Dijabetes melitus je kompleksan metabolički poremećaj u čijoj je osnovi deficit funkcije insulina i/ili produkcije in- sulina, koja je definisana kao nivo glikemije > 6,1 mmol/L. Etiološka klasifikacija dijabetesa od strane Svetske zdravs- tvene organizacije (SZO) prepoznaje više tipova ove bolesti, od kojih su najčešći dijabetes tip 1 (autoimuna bolest koja dovodi do destrukcije beta ćelija pankreasa i gubitka produk- cije i sekrecije insulina) i DMT2, kome pripada 85–90% bo- lesnika sa ovom bolesti. DMT2 najčešće se javlja posle 40. godine života, a najveća incidencija je oko 60. godine života. DMT2 je praćen funkcionalnom nesposobnošću i smanje- njem kvaliteta života. Patogeneza DMT2 uključuje različite nivoe insulinske rezistencije, poremećaj funkcije beta ćelija pankreasa i deficit sekrecije insulina. DMT2 dovodi do dis- funkcija multiplih organa ili tkiva, mikrovaskularnih (poli- neuropatija, retinopatija i nefropatija) i makrovaskularnih (kardiovaskularne bolesti) komplikacija. Istraživanja su po- kazala da je DMT2 poligenski poremaćaj, na čiji nastanak i ekspresiju značajan doprinos imaju faktori sredine. Abdomi- nalna gojaznost, povećanje indeksa telesne mase (odnos iz- među telesne mase u kilogramima i visine tela u metrima na kvadrat) (ITM) i fizička neaktivnost su najznačajnije deter- minante za razvoj DMT2. Kod oko 50% osoba, DMT2 ostaje neotkriven 2 .
The metabolic syndrome (MetS) involves a group ofriskfactorsand is associated with a significantly higher riskof developing cardiovascular diseases (CVD) andtype2diabetes. Recent studies have shown the importance of preventing CVD through early diagnosis and treatment of patients with MetS. The objective of our study was to determine the prevalence of MetS by different diagnostic criteria in postmenopausal women and analyze the influence of socioeconomic factors on cardiovascular risk in this sample of the population. A cross-sectional study involving 127 postmenopausal women (45 to 64 years) from Natal and Mossoró, Brazil. The study was approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte. The experimental protocol consisted of applying structured interview, clinical examination and implementation of dosages blood. The diagnosis of MetS was based on NCEP-ATP III (National Cholesterol Education Program-Adult Treatment Panel III) and IDF (International Diabetes Federation) criteria. The research was accomplished with the participation of an interdisciplinary team in their several phases. The result of the sample studied had mean age of 53.9 ± 4.6 years and per capita income of 54.5 dollars. The prevalence of MetS, according to NCEP-ATP III and IDF criteria, was 52.8% and 61.4$, respectively. The agreement rate between NCEP-ATP III and IDF criteria was 81.9%, with a kappa value of 0.63 (CI 95%, 0.49-0.76), indicating good agreement between the two definitions. The most prevalent cardiovascular risk factor was HDL < 50 mg/dl, observed in 96.1% of the women analyzed, followed by increased waist circumference ( 80 cm) in 78.0%, elevated blood pressure in 51.2%, triglycerides 150 mg/dl in 40.9% and glycemia 100 mg/dl in 37.0% of the women. The occurrence of MetS was significantly associated with schooling and body mass index (BMI). High blood pressure was significantly associated with low family income, low schooling and weight gain. There was no significant association between the intensity of climacteric symptomatology and the occurrence of MetS. The conclusions of the research were that MetS and its individual components show a high prevalence in postmenopausal Brazilian women, and significant associations with weight gain and low socioeconomic indicators. The data point to the need for an interdisciplinary approach at the basic health care level, directed toward the early identification ofriskfactorsand the promotion of cardiovascular health of climacteric women.
