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Objective: It was hypothesized that the presence of nonalcoholic fatty liver disease (NAFLD) at baseline predicts future conversion from the metabolically healthy (MH) to the metabolically unhealthy (MU) phenotype according to body fat mass., Methods: A total of 22,551 Korean participants (13,601 men and 8,950 women) aged 18 to 78 years in the Kangbuk Samsung Health Study cohort were enrolled from 2007 to 2013., Results: During a median of 5.1 years of follow-up (interquartile range 2.1-9.8 years), 23.5% (n = 5,298) of MH individuals converted to the MU phenotype. NAFLD at baseline predicted conversion independent of age, sex, BMI, lifestyle factors, individual components of metabolic syndrome, and insulin resistance (HR, 1.29; 95% CI: 1.19-1.39; P < 0.0001). In participants with lower BMI and fat mass, NAFLD was strongly associated with conversion; however, as BMI and fat mass increased, the risk decreased, and there was no association in participants with higher BMI and fat mass (P < 0.0001 for trend)., Conclusions: NAFLD at baseline was independently associated with future conversion from the MH to the MU phenotype., (© 2019 The Obesity Society.)

Obesity is a risk factor for many cancers including breast, esophageal, colon, and thyroid cancer. We aimed to evaluate the association of thyroid cancer with body mass index (BMI), waist circumference (WC), and weight change. This nationwide population-based cohort study included 11,323,006 adults who joined the national health screening program. Weight change was defined as the difference between the weight of the subjects measured during the study period and the weight at the time of four years ago. For evaluating the association between the weight change and the risk of thyroid cancer, subjects without weight change for four years were defined as the reference group. Mean age was 50.1 ± 13.7 years and 44% were female. In total, 50,464 subjects (0.4%) had newly-diagnosed thyroid cancer. After multivariable analyses, the incidence of thyroid cancer increased significantly in subjects with larger WC as well as higher BMI (P < 0.001 and P < 0.001, respectively). In subjects who were lean and became obese, the incidence of thyroid cancers increased significantly (hazard ratio [HR] 1.15 [1.11-1.19]). In subjects who were obese and became lean, the incidence of thyroid cancers decreased significantly (HR 0.89 [0.86-0.93]). These results demonstrated that higher BMI and larger WC were significantly associated with an increased risk of thyroid cancer. Weight gain in lean subjects was associated with an increased risk of thyroid cancer, and weight reduction in subjects with obesity was associated with a decreased risk of thyroid cancer.

Background and Aim: Helicobacter pylori (H. pylori) infection has been known to influence the gastric leptin and ghrelin secretion, for which the exact pathogenic role has not been documented yet. This study was designed to investigate the influence of H. pylori eradication on plasma or gastric levels of ghrelin, body mass index (BMI), and resultant levels of appetite in patients with peptic ulcer disease., Methods: Twenty-two patients with H. pylori-associated active duodenal or gastric ulcer were treated with 7 weeks of antisecretory medication followed with 7 days of eradication regimen. The plasma and tissue ghrelin levels, tumor necrosis factor-alpha (TNF-alpha) mRNA, BMI, and appetite scale were checked before and after treatment. An additional endoscopic examination was conducted in 10 patients taking both ulcer treatment and H. pylori eradication., Results: Gastric ghrelin mRNA expression was significantly increased after either ulcer healing or H. pylori eradication, whereas gastric TNF-alpha mRNA expression was decreased after ulcer treatment and H. pylori eradication. In parallel with these changes, the visual analog scales for hunger and prospective food consumption were significantly increased after ulcer healing and H. pylori eradication. An increase in BMI was not statistically related to ulcer healing and H. pylori eradication therapy. In the subgroup analysis of 10 patients performed with additional endoscopic examination, ulcer treatment was associated with increased plasma ghrelin level and tissue ghrelin expression irrelevant to H. pylori eradication., Conclusion: Restored tissue levels of ghrelin and improved status of appetite was achieved with gastric ulcer healing and H. pylori eradication.

