Unveiling mitochondrial mysteries:Exploring novel tRNA variants in type 2 diabetes mellitus

The recent study of Ding et al provides valuable insights into the functional implications of novel mitochondrial tRNATrp and tRNASer(AGY)variants in type 2 diabetes mellitus(T2DM).This editorial explores their findings,highlighting the role of mitochondrial dysfunction in the pathogenesis of T2DM.By examining the molecular mechanisms through which these tRNA variants contribute to disease progression,the study introduces new targets for therapeutic strategies.We discuss the broader implications of these results,emphasizing the importance of understanding mitochondrial genetics in addressing T2DM.

Genetic association of rs7754840 and rs7756992 polymorphisms in the CDKAL1 gene and gestational diabetes mellitus in selected Filipino pregnant women

Objective:To investigate the possible association between rs7754840 and rs7756992 polymorphisms of CDKAL1 gene and susceptibility to gestational diabetes mellitus(GDM)in a Filipino pregnant population.Methods:A total of 101 patients with GDM and 99 women without GDM were included.Two CDKAL1 gene single nucleotide polymorphisms(SNPs),namely rs7754840 and rs7756992,were genotyped by using TaqMan allelic discrimination assays.Mann-Whitney U test,median and interquartile range were used to describe physical and biochemical characteristics.The differences in the genotype and allele distribution of the target genetic variants among the two groups of participants were assessed by using Chi-square test.Conformity to Hardy-Weinberg equilibrium was tested prior to conducting further analysis.Multiple logistic regression model was used to investigate the effects of the genotype models on GDM development.Results:There was no observed correlation between the genotypes of the rs7754840 SNP and oral glucose tolerance test parameters.Consequently,there was no significant association between genetic models of the rs7754840 SNP and GDM risk(additive OR 1.43,95%CI 0.82-2.50,P=0.21;dominant OR 1.21,95%CI 0.57-2.59,P=0.62;recessive OR 1.63,95%CI 0.86-3.09,P=0.13).Conclusions:The results of this study suggest no association between CDKAL1 gene variant rs7754840 and GDM development in Filipino pregnant women.Further studies with a larger population should be performed to validate our findings.

Genetic Predisposition for Type 2 Diabetes Mellitus in a Cameroonian Population: Contribution of rs4731702 (C/T) Polymorphism of Krüppel-Like Factor 14 Gene

Introduction: Krüppel Like Factor 14 (KLF14) gene has recently been identified as a master gene for multiple metabolic phenotypes. The aim of the research study was to investigate the relationship between KLF14 rs4731702 (C/T) gene polymorphism with Type 2 Diabetes Mellitus (T2DM) in a Cameroonian population. Patients and Methods: This case-control study was conducted in 85 patients with T2DM and 95 healthy normoglycemic controls. All were nonrelated, of Cameroonian origin, and were adults aged 24 years old and above. Demographic, clinical and biological data were collected, and biochemical explorations were performed using enzymatic colorimetric methods. The genotyping of KLF14 rs4731702 (CT) gene polymorphism was done by the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. Results: In comparing the Cameroonian population that consisted of 85 patients with T2DM and 95 healthy controls, the minor or risk allele of the rs4731702 (C/T) polymorphism of the KLF14 gene was T (63.53% diabetic patients vs. 26.32% healthy controls, OR = 4.877 and p < 0.0001) while the protective allele was C (36.47% diabetic patients vs. 73.68% healthy controls, OR = 0.205 and p < 0.0001). The susceptibility to T2DM was higher among subjects having the CT and TT genotypes with OR = 2.721 and p = 0.0145) and OR = 3.907 and p < 0.0001) respectively. This gene polymorphism was not preferentially associated with a specific diabetes phenotype. Conclusion: This study has demonstrated for the first time the relationship between the KLF14 rs4731702 (C/T) gene polymorphism and T2DM in this Cameroonian population. This gene polymorphism could be a promising target for personalized medicine through the development of clinical genetic testing.

Pharmacogenetic studies update in type 2 diabetes mellitus

Type 2 diabetes mellitus(T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs(OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters(SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment.

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age?

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation &#x000b1; fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.

