PROSPECTS FOR PREVENTION AND PROPHYLAXIS OF TYPE 1 DIABETES MELLITUS THROUGH VITAMIN D SUPPLEMENTATION

The role of mineral and bone disorders in the development and progression of cardiac and renal pathology in patients with type 1 diabetes mellitus of long duration

Identification of KCNJ15 as a Susceptibility Gene in Asian Patients with Type 2 Diabetes Mellitus

The studies on the risk of tuberculosis (TB) in patients with type 1 diabetes mellitus (T1DM) alone are limited. We examined this relationship using a population-based retrospective cohort study. From claims data of the National Health Insurance system of Taiwan, we identified 5195 patients with T1DM newly diagnosed from 2002 to 2011 and 20,780 randomly selected controls without T1DM, frequency matched by age, sex, and year of diagnosis. Both cohorts were followed up until the end of 2011 to evaluate the risk of TB. The overall incidence of TB was 4.07-fold higher in the T1DM cohort than in the control cohort (1.18 vs 0.29 per 1000 person-years, P < 0.001). Compared with the controls, the Cox model estimated adjusted hazard ratios (HRs) of TB in patients with T1DM were greater in men than in women (4.62 vs 3.59) and in adults than in children (4.06 vs 3.37), but not significant. The adjusted HR was much greater for those with comorbidities than those without comorbidities (14.6 vs 1.62, P < 0.001). Compared with the controls, the patients with T1DM were also more likely to develop TB with multiple emergency room visits (adjusted HR: 116.1, 95% confidence interval [CI] = 43.8–307.4) or hospitalizations (adjusted HR: 86.5, 95% CI = 33.7–222.4). Patients with T1DM are at elevated risks of developing TB with much higher HRs for those with comorbidities, within the first year of diagnosis, and with frequent emergency cares or hospitalizations.

To clarify the expression of N6-methyladenosine (m6 A) modulators involved in the pathogenesis of type 2 diabetes mellitus (T2DM). We further explored the association of serum insulin-like growth factor 2 mRNA-binding proteins 3 (IGF2BP3) levels and odds of T2DM in a high-risk population. The gene expression data set GSE25724 was obtained from the Gene Expression Omnibus, and a cluster heatmap was generated by using the R package ComplexHeatmap. Differential expression analysis for 13 m6 A RNA methylation regulators between nondiabetic controls and T2DM subjects was performed using an unpaired t test. A cross-sectional design, including 393 subjects (131 patients with newly diagnosed T2DM, 131 age- and sex-matched subjects with prediabetes, and 131 healthy controls), was carried out. The associations between serum IGF2BP3 concentrations and T2DM were modeled by restricted cubic spline and logistic regression models. Two upregulated (IGF2BP2 and IGF2BP3) and 5 downregulated (methyltransferase-like 3 [METTL3], alkylation repair homolog protein 1 [ALKBH1], YTH domain family 2 [YTHDF2], YTHDF3, and heterogeneous nuclear ribonucleoprotein [HNRNPC]) m6 A-related genes were found in islet samples of T2DM patients. A U-shaped association existed between serum IGF2BP3 levels and odds of T2DM according to cubic natural spline analysis models, after adjustment for body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyeride. Multivariate logistic regression showed that progressively higher odds of T2DM were observed when serum IGF2BP3 levels were below 0.62 ng/mL (odds ratio 3.03 [95% confidence interval 1.23-7.47]) in model 4. Seven significantly altered m6 A RNA methylation genes were identified in T2DM. There was a U-shaped association between serum IGF2BP3 levels and odds of T2DM in the general Chinese adult population. This study provides important evidence for further examination of the role of m6 A RNA methylation, especially serum IGF2BP3 in T2DM risk assessment.