Osteoporosis is a growing health problem in women and in men. This cross-sectional study examined the association of anthropometric, lifestyle, and hormonal factors with bone mineral density (BMD) in 152 healthy Korean middle-aged men. Smoking habits and alcohol consumption were assessed by interview. Serum testosterone and insulin-like growth factor-I (IGF-I) levels were measured by radioimmunoassay, and serum growth hormone (GH) levels were measured by immunoradiometric assay. GH stimulation tests were performed after the ingestion of 500 mg of L-dopa. BMD was measured at the lumbar spine and at the femoral neck by dual-energy X-ray absorptiometry. Of the middle-aged men, 3.9% were osteoporotic and 28.3% were osteopenic at the lumbar spine site, and 5.9% were osteoporotic and 45.4% were osteopenic at the femoral neck site. Lumbar spine BMD correlated significantly with body mass index (BMI), and femoral neck BMD correlated significantly with age, BMI, and serum IGF-I levels. The lowest quartile group for serum IGF-I levels showed the lowest femoral neck BMD. Osteoporotic men by lumbar spine BMD showed significant differences from the normal BMD group in terms of BMI and smoking habits. Also, osteoporotic men by femoral neck BMD were significantly different for mean age, BMI, and serum IGF-I levels compared with the normal BMD group. On multiple regression analysis, BMI was found to be the only independent predictor of lumbar spine BMD, whereas both BMI and serum IGF-I levels were found to be the independent predictors of femoral neck BMD. Overall, 28.3%-45.4% of middle-aged Korean men were osteopenic. We suggest that higher age, a lower BMI, current smoking history, and lower serum IGF-I levels are risk factors for lower BMD in middle-aged Korean men; however, serum testosterone levels and GH secretory capacity were not found to be correlated with BMD.

Aim: To evaluate the efficacy and safety of gemigliptin and dapagliflozin dual add‐on therapy (GEMI + DAPA) to metformin in type 2 diabetes (T2D) patients who had inadequate glycaemic control on metformin alone, compared with a single add‐on of either gemigliptin (GEMI) or dapagliflozin (DAPA) to metformin. Materials and Methods: In this randomized, double‐blind, double‐dummy, active‐controlled, parallel‐group, phase 3 study, 469 T2D patients treated with a stable dose of metformin for 8 weeks or longer were randomized to receive GEMI + DAPA (n = 157) and either GEMI (n = 156) or DAPA (n = 156). The primary endpoint was change in HbA1c levels from baseline at week 24. Results: Baseline characteristics including body mass index and T2D duration were similar among groups. At week 24, the least square mean changes in HbA1c from baseline were −1.34% with GEMI + DAPA, −0.90% with GEMI (difference between GEMI + DAPA vs. GEMI −0.44% [95% confidence interval {CI}: −0.58% to −0.31%], P <.01) and −0.78% with DAPA (difference between GEMI + DAPA vs. DAPA −0.56% [95% CI: −0.69% to −0.42%], P <.01). Both upper CIs were less than 0, demonstrating the superiority of GEMI + DAPA for lowering HbA1c. The rates of responders achieving HbA1c less than 7% and less than 6.5% were greater with GEMI + DAPA (84.9%, 56.6%) than with GEMI (55.3%, 32.2%) and DAPA (49.3%, 15.3%). The incidence rate of adverse events was similar across groups, with low incidence rates of hypoglycaemia, urinary tract infection and genital infection. Conclusions: These results suggest that the addition of GEMI + DAPA to metformin as triple combination therapy was effective, safe and well‐tolerated, especially for T2D patients who experienced poor glycaemic control on metformin alone. [ABSTRACT FROM AUTHOR]

