Association of a SLC30A8 genetic variant with monotherapy of repaglinide and rosiglitazone effect in newly diagnosed type 2 diabetes patients in China.

OBJECTIVE: To investigate a potential relationship between Solute carrier family 30 (zinc transporter) member 8 (SLC30A8) rs13266634 variant and efficacy of rosiglitazone or repaglinide in treating newly diagnosed Chinese type 2 diabetes patients. METHODS: A total of 209 diabetic patients without any antihyperglycemic history were recruited and treated with repaglinide or rosiglitazone randomly for 48 weeks (104 and 105 patients, respectively). Anthropometric measurements and clinical laboratory tests were carried out before and after the treatment. An non-synonymous variant rs13266634 was genotyped by matrix-assisted laser desorption ionization-time of flight mass spectroscopy. RESULTS: Ninety-one patients in repaglinide group and ninety-three patients in rosiglitazone group completed the study. Δ value of homeostasis model assessment of beta cell function (HOMA-B) and Δ value of fasting proinsulin levels were statistically significant between three genotype groups (P=0.0149 and 0.0246, respectively) after rosiglitazone treatment. However, no genotype association was observed in the repaglinide or rosiglitazone group with other parameters. CONCLUSION: The SLC30A8 variant was associated with the efficacy of insulin sensitizer monotherapy on insulin secretion in patients with newly diagnosed type 2 diabetes mellitus in Shanghai, China.

Non-alcoholic fatty liver disease's prevalence and impact on alanine aminotransferase associated with metabolic syndrome in the Chinese.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is becoming a major public health hazard in China. The present study aimed to estimate the prevalence of NAFLD, NAFLD with abnormal serum alanine aminotransferase (ALT) levels, and determine the potential associations of ALT levels with the components of metabolic syndrome (MetS) in the absence or presence of NAFLD in Chinese adults. METHODS: A population-based cross-sectional survey was conducted with 2226 participants. Physical examinations, laboratory tests and hepatic ultrasounds were performed. Individuals were further stratified into higher or lower ALT subgroups with the upper quartiles of ALT in this population. The MetS was identified according to the criteria of the Chinese Joint Committee for Developing Chinese Guidelines (JCDCG). RESULTS: The standardized prevalence of NAFLD was 23.3% (NAFLD with abnormal ALT levels, 3.1%), 26.5% (NAFLD with abnormal ALT levels, 5.1%) in males, and 19.7% (NAFLD with abnormal ALT levels, 0.9%) in females. Multivariate logistic analysis revealed that higher ALT was significantly associated with elevated triglyceride (TG) in the non-NAFLD participants, independent of age, smoking status, drinking status, and other MetS-related measures with odds ratios (95% confidence intervals) of 3.4 (1.6-7.1) and 2.3 (1.4-3.7) in males and females, respectively. On the other hand, the higher ALT was statistically associated with elevated TG and hyperglycemia in the NAFLD cases with odds ratios of 2.2 to 2.5 (P<0.05). CONCLUSIONS: The prevalence of NAFLD has become epidemic in Shanghai adults. NAFLD combined with ALT levels may be used to identify the individuals at the different risk levels of metabolic disorders.

A variation in NOS1AP gene is associated with repaglinide efficacy on insulin resistance in type 2 diabetes of Chinese.

AIM: To investigate a potential association between SNP rs10494366 in the neural nitric oxide synthase adaptor protein (NOS1AP) and efficacy of repaglinide (an insulin secretagogue) in newly diagnosed Shanghai Chinese type 2 diabetes patients. METHODS: A total of 104 newly diagnosed type 2 diabetes patients (69 men, 35 women) were recruited and treated with repaglinide for 24 weeks. Anthropometric measurements, clinical laboratory tests were obtained at baseline and after 24-week treatment. Genotyping was performed by sequencing. RESULTS: The baseline value of BMI, HOMA-IR, HOMA-B, and fasting insulin level were significantly different between GG, GT, and TT genotypes (P=0.024, 0.030, 0.005, and 0.007, respectively). Carriers of TT genotype were in significant insulin resistance at baseline. After 24-week repaglinide monotherapy, the Delta value of fasting insulin (P=0.019) and HOMA-IR (P=0.011) were significantly different. TT carriers had the least insulin resistance after treatment. The mixed model analysis showed that the variation had an interaction effect with repaglinide treatment only on HOMA-IR (P=0.013). CONCLUSION: A common variant in rs10494366 is associated with repaglinide monotherapy efficacy on insulin resistance in newly diagnosed Shanghai Chinese type 2 diabetes patients.

