Altered plasma acylcarnitine and amino acid profiles in type 2 diabetic kidney disease

Introduction

Dysregulation of acylcarnitines (AcylCNs) and amino acids metabolism have implicated in abnormality of fatty acid oxidation in type 2 diabetes (T2D). However, it is not well known whether altered plasma AcylCN, and amino acid profiles are associated with albuminuria or diabetic nephropathy (DN) in T2D.

Objective

The aim of this study was to elucidate alterations in plasma levels of AcylCNs and amino acids with respect to the T2D patients with various stages of albuminuria.

Methods

We recruited 52 healthy subjects as control, and 156 T2D patients which were divided into 52 normoalbuminuria, 52 microalbuminuria, and 52 macroalbuminuria. Plasma 37 AcylCNs and 12 amino acids were analyzed by tandem mass spectrometry.

Results

We found that T2D with normoalbuminuria and microalbuminuria had lower shot-, medium-, and long-chain AcylCNs, whereas T2D with macroalbuminuria had higher short-and medium-chain AcylCNs and lower long-chain AcylCNs than healthy subjects. Moreover, estimated glomerular filtration rate (eGFR) was a negative, independent and significant predictor of albumin to creatinine ratio (ACR) levels (β = ?0.376, P < 0.001), whereas plasma Low-density lipoprotein cholesterol (LDL-C) was significantly and positively associated with ACR levels (β = 0.169, P = 0.049). Furthermore, multivariate ordinal logistic regression analysis revealed that isobutyrylcarnitine (C4) was a positive, independent, and significant predictor of ACR levels with higher odds of having T2D patients with progression normoalbuminuria to microalbuminuria [OR = 9.93, 95 % CI (3.51–28.05), P < 0.001].

Conclusions

The findings suggest that plasma C4 may serve as a potential biomarker for the early stages of DN.

     

Prevalence of microalbuminuria,arterial hypertension,retinopathy, and neuropathy in patients with insulin dependent diabetes

Diabetic nephropathy is the main cause of the increased morbidity and mortality in patients with insulin dependent diabetes. The prevalence of microalbuminuria was determined in adults with insulin dependent diabetes of five or more years'' duration that had started before the age of 41. All eligible patients (n=982) attending a diabetes clinic were asked to collect a 24 hour urine sample for analysis of albumin excretion by radio-immunoassay; 957 patients complied. Normoalbuminuria was defined as urinary albumin excretion of ≤30 mg/24 h (n=562), microalbuminuria as 31-299 mg/24 h (n=215), and macroalbuminuria as ≥300 mg/24 h (n=180). The prevalence of microalbuminuria and macroalbuminuria was significantly higher in patients whose diabetes had developed before rather than after the age of 20. The prevalence of arterial hypertension increased with increased albuminuria, being 19%, 30%, and 65% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. The prevalence of proliferative retinopathy and blindness rose with increasing albuminuria, being 12% and 1·4%, respectively, in patients with normoalbuminuria, 28% and 5·6% in those with microalbuminuria and 58% and 10·6% in those with macroalbuminuria. An abnormal vibratory perception threshold was more common in patients with microalbuminuria (31%) and macroalbuminuria (50%) than in those with normoalbuminuria (21%).This study found a high prevalence (22%) of microalbuminuria, which is predictive of the later development of diabetic nephropathy. Microalbuminuria is also characterised by an increased prevalence of arterial hypertension, proliferative retinopathy, blindness, and peripheral neuropathy. Thus, urinary excretion of albumin should be monitored routinely in patients with insulin dependent diabetes.     

