Cognitive Impairment and Glycemic Control in Elderly Patients Under Health-Care Case Management.

We aim to test whether the association between glucose control and cognitive function still holds true in elderly patients with diabetes mellitus (DM) and Alzheimer disease (AD) under health-care case management. We enrolled 100 patients with DM (mean age: 74.6 years; male: 49%) and 102 patients with AD (mean age: 77.9 years; male: 41.2%) consecutively from the Diabetes Shared Care Program and the memory clinic. These patients were followed up every 3 months with scheduled examinations. Most patients with AD were at early stage and DM was a common comorbidity (n = 42). In the DM group, there were 76 patients with subjective cognitive decline and 19 patients with mild cognitive impairment, but none sought further consultation. After adjusting for age, sex, education, and comorbidity, higher levels of glycated hemoglobin (HbA1C) were not associated with lower Mini-Mental State Examination (MMSE) scores in the DM group (coefficient: 0.03; 95% confidence interval [CI]: -0.44 to 0.50) and lower MMSE scores were not associated with higher HbA1C in the AD group either (coefficient: -0.05; 95% CI: -0.11 to 0.01). When additionally accounting for the variability of HbA1C in the DM group, higher standard deviation of HbA1C was associated with poor clock drawing test scores, but not MMSE. The coexistence of AD-DM was common, but the association between hyperglycemia and cognitive impairment was not seen in patients under regular health monitoring.

High Serum Adipocyte Fatty Acid Binding Protein Is Associated with Metabolic Syndrome in Patients with Type 2 Diabetes.

Adipocyte fatty acid binding protein (A-FABP) is a key mediator of obesity-related metabolic syndrome (MetS). The aim of this study was to evaluate the relationship between A-FABP concentration and MetS in type 2 diabetes mellitus (DM) patients. Fasting blood samples were obtained from 165 type 2 DM volunteers. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Among 165 DM patients, 113 patients (68.5%) had MetS. Diabetic persons who had MetS had significantly higher A-FABP levels (P < 0.001) than those without MetS. Female DM persons had higher A-FABP level than man (P < 0.001). No statistically significant differences in A-FABP levels were found in use of statin, fibrate, or antidiabetic drugs. Multivariate forward stepwise linear regression analysis revealed that body fat mass (P < 0.001), logarithmically transformed creatinine (log-creatinine; P < 0.001), female DM patients (P < 0.001), and logarithmically transformed high sensitive C-reactive protein (log-hs-CRP; P = 0.013) were positively correlated, while albumin (P = 0.004) and glomerular filtration rate (GFR; P = 0.043) were negatively correlated with serum A-FABP levels in type 2 DM patients. In this study, higher serum A-FABP level was positively associated with MetS in type 2 DM patients.

Association between white blood cell count and components of metabolic syndrome.

BACKGROUND: Components of metabolic syndrome (MetS) were found to be associated with several inflammatory factors including white blood cell count (WBCC), which is an easily available test in clinical practice. In the present study, the relationships between WBCC and MetS components were investigated in children. METHODS: A total of 288 Taiwanese children, under 10 years old, with normal WBCC, were enrolled in the study. They were divided into quartiles according to WBCC (lowest, WBCC1; highest, WBCC4). The mean values of each MetS component for every group were compared in boys and girls separately. Multivariate linear regression between the WBCC and the MetS components after adjusting for age and body mass index (BMI) were also evaluated. RESULTS: In group comparison, only the high-density lipoprotein-cholesterol (HDL-C) was found to be significantly lower in WBCC4 in boys. Other components were not different. After multivariate linear regression, WBCC was negatively correlated to HDL-C and positively to BMI in boys. Although not significant, similar relationships were also observed in girls. Interestingly, borderline positive correlation was noted between triglyceride (TG) and WBCC in girls. CONCLUSION: BMI was positively and HDL-C was negatively related to WBCC in boys. A similar trend could also be observed in girls but without significance. Borderline significant correlation between TG and WBCC was noted in girls. These findings suggest that cardiovascular risks might commence even in childhood. Early detection of children with these abnormalities may help to prevent cardiovascular disease and diabetes in adolescence or even adulthood.

The impact of metabolic syndrome on insulin sensitivity, glucose sensitivity, and acute insulin response after glucose load in early-onset type 2 diabetes mellitus: Taiwan Early-Onset Type 2 Diabetes Cohort Study.

