Dynamic and dual effects of glycated hemoglobin on estimated glomerular filtration rate in type 2 diabetic outpatients.

BACKGROUND: Diabetic nephropathy is the leading cause of incident end-stage renal disease in Taiwan. Previous studies on the consistent benefits of glycemic control in diabetic nephropathy focused primarily on delaying microalbuminuria. However, this effect on glomerular filtration rate (GFR) remains controversial. This study aims to establish a model that explains the controversial effects of glycated hemoglobin (HbA1C) on GFR. METHODS: This retrospective cohort study followed subjects with type 2 diabetes mellitus, who were enrolled between June 2006 and December 2006, for 4 years. The effects of HbA1C on estimated GFR (eGFR) were examined both cross-sectionally and longitudinally. The dual effects of HbA1C on eGFR, and how renal function interferes with these effects, were investigated. RESULTS: Of the 1,992 subjects enrolled, 1,699 completed the follow-up. HbA1C was positively correlated with eGFR in the cross-sectional study (ß coefficient = 1.44, 95% CI: 0.71-2.17, p = 0.0001). In the longitudinal study, higher baseline HbA1C resulted in a greater decline in eGFR. The annual eGFR decline rates were -1.89, -1.29, and -0.68 ml/min/1.73 m(2)/year for baseline HbA1C >9, 7 to ≤9, and ≤7%, respectively. The eGFR value was simultaneously affected by concurrent (ß coefficient = 0.78, 95% CI: 0.48-1.08, p < 0.0001) and preceding HbA1C (-0.52, -0.82 to -0.23, p < 0.0001). The positive effects of concurrent HbA1C on eGFR reached statistical significance at all stages of chronic kidney disease (CKD); however, the negative effects of preceding HbA1C only applied to CKD stages 3 and 4. CONCLUSIONS: We developed a new model that demonstrates how preceding and concurrent HbA1C simultaneously affect eGFR in opposing ways. The dynamic effects varied among different CKD stages. The deterioration in eGFR at CKD stages 3 and 4 may be postponed by intensive glycemic control. Further prospective studies may be necessary to clarify the specific CKD stage(s) that will benefit from intensive glycemic control.

Prevalence of hypertension and dyslipidemia and their associations with micro- and macrovascular diseases in patients with diabetes in Taiwan: an analysis of nationwide data for 2000-2009.

BACKGROUND/PURPOSE: Cardiovascular complication is the leading cause of mortality in patients with diabetes. Dyslipidemia and hypertension are the major risk factors contributing to cardiovascular disease (CVD). This study was carried out to investigate the prevalence of dyslipidemia and hypertension and their associations with microvascular and macrovascular complications in patients with type 2 diabetes in Taiwan. METHODS: Health-care data and diagnostic codes were retrieved from the Taiwan Bureau of National Health Insurance claims files for the years 2000-2009. Based on these data the annual prevalences of dyslipidemia and hypertension were calculated and patients were stratified by age, gender, and diabetic complications. RESULTS: In patients with diabetes, the prevalence of dyslipidemia increased with age, with the highest rate recorded in adults (inclusive of both genders) between 40 and 65 years of age (p for trend <0.001). The prevalence of hypertension also increased with age with the highest rate seen in adults (inclusive of both genders) >65 years of age (p for trend <0.001). The prevalence of stroke and CVD decreased gradually (p for trend 0.025 and <0.001, respectively), while the prevalence of peripheral vascular disease (PVD) increased in patients with diabetes during the study period (p for trend <0.001). The prevalence of dyslipidemia increased in diabetic patients with eye diseases and in men with nephropathies, but decreased in women with nephropathies during the study period. In contrast, the prevalence of dyslipidemia decreased in patients with macrovascular complications, including CVD and cerebrovascular disease (cerebrovascular accident), but increased in those patients with PVD (p for all trends <0.05). In diabetic patients with various macrovascular complications, except PVD, there was a decrease in the prevalence of hypertension in the past 10 years. The prevalence of hypertension increased in patients with microvascular complications including retinopathy, patients on dialysis (inclusive of both genders), and in men with nephropathy. The prevalence of hypertension along with dyslipidemia increased in patients with microvascular complications including retinopathy, patients on dialysis (inclusive of both genders), and in men with nephropathy; however, the rate decreased in all macrovascular complications except in PVD. CONCLUSION: Although progressively increased prevalence of dyslipidemia and hypertension was observed in patients with diabetes in Taiwan, there was a decrease in the prevalence of stroke and CVD in the past 10 years. Among those with macrovascular diseases, except PVD, there was a trend of decreased prevalence of hypertension and dyslipidemia during the study period. In patients with microvascular diseases, prevalence of hypertension and dyslipidemia in patients with eye diseases increased in the past 10 years. More aggressive management of different risk factors is warranted in diabetic patients with various vascular diseases.