The effect of irradiance and temperature responses and the phenology of a native alga,Undaria pinnatifida (Laminariales), at the southern limit of its natural distribution in Japan

Phenology, irradiance, and temperature characteristics of an edible brown alga, Undaria pinnatifida (Laminariales), were examined from the southernmost natural population in Japan, both by culturing gametophytes and examining the photosynthetic activity of sporophytes using dissolved oxygen sensors and pulse amplitude-modulated chlorophyll fluorometer (IMAGING-PAM). Our surveys confirmed that sporophytes were present between winter and early summer, but absent by July. IMAGING-PAM experiments were used to measure maximum effective quantum yield (ΦII at 0 μmol photons m^?2 s^?1) for each of 14 temperatures (8–36 °C). Oxygen production was also determined over a coarser temperature gradient. Net photosynthesis and ΦII (at 0 μmol photons m^?2 s^?1) were observed to be temperature-dependent; the maximum ΦII was estimated to be 0.67, occurred at 21.2 °C, and was nearly identical to the optimal temperature of the net photosynthetic rate (21.7 °C). A net photosynthesis–irradiance (P–E) model revealed that saturation irradiance (E _k) was 119.5 μmol photons m^?1 s^?1, and the compensation irradiance (E _c) was 17.4 μmol photons m^?1 s^?1. Culture experiments on the gametophytes revealed that most individuals could not survive temperatures over 28 °C and that growth rates were severely inhibited. Based on our observations, temperatures greater than 20 °C are likely to influence photosynthetic activity and gametophyte survival, and therefore, it is possible that this species might become locally extinct if seawater temperatures in this region continue to rise.     

Effect of Spironolactone Therapy on Albuminuria in Patients with Type 2 Diabetes Treated with Angiotensin-Converting Enzyme Inhibitors

ObjectiveTo investigate whether the addition of spironolactone to angiotensin-converting enzyme (ACE) inhibitors further decreases albuminuria in patients with type 2 diabetes mellitus (DM).MethodsWe conducted a prospective open-label trial in patients recruited at the Cleveland Clinic between February 2004 and November 2006. Patients with type 2 DM were eligible if they were older than 18 years of age, had been treated with any ACE inhibitor for longer than 1 month, and had a random urinary albumin to creatinine ratio (ACR) greater than 100 mg/g within 1 month of study entry. Based on screening ACR, patients were assigned to a microalbuminuria group (ACR 100-300 mg/g) or a macroalbuminuria group (ACR > 300 mg/g). Patients were followed up for 12 weeks, with 4 clinic visits, 4 weeks apart. At visit 2, spironolactone, 25 mg once daily, was initiated and continued for 4 weeks. At visit 3, spironolactone was discontinued. Clinical information was obtained at each visit as were serum chemistries and 24-hour urinary albumin excretion.ResultsTwenty-four patients with type 2 DM and albuminuria completed the study. Eleven patients had microalbuminuria and 13 had macroalbuminuria. Following treatment with spironolactone, urinary albumin excretion dropped from a mean ± SD of 404.6 ± 60.9 mg/d to 302.7 ± 52.7 mg/d (25.7% decrease, P < .001). In the microalbuminuria and macroalbuminuria groups, the urinary albumin excretion dropped 27.2% (P = .05) and 24.3% (P = .02), respectively. Despite a significant decrease in systolic blood pressure between visits 2 and 3 (141.2 ± 3.5 to 132.5 ± 3.6 mm Hg; P = .002), this change did not correlate to the change in albuminuria (r² = 0.02; P = .23). There were no withdrawals due to hyperkalemia.ConclusionSpironolactone is effective in further decreasing albuminuria in patients with type 2 DM who are already treated with ACE inhibitors. (Endocr Pract. 2008;14:985-992)     

Hydraulic adjustments in aspen (Populus tremuloides) seedlings following defoliation involve root and leaf aquaporins

Main conclusion

Changes in root and leaf hydraulic properties and stimulation of transpiration rates that were initially triggered by defoliation were accompanied by corresponding changes in leaf and root aquaporin expression. Aspen (Populus tremuloides) seedlings were subjected to defoliation treatments by removing 50, 75 % or all of the leaves. Root hydraulic conductivity (L_pr) was sharply reduced in plants defoliated for 1 day and 1 week. The decrease in L _pr could not be prevented by stem girdling and it was accompanied in one-day-defoliated plants by a large decrease in the root expression of PIP1,2 aquaporin and an over twofold decrease in hydraulic conductivity of root cortical cells (L _pc). Contrary to L _pr and L _pc, 50 and 75 % defoliation treatments profoundly increased leaf lamina conductance (K _lam) after 1 day and this increase was similar in magnitude for both defoliation treatments. Transpiration rates (E) rapidly declined after the removal of 75 % of leaves. However, E increased by over twofold in defoliated plants after 1 day and the increases in E and K _lam were accompanied by five- and tenfold increases in the leaf expression of PIP2;4 in 50 and 75 % defoliation treatments, respectively. Defoliation treatments also stimulated net photosynthesis after 1 day and 3 weeks, although the increase was not as high as E. Leaf water potentials remained relatively stable following defoliation with the exception of a small decrease 1 day after defoliation which suggests that root water transport did not initially keep pace with the increased transpirational water loss. The results demonstrate the importance of root and leaf hydraulic properties in plant responses to defoliation and point to the involvement of PIP aquaporins in the early events following the loss of leaves.     