Comparative study of type 2 diabetes mellitus-associated gut microbiota between the Dai and Han populations

BACKGROUND The global prevalence of type 2 diabetes mellitus(T2DM)is increasing.T2DM is associated with alterations of the gut microbiota,which can be affected by age,illness,and genetics.Previous studies revealed that there are discriminating microbiota compositions between the Dai and the Han populations.However,the specific gut microbiota differences between the two populations have not been elucidated.AIM To compare the gut microbiota differences in subjects with and without T2DM in the Dai and Han populations.METHODS A total of 35 subjects of the Han population(including 15 healthy children,8 adult healthy controls,and 12 adult T2DM patients)and 32 subjects of the Dai population(including 10 healthy children,10 adult healthy controls,and 12 adult T2DM patients)were enrolled in this study.Fasting venous blood samples were collected from all the subjects for biochemical analysis.Fecal samples were collected from all the subjects for DNA extraction and 16S rRNA sequencing,which was followed by analyses of the gut microbiota composition.RESULTS No significant difference in alpha diversity was observed between healthy children and adults.The diversity of gut microbiota was decreased in T2DM patients compared to the healthy adults in both the Dai and Han populations. There was a significant difference in gut microbiota between healthy children and healthy adults in the Hanpopulation with an increased abundance of Bacteroidetes and decreased Firmicutes in children. However, thisdifference was less in the Dai population. Significant increases in Bacteroidetes in the Han population and Proteobacteriain the Dai population and decreases in Firmicutes in both the Han and Dai population were observed inT2DM patients compared to healthy adults. Linear discriminant analysis Effect Size analysis also showed that thegut microbiota was different between the Han and Dai populations in heathy children, adults, and T2DM patients.Four bacteria were consistently increased and two consistently decreased in the Han population compared to theDai population.CONCLUSION Differences in gut microbiota were found between the Han and Dai populations. A significant increase inBacteroidetes was related to the occurrence of T2DM in the Han population, while a significant increase in Proteobacteriawas related to the occurrence of T2DM in the Dai population.

Parental transmission of type 2 diabetes mellitus in a highly endogamous population

AIM: To determine the parental transmission of diabetes mellitus (DM) and evaluate its influence on the clinical characteristics. METHODS: This was a cross sectional study. The survey was carried out in urban and semi-urban primary health care centers. Of the 2400 registered with diagnosed diabetes, 1980 agreed and gave their consent to take part in this study, thus giving a response rate of 82.5%. Face to face interviews were conducted using a structured questionnaire followed by laboratory tests. DM was defined according to the World Health Organization expert group. A trained nurse performedphysical examinations and measurements. RESULTS: Of the study population, 72.9% reported a family history of DM. Family history of DM was significantly higher in females (54.2%; P = 0.04) and in the age group below 30 years (24%; P < 0.001). The prevalence of diabetes was higher among patients with a diabetic mother (25.4% vs 22.1%) and maternal aunts/uncles (31.2% vs 22.2%) compared to patients with a diabetic father and paternal aunts/ uncles. Family history of DM was higher in patients of consanguineous parents (38.5%) than those of non-consanguineous parents (30.2%). The development of type 2 diabetes mellitus (T2DM) complications was higher in patients with either a paternal or maternal history of DM than in those without. No significant difference was observed in the metabolic characteristics of patients with/without family history of DM except for hypertension. Complications were higher in diabetic patients with a family history of DM. CONCLUSION: The present study found a significant maternal effect in transmission of T2DM. Family history is associated with the increased incidence of diabetes.

The relationship of Imp2 and DR3 genes with susceptibility to type Ⅰ diabetes mellitus in south China Han population