Combined assessment of glycated albumin and fasting plasma glucose improves the detection of diabetes in Chinese subjects.

1. The aim of the present study was to assess the validity of glycated albumin (GA) and fasting plasma glucose (FPG) as a screening tool for the early detection of diabetes in Chinese subjects. 2. A total of 1971 outpatient subjects underwent a 75 g oral glucose tolerance test (OGTT) and GA measurement. The receiver operating characteristic curve (ROC) was plotted to examine the sensitivity, specificity, and positive and negative predictive values of GA and FPG in detecting undiagnosed diabetes at the different cut-off levels. 3. The prevalence of impaired glucose regulation and diabetes was 27.40% and 38.30%. For these diabetic individuals, 4.64% had isolated fasting hyperglycemia, 50.86% had isolated postprandial hyperglycemia and 44.50% had both. Using ROC analysis, a GA of 17.1% gave an optimal sensitivity of 76.82% (95% confidence interval: 73.64-79.79%) and specificity of 76.89% (74.42-79.23%) for the diagnosis of diabetes. Likewise, a FPG of 6.1 mmol/L gave an optimal sensitivity of 80.93% (77.94-83.67%) and specificity of 85.94% (83.86-87.84%). If subjects met both criteria, they were regarded as having diabetes; the positive predictive value of the combined criteria, FPG ≥ 6.1 mmol/L and GA ≥ 17.1%, was relatively high (84.79% (81.62-87.60%)), and this would have avoided 76% of the OGTT in our survey. 4. In conclusion, a GA value of 17.1%, an optimal cut-off in Chinese subjects, identified a high proportion of potential diabetic individuals. Simultaneous measurement of FPG and GA would enhance the sensitivity of diabetes screening in our population and avoid 76% of OGTT.

Comparison of body mass index with body fat percentage in the evaluation of obesity in Chinese.

OBJECTIVE: To evaluate the present Chinese body mass index (BMI) criteria with body fat percentage (BF%) in determining obesity in Chinese population. METHODS: A total of 4 907 subjects (age: 20-90 yrs) were enrolled in the baseline survey of a longitudinal epidemiological study, and 2 638 of them were reevaluated in 5.5 years later. The Chinese BMI and WHO BF% were used to define obesity, respectively. RESULTS: The diagnostic agreement between the Chinese BMI and WHO BF% definitions for obesity was poor for both men (kappa: 0.210, 95% CI: 0.179-0.241) and women (kappa: 0.327, 95% CI: 0.296-0.358). However, BMI had a good correlation with BF% both in men (r: 0.785, P<0.01) and women (r: 0.864, P<0.01). The age and sex-adjusted relative risks (RR) for incidence of type 2 diabetes (T2DM) were significantly higher in subjects with intermediate BF% (BF%:20.1%-25% for men, 30.1%-35% for women) (RR: 2.35, 95% CI: 1.23-4.48) and high BF%(BF%>25% for men and > 35% for women)(RR: 2.89, 95% CI: 1.43-5.81), or in subjects with high BMI (BMI>or=28 kg/m(2)) (RR: 2.46, 95% CI: 1.31-4.63) when compared to those with low BF% (BF%

[No association of vascular endothelial growth factor A gene rs9369425 polymorphism with glucose metabolism in Chinese Han population].

OBJECTIVE: To investigate the relationship between the vascular endothelial growth factor A gene (VEGFA) rs9369425 single nucleotide polymorphism (SNP) and type 2 diabetes in Chinese Han population. METHODS: One thousand eight hundred and ninety two type 2 diabetes patients and 1808 controls with normal glucose were recruited in this study. Phenotypes including body mass index, waist, waist hip ratio, plasma glucose and serum insulin levels of blood obtained both at 0 and 120 minute during standard 75-gram glucose oral glucose tolerance tests, were analyzed. Insulin resistance and beta cell function were assessed by homeostasis model assessment (HOMA-IR and HOMA-B). Genotyping was performed by time-of-light mass spectrum using a Sequenom platform. RESULTS: The frequencies of minor allele G in the diabetic patients and controls were 10.8% and 11.3% respectively. No significant difference of allele distribution was detected between the cases and controls (P=0.5086). No significant difference (P>0.05) was detected on the association between rs9369425 SNP and clinical phenotypes. CONCLUSION: VEGFA rs9369425 was not associated with type 2 diabetes in Chinese Han population. Whether there is association in any other loci in this gene remained to be investigated.