Background: No cohort studies have evaluated the effect of obesity on the incidence of thyroid cancer according to metabolic health status. Therefore, this study examined the association of body mass index (BMI) and metabolic health status with thyroid cancer risk. Methods: A cohort study was performed involving 255,051 metabolically healthy (MH) and metabolically unhealthy (MUH) adults free of thyroid cancer at baseline who were followed for a median of 5.3 years. A parametric proportional hazard model was used to estimate the adjusted hazard ratio (aHR) and confidence interval (CI). Results: During 1,402,426.3 person-years of follow-up, 2927 incident thyroid cancers were identified. Among men, the multivariable aHR for thyroid cancer comparing obesity, defined as a BMI ≥25 kg/m2, with a BMI of 18.5–22.9 kg/m2 was 1.47 [CI 1.12–1.93] in MH individuals, whereas the corresponding HR in MUH individuals was 1.26 [CI 1.03–1.53]. Among women, the corresponding HR in MH individuals was 1.05 [CI 0.80–1.36], whereas the corresponding HR in MUH individuals was 1.43 [CI 1.22–1.69]. Increasing quartiles of waist circumference were positively associated with risk of thyroid cancer in MUH men and women (p for trend <0.005) but not in MH individuals. Conclusions: In both MH and MUH men, obesity was associated with an increased risk of incident thyroid cancer, indicating excessive adiposity per se as an independent risk factor for thyroid cancer. Conversely, women with MUH obesity but not MH obesity were found to have an increased risk of thyroid cancer, indicating that obesity with accompanying metabolic abnormalities may affect thyroid cancer risk in women. [ABSTRACT FROM AUTHOR]

Summary: Objective: Thyroid hormones play crucial roles in the control of energy homoeostasis and can influence body composition. In contrast, the changes in body composition might influence thyroid hormone levels. We evaluated associations between thyroid hormone levels, body composition and insulin resistance in euthyroid subjects with normal thyroid ultrasound (US) findings. Design and Patients: This retrospective cross‐sectional study included 36 655 euthyroid subjects who joined the medical health check‐up programme at our institution. Serum thyroid hormone levels were analysed in association with body fat percentage (BFP), skeletal muscle mass index (SMI) and homoeostatic model assessment of insulin resistance (HOMA‐IR). Linear regression analyses were performed to evaluate relationships between thyroid hormone levels and anthropometric parameters. Results: Mean age was 36.4 years, and 49% of subjects were female. In multiple linear regression analysis, serum‐free triiodothyronine (FT3) levels exhibited positive associations with waist circumference (WC) and HOMA‐IR and a negative association with body weight, body mass index (BMI) and SMI among both men and women. The association between serum‐free thyroxine (FT4) levels and anthropometric markers showed inconsistent results in men and women. Serum thyroid‐stimulating hormone (TSH) levels showed a positive association with HOMA‐IR in both men and women. Conclusions: Lower SMI was significantly associated with higher serum FT3 levels, the active form of thyroid hormone, in both men and women. Higher insulin resistance was positively associated with serum FT3 levels and inversely associated with serum TSH levels in euthyroid subjects with normal thyroid US findings. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested the importance of non-alcoholic fatty liver disease (NAFLD) and systemic inflammation in the development of atherosclerosis. The aim of this study was to compare the risk for coronary artery calcification (CAC) development according to the status of NAFLD and inflammation over four years of follow-up in subjects without baseline CAC. Methods: A total of 1,575 participants in a health screening program were divided into four groups according to baseline NAFLD state and high-sensitivity C-reactive protein (hs-CRP) (median 0.06 mg/L) levels as follows: no NAFLD and hs-CRP <0.06 mg/L, no NAFLD and hs-CRP ≥0.06 mg/L, NAFLD and hs-CRP <0.06 mg/L, and NAFLD and hs-CRP ≥0.06 mg/L. Coronary artery calcium score (CACS) was repeatedly measured by multi-detector computed tomography at four-year intervals and CAC development during those intervals was monitored in subjects with baseline CACS = 0. Results: Over four years, 148 subjects (9.4%) developed CAC. The proportion of subjects who developed CAC was significantly higher in subjects with NAFLD at baseline compared with those without NAFLD at baseline (6.8 vs. 12.4%, p<0.01), and it was also higher in subjects with hs-CRP ≥0.06 mg/L compared with those with hs-CRP <0.06 mg/L (7.2 vs. 11.5%, p<0.01). In addition, the proportion of subjects who developed CAC was highest in subjects with NAFLD and hs-CRP ≥0.06 mg/dL, followed by subjects with NAFLD, subjects without NAFLD and hs-CRP ≥0.06 mg/L, and subjects without NALFD and hs-CRP <0.05 mg/L at baseline, in that order (13.7, 10.0, 8.3, and 5.8%, respectively; p for trend<0.01). The odds ratio for CAC development was highest in subjects with NAFLD and hs-CRP ≥0.06 mg/L (1.67, 95% CI 1.01–2.77), though it was attenuated after adjustment for body mass index. Conclusions: The concomitant presence of NAFLD and systemic inflammation as assessed by hs-CRP increases the risk of CAC development over four years. [ABSTRACT FROM AUTHOR]