AIN To study the relationship of Imp2 and DR3genes with type Ⅰ diabetes mellitus.NETHODS Imp2 genotypes and DR3 wereidentified in 68 patients with type Ⅰ diabetesmellitus(Ⅰ-DM)and 71 healthy controls.Then,Ⅰ-DM patients and controls were respectivelyallocated into DR3-positive and DR3-negativegroups.The frequencies of Imp2 and DR3 genein random subjects,and Imp2 genotypes in DR3-matched subjects were compared between Ⅰ-DMpatients and controls.At the same time,Ⅰ-DMpatients were divided into 3 groups based on theonset age of diabetics:group A≤14 years,group B 15-30 years and group C≥31 years.RESULTS The frequency of DR3 in Ⅰ-DMpatients was significantly higher than that incontrols(47% vs 21%,P【0.005),and it wassignificantly higher in group A than that in groupB+C(70% vs 36%,x^2=7.07,P【0.01).Therewas a significant difference among groups withdifferent onset age of diabetics(x^2=8.19,rp=0.33,P【0.05).In random subjects,thefrequency of Imp2.R/R in Ⅰ-DM patients waslower(43% vs 61%,P【0.05)and Imp2.R/Hhigher(53% vs 28%,P【0.05)than that incontrols,and there was no significant differenceamong groups with different onset age ofdiabetics.In DR3-positive subjects,thefrequency of Imp2.R/R in Ⅰ-DM patients waslower(47% vs 87%,P【0.05)and Imp2-R/H higher(47% vs 13%,P【0.05)than that incontrols.In DR3-negative subjects,thefrequency of Imp2.R/H in Ⅰ-DM patients washigher than that in controls(58% vs 32%,P【0.01),but the frequency of Imp2-R/R and Imp2H/H was not significantly different betweenthese two groups.CONCLUSION DR3 gene may be one of thesusceptible genes of Ⅰ-DM,and significantlyrelated to the onset age of diabetics,and thepersons with DR3 may have an younger onsetage of diabeteS.The Imp2-R/R may be theprotective genotype of Ⅰ-DM,and Imp2-R/H thesusceptible genotype.These were not affectedby DR3 gene.Imp-2 genotypes were not relatedwith the onset age of diabetics.

Research progress on etiology of gestational diabetes mellitus

As a metabolic disorder during pregnancy,gestational diabetes mellitus (GDM) has an important effects on fetal development,neonatal health and maternal long-term health,and is one of the pregnancy complications with high incidence.It is of great significance that we have an accurate understanding of the etiology and risk factors of GDM for its prevention and control.GDM is a complex disease with multiple etiologies.Current studies have shown that the occurrence of GDM may be the result of combined effect of heredity and environment,but the exact etiology is still unclear.In this paper,we summarized the possible etiologies and risk factors of GDM,so as to understand the occurrence and development of GDM better and to provide possible references for prevention and further etiological studies of GDM.

Bidirectional relationship between type 2 diabetes mellitus and coronary artery disease:Prospective cohort study and genetic analyses

Background:While type 2 diabetes mellitus(T2DM)is considered a putative causal risk factor for coronary artery disease(CAD),the intrinsic link underlying T2DM and CAD is not fully understood.We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods:We evaluated phenotypic associations using data from the United Kingdom Biobank(N=472,050).We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM,with and without adjustment for body mass index(BMI)(T2DM:N_(case)/N_(control)=74,124/824,006;T2DM adjusted for BMI[T2DM_(adj)BMI]:N_(case)/N_(control)=50,409/523,897)and for CAD(N_(case)/N_(control)=181,522/984,168).We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM(N_(case)/N_(control)=180,834/1,159,055).Results:Observational analysis suggested a bidirectional relationship between T2DM and CAD(T2DM→CAD:hazard ratio[HR]=2.12,95%confidence interval[CI]:2.01–2.24;CAD→T2DM:HR=1.72,95%CI:1.63–1.81).A positive overall genetic correlation between T2DM and CAD was observed(r_(g)=0.39,P=1.43×10^(-75)),which was largely independent of BMI(T2DM_(adj)BMI–CAD:r_(g)=0.31,P=1.20×10^(–36)).This was corroborated by six local signals,among which 9p21.3 showed the strongest genetic correlation.Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci.Mendelian randomization analysis supported a bidirectional causal relationship(T2DM→CAD:odds ratio[OR]=1.13,95%CI:1.11-1.16;CAD→T2DM:OR=1.12,95%CI:1.07-1.18),which was confirmed in multiancestry individuals(T2DM→CAD:OR=1.13,95%CI:1.10-1.16;CAD→T2DM:OR=1.08,95%CI:1.04-1.13).This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors,with mediation proportions of 54.1%(95%CI:24.9-83.4%)and 90.4%(95%CI:29.3-151.5%),respectively.Conclusion:Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Effect of Yanggyuksanhwa-Tang on Non-Insulin-Dependent Diabetes Mellitus Unresponsive to Oral Hypoglycemic Agents:A Case Report

Diabetes mellitus is the fourth leading cause of death worldwide, following cancer, cerebrovascular disease, and heart disease. It is triggered by hyperglycemia and other metabolic disorders. Diabetes is a complex endocrine disease that causes chronic vascular complications such as diabetic nephropathy, retinopathy, and polyneuropathy.