Subclinical left ventricular (LV) dysfunction is prevalent in type 2 diabetes (T2DM). As obesity has been proposed as one causal factor in the disease process, this could bias the reported prevalences. We wanted to characterize echocardiographic LV dysfunction in obese T2DM subjects as compared to non-diabetic obese controls. One hundred patients with T2DM without clinical signs of heart failure (29% females, mean ± SD age 58.4 ± 10.5 years, body mass index (BMI) 30.1 ± 5.5 kg/m(2), blood pressure (BP) 141 ± 18/83 ± 9 mmHg) and 100 non-diabetic controls (29% females) matched for age (58.6 ± 10.5 years), BMI (29.8 ± 4.0 kg/m(2) and systolic BP (140 ± 14 mmHg) underwent echocardiography and color tissue Doppler imaging (TDI). Diastolic function was evaluated with conventional Doppler recordings and early (e') and late (a') myocardial velocities. The ratio between early transmitral filling (E) and the corresponding myocardial tissue velocity (e') served as an index of LV filling pressure. T2DM patients had more concentric hypertrophy with a relative wall thickness of 0.42 ± 0.07 vs controls 0.38 ± 0.07, P < 0.001. The T2DM group had signs of diastolic dysfunction with lower E/A ratio (0.91 ± 0.27 vs. 1.12 ± 0.38, P < 0.001), deceleration time (195 ± 49 vs 242 ± 72 ms, P < 0.001), e' (5.7 ± 2.0 vs. 6.6 ± 1.8 cm/s, P = 0.001), and a' (6.5 ± 2.0 vs. 7.6 ± 1.5 cm/s, P < 0.001) compared to the controls, and higher E/e' (13.3 ± 4.7 vs. 11.1 ± 3.5, P < 0.001). Thus, there were indications of pseudo normalization and increased filling pressure in the T2DM group, whereas the controls had evidence for relaxation abnormalities without elevated filling pressure. Compared to a non-diabetic obese group, more advanced subclinical impairment of diastolic function was seen in T2DM.

Glycemic control and outcome of cancer patients.

The Effect of Vitamin D Supplementation on Glycemic Control and Body Mass Index in the Obese, Vitamin D Deficient Adult with Type 2 Diabetes Mellitus: A Systematic Review Protocol

Objective To study the serum levels of oxidative stress markers in the new type 2 diabetes mellitus(T2DM) patients with nonalcoholic fatty liver disease(NAFLD), and the effect of α-lipoic acid(A-LA) on oxidative stress markers. Methods From August 2016 to August 2017, 80 new T2DM patients complicated with NAFLD (T2DM + NAFLD group) and 80 new T2DM patients without NAFLD (T2DM group) admitted to Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University were selected.The serum levels of Fasting blood glucose(FPG), body mass index(BMI), triglyceride(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C), insulin resistance index(HOMA-IR), serum superoxide dismutase(SOD), serum malondialdehyde(MDA), glutathione peroxidase(GSH-PX) were detected and compared between the two groups.And then, the T2DM patients with NAFLD were treated by A-LA for two weeks.The SOD, MDA, GSH-PX levels were compared before and after treatment. Results The FPG, BMI, TG, HOMA-IR of the T2DM+ NAFLD group were (10.71±3.63)mmol/L, (27.08±3.87)kg/m2, (3.40±1.85)mmol/L, (5.40±2.98), respectively, which were significantly higher than those of the T2DM group[(9.50±3.78)mmol/L, (23.58±2.75)kg/m2, (1.79±1.44)mmol/L, (2.41±1.18)](t=2.022, 6.603, 2.829, 4.157, all P 0.05). The level of MDA in the T2DM+ NAFLD group was (5.11±0.25)μmol/L, which was significantly higher than (4.56±0.28)μmol/L in the T2DM group(t=2.106, P<0.05). The levels of SOD, GSH-PX, SOD/MDA in the T2DM+ NAFLD group were (77.42±10.31)U/mL, (69.62±9.24)U, (15.39±2.23), respectively, which were significantly lower than those in the T2DM group[(93.26±11.21)U/mL, (87.54±9.58)U, (20.33±2.93)](t=2.455, 2.653, 3.148, all P<0.05). After treatment with A-LA, the MDA level of the T2DM+ NAFLD group was (4.81±0.26)μmol/L, which was significantly lower than that before treatment[(5.11±0.25)μmol/L, t=2.117, P<0.05], the levels of SOD, GSH-PX, SOD/MDA of the T2DM+ NAFLD group were (87.15±10.88)U/mL, (78.73±9.57)U, (18.05±2.51), respectively, which were significantly higher than those before treatment(t=2.117, 2.207, 2.228, 3.148, all P<0.05). Conclusion A-LA might prove usefully in the treatment of patients with T2DM and NAFLD by change the oxidative stress. Key words: Diabetes mellitus, Type 2; Fatty liver; Oxidative stress; Thioctic acid

