Association of Thigh Muscle Mass with Insulin Resistance and Incident Type 2 Diabetes Mellitus in Japanese Americans (Diabetes Metab J 2018;42:488-95)

한승진,Edward J. Boyko 대한당뇨병학회 2019 Diabetes and Metabolism Journal Vol.43 No.1

The Evidence for an Obesity Paradox in Type 2 Diabetes Mellitus

한승진,Edward J. Boyko 대한당뇨병학회 2018 Diabetes and Metabolism Journal Vol.42 No.3

Although overweight/obesity is a major risk factor for the development of type 2 diabetes mellitus, there is increasing evidence that overweight or obese patients with type 2 diabetes mellitus experience lower mortality compared with patients of normal weight. This paradoxical finding, known as the “obesity paradox,” occurs in other chronic diseases, and in type 2 diabetes mellitus is particularly perplexing given that lifestyle intervention with one goal being weight reduction is an important feature of the management of this condition. We summarize in this review the findings from clinical and epidemiologic studies that have investigated the association between overweight and obesity (usually assessed using body mass index [BMI]) and mortality in type 2 diabetes mellitus and discuss potential causes of the obesity paradox. We conclude that most studies show evidence of an obesity paradox, but important conflicting findings still exist. We also evaluate if potential bias might explain the obesity paradox in diabetes, including, for example, the presence of confounding factors, measurement error due to use of BMI as an index of obesity, and reverse causation.

Association of Thigh Muscle Mass with Insulin Resistance and Incident Type 2 Diabetes Mellitus in Japanese Americans

한승진,Edward J. Boyko,김수경,Wilfred Y. Fujimoto,Steven E. Kahn,Donna L. Leonetti 대한당뇨병학회 2018 Diabetes and Metabolism Journal Vol.42 No.6

Background: Skeletal muscle plays a major role in glucose metabolism. We investigated the association between thigh muscle mass, insulin resistance, and incident type 2 diabetes mellitus (T2DM) risk. In addition, we examined the role of body mass index (BMI) as a potential effect modifier in this association. Methods: This prospective study included 399 Japanese Americans without diabetes (mean age 51.6 years) who at baseline had an estimation of thigh muscle mass by computed tomography and at baseline and after 10 years of follow-up a 75-g oral glucose tolerance test and determination of homeostasis model assessment of insulin resistance (HOMA-IR). We fit regression models to examine the association between thigh muscle area and incidence of T2DM and change in HOMA-IR, both measured over 10 years. Results: Thigh muscle area was inversely associated with future HOMA-IR after adjustment for age, sex, BMI, HOMA-IR, fasting plasma glucose, total abdominal fat area, and thigh subcutaneous fat area at baseline (P=0.033). The 10-year cumulative incidence of T2DM was 22.1%. A statistically significant interaction between thigh muscle area and BMI was observed, i.e., greater thigh muscle area was associated with lower risk of incident T2DM for subjects at lower levels of BMI, but this association diminished at higher BMI levels. Conclusion: Thigh muscle mass area was inversely associated with future insulin resistance. Greater thigh muscle area predicts a lower risk of incident T2DM for leaner Japanese Americans.

Higher High Density Lipoprotein 2 (HDL2) to Total HDL Cholesterol Ratio Is Associated with a Lower Risk for Incident Hypertension

황유철,Wilfred Y. Fujimoto,Steven E. Kahn,Donna L. Leonetti,Edward J. Boyko 대한당뇨병학회 2019 Diabetes and Metabolism Journal Vol.43 No.1

Background: Recent studies have suggested that high density lipoprotein (HDL) cholesterol is inversely associated with the development of hypertension. We aimed to determine the association between different HDL cholesterol subclasses and risk of future hypertension. Methods: A total of 270 Japanese Americans (130 men, 140 women) without hypertension between the ages of 34 to 75 years were enrolled. Blood pressure was measured with a mercury sphygmomanometer, and average blood pressure was calculated. Incident hypertension was determined 5 to 6 and 10 to 11 years after enrollment. HDL2, HDL3, and total HDL cholesterol were measured at baseline. Results: During 10 years of follow-up, the cumulative incidence of hypertension was 28.1% (76/270). In univariate analysis, age, diabetes, waist circumference, systolic and diastolic blood pressure, fasting glucose, insulin resistance index, total and low density lipoprotein cholesterol, and visceral adipose tissue were significant predictors for incident hypertension. Among the HDL cholesterol subclass, HDL2 cholesterol was inversely associated with hypertension incidence, but both total and HDL3 cholesterol were not. In addition, HDL2/HDL cholesterol was inversely associated with future hypertension risk. In multivariate analysis, age (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26 to 2.31; P=0.001), systolic blood pressure (OR, 1.83; 95% CI, 1.31 to 2.56; P<0.001), and HDL2/HDL cholesterol (OR, 0.71; 95% CI, 0.52 to 0.98; P=0.035), were associated with future development of hypertension. Conclusion: A higher proportion of HDL2 cholesterol among total HDL cholesterol predicted a lower risk for incident hypertension. However, concentrations of total HDL, HDL2, and HDL3 cholesterol were not independent predictors of incident hypertension.