Diabetic patients with metabolic syndrome (MetS) have higher lifetime risks for cardiovascular disease, especially in early-onset type 2 diabetes mellitus (EODM). Increased insulin resistance (IR) and impaired insulin secretion are important pathophysiologies in diabetic patients. Therefore, the effects of MetS on IR and insulin secretion in EODM were investigated. Forty-eight EODM (mean age, 22.8 +/- 0.6 years) patients were enrolled in this study. Two grouping criteria were used: the first was whether the patient had MetS or not (MetS+ or Met-, with 31 and 17 patients, respectively); and the second was the number of MetS components each group had, that is, MetS (1,2) with 1 to 2, MetS (3) with 3, and MetS (4,5) with 4 to 5 components (17, 17, and 14 patients in each group, respectively). A frequently sampled intravenous glucose tolerance test was performed to measure insulin sensitivity, glucose sensitivity, acute insulin response after glucose load, and disposal index. Severe IR was noted with both homeostasis model assessment and frequently sampled intravenous glucose tolerance test both in MetS+ and MetS-. However, significantly higher acute insulin response after glucose load and disposal index were noted in MetS+ and MetS (4,5) than in Met-, MetS (1,2), and MetS (3), respectively. Early-onset type 2 diabetes mellitus patients with MetS had similar IR to those without MetS. This may be due to early deterioration of insulin action in these subjects. In addition, insulin secretion was higher in subjects with more MetS components, suggesting that EODM patients with MetS had better preserved ability of beta-cell compensation for IR than those without MetS.

Factor analysis of metabolic syndrome using direct measurement of insulin resistance in Chinese with different degrees of glucose tolerance.

BACKGROUND & OBJECTIVE: With the increasing prevalence of type 2 diabetes and cardiovascular disease in Taiwan, the understanding of metabolic syndrome (MetS) becomes more important. The purpose of this study was to investigate the clustering patterns of the risk variables of the MetS with factor analysis (FacAn). METHODS: A total of 564 Chinese individuals with normal glucose tolerance (N, n=345), impaired glucose tolerance (IGT, n=164) or diabetes mellitus (DM, n=55) were enrolled. Insulin resistance was measured by insulin suppression test (IST). The components of MetS such as waist hip ratio (WHR), fasting plasma glucose (FPG), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), high density lipoprotein cholesterol (HDLC) and steady state plasma glucose (SSPG) from IST were put into the model of exploratory FacAn. RESULTS: In spite of the minor different loading patterns, three dimensions were identified in the three subgroups; a "blood pressure" dimension, loading with mainly SBP and DBP, an "insulin resistance" dimension, loading mainly with SSPG, and an "adiposity/glucose" dimension loading with TG, WHR or FPG. INTERPRETATION & CONCLUSION: Our results were consistent with different ethnic groups in earlier reports that more than two dimensions were identified and that the MetS is not unified by a single underlying aetiology, i.e., insulin resistance. Longitudinal analysis in this and other populations will be required to validate our findings and to test their generalisability.

Predicting glucose intolerance with normal fasting plasma glucose by the components of the metabolic syndrome.

BACKGROUND: Surprisingly, it is estimated that about half of type 2 diabetics remain undetected. The possible causes may be partly attributable to people with normal fasting plasma glucose (FPG) but abnormal postprandial hyperglycemia. We attempted to develop an effective predictive model by using the metabolic syndrome (MeS) components as parameters to identify such persons. SUBJECTS AND METHODS: All participants received a standard 75-g oral glucose tolerance test, which showed that 106 had normal glucose tolerance, 61 had impaired glucose tolerance, and 6 had diabetes-on-isolated postchallenge hyperglycemia. We tested five models, which included various MeS components. Model 0: FPG; Model 1 (clinical history model): family history (FH), FPG, age and sex; Model 2 (MeS model): Model 1 plus triglycerides, high-density lipoprotein cholesterol, body mass index, systolic blood pressure and diastolic blood pressure; Model 3: Model 2 plus fasting plasma insulin (FPI); Model 4: Model 3 plus homeostasis model assessment of insulin resistance. A receiver-operating characteristic (ROC) curve was used to determine the predictive discrimination of these models. RESULTS: The area under the ROC curve of the Model 0 was significantly larger than the area under the diagonal reference line. All the other 4 models had a larger area under the ROC curve than Model 0. Considering the simplicity and lower cost of Model 2, it would be the best model to use. Nevertheless, Model 3 had the largest area under the ROC curve. CONCLUSION: We demonstrated that Model 2 and 3 have a significantly better predictive discrimination to identify persons with normal FPG at high risk for glucose intolerance.