Objective To investigate the association of obstructive sleep apnea hypopnea syndrome (OSAHS) and type 2 diabetes mellitus. Methods This study was conducted from May 2008 to December 2009 from the subjects diagnosed at the Sleep Center of the First Affiliated Hospital of Nanjing Medical University. Based on polysomnography examination, 104 habitual snorers were assigned to the simple snorer group (control group) and the OSAHS group which was further assigned to the mild OSAHS group and the moderate-to-severe OSAHS group according to the apnea hypopnea index (AHI) during sleep to compare the incidence of type 2 diabetes mellitus. Parameters among different groups were compared with Chi-square test and analysis of variance respectively. Spearman correlation analysis and Logistic regressive analysis were used to evaluate the correlation among AHI, minimal SaO2 (mini-SpO2), mean SaO2, fasting blood glucose, true insulin, proinsulin, HOMA index, body mass index (BMI), waist circumference (WC) and neck circumference (NC). Results Type 2 diabetes mellitus was found in 15.3%(13/85) of all the OSAHS patients. The incidence of type 2 diabetes mellitus in moderate-to-severe OSAHS group (25.7%(9/35)) was significantly higher than that in the control group (5.3%(1/19), χ2=4.942, P=0.026) and in the mild OSAHS group (8.0% (4/50), χ2=4.011, P=0.045). Spearman correlation analysis indicated that HOMA index and PI were negatively correlated with nocturnal mini-SpO2 and mean SpO2. There was no statistically significant correlation of HOMA index and PI with AHI. Mini-SpO2 and mean SpO2 were negatively correlated with BMI, WC, and NC. Univariate logistic regression analysis suggested that the HOMA index and PI were risk factors of severe OSAHS (odds ratio was 1.924 (1.302 to 2.847; P<0.01) or 1.714 (1.175 to 2.507; P<0.01)). Conclusion There is an association between OSAHS and type 2 diabetes mellitus. Insulin resistance may play an important role in the coexistence of OSAHS and type 2 diabetes mellitus. The OSAHS patients with a lower SpO2 can be more susceptible to type 2 diabetes mellitus. Key words: Type 2 diabetes mellitus; Obstructive sleep apnea hypopnea syndrome; Insulin resistance

Background : Globally incidence of Type 2 Diabetes Mellitus (T2DM) shows an upward trend which a challenge for physicians and public health specialists. Patients with T2DM have 2- 4-fold increased risk of coronary artery disease (CAD), the leading cause of death among people with T2DM. Dyslipidemia considered an important factor for cardiovascular complication of T2DM. Objective : Assessment of dyslipidemia and its association with T2DM in Bangladeshi subjects. Methods : A case control study was conducted in CARe Medical College Hospital, Dhaka, during the period of July 2018 to June 2019. A total 153 subjects were included in study of which 90 belonged to Group-I were T2DM and 63 subjects were healthy Controls in Group-II. The Fasting glucose, postprandial glucose. Serum Lipid Profile were assayed in patients and controls, using standardized assay methods. Data were analyzed by using SPSS version 21. Results : Fasting plasma glucose levels [mmol/l, (Mean± SD)] of the study group were Control (4.96 ± 0.76) and T2DM (8.27±2.19) difference was statistically significant (p &lt;0.001), 2 hours post prandial plasma glucose level [mmol/l, (Mean± SD)] of the study groups were Control (5.81±0.87) and T2DM (11.79 ± 2.69). A significant difference found between Control vs T2DM (p &lt;0.001). Fasting Triglyceride [mg/dl, (Mean± SD) was higher in T2DM (189±82.06), compared to Control (142±80.14) and statistically significant p=0.001. Total Cholesterol [mg/dl, (Mean± SD), Control (172±45) and T2DM (189±50.76) p=0.029] was significantly higher in T2DM than healthy subjects. HDL cholesterol [mg/dl, (Mean± SD); Control (30.6±8.10) and T2DM (26±9.94), p&lt;0.001] significantly increased in healthy Controls compared to T2DM subjects. LDL cholesterol [kg/m,2 (Mean± SD); Control (114±43.54) and T2DM (118±49.66), p=0.572] which was not significantly different among the study subjects. Conclusion : The present study concludes that important parameter of dyslipidemia, Fasting Triglyceride, total Cholesterol, were higher in T2DM patients and statistically significant. LDL cholesterol higher and not significant on the other hand HDL cholesterol was lower but significant difference between T2DM and healthy control found. Therefore, T2DM is associated with higher incidence of dyslipidemia Northern International Medical College Journal Vol. 12 No.1 July 2020, Page 507-510

