The influence of prehypertension, hypertension, and glycated hemoglobin on the development of type 2 diabetes mellitus in prediabetes: the Korean Genome and Epidemiology Study (KoGES).

BACKGROUND: It has been reported that elevated blood pressure (BP) was significantly associated with the increased risk for type 2 diabetes mellitus (T2DM). However, there is still limited information about the influence of BP on the risk for T2DM across the level of glycated hemoglobin (HbA1c). METHOD: In a cohort of the Korean Genome and Epidemiology Study (KoGES), 2830 non-diabetic Korean adults with prediabetes defined by HbA1c level of 5.7-6.4% were followed-up for 10 years. Multivariate cox proportional hazards assumption was used to assess the risk for T2DM according to the baseline BP categories (normal, prehypertension and hypertension) and HbA1c level (low: 5.7-5.9% and high: 6.0-6.4%). RESULTS: The risk for T2DM significantly increased proportionally to BP categories (adjusted HR; reference in normal BP, 1.32 [1.10-1.59] in prehypertension and 1.61 [1.35-1.92] in hypertension). Subgroup analysis indicated that individuals with high HbA1c had the higher risk for T2DM than individuals with low HbA1c regardless of BP. Additionally, combined presence of hypertension and high HbA1c had the highest risk for T2DM (adjusted HR: 3.82 [3.00-4.87]). In each systolic and diastolic BP level, the risk for T2DM significantly increased from systolic BP ≥ 130 mmHg (adjusted HRs: 1.39 ([1.15-1.71]) and diastolic BP ≥ 80 mmHg (adjusted HRs: 1.30 ([1.07-1.58]). CONCLUSION: BP and HbA1c may be useful tools in identifying individuals with prediabetes more potentially predisposed to T2DM. Prospective studies should be considered to examine whether controlling BP actually lowers the risk for T2DM.

Evaluating the risk of hypertension according to the metabolic health status stratified by degree of obesity.

Despite the accumulated evidence showing the significant association between hypertension and obesity, it remains unclear how metabolic healthy status of obesity have an impact on the development of hypertension. Thus, this study was to investigate the risk of hypertension according to the metabolic healthy status stratified by the degree of obesity. A cohort of 25,442 Korean men without hypertension at baseline was followed-up from 2005 to 2010. They were divided into the following 6 phenotypes according to their baseline metabolic health and obesity status: metabolically healthy normal weight (MH-NW), metabolically healthy overweight (MH-OW), metabolically healthy obese (MHO), metabolically unhealthy normal weight (MU-NW), metabolically unhealthy overweight (MU-OW), and metabolically unhealthy obese (MUO). Cox proportional hazard model was used to evaluate the risk for hypertension according to the metabolically healthy status stratified by degree of obesity. During 91,256.4 person-years of follow-up, 4633 participants (18.2%) developed hypertension. The adjusted hazard ratios (95% confidence intervals) for hypertension in MH-OW, MHO, MU-NW, MU-OW, and MUO phenotypes compared with MH-NW phenotype were 1.13 (1.04-1.23), 1.43 (1.15-1.69), 1.17 (1.02-1.34), 1.49 (1.27-1.72), and 1.54 (1.36-1.88), respectively. The interaction between metabolically healthy status and degree of obesity was not significant (P for interaction = .29). Compared with MH-NW, both the obese phenotype and metabolically unhealthy phenotype independently had an increased risk for hypertension. These results imply that both metabolic health status and obesity status play important roles independently in the risk of hypertension in Korean men.

The Risk for Insulin Resistance according to the Degree of Non-Alcoholic Fatty Liver Disease in Korean Men.

Insulin resistance (IR) plays a significant role in the development and progression of non-alcoholic fatty liver disease (NAFLD). However, the natural course of insulin sensitivity under NAFLD remained unclear. Accordingly, this study was designed to investigate the effect of NAFLD on insulin resistance. A total of 20,628 Korean men without homeostasis model assessment of insulin resistance (HOMA-IR < 2.7) were followed-up for 5 years. They were serially checked for HOMA-IR to monitor the development of IR (HOMA-IR ≥ 2.7). The incidence rate of IR increased according to the degree of NAFLD (normal: 11.6%, mild: 28.8%, moderate to severe: 40.5%, P < 0.001). Cox proportional hazards model showed that HRs (95% CI) for IR increased proportionally to the degree of NAFLD (mild: 1.19 [1.02-1.39], moderate to severe: 1.32 [1.08-1.57]). IR was more potentially associated with the more progressive NAFLD than normal and milder state. In addition, NAFLD was the independent risk factor of the development of IR. These results suggest the potential availability of NAFLD as a predictor of IR.

