Sun Kim, MD, MS

All Publications

• Relationship among age, insulin resistance, and blood pressure. Journal of the American Society of Hypertension Jung, C., Jung, S. H., Lee, B., Rosenberg, M., Reaven, G. M., Kim, S. H. 2017

  Abstract

  The effect of age to modify the relationship between insulin resistance and hypertension is unclear. In this retrospective, cross-sectional study, median age was used to create two age groups (<52 vs. ?52 years), and comparisons were made of metabolic characteristics, including steady-state plasma glucose (SSPG) concentrations measured during the insulin suppression test to quantify insulin resistance. Individuals were stratified into SSPG tertiles and categorized as having normal blood pressure (BP), prehypertension, or hypertension. SSPG concentrations were similar in the two age groups (161 vs. 164 mg/dL). In the most insulin-resistant tertile, distribution of normal BP, prehypertension, and hypertension was equal in those aged <52 years, whereas in those aged ?52 years, prevalence of hypertension was increased approximately fivefold compared with those with normal BP. Multivariate regression analysis demonstrated significant interaction between age and SSPG in predicting systolic BP (P = .023). In stratified analysis, SSPG, but not age, was an independent predictor of systolic BP and diastolic BP in ?52 years group, whereas the reverse was true in the younger group. The adverse impact of insulin resistance on BP was accentuated in older individuals and may have a greater impact than further aging.

  View details for DOI 10.1016/j.jash.2017.04.005

  View details for PubMedID 28558951

• Insulin clearance: an underappreciated modulator of plasma insulin concentration. Journal of investigative medicine Kim, S. H., Reaven, G. M. 2016; 64 (7): 1162-1165

  Abstract

  Plasma glucose concentrations are tightly regulated and maintained within a narrow range in non-diabetic individuals. Maintenance of this physiological state is primarily a function of the ability of the pancreatic ?-cells to modify insulin secretion rate (ISR), thus preventing wide-swings in plasma glucose concentrations. As a consequence, and in contrast to plasma glucose concentrations, plasma insulin concentrations vary substantially in non-diabetic individuals. Although differences in ISR are primarily responsible for the variability in plasma insulin concentration, there is increasing evidence that differences in insulin clearance rate (ICR) also play a role in regulation of plasma insulin concentration. The goal of this mini-review is to highlight situations that demonstrate the important role of ICR in both insulin and glucose homeostasis.

  View details for DOI 10.1136/jim-2016-000149

  View details for PubMedID 27229887

• Does enhanced insulin sensitivity improve sleep measures in patients with obstructive sleep apnea: a randomized, placebo-controlled pilot study. Sleep medicine Liu, A., Kim, S. H., Ariel, D., Abbasi, F., Lamendola, C., Cardell, J., Xu, S., Patel, S., Tomasso, V., Mojaddidi, H., Grove, K., Tsao, P. S., Kushida, C. A., Reaven, G. M. 2016; 22: 57-60

  Abstract

  High fasting insulin levels have been reported to predict development of observed apneas, suggesting that insulin resistance may contribute to the pathogenesis of obstructive sleep apnea (OSA). The aim of this study was to determine whether enhancing insulin sensitivity in individuals with OSA would improve sleep measures.Insulin-resistant, nondiabetic individuals with untreated OSA were randomized (2:1) to pioglitazone (45?mg/day) or placebo for eight weeks in this single-blind study. All individuals had repeat measurements pertaining to sleep (overnight polysomnography and functional outcomes of sleep questionnaire) and insulin action (insulin suppression test).A total of 45 overweight/obese men and women with moderate/severe OSA were randomized to pioglitazone (n?=?30) or placebo (n?=?15). Although insulin sensitivity increased 31% among pioglitazone-treated compared with no change among individuals receiving placebo (p?<0.001 for between-group difference), no improvement in quantitative or qualitative sleep measurements was observed.Pioglitazone administration increased insulin sensitivity in otherwise untreated individuals with OSA, without any change in polysomnographic sleep measures over an eight-week period. These findings do not support a causal role for insulin resistance in the pathogenesis of OSA.

  View details for DOI 10.1016/j.sleep.2016.06.005

  View details for PubMedID 27544837

• Cardiometabolic Effects of Glucagon-Like Peptide-1 Agonists. Current atherosclerosis reports Sarraju, A., Kim, S. H., Knowles, J. W. 2016; 18 (2): 7-?

  Abstract

  Cardiovascular disease is the leading cause of death among adults in the USA. Both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) are known risk factors for cardiovascular disease. Despite the development of numerous effective anti-glycemic therapies, we have been unable to completely mitigate cardiovascular risk with glucose lowering alone, and prevention of cardiovascular disease in patients with diabetes is primarily achieved with the use of medications that address other risk factors such as anti-hypertensives or statins. Glucagon-like peptide-1 (GLP-1) is a key hormone in the pathophysiology of diabetes. GLP-1 agonists have been recently approved for the treatment of T2DM as well as for chronic weight management. In this review, we aim to explore the effects of GLP-1 agonists on cardiovascular health with a focus on cardiometabolic variables and cardiac function.

  View details for DOI 10.1007/s11883-016-0558-5

  View details for PubMedID 26782825

• Hyperinsulinemia in Individuals with Obesity: Role of Insulin Clearance OBESITY Kim, M. K., Reaven, G. M., Chen, Y. I., Kim, E., Kim, S. H. 2015; 23 (12): 2430-2434

  View details for DOI 10.1002/oby.21256

  View details for Web of Science ID 000367189300023

• Salsalate-induced changes in lipid, lipoprotein, and apoprotein concentrations in overweight or obese, insulin-resistant, nondiabetic individuals. Journal of clinical lipidology Ariel, D., Kim, S. H., Liu, A., Abbasi, F., Lamendola, C. A., Grove, K., Tomasso, V., Reaven, G. M. 2015; 9 (5): 658-663

  Abstract

  Although salsalate administration consistently lowers plasma triglyceride concentrations in patients with type II diabetes, prediabetes, and/or insulin resistance, changes in low-density lipoprotein cholesterol (LDL-C) concentrations have been inconsistent; varying from no change to a significant increase. To evaluate the clinical relevance of this discordance in more detail, we directly measured LDL-C and obtained a comprehensive assessment of changes in lipid, lipoprotein, and apoprotein concentrations associated with salsalate use in insulin-resistant individuals, overweight or obese, but without diabetes, using vertical auto profile method.A single-blind, randomized, placebo-controlled study was performed in volunteers who were overweight or obese, without diabetes, and insulin resistant on the basis of their steady-state plasma glucose concentration during an insulin suppression test. Participants were randomized 2:1 to receive salsalate 3.5 g/d (n = 27) or placebo (n = 14) for 4 weeks. Comprehensive lipid, lipoprotein, and apoprotein analysis by vertical auto profile was obtained after an overnight fast, before and after study intervention.There was no change in directly measured LDL-C concentration in salsalate-treated individuals. However, salsalate administration was associated with various changes considered to decrease atherogenicity; including decreases in triglyceride and total very low-density lipoprotein cholesterol (VLDL-C) concentrations, a shift from small denser LDL lipoproteins toward larger, more buoyant LDL particles, decreases in VLDL1+2-C and LDL4-C, and nonsignificant decreases in non-high-density lipoprotein cholesterol and apolipoprotein B. No significant changes occurred in the placebo-treated group.Atherogenicity of the lipid, lipoprotein, and apoprotein profile of insulin-resistant individuals who were overweight or obese improved significantly in association with salsalate treatment. The clinical importance of this finding awaits further study.

