[Detection rates of atherosclerosis by carotid versus lower limb ultrasonography in newly diagnosed type 2 diabetics].

OBJECTIVE: To compare the detection rates of atherosclerosis by carotid versus lower limb ultrasound in newly diagnosed type 2 diabetics and analyze the relationship between atherosclerosis and cardio-cerebrovascular events. METHODS: A total of 148 newly diagnosed type 2 diabetics were recruited. Both carotid and lower extremity atherosclerosis were assessed by Doppler ultrasound. Diabetic atherosclerosis was defined as the presence of either carotid or lower extremity plaques in any of the above-mentioned arterial segments. A kappa value was computed to document the agreement between isolated carotid (or lower limb) atherosclerosis and diabetic atherosclerosis. The prevalence of cardio-cerebrovascular events was compared among different distribution types of atherosclerosis. RESULTS: According to the diagnostic criteria, the prevalence of diabetic atherosclerosis was 66.2% in the newly diagnosed type 2 diabetes. Based on carotid or lower extremity ultrasound, the prevalence of diabetic atherosclerosis was 27.0% and 62.2% respectively in newly diagnosed type 2 diabetes. The kappa values for the agreement between carotid/lower limb atherosclerosis and diabetic atherosclerosis were 0.32/0.91 (95% confidence interval 0.22-0.42 for carotid vs 0.84-0.98 for lower extremity). The combination of carotid and lower extremity arterial atherosclerosis was associated with a significantly increased detection rate of cardio-cerebrovascular events (26.5%) versus those with either carotid or lower extremity arterial atherosclerosis (0% and 10.3% respectively). CONCLUSION: The combination of carotid and lower extremity ultrasonography can more accurately reflect the atherosclerotic lesions in type 2 diabetes. Due to a higher prevalence of cardio-cerebrovascular events, type 2 diabetics with both carotid and lower extremity atherosclerosis should be managed more aggressively to reduce the risk of cardio-cerebrovascular events.

Contribution of myostatin gene polymorphisms to normal variation in lean mass, fat mass and peak BMD in Chinese male offspring.

AIM: Myostatin gene is a member of the transforming growth factor-ß (TGF-ß) family that negatively regulates skeletal muscle growth. Genetic polymorphisms in Myostatin were found to be associated with the peak bone mineral density (BMD) in Chinese women. The purpose of this study was to investigate whether myostatin played a role in the normal variation in peak BMD, lean mass (LM), and fat mass (FM) of Chinese men. METHODS: Four hundred male-offspring nuclear families of Chinese Han ethnic group were recruited. Anthropometric measurements, including the peak BMD, body LM and FM were measured using dual-energy X-ray absorptiometry (DXA). The single nucleotide polymorphisms (SNPs) studied were tag-SNPs selected by sequencing. Both rs2293284 and +2278GA were genotyped using TaqMan assay, and rs3791783 was genotyped with PCR-restriction fragment length polymorphism (RFLP) analysis. The associations of the SNPs with anthropometric variations were analyzed using the quantitative transmission disequilibrium test (QTDT). RESULTS: Using QTDT to detect within-family associations, neither single SNP nor haplotype was found to be associated with peak BMD at any bone site. However, rs3791783 was found to be significantly associated with fat mass of the trunk (P<0.001). Moreover, for within-family associations, haplotypes AGG, AAA, and TGG were found to be significantly associated with the trunk fat mass (all P<0.001). CONCLUSION: Our results suggest that genetic variation within myostatin may play a role in regulating the variation in fat mass in Chinese males. Additionally, the myostatin gene may be a candidate that determines body fat mass in Chinese men.

[Comparison of the application of three diagnostic criteria of metabolic syndrome in familial type 2 diabetic pedigrees].