The relationship between type 1 diabetes mellitus (T1DM) and periodontal disease may exhibit by the alteration of bone metabolism. However, evidence for this relationship is scarce and inconclusive. Thus, the aims of the present study were to investigate salivary receptor activator of nuclear factor kappa-β (RANK), receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG) gene expression and the RANKL:OPG ratio in T1DM and non-T1DM. Secondary objective was to determine the relationships of RANK, RANKL and OPG gene expression to clinical parameters of T1DM and periodontal disease. Twenty patients with T1DM and twenty age-matched non-T1DM were recruited. Clinical periodontal parameters were measured. Total RNA was isolated from non-stimulated saliva, and the relative gene expressions of RANK, RANKL, OPG and RANKL:OPG ratio were determined by quantitative real-time polymerase chain reaction. The T1DM group had significantly higher mean periodontal parameters than the non-T1DM group, while the mean plaque scores of both groups were not significantly different. There was a trend of higher relative gene expression of RANK, RANKL, and the RANKL:OPG ratio and lower expression of OPG in T1DM group but no statistic significant different when compared to non-T1DM. In the T1DM group, RANKL:OPG correlated with the percentage of bleeding sites, whereas RANK, RANKL, and HbA1c levels correlated with pocket depth. Bone metabolisms demonstrating by decreased OPG gene expression and upregulated of RANK, RANKL, RANKL:OPG with higher pocket depth and bleeding in T1DM may play an important role in periodontal destruction in T1DM.

Objective To evaluate the association between programmed cell death 1 (PDCD1) gene variants and type 1 diabetes mellitus (T1DM). Methods A case-control study was conducted in 585 T1DM patients from August 2014 to December 2016 in the Department of Endocrinology of the First Affiliated Hospital of Nanjing Medical University and 761 healthy controls in the same period in this region. PDCD1 rs2227981 and rs2227982 genotypes were analyzed by SNaPshot and the association of rs2227981 and rs2227982 locus genotype and allele frequency distribution with T1DM susceptibility was analyzed. Results Our study indicated that the frequency of CC, CT and TT genotype of rs2227981 in T1DM patients were 50.6%, 40.0% and 9.4% respectively and 56.6%, 37.2% and 6.3% respectively in healthy subjects. PDCD1 rs2227981 polymorphism was significantly associated with T1DM (OR=1.25, 95%CI: 1.06-1.48, P=0.01). Allelic gene C and T frequency were 70.6% and 29.4% in T1DM group, and 75.1% and 24.8% in control group, the T allele increased the risk of T1DM (OR=1.26, 95%CI: 1.06-1.49, P=0.009). The frequency of TT, TC and CC genotype of rs2227982 in T1DM patients were 20.2%, 51.8% and 28% respectively and 25.8%, 49% and 25.2% respectively in healthy subjects. PDCD1 rs2227982 polymorphism was also associated with T1DM (OR=1.18, 95%CI: 1.02-1.38, P=0.031). Allelic gene T and C frequency were 46.1% and 53.9% in T1DM group, and 50.3% and 49.7% in control group, the C allele increased the risk of T1DM (OR=1.15, 95%CI: 1.01-1.30, P=0.028). Conclusion The results indicate that PDCD1 rs2227981 and rs2227982 polymorphism are associated with increased risk of T1DM. Key words: Diabetes mellitus, type 1; Programmed cell death 1; Polymorphism

Background Despite the advances in treatment of type 1 diabetes mellitus (T1DM), diabetic complications constitute the main cause of morbidity and mortality. Moreover, T1DM is often associated with other autoimmune diseases. Aim To study children with T1DM of long duration, attending the diabetes clinic of Alexandria University Children’s Hospital, regarding the glycemic control and presence of complications and associated autoimmune diseases. Patients and methods A total of 50 children and adolescents with T1DM of more than or equal to 5-year duration were assessed for the presence of diabetic complications and their relation to the glycemic control and duration of diabetes. The investigations included glycosylated hemoglobin, estimated glomerular filtration rate, microalbuminuria, complete liver profile, lipid profile, thyroid profile, tests for celiac disease, abdominal ultrasound, fundus examination, and echocardiography. Results The majority (70%) of the patients had poor glycemic control, and 64% of them were receiving premixed insulin. Lipohypertrophy, fatty liver, dyslipidemia, and nephropathy were very prevalent complications. Hypothyroidism, neuropathy, and celiac disease were less common complications. Conclusion All our diabetic patients should be treated with basal-bolus insulin, with emphasis on education about proper comprehensive management of the disease.