Background: In contrast to type 2 diabetes, the association of body mass index (BMI) with glycemic control in type 1 diabetes (T1D) remains unclear. We investigated the relationship between BMI and average HbA1c levels in subjects with T1D.Method: In this multi-centre observational study, we analysed 719 subjects with T1D aged ≥18 years. Average HbA1c levels over 18 months and other clinical and laboratory parameters were evaluated.Results: The mean age and duration of diabetes at baseline were 41.5 ± 13.9 and 11.3 ± 8.7 years, respectively. A U-shaped correlation between BMI and 18-month average HbA1c levels was documented by a spline curve. Based on this finding, subjects were divided into three groups according to BMI (group I, <21; group II, 21-23; and group III, ≥23 kg/m2 ). In group I, the BMI negatively correlated with average HbA1c (r = -0.172, p = 0.011), while a positive relationship was observed (r = 0.162, p = 0.012) in group III. Average HbA1c levels were lower and the proportion of individuals with well-controlled glycemia (HbA1c <7%) were increased in the higher BMI tertile group among subjects with group I as well as in the lower BMI tertile group among subjects with group III BMI. After adjustment with additional covariates in the multiple regression model, these associations between BMI and HbA1c levels according to the different BMI ranges remained significant.Conclusions: In Korean subjects with T1D, an inverse relationship of BMI with HbA1c levels was observed in the low BMI group, while a positive correlation was shown in the high BMI group. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The Triglyceride Glucose Index (TyG index) is considered a surrogate marker of insulin resistance. The aim of this study is to investigate whether the TyG index has a predictive role in identifying individuals with a high risk of incident diabetes and to compare it with other indicators of metabolic health. A total 2900 non-diabetic adults who attended five consecutive annual health check-ups at Kangbuk Samsung Hospital was divided into four subgroups using three methods: (1) baseline TyG index; (2) obesity status (body mass index ≥25 kg/m2) and cutoff value of TyG index; (3) obesity status and metabolic health, defined as having fewer than two of the five components of high blood pressure, fasting blood glucose, triglyceride, low high-density lipoprotein cholesterol, and highest decile of homeostasis model assessment-insulin resistance. The development of diabetes was assessed annually using self-questionnaire, fasting glucose, and glycated hemoglobin. We compared the risk of incident diabetes using multivariate Cox analysis. During 11623 person-years there were 101 case of incident diabetes. Subjects with high TyG index had a high risk of diabetes. For TyG index quartiles, hazard ratios (HRs) of quartiles 3 and 4 were 4.06 (p = 0.033) and 5.65 (p = 0.006) respectively. When the subjects were divided by obesity status and cutoff value of TyG index of 8.8, the subgroups with TyG index ≥ 8.8 regardless of obesity had a significantly high risk for diabetes (HR 2.40 [p = 0.024] and 2.25 [p = 0.048]). For obesity status and metabolic health, the two metabolically unhealthy subgroups regardless of obesity had a significantly high risk for diabetes (HRs 2.54 [p = 0.024] and 2.73 [p = 0.021]). In conclusion, the TyG index measured at a single time point may be an indicator of the risk for incident diabetes. The predictive value of the TyG index was comparable to that of metabolic health. [ABSTRACT FROM AUTHOR]