The Electrophoretical Determination of Serum Protein Fractions in Lycopene Treated Experimental Diabetic Rats

This study was planned to determine the effects of lycopene treatment on serum protein fractions in experimental diabetic rats. In order to induce diabetes in rats in the diabetes (D) and diabetes + lycopene (DL) groups, rats were given 45 mg/kg single-dose streptozotocin intraperitoneally. Lycopene (10 mg/kg/day dissolved in sunflower oil) was administered to the rats in the lycopene-only (L) and DL groups. Blood glucose levels and HbA1c% in DL group and diabetes group increased (p < 0.05) compared to control and L group. Total protein, albumin, α₁, α₂, and β globulin fractions of diabetic and DL groups were lower than control and L groups (p < 0.05). D group had lowest gamma (γ) globulin levels among other groups (p < 0.05). The γ globulin levels was slightly increased than diabetic groups (D and DL), but it was still lower than control and L groups (p < 0.05). The highest value of A/G ratio was observed in diabetic group. Similarly, the % level of A/G ratio of D group was higher than other groups. It was noted that the A/G ratio decreased and reached to control group levels after lycopene treatment.     

Does polyamine oxidase activity influence the oxidative metabolism of children who suffer of diabetes mellitus?

Diabetes mellitus is a metabolic disease characterized by inadequate secretion of insulin. Polyamine oxidase (PAO), a FAD-containing enzyme is involved in the biodegradation of Sp and Spd, catalyzing the oxidative deamination of Sp and Spd, resulting in production of amonia (NH₃), corresponding amino aldehydes and H₂O₂. Malondialdehyde (MDA) and acrolein (CH2=CHCHO), potentially toxic agents, which induce oxidative stress in mammalian cells, are then spontaneously formed from aminoaldehydes. The main signs of oxidative stress in diabetic children were the values of HbA1c and MDA levels. Polyamines have an insulin-like action. Antiglycation property of spermine and spermidine has been recently confirmed. There are no data in the literature about plasma polyamine oxidase (PAO) activities in children with type 1 diabetes. The idea of this study was to evaluate the polyamine metabolism through the estimation of polyamine oxidase activity. We have study children with newly diagnosed type 1 diabetes mellitus (n = 35, age group of 5–16 years, as well as age-matched healthy control subjects (n = 25). The biochemical investigations were done on diabetic children who have the pathological values of glucose (9.11–17.33 mmol/l) and glycosylated Hb (7.57–14.49% HbA_1c). The children in the control group have referent values of glucose and glycated hemoglobin (4.11-5.84 mmol/L and HbA_1c 4.22-6.81% of the total Hb. Glucose levels in blood plasma and glycosylated hemoglobin in erythrocythes hemolysates (HbA1c) were measured by using standard laboratory methods. PAO activity in venous blood plasma and the amount of malondialdehyde (MDA) were measured by the spectrophotometric methods. PAO activity, glycemia, HbA1c and MDA were significantly increased in diabetic children compared to the control subjects. PAO activity in children with type 1 diabetes mellitus was very high. The findings of higher blood HbA_1C and MDA levels confirm the presence of oxidant stress in children with type 1 diabetes mellitus and demonstrate that PAO activity may participate in these circumstances.     