Clinical significance of serum ferritin level as an independent predictor of insulin resistance in Korean men.

AIMS: Elevated serum ferritin level has been reported to be associated with type 2 diabetes mellitus and metabolic syndrome, which have significant relation with insulin resistance (IR). However, clinical association between serum ferritin level and IR remained unclear. Accordingly, this study was designed to evaluate the longitudinal effects of baseline serum ferritin level on the development of IR. METHODS: An IR-free 22,057 healthy Korean men (HOMA-IR<2.7), who had participated in a medical health check-up program in 2005, were followed up until 2010. During follow up, the development rate of IR, defined in case of HOMA-IR≥2.7, was monitored according to the quartile groups of serum ferritin levels. Cox proportional hazards models were used to measure the hazard ratios (HRs) of baseline serum ferritin levels on IR. RESULTS: During 77,471.1 person-years of follow-up, 4494 incident cases of insulin resistance developed between 2006 and 2010 (overall development rate: 20.4%). The development rate of IR increased in proportion to the baseline serum ferritin levels (quartile 1: 16.7%, quartile 2: 18.5%, quartile 3: 19.9%, quartile 4: 25.5%, P<0.001). After adjusting for multiple covariates, the HRs (95% CI) for IR, comparing the second to the fourth quartile of serum ferritin levels with the first quartile, were 1.11 (0.99-1.24), 1.19 (1.07-1.33) and 1.51 (1.35-1.68), respectively (P for trend <0.001). CONCLUSIONS: Elevated serum ferritin level was independently associated with the future development of IR in Korean men.

Clinical significance of non-alcoholic fatty liver disease as a risk factor for prehypertension.

Previous epidemiologic studies have shown the clinical association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). However, there is only limited information about the effect of NAFLD on the development of hypertension. Accordingly, we investigated the clinical association between NAFLD and prehypertension. A prospective cohort study was conducted on the 11,350 Korean men without prehypertension for 5 yr. The incidences of prehypertension were evaluated, and Cox proportional hazard model was used to measure the hazard ratios (HRs) for the development of prehypertension according to the degree of NAFLD (normal, mild, moderate to severe). The incidence of prehypertension increased according to NAFLD states (normal: 55.5%, mild: 63.7%, moderate to severe: 70.3%, P<0.001). Even after adjusting for multiple covariates, the HRs (95% confidence interval) for prehypertension were higher in the mild group (1.18; 1.07-1.31) and moderate to severe group (1.62; 1.21-2.17), compared to normal group, respectively (P for trend <0.001). The development of prehypertension is more potentially associated with the more progressive NAFLD than normal and milder state. These findings suggest the clinical significance of NAFLD as one of risk factors for prehypertension.

Elevated fasting serum insulin level predicts future development of hypertension.

BACKGROUND: Studies have investigated clinical association between fasting insulin level and hypertension. However, it is still debatable whether elevated fasting insulin actually increases the risk of hypertension with the passage of time. Thus, this study was aimed at investigating the association between baseline fasting insulin level and the development of hypertension. METHODS: 25,062 normotensive, non-diabetic Korean men participating in a medical health check-up program were followed up from 2005 until 2010. They were divided into 4 groups according to baseline fasting insulin levels (first quartile-fourth quartile). The incidence of hypertension was compared among 4 groups, and Cox proportional hazards model was used to determine if hypertension was associated with higher baseline fasting insulin level. RESULTS: The incidence of hypertension increased according to the baseline fasting insulin level (first quartile: 13.3%, second quartile: 15.4%, third quartile: 17.5%, fourth quartile: 23.2%, P<0.001). Even after adjusting for multiple covariates, the HRs (95% CI) for hypertension were higher for the second (1.12; 0.96-1.31), third (1.39; 1.20-1.62) and fourth quartile group (1.75; 1.51-2.03), compared to the first quartile group, respectively (P for trend<0.001). CONCLUSION: The risk of hypertension was in proportion to the baseline fasting insulin level. In addition, hyperinsulinemia was an independent risk factor for the future development of hypertension. These findings suggest the value of fasting insulin level as an early predictor of hypertension.