Styrene and ethylbenzene exposure and type 2 diabetes mellitus:A longitudinal gene-environment interaction study

Styrene and ethylbenzene(S/EB)are identified as hazardous air contaminants that raise significant concerns.The association between S/EB exposure and the incidence of type 2 diabetes mellitus(T2DM),and the interaction between genes and environment,remains poorly understood.Our study consisted of 2219 Chinese adults who were part of the Wuhan-Zhuhai cohort.A follow-up assessment was conducted after six years.Exposure to S/EB was quantified by determining the concentrations of urinary biomarkers of exposure to S/EB(UBE-S/EB;urinary phenylglyoxylic acid level plus urinary mandelic acid level).Logistic regression models were constructed to investigate the relations of UBE-S/EB and genetic risk score(GRS)with T2DM prevalence and incidence.The interaction effects of UBE-S/EB and GRS on T2DM were investigated on multiplicative and additive scales.UBE-S/EB was dose-dependently and positively related to T2DM prevalence and incidence.Participants with high levels of UBE-S/EB[relative risk(RR)=1.930,95%confidence interval(CI):1.157-3.309]or GRS(1.943,1.110-3.462)demonstrated the highest risk of incident T2DM,in comparison to those with low levels of UBE-S/EB or GRS.Significant additive interaction between UBE-S/EB and GRS on T2DM incidence was discovered with relative excess risk due to interaction(95%CI)of 0.178(0.065-0.292).The RR(95%CI)of T2DM incidence was 2.602(1.238-6.140)for individuals with high UBE-S/EB and high GRS,compared to those with low UBE-S/EB and low GRS.This study presented the initial evidence that S/EB exposure was significantly related to increased risk of T2DM incidence,and the relationship was interactively aggravated by genetic predisposition.

Gestational diabetes from A to Z

Gestational diabetes mellitus(GDM) is defined as any degree of hyperglycaemia that is recognized for the first time during pregnancy. This definition includes cases of undiagnosed type 2 diabetes mellitus(T2 DM) identified early in pregnancy and true GDM which develops later. GDM constitutes a greater impact on diabetes epidemic as it carries a major risk of developing T2 DM to the mother and foetus later in life. In addition, GDM has also been linked with cardiometabolic risk factors such as lipid abnormalities, hypertensive disorders and hyperinsulinemia. These might result in later development of cardiovascular disease and metabolic syndrome. The understanding of the different risk factors, the pathophysiological mechanisms and the genetic factors of GDM, will help us to identify the women at risk, to develop effective preventive measures and to provide adequate management of the disease. Clinical trials have shown that T2 DM can be prevented in women with prior GDM, by intensive lifestyle modification and by using pioglitazone and metformin. However, a matter of controversy surrounding both screening and management of GDM continues to emerge, despite several recent welldesigned clinical trials tackling these issues. The aim of this manuscript is to critically review GDM in a detailed and comprehensive manner, in order to provide a scientific analysis and updated write-up of different related aspects.

Polymorphisms and functions of the aldose reductase gene 5' regulatory region in Chinese patients with type 2 diabetes mellitus

OBJECTIVE: To screen the 5' regulatory region of the aldose reductase (AR) gene for genetic variabilities causing changes in protein expression and affecting the promoter function. METHODS: The screenings were carried out by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). All SSCP variants were submitted for DNA sequencing and inserted into the plasmid chloromycetin acetyl transferase (CAT) enhancer vector. The constructs were used to transfect Hela cells, and CAT assays were performed to assess promoter activity. Gel mobility shift and footprinting assays were also performed to determine the interaction between the DNA and nuclear proteins. RESULTS: Two polymorphisms, C (-106) T and C (-12) G, were identified in the regulatory region in 123 Chinese control subjects and 145 patients with type 2 diabetes mellitus. The frequencies of genotypes WT/WT, WT/C (-12) G and WT/C (-106) T were not significantly different between the subjects and patients. In the patients with and without retinopathy, frequencies of WT/C (-106) T were 31.5% and 17.5% (P 0.05) respectively. The total frequency of WT/C (-12) G and WT/C (-106) T in patients with retinopathy was 41.8%, significantly higher than that (20.0%) in patients without retinopathy (P