Objectives: HDLs have many diverse functions. The goal of this study was to determine the association of HDL cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) with the development of type 2 diabetes (T2D). In particular, this study determined d the association between the ratio of HDL-C to apoA-I (HA) and incident T2D. Design and methods: A total of 27 988 subjects with impaired fasting glucose (IFG) (18 266 men and 9722 women) aged & 21-91 years (mean age 40.7 years) were followed for a mean duration of 2.81 years Results: Study subjects were divided into quartiles according to the baseline HA ratio. Age, male sex, current smoking, BMI, waist circumference, and high-sensitivity C-reactive protein decreased across the quartiles, and all metabolic profiles, including blood pressure, fasting glucose, insulin resistance as determined by homeostasis model assessment of insulin resistance, and lipid measurements such as total cholesterol, LDL cholesterol, non-HDL-C, and apoB, improved as the HA ratio increased. In addition, incident cases of T2D decreased as ra the HA ratio increased, independent of age, sex, BMI, current smoking, systolic blood pressure, HbA1c, fasting serum insulin, family history of diabetes, and serum triglyceride concentrations (HR (95% CI) of fourth quartile vs first quartile; 0.76 (0.67-0.86), P<0.0001). Conclusions: A higher HA ratio was associated with favorable metabolic profiles and a lower risk of T2D development in subjects with IFG. [ABSTRACT FROM AUTHOR]

Background: Recent studies report the importance of metabolic health beyond obesity. The aim of this study is to compare the risk for diabetes development according to different status of metabolic health and obesity over a median follow-up of 48.7 months. Methods: 6,748 non-diabetic subjects (mean age 43 years) were divided into four groups according to the baseline metabolic health and obesity status: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUHNO) and metabolically unhealthy obese (MUHO). Being metabolically healthy was defined by having less than 2 components among the 5 components, that is, high blood pressure, high fasting blood glucose, high triglyceride, low high-density lipoprotein cholesterol and being in the highest decile of homeostasis model assessment-insulin resistance (HOMA-IR) index. Obesity status was assessed by body mass index (BMI) higher than 25 kg/m2. The development of diabetes was assessed annually from self-questionnaire, fasting glucose and HbA1c. Results: At baseline, 45.3% of the subjects were MHNO, 11.3% were MHO, 21.7% were MUHNO, and 21.7% were MUHO. During a median follow-up of 48.7 months, 277 subject (4.1%) developed diabetes. The hazard ratio for diabetes development was 1.338 in MHO group (95% CI 0.67–2.672), 4.321 in MUHNO group (95% CI 2.702–6.910) and 5.994 in MUHO group (95% CI 3.561–10.085) when MHNO group was considered as the reference group. These results were similar after adjustment for the changes of the risk factors during the follow-up period. Conclusion: The risk for future diabetes development was higher in metabolically unhealthy subgroups compared with those of metabolically healthy subjects regardless of obesity status. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested that metabolic health may contribute more to the atherosclerosis than obesity. The aim of this study is to compare coronary artery calcium scores (CACS) among patients with different metabolic health and obesity status. Methods: A health-screening program of 24,063 participants (mean age 41 years) was conducted, and CACS was assessed by multi-detector computerized tomography (MDCT). Being metabolically healthy was defined as having fewer than two of the following risk factors: high blood pressure, high fasting blood glucose, high triglyceride, low high-density lipoprotein cholesterol, highest decile of homeostasis model assessment-insulin resistance (HOMA-IR) index, and highest decile of high-sensitivity C-reactive protein (hs-CRP). Obesity status was defined as body mass index (BMI) higher than 25 kg/m2. Analyses were performed in four groups divided according to metabolic health and obesity: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUHNO), and metabolically unhealthy obese (MUHO). Results: Mean values of CACS in the four groups were significantly different, except those between MHNO and MHO and between MUHNO and MUHO. When multinomial logistic regression analysis was performed with five CACS categories as the dependent variables and after adjusting for age, sex, and smoking status, the MHO, MUHNO, and MUHO groups showed significantly increased odds ratio for increasing CACS categories compared with no calcification status (5.221 for CACS >400 in MUHO group with 95% CI 2.856∼5.032 with MHNO group as the reference). When other variables including the metabolic parameters were included in the same model, the risks were attenuated. Conclusion: Metabolic health is more closely associated with subclinical atherosclerosis than obesity as assessed by CACS. [ABSTRACT FROM AUTHOR]

