Rosa Tsuneshiro Fukui

Positive effects of football on fitness, lipid profile, and insulin resistance in Brazilian patients with type 2 diabetes

We evaluated the effects of recreational football training combined with calorie‐restricted diet (football + diet) vs calorie‐restricted diet alone (diet) on aerobic fitness, lipid profile, and insulin resistance indicators in type 2 diabetes (T2D) patients. Forty‐four T2D patients aged 48–68 years (27 females, 17 males) were randomly allocated to the football + diet group (FDG; n = 22) or to the diet group (DG; n = 22), of whom 19 FDG and 15 DG subjects completed the study. The football training was performed for 3 × 40 min/week for 12 weeks. Dual‐energy X‐ray absorptiometry scanning, treadmill testing, and fasting blood samplings were performed pre and post‐intervention. After 12 weeks, maximal oxygen uptake (VO2max) was elevated (P < 0.05) by 10 ± 4% in FDG but not in DG (−3 ± 4%, P < 0.05). After 12 weeks, reductions in blood triglycerides (0.4 ± 0.1 mmol/L), total cholesterol (0.6 ± 0.2 mmol/L), low‐density lipoprotein, and very low‐density lipoprotein levels were observed only in FDG. Fat mass decreased (P < 0.05) by 3.4 ± 0.4 kg in FDG and 3.7 ± 0.4 kg in DG. The lower (P < 0.05) glucagon and homeostatic model assessment of insulin resistance indicated an improvement in insulin sensitivity in FDG. In conclusion, football combined with restricted diet was effective in enhancing VO2max, reducing total cholesterol and triglycerides, and increasing insulin sensitivity, potentially providing better tools for the prevention of T2D complications than diet alone.

The PTPN22 1858T allele but not variants in the proximal promoter region of IL-21 gene is associated with the susceptibility to type 1 diabetes and the presence of autoantibodies in a Brazilian cohort

Interleukin (IL)‐21 and protein tyrosine phosphatase non‐receptor 22 (PTPN22) regulate lymphocyte function and have been implicated in the pathogenesis of autoimmune diabetes. We sequenced the proximal promoter of the IL‐21 gene for the first time and analysed the PTPN22 1858T polymorphism in type 1A diabetes (T1AD) patients and healthy controls (HC). We correlated the frequencies of islet and extra‐pancreatic autoantibodies with genotypes from both loci. The case series comprised 612 T1AD patients and 792 HC. Genotyping of PTPN22 C1858T was performed on 434 T1AD patients and 689 HC. The −448 to +83 base pairs (bp) region of the IL‐21 gene was sequenced in 309 Brazilian T1AD and 189 HC subjects. We also evaluated human leucocyte antigen (HLA) DR3/DR4 alleles. The frequencies of glutamic acid decarboxylase (GAD65), tyrosine phosphatase‐like protein (IA)‐2, anti‐nuclear antibody (ANA), thyroid peroxidase (TPO), thyroglobulin (TG), thyrotrophin receptor autoantibody (TRAb), anti‐smooth muscle (ASM) and 21‐hydroxylase (21‐OH) autoantibodies were higher in T1AD patients than in HC. The PTPN22 1858T allele was associated with an increased risk for developing T1AD [odds ratio (OR) = 1·94; P < 0·001], particularly in patients of European ancestry, and with a higher frequency of GAD65 and TG autoantibodies. HLA‐DR3/DR4 alleles predominated in T1AD patients. A heterozygous allelic IL‐21 gene variant (g.‐241 T > A) was found in only one patient. In conclusion, only PTPN22 C1858T polymorphism and HLA‐DR3 and/or DR4 alleles, but not allelic variants in the 5′‐proximal region of the IL‐21 gene were associated with T1AD risk. Patients with T1AD had increased frequencies of anti‐islet‐cell, anti‐thyroid, anti‐nuclear, anti‐smooth muscle and anti‐21‐OH autoantibodies. The C1858T PTPN22 polymorphism was also associated with a higher frequency of GAD65 and TG autoantibodies.

Cardiovascular, metabolic and hormonal responses to the progressive exercise performed to exhaustion in patients with type 2 diabetes treated with metformin or glyburide.

Objectives:  To evaluate the effects of Metformin and Glyburide on cardiovascular, metabolic and hormonal parameters during progressive exercise performed to exhaustion in the post‐prandial state in women with type 2 diabetes (T2DM).

