Non-Alcoholic Fatty Liver Disease in Long-Term Type 2 Diabetes: Role of rs738409 PNPLA3 and rs499765 FGF21 Polymorphisms and Serum Biomarkers.

Fibroblast growth factor 21 (FGF21) signaling and genetic factors are involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. However, these factors have rarely been studied in type 2 diabetes mellitus (T2D) patients from admixed populations such as in those of Brazil. Therefore, we aimed to evaluate rs738409 patanin-like phospholipase domain-containing protein (PNPLA3) and rs499765 FGF21 polymorphisms in T2D, and their association with NAFLD, liver fibrosis, and serum biomarkers (FGF21 and cytokeratin 18 levels). A total of 158 patients were included, and the frequency of NAFLD was 88.6%, which was independently associated with elevated body mass index. Significant liver fibrosis (≥F2) was detected by transient elastography (TE) in 26.8% of NAFLD patients, and was independently associated with obesity, low density lipoprotein, and gamma-glutamyl transferase (GGT). PNPLA3 GG genotype and GGT were independently associated with cirrhosis. PNPLA3 GG genotype patients had higher GGT and AST levels; PNPLA3 GG carriers had higher TE values than CG patients, and FGF21 CG genotype patients showed lower gamma-GT values than CC patients. No differences were found in serum values of FGF21 and CK18 in relation to the presence of NAFLD or liver fibrosis. The proportion of NAFLD patients with liver fibrosis was relevant in the present admixed T2D population, and was associated with PNPLA3 polymorphisms.

Baseline characteristics and risk factors for ulcer, amputation and severe neuropathy in diabetic foot at risk: the BRAZUPA study.

BACKGROUND: Studies on diabetic foot and its complications involving a significant and representative sample of patients in South American countries are scarce. The main objective of this study was to acquire clinical and epidemiological data on a large cohort of diabetic patients from 19 centers from Brazil and focus on factors that could be associated with the risk of ulcer and amputation. METHODS: This study presents cross sectional, baseline results of the BRAZUPA Study. A total of 1455 patients were included. Parameters recorded included age, gender, ethnicity, diabetes and comorbidity-related records, previous ulcer or amputation, clinical symptomatic score, foot classification and microvascular complications. RESULTS: Patients with ulcer had longer disease duration (17.2 ± 9.9 vs. 13.2 ± 9.4 years; p < 0.001), and poorer glycemic control (HbA1c 9.23 ± 2.03 vs. 8.35 ± 1.99; p < 0.001). Independent risk factors for ulcer were male gender (OR 1.71; 95 % CI 1.2-3.7), smoking (OR 1.78; 95 % CI 1.09-2.89), neuroischemic foot (OR 20.34; 95 % CI 9.31-44.38), region of origin (higher risk for those from developed regions, OR 2.39; 95 % CI 1.47-3.87), presence of retinopathy (OR 1.68; 95 % CI 1.08-2.62) and absence of vibratory sensation (OR 7.95; 95 % CI 4.65-13.59). Risk factors for amputation were male gender (OR 2.12; 95 % CI 1.2-3.73), type 2 diabetes (OR 3.33; 95 % CI 1.01-11.1), foot at risk classification (higher risk for ischemic foot, OR 19.63; 95 % CI 3.43-112.5), hypertension (lower risk, OR 0.3; 95 % CI 0.14-0.63), region of origin (South/Southeast, OR 2.2; 95 % CI 1.1-4.42), previous history of ulcer (OR 9.66; 95 % CI 4.67-19.98) and altered vibratory sensation (OR 3.46; 95 % CI 1.64-7.33). There was no association between either outcome and ethnicity. CONCLUSIONS: Ulcer and amputation rates were high. Age at presentation was low and patients with ulcer presented a higher prevalence of neuropathy compared to ischemic foot at risk. Ischemic disease was more associated with amputations. Ethnical differences were not of great importance in a miscegenated population.