Intra-Abdominal Fat and High Density Lipoprotein Cholesterol Are Associated in a Non-Linear Pattern in Japanese-Americans

송선옥,황유철,Steven E. Kahn,Donna L. Leonetti,Wilfred Y. Fujimoto,Edward J. Boyko 대한당뇨병학회 2020 Diabetes and Metabolism Journal Vol.44 No.2

Background: We describe the association between high density lipoprotein cholesterol (HDL-C) concentration and computed tomography (CT)-measured fat depots. Methods: We examined the cross-sectional associations between HDL-C concentration and intra-abdominal (IAF), abdominal subcutaneous (SCF), and thigh fat (TF) areas in 641 Japanese-American men and women. IAF, SCF, and TF were measured by CT at the level of the umbilicus and mid-thigh. The associations between fat area measurements and HDL-C were examined using multivariate linear regression analysis adjusting for age, sex, diabetes family history, homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index (BMI). Non-linearity was assessed using fractional polynomials. Results: Mean±standard deviation of HDL-C concentration and IAF in men and women were 1.30±0.34 mg/dL, 105±55.3 cm2, and 1.67±0.43 mg/dL, 74.4±46.6 cm2 and differed significantly by gender for both comparisons (P<0.001). In univariate analysis, HDL-C concentration was significantly associated with CT-measured fat depots. In multivariate analysis, IAF was significantly and non-linearly associated with HDL-C concentration adjusted for age, sex, BMI, HOMA-IR, SCF, and TF (IAF: β=–0.1012, P <0.001; IAF2: β=0.0008, P<0.001). SCF was also negatively and linearly associated with HDL-C (β=–0.4919, P=0.001). Conclusion: HDL-C does not linearly decline with increasing IAF in Japanese-Americans. A more complex pattern better fits this association.

Metabolic Consequences of Obstructive Sleep Apnea Especially Pertaining to Diabetes Mellitus and Insulin Sensitivity

송선옥,Ken He,Radhika R. Narla,강현구,류한욱,Edward J. Boyko 대한당뇨병학회 2019 Diabetes and Metabolism Journal Vol.43 No.2

Obstructive sleep apnea (OSA) and diabetes has been known to be closely related to each other and both diseases impact highly on the public health. There are many evidence of reports that OSA is associated with diabetes with a bidirectional correlation. A possible causal mechanism of OSA to diabetes is intermittent hypoxemia and diabetes to OSA is microvascular complication. However, OSA and diabetes have a high prevalence rate in public and shares the common overlap characteristic and risk factors such as age, obesity, and metabolic syndrome that make it difficult to establish the exact pathophysiologic mechanism between them. In addition, studies demonstrating that treatment of OSA may help prevent diabetes or improve glycemic control have not shown convincing result but have become a great field of interest research. This review outlines the bidirectional correlation between OSA and diabetes and explore the pathophysiologic mechanisms by approaching their basic etiologies.

Lower High-Density Lipoprotein Cholesterol Concentration Is Independently Associated with Greater Future Accumulation of Intra-Abdominal Fat

송선옥,황유철,류한욱,Steven E. Kahn,Donna L. Leonetti,Wilfred Y. Fujimoto,Edward J. Boyko 대한내분비학회 2021 Endocrinology and metabolism Vol.36 No.4

Background: Both intra-abdominal fat (IAF) and high-density lipoprotein cholesterol (HDL-C) are known to be associated withcardiometabolic health. We evaluated whether the accumulation of computed tomography (CT)-measured IAF over 5 years was related to baseline HDL-C concentration in a prospective cohort study. Methods: All participants were Japanese-Americans between the ages of 34 and 74 years. Plasma HDL-C concentration and CTmeasurements of IAF, abdominal subcutaneous fat (SCF), and thigh SCF cross-sectional areas were assessed at baseline and at5-year follow-up visits. Results: A total of 397 subjects without diabetes were included. The mean±standard deviation HDL-C concentration was 51.6±13.0mg/dL in men and 66.0±17.0 mg/dL in women, and the IAF was 91.9±48.4 cm2 in men and 63.1±39.5 cm2 in women. The baselineplasma concentration of HDL-C was inversely associated with the change in IAF over 5 years using multivariable regression analysiswith adjustment for age, sex, family history of diabetes, weight change over 5 years, and baseline measurements of body mass index,IAF, abdominal SCF, abdominal circumference, thigh SCF, and homeostatic model assessment for insulin resistance. Conclusion: These results demonstrate that HDL-C concentration significantly predicts future accumulation of IAF over 5 years independent of age, sex, insulin sensitivity, and body composition in Japanese-American men and women without diabetes.