The link between vascular deterioration and branched chain amino acids in a population with high glycated haemoglobin: the SABPA study

Globally the prevalence of non-communicable diseases, such as hypertension and type 2 diabetes, are escalating. Metabolomic studies indicated that circulating branched chain amino acids (BCAAs) are associated with insulin resistance, coronary artery disease and increased risk for cardiovascular events. We aimed to extend the current understanding of the cardiovascular risk associated with BCAAs. We explored whether BCAAs are related to markers of cardiovascular disease in a bi-ethnic population and whether this relationship was influenced by chronic hyperglycaemia. We included 200 African and 209 Caucasian participants, and determined their ambulatory blood pressure and carotid intima-media thickness (cIMT). We analysed blood samples for glycated haemoglobin (HbA1c) and BCAAs. Participants were stratified into two groups according to their HbA1c value using the median cut-off value of 5.6 %. Ambulatory BP, cIMT and BCAAs were significantly higher (all p < 0.001) in the high HbA1c group. Single regression analyses indicated significant positive associations of ambulatory blood pressure and cIMT with BCAAs (all p < 0.05) in both the groups. These associations between ambulatory systolic blood pressure (SBP) (r = 0.16, p = 0.035) and cIMT (r = 0.22, p = 0.004) with BCAAs remained in the high HbA1c group after adjusting for age, gender, ethnicity and body mass index (BMI) and were confirmed in multiple regression analyses (ambulatory SBP: R ² = 0.17, β = 0.21, p = 0.005 and cIMT: R ² = 0.30, β = 0.19, p = 0.003). Our results demonstrate that BCAAs are independently related to ambulatory BP and cIMT in individuals with high HbA1c levels and suggest that potential cardiovascular deterioration accompany the rise in BCAAs in conditions of hyperglycaemia.     

西格列汀对2 型糖尿病患者微量白蛋白尿影响的研究

目的:研究西格列汀对2型糖尿病患者微量白蛋白尿的影响,分析其可能机制和临床应用价值。方法:选取160例伴微量白蛋白尿的2型糖尿病患者,随机分为西格列汀组和其他药物组,各80例。比较两组患者治疗前和治疗3个月后血糖水平、尿微量白蛋白、超敏C反应蛋白及血浆还原型谷胱甘肽水平。结果:经3个月治疗,两组患者空腹血糖、餐后2 h血糖、Hb A1c均较治疗前下降,但差异无明显统计学意义(P0.05);西格列汀治疗组患者尿微量白蛋白和血浆Hs-CRP水平明显下降,血浆还原型谷胱甘肽水平明显升高,与其他口服药物治疗组相比差异具有统计学意义(P0.05)。结论:西格列汀可能通过改善机体炎症状态,降低氧化和应激水平等机制降低2型糖尿病患者的尿微量白蛋白水平。     

Serum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes

Objective

To determine the role of markers of plasma protein damage by glycation, oxidation and nitration in microalbuminuria onset or subsequent decline of glomerular filtration rate (termed “early GFR decline”) in patients with type 1 diabetes.

Methods

From the 1^st Joslin Kidney Study, we selected 30 patients with longstanding normoalbuminuria and 55 patients with new onset microalbuminuria. Patients with microalbuminuria had 8–12 years follow-up during which 33 had stable GFR and 22 early GFR decline. Mean baseline GFR_{CYSTATIN C} was similar between the three groups. Glycation, oxidation and nitration markers were measured in protein and ultrafiltrate at baseline by liquid chromatography-tandem mass spectrometry using the most reliable methods currently available.

Results

Though none were significantly different between patients with microalbuminuria with stable or early GFR decline, levels of 6 protein damage adduct residues of plasma protein and 4 related free adducts of plasma ultrafiltrate were significantly different in patients with microalbuminuria compared to normoalbuminuria controls. Three protein damage adduct residues were decreased and 3 increased in microalbuminuria while 3 free adducts were decreased and one increased in microalbuminuria. The most profound differences were of N-formylkynurenine (NFK) protein adduct residue and N_ω-carboxymethylarginine (CMA) free adduct in which levels were markedly lower in microalbuminuria (P<0.001 for both).

