Diabetes mellitus is associated with an increased risk of dementia. We aimed to comprehensively analyze the incidence and risk factors for dementia and young-onset dementia (YOD) in diabetic patients in Korea using the National Health Insurance Service data.Between January 1, 2009 and December 31, 2012, a total of 1,917,702 participants with diabetes were included and followed until the date of dementia diagnosis or until December 31, 2015. We evaluated the incidence and risk factors for all dementia, Alzheimer's disease (AD), and vascular dementia (VaD) by Cox proportional hazards analyses. We also compared the impact of risk factors on the occurrence of YOD and late-onset dementia (LOD).During an average of 5.1 years of follow-up, the incidence of all types of dementia, AD, or VaD was 9.5, 6.8, and 1.3/1,000 person-years, respectively, in participants with diabetes. YOD comprised 4.8% of all dementia occurrence, and the ratio of AD/VaD was 2.1 for YOD compared with 5.5 for LOD. Current smokers and subjects with lower income, plasma glucose levels, body mass index (BMI), and subjects with hypertension, dyslipidemia, vascular complications, depression, and insulin treatment developed dementia more frequently. Vascular risk factors such as smoking, hypertension, and previous cardiovascular diseases were more strongly associated with the development of VaD than AD. Low BMI and a history of stroke or depression had a stronger influence on the development of YOD than LOD.The optimal management of modifiable risk factors may be important for preventing dementia in subjects with diabetes mellitus.
This study investigated the incidence of β-cell dysfunction and the clinical and biochemical factors affecting that in patients with type 2 diabetes having more than 3 years of follow-up.β-Cell dysfunction was assessed by measuring changes in the fasting serum C-peptide concentrations. Patients were classified into two groups: cases showing a decreased (Group D) or an unchanged or increased (Group I) C-peptide concentration from the baseline.Of the 504 patients included in this study, 259 (51%) showed decreased C-peptide concentrations, of whom 20% showed a decrease of ≥50%. Most patients, however, had a final C-peptide concentration of ≥1 ng/mL, with only 18 (4%) individuals having a level <0.6 ng/mL. Patients in Group D had a longer duration of diabetes, higher initial hemoglobin A1c concentration, and longer treatment durations with sulfonylurea and insulin compared with Group I. After adjusting for diabetes duration and C-peptide follow-up period, the duration of sulfonylurea treatment was found to be the only factor independently associated with decreases in the C-peptide concentration.Although β-cell function deteriorates over time in patients with type 2 diabetes, these cases mainly have fasting serum C-peptide concentrations of ≥1 ng/mL. A longer treatment duration with sulfonylurea is associated with a more rapid decline in the C-peptide concentration.
Background: We investigated whether fasting glucose (FG) variability could predict the risk of dementia.Methods: This cohort study analyzed data from Koreans with diabetes after at least three health examinations by the Korean National Health Insurance Corporation between 2005 and 2010, which included at least one examination between 2009 and 2010. A total of 769,554 individuals were included, excluding those aged <40 years and those with dementia. FG variability was measured using the variability independent of the mean (FG-VIM). The incidence of dementia was defined by the International Classification of Diseases 10th Revision codes and prescription of anti-dementia medication and was subdivided into Alzheimer’s disease (AD) and vascular dementia (VD).Results: During the 6.9-year follow-up, 54,837, 41,032, and 6,892 cases of all-cause dementia, AD, and VD, respectively, were identified. Cox proportional regression analyses showed that as the FG-VIM quartile increased, the risk of dementia serially increased after adjustment for metabolic factors, income status, and diabetes-related characteristics, including the mean FG. Participants in FG-VIM quartile 4 showed a 18%, 19%, and 17% higher risk for all-cause dementia, AD, and VD, respectively, than those in quartile 1; this particularly included non-obese patients with a longer duration of diabetes, high FG levels, dyslipidemia, and those taking glucose-lowering medications. Conversely, the baseline FG status and dementia showed a U-shaped association.Conclusion: Increased FG variability over 5 years can predict the risk of dementia in individuals with diabetes in Korea. This finding was more pronounced in patients with less favorable metabolic profiles.
Abstract Background — Athough an association exists between type 2 diabetes and Parkinson’s disease (PD), the implications of glycemic variability on PD are unknown. We assessed the future risk of incident PD according to visit-to-visit fasting plasma glucose (FPG) variability; this was calculated using standard deviation (FPG-SD), coefficient variance (FPG-CV), and variability independent of the mean (FPG-VIM). Methods — Using the Korean National Health Insurance Service–Health Screening Cohort, we followed 131,625 Korean adults without diabetes. This study population was divided into a midlife group (<65 years) and an elderly group (≥65 years), during a median follow-up of 8.4 years. Results — The adjusted hazard ratios (HRs) were calculated using a multivariable Cox proportional hazard analysis. In the midlife group, the HRs for incident PD in the highest quartile of FPG variability, as measured using SD, CV, and VIM, were 1.35 (95% confidence interval (CI), 1.07–1.70), 1.31 (95% CI, 1.04–1.65), and 1.33 (95% CI, 1.06–1.67), respectively, when compared to the lowest quartile group. However, the incident PD was not different depending on FPG variability in the elderly group. Kaplan–Meier curves of PD probability showed a progressively increasing risk of PD according to the higher FPG variability in the midlife group. According to a multivariable adjusted model, a 1-SD unit increment in glycemic variability was associated with a 9% higher risk for incident PD in the midlife group. Conclusions — Increased long-term glycemic variability is a preceding risk factor for developing PD in the midlife population without diabetes.