  View details for DOI 10.1016/j.jacl.2015.06.009

  View details for PubMedID 26350812

• Salsalate-induced changes in lipid, lipoprotein, and apoprotein concentrations in overweight or obese, insulin-resistant, nondiabetic individuals. Journal of clinical lipidology Ariel, D., Kim, S. H., Liu, A., Abbasi, F., Lamendola, C. A., Grove, K., Tomasso, V., Reaven, G. M. 2015; 9 (5): 658-663

  View details for DOI 10.1016/j.jacl.2015.06.009

  View details for PubMedID 26350812

• Increased body mass index negatively impacts blastocyst formation rate in normal responders undergoing in vitro fertilization JOURNAL OF ASSISTED REPRODUCTION AND GENETICS Comstock, I. A., Kim, S., Behr, B., Lathi, R. B. 2015; 32 (9): 1299-1304

  View details for DOI 10.1007/s10815-015-0515-1

  View details for Web of Science ID 000362519600002

  View details for PubMedID 26109331

• Usefulness of Fetuin-A to Predict Risk for Cardiovascular Disease Among Patients With Obstructive Sleep Apnea. American journal of cardiology Liu, A., Lamendola, C., Ariel, D., Abbasi, F., Kim, S. H., Cardell, J., Tomasso, V., Xu, S., Patel, S., Mojaddidi, H., Grove, K., Kushida, C. A., Reaven, G. M. 2015; 116 (2): 219-224

  Abstract

  Patients with obstructive sleep apnea (OSA) are at increased risk for cardiovascular diseases (CVDs). Fetuin-A, a novel hepatokine, has been associated with the metabolic syndrome (MetS), insulin resistance, and type 2 diabetes mellitus, all of which are highly prevalent in patients with OSA and associated with increased CVD risk. The goal of this study was to determine whether fetuin-A could be involved in the pathogenesis of CVD risk in patients with OSA, through relations of fetuin-A with MetS components and/or insulin resistance. Overweight or obese, nondiabetic volunteers (n = 120) were diagnosed with OSA by in-laboratory nocturnal polysomnography. Steady-state plasma glucose concentrations derived during the insulin suppression test were used to quantify insulin-mediated glucose uptake; higher steady-state plasma glucose concentrations indicated greater insulin resistance. Fasting plasma fetuin-A and lipoprotein concentrations were measured. Whereas neither the prevalence of MetS nor the number of MetS components was associated with tertiles of fetuin-A concentrations, the lipoprotein components of MetS, triglycerides and high-density lipoprotein cholesterol, increased (p <0.01) and decreased (p <0.05), respectively, across fetuin-A tertiles. Additionally, comprehensive lipoprotein analysis revealed that very low density lipoprotein (VLDL) particles and VLDL subfractions (VLDL1+2 and VLDL3) were increased across fetuin-A tertiles. In contrast, neither insulin resistance nor sleep measurements related to OSA were found to be modified by fetuin-A concentrations. In conclusion, abnormalities of lipoprotein metabolism, but not MetS or insulin resistance per se, may represent a mechanism by which fetuin-A contributes to increased CVD risk in patients with OSA.

  View details for DOI 10.1016/j.amjcard.2015.04.014

  View details for PubMedID 25960379

• Abnormalities of lipoprotein concentrations in obstructive sleep apnea are related to insulin resistance. Sleep Liu, A., Cardell, J., Ariel, D., Lamendola, C., Abbasi, F., Kim, S. H., Holmes, T. H., Tomasso, V., Mojaddidi, H., Grove, K., Kushida, C. A., Reaven, G. M. 2015; 38 (5): 793-799

  Abstract

  Prevalence of cardiovascular disease (CVD) is increased in patients with obstructive sleep apnea (OSA), possibly related to dyslipidemia in these individuals. Insulin resistance is also common in OSA, but its contribution to dyslipidemia of OSA is unclear. The study’s aim was to define the relationships among abnormalities of lipoprotein metabolism, clinical measures of OSA, and insulin resistance.Cross-sectional study. OSA severity was defined by the apnea-hypopnea index (AHI) during polysomnography. Hypoxia measures were expressed as minimum and mean oxygen saturation, and the oxygen desaturation index. Insulin resistance was quantified by determining steady-state plasma glucose (SSPG) concentrations during the insulin suppression test. Fasting plasma lipid/ lipoprotein evaluation was performed by vertical auto profile methodology.Academic medical center.107 nondiabetic, overweight/ obese adults.Lipoprotein particles did not correlate with AHI or any hypoxia measures, nor were there differences noted by categories of OSA severity. By contrast, even after adjustment for age, sex, and BMI, SSPG was positively correlated with triglycerides (r = 0.30, P < 0.01), very low density lipoprotein (VLDL) and its subclasses (VLDL1+2) (r = 0.21-0.23, P < 0.05), and low density lipoprotein subclass 4 (LDL4) (r = 0.30, P < 0.01). SSPG was negatively correlated with high density lipoprotein (HDL) (r = -0.38, P < 0.001) and its subclasses (HDL2 and HDL3) (r = -0.32, -0.43, P < 0.01), and apolipoprotein A1 (r = -0.33, P < 0.01). Linear trends of these lipoprotein concentrations across SSPG tertiles were also significant.Pro-atherogenic lipoprotein abnormalities in OSA are related to insulin resistance, but not to OSA severity or degree of hypoxia. Insulin resistance may represent the link between OSA-related dyslipidemia and increased CVD risk.

  View details for DOI 10.5665/sleep.4678

  View details for PubMedID 25348129

• Abnormalities of Lipoprotein Concentrations in Obstructive Sleep Apnea Are Related to Insulin Resistance SLEEP Liu, A., Cardell, J., Ariel, D., Lamendola, C., Abbasi, F., Kim, S. H., Holmes, T. H., Tomasso, V., Mojaddidi, H., Grove, K., Kushida, C. A., Reaven, G. M. 2015; 38 (5): 793-?

  View details for DOI 10.5665/sleep.4678

  View details for Web of Science ID 000353876600017

  View details for PubMedID 25348129

• Relationship between insulin resistance and amino acids in women and men. Physiological reports Seibert, R., Abbasi, F., Hantash, F. M., Caulfield, M. P., Reaven, G., Kim, S. H. 2015; 3 (5)

  Abstract

  Insulin resistance has been associated with higher plasma amino acid (AA) concentrations, but majority of studies have used indirect measures of insulin resistance. Our main objective was to define the relationship between plasma AA concentrations and a direct measure of insulin resistance in women and men. This was a cross-sectional study of 182 nondiabetic individuals (118 women and 64 men) who had measurement of 24 AAs and steady-state plasma glucose (SSPG) concentration (insulin resistance) using the insulin suppression test. Fourteen out of 24 AA concentrations were significantly (P < 0.05) higher in men than women; only glycine was lower in men. Majority of these AAs were positively associated with SSPG; only glycine concentration was negatively associated. Glutamic acid, isoleucine, leucine, and tyrosine concentrations had the strongest correlation with SSPG (r ? 0.4, P < 0.001). The degree of association was similar in women and men, independent of obesity, and similar to traditional markers of insulin resistance (e.g., glucose, triglyceride, high-density lipoprotein cholesterol). Compared with women, men tended to have a more unfavorable AA profile with higher concentration of AAs associated with insulin resistance and less glycine. However, the strength of association between a direct measurement of insulin resistance and AA concentrations were similar between sexes and equivalent to several traditional markers of insulin resistance.