Conclusions

Complex processes influence levels of plasma protein damage and related proteolysis product free adducts in type 1 diabetes and microalbuminuria. The effects observed point to the possibility that patients who have efficient mechanisms of disposal of damaged proteins might be at an increased risk of developing microalbuminuria but not early renal function decline. The findings support the concept that the mechanisms responsible for microalbuminuria may differ from the mechanisms involved in the initiation of early renal function decline.     

Patient Perspectives on Obesity Management: Need for Greater Discussion of BMI and Weight-Loss Options Beyond Diet and Exercise,Especially in Patients With Diabetes

Objective: To identify perceptions of obesity management in patients with and without diabetes.Methods: A 48-question survey was administered in 2018 to our Endocrinology Clinic's adult patients with a body mass index (BMI) ≥30 kg/m². Chi-squared or Fisher's exact tests were used to compare variables between groups.Results: Of 146 respondents, 105 had diabetes and 41 did not. Most respondents were female (61.4%), African American (66.4%), and with an income <$50,000 (58.6%). Those with diabetes had significantly greater comorbidities of hypertension, high cholesterol, and arthritis. Over 90% in both groups agreed that obesity is related to hypertension, diabetes, heart disease, and early death. Only 48% were aware of their BMI, and only 30.5% with diabetes and 41.5% without diabetes perceived themselves to be obese. Over 60% in each group reported discussion of diet and exercise with their providers, whereas few in both groups reported referral to a formal weight-loss program (18.9%) or to a specialty that manages obesity (4.2%), or discussion of anti-obesity medications (11.2%) or bariatric surgery (8.4%). Reported concerns with anti-obesity medications and bariatric surgery included lack of knowledge and side effects or complications.Conclusion: These findings revealed excellent patient awareness of obesity as a health problem but misperception of obese status and unawareness of BMI. Presence of diabetes and other comorbidities did not result in greater discussion of weight-loss methods beyond diet and exercise. Increased patient education and discussion of specific weight-loss services, anti-obesity medications, and bariatric surgery are needed.Abbreviations: BMI = body mass index; DM = diabetes mellitus; HbA1c = hemoglobin A1c; HCP = healthcare provider     

The Antiepileptic Effect of Ghrelin During Different Phases of the Estrous Cycle in PTZ-Induced Seizures in Rat

Catamenial epilepsy is a special form of epilepsy in women whom seizure aggravation is arranged with menstrual cycle that may affect up to 70 % of epileptic women. Antiepileptic effect of Ghrelin hormone has been proved recently. Due to effects of Ghrelin on GABA and LH concentration and periodic variation in the level of estrogen (E₂) and progesterone (P₄) during menstrual cycle, it seems that antiepileptic effect of Ghrelin can be different during various phases of estrous cycle. So this study was conducted to survey antiepileptic effect of Ghrelin during various phases of estrous cycle in rats. 72 adult female Wistar rats in three groups (control, 40 and 80 μg/kg of Ghrelin), each with four subgroups (proestrus, estrus, metestrus and diestrus) were used (n = 6). Then, intracerebroventricular (ICV) injection of Ghrelin (40 and 80 μg/kg) followed by intraperitoneal injection of 80 μg/kg pentylenetetrazole in control and treatment groups were done. Initiation time of myoclonic seizures (ITMS), initiation time of tonic–clonic seizures (ITTS), seizures duration and mortality rate were monitored and recorded for 30 min. Results showed that, ICV injection of Ghrelin significantly increased ITMS and ITTS during luteal phase than follicular phase compared to control group (P < 0.05). Also, seizure duration significantly decreased after ICV injection of Ghrelin during luteal phase and follicular phase compared to control group (P < 0.05). Furthermore, there was no mortality after ICV injection of Ghrelin (40 and 80 μg/kg) during luteal and follicular phases compared to control group (P < 0.05). These results suggest that Ghrelin has antiepileptic effects which are more prominent during luteal phase than follicular phase.     

