The GS-ISR AUC was independently associated with
In addition, race/ethnicity is a risk factor for
rate during glucose infusion test was calculated SSPG levels (coef 3.5, 95%CI 2.1-4.8, P<0.0001) when
diabetes and Latinos represent a particularly high-
using the trapezoidal method. controlling for age, BMI, and gender.
risk group.
Limited data using indirect measures of insulin Statistical analysis was performed using unpaired t Latinos (compared to Whites) had lower insulin secretion
secretion in HCV infection show conflicting test and Spearman’s Rank Correlation. Regression (GS-ISR AUC coef -410, 95%CI -834 to -69 pmol/min,
results. Data evaluating a racially diverse HCV- modeling was used to assess factors associated p=0.038) when controlling for severity of insulin
infected population using direct methods for with insulin secretion. resistance (SSPG). Other factors, such as current or
measuring insulin secretion is lacking. past alcohol intake, duration of alcohol intake, family
history of diabetes, liver disease findings on biopsy
(inflammation, fibrosis, steatosis), HCV viral levels, and
HCV genotype, were not associated with GS-ISR AUC
Aim Results when controlling for SSPG levels.
Table 1. Patient characteristics (N=74)
To assess the host and viral factors associated with Figure 1. Insulin secretion rate (GS-ISR) in Conclusions
impaired insulin secretion in relation to the severity of Mean Age (yr) 48 ± 9 Latinos compared to Whites
Male 68% Latinos with HCV infection have a lower degree of
insulin resistance in HCV using a direct and insulin secretion in relation to severity of insulin
White 54%
GS-ISR (pmol/min)
validated method. 1200
African American 17% 1000 resistance.
Latino 16%
800
Mean BMI (Kg/m2) 26 ± 4 White There is a potential impairment of insulin secretion
600
IVDU 77% Latino amongst the HCV-infected Latinos compared to
400
Mean HCV Duration (yr) 27±9 other HCV-infected racial groups that may
Methods HCV Genotype 1 71%
200
contribute to a higher prevalence of diabetes in this
Mean log10 HCV RNA (IU/mL) 6±1 0
population.
74 consecutive non-diabetics with detectable HCV Median ALT (IU/L) 68 (19- 5 6 7 8 9
RNA (by PCR) and no evidence of cirrhosis were 556) Glucose (mmol/L) Our data suggests a need for further evaluation of
enrolled. Mean SSPG (mmol/dL) 7±4 contribution of HCV per se to abnormalities in
Mean Fasting Glucose (mmol/L) 5±1 insulin secretory function in this at-risk population.
Insulin-mediated glucose uptake (insulin Mean Fasting Insulin (pmol/L) 112 ± 69
resistance) was quantified by measuring the When assessing all the host and viral factors, Latino
Family History of Diabetes 40%
steady-state plasma glucose (SSPG) ethnicity (compared to Whites) was the only predictor of This work was supported by Grant Number R01 DK074673,
concentration during the last 30 minutes of a 240- lower GS-ISR AUC (coef -263.6, 95%CI -520.4 to -6.9 ADA 1-07-CR-70 from NIH/NIDDK and American Diabetes
minute continuous infusion of octreotide, glucose pmol/min, P=0.04) after controlling for age, BMI, gender, Foundation, and UL1 RR024131 from the National Center
for Research Resources (NCRR), and the UCSF Liver
and insulin. and SSPG.
Center (NIH P30 DK 026743). There are no conflicts of
interest to report. This poster does not include any off label
or investigational use.