  View details for DOI 10.14814/phy2.12392

  View details for PubMedID 25952934

• Effect of Salsalate on Insulin Action, Secretion, and Clearance in Nondiabetic, Insulin-Resistant Individuals: A Randomized, Placebo-Controlled Study DIABETES CARE Kim, S. H., Liu, A., Ariel, D., Abbasi, F., Lamendola, C., Grove, K., Tomasso, V., Ochoa, H., Reaven, G. 2014; 37 (7): 1944-1950

  View details for DOI 10.2337/dc13-2977

  View details for Web of Science ID 000338020400030

• Effect of salsalate on insulin action, secretion, and clearance in nondiabetic, insulin-resistant individuals: a randomized, placebo-controlled study. Diabetes care Kim, S. H., Liu, A., Ariel, D., Abbasi, F., Lamendola, C., Grove, K., Tomasso, V., Ochoa, H., Reaven, G. 2014; 37 (7): 1944-1950

  Abstract

  Salsalate treatment has been shown to improve glucose homeostasis, but the mechanism remains unclear. The aim of this study was to evaluate the effect of salsalate treatment on insulin action, secretion, and clearance rate in nondiabetic individuals with insulin resistance.This was a randomized (2:1), single-blind, placebo-controlled study of salsalate (3.5 g daily for 4 weeks) in nondiabetic individuals with insulin resistance. All individuals had measurement of glucose tolerance (75-g oral glucose tolerance test), steady-state plasma glucose (SSPG; insulin suppression test), and insulin secretion and clearance rate (graded-glucose infusion test) before and after treatment.Forty-one individuals were randomized to salsalate (n = 27) and placebo (n = 14). One individual from each group discontinued the study. Salsalate improved fasting (% mean change -7% [95% CI -10 to -14] vs. 1% [-3 to 5], P = 0.005) but not postprandial glucose concentration compared with placebo. Salsalate also lowered fasting triglyceride concentration (-25% [-34 to -15] vs. -6% [-26 to 14], P = 0.04). Salsalate had no effect on SSPG concentration or insulin secretion rate but significantly decreased insulin clearance rate compared with placebo (-23% [-30 to -16] vs. 3% [-10 to 15], P < 0.001). Salsalate was well tolerated, but four individuals needed a dose reduction due to symptoms.Salsalate treatment in nondiabetic, insulin-resistant individuals improved fasting, but not postprandial, glucose and triglyceride concentration. These improvements were associated with a decrease in insulin clearance rate without change in insulin action or insulin secretion.

  View details for DOI 10.2337/dc13-2977

  View details for PubMedID 24963111

• C-reactive protein and risk of cardiovascular and all-cause mortality in 268 803 East Asians EUROPEAN HEART JOURNAL Sung, K., Ryu, S., Chang, Y., Byrne, C. D., Kim, S. H. 2014; 35 (27): 1809-1816

  Abstract

  C-reactive protein concentrations are decreased in Asians compared with people of white European ethnicity. It is uncertain whether C-reactive protein is a robust biomarker of cardiovascular disease (CVD) in Asians. This study aimed to determine the association between C-reactive protein and CVD and all-cause mortality in a large population of Koreans.Mortality outcomes for 268 803 Koreans enrolled in a health screening programme with measurements of C-reactive protein at baseline and median follow-up of 4.49 years (1 155 930 person-years) were analysed. A subset (48%) of subjects had a repeat C-reactive protein measurement during follow-up. The median (interquartile) baseline C-reactive protein values were higher in men than in women [0.6 (0.3-1.3) vs. 0.4 (0.1-1.1), P < 0.001]. Only 8.6% of men and 6.2% of women met the standard cut point for C-reactive protein >3 mg/L, which represents the top tertile in white populations. During a median follow-up of 4.49 years (1 155 930 person-years), 1047 died; 187 died of CVD causes. In men but not women, baseline C-reactive protein quartiles were linearly associated with both CVD and all-cause mortality (P < 0.001), even after adjustment for known CVD risk factors. Regardless of baseline C-reactive protein concentration, any increase or decrease in C-reactive protein over time did not affect the HR for all-cause, or CVD mortality. Models with C-reactive protein yielded a net reclassification improvement for CVD mortality of 24.9% (P = 0.04) for individuals with intermediate risk.C-reactive protein concentrations are substantially lower in Koreans than reported for whites populations. Nonetheless, C-reactive protein levels are associated with CVD and all-cause mortality in Korean men. Standard cut points for C-reactive protein may under-represent Asians at risk for CVD.

  View details for DOI 10.1093/eurheartj/ehu059

  View details for Web of Science ID 000340067200014

  View details for PubMedID 24569028

• Ability of the plasma concentration ratio of triglyceride/high-density lipoprotein cholesterol to identify increased cardio-metabolic risk in an east Asian population DIABETES RESEARCH AND CLINICAL PRACTICE Sung, K., Reaven, G., Kim, S. 2014; 105 (1): 96-101

  View details for DOI 10.1016/j.diabres.2014.04.021

  View details for Web of Science ID 000338715400014

• A retrospective cohort study to evaluate the impact of meaningful weight loss on fertility outcomes in an overweight population with infertility FERTILITY AND STERILITY Kort, J. D., Winget, C., Kim, S. H., Lathi, R. B. 2014; 101 (5): 1400-1403

  Abstract

  To determine if meaningful weight loss (?10%) improved conception and live birth rates of overweight patients with infertility.A retrospective cohort study.Academic medical center.Overweight patients (body mass index ?25 kg/m(2); n = 52) being treated for infertility and referred for weight loss counseling.Patients were given a "meaningful" weight loss goal of 10%. They were followed by an endocrinologist who provided diet and exercise recommendations, metabolic screening, and pharmacologic intervention when indicated.Pregnancy rate, live birth rate, weight loss.Thirty-two percent of the patients achieved meaningful weight loss. Patients achieving meaningful weight loss had significantly higher conception (88% vs. 54%) and live birth rates (71% vs. 37%) than those who did not.Weight loss improves live birth rates in overweight patients with infertility. Health care providers should incorporate weight loss counseling when caring for overweight patients who plan to conceive.

  View details for DOI 10.1016/j.fertnstert.2014.01.036

  View details for Web of Science ID 000335504600043

  View details for PubMedID 24581574

• Pancreatic beta cell function following liraglutide-augmented weight loss in individuals with prediabetes: analysis of a randomised, placebo-controlled study. Diabetologia Kim, S. H., Liu, A., Ariel, D., Abbasi, F., Lamendola, C., Grove, K., Tomasso, V., Reaven, G. 2014; 57 (3): 455-462

  Abstract

  Liraglutide can modulate insulin secretion by directly stimulating beta cells or indirectly through weight loss and enhanced insulin sensitivity. Recently, we showed that liraglutide treatment in overweight individuals with prediabetes (impaired fasting glucose and/or impaired glucose tolerance) led to greater weight loss (-7.7% vs -3.9%) and improvement in insulin resistance compared with placebo. The current study evaluates the effects on beta cell function of weight loss augmented by liraglutide compared with weight loss alone.This was a parallel, randomised study conducted in a single academic centre. Both participants and study administrators were blinded to treatment assignment. Individuals who were 40-70 years old, overweight (BMI 27-40 kg/m(2)) and with prediabetes were randomised (via a computerised system) to receive liraglutide (n?=?35) or matching placebo (n?=?33), and 49 participants were analysed. All were instructed to follow an energy-restricted diet. Primary outcome was insulin secretory function, which was evaluated in response to graded infusions of glucose and day-long mixed meals.Liraglutide treatment (n?=?24) significantly (p???0.03) increased the insulin secretion rate (% mean change [95% CI]; 21% [12, 31] vs -4% [-11, 3]) and pancreatic beta cell sensitivity to intravenous glucose (229% [161, 276] vs -0.5% (-15, 14]), and decreased insulin clearance rate (-3.5% [-11, 4] vs 8.2 [0.2, 16]) as compared with placebo (n?=?25). The liraglutide-treated group also had significantly (p???0.03) lower day-long glucose (-8.2% [-11, -6] vs -0.1 [-3, 2]) and NEFA concentrations (-14 [-20, -8] vs -2.1 [-10, 6]) following mixed meals, whereas day-long insulin concentrations did not significantly differ as compared with placebo. In a multivariate regression analysis, weight loss was associated with a decrease in insulin secretion rate and day-long glucose and insulin concentrations in the placebo group (p???0.05), but there was no association with weight loss in the liraglutide group. The most common side effect of liraglutide was nausea.A direct stimulatory effect on beta cell function was the predominant change in liraglutide-augmented weight loss. These changes appear to be independent of weight loss.ClinicalTrials.gov NCT01784965 FUNDING: The study was funded by the ADA.