Hydrolytic Enzyme Production is Associated with Candida Albicans Biofilm Formation from Patients with Type 1 Diabetes

Oral candidosis is common in patients with diabetes mellitus, as yeasts, particularly Candida albicans, have the propensity to colonise, form biofilms and release hydrolytic enzymes which cause inflammation. This study aimed to investigate these characteristics in isolates from three groups of patients with type 1 diabetes: individuals with better controlled diabetes (BCD; ≥6 <8%), individuals with poorly controlled diabetes (PCD; ≥8%) and non-diabetics (ND; HbA_1c <5.9%). The biomass (Bm), phospholipase (P_z), haemolysin (H_z) and proteinase (Pr_z) were assessed using a microtitre biofilm assay and agar-based hydrolytic enzyme assays. Biofilm formation was significantly increased in the PCD group compared to ND and BCD groups (P < 0.05). No significant differences in P_z levels were observed between groups, whereas both H_z and Pr_z were significantly greater in the diabetes groups than in the healthy control group (P < 0.05). Statistically significant correlations were found to exist between the HbA_1c levels of the patients and the Bm (R = 0.384; P = 0.033), haemolysin activity (R = ?0.455; P = 0.010) and proteinase activity (R =  ?0.531; P = 0.002). There was no apparent correlation between the Bm and P_z activity (R = ?0.305; P = 0.053) or H_z activity (R = ?0.100; P = 0.296). However, a negative correlation was found between Bm and Pr_z values (R = ?0.343; P = 0.030). These data suggest that biofilm formation is likely to play a role in the pathogenicity of oral candidosis, and in patients with diabetes, this may be due to the ability of C. albicans to adapt to the altered physiological environment. The production of hydrolytic enzymes is independently associated with this growth modality.     

Liraglutide as Additional Treatment to Insulin in Obese Patients with Type 1 Diabetes Mellitus

ObjectiveBecause approximately 40% of patients with type 1 diabetes have the metabolic syndrome, we tested the hypothesis that addition of liraglutide to insulin in obese patients with type 1 diabetes will result in an improvement in plasma glucose concentrations, a reduction in hemoglobin A1c (HbA1c), a fall in systolic blood pressure, and weight loss.MethodsThis is a retrospective analysis of data obtained from 27 obese patients with type 1 diabetes treated with liraglutide in addition to insulin. Patients were also treated for hypertension. Paired t tests were used to compare the changes in HbA1c, insulin doses, body weight, body mass index, 4-week mean blood glucose concentrations (28-day insulin pump mean blood glucose), blood pressure, and lipid parameters prior to and 180 ± 14 days after liraglutide therapy.ResultsMean glucose concentrations fell from 191 ± 6 to 170 ± 6 mg/dL (P = .002). HbA1c fell from 7.89 ± 0.13% to 7.46 ± 0.13% (P = .001), without an increase in frequency of hypoglycemia. Mean body weight fell from 96.20 ± 3.68 kg to 91.56 ± 3.78 kg (P<.0001). Daily total and bolus doses of insulin fell from 73 ± 6 to 60 ± 4 (P = .008) units and from 40 ± 5 to 29 ± 3 units (P = .011), respectively. Mean systolic blood pressure fell from 130 ± 3 to 120 ± 4 mm Hg (P = .020).ConclusionAddition of liraglutide to insulin in obese patients with type 1 diabetes mellitus leads to improvements in glycemic control and HbA1c and to reductions in insulin dose, systolic blood pressure, and body weight. (Endocr Pract. 2013;19:963-967)     

Drosophila lactate dehydrogenase: Molecular and genetic aspects

(LDH) obtained from larvae of Drosophila melanogaster was purified to homogeneity by affinity chromatography on oxamate-Sepharose. The purification procedure is simple to operate and gives a homogeneous preparation in a good yield (34.86%) after only two steps. Utilizing the homogeneous LDH preparation, an attempt was made to characterize the LDH molecule. Thus, it was found that the N-terminal amino acid is isoleucine, and the enzyme is tetrameric and composed of four identical subunits of apparent molecular weight 38,000, suggesting that it is controlled by a single gene. Homogeneous LDH preparations exhibit one band on neutral acrylamide gels when the substrate is either dl-lactic acid or l-(+)-lactate. The optimum temperature is 45°C for the purified enzyme and 40°C for the crude homogenate. The K _m values for pyruvate and NADH are 0.154 and 0.027mm, respectively, while the K _m values for lactate and NAD are 29.4 and 1.33mm, respectively. A discontinuity in the E _a slope was observed at a transition temperature of 30°C. The E _a value between 20 and 30°C was calculated as 12.06 kcal/mol, while between 30 and 45°C the E _a value was 4.01 kcal/mol. This evidence, together with other observations reported in the literature, suggests that the LDHs of invertebrates and vertebrates have arisen by divergent evolution from a common ancestral gene.     