Electronic medical health systems have made chronic diseases like diabetes mellitus easier to monitor and understand through large data base registries. Diabetes Registry is gaining popularity nowadays as a result of its advantages in collecting and characterizing data about the disease for clinicaland scientific studies. The prevalence ofdiabetes is increasing globally as a result of urbanization, human aging and lifestyle changes. Diabetes registries track this disease behavior, and provide a better understanding of its clinical, social, cultural and economic impact. Disease registries not only improve perception of the disease, but help in the health planning and assessment of health care quality. They are considered to be a reliable source of epidemiology data that serve to highlight both morbidity and mortality from such
Diabetes mellitus (DM) and osteoporosis are the two important public health problems in India. The burden of both these conditions is expected to increase in the near future in view of changing lifestyle habits and ageing population. Indians are at riskof osteoporosis due to their low body mass index (BMI), genetic predisposition and nutritional factors. The diseases type 1 DM andtype2 DM (T2DM) are associated with increased fracture risk in the disease population, in spite of difference in the bone mineral density (BMD). An increase in fracture risk is also reported among older patients with T2DM despite frequently reported normal or increased BMD. Administration of insulin stimulates osteoblast activity and bone mineral apposition rates. The impact of endogenous insulin production, insulin sensitivity, and exogenous insulin administration as an anabolic agent for bone in T2DM has not been clarified. Biguanides and sulphonylureas do not appear to have adverse effects on BMD. Preclinical evidence suggests that incretin-based drugs may be beneficial for bone, but clinical evidence to support this hypothesis is not yet available. Thiazolidinedione (TZD) group of agents have been implicated in causing osteoporosis in various animal studies and some human studies available till date. The debate regarding this is issue is still ongoing. Randomized controlled studies with larger sample size preferably involving multiple centres, multiple ethnicities are required to answer these queries.
Summary of the findings: The metabolic syndrome is characterized by insulin resistance and the presence ofriskfactors for cardiovascular diseases anddiabetes mellitus type2. Consensus has not yet been reached on its diagnostic criteria. This review presents diagnostic criteria defined by the American Heart Association (US National Cholesterol Education Program), the American Association ofClinical Endocrinologists, the World Health Organization and the International Diabetes Federation and discusses the possibilities of applying them to children. Pathophysi- ologic features of the syndrome are also covered, principally those related to the perinatal period and childhood.
More than 40 genetic susceptibility loci have been reported for type2diabetes (T2D). Recently, the combined effect of genetic variants has been investigated by calculating a genetic risk score. We evaluated 36 genome-wide association study (GWAS) identified SNPs in 2,679 T2D cases and 3322 controls in middle-age Han Chinese. Fourteen SNPs were significantly associated with T2D in analysis adjusted for age, sex and BMI. We calculated two genetic risk scores (GRS) (GRS1 with all the 36 SNPs and GRS2 with the 14 SNPs significantly associated with T2D). The odds ratio for T2D with each GRS point (per risk allele) was 1.08 (95% CI: 1.06–1.09) for GRS1 and 1.15 (95% CI: 1.13–1.18) for GRS2. The OR for quintiles were 1.00, 1.26, 1.69, 1.95 and 2.18 (P,0.0001) for GRS1 and 1.00, 1.33, 1.60, 2.03 and 2.80 (P,0.001) for GRS2. Participants in the higher tertile of GRS1 and the higher BMI category had a higher riskof T2D compared to those on the lower tertiles of the GRS1 andof BMI (OR = 11.08; 95% CI: 7.39–16.62). We found similar results when we investigated joint effects between GRS1 and WHR terciles and exercise participation. We finally investigated the joint effect between tertiles of GRSs and a composite high risk score (no exercise participation and high BMI and WHR) on T2D risk. We found that compared to participants with low GRS1 and no high riskfactors for T2D, those with high GRS1 and three high riskfactors had a higher riskof T2D (OR = 13.06; 95% CI: 8.65–19.72) but the interaction factor was of marginal significance. The association was accentuated when we repeated analysis with the GRS2. In conclusion we found an association between GRS and lifestyle factors, alone and in combination, contributed to the riskofand T2D among middle age Chinese.
