Maturity-onset diabetes of the young type 9 or latent autoimmune diabetes in adults:A case report and review of literature

BACKGROUND Maturity-onset diabetes of the young(MODY)is a monogenic genetic disease often clinically misdiagnosed as type 1 or type 2 diabetes.MODY type 9(MODY9)is a rare subtype caused by mutations in the PAX4 gene.Currently,there are limited reports on PAX4-MODY,and its clinical characteristics and treatments are still unclear.In this report,we described a Chinese patient with high autoimmune antibodies,hyperglycemia and a site mutation in the PAX4 gene.CASE SUMMARY A 42-year-old obese woman suffered diabetes ketoacidosis after consuming substantial amounts of beverages.She had never had diabetes before,and no one in her family had it.However,her autoantibody tested positive,and she managed her blood glucose within the normal range for 6 mo through lifestyle interventions.Later,her blood glucose gradually increased.Next-generation sequencing and Sanger sequencing were performed on her family.The results revealed that she and her mother had a heterozygous mutation in the PAX4 gene(c.314G>A,p.R105H),but her daughter did not.The patient is currently taking liraglutide(1.8 mg/d),and her blood glucose levels are under control.Previous cases were retrieved from PubMed to investigate the relationship between PAX4 gene mutations and diabetes.CONCLUSION We reported the first case of a PAX4 gene heterozygous mutation site(c.314G>A,p.R105H),which does not appear pathogenic to MODY9 but may facilitate the progression of latent autoimmune diabetes in adults.

Six-year follow-up of pancreatic β cell function in adults with latent autoimmune diabetes

AIM: To investigate the characteristics of the progression of islet β cell function in Chinese latent autoimmune diabetes in adult (LADA) patients with glutamic acid decarboxylase antibody (GAD-Ab) positivity, and to explore the prognostic factors for β cell function. METHODS: Forty-five LADA patients with GAD-Ab positivity screened from phenotypic type 2 diabetic (T2DM) patients and 45 T2DM patients without GAD-Ab matched as controls were followed-up every 6 mo. Sixteen patients in LADA1 and T2DM1 groups respectively have been followed-up for 6 years, while 29 patients in LADA2 and T2DM2 groups respectively for only 1.5 years. GAD-Ab was determined by radioligand assay, and C-peptides (CP) by radioimmune assay.RESULTS: The percentage of patients whose fasting CP(FCP) decreased more than 50% compared with thebaseline reached to 25.0% at 1.5th year in LADA1 group, and FCP level decreased (395.8±71.5 vs 572.8±72.3 pmol/L, P＜0.05) at 2.5th year and continuously went down to the end of follow-up. No significant changes of the above parameters were found in T2DM1 group. The average decreased percentages of FCP per year in LADA and T2DM patients were 15.8% (4.0-91.0%) and 5.2% (-3.5 to 35.5%, P= 0.000) respectively. The index of GAD-Ab was negatively correlated with the FCP in LADA patients (rs= -0.483, P = 0.000). The decreased percentage of FCP per year in LADA patients were correlated with GAD-Ab index, body mass index (BMI) and age at onset (rs = 0.408, -0.301 and -0.523 respectively, P＜0.05). Moreover, GAD-Ab wasthe only risk factor for predicting βcell failure in LADA patients (B = 1.455, EXP (B) = 4.283, P = 0.023). CONCLUSION: The decreasing rate of islet β cell function in LADA, being highly heterogeneous, is three times that of T2DM patients. The titer of GAD-Ab is an important predictor for the progression of islet β cell function, and age at onset and BMI could also act as the predictors.

Newly diagnosed diabetes mellitus patients presenting with proliferative diabetic retinopathy as an initial sign

AIM: To investigate the clinical features of newly diagnosed diabetes mellitus(NDM) patients showing proliferative diabetic retinopathy(PDR) as an initial sign. ·METHODS: As a retrospective case series,the medical records of a total of four hundred and thirty-two patients who underwent a vitrectomy due to PDR were reviewed to find the subjects. Of 432 patients,six cases of NDM patients showing PDR as an initial sign were included and analyzed with their systemic and ocular features. Main outcome measures: the systemic features and ocular features [preoperative and postoperative best corrected visual acuity(BCVA),intraoperative findings]. ·RESULTS: The mean onset age of visual symptoms was 36.3 years old. The mean serum insulin and C-peptide titer was below the normal range. The mean fasting plasma glucose was 178mg/dL and the mean postprandial 2h plasma glucose was 306mg/dL. The mean HbA1c at diagnosis was 11.02%. In all cases,an acute progressive fibrovascular proliferation was observed. Intraoperative retinal tears were found in three cases of six. The mean preoperative BCVA was +0.67 ± 0.58 logMAR and the mean BCVA at postoperative 6 months was +0.20±0.30 logMAR. ·CONCLUSION: All patients were considered to have latent autoimmune diabetes in adults(LADA). A rapid deterioration of kidney function as well as poor diabetic control status at diagnosis was observed in all six cases. The ocular features of the patients showed acute progressive fibrovascular proliferation and relatively favorable postoperative visual acuity.