The protective effect of the RAS inhibitor on diabetic patients with nephropathy in the context of VEGF suppression.

AIM: The aim of the present study was to explore whether renin angiotensin system (RAS) inhibitor can reduce the production of vascular endothelium growth factor (VEGF). Further, we sought to elucidate the correlation between VEGF level and certain clinical parameters, such as albumin excretion rate (AER), before and after treatment with angiotensin type 1 receptor blocker. METHODS: We recruited 166 type 2 diabetic patients at various stages of diabetic nephropathy (DN) and 46 healthy control subjects for a cross-sectional study. We recruited another 42 hypertensive type 2 diabetic patients with microalbuminuria for a longitudinal study involving a 6-month irbesartan treatment protocol. Urinary VEGF (uVEGF) levels were determined using ELISA. RESULTS: In the cross-sectional study, hypertensive type 2 diabetic patients who received RAS inhibitor presented lower uVEGF levels than those who did not receive the RAS inhibitor. Statistical analysis indicated that uVEGF level was independently correlated with the AER. In the longitudinal study involving the 6-month irbesartan treatment, we demonstrated that uVEGF levels decreased significantly in patients who achieved a 50% AER reduction (remission group, n=32). In contrast, uVEGF levels remained unchanged in patients who did not exhibit a 50% AER reduction (nonremission group, n=10). Furthermore, the change in uVEGF was significantly correlated with the change in AER (r=0.65, P<0.01) before and after 6 months of irbesartan treatment. This result held true even after we had adjusted for the decrease in average blood pressure. CONCLUSION: The protective effect of the RAS inhibitor in DN patients is associated with the suppression of VEGF. Accordingly, it may be possible to use uVEGF as a marker of DN progression. We suggest that uVEGF may be an important target for therapeutic intervention in the context of DN.

[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.

[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 prevalence of latent autoimmune diabetes in adults and its relationship with metabolic syndrome].

OBJECTIVE: To investigate the prevalence, clinical features of latent autoimmune diabetes in adults (LADA) from phenotypic type 2 diabetic patients and the relationship between LADA and metabolic syndrome (MS). METHODS: Sera from 1711 phenotypic type 2 diabetic patients were screened for glutamic acid decarboxylase antibody (GAD-Ab) and protein tyrosine phosphatase antibody (IA2-Ab) through radioligand assay. The prevalence of LADA and its relation with clinical features were analyzed. RESULTS: (1) The prevalence of LADA in phenotypic type 2 diabetic patients was 6.7% (115/1711), the positive frequency of GAD-Ab and IA2-Ab was 6.0% and 2.4% respectively. (2) The prevalence of LADA from phenotypic type 2 diabetic patients with a duration of diabetes less than 1 year which was much higher than that of patients with a duration over 1 year (10.4% vs 5.9%, P < 0.01). (3) The prevalence of LADA was higher in patients with younger age at onset, lower body mass index and lower level of postprandial C peptide and without diabetes family history. (4) 51.3% of LADA patients were suffered from at least one kind of metabolic disorders besides hyperglycemia, 21.7% of them were with MS. The prevalence from high to low of those metabolic disorders were as follows: hypertension, dyslipidemia, overweight/obesity. CONCLUSION: (1) 6.7% of phenotypic type 2 diabetic patients were LADA, of whom early diagnosis of diabetic type should be made to guide clinical therapies. (2) More than 1/5 patients with MS were found in LADA patients, indicating an overall screening and intervention of metabolic disorder factors is important in LADA patients.

[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.

Association of KCNJ11 and ABCC8 genetic polymorphisms with response to repaglinide in Chinese diabetic patients.