Abstracts: Background and Aims: This study aimed to investigate the association between baseline fasting insulin levels, changes in fasting insulin levels, and future development of hypertension in normotensive, non-diabetic, healthy adults. Methods: We analyzed data from 11,123 adults, aged 20–65years, who had no history of hypertension or diabetes mellitus at a 2004 medical examination in a health promotion program and had attended a repeat examination in 2008. Subjects were divided into four groups according to baseline quartiles of fasting insulin and dichotomized fasting insulin levels at baseline and after 4years: low–low, low–high, high–low, high–high. We also assessed whether the association differed between the younger (20–40years) and older subjects (41–65years). Results: In four years, 1142 subjects (10.3%) developed hypertension. The odds ratio (OR) for the development for hypertension increased as the quartiles of baseline fasting insulin levels and changes in fasting insulin levels increased from the first to the fourth quartile (OR 1.15, 1.35, and 1.95 vs. 1.07, 1.22, and 1.41, respectively), after adjusting for multiple factors. The OR for hypertension was 2.0-fold higher in the high–high group and 1.34-fold higher in the low–high group than in the low–low group. In comparing the results by age group, we found that these relationships were more prominent in younger subjects. Conclusion: High baseline and continuously increasing fasting insulin levels appeared to be independent determinants for the future development of hypertension during this 4-year follow-up study in normotensive, non-diabetic, healthy adults. [Copyright &y& Elsevier]

BackgroundWe aimed to examine the relationship between iron status and hypertension as few studies have addressed this.MethodsWe analyzed the association between ferritin/total iron-binding capacity (TIBC) and the subsequent development of hypertension. A total of 8,580 men who visited the Health Promotion Center for a medical checkup in 2005 were followed-up after 4 years.ResultsOf the 8,580 men who were not hypertensive at baseline, 818 were found to be hypertensive at the 4-year follow-up. Compared with those who remained normotensive, these hypertensive subjects had higher levels of ferritin and TIBC at baseline, but had no significant difference in iron levels. After adjustment for age and body mass index (BMI), the odds ratios (OR) was substantially higher for new hypertension (OR 1.54, 95% confidence intervals (CIs) 1.26-1.88; P for trend <0.001) in subjects with the highest ferritin quartiles compared with those in the lowest quartiles. The association of serum ferritin levels with the incidence of hypertension was unchanged after adjustment for baseline blood pressure (BP). Adjustment for insulin resistance as measured by the homeostasis model assessment and the presence of a fatty liver reduced the magnitude of the OR for hypertension (first quartile reference, fourth quartiles OR 1.24, 95% CI 1.01-1.53, P for trend = 0.012), but did not affect their statistical significance.ConclusionSerum ferritin, but not iron level, was a significant predictor of hypertension in middle-aged Korean men. Fatty liver disease and insulin resistance may be mediators of this high ferritin-hypertension association.American Journal of Hypertension (2012); doi:10.1038/ajh.2011.241 [ABSTRACT FROM AUTHOR]