Apolipoprotein B Levels Predict Future Development of Hypertension Independent of Visceral Adiposity and Insulin Sensitivity

한승진,Wilfred Y. Fujimoto,Steven E. Kahn,Donna L. Leonetti,Edward J. Boyko 대한내분비학회 2020 Endocrinology and metabolism Vol.35 No.2

Background: High plasma apolipoprotein B (apoB) levels have been shown to be associated with hypertension, central obesity, andinsulin resistance in cross-sectional research. However, it is unclear whether apoB levels predict future hypertension independent ofbody composition and insulin sensitivity. Therefore, we prospectively investigated whether plasma apoB concentrations independently predicted the risk of hypertension in a cohort of Japanese Americans. Methods: A total of 233 normotensive Japanese Americans (77 men, 156 women; mean age, 46.4±11.0 years) were followed over10 years to monitor them for the development of hypertension. Fasting plasma concentrations of apoB, glucose, and insulin weremeasured at baseline. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). The abdominal visceral and subcutaneous fat areas were measured at baseline using computed tomography. Logistic regression analysis was used to estimate the association between apoB concentrations and the odds of incident hypertension. Results: The 10-year cumulative incidence of hypertension was 21.5%. The baseline apoB level was found to be positively associated with the odds of incident hypertension over 10 years after adjustment for age, sex, body mass index, systolic blood pressure, abdominal visceral fat area, abdominal subcutaneous fat area, total plasma cholesterol concentration, diabetes status, and HOMA-IR atbaseline (odds ratio and 95% confidence interval for a 1-standard deviation increase, 1.89 [1.06 to 3.37]; P=0.030). Conclusion: Higher apoB concentrations predicted greater risks of future hypertension independent of abdominal visceral fat areaand insulin sensitivity in Japanese Americans

Predictors of Incident Type 2 Diabetes Mellitus in Japanese Americans with Normal Fasting Glucose Level

황유철,Wilfred Y. Fujimoto,Steven E. Kahn,Donna L. Leonetti,Edward J. Boyko 대한당뇨병학회 2018 Diabetes and Metabolism Journal Vol.42 No.3

Background: Little is known about the natural course of normal fasting glucose (NFG) in Asians and the risk factors for future diabetes. Methods: A total of 370 Japanese Americans (163 men, 207 women) with NFG levels and no history of diabetes, aged 34 to 75 years, were enrolled. Oral glucose tolerance tests were performed at baseline, 2.5, 5, and 10 years after enrollment. Results: During 10 years of follow-up, 16.1% of participants met criteria for diabetes diagnosis, and 39.6% of subjects still had NFG levels at the time of diabetes diagnosis. During 5 years of follow-up, age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01 to 1.10; P=0.026) and family history of diabetes (OR, 3.24; 95% CI, 1.42 to 7.40; P=0.005) were independently associated with future diabetes diagnosis; however, fasting glucose level was not an independent predictor. During 10 years of follow-up, family history of diabetes (OR, 2.76; 95% CI, 1.37 to 5.54; P=0.004), fasting insulin level (OR, 1.01; 95% CI, 1.00 to 1.02; P=0.037), and fasting glucose level (OR, 3.69; 95% CI, 1.13 to 12.01; P=0.030) were associated with diabetes diagnosis independent of conventional risk factors for diabetes. Conclusion: A substantial number of subjects with NFG at baseline still remained in the NFG range at the time of diabetes diagnosis. A family history of diabetes and fasting insulin and glucose levels were associated with diabetes diagnosis during 10 years of follow-up; however, fasting glucose level was not associated with diabetes risk within the relatively short-term follow-up period of 5 years in subjects with NFG.

Clinical Outcomes of COVID-19 Patients with Type 2 Diabetes: A Population-Based Study in Korea

유지홍,이상아,Sung-Youn Chun,송선옥,이병완,김대중,Edward J. Boyko 대한내분비학회 2020 Endocrinology and metabolism Vol.35 No.4

Background: The aim of this study was to evaluate clinical outcomes in coronavirus disease 2019 (COVID-19) positive patients with type 2 diabetes compared to those without diabetes in Korea. Methods: We extracted claims data for patients diagnosed with COVID-19 from the National Health Insurance Service database in Korea from January 20, 2020 to March 31, 2020. We followed up this cohort until death from COVID-19 or discharge from hospital. Results: A total of 5,473 patients diagnosed with COVID-19 were analyzed, including 495 with type 2 diabetes and 4,978 without diabetes. Patients with type 2 diabetes were more likely to be treated in the intensive care unit (ICU) (P<0.0001). The incidence of in hospital mortality was higher in patients with type 2 diabetes (P<0.0001). After adjustment for age, sex, insurance status, and comorbidities, odds of ICU admission (adjusted odds ratio [OR], 1.59; 95% confidence interval [CI], 1.02 to 2.49; P=0.0416) and in-hospital mortality (adjusted OR, 1.90; 95% CI, 1.13 to 3.21; P=0.0161) among patients with COVID-19 infection were significantly higher in those with type 2 diabetes. However, there was no significant difference between patients with and without type 2 diabetes in ventilator, oxygen therapy, antibiotics, antiviral drugs, antipyretics, and the incidence of pneumonia after adjustment. Conclusion: COVID-19 positive patients with type 2 diabetes had poorer clinical outcomes with higher risk of ICU admission and in-hospital mortality than those without diabetes. Therefore, medical providers need to consider this more serious clinical course when planning and delivering care to type 2 diabetes patients with COVID-19 infection.