The influence of population stratification on genetic markers associated with type 1 diabetes

Ethnic admixtures may interfere with the definition of type 1 diabetes (T1D) risk determinants. The role of HLA, PTPN22, INS-VNTR, and CTLA4 in T1D predisposition was analyzed in Brazilian T1D patients (n = 915), with 81.7% self-reporting as white and 789 controls (65.6% white). The results were corrected for population stratification by genotyping 93 ancestry informative markers (AIMs) (BeadXpress platform). Ancestry composition and structural association were characterized using Structure 2.3 and STRAT. Ethnic diversity resulted in T1D determinants that were partially discordant from those reported in Caucasians and Africans. The greatest contributor to T1D was the HLA-DR3/DR4 genotype (OR = 16.5) in 23.9% of the patients, followed by -DR3/DR3 (OR = 8.9) in 8.7%, -DR4/DR4 (OR = 4.7) in 6.0% and -DR3/DR9 (OR = 4.9) in 2.6%. Correction by ancestry also confirmed that the DRB1*09-DQB1*0202 haplotype conferred susceptibility, whereas the DRB1*07-DQB1*0202 and DRB1*11-DQB1*0602 haplotypes were protective, which is similar to reports in African-American patients. By contrast, the DRB1*07-DQB1*0201 haplotype was protective in our population and in Europeans, despite conferring susceptibility to Africans. The DRB1*10-DQB1*0501 haplotype was only protective in the Brazilian population. Predisposition to T1D conferred by PTPN22 and INS-VNTR and protection against T1D conferred by the DRB1*16 allele were confirmed. Correcting for population structure is important to clarify the particular genetic variants that confer susceptibility/protection for T1D in populations with ethnic admixtures.

The effects of metformin and glibenclamide on glucose metabolism, counter-regulatory hormones and cardiovascular responses in women with Type 2 diabetes during exercise of moderate intensity.

Aims  To compare the effects of metformin and glibenclamide on cardiovascular, metabolic and hormonal parameters during exercise of moderate intensity performed in the postprandial state, in women with Type 2 diabetes.

Importance of Zinc Transporter 8 Autoantibody in the Diagnosis of Type 1 Diabetes in Latin Americans

There is a scarcity of data of zinc transporter-8 autoantibody (ZnT8A) on mixed populations such as Brazilian. Therefore, we evaluated the relevance of ZnT8A for type 1 diabetes (T1D) diagnosis and the role of ZnT8 coding gene (SLC30A8) in T1D predisposition. Patients with T1D (n = 629; diabetes duration = 11 (6–16) years) and 651 controls were genotyped for SLC30A8 rs16889462 and rs2466295 variants (BeadXpress platform). ZnT8 triple antibody was measured by ELISA; glutamic acid decarboxylase (GAD65A) and protein tyrosine phosphatase (IA-2A) autoantibodies by radioimmunoassay. Results: Znt8A was detected in 68.7% of recent-onset T1D patients and 48.9% of the entire patient cohort, similar to GAD65A (68.3% and 47.2%) and IA-2A (64.8% and 42.4%) positivities respectively. ZnT8A was the only antibody in 8.4% of patients. Znt8A and IA2A frequencies and titers were independent of gender and ethnicity, whereas GAD65A titers were greater in females. The diabetes duration-dependent decline in ZnT8A frequency was similar to GAD65A and IA-2A. The SLC30A8 rs2466293 AG + GG genotypes were associated with T1D risk in non-European descents (56.2% × 42.9%; p = 0.018), and the GG genotype with higher ZnT8A titers in recent-onset T1D: 834.5 IU/mL (711.3–2190.0) × 281 IU/mL (10.7–726.8); p = 0.027. Conclusion ZnT8A detection increases T1D diagnosis rate even in mixed populations. SLC30A8 rs2466293 was associated with T1D predisposition in non-European descents.

Combination of recreational soccer and caloric restricted diet reduces markers of protein catabolism and cardiovascular risk in patients with type 2 diabetes