  View details for DOI 10.1007/s00125-013-3134-3

  View details for PubMedID 24326527

• Sex differences in insulin resistance and cardiovascular disease risk. journal of clinical endocrinology and metabolism Kim, S. H., Reaven, G. 2013; 98 (11): E1716-21

  Abstract

  The possibility that differences in insulin sensitivity explain why women, especially younger women, have a lower cardiovascular disease (CVD) risk than men remains an unsettled issue.The objective of this study was to evaluate whether sex disparities in CVD risk are associated with differences in insulin resistance.This was a cross-sectional study of women (n = 468) and men (n = 354) who had the measurement of CVD risk factors and steady-state plasma glucose (SSPG) concentration (insulin resistance) using the insulin suppression test. The population was also divided by median age (51 y) to evaluate the effect of age on sex differences. MAIN OUTCOME MEASURES/RESULTS: In general, the SSPG concentration was similar between sexes. At higher BMI (?30 kg/m(2)), women had significantly lower SSPG concentration than men (sex × BMI interaction, P = .001). However, sex differences in CVD risk factors were not due to differences in SSPG but accentuated by a higher degree of insulin resistance in younger (age < 51 y) but not older (? 51 y) individuals. In younger individuals, women had significantly (P ? .007) lower diastolic blood pressure and fasting glucose and triglyceride concentration compared with men in SSPG tertile 3 (most insulin resistant) but not in tertile 1 (least insulin resistant). Older women had lower diastolic blood pressure compared with men, regardless of SSPG. High-density lipoprotein cholesterol remained higher in women, regardless of age or SSPG.The female advantage is not due to a difference in insulin action but results from an attenuation of the relationship between insulin resistance and CVD risk, especially in younger individuals.

  View details for DOI 10.1210/jc.2013-1166

  View details for PubMedID 24064694

• Benefits of liraglutide treatment in overweight and obese older individuals with prediabetes. Diabetes care Kim, S. H., Abbasi, F., Lamendola, C., Liu, A., Ariel, D., Schaaf, P., Grove, K., Tomasso, V., Ochoa, H., Liu, Y. V., Chen, Y. I., Reaven, G. 2013; 36 (10): 3276-3282

  Abstract

  OBJECTIVEThe aim was to evaluate the ability of liraglutide to augment weight loss and improve insulin resistance, cardiovascular disease (CVD) risk factors, and inflammation in a high-risk population for type 2 diabetes (T2DM) and CVD.RESEARCH DESIGN AND METHODSWe randomized 68 older individuals (mean age, 58 ± 8 years) with overweight/obesity and prediabetes to this double-blind study of liraglutide 1.8 mg versus placebo for 14 weeks. All subjects were advised to decrease calorie intake by 500 kcal/day. Peripheral insulin resistance was quantified by measuring the steady-state plasma glucose (SSPG) concentration during the insulin suppression test. Traditional CVD risk factors and inflammatory markers also were assessed.RESULTSEleven out of 35 individuals (31%) assigned to liraglutide discontinued the study compared with 6 out of 33 (18%) assigned to placebo (P = 0.26). Subjects who continued to use liraglutide (n = 24) lost twice as much weight as those using placebo (n = 27; 6.8 vs. 3.3 kg; P < 0.001). Liraglutide-treated subjects also had a significant improvement in SSPG concentration (-3.2 vs. 0.2 mmol/L; P < 0.001) and significantly (P ? 0.04) greater lowering of systolic blood pressure (-8.1 vs. -2.6 mmHg), fasting glucose (-0.5 vs. 0 mmol/L), and triglyceride (-0.4 vs. -0.1 mmol/L) concentration. Inflammatory markers did not differ between the two groups, but pulse increased after liraglutide treatment (6.4 vs. -0.9 bpm; P = 0.001).CONCLUSIONSThe addition of liraglutide to calorie restriction significantly augmented weight loss and improved insulin resistance, systolic blood pressure, glucose, and triglyceride concentration in this population at high risk for development of T2DM and CVD.

  View details for DOI 10.2337/dc13-0354

  View details for PubMedID 23835684

• Beyond fasting plasma glucose: The association between coronary heart disease risk and postprandial glucose, postprandial insulin and insulin resistance in healthy, nondiabetic adults. Metabolism: clinical and experimental Bhat, S. L., Abbasi, F. A., Blasey, C., Reaven, G. M., Kim, S. H. 2013; 62 (9): 1223-1226

  Abstract

  Prediabetes is defined by elevations of plasma glucose concentration, and is aimed at identifying individuals at increased risk of type 2 diabetes and coronary heart disease (CHD). However, since these individuals are also insulin resistant and hyperinsulinemic, we evaluated the association between several facets of carbohydrate metabolism and CHD risk profile in apparently healthy, nondiabetic individuals.Plasma glucose and insulin concentrations were measured before and at hourly intervals for eight hours after two test meals in 281 nondiabetic individuals. Insulin action was quantified by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test. CHD risk was assessed by measurements of blood pressure and fasting lipoprotein profile.For purposes of analysis, the population was divided into tertiles, and the results demonstrated that the greater the 1) fasting plasma glucose (FPG) concentration, 2) incremental plasma insulin response to meals, and 3) SSPG concentration, the more adverse the CHD risk profile (p<0.05). In contrast, the CHD risk profile did not significantly worsen with increases in the incremental plasma glucose response to meals.In nondiabetic individuals, higher FPG concentrations, accentuated daylong incremental insulin responses to meals, and greater degrees of insulin resistance are each associated with worse CHD risk profile (higher blood pressures, higher triglycerides, and lower high density lipoprotein cholesterol concentrations). Interventional efforts aimed at decreasing CHD in such individuals should take these abnormalities into consideration.

  View details for DOI 10.1016/j.metabol.2013.04.012

  View details for PubMedID 23809477

• Relationship between Insulin Resistance and Coronary Artery Calcium in Young Men and Women PLOS ONE Sung, K., Choi, J., Gwon, H., Choi, S., Kim, B., Kwag, H. J., Kim, S. H. 2013; 8 (1)

  Abstract

  The gender disparity in cardiovascular disease (CVD) risk is greatest between young men and women. However, the causes of that are not fully understood. The objective of this study was to evaluate the relationship between insulin resistance and the presence of coronary artery calcium (CAC) to identify risk factors that may predispose young men and women to CVD.Insulin resistance and CVD risk factors were examined in 8682 Korean men and 1829 women aged 30-45 years old. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR), and CAC was measured using computed tomography. Women were less likely to be insulin resistant (upper quartile of HOMA-IR, 18% vs. 27%, p<0.001) and had a lower prevalence of CAC (1.6% vs. 6.4%, p<0.001). Even when equally insulin resistant men and women were compared, women continued to have lower prevalence of CAC (3.1% vs. 7.2%, p = 0.004) and a more favorable CVD risk profile. Finally, after adjustment for traditional CVD risk factors, insulin resistance remained an independent predictor of CAC only in men (p = 0.03).Young women have a lower risk for CVD and a lower CAC prevalence compared with men. This favorable CVD risk profile in women appears to occur regardless of insulin sensitivity. Unlike men, insulin resistance was not a predictor of CAC in women in this cohort. Therefore, insulin resistance has less impact on CVD risk and CAC in young women compared with men, and insulin resistance alone does not explain the gender disparity in CVD risk that is observed at an early age.

  View details for DOI 10.1371/journal.pone.0053316

  View details for Web of Science ID 000313682700025

  View details for PubMedID 23341938

  View details for PubMedCentralID PMC3547016

• Metabolic syndrome, insulin resistance and kidney function in non-diabetic individuals NEPHROLOGY DIALYSIS TRANSPLANTATION Johns, B. R., Pao, A. C., Kim, S. H. 2012; 27 (4): 1410-1415

  Abstract

  Metabolic syndrome has been recently identified as a risk factor for chronic kidney disease (CKD). Since the five individual components of the metabolic syndrome have also been identified as risk factors for CKD, the metabolic syndrome diagnosis may represent an aggregate of CKD risk factors. On the other hand, the components of the metabolic syndrome are also associated with insulin resistance, which may directly mediate the increased CKD risk.This study was a cross-sectional evaluation of the relationship between metabolic syndrome, insulin resistance and estimated glomerular filtration rate (eGFR) in 574 non-diabetic individuals. Insulin resistance was directly quantified using the insulin suppression test, and the metabolic syndrome components were measured. eGFR was calculated using the three validated estimation equations: the Chronic Kidney Disease Epidemiology Collaboration equation, the Mayo quadratic equation and the Modification of Diet in Renal Disease study equation.While CKD prevalence was higher and mean eGFR was lower in individuals who met the metabolic syndrome criteria compared with those who did not, we did not observe a significant relationship between insulin resistance and eGFR. Of all of the components of the metabolic syndrome, only hypertension was significantly associated with CKD prevalence [odds ratio (95% confidence interval), 3.5 (1.2-10.1), P=0.02].Although CKD is more common among individuals with the metabolic syndrome, insulin resistance is not a common factor.