OBJECTIVE: To compare the significance of the application of three diagnostic criteria of metabolic syndrome (MS), issued by the National Cholesterol Education Program Adult Treatment Panel II (ATPIII) in 2005, International Diabetes Federation (IDF) in 2005 and Chinese Diabetes Society (CDS) in 2004, in type 2 diabetes mellitus pedigrees. METHODS: Totally,4468 subjects (including spouses) from 715 type 2 diabetic pedigrees were selected in this study. Complete laboratory data, including blood pressure, lipid profile and plasma glucose, were collected. The prevalence rates of MS and the unity of three criteria were analyzed. RESULTS: The prevalence rates of MS were 44.94% (2008/4468), 37.87% (1692/4468) and 23.86% (1066/4468) according to the ATPIII, IDF and CDS criteria respectively. It subsequently increased in second-degree relatives, spouses, first-degree relatives and probands (ATP III: 23.78% (117/492), 35.77% (318/889), 45.40% (1077/2372) and 69.37% (496/715); IDF: 20.53% (101/492), 31.61% (281/889), 38.74% (919/2372) and 54.69% (391/715); CDS: 8.94% (44/492), 16.99% (151/889), 25.08% (595/2372) and 38.60% (276/715); ATPIII: chi2 = 266.359, IDF: chi2 = 155.950, CDS: chi2 = 165.087, respectively, P < 0.01). The prevalence rates of MS, as defined by the ATP III and IDF criteria, were higher in females than in males (ATP III: 47.47% (1156/2435) and 41.91% (852/2033); IDF: 43.00% (1047/2435) and 31.73% (645/2033); chi2 = 13.871 and 60.169, respectively, P < 0.01), and was lower in females than in males as defined by the CDS criterion (22.38% and 25.63%, respectively, chi2 = 6.423, P = 0.011). The agreement in the diagnosis of MS using ATPIII and IDF, ATPIII and CDS, IDF and CDS was 92.93%, 75.56% and 77.21% respectively. Kappa index were 0.855, 0.484 and 0.478 respectively (P < 0.01). CONCLUSION: ATP III criterion showed the highest prevalence of MS and the percent of risk factor aggregation which best reflected the characteristics of MS in familial type 2 diabetic pedigrees.

[Prevalence and clinical characteristics of the mitochondrial tRNA(Leu(UUR)) gene 3243 A to G mutation in familial diabetes mellitus in Chinese population].

OBJECTIVE: To study the prevalence and clinical characteristics of the A to G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene in familial diabetes in Shanghai, Jiangsu and Zhejiang Province of China. METHODS: The mt3243 A to G mutation in 770 randomly selected, unrelated probands of diabetic pedigrees were screened by PCR-RFLP technique and PCR-direct sequencing. Genetic and clinical analyses were further performed in the probands and their family members. RESULTS: Thirteen diabetic patients (13/770, 1.69%) with mt3243 A to G mutation were detected. Eleven diabetic patients and 8 normal glucose tolerance (NGT) first-degree relatives of these 13 probands were also found bearing the mutation. Seventeen patients were associated with sensory hearing loss. In the 24 patients harboring the mutation, the majority had lower body mass index (BMI), 18 showed typical maternal inheritance, 15 had sensory hearing loss, 13 had insulin resistance and 14 required insulin therapy due to secondary failure to oral hypoglycemic agents. CONCLUSION: The mutation of mt3243 A to G in the mitochondrial tRNA(Leu(UUR)) gene is an important cause of diabetes in Shanghai, Jiangsu and Zhejiang Province of China. Mitochondrial gene mutation diabetes (MDM) is clinically characterized by early onset, emaciation, maternal inheritance, sensorineural hearing loss, and lower islet beta cell function, and some have insulin resistance.

[Study on the mitochondrial DNA mutations in familial diabetes mellitus in Chinese population].

OBJECTIVE: To assess the prevalence of mutations or variants of the mitochondrial DNA (mtDNA) in familial diabetes mellitus in Chinese population, and to explore the relationship between mtDNA mutations or variants and diabetes. METHODS: Seven hundred and seventy randomly selected, unrelated probands of diabetes pedigrees and 309 controls over 60 years of age with normal glucose tolerance were recruited. PCR-RFLP and PCR-direct sequencing were applied to the screening of mtDNA mutations or variants, including the mutations at nucleotides 3243, 3256 in tRNALeu region, 12258 in tRNASer region, 14709 in tRNAGlu region, 8296, 8344, 8363 in tRNALys region, 3316, 3394, 3426 in ND1 region and 12026 in ND4 region. RESULTS: In the diabetic group, 13 (1.69%) had mt3243 A>G mutation, 9(1.17%) had tRNAGlu 14709 T>C variant, 17 (2.21%) carried mt3316 G>A variant, 18 (2.34%) had mt3394 T>C variant, and 28 (3.63%) harbored the 12026 A>G variant. In the control group, the 14709, 3316, 3394, 12026 variants were detected in 5(1.62%), 5(1.62%), 6(1.94%), and 9(2.91%) subjects respectively. The 3256, 8296, 8344, 8363, 3426 and 12258 point mutations were not detected both in the diabetic patients and the controls. In the diabetic group, we found two double mutations, one was A3243G and T3394C, the other was A3243G and A12026G. Except that the A3243G mutation was only observed in the diabetic group, the frequencies of the other variants mentioned above were not statistically different between the diabetic and control groups. Moreover, clinical characteristics such as age of onset, BMI, and insulin resistance index were not different between diabetic patients with and without the variants. CONCLUSION: The tRNA (LeuUUR) 3243 A>G mutation may be the major cause of diabetes, representing 1.69% of the familial diabetes mellitus in Chinese. The other variants may be polymorphisms in this population, and the mutations not detected in our studied population may not be common contributors to diabetes mellitus in Chinese.