AIM: The aim of this study was to investigate the association of KCNJ11 E23K and ABCC8 exon16-3T/C with the therapeutic effect of repaglinide in patients with type 2 diabetes. METHODS: A total of 100 Chinese patients with newly diagnosed type 2 diabetes were treated with repaglinide for 24 weeks. Arginine stimulation tests were performed to evaluate beta cell function. Gene variations were detected with PCR-restriction fragment length polymorphism. Responders were defined by a greater than 25% decrease in fasting plasma glucose or a greater than 20% decrease in hemoglobin A1c (HbA1c) values (or both) after the 24 week repaglinide treatment. RESULTS: Both baseline HbA1c and the decrease of HbA1c were significantly higher in patients with E/K and K/K genotypes of the KCNJ11 E23K variant when compared with E/E homozygotes (P=0.0103 and 0.0221, respectively). The decrease in 2 h postprandial plasma glucose (2hPG) was significantly greater in E/K heterozygotes than E/E homozygotes (P=0.0367). There was a significant difference in the response rate to repaglinide treatment between the E and K alleles (68% vs 82%, P=0.0324). The changes in fasting insulin and the homeostasis model assessment of insulin resistance were significantly greater in patients with ABCC8 exon16-3 C/C versus the T/C and T/T genotypes (P=0.0372 and 0.0274, respectively). CONCLUSION: The KCNJ11 E23K variant was associated with the therapeutic effect of repaglinide. In addition, The C/C homozygotes of the ABCC8 exon16-3T/C variant responded better to repaglinide in insulin sensitivity than the T/C and T/T genotypes.

Relationship between the level of fasting plasma glucose and beta cell functions in Chinese with or without diabetes.

BACKGROUND: Type 2 diabetes is a chronic disease characterized by a progressive loss of beta cell functions. However, the evaluation of beta cell functions is either expensive or inconvenient for clinical practice. We aimed to elucidate the association between the changes of insulin responsiveness and the fasting plasma glucose (FPG) during the development of diabetes. METHODS: A total of 1192 Chinese individuals with normal blood glucose or hyperglycemia were enrolled for the analysis. The early insulinogenic index (DeltaI30/DeltaG30), the area under the curve of insulin (AUC-I), and homeostasis model assessment were applied to evaluate the early phase secretion, total insulin secretion, and insulin resistance respectively. Polynomial regression analysis was performed to estimate the fluctuation of beta cell functions. RESULTS: The DeltaI30/DeltaG30 decreased much more rapidly than the AUC-I accompanying with the elevation of FPG. At the FPG of 110 mg/dl (a pre-diabetic stage), the DeltaI30/DeltaG30 lost 50% of its maximum while the AUC-I was still at a compensated normal level. The AUC-I exhibited abnormal and decreased gradually at the FPG of from 130 mg/dl to higher (overt diabetes), while the DeltaI30/DeltaG30 almost remained at 25% of its maximum value. When hyperglycemia continuously existed at > 180 mg/dl, both the DeltaI30/DeltaG30 and AUC-I were totally lost. CONCLUSION: The increased fasting plasma glucose reflects progressive decompensation of beta cell functions, and could be used to guide the strategy of clinical treatments.

Intracellular retention of human melanocortin-4 receptor: a molecular mechanism underlying early-onset obesity in F261S pedigree of Chinese.

OBJECTIVE: To investigate how F261S mutation identified from Chinese obese patients affects the function of melanocortin 4 receptor (MC4R) and to analyze the obesity-related phenotypes in subjects carrying the F261S mutation. METHODS: F261S mutant of MC4R was generated by site-directed mutagenesis. Plasmids encoding wild-type or F261S mutant of MC4R were transfected into HEK293 and COS-7 cells to examine their functional characteristics. Signaling properties of F261S MC4R were assessed by measuring intracellular cAMP levels in response to alpha-MSH stimulation. Cell surface expression of F261S MC4R was compared with that of wild-type MC4R. Clinical examinations were performed in subjects carrying F261S mutation and in non-mutated controls. RESULTS: The alpha-MSH-stimulated reporter gene activity was significantly reduced in cells expressing F261S MC4R, with a maximal response equal to 57% of wild-type MC4R. The F261S mutation also led to a significant change in the Es50 value compared with the wild-type receptor (P<0.01). Immunofluorescent assay revealed a marked reduction in plasma membrane localization of the MC4R in cells expressing the F261S mutant receptor. The resting metabolic rate and fat composition of the mutant carriers were not significantly different from those of the non-mutated obese controls. CONCLUSIONS: The decreased response to alpha-MSH due to the intracellular retention of MC4R may cause early-onset obesity in the F261S pedigree of Chinese.