BackgroundThe induction of heat shock protein (HSP) 72 by mild electrical stimulation with heat shock (MES+HS), which improves visceral adiposity and insulin resistance in mice, may be beneficial in treating metabolic syndrome (MS) or type 2 diabetes mellitus (T2DM). MethodsUsing open-label crossover trials, 40 subjects with MS or T2DM were randomly assigned using computer-generated random numbers to 12weeks of therapeutic MES+HS followed by 12weeks of no treatment, or vice versa. During the intervention period, physical and biochemical markers were measured. FindingsCompared to no treatment, MES+HS treatment was associated with a significant decrease in visceral adiposity (−7.54cm2 (−8.61%), 95% CI −8.55 to −6.53 (p=0.037) in MS, −19.73cm2 (−10.89%), 95% CI −20.97 to −18.49 (p=0.003) in T2DM). Fasting plasma glucose levels were decreased by 3.74mg/dL (−5.28%: 95% CI −4.37 to −3.09mg/dL, p=0.029) in MS and by 14.97mg/dL (10.40%: 95% CI −15.79 to 14.15mg/dL, p<0.001) in T2DM, and insulin levels were also reduced by 10.39% and 25.93%, respectively. HbA1c levels showed a trend toward reduction (−0.06%) in MS, and was significantly declined by −0.43% (95% CI −0.55 to −0.31%, p=0.009) in T2DM. HbA1c level of less than 7.0% was achieved in 52.5% of the MES+HS-treated T2DM patients in contrast to 15% of the non-treated period. Several insulin resistance indices, inflammatory cytokines or adipokines, including C-reactive protein, adiponectin, and tumor necrosis factor-α, were all improved in both groups. In isolated monocytes, HSP72 expression was increased and cytokine expression was reduced following MES+HS treatment. Glucose excursions on meal tolerance test were lower after using MES+HS in T2DM. InterpretationThis combination therapy has beneficial impacts on body composition, metabolic abnormalities, and inflammation in subjects with MS or T2DM. Activation of the heat shock response by MES+HS may provide a novel approach for the treatment of lifestyle-related diseases. FundingFunding for this research was provided by MEXT KAKENHI (Grants-in-Aid for Scientific Research from Ministry of Education, Culture, Sports, Science and Technology, Japan).

Prospective observational studies uniformly link vitamin D deficiency with the incidence of type 2 diabetes mellitus (T2DM), yet trials supplementing participants at risk of T2DM with vitamin D to reduce progression to T2DM have yielded inconsistent results. Inconsistencies between supplementation trials may be due to insufficient dosing or small sample sizes. Observational studies may also have reported spurious associations due to uncontrolled confounding by lifestyle or genetic factors. Alternatively, observational and intervention studies may not be entirely comparable. Observational studies show an association between higher vitamin D status, which is predominantly derived from sun exposure, and decreased incidence of T2DM. Trials intervene with vitamin D supplementation, and therefore may be missing alternate causes of the effect of sun exposure, as seen in observational studies. We propose that sun exposure may be the driving force behind the associations seen in observational studies; sun exposure may have additional benefits beyond increasing serum 25-hydroxyvitamin D (25OHD) levels. We performed an electronic literature search to identify articles that examined associations between sun exposure and T2DM and/or glucose metabolism. A best evidence synthesis was then conducted using outcomes from analyses deemed to have high methodological quality. Ten eligible full-text articles were identified, yielding 19 T2DM-related outcomes. The best evidence analysis considered 11 outcomes which were grouped into six outcome types: T2DM, fasting glucose, glucose tolerance, fasting insulin, insulin secretion and insulin sensitivity. There was moderate evidence to support a role of recreational sun exposure in reducing odds of T2DM incidence. High-level evidence was lacking; evidence presented for other outcomes was of low or insufficient level. This review highlights significant gaps in research pertaining to sun exposure and T2DM-related outcomes. Further research is encouraged as we aim to identify novel preventative strategies for T2DM.