[Genetic characteristics of familial type 2 diabetes pedigrees: a preliminary analysis of 4468 persons from 715 pedigrees].

OBJECTIVE: To analyze the inheritance character of type 2 diabetes mellitus (T2DM) pedigrees. METHODS: 4468 persons from 715 T2DM pedigrees (including the spouses) undergo peripheral blood sample collection to examine blood sugar and physical examination. Questionnaire survey was conducted to explore the family history. Type 1 DM and maturity-onset DM of young people were to be ruled out. Pedigree chart were made. RESULTS: The prevalence rates of T2DM and impaired glucose regulation (IGR) was 47.62%, including 218 T2DM and 422 IGR newly discovered. The prevalence rates of T2DM and IGR were 38.33% and 14.25% in the siblings, and 56.81% and 12.58% in the parents, all significantly higher than those in the second-degree relatives (9.55% and 6.10%) and spouses (10.57% and 9.55% respectively, all P < 0.01). The prevalence and newly discovered rates of IGR in the offspring were 12.46% and 11.73% respectively, both significantly higher than those in the spouses (9.55% and 9.55% respectively, all P < 0.01). CONCLUSION: There is significant familial aggregation in T2DM. The first-degree relatives of T2DM patients are high risk populations, so long term monitoring and early screening should be performed.

[Study on the status of metabolic syndrome in familial type 2 diabetes pedigrees].

OBJECTIVE: To investigate the prevalence of metabolic syndrome (MS) and its components in type 2 diabetes mellitus pedigrees. METHODS: A total number of 4468 subjects (including spouses) from 715 type 2 diabetic pedigrees were selected in this study. Complete laboratory data including blood pressure, lipid profile and plasma glucose, were collected. All subjects who were not defined as diabetic were valued by oral glucose tolerance test. MS was diagnosed according to the definition proposed by the China Diabetes Society (CDS) in 2004. RESULTS: (1) The prevalence of MS was 23.86% in diabetic pedigrees, and subsequently increased in second-degree relatives, spouses, first-degree relatives and probands. (2) The prevalence rates of 'at least' 1 metabolic abnormality in first-degree relatives, second-degree relatives and spouses were 80.10%, 59.76% and 70.30%, respectively. (3) Ratios on non-metabolic abnormality, 1 - 2 metabolic abnormality and MS were 19.90%, 55.02% and 25.08% in first-degree relatives, 40.24%, 50.82% and 8.94% in second-degree relatives, 29.70%, 53.31% and 16.99% in spouses, respectively. (4) Among the first-degree relatives, the common manifestation of metabolic abnormality was dyslipidemia for subjects aged below 40 years, and hyperglycemia for subjects aged over 40 years of age. (5) The prevalence of MS in first-degree relatives was higher in males than in females for subjects aged below 60 and it was higher in females than in males for subjects aged over 60. CONCLUSION: There was significant familial aggregation of MS found in our study. The first-degree relatives of type 2 diabetic patients were high risk populations, suggesting that early recognition and prevention were important issues to be carried out.

High spatial and temporal resolution mobile incoherent Doppler lidar for sea surface wind measurements.

A mobile Doppler lidar based on an injection-seeded diode-pumped Nd:YAG pulsed laser with a high repetition rate was developed to measure the sea surface wind (SSW) with high spatial and temporal resolution. The system was operated during the 2007 Qingdao International Regatta to measure the distribution of SSW in the racing area in real time with 50-100 m horizontal resolution and 2-10 min temporal resolution. An observation of nonuniform distribution of SSW is presented. The lidar results are compared with both buoy and wind tower measurements, which show good agreement. This lidar can be used advantageously for the 2008 Olympic sailing games as well as for observing mesoscale and microscale meteorology processes.

