Hypoadiponectinemia predicts impaired endothelium-independent vasodilation in newly diagnosed type 2 diabetic patients: an 8-year prospective study.

BACKGROUND: Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. The aim of this study was to investigate whether low adiponectin levels predict the impairment of endothelial function in newly diagnosed type 2 diabetic patients in an 8-year prospective study. METHODS: In the prospective study, we enrolled 133 newly diagnosed type 2 diabetic patients without subclinical atherosclerosis and gave them intensive therapy; the mean treatment period was 8 years. Intensive treatment was a stepwise implementation of behavior modification and pharmacological therapy targeting hyperglycaemia, hypertension, dyslipidaemia and obesity. We measured baseline circulating adiponectin with an enzyme-linked immunosorbent assay, endothelium-dependent and -independent vasodilation by high-resolution vascular ultrasound. At year 8, 102 patients were reexamined for endothelium-dependent and -independent vasodilation. RESULTS: Sex-adjusted adiponectin level was positively correlated with endothelium-independent vasodilation both at baseline (r = 0.150, P = 0.043) and at year 8 (r = 0.339, P = 0.001), whereas no association was found between adiponectin and endothelium-dependent vasodilation. In a stepwise multivariate linear regression model, adiponectin was an independent predictor for impaired endothelium-independent vasodilation at year 8 (P = 0.001). CONCLUSIONS: Plasma adiponectin concentration was associated with endothelium-independent vasodilation and hypoadiponectinemia predicted the impairment of endothelium-independent vasodilation in newly diagnosed type 2 diabetic patients under multifactorial intervention. These data support the causative link of impairment of endothelium-independent vasodilation with hypoadiponectinemia.

[The effect and mechanism of transient continuous subcutaneous insulin infusion therapy on beta cell function, insulin resistance and vascular endothelial injury in newly diagnosed type 2 diabetes].

OBJECTIVES: To explore the effect of transient continuous subcutaneous insulin infusion (CSII) on ß cell function, insulin resistance and vascular endothelial injury in newly diagnosed type 2 diabetic patients and its potential mechanism. METHODS: Ten patients with newly diagnosed type 2 diabetes mellitus (T2DM) accepted CSII for two weeks. Intravenous glucose tolerance test (IVGTT) and hyperinsulinemia euglycemia clamp test were performed before and after CSII. Serum soluble E-selectin (sE-selectin) was used to evaluate the injury of vascular endothelial cell, while serum high sensitivity C reactive protein (hsCRP) and soluble CD14 (sCD14) were both used to assess inflammatory condition. RESULTS: (1) Compared with those before treatment, the blood glucose levels of IVGTT, the area under the curve of the blood glucose, glycosylated hemoglobin, TC and LDL-C in the patients were decreased after CSII (P < 0.05 or 0.01). (2) Compared with those before treatment, the insulin levels of IVGTT (except the fasting insulin), the area under the curve of insulin and acute insulin response were all increased after CSII (P < 0.05 or 0.01). (3) Compared with that before treatment, the glucose infusion ratio in the clamp test [(3.46 ± 1.66) mg x kg⁻¹ x min⁻¹ increased to (7.14 ± 2.37) mg x kg⁻¹ x min⁻¹] and HOMA-beta elevated, while HOMA-IR declined (P < 0.05 or 0.01 in all). (4) Compared with those before treatment, the levels of serum sE-selectin, sCD14 and hsCRP were decreased (P < 0.01, except for hsCRP). CONCLUSION: Transient intensive insulin therapy in patients with newly diagnosed T2DM is useful to restore beta cell function, attenuate insulin resistance, repair vascular endothelial injury and improve the disorder of blood sugar and lipid. The mechanism may be related with the inhibition of inflammation in patients.

[Relationship of adipocyte fatty acid-binding protein to adiponectin ratio with femoral intima-media thickness and endothelium-dependent vasodilation in patients with newly-diagnosed type 2 diabetes mellitus].