[Evaluating the feature of hypoglycemia detected by continuous glucose monitoring system during temporary continuous subcutaneous insulin infusion in type 2 diabetes patients].

OBJECTIVE: To use continuous glucose monitoring system (CGMS) to investigate the features of hypoglycemia in control of hyperglycemia in T2DM patients by continuous subcutaneous insulin infusion (CSII) and to study the influencing factors of hypoglycemia. METHODS: Sixty-one T2DM patients, 35 males and 26 females, age 23-88, with the disease duration of 0.5-12 years, HbA1c level of (11.1 +/- 1.6)%, and glycosylated serum protein of (32 +/- 6)%, underwent. CSII and finger blood sugar test. On the second day CGMS was used for 72 hours. Logistic regression was used to analyze the correlation among different factors. RESULTS: CGMS discovered 31 hypoglycemic events in 18 patients in the early stage of CSII treatment, 20 events occurring at night, a number significantly higher than that by self-monitoring of blood sugar. The C-peptide and mean blood glucose (BMG) of the patients with hypoglycemia.were significantly lower than those of the patients without hypoglycemia, and the total cholesterol, standard deviation of blood glucose (SDBG), and insulin pump basal rate of the patients with hypoglycemia were significantly higher than those of the patients without hypoglycemia (all P < 0.05). Multiple regression indicated that MBG was negatively correlated with hypoglycemia but SDBG and basal rate were positively correlated with hypoglycemia. CONCLUSION: (1) Hypoglycemia detected by CGMS occurs in about 1/3 of the type 2 diabetes patients at the early stage of CSII therapy. (2) In addition of MBG and insulin pump basal rate, glycemic excursion is related closely to hypoglycemia.

[Relationship between blood glucose variability and microalbuminuria in type 2 diabetic patients with well-controlled glycosylated hemoglobin].

OBJECTIVE: To investigate the relationship between the blood glucose variability and microalbuminuria (MAU) in type 2 diabetic patients with well-controlled glycosylated hemoglobin (HbA1c) and the influencing factors of blood glucose variability. METHODS: One hundred and seventy-six type 2 diabetic patients with HbA1c under 6.5% and 48 subjects with normal glucose regulation were monitored using the continuous glucose monitoring system (CGMS). The mean blood glucose (MBG) and mean amplitude of glucose excursions (MAGE) were analyzed. RESULTS: (1) The MBG and MAGE levels of type 2 diabetic patients were (7.0+/-0.9) and (3.8+/-2.5) mmol/L respectively, both higher than those of the subjects with normal glucose regulation [(5.4+/-0.6) and (2.0+/-0.7) mmol/L respectively, both P<0.01]. (2) The incidence ratio of MAU of the patients with ascended MAGE level was 18.7%, significantly higher of those with normal MAGE (7.1%, P<0.05). (3) The MAGE level was positively correlated with age, duration of diabetes, and systolic blood pressure, and negatively correlated with glomerular filtration rate and the levels of fasting and postprandial C-peptide. Multivariant regression analyses indicated that duration of diabetes and the level of postprandial C-peptide 30 min after meal were the independent influential factors of MAGE. (4) In the type 2 diabetic patients, the MAGE of the MAU group was higher than that of the non-MAU group (P<0.05). Logistic regression analyses indicated that diastolic blood pressure and MAGE were the risk factors of MAU (OR=1.201 and 1.357, both P<0.05). CONCLUSION: In well-controlled patients with type 2 diabetes, blood glucose variability is one of the risk factors for MAU, duration of diabetes and early stage of insulin secretion function are the main factors influencing glycemic variability.

[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.

[Association of -6735T-->C variant of glucokinase-associated dual-specificity phosphatase 12 gene with type 2 diabetes in Chinese].