Direct-detection Doppler wind measurements with a Cabannes-Mie lidar: a. Comparison between iodine vapor filter and Fabry-Perot interferometer methods.

Atmospheric line-of-sight (LOS) wind measurement by means of incoherent Cabannes-Mie lidar with three frequency analyzers with nearly the same maximum transmission of ~80% that could be fielded at different wavelengths is analytically considered. These frequency analyzers are (a) a double-edge Fabry-Perot interferometer (FPI) at 1064 nm (IR-FPI), (b) a double-edge Fabry-Perot interferometer at 355 nm (UV-FPI), and (c) an iodine vapor filter (IVF) at 532 nm with two different methods, using either one absorption edge, single edge (se-IVF), or both absorption edges, double edge (de-IVF). The effect of the backscattered aerosol mixing ratio, R(b), defined as the ratio of the aerosol volume backscatter coefficient to molecular volume backscatter coefficient, on LOS wind uncertainty is discussed. Assuming a known aerosol mixing ratio, R(b), and 100,000 photons owing to Cabannes scattering to the receiver, in shot-noise-limited detection without sky background, the LOS wind uncertainty of the UV-FPI in the aerosol-free air (R(b)=0), is lower by ~16% than that of de-IVF, which has the lowest uncertainty for R(b) between 0.02 and 0.08; for R(b)>0.08, the IR-FPI yielded the lowest wind uncertainty. The wind uncertainty for se-IVF is always higher than that of de-IVF, but by less than a factor of 2 under all aerosol conditions, if the split between the reference and measurement channels is optimized. The design flexibility, which allows the desensitization of either aerosol or molecular scattering, exists only with the FPI system, leading to the common practice of using IR-FPI for the planetary boundary layer and using UV-FPI for higher altitudes. Without this design flexibility, there is little choice but to use a single wavelength IVF system at 532 nm for all atmospheric altitudes.

Direct-detection Doppler wind measurements with a Cabannes-Mie lidar: b. Impact of aerosol variation on iodine vapor filter methods.

Atmospheric line-of-sight (LOS) wind measurement by means of incoherent Cabannes- Mie lidar with three frequency analyzers, two double-edge Fabry-Perot interferometers, one at 1064 nm (IR-FPI) and another at 355 nm (UV-FPI), as well as an iodine vapor filter (IVF) at 532 nm, utilizing either a single absorption edge, single edge (se-IVF), or both absorption edges, double edge (de-IVF), was considered in a companion paper [Appl. Opt. 46, 4434 (2007)], assuming known atmospheric temperature and aerosol mixing ratio, Rb. The effects of temperature and aerosol variations on the uncertainty of LOS wind measurements are investigated and it is found that while the effect of temperature variation is small, the variation in R(b) can cause significant errors in wind measurements with IVF systems. Thus the means to incorporate a credible determination of R(b) into the wind measurement are presented as well as an assessment of the impact on wind measurement uncertainty. Unlike with IVF methods, researchers can take advantage of design flexibility with FPI methods to desensitize either molecular scattering for IR-FPI or aerosol scattering for UV-FPI. The additional wind measurement uncertainty caused by R(b) variation with FPI methods is thus negligible for these configurations. Assuming 100,000 photons from Cabannes scattering, and accounting for the Rb measurement incorporated into the IVF method in this paper, it is found that the lowest wind uncertainty at low wind speeds in aerosol-free air is still with UV-FPI, ~32% lower than with de-IVF. For 0.050.07, the IR-FPI outperforms all other methods. In addition to LOS wind uncertainty comparison under high wind speed conditions, the need of an appropriate and readily available narrowband filter for operating the wind lidar at visible wavelengths under sunlit condition is discussed; with such a filter the degradation of LOS wind measurement attributable to clear sky background is estimated to be 5% or less for practical lidar systems.

[The genetic and clinical characteristics of transcription factor 1 gene mutations in Chinese diabetes].