OBJECTIVE: To explore the relationship between plasma adipocyte fatty acid-binding protein (A-FABP), adiponectin (APN) levels and A-FABP/APN ratio with femoral intima-media thickness (FA-IMT) and endothelium-dependent vasodilation in patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: Plasma A-FABP and APN in 133 patients with newly diagnosed T2DM were measured by enzyme-linked immunosorbent assays. FA-IMT, endothelium-dependent and independent vasodilation of brachial artery was measured by high-resolution vascular ultrasound. Upper quartile of FA-IMT was regarded as a criterion of elevated FA-IMT, defined as early atherosclerosis (AS). The patients were subdivided into low FA-IMT group (FA-IMT < 0.60 mm, n = 34), middle FA-IMT group (0.60 mm /= 0.80 mm, n = 33). RESULTS: Plasma A-FABP/APN ratio was higher in early AS group than in low IMT control group [A-FABP/APN x 1000, 3.9(2.8 approximately 6.1) vs 2.9(1.8 approximately 5.7), P < 0.05]. FA-IMT correlated positively with plasma A-FABP/APN ratio (r = 0.216, P = 0.006) and negatively with APN (r = -0.179, P = 0.020). After adjusted for age, gender and BMI, FA-IMT still correlated positively with plasma A-FABP/APN ratio (r = 0.217, P = 0.007) and negatively with APN (r = -0.172, P = 0.026). Endothelium-dependent vasodilation correlated negatively with plasma A-FABP/APN ratio (r = -0.166, P = 0.028). After adjusted for age, gender and BMI, endothelium-dependent vasodilation still correlated negatively with plasma A-FABP/APN ratio (r = -0.153, P = 0.042). CONCLUSION: Plasma A-FABP/APN ratio is closely associated with FA-IMT and endothelium-dependent vasodilation. Plasma A-FABP/APN ratio may be a better clinical marker of AS and endothelial dysfunction than A-FABP or APN alone in patients with newly diagnosed T2DM.

[Killer cell immunoglobin-like receptor and its ligand gene polymorphisms in Hunan Han patients with type 1 diabetes].

OBJECTIVE: To investigate the association of Killer cell immunoglobin-like receptor (KIR) gene and KIRs'ligand (HLA-C) gene polymorphisms with type 1 diabetes (T1DM). METHODS: Using polymerase chain reaction-sequence specific primer (PCR-SSP) to detect KIR and HLA-C genotype in 180 T1DM patients and 199 healthy controls from Hunan Han population. RESULTS: (1) The frequencies of KIR 2DL1 (98.9% vs 92.0%, OR = 7.78, P = 0.002), 3DL1 (94.3% vs 86.4%, OR = 2.67, P = 0.009) and 2DS4 (83.9% vs 70.9%, OR = 2.14, P = 0.003) were significantly higher in T1DM patients than those in the controls. (2) There were no differences in the frequencies of HLA-C1 and HLA-C2 between the patients and the controls, but the frequency of HLAC1+/C2+ (3.9% vs 9.6%, OR = 0.38, P = 0.03) was significantly lower in the T1DM patients. (3) The combination KIR2DL1-/HLA-C2-(0.6% vs 6.0%, OR = 0.087, P = 0.003) and KIR 2DS1-/HLA-C2-(53.3% vs 64.8%, OR = 0.62, P = 0.023) was significantly lower in the T1DM patients. CONCLUSION: The KIR gene polymorphism and KIR/HLA-C gene compatibility are associated with T1DM.

[Decrease of FOXP3 mRNA in CD4+ T cells in latent autoimmune diabetes in adult].