BackgroundModerate calorie-restricted diets and exercise training prevent loss of lean mass and cardiovascular risk. Because adherence to routine exercise recommendation is generally poor, we utilized recreational soccer training as a novel therapeutic exercise intervention in type 2 diabetes (T2D) patients.ObjectiveWe compared the effects of acute and chronic soccer training plus calorie-restricted diet on protein catabolism and cardiovascular risk markers in T2D.Design, setting and subjectsFifty-one T2D patients (61.1±6.4 years, 29 females: 22 males) were randomly allocated to the soccer+diet-group (SDG) or to the dietgroup (DG). The 40-min soccer sessions were held 3 times per week for 12 weeks.ResultsNineteen participants attended 100% of scheduled soccer sessions, and none suffered any injuries. The SDG group showed higher levels of growth hormone (GH), free fatty acids and ammonia compared with DG. After 12 weeks, insulin-like growth factor binding protein (IGFPB)-3 and glucose levels were lower in SDG, whereas insulin-like growth factor (IGF)-1/ IGFBP-3 ratio increased in both groups. After the last training session, an increase in IGF-1/IGFBP-3 and attenuation in ammonia levels were suggestive of lower muscle protein catabolism.ConclusionsRecreational soccer training was popular and safe, and was associated with decreased plasma glucose and IGFBP-3 levels, decreased ammoniagenesis, and increased lipolytic activity and IGF-1/IGFBP-3 ratio, all indicative of attenuated catabolism.

CD226 rs763361 Is Associated with the Susceptibility to Type 1 Diabetes and Greater Frequency of GAD65 Autoantibody in a Brazilian Cohort

CD226 rs763361 variant increases susceptibility to type 1 diabetes (T1D) in Caucasians. There is no data about CD226 variants in the very heterogeneous Brazilian population bearing a wide degree of admixture. We investigated its association with T1D susceptibility, clinical phenotypes, and autoimmune manifestations (islet and extrapancreatic autoantibodies). Casuistry. 532 T1D patients and 594 controls in a case-control study. Initially, CD226 coding regions and boundaries were sequenced in a subset of 106 T1D patients and 102 controls. In a second step, two CD226 variants, rs763361 (exon 7) and rs727088 (3′ UTR region), involved with CD226 regulation, were genotyped in the entire cohort. C-peptide and autoantibody levels were determined. No new polymorphic variant was found. The variants rs763361 and rs727088 were in strong linkage disequilibrium. The TT genotype of rs763361 was associated with TID risk (OR = 1.503;  95%  CI = 1.135–1.991; P = 0.0044), mainly in females (P = 0.0012), greater frequency of anti-GAD autoantibody (31.9% × 24.5%; OR = 1.57; CI = 1.136–2.194; P = 0.0081), and lower C-peptide levels when compared to those with TC + CC genotypes (0.41 ± 0.30 ng/dL versus 0.70 ± 0.53 ng/dL P = 0.0218). Conclusions. The rs763361 variant of CD226 gene (TT genotype) was associated with susceptibility to T1D and with the degree of aggressiveness of the disease in T1D patients from Brazil. Ancestry had no effect.

Short and Long Term Effects of a DPP-4 Inhibitor Versus Bedtime NPH Insulin as ADD-ON Therapy in Patients with Type 2 Diabetes

BACKGROUND We conducted a comparison between the dipeptidyl-peptidase-4(DPP-4) inhibitor sitagliptin versus NPH insulin as an add-on therapies in patients with type 2 diabetes mellitus (T2D) failing oral medications. The objective was to ascertain the better indication in long-duration diabetes. METHODS thirty-five T2D patients inadequately controlled with metformin plus glyburide were randomized to receive sitagliptin (n=18) or bedtime NPH insulin (n=17) for 12 months. HbA1c levels and a metabolic and hormonal profile at fasting and post-meal (every 30 minutes for 4 hours) were evaluated before and after 6 months (short-term) and 12 months (long-term) after adding sitagliptin or bedtime NPH insulin to their drug regime. RESULTS Sitagliptin and NPH insulin decreased HbA1c levels equally after 6 months (p<0.001) with no further improvement after 12 months: sitagliptin (8.1±0.7% vs. 7.3±0.8% vs. 7.4±1.9%) and insulin (8.1±0.6% vs. 7.3±0.7% vs. 7.2±1.0%). Fasting glucose, fasting and postprandial triglyceride and C-peptide levels were also reduced by NPH insulin whereas postprandial insulin was decreased by sitagliptin. Body weight and postchallenge free fatty acid levels increased with insulin treatment. The transitory suppression (at 6 months) of postprandial proinsulin levels with both therapies, and of glucagon with sitagliptin, was followed by values similar or worse to those at pre-treatment. CONCLUSION The use of either NPH insulin or a DPP-4 inhibitor as add-on treatments improves glucose control in patients with T2D failing on metformin plus glyburide therapy. The results were not attributed to a permanent improvement in alpha or beta cell function in patients with long-duration diabetes.