High metabolic dysfunction-associated steatotic liver disease prevalence in type 2 diabetes: Urgent need for integrated screening and lifestyle intervention

This letter discusses the recent study by Mukherjee et al,which identifies a significant prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)among newly diagnosed type 2 diabetes mellitus(T2DM)patients in Bihar,India,and underscores the pressing need for integrated MASLD mana-gement within T2DM care.With 72.3%of the study cohort affected by MASLD,implementing routine liver function tests and ultrasound screenings is recom-mended as a standard practice in diabetes care,especially in regions with high prevalence rates.The study also advocates for dietary and lifestyle modifications,particularly the reduction of saturated fats,to slow MASLD progression.Patient education on monitoring body mass index and waist circumference,coupled with the integration of these metrics into digital health records,could enhance patient involvement and support proactive health management.Moreover,the letter emphasizes the advantages of developing a region-specific MASLD risk model that incorporates local dietary patterns and socioeconomic factors.Continued research into genetic and environmental determinants of MASLD remains es-sential for advancing our understanding of its etiology and informing targeted public health strategies.

CTLA-4 gene A/G polymorphism associated with diabetes mellitus in Han Chinese

OBJECTIVE: To investigate the association of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene A/G polymorphism with susceptibility to diabetes mellitus in Han Chinese. METHODS: An A/G transition at position 49 of exon 1 was analyzed in 31 patients with type 1 diabetes, 31 patients with type 2 diabetes, and 36 controls were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: A highly significant increase in the frequency of the G allele was seen in patients with type 1 diabetes compared with controls (66.1 % vs. 34.7%, respectively; P

Exploring the genetic basis of childhood monogenic diabetes

Monogenic diabetes is caused by one or even more genetic variations,which may be uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1%to 5%of children,and early detection and genetically focused treatment of neonatal diabetes and maturity-onset diabetes of the young can significantly improve long-term health and well-being.The etiology of monogenic diabetes in childhood is primarily attributed to genetic variations affecting the regulatory genes responsible for beta-cell activity.In rare instances,mutations leading to severe insulin resistance can also result in the development of diabetes.Individuals diagnosed with specific types of monogenic diabetes,which are commonly found,can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguish individuals with type 1 or 2 diabetes from those more prone to monogenic diabetes.Genetic screening with appropriate findings and interpretations is essential to establish a prognosis and to guide the choice of therapies and management of these interrelated ailments.This review aims to design a comprehensive literature summarizing genetic insights into monogenetic diabetes in children and adolescents as well as summarizing their diagnosis and management.

Affection of Single-Nucleotide Polymorphisms in miR-27a, miR-124a, and miR-146a on Susceptibility to Type 2 Diabetes Mellitus in Chinese Han People

Background：Polymorphisms of microRNA （miRNA）,as a novel mechanism,are closely associated with disease states by interfering with miRNA function.Direct correlations have been identified between single-nucleotide polymorphisms （SNPs） in miRNA,but the effect on type 2 diabetes mellitus （T2DM） onset among Chinese population remains unclear.Therefore,the aim of this study was to identify correlations between common SNPs in miR-27a,miR-146a,and miR-124a with T2DM among a Chinese population,as well as to explore diabetic pathological mechanisms and the impact of environmental factors.Methods：SNPscan technology was used to genotype 995 patients newly diagnosed with T2DM and 967 controls.Logistic regression analysis was performed to compare mutation frequencies between cases and controls.Results：We found no significant correlations between all genotypes of these miRNAs and T2DM in our research.However,stratification analysis identified a lower risk of T2DM associated with the rs531564GC genotype among younger subjects （age ＜ 45 years） （adjusted P =0.043; odds ratio [OR] =0.73; 95％ confidence interval [CI] =0.54-0.99）.Furthermore,the rs895819CC genotype in overweight people （24 ＜ body mass index [BMI] ＜ 28） was significantly associated with an increased risk of T2DM （adjusted P =0.042; OR =1.73; 95％ CI =1.02-2.94）,while the rs2910164 genotype in miR-146a was not significantly correlated with T2DM.The genetic risk score was calculated based on the number of risk alleles of the three SNPs and was found to be correlated to total cholesterol （adjusted P =0.021）.Conclusions：The rs531564GC genotype acted as a protective factor to decrease the risk of T2DM in younger subjects （age ＜ 45 years）,while the presence of the rs895819CC genotype increased the risk of illness among overweight subjects （24 ＜ BMI ＜ 28 kg/m2）.The presence of SNPs in miRNA might promote disease by affecting miRNA expression and gene function.Thus,miRNA mimics or inhibitors that directly regulate miRNA expression present novel and promising therapeutic targets.