OBJECTIVE: To study the percentage of peripheral blood CD4(+)CD25(+) T cells and the expression of FOXP3 mRNA in the patients with latent autoimmune diabetes in adult (LADA). METHODS: Fresh peripheral blood samples were obtained from 60 patients with LADA, 30 patients with type 2 diabetes and 30 age- and sex-matched matched healthy nondiabetic control subjects without diabetic family history. Two-color staining (anti-CD4, anti-CD25, anti-CD3, and anti-CD8) flow cytometric analysis was employed to measure the CD4(+)CD25(+) T cells. The CD4 positive human cells were isolated with immunomagnetic beads, and then real time-PCR was used to test the expression of FOXP3 mRNA in the CD4(+) T cells. RESULTS: In the LADA group, the percentage of CD4(+)CD25(+) T cells was 4.1 +/- 1.9, significantly higher than that of the normal control group (2.8 +/- 1.5, P < 0.01), the ratio of CD4(+)CD25(+) to the CD4(+) T cells was 11.9 +/- 5.0, significantly higher than that of the normal control group (8.2 +/- 3.7, P < 0.01), the percentage CD8(+) T cells was 24.6 +/- 6.8, significantly higher than that of the normal control group (19.4 +/- 7.1, P < 0.01) and the CD4(+)/CD8(+) ratio was 1.5 +/- 0.5, significantly lower (1.9 +/- 0.6, P < 0.01). The expression of FOXP3 mRNA in CD4(+) T cells of the LADA group was 0.52 time that of the control group (P < 0.01). The CD4(+)/CD8(+) ratio of LADA group was significantly lower that of the type 2 diabetes group (1.8 +/- 0.8, P < 0.05), however, the other results were not significantly different between these 2 groups. The percentage of was positively correlated with the titer of glutamic acid decarboxylase antibody (GADA) (r = 0.292, P < 0.05). CONCLUSION: Though the percentage of CD4(+)CD25(+) T cells and the level of CD25 expression in CD4(+) T cells are elevated, the expression of FOXP3 mRNA in CD4(+) T cells is lower. in the patients with LADA. The regulatory T cells may have defective suppressor function in patients with LADA.

[Comparison of 3 working definitions of metabolic syndrome in male medical examinees].

OBJECTIVE: To compare the prevalence of the metabolic syndrome (MS) using 3 working definitions proposed respectively by the World Health Organization (WHO, 1999) , the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults ( ATP III, 2001 ), and the Chinese Diabetes Society ( CDS, 2003). METHODS: MS was diagnosed in 739 male medical examinees by the 3 working definitions respectively, then the prevalence and the concordance of 3 working definitions was compared. RESULTS: Among 739 participants the prevalence was 36.9% by the WHO definition, 11.8% by the ATP III definition and 21.0% by the CDS definition. Among all the testees 68.6% were classified as either having or not having the MS under the 3 definitions. The consistency in the diagnosis of MS was 72.5% by the WHO definition and the ATP III definition, 81.2% by the WHO definition and the CDS definition, and 83.5% by the ATP III definition and the CDS definition. The prevalence of insulin resistance was the highest among the components of the WHO definition. The prevalence of hypertension was the highest while the prevalence of obesity was the lowest by the ATP III definition. Among the components of the CDS definition, the prevalence of obesity was the highest. The fasting insulin and insulin resistant index (HOMA-IR) were both significantly higher in the MS subjects than that in the non-MS subjects. CONCLUSION: A universally accepted definition of the metabolic syndrome is needed.

[Effects of glimepiride and metformin on free fatty acid in patients with Type 2 diabetes mellitus].

OBJECTIVE: To investigate the effect of glimepiride and metformin on free fatty acid (FFA) in patients with Type 2 diabetes mellitus and to further study the relationship between free fatty acid and insulin resistance in patients with Type 2 diabetes mellitus. METHODS: A prospective and case-control study was conducted. Ninty-four patients with Type 2 diabetes mellitus (35-70 year-old) were divided into 3 groups: glimepiride treated group (n=33), metformin treated group (n=29) and glimepiride plus metformin treated group (n=32). These patients were followed up for 6 months. Free fatty acids were measured by using an enzymatic colorimetry. RESULTS: The concentration of FFA didn't significantly change in the glimepiride treated group at the end of treatment, but it obviously decreased in the metformin treated group and in the glimepiride plus metformin treated group (P < 0.05 and P < 0.001, respectively). The decrease of FFA in the glimepiride plus metformin treated group was more obvious than that in the glimepiride treated group (P < 0.05). The fasting serum FFA concentration is positively related to HOMA-IR( homeostasis model assessment-insulin resistance) and the choice of drugs by stepwise regression analysis. CONCLUSION: Metformin alone or metformin plus glimepiride can decrease FFA levels, body weight index, blood glucose and insulin resistance. FFA level can reflect the index of insulin resistance to some degree.