OBJECTIVE: To investigate the genetic and clinical features of mutations and sequence variations of the transcription factor 1 gene (TCF1, HNF-1A) in Chinese with familial early-onset and/or multiplex diabetes mellitus. METHODS: All ten exons of the TCF1 gene were screened, including exon and intron junctions, by direct sequencing method in 341 unrelated Chinese subjects, including 80 healthy controls and 261 probands of early-onset and/or multiplex diabetes pedigrees. RESULTS: Five mutations were found in all. Four of the 5 different TCF1 mutations were newly identified novel mutations(T82M, Q130H, G253G, P353fsdelACGGGCCTGGAGC), mean body mass index of mutation carriers was 21.9 kg/m (2), and insulin secretion was impaired in the mutation carriers. In this study, the maturity-onset diabetes of the young type III (MODY3) only accounted for 3% of Chinese early-onset diabetes. Moreover, eleven substitutions were identified in 261 probands. Of them, three variants IVS1-8 (G-->A), IVS1 -128 (T-->G ) and IVS2+21 (G-->A) were not observed in 80 healthy controls and one of them IVS1-8 (G-->A) was not reported previously and the two promoter variants co-segregated with diabetes. CONCLUSION: TCF1 gene is not a common cause of early-onset and/or multiplex diabetes among Chinese patients.

[Glycated albumin level and its influential factors in type 2 diabetes mellitus].

OBJECTIVE: To provide evidence for assessing glycated albumin (GA) appropriately cliniccally through determining the GA level of type 2 diabetes mellitus (DM) patients and analyzing its influential factors. METHOD: Continuous glucose monitor system was used to monitor the levels of fasting plasmic glucose (FPG), 2-hour post-prandial plasmic glucose (2hPG), GA, and glycated hemoglobin (HbA1c) in 445 type 2 DM in-patients. RESULTS: (1) The mean GA value was 24.9% +/- 7.0% and the mean HbA1c was 8.9% +/- 2.2%. (2) GA value was associated with HbA1c (P < 0.001). GA was positively correlated with FPG, 2hPG, and mean blood glucose (MBG) (all P < 0.01). (3) GA value was negatively correlated with BMI (P < 0.01). (4) Multiple stepwise regression analysis showed that HbA1c, BMI, and FPG were the main influential factors of GA. CONCLUSION: (1) GA value has good relationship with HbA1c, a golden standard to reflect the glycemic control in a long period. (2) BMI should be concerned when assessing GA value of DM patients, especially of the obese and thin subjects.

[Prevalence and clinical characteristics of the A to G variant at position 12026 of the mitochondrial ND4 gene in familial diabetes mellitus in Chinese population].

OBJECTIVE: To assess the prevalence of the A to G variant at nucleotide 12026 (mt12026) of the mitochondrial NADH-dehydrogenase subunit 4 (ND4) gene in familial diabetes mellitus in Chinese population. METHODS: The authors screened 770 randomly selected, unrelated probands of diabetic pedigrees, and 309 controls with normal glucose tolerance for the variant by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and PCR-direct-sequencing. RESULTS: The mt12026 A --> G variant was detected in 28 diabetic patients (3.63%) and 9 controls (2.91%). The frequency of the variant mt12026 A --> G was not statistically different between diabetic patients and controls. Moreover, clinical characteristics such as age, body mass index (BMI), and insulin resistant index were not different between diabetic patients with and without the mt12026 mutation. CONCLUSION: The mt12026 A --> G variant is a mitochondrial gene polymorphism in Chinese population, and it is unlikely that the mutation is in itself the cause of diabetes.

A20 overexpression under control of mouse osteocalcin promoter in MC3T3-E1 cells inhibited tumor necrosis factor-alpha-induced apoptosis.