Advances in genetic discovery coupled with the decreasing costs of sequencing an individual’s entire genome have set the stage for personalized medicine to improve health outcomes. There is a small and growing group of physicians who constitute ‘early adopters’ of this source of informa- tion who have begun integrating patient’s genetic information into their clinical care. Further work is needed to make genetic testing for T2D useful for widespread use by primary care provid- ers. An expanding number of alleles associated with the risk for T2D requires more discovery research to determine the individual and combined contribution of these SNPs on disease sub- types, T2D initiation and outcomes. In advance of refined prediction, it is possible that T2D genetic risk testing may have the most utility in high-risk patient groups. T2D genetic risk testing may also evolve for use as an intervention early in life to prevent the onset of the riskfactors (i.e. weight, dietary and physical activity behaviors) or to tailor prevention and treatment options to the individual. Research is needed to develop and test the efficacy and effectiveness of this work with the goal of reducing the overall burden of T2D in the general population.
The computer package IBM SPSS Statistics 19 (IBM Corpo- ration, Armonk, New York, United States) was used for statistical analysis. Data are presented as proportions, mean6SD, geometric mean (SD range), or, in the case of variables which did not conform to a normal or log-normal distribution, median [inter- quartile range, IQR]. For independent samples, two-way com- parisons for proportions were by Fisher’s exact test, for normally distributed variables by Student’s t-test, and for non-normally distributed variables by Mann-Whitney U-test. Multiple compar- isons were by Fisher’s exact or chi-squared tests for proportions, one-way ANOVA for normally-distributed variables, and the Kruskal-Wallis test for non-normally distributed variables. To further examine differences between groups 1 and2, a nested case- control study was conducted with each group 2 case matched by age, sex anddiabetes duration to a control from group 1 in a 1:1 ratio. A two-tailed significance level of P,0.05 was used throughout.
Table S5 Association of rs3737884 and rs16850797 with diseases in three types of genetic models. CAD, coronary artery disease; T2D, type2diabetes; T2D+CAD: T2D with CAD; OR, odds ratios; CI, confidence interval. All OR and P values are obtained by Pearson’s x 2 or unconditional logistic regression and adjusted for gender, age and body mass index. All variants with nominal significance (P #0.05) are listed; the threshold for significance by Bonferroni correction is 0.05/3 = 0.017 (three independent hypotheses: T2D vs. Control, CAD vs. Control, T2D with CAD vs. Control).*P value that can pass multiple testing correction (P #0.017); E indicates the power of the base-10 exponent (i.e. 9.80E-05 = 9.80610 25 ). The df of a per-allele OR value is 2 in the additive genetic model analysis. ORs are computed using wild homozygous carriers of variant as the reference group in the dominance model analysis and non-risk homozygous carriers of variant as the reference group in the recessive model. The risk alleles are rs3737884, G and rs16850797, C, respectively.
Although the link between DM2 and carcinogenesis was first reported in 1910 by Maynard and Pearson (1910 apud Wojciechowska, 2016) (10), it was over 100 years later that the American Diabetes Association (ADA) and American Society ofClinical Oncology (ASCO) presented their consensus on the factors that link diabetesand cancer (10,12). Notably, DM2 and cancer share many riskfactors, especially obesity (12), and DM2 and malignancies are correlated through several conditions, such as hyperinsulinemia (due to resistance to endogenous or exogenous insulin), hyperglycemia, and chronic inflammation due to overweight and body fat mass (10,12). Adiposity has been correlated with an increased riskof several cancers, including breast, endometrial, pancreatic, and colon cancer. In addition, obese men and women with esophageal, gallbladder, colorectal, pancreatic, liver, and kidney cancer have an elevated riskof cancer-related deaths (Table 1) (13). Notably, BMI consistently has a moderate but direct effect on the rates andriskof death due to lymphoma and MM and is associate with an increased riskof leukemia in adults (Table 2) andof monoclonal gammopathy of uncertain significance (MGUS) transforming into MM (3,6-8,3-26).