  View details for DOI 10.1093/ndt/gfr498

  View details for Web of Science ID 000302310700022

  View details for PubMedID 21908415

• Measurement of insulin action: a tribute to Sir Harold Himsworth DIABETIC MEDICINE Kim, S. H. 2011; 28 (12): 1487-1493

  Abstract

  Sir Harold Himsworth was a renowned clinician and researcher. Among his myriad of accomplishments, he was the first to differentiate diabetes mellitus into 'insulin-sensitive' and 'insulin-insensitive' forms. To help distinguish these two types, he developed the first test to measure insulin sensitivity, the insulin-glucose test. This article reviews Himsworth's pioneer methods and subsequent advances in the measurement of insulin action. The advantages and limitations of commonly used methods to assess insulin sensitivity are also examined.

  View details for DOI 10.1111/j.1464-5491.2011.03409.x

  View details for Web of Science ID 000297118400009

  View details for PubMedID 21838770

• Plasma glucose and insulin responses to mixed meals: Impaired fasting glucose re-visited DIABETES & VASCULAR DISEASE RESEARCH BHAT, S. L., Abbasi, F., Blasey, C., Reaven, G. M., Kim, S. H. 2011; 8 (4): 271-275

  Abstract

  In individuals with varying glucose tolerance, glucose and insulin comparisons are usually made based on response to oral glucose challenge. However, an oral glucose tolerance test may not reflect daylong glucose and insulin excursions in response to meals. To better understand individuals with impaired fasting glucose (IFG), we compared insulin action as well as plasma glucose and insulin responses to mixed meals in individuals with normal fasting glucose (NFG; n = 141) and IFG (n = 148) concentrations.Insulin action was quantified by determining steady-state plasma glucose (SSPG) concentrations during the insulin suppression test. Plasma glucose and insulin concentrations were measured before and hourly after two mixed meals.SSPG concentrations were significantly higher in the IFG group (11.8 ± 3.6 vs. 9.1 ± 3.8 mmol/l). Mean hourly daylong glucose (6.4 ± 0.07 vs. 5.5 ± 0.04 mmol/l) and insulin (390 ± 20 vs. 279 ± 15 pmol/l) concentrations were also higher in those with IFG (p < 0.001). Daylong incremental meal-stimulated glucose response, however, was comparable (p = 0.77) in the two groups, whereas the incremental insulin response was 44% higher in the IFG group.Although individuals are currently defined as having IFG based on fasting plasma glucose concentration, our data show that these individuals with IFG also are insulin resistant and have higher daylong insulin concentrations.

  View details for DOI 10.1177/1479164111421036

  View details for Web of Science ID 000296976700004

  View details for PubMedID 21933842

• Interrelationship between Fatty Liver and Insulin Resistance in the Development of Type 2 Diabetes JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Sung, K., Kim, S. H. 2011; 96 (4): 1093-1097

  Abstract

  Although fatty liver and insulin resistance are known to be associated, the relationship between the two in the development of type 2 diabetes mellitus (T2DM) is unclear.We investigated the 5-yr risk of developing T2DM in individuals diagnosed with fatty liver using ultrasound and stratified by insulin sensitivity using quartiles of fasting insulin concentration.We examined the clinical and laboratory data of 11,091 Koreans who had a medical evaluation including fasting insulin concentration and abdominal ultrasound at baseline and had a follow-up after 5 yr.At baseline, 27% of the population had fatty liver. Almost half (47%) of the individuals with fatty liver had baseline insulin concentration in the highest quartile compared with 17% in those without fatty liver (P < 0.001). Regardless of baseline insulin concentration, individuals with fatty liver had significantly (P < 0.001) more baseline clinical and metabolic abnormalities, including higher glucose and triglyceride concentration and lower high-density lipoprotein cholesterol concentration. In addition, regardless of baseline insulin concentration, individuals with fatty liver had a significantly increased risk for incident T2DM compared with those without fatty liver [crude odds ratio, 5.05 (95% confidence interval, 2.08-12.29) in the lowest insulin quartile and 6.34 (3.58-11.21) in the highest quartile]. In individuals in the highest insulin quartile, the odds ratio for developing T2DM remained significant even after multivariate adjustment including baseline glucose concentration [2.42 (1.23-4.75)].Although associated with insulin resistance, fatty liver diagnosed by ultrasound appears to independently increase the risk of T2DM.

  View details for DOI 10.1210/jc.2010-2190

  View details for Web of Science ID 000289242800053

  View details for PubMedID 21252243

• Relationship between insulin resistance and C-reactive protein in a patient population treated with second generation antipsychotic medications INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY Kim, S. H., Reaven, G., Lindley, S. 2011; 26 (1): 43-47

  Abstract

  C-reactive protein (CRP) is an inflammatory marker associated with obesity, insulin resistance, and cardiovascular disease. A recent study found CRP levels to be higher in individuals treated with certain antipsychotic medications such as olanzapine; however, it is not clear whether this is associated directly with drug intake or indirectly with drug-associated weight gain and insulin resistance. The objective of this study was to explore the potential predictors of CRP including insulin resistance, components of the metabolic syndrome, psychiatric diagnosis, and antipsychotic medication in patients treated with antipsychotics. Sixty-four outpatients without diabetes being treated with a single second generation antipsychotic medication had direct measurements of insulin resistance at the end of a 180-min infusion of glucose, insulin, and octreotide (insulin suppression test) as well as components of the metabolic syndrome. Insulin resistance was the strongest predictor of CRP (r=0.52, P<0.001). When adjusted for insulin resistance, there was no significant relationship between CRP and any of the components of the metabolic syndrome criteria, specific drug treatment or psychiatric diagnoses. In conclusion, insulin resistance is strongly associated with CRP levels and likely contributes to earlier associations between CRP and certain antipsychotic treatments.

  View details for DOI 10.1097/YIC.0b013e3283400cd3

  View details for Web of Science ID 000285083700005

  View details for PubMedID 20861740

• Obesity and Insulin Resistance: An Ongoing Saga DIABETES Kim, S. H., Reaven, G. 2010; 59 (9): 2105-2106

  View details for DOI 10.2337/db10-0766

  View details for Web of Science ID 000281612000004

  View details for PubMedID 20805385

• Glucose-Stimulated Insulin Secretion in Gastric Bypass Patients with Hypoglycemic Syndrome: No Evidence for Inappropriate Pancreatic beta-cell Function OBESITY SURGERY Kim, S. H., Abbasi, F., Lamendola, C., Reaven, G. M., McLaughlin, T. 2010; 20 (8): 1110-1116

  Abstract

  Roux-en-Y gastric bypass surgery (RYGB) has been associated with a hypoglycemic syndrome characterized by postprandial hypoglycemia and hyperinsulinemia. The syndrome is believed to occur due to insulin hypersecretion from either pancreatic beta-cell hyperplasia or hyperfunction.Eight RYGB patients with hypoglycemic syndrome had insulin secretion rates determined during a 240-min graded intravenous glucose infusion. They were compared to 34 nondiabetic, nonsurgical individuals who were divided based on their insulin sensitivity status as measured by the insulin suppression test: insulin-sensitive (n = 8), insulin intermediate (n = 7), and insulin-resistant (n = 19).RYGB patients had insulin concentrations and HOMA-IR similar to the insulin-sensitive reference group. In addition, integrated insulin secretion rates were comparable to the insulin-sensitive group and significantly lower than the insulin intermediate (p