AIM: To construct an A20 expression vector under the control of mouse osteocalcin promoter (OC-A20), and investigate osteoblastic MC3T3-E1 cell line, which stably overexpresses A20 protein prevented tumor necrosis factor (TNF)-alpha-induced apoptosis. METHODS: OC-A20 vector was constructed by fusing a fragment of the mouse osteocalcin gene-2 promoter with human A20 complementary DNA. Then the mouse MC3T3-E1 cell line, stably transfected by A20, was established. The expression of A20 mRNA and A20 protein in the cells were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. To determine the specificity of A20 expression in osteoblast, the mouse osteoblastic MC3T3-E1 cell line and mouse embryo fibroblast NIH3T3 cell line were transiently transfected with OC-A20. The anti-apoptotic role of A20 in MC3T3-E1 cells was determined by Flow cytometric analysis (FACS), terminal dUTP nick endo-labeling (TUNEL) and DNA gel electrophoresis analysis (DNA Ladder), respectively. RESULTS: Weak A20 expression was found in MC3T3-E1 cells with the primers of mouse A20. A20 mRNA and A20 protein expression were identified in MC3T3-E1 cells transfected with OC-A20 using RT-PCR and Western blot analysis. Only A20 mRNA expression was found in MC3T3-E1 cell after MC3T3-E1 cells and NIH3T3 cells were transient transfected with OC-A20. A decrease obviously occurred in the rate of apoptosis in the OC-A20 group compared with the empty vector (pcDNA3) group by FACS (P< 0.001). A significant increase in TUNEL positive staining was found in the pcDNA group compared with OC-A20 group (P< 0.001). Simultaneously, similar effects were demonstrated in DNA gel electrophoresis analysis. CONCLUSION: We constructed an osteoblast-specific expression vector that expressed A20 protein in MC3T3-E1 cells and confirmed that A20 protects osteoblast against TNF-alpha-induced apoptosis.

Identification of four novel mutations in the HNF-1A gene in Chinese early-onset and/or multiplex diabetes pedigrees.

BACKGROUND: Mutations in the hepatocyte nuclear factor-1A gene cause the type 3 form of maturity-onset diabetes of the young (MODY3). This study was undertaken to determine mutations and sequence variations of the HNF-1A gene in Chinese with familial early-onset and/or multiplex diabetes mellitus. METHODS: We screened all ten exons of the HNF-1A gene, including exon/intron junctions, by direct sequencing in 272 unrelated Chinese, including 80 healthy controls and 192 probands of early-onset and/or multiplex diabetes pedigrees. RESULTS: In addition to one silent mutation of c.864 G > C [p.G288G] in exon4 at codon 288, which had been reported previously, a total of four novel mutations including two missense mutations (c.245C > T [p.T82M] and c. 390 G > T [p.Q130H]) and one frameshift mutation P353fsdelACGGGCCTGGAGC and one silent mutation c.759 G > T [p.G253G] were identified. Moreover, eleven substitutions were identified in 192 probands. Of these, three variants (-8 G > A, -128 T > G and IVS2 + 21 G > A) were not observed in 80 healthy controls and one of them (-8 G > A) was not reported previously and the two promoter variants co-segregated with diabetes. The genotype and allele frequencies of the other eight variants in the diabetic patients were not significantly different from those in the healthy controls. No significant relationships were observed between the eight variants of the HNF-1A gene and clinical variables (plasma glucose, insulin, C-peptide and fasting lipid profile). CONCLUSION: The prevalence of structural mutations in the HNF-1A gene responsible for familial early-onset and/or multiplex diabetes appears to be rare among Chinese patients.

[Blood levels of true insulin and immunoreactive insulin in evaluating beta-cell function with arginine stimulation test].

OBJECTIVE: To investigate the difference between serum true insulin (TI) and immunoreactive insulin (IRI) in evaluating islet beta-cell function and insulin resistance. METHODS: The arginine stimulation test was performed in 141 individuals, including 35 with normal glucose tolerance (NGT) and 106 with type 2 diabetes (T2DM). Plasma glucose (PG), TI, IRI and proinsulin (PI) levels were measured; the incremental value of TI/PG, (TI+PI)/PG and IRI/PG (delta TI/PG, delta(TI+PI)/PG and deltaIRI/PG) and the area under curve of TI/PG, (TI+PI)/PG and IRI/PG (AUC [TI/PG], AUC[(TI+PI)/PG] and AUC [IRI/PG]) after arginine stimulation were calculated to evaluate beta-cell function. RESULT: There were positive correlations of delta TI/PG with delta (TI+PI)/PG and delta IRI/PG in both NGT and T2DM patients (r=0.68 - 0.99, P<0.01). The similar correlations of AUC [TI/PG] with AUC [(TI+PI)/PG] and AUC [IRI/PG] were also shown (r=0.62 - 0.99, P<0.01). delta TI/PG was correlated with AUC [TI/PG] in two groups (NGT r=0.96, T2DM r=0.82, P<0.01). HOMA-IRTI, HOMA-IR(TI+PI) and HOMA-IRIRI in T2DM were higher than those in NGT (P<0.01). After arginine stimulation T2DM subjects mainly presented insulin resistance and decreased insulin secretion. CONCLUSION: The determination of TI may be more accurate than IRI in evaluating beta-cell function and insulin resistance.