Background: The triglyceride glucose (TyG) index is an inexpensive clinical surrogate marker for insulin resistance. However, the relationship between TyG index and atherosclerotic cardiovascular disease (CVD) remains unclear. We evaluated the relationship between TyG index and CVD using a large-scale population dataset from the National Health Information Database (NHID).Methods: We performed a retrospective observational cohort study of 5,593,134 persons older than 40 years from 2009 to 2017 using the NHID. We divided the participants into TyG index quartiles. Outcome variables were stroke, myocardial infarction, and both. The incidence of outcomes was estimated for each TyG quartile over the total follow-up period. All outcomes were analyzed by Cox proportional hazards regression analysis while controlling for baseline covariates.Results: During 8.2 years of mean follow-up, stroke was diagnosed in 89,120 (1.59%), MI in 62,577 (1.12%), and both stroke and MI in 146,744 (2.62%) participants. Multivariate-adjusted hazard ratios (HRs) for patients in the highest TyG index quartile demonstrated that these patients were at higher risk for stroke (HR = 1.259; 95% confidence interval [CI] 1.233-1.286), for MI (HR = 1.313; 95% CI 1.28-1.346), and for both (HR = 1.282; 95% CI 1.261-1.303) compared with participants in the lowest TyG index quartile. These effects were independent of age, sex, smoking, alcohol consumption, physical activity, body mass index, systolic blood pressure, and total cholesterol.Conclusions: In our large population study, TyG index, a simple measure reflecting insulin resistance, was potentially useful in the early identification of individuals at high risk of experiencing a cardiovascular event. [ABSTRACT FROM AUTHOR]

Chronic hyperglycaemia and glucose variability are associated with the development of chronic diabetes-related complications. We conducted a pooled analysis of patient-level data from three 24-week, randomized, phase III clinical trials to evaluate the impact of lixisenatide ( LIXI) on glycaemic variability ( GV) vs placebo as add-on to basal insulin. The main outcome GV measures were standard deviation (s.d.), mean amplitude of glycaemic excursions ( MAGE), mean absolute glucose ( MAG) level, area under the curve for fasting glucose ( AUC-F), and high ( HBGI) and low blood glucose index ( LBGI). The change in GV metrics over 24 weeks and relationships among baseline GV, patient characteristics and outcomes were assessed. Data were pooled from 1198 patients (665 LIXI, 533 placebo). Values for s.d., MAG level, MAGE, HBGI, and AUC-F significantly decreased with LIXI vs placebo, while LBGI values were unchanged. Higher baseline GV measures correlated with older age, longer type 2 diabetes duration, lower body mass index, higher baseline glycated/haemogobin, greater reduction in postprandial glucose ( PPG) level, and higher rates of symptomatic hypoglycaemia. These data show that LIXI added to basal insulin significantly reduced GV and PPG excursions vs placebo, without increasing the risk of hypoglycaemia ( LBGI). [ABSTRACT FROM AUTHOR]