Effects of patient volume on quality of outpatient diabetes care.

In this study we aimed to evaluate the effects of practice size (patient volume) and diabetes caseload in outpatient services on the quality of diabetes care in a teaching hospital. We analyzed the medical records of 2038 diabetic patients treated at a medical center in central Taiwan between January and June 2007. Outpatient practice size (including diabetic and non-diabetic patients) per clinic decreased the odds of glycated hemoglobin (A1C) testing (13% less for every 10 increase in outpatient encounters; p<0.001), and the percentage of A1C values<7% (8% less for every 10 increase in outpatient encounters; p=0.03) in diabetic patients treated by non-endocrinologists. However, a higher caseload of patients with diabetes was associated with an increased lipid profile measurement (19% more for every 5 increase in diabetic patients; p<0.001). In diabetic patients treated by endocrinologists, a higher patient volume was associated with increased odds of low-density-lipoprotein cholesterol (LDL-C) levels<100mg/dl, although there was no effect on the measurement and values of A1C. In conclusion, our study demonstrated some evidence of patient volume-outcome relationship in the management of diabetes in different specialties. This finding can have some implications to the health care system and the referral policy.

Effect of weight loss on proinflammatory state of mononuclear cells in obese women.

In order to investigate whether weight loss can lead to improvement of the mononuclear cell (MNC) proinflammatory state, 21 nondiabetic obese women with mean age 34+/-2 years (mean+/-s.e.m.) and BMI 32.5+/-1.2 kg/m2 were enrolled in a 12-week caloric restriction and light exercise-based weight loss program. Ten lean women served as controls. Reverse transcription-PCR of proinflammatory cytokines and adipocytokines as well as homeostasis model assessment of insulin resistance (HOMA-IR) were determined before and after weight reduction. Nuclear factor kappaB (NF-kappaB) binding to DNA and inhibitors of NF-kappaB (IkappaB-alpha and IkappaB-beta) obtained from peripheral MNCs were measured. Overall, subjects lost a mean of 4.0+/-0.4 kg (5.0+/-0.3% of their initial body weight) (P<0.01). In addition to significant reductions in BMI, fasting glucose and insulin concentrations, mean serum high-sensitivity C-reactive protein (hs-CRP), migration inhibitor factor (MIF), leptin and visfatin levels decreased by 49.0, 66.6, 17.2, and 50.2%, respectively (all P<0.05), while adiponectin concentrations rose by 33.9% (P<0.05). The DNA binding of the transcriptionally active NF-kappaB from (p65/p50) decreased by 38.1% (P<0.05). Elevated levels of mRNA of NF-kappaB related proinflammatory genes, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), MIF, and matrix metalloproteinase-9 (MMP-9), decreased significantly after weight loss. Although mRNA expression of Rel-A, p105, IkappaB-alpha, IkappaB-beta decreased significantly, their protein levels did not change after weight loss. As a group, NF-kappaB binding activity correlated with HOMA-IR (r=0.332, P=0.049) and marginally with values of BMI (r=0.308, P=0.059). In conclusion, weight loss by 5% of initial weight in nondiabetic obese women led to significant improvement in activated intranuclear NF-kappaB binding as well as several transcriptions of proinflammatory genes regulated by NF-kappaB.