[Proportion of proinsulin two minutes after arginine stimulation: a pilot study].

OBJECTIVE: To seek an easy way to evaluate islet beta cell function. METHODS: 214 residents of Shanghai, aged 20-70, all of Han nationality, were divided into 3 groups according the 1999 WHO standard: 39 in the normal glucose tolerance (NGT) group, aged 52 years +/- 6 years, with the BMI of 22.3 kg/m(2) +/- 0.4 kg/m(2); 29 in the impaired glucose tolerance (IGT) group, aged 54 years +/- 9 years, with the BMI of 24.4 kg/m(2) +/- 0.6 kg/m(2); and 146 in the T2DM group, that was subdivided into 2 subgroups: 43 in the newly diagnosed T2DM (NT2DM) group, aged 52 years +/- 9 years, with the BMI of 24.4 kg/m(2) +/- 0.5 kg/m(2), and 103 in the previously diagnosed T2DM (PT2DM) group, aged 57 years +/- 9 years, with the BMI of 23.5 kg/m(2) +/- 0.3 kg/m(2). Arginine at the dose of 10% 50 ml was injected intravenously in fasting situation. Two, four, and six minutes after blood samples were collected from a needle indwelling in the contralateral vein to examine the levels of plasma glucose (PG), true insulin (TI), and proinsulin (PI). RESULTS: (1) The TI and TI/PG levels of all groups peaked 2 minutes after arginine stimulation and then gradually decreased, however, the levels 6 minutes after stimulation were still higher than the baseline values. The peak values of TI and TI/PG were arranged from high to low in the order of IGT, NGT, NT2DM and PT2DM. The peak values of NT2DM and PT2DM groups were significantly lower than those of the NGT and IGT groups (all P < 0.01). The peak values of the NT2DM group were significantly higher than those of the PT2DM group (both P < 0.01). (2) The PI value of the IGT, NT2DM and PT2DM groups peaked 2 minutes after the stimulation and then gradually decreased with the peak values significantly higher than that of the NGT group (all P < 0.05). The fasting PI/TI and PI/(TI + PI) of the NGT group were all significantly lower than those of the IGT group (both P < 0.05). (3) The changes of PI/TI in each groups manifested almost the mirror image of TI/PG mentioned above, and the lowest PI/TI levels were observed 2 minutes after stimulation. The similar changes of PI/(TI + PI) were found. The lowest points of groups 2 minutes after stimulation was arranged from low to high in the order of NGT, IGT, NT2DM and PT2DM. CONCLUSION: The PI/TI and PI/(TI + PI) values 2 minutes after arginine stimulation may be used as predictors for beta cell function in clinical practice.

[Mutation screening of GCK gene in Chinese early-onset diabetes population].

OBJECTIVE: To investigate the prevalence of mutations and sequence variations of glucokinase gene GCK in Chinese early-onset diabetes population. METHODS: The study was conducted in 174 unrelated Chinese residents, including 80 nondiabetic controls, 94 probands of early-onset diabetes pedigree. Direct sequencing was performed to screen all 10 exons of glucokinase gene, including promoter and exon/intron junctions. RESULTS: No mutations were identified in coding region, but several previously reported sequence variants were identified. 5'-untranslated region of exon 1a, 84 bp upstream of the translation initiation site GGCGG to GGGGG(early-onset diabetes group G allele frequency 0.106 vs control group 0.075, P=0.355); IVS1b+12 (A-->T) (early-onset diabetes group T allele frequency 0.005 vs non-identity of this variation in control group); IVS 5+29 (G-->T) (early-onset diabetes group T allele frequency 0.027 vs control group 0.019, P=0.731); IVS 9+8 (T-->C) (early-onset diabetes group C allele frequency 0.585 vs 0.694, P=0.044). A novel variation IVS 9+49 (G-->A) (early-onset diabetes group A allele frequency 0.011 vs control 0.006, P=1.000) was identified. There were no significant relationships of the exon 1a 5'-untransted region -84 bp(C-->G), IVS 5+29 (G-->T), IVS 9+8 (T-->C) and IVS 9+49 (G-->A) variants of GCK gene to the clinical variables such as plasma glucose, insulin, C-peptide and fasting lipid profile. CONCLUSION: The prevalence of structural mutations in glucokinase gene responsible for early-onset diabetes appears to be rare among Chinese patients.