There are very few predictive indexes for long-term mortality among community-dwelling elderly Asian individuals, despite its importance, given the rapid and continuous increase in this population. We aimed to develop 10-year predictive mortality indexes for community-dwelling elderly Korean men and women based on routinely collected clinical data. We used data from 2244 elderly individuals (older than 60 years of age) from the southwest Seoul Study, a prospective cohort study, for the development of a prognostic index. An independent longitudinal cohort of 679 elderly participants was selected from the Korean Genome Epidemiology Study in Ansan City for validation. During a 10-year follow-up, 393 participants (17.5%) from the development cohort died. Nine risk factors were identified and weighed in the Cox proportional regression model to create a point scoring system: age, male sex, smoking, diabetes, systolic blood pressure, triglyceride, total cholesterol, white blood cell count, and hemoglobin. In the development cohort, the 10-year mortality risk was 6.6%, 14.8%, 18.2%, and 38.4% among subjects with 1 to 4, 5 to 7, 8 to 9, and ≥10 points, respectively. In the validation cohort, the 10-year mortality risk was 5.2%, 12.0%, 16.0%, and 16.0% according to these categories. The C-statistic for the point system was 0.73 and 0.67 in the development and validation cohorts, respectively. The present study provides valuable information for prognosis among elderly Koreans and may guide individualized approaches for appropriate care in a rapidly aging society.
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Melatonin plays an important role in regulating circadian rhythms. It also acts as a potent antioxidant and regulates glucose and lipid metabolism, although the exact action mechanism is not clear. The α2-HS-glycoprotein gene (AHSG) and its protein, fetuin-A (FETUA), are one of the hepatokines and are known to be associated with insulin resistance and type 2 diabetes. The aim of this study was to determine whether melatonin improves hepatic insulin resistance and hepatic steatosis in a FETUA-dependent manner. In HepG2 cells treated with 300 μmol/L of palmitic acid, phosphorylated AKT expression decreased, and FETUA expression increased, but this effect was inhibited by treatment with 10 μmol/L of melatonin. However, melatonin did not improve insulin resistance in FETUA-overexpressing cells, indicating that improvement in insulin resistance by melatonin was dependent on downregulation of FETUA. Moreover, melatonin decreased palmitic acid-induced ER stress markers, CHOP, Bip, ATF-6, XBP-1, ATF-4, and PERK. In addition, in the high-fat diet (HFD) mice, oral treatment with 100 mg/kg/day melatonin for 10 weeks reduced body weight gain to one-third of that of the HFD group and hepatic steatosis. Insulin sensitivity and glucose intolerance improved with the upregulation of muscle p-AKT protein expression. FETUA expression and ER stress markers in the liver and serum of HFD mice were decreased by melatonin treatment. In conclusion, melatonin can improve hepatic insulin resistance and hepatic steatosis through reduction in ER stress and the resultant AHSG expression.
Abstract Background Substantial evidence supports an association between physical activity and cognitive function. However, the role of muscle mass and function in brain structural changes is not well known. This study investigated whether sarcopenia, defined as low muscle mass and strength, accelerates brain volume atrophy. Methods A total of 1284 participants with sarcopenic measurements and baseline and 4-year follow-up brain magnetic resonance images were recruited from the Korean Genome and Epidemiology Study. Muscle mass was represented as appendicular skeletal muscle mass divided by the body mass index. Muscle function was measured by handgrip strength. The low mass and strength groups were defined as being in the lowest quintile of each variable for one’s sex. Sarcopenia was defined as being in the lowest quintile for both muscle mass and handgrip strength. Results Of the 1284 participants, 12·6%, 10·8%, and 5·4% were classified as the low mass, low strength, and sarcopenia groups, respectively. The adjusted mean changes of gray matter (GM) volume during 4-year follow-up period were − 9·6 mL in the control group, whereas − 11·6 mL in the other three groups ( P < 0·001). The significantly greater atrophy in parietal GM was observed in the sarcopenia group compared with the control group. In a joint regression model, low muscle mass, but not muscle strength, was an independent factor associated with a decrease of GM volume. Conclusions Sarcopenia is associated with parietal GM volume atrophy, in a middle-aged population. Maintaining good levels of muscle mass could be important for brain health in later adulthood.
Chronotype is a trait determining individual circadian preference in behavioral and biological rhythm relative to external light-dark cycle. However, little is known about the relationship between chronotype and metabolic disorders. The aim of this study was to examine whether late chronotype is related to metabolic abnormalities and body composition in middle-aged adults, independent of sleep duration and lifestyle. A total of 1620 participants aged 47–59 years were recruited from the Korean Genome and Epidemiology Study. Chronotype was assessed by the Morningness-Eveningness Questionnaire. Associations of chronotype with diabetes, metabolic syndrome, sarcopenia, and visceral obesity were analyzed. All participants underwent the oral glucose tolerance test, and body composition was measured with dual energy x-ray absorptiometry. Visceral obesity was designated as visceral fat area, measured by abdominal computed tomography, of >100 cm2. Chronotype was classified as morning in 29.6% of subjects, evening in 5.9%, neither morning nor evening in 64.5%. Evening type, when compared with morning type, was significantly associated with diabetes (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.01–2.95), metabolic syndrome (OR, 1.74; 95% CI, 1.05–2.87), and sarcopenia (OR, 3.16; 95% CI, 1.36–7.33) after adjusting for confounding factors. Gender differences in the associations were evident. In men, evening type was associated with diabetes (OR, 2.98; 95% CI, 1.39–6.39) and sarcopenia (OR, 3.89; 95% CI, 1.33–11.33). Only metabolic syndrome was associated with evening type in women (OR, 2.22; 95% CI, 1.11–4.43). At the population level, evening chronotype was independently associated with diabetes, metabolic syndrome, and sarcopenia. These results support the importance of circadian rhythms in metabolic regulation.
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