Study of Tripterygium Associated with Nicotinamide in Treating Late-onset Autoimmune Diabetes Mellitus in Adults

Objective: To explore the effect of Tripterygium polyglycoside (TP) associated with nicotinamide on the islet cell function, immune parameters and lipoperoxide (LPO) in adult patients with late-onset autoimmune diabetes mellitus (LADA). Methods: Thirty-six cases of LADA were randomly divided into three groups: TP group (n=12), treated with TP plus orally taken metformin; combined treatment group (n= 12), treated with TP combined with nicotinamide and metformin, and control group (n=12) treated with metformin alone. They were followed-up for 18 months. Results: (1) Compared with the control group after 9 months of treatment, postprandial plasma glucose and LPO in combined treatment group were decreased (P <0.05), and the postprandial C-peptide was higher (P<0.05). At the 18th month, the value of postprandial C-peptide in the TP and combined treatment group was higher than that in the control group. The slL-2R level of both TP and combined treatment groups were lowered (P<0.01); (2) Islet cell antibody (ICA) positive of 5 cases in the TP group and 6 cases in the combined treatment group got converted to the negative respectively , while only one in the control group at the time (P<0.05); (3) The level of LPO in the combined treatment group was significantly lower than that in the TP group at the 18th month of treatment (P<0. 05). Conclusion: TP combined with nicotinamide played a role in immunity regulation, decreasing the titer of islet cell antibody and slL-2R, which also reduced the production of LPO and had a tendency to improve islet cell function in early LADA patients.

The Ability of Baseline Triglycerides and Total Cholesterol Concentrations to Predict Incidence of Type 2 Diabetes Mellitus in Chinese Men and Women:A Longitudinal Study in Qingdao, China

Objectives The purpose of this study was to assess the association between triglycerides(TG),total cholesterol(TC)at baseline,and type 2 diabetes mellitus(T2DM)incidence in a general Chinese population.Further,it aimed to evaluate the ability of TG and TC to predict T2DM incidence.Methods Qingdao Diabetes Prevention Program participants recruited between 2006 and 2009 were followed up in 2012–2015.TG,TC,and T2DM status were measured.Cox proportional hazards models were used to estimate the association between TG,TC,and T2DM incidence.The receiver operating characteristic(ROC)curve was used to evaluate the ability of TG and TC to identify T2DM participants.Results The incidence of T2DM significantly increased with TG in women and TC in both men and women(Ptrend<0.05).Univariate Cox regression indicated that higher TG{borderline high TG[hazards ratio(HR):2.05;95%confidence interval(CI):1.40,3.00]and hypertriglyceridemia[HR:2.64;95%CI:1.68,4.15]}and TC[hypercholesterolemia(HR:2.05;95%CI:1.43,2.95)]were significantly associated with increased risk of T2DM incidence in women but not in men.Multivariate Cox regression showed that hypertriglyceridemia in women(HR:1.78,95%CI:1.07,2.97),borderline high TC in men(HR:1.61,95%CI:1.04,2.48),and hypercholesterolemia in women(HR:1.68,95%CI:1.81,2.61)had a higher significant risk of T2DM incidence.The optimal cutoff values of TG were>1.15 and>1.23 mmol/L in men and women,respectively.For TC,they were>5.17 and>5.77 mmol/L in men and women,respectively.The area under the ROCs of TG and TC were 0.54(0.51–0.57)and 0.55(0.52–0.58),respectively,in men,and 0.60(0.58–0.62)and 0.59(0.56–0.61),respectively,in women.Conclusion Elevated TG and TC were risk factors for T2DM incidence.However,no predictive capacity was found for both factors to identify T2DM incidence in Chinese men and women.Hence,TG and TC levels in both Chinese men and women might be used for decreasing the incidence of T2DM but no clinical predictive capacity for T2DM.

Age at diagnosis of type 2 diabetes and cardiovascular risk factor profile:A pooled analysis

BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.AIM To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.METHODS A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years.Anthropometric and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood pressure.Univariable and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk factor.RESULTS A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in life.Participants diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older age.Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(CI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%CI:0.10-0.25)and 0.32 cm higher waist circumference(95%CI:0.14-0.49),after adjustment for duration of diabetes and other confounders.Younger age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and triglycerides.CONCLUSION The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile,compared to those diagnosed later in life.

Latent autoimmune diabetes in adults： evidences for diabetes spectrum？

In 1936, Himworth first investigated insulin resistance and non-insulin resistance in diabetes. Then the terminology ＂type 1 diabetes （T1D）＂ and ＂type 2 diabetes （T2D）＂ were first used in 1951. In 1999, the World Health Organization （WHO） announced the classification of diabetes： as we all known, T1D and T2D.1 This classification is widely accepted and used. However, in clinical practice, it is quite often to find some patients cannot be simply diagnosed as T1D or T2D.

Acute Epiglottitis in a Diabetic Adult Patient

Acute epiglottitis （AE） is a potentially life-threatening infection of the supraglottic structures, which can lead to sudden, fatal airway obstruction, may require urgent tracheal intubation or tracheotomy. However, there are no putative predictors for urgent airway intervention in AE, and the timing to establish an artificial airway for adult AE patients remains controversial.