Impaired glucose tolerance and impaired fasting glucose share similar underlying pathophysiologies.

Both impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are pre-diabetic states. IGT was defined as having normal fasting plasma glucose (< 6.1 mmol/l) and abnormal 2-hr post-challenge plasma glucose. IFG was defined as having abnormal fasting plasma and normal 2-hr post-challenge plasma glucose (< 7.8 mmol/l). To explore whether these two abnormalities share similar underlying pathophysiologies, we evaluated risk factors of IGT and IFT using the models of factor analysis. The present study included 107 subjects with IGT and 52 with IFG. An oral glucose tolerance test and insulin suppression test, which could quantify insulin resistance, were performed on separate days. The risk factors include waist-to-hip ratio (WHR), triglycerides, high-density lipoprotein (HDL)-cholesterol, blood pressure, and fasting plasma glucose, which are associated with metabolic syndrome and insulin resistance. Factor analysis is a commonly used statistical method that could reduce a large number of risk factors into smaller numbers of groups, also called dimension. Accordingly, the complicated data could be interpreted more easily, since the related risk factors are grouped in one dimension. The results showed that the risk factors of IGT and IFG have similar grouping patterns. Triglyceride, insulin resistance, and HDL-cholesterol were grouped in one dimension (the lipid dimension), while WHR, mean blood pressure and fasting plasma glucose were grouped in another dimension (the metabolic dimension). In conclusion, except for WHR, the grouping patterns of the components in both IGT and IFG were nearly identical. These results suggest that IGT and IFG may share similar pathophysiologies.

Impact of clinical characteristics of individual metabolic syndrome on the severity of insulin resistance in Chinese adults.

The impact the metabolic syndrome (MetS) components on the severity of insulin resistance (IR) has not been reported. We enrolled 564 subjects with MetS and they were divided into quartiles according to the level of each component; and an insulin suppression test was performed to measure IR. In males, steady state plasma glucose (SSPG) levels in the highest quartiles, corresponding to body mass index (BMI) and fasting plasma glucose (FPG), were higher than the other three quartiles and the highest quartiles, corresponding to the diastolic blood pressure and triglycerides, were higher than in the lowest two quartiles. In females, SSPG levels in the highest quartiles, corresponding to the BMI and triglycerides, were higher than in all other quartiles. No significant differences existed between genders, other than the mean SSPG levels in males were greater in the highest quartile corresponding to BMI than that in the highest quartile corresponding to HDL-cholesterol levels. The factor analysis identified two underlying factors (IR and blood pressure factors) among the MetS variables. The clustering of the SSPG, BMI, triglyceride and HDLcholesterol was noted. Our data suggest that adiposity, higher FPG and triglyceride levels have stronger correlation with IR and subjects with the highest BMI have the highest IR.

Correlations between white blood cell count and metabolic syndrome in middle-age Taiwanese.

Metabolic syndrome was first proposed in 1988 and has been recognized as a powerful predictor for cardiovascular disease and diabetes. At the same time, white blood cell count (WBCC) was proposed to have significant correlation with metabolic syndrome (MS). In this study, we attempted to investigate the relationship between WBCC and components of metabolic syndrome in subjects in Taiwan with normal WBCC, no significant medical disease, and no medications known to affect the components of MS. We enrolled 1185 subjects with age > or = 40 years in 1997. These subjects participated in the annual health examination of the MJ Life Clinic. Subjects with abnormal WBCC (> 10x 10(9) cells/l), history of diabetes, hypertension or hyperlipidemia, or taking medications for these diseases or medications known to affect components of MS, were excluded. Because the menstrual cycle has an effect on the components of MS, we divided the subjects into three groups: male (M group, n = 576), old female (OF group, aged > or = 50 years, n = 307), and young female (YF group: aged < 50 years, n = 302). Each group was further divided into four quartiles according to WBCC (WBCC1 to WBCC4, from the lowest to highest WBCC). The body mass index (BMI) of YF was significantly lower than both M and OF. The diastolic blood pressure (DBP) and triglycerides (TG) were higher in M than YF. High-density lipoprotein cholesterol (HDLC) was lower in M compared to both YF and OF. When evaluating the metabolic components in different quartiles of WBCC in M, only WBCC1 had lower BMI and TG than WBCC4 after adjustment for age and BMI. For OF, the results were similar, the BMI of both WBCC1 and WBCC2 was lower than WBCC3 and TG of WBCC1 was lower than WBCC4. Finally, in YF, none of the BMI, blood pressure, FPG, HDLC, or TG was different in the four WBCC quartiles. The results of multiple regression between the WBCC and components of MS after adjustment for age and BMI were also evaluated. Significant correlations could only be noted in WBCC with BMI and TG in M and OF. In conclusion, in subjects with normal WBCC and no history of significant medical diseases, BMI and TG are significantly related to the levels of WBCC and are the two earliest components of MS to be noted, especially in males and post-menopausal females.