  View details for DOI 10.1007/s11695-010-0183-2

  View details for Web of Science ID 000280746100304

  View details for PubMedID 20665189

• Relationship between body mass index and insulin resistance in patients treated with second generation antipsychotic agents JOURNAL OF PSYCHIATRIC RESEARCH Kim, S. H., Nikolics, L., Abbasi, F., Lamendola, C., Link, J., Reaven, G. M., Lindley, S. 2010; 44 (8): 493-498

  Abstract

  Second generation antipsychotics (SGAs) can increase weight gain and weight-induced insulin resistance. Recent studies have suggested weight-independent effects of certain SGAs on insulin resistance; however the magnitude of these effects and the relationship between BMI and insulin resistance in patients on SGAs are not established. To evaluate, the relationship between body mass index (BMI) and insulin resistance in 54 patients being stably treated with olanzapine (n=19), risperidone (n=16), or aripiprazole (n=19) was compared with data from a large reference population (n=201) not on SGAs. Insulin resistance was directly quantified by measuring the steady-state plasma glucose (SSPG) concentration during the insulin suppression test. The relationship between BMI and SSPG was similar between the SGA (r=0.58) and the reference population (r=0.50). When SSPG was standardized based on expected values for the reference population, patients on olanzapine had a higher degree of insulin resistance (mean z-score+/-SD, 0.68+/-0.9) than expected for level of BMI compared with those on aripiprazole (-0.25+/-1) and risperidone (-0.3+/-0.9), F(2,51)=6.28 (p=0.004). Thus, olanzapine group was 0.76 SD above the reference population or in the 78 percentile for insulin resistance. SSPG was correlated with fasting plasma insulin concentration (0.78 (0.64-0.87), p<0.001) but not fasting glucose concentration (0.15 (-0.13-0.40), p=0.29). In conclusion, BMI contributes a quarter to a third of the variance in insulin resistance in the SGA population similar to the reference population. Olanzapine also appears to have an independent effect on insulin resistance that is above and beyond obesity.

  View details for DOI 10.1016/j.jpsychires.2009.11.007

  View details for Web of Science ID 000278653500002

  View details for PubMedID 19962157

• Utility of Homeostasis Model Assessment of beta-Cell Function in Predicting Diabetes in 12,924 Healthy Koreans DIABETES CARE Sung, K., Reaven, G. M., Kim, S. H. 2010; 33 (1): 200-202

  Abstract

  It is unclear how well homeostasis model assessment of beta-cell function (HOMA-beta) predicts diabetes development beyond its components, especially glucose.We identified 12,924 nondiabetic Koreans who had fasting plasma glucose and insulin concentrations measured in 2003 and again in 2008. To minimize the impact of differences in baseline glucose concentration, individuals were divided into three glucose categories: normal fasting glucose (NFG, glucose <5.6 mmol/l), impaired fasting glucose (IFG-100) (5.6-6.0 mmol/l), and IFG-110 (6.1-6.9 mmol/l).Diabetes developed in 29% of individuals in the IFG-110 group, compared with 5% in IFG-100 and 0.3% in NFG groups. Within each glucose category, those who progressed to diabetes had higher baseline glucose concentrations (P < or = 0.04). Baseline HOMA-beta, however, was not lower but higher in individuals who developed diabetes in the NFG group (P = 0.009) and similar in the IFG-100 and IFG-110 groups.These data question the utility of using HOMA-beta to predict the development of diabetes.

  View details for DOI 10.2337/dc09-1070

  View details for Web of Science ID 000273622200040

  View details for PubMedID 19808927

• Plasma Glucose and Insulin Regulation Is Abnormal Following Gastric Bypass Surgery with or Without Neuroglycopenia OBESITY SURGERY Kim, S. H., Liu, T. C., Abbasi, F., Lamendola, C., Morton, J. M., Reaven, G. M., McLaughlin, T. L. 2009; 19 (11): 1550-1556

  Abstract

  Enhanced insulin sensitivity is commonly seen following Roux-en-Y gastric bypass surgery (RYGB) whereas symptomatic hypoglycemia post-RYGB seems to occur infrequently. It is unclear how different plasma glucose and insulin responses are in patients with symptomatic hypoglycemia (SX-RYGB) versus those who remain asymptomatic (ASX-RYGB), nor when compared with non-surgical controls with varying degrees of insulin sensitivity.Plasma glucose and insulin concentrations were determined following a 75-g oral glucose challenge in five groups: symptomatic and asymptomatic patients following RYGB (n = 9 each) and overweight/obese controls, divided into three subgroups (n = 30 each) on the basis of degree of insulin sensitivity measured by the insulin suppression test.SX-RYGB group had higher 30-min glucose after oral glucose compared with the ASX-RYGB group (p = 0.04). The two groups did not differ in peak glucose and insulin concentrations, nadir glucose concentration, or insulin-to-glucose ratio 30 min after oral glucose. These values were significantly different from the three control groups, and peak insulin concentrations post-RYGB were increased at every degree of insulin sensitivity as compared with the control groups.Plasma glucose and insulin responses to oral glucose in patients with symptomatic hypoglycemia post-RYGB are minimally different when compared to individuals who remain asymptomatic, and both groups demonstrate hyperinsulinemia out of proportion to their degree of insulin sensitivity.

  View details for DOI 10.1007/s11695-009-9893-8

  View details for Web of Science ID 000271282900014

  View details for PubMedID 19557485

• Effect of moderate alcoholic beverage consumption on insulin sensitivity in insulin-resistant, nondiabetic individuals METABOLISM-CLINICAL AND EXPERIMENTAL Kim, S. H., Abbasi, F., Lamendola, C., Reaven, G. M. 2009; 58 (3): 387-392

  Abstract

  Although moderate alcohol consumption has been associated with a decrease in plasma insulin concentrations, relatively few studies have been conducted to evaluate the effect of alcohol on insulin sensitivity, particularly in nondiabetic, insulin-resistant individuals. Because enhanced insulin sensitivity could contribute to the reported association between moderate alcohol consumption and reduced risk of heart disease and diabetes, we believed it is important to address this issue. Consequently, we evaluated the ability of moderate alcohol consumption to improve insulin sensitivity, as measured by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test, in 20 nondiabetic, insulin-resistant individuals. Measurements were made of SSPG, glucose, insulin, and lipoprotein concentrations before and after consuming 30 g of alcohol for 8 weeks, either as vodka (n = 9) or red wine (n = 11). The SSPG concentrations (insulin resistance) decreased by approximately 8% in the total group (P = .08), and high-density lipoprotein cholesterol concentration increased by a mean of 0.09 mmol/L (P = .02). Trends were similar in individuals who consumed vodka or red wine. Men tended to have greater decline in SSPG and increase in high-density lipoprotein cholesterol compared with women. There were no other metabolic changes in fasting plasma glucose, insulin, and triglyceride concentrations. These data demonstrate that 8 weeks of moderate alcohol consumption had minimal impact on enhancing insulin sensitivity in nondiabetic, insulin-resistant individuals, raising questions as to the role, if any, of improved insulin sensitivity in the purported clinical benefits associated with moderate alcohol consumption.