Predictors of mortality in hospitalized diabetic patients: A 7-year prospective study.

UNLABELLED: This study was conducted to investigate the mortality rate, causes of death, and standardized mortality ratio (SMR), and to identify the significant predictive factors of mortality in diabetic patients at a medical center in Taiwan. Clinical data were obtained from 1792 diabetic inpatients discharged from the metabolism department of a medical center during the years 1996-2002. Underlying causes of death were determined from death certificates. Predictors of mortality were assessed by uni- and multivariate Cox survival analyses. Of 1792 patients studied, 410 (22.9%) patients died. The crude mortality rate was 93.2/1000 person-years, and the overall SMR was 2.98 (2.71-3.28). The percentages of causes of death ascribed to diabetes, cancer, cardiopulmonary disease, infection, stroke, digestive diseases, nephropathy, accidents, suicide, and disease of arteries, arterioles, and capillaries were 38.0, 13.2, 9.5, 7.8, 7.6, 6.8, 5.1, 2.0, 0.5, and 0.2%, respectively. The independent predictors of mortality were age greater than 65, duration of hypertension more than 5 years, 24h proteinuria greater than 0.3g, and estimated creatinine clearance less than 60mL/min. CONCLUSION: The mortality of diabetic inpatients was about threefold that of the general population. The predictors of mortality included older age, longer duration of hypertension, increased 24h proteinuria, and decreased creatinine clearance.

Effects of alendronate combined with hormone replacement therapy on osteoporotic postmenopausal Chinese women.

To evaluate the effect of alendronate combined with hormone replacement therapy (HRT) on postmenopausal osteoporotic Chinese women living in Taiwan, we treated 151 women (age range, 47-70 years; mean, 61 years) with conjugated equine estrogen (0.625 mg), medroxyprogesterone 5 mg, and elemental calcium 500 mg daily with either alendronate 10 mg (n = 79) or placebo (n = 72), and measured their bone mineral density (BMD) at the lumbar spine and hip every 6 months for 3 years. Urine N-telopeptide of type I collagen corrected by concentration of urine creatinine (NTx/Cr) and serum osteocalcin (OC) concentration was also measured at weeks 2, 4, and every 3 months from month 3 for 2 years. Significantly higher percentage increases in BMD at the lumbar spine (P < .0001, 2-way analysis of variance) throughout the 36-month treatment period were found in the alendronate plus HRT group than in the HRT-only group. However, there was no difference in BMD at the femoral neck and trochanter between these 2 groups. Treatment with alendronate plus HRT resulted in a 10.1% increase at the L-spine BMD and a 7.7% increase at the trochanter BMD at the end of the 3-year study period (P < .01, compared with baseline at both sites). A significant decline in urine NTx/Cr was observed at week 4 in the alendronate plus HRT group, whereas in the HRT-only group, a significant decline in urine NTx/Cr occurred at month 9. By the end of 24 months, urine NTx/Cr decreased by 49.7% in the alendronate plus HRT group (P = .001 compared with a 20.4% increase in the HRT group). A significant decline in serum OC level occurred at month 3 in the alendronate plus HRT group, whereas a similar decline was observed at month 6 in the HRT-only group. By the end of 24 months, serum OC decreased by 52.2% in the alendronate plus HRT group (P < .001 compared with a 1.5% increase in the HRT-only group). Subjects treated with alendronate plus HRT had a significantly greater percentage decrease in urine NTx/Cr (P = .0001) and serum OC (P = .0007) than subjects treated with HRT only throughout the 24-month treatment period by 2-way analysis of variance comparison. There was no difference in upper gastrointestinal or drug-related side effects between groups. In conclusion, our data suggest that the use of alendronate combined with HRT for 3 years was well tolerated and it significantly increased BMD at the L-spine and hip in postmenopausal Chinese women with osteoporosis. This regimen is safe and can be used in subjects who have no satisfactory response to a single agent or who have very low BMD with multiple risks. However, this study does not indicate whether HRT plus alendronate has any greater effect on BMD than alendronate alone.