The effect of combination therapy with propylthiouracil and cholestyramine in the treatment of Graves' hyperthyroidism.

OBJECTIVE: The study aims to evaluate the efficacy of combination therapy with propylthiouracil (PTU) and cholestyramine in the treatment of Graves' hyperthyroidism. BACKGROUND: Thyroxine (T4) is metabolized mainly in the liver by conjugation to glucuronides and sulphates that enter the enterohepatic circulation. Thyrotoxic patients have an abnormal increase in thyroid hormone in their enterohepatic circulation. Previous studies on combination therapy with methimazole and cholestyramine for Graves' hyperthyroidism have shown it to be an effective adjunctive treatment. In this study, we examined the efficacy of combination therapy with PTU and cholestyramine in the treatment of Graves' hyperthyroidism. METHODS: Thirty patients with newly diagnosed Graves' hyperthyroidism were randomly divided into two groups: group I (n = 15) received PTU 100 mg twice a day, propranolol 40 mg twice a day and cholestyramine 4 g twice a day for 4 weeks; group II (n = 15) received PTU 100 mg twice a day and propranolol 40 mg twice a day for 4 weeks. The therapeutic efficacy was determined by serum total triiodothyronine (TT3), free thyroxine (FT4) and TRAb levels at baseline, and at the end of 2 and 4 weeks during the study period. RESULTS: There was no significant difference in baseline thyroid function parameters. At the end of 2 and 4 weeks of the study period, serum TT3 and FT4 levels of group I were significantly lower than those of group II. No significant differences in the TRAb level were found between the two groups. CONCLUSION: Cholestyramine contributed to a more rapid and complete decline in thyroid hormone levels in patients with Graves' hyperthyroidism. It was thus proved to be an effective and well-tolerated adjunctive therapy.

Primary hypothalamic lymphoma with panhypopituitarism presenting as stiff-man syndrome.

We report an unusual case of primary hypothalamic lymphoma with hypopituitarism presenting as Stiff-man syndrome (SMS). A 64-year-old man was hospitalized due to a 3-week history of general weakness, anorexia, vomiting, weight loss, and muscle pain and spasms precipitated by motion and tactile stimuli resulting in muscle stiffness and difficulty in mobility. Physical examination revealed normal sensorimotor function and reflexes, except for bitemporal visual field defect. Routine laboratory and gastrointestinal examinations provided no remarkable clues. Endocrine assessment revealed low levels of morning cortisol, thyroxine, and anterior pituitary hormones but an increase in prolactin level. The patient's muscle pain and stiffness improved dramatically within 2 days after hydrocortisone therapy and thyroxine replacement. Magnetic resonance imaging (MRI) of the brain confirmed an 18-mm enhancing hypothalamic tumor with optic chiasm involvement, which proved to be a B-cell lymphoma. The results of the extensive studies for systemic lymphoma were negative, suggesting a primary hypothalamic lymphoma. The tumor regressed completely and was invisible on MRI scan after adjuvant radiotherapy. The patient's condition was satisfactory and there was no recurrence of SMS during the 2-year follow-up period. This case demonstrated that primary hypothalamic lymphoma complicated with adrenal insufficiency may manifest as SMS. Early diagnosis and prompt intervention can lead to a favorable outcome and reduce morbidity.