OBJECTIVE: To investigate the impact of glucokinase-associated dual-specificity phosphatase 12 gene (DUSP12) single nucleotide polymorphism (SNP) on type 2 diabetes mellitus in Chinese. METHODS: The genotypes of -6735T-->C of DUSP12 were determined by PCR-RFLP in 577 Chinese in Shanghai, 359 with normal glucose tolerance (NGT) and 218 being newly diagnosed DM patients without taking any drug. Oral glucose tolerance test was conducted. Height, weight, glucose and insulin concentrations, serum lipid profiles, and fat distribution parameters were determined. RESULTS: The genotype frequency distributions of -6735T-->C variant in DUSP12 gene of the DM group and NGT group were not significantly different (all P > 0.05). The fasting plasma glucose concentration of the NGT subjects with C allele was 5.00 (4.69 - 5.28) mmol/L, significantly higher than that of the subjects with TT genotype [4.90 (4.50 - 5.26) mmol/L, P = 0.035]. The serum HDL-c concentration of the NGT subjects with C allele was (1.25 +/- 0.30) mmol/L, significantly lower than that of those with TT genotype [(1.34 +/- 0.30) mmol/L, P = 0.010]. These two results still showed significant statistical differences after adjusted with sex, age, and BMI (P = 0.035). CONCLUSION: -6735T-->C variant in DUSP12 doesn't play a major role in diabetes, but it may have some effects on glucose and lipid metabolism.

[Use of modification of diet in renal disease equation in estimating renal insufficiency in type 2 diabetes patients].

OBJECTIVE: To investigate the significance of use of modification of diet in renal disease (MDRD) equation in calculating glomerular filtration rate (GFR) so as to estimate the prevalence of "renal insufficiency" in type 2 diabetes patients. METHODS: Serum creatinine (Scr) and 24h-urinary albumin excretion (24 h-UAE) were measured in 1576 hospitalized type 2 diabetes patients. MDRD equation was used to calculate the GFR (GFR(MDRD)). GFR(MDRD) < 60 ml/min per 1.73 m2 was defined as "renal insufficiency". RESULTS: (1) Of the 1576 subjects, 908 (57.6%), 503 (31.9%), and 165 (10.5%) had GFR(MDRD) > or =90, 90-60, and <60 ml/min per 1.73 m2 respectively. The prevalence of "renal insufficiency" was increased with aging (P < 0.01). (2) The prevalence rates of "renal insufficiency" of the normo-, micro-, and macroalbuminuric groups were 4.8%, 14.4%, and 43.4% respectively, with significant differences among them (all P < 0.01). (3) Of the 165 subjects with "renal insufficiency", 21 (12.7%) had neither abnormal Scr nor abnormal albuminuria. CONCLUSION: Able to discover renal insufficiency early, MDRD equation has important clinical significance in evaluating the progression of renal dysfunction in type 2 diabetes patients.

[Association of variants in APPL1 gene with body fat and its distribution in Chinese patients with type 2 diabetic mellitus].

OBJECTIVE: To investigate the impact of single nucleotide polymorphisms (SNPs) in APPL1 gene on body fat and its distribution. METHODS: 590 unrelated Shanghai residents of Han nationality, including 358 subjects with normal glucose tolerance (NGT) and 232 subjects with type 2 diabetes mellitus (T2DM), underwent measurement of body mass index (BMI), waist circumference (W), hip circumference (H), and femoral circumference (F). Peripheral blood samples were collected to detect the blood sugar, blood lipids, fasting C - peptide (FCP), fasting insulin (FINS), fasting plasma glucose (FGLU), total cholesterol (TC), and triglyceride (TG) 0 and 120 minutes after glucose challenge. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the 2 SNPs (rs3806622 and rs4640525). RESULTS: No differences in the frequencies of rs3806622 and rs4640525 genotypes between the subjects with the BMI < 25 kg/m2 and those with the BMI > or = 25 kg/m2 either in the NGT group or T2DM group. The G allele frequencies of the rs3806622 and rs4640525 genotypes in the T2DM patients with longer W values were significantly higher than those in the patients with shorter W value (OR = 2.26, 95% CI 1.05 - 4.86, and OR = 4.3, 95% CI 1.21 - 14.09). The W values of the T2DM subjects with G alleles were significantly higher than those of the T2DM subjects without G alleles after adjustment of age, sex, and BMI (all P < 0.05). Stepwise regression analysis showed that in addition to sex and BMI, rs4640525 was also an associated factor of waist circumference (all P < 0.05). CONCLUSION: SNPs (rs3806622 and rs4640525) in APPL1 gene are correlated with body fat distribution in T2DM.