[Relationship between Ala98Val variant of hepatocyte nuclear factor-1 alpha gene and late-onset type 2 diabetes in Han nationality].

OBJECTIVE: To ascertain whether Ala98Val variant in exon 1 of hepatocyte nuclear factor-1 alpha (HNF-1 alpha) gene is associated with late-onset Type 2 diabetes in Chinese Han nationality. METHODS: We selected 150 patients with late-onset Type 2 diabetes and 155 controls, and detected Ala98Val variant with polymerase chain reaction-single strand conformational polymorphism(PCR-SSCP) and direct sequencing. RESULTS: None of Ala98Val variant was found in all of the subjects. CONCLUSION: The Ala98Val variant doesn't play an important role in late-onset Type 2 diabetes in Chinese Han nationality.

[Mutation of GCK gene of Chinese patients with late-onset type 2 diabetes].

OBJECTIVE: To determine the mutation of the Glucokinase (GCK) gene in Chinese patients with Type 2 diabetes. METHODS: Forty-seven families with Type 2 diabetes were recruited. GCK gene was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing. RESULTS: Sequence analysis of two abnormal DNA fragments demonstrated a replacement of C-->T at the 38th base in intron 6 and a replacement of C-->T at the 8th base in intron 9, forming two polymorphic sites. CONCLUSION: IVS6--38C-->T and IVS9--8C-->T were found and mutation of GCK gene may not be a major genetic factor in Chinese patients with Type 2 diabetes.

Age-related bone mineral density, accumulated bone loss rate and prevalence of osteoporosis at multiple skeletal sites in chinese women.

We investigated the age-related bone mineral density (BMD), accumulated bone loss rate (ABLR) and the prevalence of osteoporosis at different skeletal sites in Chinese women. BMD was measured at the anteroposterior (AP) spine, supine lateral spine (areal BMD at the midarea [mLat] and the whole region [Lat], volumetric BMD at the middle region [MVD] and total region [TVD]), hip (femoral neck [FN], trochanter [Troc] and Ward's triangle [Ward's]) and forearm (radius + ulna ultradistal [RUUD], 1/3 region [RU1/3] and total region [RUT]) using a dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) in 2702 females aged from 5 to 96 years old. Data were analyzed by eight different regression models. We found that the cubic regression model was the best for describing age-related changes in BMD. The coefficients of determination ( R(2)) of the fitting curve were 0.398 to 0.612 ( p = 0.000). The data were then analyzed by 5-year age groups. This showed that the earliest peak BMD was at the age of 20-24 years at Troc and Ward's, and the latest at the age of 40-44 years at RU1/3 and RUT of the distal forearm. Compared with BMD, the ABLRs were highest at Ward's (-66.2%) and the lowest at RU1/3 of the distal forearm (-31.3%) in subjects over 80 years old. The prevalence of osteoporosis at at least one site in these women was 0.5 +/- 0.4% in those 30-39, 4.6 +/- 4.4% in those 40-49, 23.9 +/- 13.3% in those 50-59, 56.3 +/- 20.3% in those 60-69, 71.8 +/- 16.7% in those 70-79 and 83.2 +/- 12.1% those over 80 years of age, respectively. The prevalence of osteoporosis in these women was 8.6-11.1% at the age of 40-49 and 36.5-40.6% at the age of 50-59 at the lateral spine regions (mLat, Lat, MVD and TVD), and 0.5-3.7% at the age of 40-49 and and 3.9-21.7% at the age of 50-59 years at the other skeletal sites (AP, FN, Troc, Ward's, RUUD, RU1/3 and RUT). Significant differences were found in the prevalence of osteoporosis between the lateral spine regions and other skeletal sites ( p<0.001) at the age of 40-59 years. In summary, we demonstrated significant age-related differences in peak BMD, ABLR and osteoporosis prevalence among various skeletal sites. Our data suggest that the supine lateral spine is the most sensitive site for the diagnosis of osteoporosis, especially in the early menopausal period, although the prevalence of osteoporosis varied with age and with different sites measured.