Diabetic retinopathy (DR) is an important cause of acquired blindness among diabetics. Clinicalfactors are related to the risk for DR, in addition, genetic markers have been investigated, among them VDR and MTHFR polymorphisms, however, the impact of rs1801131 and rs1801133 polymorphisms is still inconclusive, while for rs1544410 there is a shortage in the literature. In this work the relationship of polymorphisms rs1544410, rs1801131 and rs1801133 with DR was investigated by cross-sectional study in a sample of 109 individuals with type2diabetes (T2DM) duration between 5 and 10 years. After ophthalmological screening a group of 40 affected and 69 unaffected by DR was composed. Genomic DNA was extracted from buccal cells. Genetic data were obtained by PCR-RFLP and analyzed using Fisher's exact test. Blood sample and urine for metabolic markers determinations were obtained in 62 subjects and the mean values were compared to the allele and genotype distribution of rs1544410. There was no association between alleles or genotypes of polymorphisms rs1801131 and rs1801133 with RD. The polymorphic allele b and genotypic group Bb + bb of rs1544410 were more frequent in the affected group with mild significance: [OR 0.5 (95% CI 0.31- 0.98) p = 0.0478] and [OR 3.4 (95% CI 1.07-10.9) p = 0.496], respectively. None of the clinical variables were associated with rs1544410 although a trend towards higher values of C-reactive protein in patients allele b has been identified but not statistically significant. In conclusion, this study suggests that the sample investigated rs1544410 polymorphism of the VDR was related to the riskof DR, but not rs1801131 and rs1801133 MTHFR polymorphisms.
In the present study, some limitations must be taken into account. The cross-sectional design of the study makes it impossible to determine cause and effect between the exploratory variables and the outcome. Based on the results obtained, the possibility of reverse causality, characteristic in cross-sectional studies, is highlighted. Another factor to consider is the possibility of memory bias in the collection of some information, which is attenuated by the common characteristic of RA being a chronic illness. Finally, the self- reported data on comorbidities have not been confirmed by a physician. On the other hand, health surveys reveal that the information obtained on the prevalence of chronic dis- eases presents good agreement, when compared to medical records or clinical exams, especially for some chronic diseases such as hypertension anddiabetes mellitus (DM). 38,39 It should
syndrome (Romano-Ward syndrome). It is expressed in the pancreatic islet cells as well as the heart and encodes a protein which combines with KCNE proteins to form voltage charged potassium channels found in the membranes. The KCNQ1 proteins form the structure of the channel while the KCNE proteins regulate the activity of the channel . Pancreatic beta cell survival rate is thought to be affected by these potassium channels. It is thought that dysfunc- tion of these potassium channels could alter cell membrane potential and contribute to devel- opment of T2D or NODAT. A specific KCNQ1 blocker 293B has been shown to increase insulin production . The variant rs2237892 C risk allele has been shown to be associated with fasting plasma glucose concentration, suggesting that C homozygous individuals have impaired baseline insulin secretion. The gene is also under the control of tissue specific imprinting .