Association of vitamin D receptor FokI and ApaI polymorphisms with lung cancer risk in Tunisian population

Many studies reported that Vitamin D Receptor (VDR) gene polymorphisms might influence the cancer risk due to their antiproliferative, antiangiogenic, and apoptotic effects. The aim of this study was to explore the genetic association of VDR polymorphisms with lung cancer risk in Tunisian population. The genotype and haplotype frequencies of four VDR polymorphisms, FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) were studied using polymerase chain reaction and restriction fragment length polymorphism analysis in 240 patients with lung cancer and 280 healthy controls. The distribution of genotype frequencies differed significantly between lung cancer subjects and controls (FokI P _adj  = 0.002; ApaI P _adj  = 0.013). Haplotype analyses revealed a significant association between G-A-C and A-C-T haplotypes and lung cancer risk (P _corr  = 0.0128, P _corr  = 0.008). When patients were stratified according to gender, age, and smoking, significant associations were detected with FokI and TaqI polymorphisms. We found a lack of association between BsmI, TaqI polymorphisms and lung cancer risk (P > 0.05). Only, the attributable proportion due to interaction and the synergic index for interaction between ApaI polymorphism and smoking were statistically significant (P _adj  = 0.74, 95 % CI = 0.38–1.20) and (P _adj  = 0.63, 95 % CI = 0.05–1.21), respectively. Both the additive interaction measures suggested the existence of a biological interaction between SNP ApaI, but not FokI, and smoking. The multiplicative interaction measure was not statistically significant (P > 0.05). This is the first study in Tunisia, which suggested that VDR FokI and ApaI polymorphisms might be risk factors for lung cancer development.     

Screening for celiac disease in poorly controlled type 2 diabetes mellitus: worth it or not?

Background

Recent studies have demonstrated that immune factors might have a role in the pathophysiology of insulin resistance and type 2 diabetes mellitus (T2DM). Inappropriate glycemic control in patients with T2DM is an important risk factor for the occurrence of diabetes complications. The prevalence of celiac disease (CD) is high in type 1 diabetes mellitus however, there are scarce data about its prevalence in T2DM. Our aim was to investigate the prevalence of celiac disease among insulin-using type 2 diabetes patients with inappropriate glycemic control.

Methods

IgA tissue transglutaminase antibodies (tTGA IgA) test was performed as a screening test. A total of 135 patients with T2DM whose control of glycemia is inappropriate (HbAlc value >7%) in spite of using insulin treatment for at least 3-months (only insulin or insulin with oral antidiabetic drugs) and 115 healthy controls were enrolled in the study. Upper gastrointestinal endoscopy with duodenal biopsy was performed to all patients with raised tTGA IgA or selective lgA deficiency.

Results

Gender, age, body mass index (BMI) and tTGA IgA, kreatinin, calcium, LDL-cholesterol (LDL-C), total cholesterol, 25-OH vitamin D₃ levels were similar between groups. Systolic and diastolic blood pressure, waist circumference, fasting plasma glucose, postprandial plasma glucose, urea, sodium, HbA1c, LDL-C, triglyceride, vitamin B12 levels were significantly higher in DM group (p < 0.0001). BMI, high-sensitive CRP, microalbuminuria, and AST, ALT, potassium, phosphorus levels were significantly higher in the T2DM group (p < 0.05). HDL-cholesterol and parathormone levels were significantly lower in the T2DM group (p < 0.05). Two of the 135 patients with T2DM were diagnosed with CD (1.45%).

Conclusions

The prevalence of celiac disease among patients with type 2 diabetes, with poor glycemic control despite insulin therapy, is slightly higher than the actual CD prevalence in general population. Type 2 diabetic patients with inappropriate control of glycemia in spite of insulin treatment might be additionally tested for Celiac disease especially if they have low C-peptide levels.