  View details for DOI 10.1016/j.metabol.2008.10.013

  View details for Web of Science ID 000263882400019

  View details for PubMedID 19217456

• Insulin resistance and hyperinsulinemia - You can't have one without the other DIABETES CARE Kim, S. H., Reaven, G. M. 2008; 31 (7): 1433-1438

  Abstract

  Recently, it has been suggested that insulin resistance and hyperinsulinemia can exist in isolation and have differential impacts on cardiovascular disease (CVD). To evaluate this suggestion, we assessed the degree of discordance between insulin sensitivity and insulin response in a healthy, nondiabetic population.Insulin sensitivity was quantified by determining the steady-state plasma glucose (SSPG) concentration during an insulin suppression test in 446 individuals. The integrated insulin response was calculated after a 75-g oral glucose challenge. We analyzed the correlation between insulin resistance and insulin response in addition to quantifying the proportion in quartiles of insulin response by quartiles of insulin sensitivity. Then we compared CVD risk factors between individuals within the same insulin sensitivity quartile but within different insulin response quartiles to evaluate the differential clinical impact of insulin resistance and hyperinsulinemia.Insulin resistance and insulin response were highly correlated (r = 0.76, P < 0.001). A majority (95%) of the most insulin-resistant individuals (top SSPG quartile) were either in the highest insulin response quartile (71%) or second highest (24%). Similarly, 92% of the most insulin-sensitive individuals (lowest SSPG quartile) were in the lowest two insulin response quartiles. There were minimal differences in CVD risk factors between individuals with different insulin responses but within the same insulin sensitivity quartile.Although not perfectly related, insulin resistance and hyperinsulinemia rarely exist in isolation in a nondiabetic population. It is difficult to discern an independent impact of hyperinsulinemia on CVD risk factors associated with insulin resistance.

  View details for DOI 10.2337/dc08-0045

  View details for Web of Science ID 000257421000032

  View details for PubMedID 18594063

• Isolated Impaired Fasting Glucose and Peripheral Insulin Sensitivity Not a simple relationship DIABETES CARE Kim, S. H., Reaven, G. M. 2008; 31 (2): 347-352

  Abstract

  In a recent consensus statement, the American Diabetes Association (ADA) concluded that individuals with impaired fasting glucose (IFG) have "normal muscle insulin sensitivity." To subject this conclusion to further validation, we evaluated the relationship between glucose tolerance categories and peripheral insulin sensitivity in a large nondiabetic population.Insulin sensitivity was directly quantified by determining the steady-state plasma glucose (SSPG) concentration during an insulin suppression test in 446 nondiabetic individuals divided into four groups: normal glucose tolerance (NGT, n = 318), isolated IFG (n = 63), isolated impaired glucose tolerance (IGT, n = 33), and combined IFG and IGT (IFG/IGT, n = 32).Insulin sensitivity was significantly different in all three groups with pre-diabetes (IFG, IGT, IFG/IGT) as compared with NGT (P < 0.05). Using tertiles of SSPG concentration in the NGT group as operational definitions of insulin resistance (highest tertile) and insulin sensitivity (lowest tertile), there was considerable heterogeneity within the pre-diabetic groups. Thus, 57% of IFG individuals were insulin resistant, and 13% were insulin sensitive. The IFG/IGT group was most homogeneous, with 94% classified as insulin resistant and only 3% as insulin sensitive.Peripheral insulin sensitivity varies considerably in nondiabetic individuals, with IFG individuals showing the most heterogeneity within the pre-diabetes group. We believe that this heterogeneity in insulin sensitivity, and the relatively few patients in whom insulin sensitivity has been measured directly in the past, explain the discrepancy between our findings and those of the recent ADA consensus statement.

  View details for DOI 10.2337/dc07-1574

  View details for Web of Science ID 000266563300033

  View details for PubMedID 18000184

• Relationship among alcohol, body weight, and cardiovascular risk factors in 27,030 Korean men DIABETES CARE Sung, K., Kim, S. H., Reaven, G. M. 2007; 30 (10): 2690-2694

  Abstract

  Recent studies suggest a lower risk for overweight/obesity in moderate alcohol drinkers. However, the validity of this relationship and its impact on the putative benefits of alcohol consumption on cardiovascular disease (CVD) risk has not been well evaluated.We assessed the impact of BMI on the relationship between alcohol consumption and CVD risk factors (blood pressure, lipid panel, and glucose and insulin concentrations) in 27,030 healthy Korean men with no major comorbidities or medication intake seen in a large urban Korean hospital.BMI and overweight prevalence increased linearly with alcohol intake (P < 0.001). Alcohol intake was also positively associated with blood pressure and triglyceride, HDL, and fasting glucose concentrations (P < 0.001) and negatively associated with LDL and insulin concentrations (P < 0.001). With nondrinkers as the reference group, the odds ratio for having insulin in the top quartile also declined linearly when adjusted for age, BMI, smoking, and exercise, with the heaviest drinkers (>40 g/day) having an odds ratio of 0.71 (95% CI 0.62-0.82) (P < 0.001). The relationship between alcohol and CVD risk factors was similar in normal-weight and overweight individuals.Alcohol intake is associated with increasing BMI and several metabolic abnormalities, including higher fasting glucose. Paradoxically, it is also associated with lower insulin concentrations. The clinical significance of these findings needs further investigation.

  View details for DOI 10.2337/dc07-0315

  View details for Web of Science ID 000250223400056

  View details for PubMedID 17623829

• Metabolic impact of switching antipsychotic therapy to aripiprazole after weight gain - A pilot study JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY Kim, S. H., Ivanova, O., Abbasi, F. A., Lamendola, C. A., Reaven, G. M., Glick, I. D. 2007; 27 (4): 365-368

  Abstract

  Switching antipsychotic regimen to agents with low weight gain potential has been suggested in patients who gain excessive weight on their antipsychotic therapy. In an open-label pilot study, we evaluated the metabolic and psychiatric efficacy of switching to aripiprazole in 15 (9 men, 6 women) outpatients with schizophrenia who had gained at least 10 kg on their previous antipsychotic regimen. Individuals had evaluation of glucose tolerance, insulin resistance (insulin suppression test), lipid concentrations, and psychiatric status before and after switching to aripiprazole for 4 months. A third of the individuals could not psychiatrically tolerate switching to aripiprazole. In the remaining individuals, psychiatric symptoms significantly improved with decline in Clinical Global Impression Scale (by 26%, P = 0.015) and Positive and Negative Syndrome Scale (by 22%, P = 0.023). Switching to aripiprazole did not alter weight or metabolic outcomes (fasting glucose, insulin resistance, and lipid concentrations) in the patients of whom 73% were insulin resistant and 47% had impaired or diabetic glucose tolerance at baseline. In conclusion, switching to aripiprazole alone does not ameliorate the highly prevalent metabolic abnormalities in the schizophrenia population who have gained weight on other second generation antipsychotic medications.

  View details for DOI 10.1097/JCP.0b013e3180a9076c

  View details for Web of Science ID 000248062400007

  View details for PubMedID 17632220

• The relationship between insulin resistance and dyslipidaemia in cigarette smokers DIABETES OBESITY & METABOLISM Farin, H. M., Abbasi, F., Kim, S. H., Lamendola, C., McLaughlin, T., Reaven, G. M. 2007; 9 (1): 65-69

  Abstract

  Considerable evidence shows that cigarette smokers tend to have the dyslipidemic pattern of high plasma triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations, a highly atherogenic lipoprotein profile also typical of the insulin-resistant state even in the absence of cigarette smoking. However, because cigarette smokers are frequently insulin resistant, it is unclear if this dyslipidaemia is secondary to smoking, per se, or simply to the fact that smokers tend to be insulin resistant. The present study was initiated to determine whether this dyslipidaemia prevalent in cigarette smokers and characteristic of insulin-resistant individuals is a function of cigarette smoking or of insulin resistance.As measured using vertical auto profile-II methodology, the lipid and lipoprotein concentrations were compared in 34 cigarette smokers divided into insulin-sensitive and insulin-resistant subgroups. The two groups were similar in age and body mass index, differing only in their insulin-mediated glucose uptake as quantified by the steady-state plasma glucose concentration determined during the insulin suppression test.While levels of TG and very low-density lipoprotein cholesterol (VLDL-C) were significantly elevated in insulin-resistant cigarette smokers, total cholesterol (C), low-density lipoprotein cholesterol (LDL-C), narrow-density (ND) LDL-C, intermediate-density lipoprotein-C (IDL-C), HDL-C and non-HDL-C were not different in the two groups. The insulin-resistant smokers also had a preponderance of small, dense LDL particles, while the reverse was true of the insulin-sensitive cigarette smokers.These data suggest that the dyslipidaemia previously attributed to smoking occurs primarily in those smokers who are also insulin resistant.