Diabetic retinopathy (DR) occurs in about 95% of patients with type 1 diabetes mellitus (DM) and in 60% oftype2 DM patients and it is the main cause of legal blindness in adult people. The aim of this manuscript was to review the main riskfactors for DR. The major environmental riskfactors are hyperglyce- mia, high blood pressure levels, and long-term duration of DM. However, not all patients will not develop DR, suggesting the presence of a genetic predis- position to DR, especially for severe forms of DR. Special strategies has been used to evaluate the genetic role in DR. Family studies shown that there is a familial aggregation of DR. Candidates genes have been studied (RAGE; VEGF; PPAR-δ; ICAM-1; ECA; ENPP 1; eNOS) and positive or negative associa- tions with DR were demonstrated. Some chromosomes were also associated to DR in selected populations. Finally, genetic expression studies reinforce the association of candidate genes, or participation of others genes, with the presence of DR. DR is a common complication of DM and, along with non- genetic or environmental riskfactors, the identification of genes related to DR could result in more specific and efficient DR treatment. (Arq Bras Endocri- nol Metab 2008; 52/3:431-441)
Several limitations of this study need to be outpoin- ted. All our patients were recruited from one primary care setting, and thus might not be representative of the general diabetic population in Portugal. The use of self- report data on medication adherence may have a ten- dency to overestimate adherence, due to recall biases and social desirability. Moreover, the exclusion of anal- phabet patients who were not accompanied by someone of their trust to help them answering the questionnaire may be an important bias. On the other hand, our sam- ple is based on the patients present in a primary care ap- pointment with their doctor. We notice a deviation in ge- neral characteristics from those we could expect from the diabetic population of an entire health center, but it does not seem to interfere in the conclusion about the
surface receptors that possess an intrinsic tyrosine kinase activity, called tyrosine kinase receptors. The InsR is composed by two extracellular α-subunits and two transmembrane β-subunits linked by disulfide bonds. When insulin is not present, the unbound extracellular α-subunits inhibit the intrinsic intracellular tyrosine kinase (White & Kahn, 1994). In contrast, when insulin binds to one of the α-subunits this inhibition is removed, and the adjacent intracellular β-subunit is autophosphorylated at its tyrosine residues of the regulatory domain (Lee et al., 1993). Subsequently, the autophosphorylation of the tyrosine residues allows the InsR to activate a panel of intracellular InsR substrate proteins (IRS) (Pessin & Saltiel, 2000; Sun et al., 1995; White, 1998). These IRS proteins act as InsR specific docking proteins that create recognition sites for additional effector molecules with Src homology (SCH) domains, such as the p85 regulatory subunit of the type 1A phosphatidylinositol 3-kinase (PI3K) (Pessin & Saltiel, 2000; Saltiel & Kahn, 2001). These IRS docking proteins serve multiple functions, as they allow the amplification of the InsR signal, the dissociation of the intracellular signaling cascade from the membrane bound InsR, to expand the number of pathways that can be regulated through one InsR, and the integration of multiple metabolic signals (Hotamisligil & Spiegelman, 1994; White & Kahn, 1994). The insulin signaling cascade encompasses several known downstream intermediates (Krüger et al., 2008) involved in three primary pathways: the PI3K – Akt/protein kinase B (PKB), the Cb1/CAP pathway, and the mitogen activated protein kinase (MAPK) cascade (Saltiel & Kahn, 2001) (Figure 1.4). The PI3K pathway appears to play the biggest role in the maintenance of the whole body glucose homeostasis. However, the MAPK and Cb1/CAP pathways are also of key importance for the maintenance of glucose homeostasis. The PI3K plays a significant role in many of the metabolic processes associated with insulin including: glucose uptake, growth factors, protein synthesis, and glycogen synthesis (White, 1998). Insulin stimulates glucose uptake via PI3K pathway through multiple steps including: activation of IRS by the InsR, binding of IRS to PI3K regulatory subunit p85, phosphorylation of phosphotidylinositol (3, 4,5) – triphosphate (PIP 3 ), activation of atypical protein kinase C (aPKC) and Akt through
