Study on the mitochondrial DNA mutations in familial diabetes mellitus in Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Prevalence and clinical characteristics of the mitochondrial tRNA(Leu(UUR)) gene 3243 A to G mutation in familial diabetes mellitus in Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Comparison of the application of three diagnostic criteria of metabolic syndrome in familial type 2 diabetic pedigrees / 中华预防医学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Study on the status of metabolic syndrome in familial type 2 diabetes pedigrees / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of metabolic syndrome (MS) and its components in type 2 diabetes mellitus pedigrees.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>(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.</p><p><b>CONCLUSION</b>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.</p>

The genetic and clinical characteristics of transcription factor 1 gene mutations in Chinese diabetes / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>TCF1 gene is not a common cause of early-onset and/or multiplex diabetes among Chinese patients.</p>

Primary assessment of enzymatic measurement of glycated albumin / 上海第二医科大学学报

Objective To evaluate the clinical significance of glycated albumin(GA),a parameter in reflection of recent glycemic control in patients with diabetes mellitus. Methods Four hundred and forty-five patients with type 2 diabetes mellitus who were hospitalized in our hospital from May to November 2006 were enrolled into the study.The fasting plasma glucose(FPG),postprandial 2-hour blood glucose(P2hBG) and glycated hemoglobin(HbA1c) were measured,the enzymatic measurement of GA was conducted and the CGMS was performed.The correlation between GA and the other parameters monitored was analysed. Results The correlation analysis indicated that GA was well correlated with HbA1c(r=0.818,P0.05),respectively for those with HbA1c more than 7.5%,between 6.5% and 7.5%,and less than 6.5%. Conclusion GA is well correlated with HbA1c,especially in those with poor glycemic control for a long time.The correlation between GA and long-term glycemic control is stronger than that between GA and instant plasma glucose or MBG in three days.

Blood levels of true insulin and immunoreactive insulin in evaluating beta-cell function with arginine stimulation test / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the difference between serum true insulin (TI) and immunoreactive insulin (IRI) in evaluating islet beta-cell function and insulin resistance.</p><p><b>METHODS</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>The determination of TI may be more accurate than IRI in evaluating beta-cell function and insulin resistance.</p>

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 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Identification of four novel mutations in the HNF-1A gene in Chinese early-onset and/or multiplex diabetes pedigrees / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Mutation screening of GCK gene in Chinese early-onset diabetes population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of mutations and sequence variations of glucokinase gene GCK in Chinese early-onset diabetes population.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>The prevalence of structural mutations in glucokinase gene responsible for early-onset diabetes appears to be rare among Chinese patients.</p>

Comparison of the effect between insulin lispro 75/25 and humulin 70/30 on the postprandial blood glucose excursion in patients with diabetes / 中华内分泌代谢杂志

The effects of human insulin 70/30 and insulin lispro 75/25 were compared in improving postprandial blood glucose excursions in 106 patients with type 1 or 2 diabetes in a one-month,open-labelled,self- controlled trial .The results showed that treatment of diabetic patients with insulin lispro 75/25 significantly improved 2 h postprandial blood glucose excursion compared to pre-study with human insulin 70/30 (baseline) without any significant adverse events or sustained hypoglycemic episodes.These physiological benefits were associated with a patient preference for insulin lispro 75/25.