Polymorphism of the leptin gene promoter in pedigrees of type 2 diabetes mellitus in Chongqing, China

Background It has been shown that the presence of leptin is associated with deabefes, glucose wefabolism and insulin metablism. In this research, we evaluated the presence of the leptin C -2549A polymorphism in the Chinese population in Chongqing and verified its association with plasma leptin levels and anthropometric, metabolic, and clinical parameters. Methods Two hundred and sixty-nine patients with diabetes, 135 non-diabetic first-degree relatives of the patients, and 85 healthy controls were screened for the presence of C -2549A polymorphism using a PCR-RFLP assay. Body mass index, fasting leptin, fasting insulin, fasting glucose and homeostatic model assessment for insulin resistance (HOMA)-IR were also determined.Results In the type 2 diabetes group, AA genotype frequency (6.32%) and A allele frequency (34.94%) was higher than in normal controls (1.18% and 25.29%, respectively). Diabetic patients with the AA genotype had lower fasting leptin and insulin levels than those with other genotypes. Carriers with the AC genotype had decreased fasting leptin and insulin levels and longer duration of disease as compared with those with CC genotype. The HOMA-IR of patients with AA or AC genotypes was lower than those with the CC genotype. In non-diabetic relatives group, individuals with the AA genotype had a lower fasting leptin level than those with the AC genotype. The fasting insulin and HOMA-IR level of carriers of the AA or AC genotype were lower than those of the CC genotype.Conclusion The C -2549A polymorphism in the leptin gene is associated with fasting leptin in patients with type 2 diabetes. The distribution of the genotypes in diabetic subjects from diabetic pedigrees differs from those in normal controls. The A allele frequency in diabetic patients is higher than that in normal controls. The haplotypes defined by genotypes are different in the familial subjects.

Mitochondrial gene variation in type 2 diabetes mellitus: detection of a novel mutation associated with maternally inherited diabetes in a Chinese family

Objective To explore the relationship between type 2 diabetes mellitus and the mutation(s) in mitochondrial DNA Methods According to the previous literature, the fragment of mitochondrial DNA from nucleotide 3153 to 3551, which had shown high frequency of point mutation, was scanned with the technique of polymerase chain reaction single strand conformation polymorphism (PCR SSCP) in Chinese normal control, type 2 diabetic population, and 12 families suffered from maternally inherited type 2 diabetes mellitus Direct sequencing was applied to detect the fragments with abnormal conformation Results No special band was found in SSCP electrophoreses in Chinese normal control, and only one subject (No 81) of diabetic population indicated the abnormality in SSCP study, which was affirmed to be a silent point mutation of T to C at nucleotide 3336 inducing no change in amino acid (ATT→ATC, Ile ) Pedigree 25?001 was the only family that exhibited strongly different SSCP characteristic from the other 11 ones, which was confirmed to be caused by a single point mutation mt3285T→C/T in the coding region of tRNA Leu(UUR) gene by the technique of direct sequencing Conclusions The variation within mt DNA 3153-3551 is not the major cause of type 2 diabetes in Chinese population suffered from this disease in this study The point mutation T→C/T at the mitochondrial nucleotide 3285, which was found in pedigree 25?001, is located in the highly conservative region of tRNA Leu(UUR) gene It is strongly suggested that this mutation cause the conversion in the 3 dimentional structure of tRNA Leu(UUR) , which might disturb the normal translation and lead to the impairment in mitochondrial oxidative phosphorylation characterized by the defects of the polypeptides involved in the respiratory chain Thus, insulin secretion deficiency and insulin resistance might occur