current treatment results in clinical trials, is that complications are not prevented by glycemic control, intensive or not [5–7], confirmed by the latest very large trials of dipeptidyl peptidase-4 (DPP-4) inhibitors . Earlier evidence suggested that microvas- cular components were delayed more by lowered blood pressure [6,9–11] than by tight blood glucose control. The ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial reported no overall difference in microvascular outcomes in diabetic subjects at riskof cardiovascular events, and intensive glycemic treatment was associated with higher mortality . HMG CoA reductase inhibitors with its anti-flammatory and anti-thrombotic effects [13,14], have been used to target successfully total and LDL-cholesterol [15,16]. Despite such reductions, intriguingly statin treatment may marginally increase glycemia [17–19]. A second line of evidence is that the impaired blood vessel responsiveness is in both large arteries in vivo  and smaller arteries in tissue biopsy studies, which occurs even when blood glucose is normal . A third set of arguments, coupled to an extensive literature reviewed elsewhere, is that iron and copper dysregulation are implicated in diseases that manifest in changes in both lipid and carbohydrate metabolism (and their attendant co- morbidities) [21,22]
El objetivo de este estudio fue verificar los factores de riesgo de las complicaciones de la diabetes mellitus tipo 2, por medio del levantamiento de datos sociodemográficos, hábitos de salud, perfil antropométrico y bioquímico, de pacientes diabéticos tipo 2 atendidos en una Unidad Básica de Salud en la ciudad de Maringá, Paraná. Fueron entrevistados y evaluados 66 pacientes con más de 50 años; 56 eran del sexo femenino. Se verificó una elevada presencia de factores de riesgo cardiovascular en los pacientes investigados: sobrepeso y obesidad, hipertensión, dislipidemia, sedentarismo y dieta no saludable. Los resultados indican la necesidad de la implantación de programas de intervención multidisciplinares en unidades básicas de la salud asociada a prácticas educativas, estimulando la adopción de una dieta saludable y la práctica de actividad física regular para estos pacientes.
The aim of this study was to measure, in relation to depressive symptoms, the neuropsychological changes among individuals living with Type2diabetes mellitus (DM2) in Ghana. One hundred (100) participants comprising 50 patients with DM2 and 50 healthy controls matched on age and education were recruited. The raw scores were standardised into composite variables of executive function, learning/memory, visuoconstructional skills, visuospatial function and overall cognitive function. For all the neuropsychological domains, the diabetic group obtained significantly lower scores than the healthy control group. Depression was noted to have a negative relationship with all the neuropsychological domains. In addition, there was no significant difference between the depressed (diabetic and healthy control) subgroups on visuoconstructional skills. Likewise, there was no significant difference between the non-depressed (diabetic and healthy control) subgroups on visuospatial performance. These findings underscore the importance of early clinical neuropsychological assessment and further studies on DM2 neuropsychology.
Few studies have addressed the putative association between glucose abnormalities with NETs and the majority refers to pNETs. Diabetes is a hallmark of some rare functioning (RF) GEP-NET such as glucagonomas, vasoactive intestinal polypeptide secreting tumors (VIPomas), and somatostatinomas and is present in 70% of non-functioning pNETS . Moreover, hyperglycemia can also be a side effect of chemotherapy, SA, everolimus, and more recently PRRNT . Our results show that not only patients with pancreatic NETs but also GI-NETs especially small bowel have a higher prevalence of MetS and glucose metabolism abnormalities. The present study points to a strong association between all sites WD GEP-NETs and IFG even before the initiation of treatments that can cause altered glucose homeostasis. This association was not exclusive of pNETs since it was also found in GI-NETs. No RF GEP-NET characterized by hyperglycemia were included in this cohort. A strong association between diabetesand pNETs with an estimate effect of 2.76 (95% CI 1.65–4.64, p = 0.090) was formerly found in three case-control studies [24,25,29]. This effect was even higher in cases with recent onset diabetes (OR 12.80, 95%CI 2.47–66.42, p = 0.135) and insulin treated patients (OR 4.80, 95% CI 1.20–18.90). Two studies previously described the association between diabetesand tumors other than pNETs. In women with pre-existing T2DM, gastric endocrine tumors (especially T1-GET) and small bowel NETs were found to be increased seven-fold and two-fold, respectively . Increased prevalence of impaired glucose tolerance in patients with serotonin secreting metastatic NETs when compared to non-secreting tumors was initially reported in 1975 . Moreover, a recent publication from Valente et al. concluded that non-recent diabetes was associated with an increased occurrence of pNETs especially in metastatic disease and an advanced grade .