  View details for DOI 10.1111/j.1463-1326.2006.00574.x

  View details for Web of Science ID 000242781700008

  View details for PubMedID 17199720

• Comparison of the 1997 and 2003 American Diabetes Association classification of impaired fasting glucose - Impact on prevalence of impaired fasting glucose, coronary heart disease risk factors, and coronary heart disease in a community-based medical practice JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Kim, S. H., Chunawala, L., Linde, R., Reaven, G. M. 2006; 48 (2): 293-297

  Abstract

  The goals of this study were to assess the effect of the 2003 American Diabetes Association definition of impaired fasting glucose (IFG) on prevalence of IFG, coronary heart disease (CHD) risk factors, and CHD compared with the 1997 IFG definition.Although IFG is viewed as increasing CHD risk, this association is unclear and has not been well studied after changing the IFG criterion, especially in a clinical practice setting.This was a cross-sectional evaluation of 8,295 members (3,763 men and 4,532 women) of a community medical center who were between the ages of 30 and 69 years, without a history of diabetes mellitus, and who had available measurements of fasting plasma glucose and lipid concentrations within the past 2 years. The prevalence of IFG, CHD risk factors, and CHD with the 1997 and 2003 IFG definition was compared.The prevalence of IFG increased from 8% to 35% with the 2003 criterion. Individuals with glucose of 100 to 109 mg/dl had lower prevalence of most CHD risk factors (hypertension, triglyceride > or =150 mg/dl, high-density lipoprotein cholesterol <40 mg/dl, meeting 2 components of the metabolic syndrome criteria, CHD risk > or =10% by Framingham score) compared with individuals with glucose 110 to 125 mg/dl. Individuals identified with the 2003 IFG definition did not have an increase in known CHD when adjusted for covariates (odds ratio 1.4 [95% confidence interval (CI) 0.7 to 2.3] vs. 3.2 [95% CI 1.8 to 5.9]).One-third of the population has IFG with the 2003 definition, yet many of these individuals do not have increased prevalence of CHD risk factors or CHD.

  View details for DOI 10.1016/j.jacc.2006.03.043

  View details for Web of Science ID 000239080000011

  View details for PubMedID 16843178

• Rosiglitazone reduces glucose-stimulated insulin secretion rate and increases insulin clearance in nondiabetic, insulin-resistant individuals DIABETES Kim, S. H., Abbasi, F., Chu, J. W., McLaughlin, T. L., Lamendola, C., Polonsky, K. S., Reaven, G. M. 2005; 54 (8): 2447-2452

  Abstract

  Compensatory hyperinsulinemia permitting insulin-resistant individuals to maintain normal glucose tolerance is associated with a left shift in the glucose-stimulated insulin secretion rate (GS-ISR) dose-response curve and decrease in the insulin metabolic clearance rate (I-MCR). To see whether these changes would reverse with improvement in insulin sensitivity, 14 nondiabetic insulin-resistant subjects received rosiglitazone for 12 weeks (4 mg daily for 4 weeks and then 8 mg daily for 8 weeks). Insulin-mediated glucose uptake was quantified by measuring the steady-state plasma glucose concentration during the insulin suppression test. GS-ISR and I-MCR were determined during a 240-min graded intravenous glucose infusion. I-MCR was also calculated during the insulin suppression test. After rosiglitazone treatment, insulin sensitivity improved with significant fall in steady-state plasma glucose (means +/- SE from 13.5 +/- 0.62 to 9.8 +/- 1.02 mmol/l, P < 0.001). In response, the integrated GS-ISR decreased by 21% (P < 0.001), with a right shift in the dose-response curve. Calculated I-MCR increased by 34% (P = 0.008) during the insulin suppression test and by 21% (P = 0.03) during the graded glucose infusion. In conclusion, enhanced insulin sensitivity in rosiglitazone-treated nondiabetic insulin-resistant individuals was associated with a shift to the right in the GS-ISR dose-response curve and an increase in I-MCR.

  View details for Web of Science ID 000230869500023

  View details for PubMedID 16046313

• The metabolic syndrome: one step forward, two steps back. Diabetes & vascular disease research Kim, S. H., Reaven, G. M. 2004; 1 (2): 68-75

  Abstract

  Individuals with insulin resistance are at increased risk of glucose intolerance, dyslipidaemia and essential hypertension. In 1988, it was proposed that this cluster of abnormalities associated with insulin resistance identifies individuals at increased risk for cardiovascular disease. Recently, in an effort to raise awareness of this problem, both the World Health Organisation (WHO) and the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program have suggested a set of clinical criteria to diagnose individuals with what they both refer to as the metabolic syndrome. Although using the same term, the two groups have different goals for creating this diagnosis and different criteria to identify individuals, which relate to their different institutional goals. This review critically evaluates the similarities and differences between the two groups' concepts of the metabolic syndrome and questions the clinical utility of making the diagnosis with either set of definitions.

  View details for PubMedID 16304726

• Impact of degree of obesity on surrogate estimates of insulin resistance DIABETES CARE Kim, S. H., Abbasi, F., Reaven, G. M. 2004; 27 (8): 1998-2002

  Abstract

  To evaluate the role of adiposity in the relationship between specific and surrogate estimates of insulin-mediated glucose uptake (IMGU) in a large nondiabetic population.Healthy volunteers were classified by BMI into normal weight (<25.0 kg/m(2), n = 208), overweight (25.0-29.9 kg/m(2), n = 168), and obese (>or=30.0 kg/m(2), n = 109) groups. We then assessed how differences in BMI affect the correlation between steady-state plasma glucose (SSPG) concentration at the end of a 180-min infusion of octreotide, glucose, and insulin (a specific measure of IMGU) and five surrogate estimates: fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and area under the curve for insulin in response to oral glucose (I-AUC).Correlation coefficients (r values) between SSPG and surrogate measures of IMGU were all significant (P < 0.05), but the magnitude varied between BMI groups: normal weight: fasting plasma glucose 0.20, fasting plasma insulin 0.33, HOMA-IR 0.36, QUICKI -0.33, and I-AUC 0.69; overweight: fasting plasma glucose 0.19, fasting plasma insulin 0.55, HOMA-IR 0.55, QUICKI -0.54, and I-AUC 0.72; and obese: fasting plasma glucose 0.40, fasting plasma insulin 0.56, HOMA-IR 0.60, QUICKI -0.61, and I-AUC 0.69.The relationship between direct and surrogate estimates of IMGU varies with BMI, with the weakest correlations seen in the normal-weight group and the strongest in the obese group. In general, I-AUC is the most useful surrogate estimate of IMGU in all weight groups. Fasting plasma insulin, HOMA-IR, and QUICKI provide comparable information about IMGU. Surrogate estimates of IMGU based on fasting insulin and glucose account for no more than 13% of the variability in insulin action in the normal-weight group, 30% in the overweight group, and 37% in the obese group.

  View details for Web of Science ID 000223026200023

  View details for PubMedID 15277430

• Carbonated beverage consumption and bone mineral density among older women: The Rancho Bernardo study AMERICAN JOURNAL OF PUBLIC HEALTH Kim, S. H., Morton, D. J., BARRETTCONNOR, E. L. 1997; 87 (2): 276-279

  Abstract

  The association between carbonated beverage consumption and bone mineral density was examined in a community-based cohort of older White women.One thousand women 44 to 98 years of age had bone mineral density measured at four sites and provided medical and behavioral histories, including type and quantity of carbonated beverages consumed.Bone mineral density levels were not associated with intake of any type of carbonated beverage after adjustment for age, obesity, calcium intake, exercise, and current use of tobacco and alcohol, thiazides, estrogen, or thyroid hormone.Modest intake of carbonated beverages does not appear to have adverse effects on bone mineral density in older women.

  View details for Web of Science ID A1997WN49300026

  View details for PubMedID 9103110