Aims: Weight cycling is defined as cyclical loss and gain of weight and recent studies suggest deleterious effects of weight cycling on cardiometabolic health. We aimed to analyze the risk for diabetes development in association with weight cycling over 4 years of follow-up.Methods: A retrospective study performed in 4,818 non-diabetic participants (mean age 43 years, 78.3% men) in a health screening program in whom serial health examinations were performed in 5 consecutive years from 2010 to 2014. Average successive variability of weight (ASVW) was defined by the amount of body weight change in absolute value between the successive years over 5 years summed and divided by four. The subjects were divided into two groups according to body mass index (BMI), normal weight (<23 kg/m2) and overweight (≥23 kg/m2).Results: Over 4 years, 3.2% developed diabetes. When the subjects were divided into 3 groups according to tertile groups of ASVW, those in the highest tertile showed significantly increased risk for diabetes development compared to those with the lowest tertile {odds ratio (OR) 1.860; 95% CI 1.130-3.063}. When similar analyses were performed according to the 4 groups divided by baseline body weight and ASVW over four years, those who were more than overweight at baseline with high ASVW showed significantly increased risk of diabetes development compared to those had normal weight and low ASVW (OR 2.266; 95% 1.123-4.572). When the subjects were divided into six group according to weight change and ASVW, those with increased weight over 4 years and high ASVW showed the highest risk for diabetes development among the groups compared to those with stable weight and low ASVW over four years (OR 3.660; 95% CI 1.402-9.553).Conclusions: Those with high ASVW showed significantly increased risk for diabetes development over four years compared with those who had low ASVW. Weight cycling was significantly associated with increased risk for diabetes. [ABSTRACT FROM AUTHOR]

Aims: To evaluate whether variable fatty liver status over time influence the risk of type 2 diabetes differently.Methods: We analyzed the data from 7849 subjects without type 2 diabetes who underwent comprehensive health check-ups annually for 5 years. All subjects had an abdominal ultrasonography annually. The risk of incident diabetes was assessed in individuals with sustained non-alcoholic fatty liver disease (NAFLD), individuals with changed fatty liver status (intermittent NAFLD group), and individuals who did not have NAFLD (never NAFLD group) during the study period. A subgroup analysis was done in subjects of the intermittent NAFLD group. Incident diabetes was compared according to the number of time diagnosed as NAFLD by annual ultrasonography.Results: During the mean follow-up of 4 years, subjects in the sustained NAFLD group had a HR of 1.50 (95% CI 1.13-1.98) for the development of diabetes compared with those in the never NAFLD group, whereas the risk was not higher in the intermittent NAFLD group (HR 0.99, 95% CI 0.76-1.31). When compared with the intermittent NAFLD group, multivariable adjusted HR for incident diabetes was 1.50 (95% CI 1.20-1.89) in the sustained NAFLD group. As the number of times diagnosed as NAFLD increased, the proportion of subjects who developed diabetes also increased (p = .002).Conclusions: The presence of fatty liver was differentially associated with incident diabetes based on its duration. The persistence of fatty liver status is an important factor for an independent association between NAFLD and incident diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Non-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of the metabolic syndrome (MetS), with insulin resistance as the common pathophysiology. In a current longitudinal cohort study, we evaluated the separate and combined effects of MetS and NAFLD on incident diabetes risk.Methods: Participants were categorized into four groups on the basis of the presence of NAFLD and MetS at baseline (i.e., with NAFLD, with MetS, with both, or without either). We compared the development of diabetes among these four groups.Results: During the mean follow up of 4years, 435 of the 7849 participants (5.5%) developed diabetes. The age, sex, and smoking-adjusted risk of incident diabetes was higher in the NAFLD only group (HR 1.51, 95% CI 1.14-1.99), MetS only group (HR 2.82, 95% CI 2.01-3.95), and both group (HR 5.45, 95% CI 4.32-6.82) compared with the group of neither. When compared with the NAFLD only group, the adjusted HR for incident diabetes was 1.87 (95% CI 1.29-2.72) in the MetS only group and 3.62 (95% CI 2.74-4.77) in both group. Among individuals with MetS, the presence of NAFLD showed a significant increase in risk of incident diabetes even after further adjustment for MetS components including fasting glucose, TG, BMI, systolic BP, and HDL-C (HR 1.53, 95% CI 1.09-2.16).Conclusion: The presence of NAFLD further increased the risk of incident diabetes in individuals with metabolic syndrome. Our results suggest that the coexistence of NAFLD has an additive effect on the development of diabetes in individuals with MetS. [ABSTRACT FROM AUTHOR]