Cintilografia de perfusão miocárdica na detecção da isquemia silenciosa em pacientes diabéticos assintomáticos / Myocardial perfusion scintigraphy in the detection of silent ischemia in asymptomatic diabetic patients

OBJECTIVE: This study was aimed to evaluate myocardial perfusion in asymptomatic patients with type 1 (DM1) and type 2 diabetes mellitus (DM2) without previous diagnoses of coronary artery disease (CAD) or cerebral infarction. MATERIALS AND METHODS: Fifty-nine consecutive asymptomatic patients (16 DM1, 43 DM2) underwent myocardial perfusion scintigraphy with 99mTc-sestamibi (MPS). They were evaluated for body mass index, metabolic control of DM, type of therapy, systemic arterial hypertension, dyslipidemia, nephropathy, retinopathy, peripheral neuropathy, smoking, and familial history of CAD. RESULTS: MPS was abnormal in 15 patients (25.4%): 12 (20.3%) with perfusion abnormalities, and 3 with isolated left ventricular dysfunction. The strongest predictors for abnormal myocardial perfusion were: age 60 years and above (p = 0.017; odds ratio [OR] = 6.0), peripheral neuropathy (p = 0.028; OR = 6.1), nephropathy (p = 0.031; OR = 5.6), and stress ECG positive for ischemia (p = 0.049; OR = 4.08). CONCLUSION: Silent myocardial ischemia occurs in more than one in five asymptomatic diabetic patients. The strongest predictors of ischemia in this study were: patient age, peripheral neuropathy, nephropathy, retinopathy and a stress ECG positive for ischemia.

OBJETIVO: Este estudo teve por finalidade avaliar a perfusão miocárdica de pacientes com diabetes mellitus tipo 1 (DM1) e tipo 2 (DM2) assintomáticos, sem diagnóstico prévio de doença arterial coronariana (DAC) ou acidente vascular cerebral. MATERIAIS E MÉTODOS: Cinquenta e nove pacientes consecutivos (16 DM1, 43 DM2) foram submetidos a cintilografia de perfusão miocárdica com sestamibi-99mTc (CPM). Foram avaliados quanto ao índice de massa corpórea, controle metabólico do diabetes, dislipidemia, terapia para o diabetes, hipertensão arterial sistêmica, nefropatia, retinopatia, neuropatia periférica, tabagismo e história familiar de DAC. RESULTADOS: CPM foi anormal em 25,4%: 12 (20,3%) com alterações de perfusão e 3 com disfunção ventricular esquerda isolada. Os mais fortes preditores de perfusão miocárdica anormal foram: idade igual ou maior a 60 anos (p = 0,017, odds ratio [OR] = 6,0), neuropatia periférica (p = 0,028, OR = 6,1), nefropatia (p = 0,031, OR = 5,6) e ECG de esforço positivo para isquemia (p = 0,049, OR = 4,08). CONCLUSÃO: A isquemia miocárdica silenciosa ocorre em mais de um em cada cinco diabéticos assintomáticos. Os mais fortes preditores de isquemia foram: idade avançada, neuropatia periférica, nefropatia, retinopatia e ECG de esforço positivo para isquemia.

Comparison of three systems of classification in predicting the outcome of diabetic foot ulcers in a Brazilian population.

OBJECTIVE: The aim was to compare three ulcer classification systems as predictors of the outcome of diabetic foot ulcers: the Wagner, the University of Texas (UT) and the size (area, depth), sepsis, arteriopathy, denervation system (S(AD)SAD) systems in a specialist clinic in Brazil. METHODS: Ulcer area, depth, appearance, infection and associated ischaemia and neuropathy were recorded in a consecutive series of 94 subjects. A novel score, the S(AD)SAD score, was derived from the sum of individual items of the S(AD)SAD system, and was evaluated. Follow-up was for at least 6 months. The primary outcome measure was the incidence of healing. RESULTS: Mean age was 57.6 years; 57 (60.6%) were male. Forty-eight ulcers (51.1%) healed without surgery; 11 (12.2%) subjects underwent minor amputation. Significant differences in terms of healing were observed for depth (P=0.002), infection (P=0.006) and denervation (P=0.002) using the S(AD)SAD system, for UT grade (P=0.002) and stage (P=0.032) and for Wagner grades (P=0.002). Ulcers with an S(AD)SAD score of or=10 (P<0.001). CONCLUSIONS: All three systems predicted ulcer outcome. The S(AD)SAD score of ulcer severity could represent a useful addition to routine clinical practice. The association between outcome and ulcer depth confirms earlier reports. The association with infection was stronger than that reported from the centres in Europe or North America. The very strong association with neuropathy has only previously been observed in Tanzania. Studies designed to compare the outcome in different countries should adopt systems of classification, which are valid for the populations studied.