Maria Mota

Association of SGK1 gene polymorphisms with type 2 diabetes.

The serum and glucocorticoid inducible kinase SGK1 is genomically upregulated by glucocorticoids and in turn stimulates a variety of carriers and channels including the renal epithelial Na+ channel ENaC and the intestinal Na+ glucose transporter SGLT1. Twin studies disclosed an association of a specific SGK1 haplotype with moderately enhanced blood pressure in individuals who are carrying simultaneously a homozygous genotype for a variant in intron 6 [I6CC] and a homozygous or heterozygous genotype for the C allele of a polymorphism in exon 8 [E8CC/CT] of the SGK1 gene. A subsequent study confirmed the impact of this risk haplotype on blood pressure. SGK1 knockout mice are resistant to the insulin and high salt induced increase of blood pressure, glucocorticoid induced increase of electrogenic glucose transport, and glucocorticoid induced suppression of insulin release. The present study explored whether the I6CC/E8CC/CT haplotype impacts on the prevalence of type 2 diabetes. The prevalence of the I6CC genotype was 3.1% in a healthy German, 2.4 % in a healthy Romanian and 11.6 % in a healthy African population from Ghana (p=0.0006 versus prevalence in Caucasians). Comparison of genotype frequencies between type 2 diabetic patients and the respective control groups revealed significant differences for the intron 6 T>C variant. Carriers of at least one T allele were protected against type 2 diabetes (Romanians: p=0.023; OR 0.29; 95% CI 0.09-0.89; Germans: p=0.01; OR 0.37; 95% CI 0.17-0.81). The SGK1 risk haplotype (I6CC/E8CC/CT) was significantly (p=0.032; OR 4.31, 95% CI 1.19-15.58) more frequent in diabetic patients (7.2 %) than in healthy volunteers from Romania (1.8%). The observations support the view that SGK-1 may participate in the pathogenesis of metabolic syndrome.

Prevalence of diabetes mellitus and prediabetes in the adult Romanian population: PREDATORR study†

The PREDATORR (PREvalence of DiAbeTes mellitus, prediabetes, overweight, Obesity, dyslipidemia, hyperuricemia and chronic kidney disease in Romania) study is the first national study analyzing the prevalence of diabetes mellitus (DM) and prediabetes, and their association with cardiometabolic, sociodemographic, and lifestyle risk factors in the Romanian population aged 20–79 years.

Insulin resistance is associated with all chronic complications in type 1 diabetes.

Insulin resistance (IR) is present in type 1 diabetes mellitus (T1DM) and is suggested to be related to chronic diabetic complications. The primary aim of our study was to assess IR in T1DM patients with and without chronic complications. A secondary aim was to evaluate the possible association between IR and chronic diabetic complications.

WRIST CIRCUMFERENCE: AN INDEPENDENT PREDICTOR OF BOTH INSULIN RESISTANCE AND CHRONIC KIDNEY DISEASE IN AN ELDERLY POPULATION

Abstract Background and aim: It was recently reported that wrist circumference is associated with insulin resistance (IR) both in children and adults. We aimed to evaluate whether wrist circumference is a useful anthropometrical parameter for the evaluation of IR in an elderly population. Material and method: We performed a study on 40 subjects, 20 with type 2 diabetes (T2D) and 20 control subjects. IR was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). We measured the following anthropometrical parameters: weight, height, waist circumference (WC), hip circumference, wrist circumference, waist to hip ratio (WHR), waist to height ratio (WHtR), body mass index (BMI) and body adiposity index (BAI). Results: We found statistically significant differences between the subjects with T2D and the control group for all the analyzed parameters. Statistically significant correlations between all the anthropometrical parameters and HOMA-IR were observed. However, only WC was an independent predictor of IR. Wrist circumference was the only parameter negatively correlated with the estimated glomerular filtration rate (eGFR). Furthermore, this measurement was an independent predictor of chronic kidney disease (CKD) in the studied subjects. Conclusion: Wrist circumference can be used in the general practice as a surrogate marker of IR in the elderly, being both easily determined and a cost-free method

The Analysis of Prevalence and Incidence of Diabetes Mellitus in Romania

Abstract Background and Aims Diabetes mellitus (DM) represents a worldwide health problem and a major epidemic during the past decades. The exact number of people with diabetes in Romania is unknown. The aim of this paper was to determine the number of subjects registered with diabetes in Romania. Material and Method: The Romanian Society of Diabetes, Nutrition and Metabolic Diseases (RSDNMD) asked the representatives in charge with DM in each county about the total number of subjects registered with DM, the number of subjects with newly diagnosed DM in 2011 and their treatment (insulin or oral drugs). Results: There are 803,489 persons registered with DM, with a national prevalence of 4.21%. The lowest prevalence was observed in Ilfov (0.9%) and the highest prevalence (7.83%) in Bucharest. A total of 125,574 diabetics (15.62%) are treated only with insulin while 81,910 (10.19%) with combined insulin and oral medication. In 2011 have been registered 68.294 new cases of diabetes, with an incidence of 358.63/100,000 persons. The lowest incidence was 91.15 in Giurgiu county and the highest incidence was 718.94 in Arad county. Conclusions: There are large and unexplained differences between counties for both diabetes prevalence and incidence. Consequently, RSDNMD decided to start a national epidemiological study (PREDATORR) that will be carried out in 2013.

Type 2 Diabetes and its Implications in Cerebrovascular Disease

Type 2 Diabetes and its Implications in Cerebrovascular Disease Type 2 diabetes represents an independent risk factor for vascular cerebral pathology, with a 2-3 times greater probability of stroke. The number of diabetic patients with stroke increased substantially from 6.2% to 11.3% during 1996-2006. Ischemic stroke, small or large vessels occlusion, is the main subtype of cerebrovascular disease, while a smaller percentage is attributed to cerebral hemorrhage. Hyperglycemia and hyperinsulinemia, excess free fatty acids, prothrombotic state cause endothelial dysfunction with blood flow disturbance and major cerebral vessels injury. Elevated blood sugar levels are also associated with a poor prognosis during post-stroke phase. From the total number of deaths caused by acute cerebrovascular events, 16% for men and 33% for women are due to diabetes.

The role of the central nervous system in glucose homeostasis

Abstract Central nervous system, mainly the hypothalamus and the brainstem are important keys in glucose homeostasis. Not only do they use glucose as primary fuel for their functioning but they are part of intricate neuronal circuits involved in glucose uptake and production as was first shown by Claude Bernard. Moreover electrophysiological analysis of hypothalamus revealed the existence of glucosensing neurons whose firing rates are controlled by glucose extracellular level. Further information was obtained regarding the importance of leptin, insulin and free fatty acids as afferent signals received by these neural structures. As for the main efferent pathways, autonomic system is the one connecting CNS with the effector organs (the liver, the pancreas and the adrenal glands).

Beta-Cell Function and Failure in Type 2 Diabetes

The main role of beta-cell is to synthesize and secrete insulin in order to maintain circulating glucose levels within physiological range. Although there exist several triggers of insulin secretion like nutrients (amino acids such as leucine, glutamine in combination with leucine, nonesterified fatty acid), hormones, neurotransmitters and drugs (sulfonylurea, glinides), glucose represents the main physiological insulin secretagogue [1].

Elevated 1 Hour Glucose During Oral Glucose Tolerance Test- A New Parameter of Impaired Metabolism

Abstract Background and aims: Recently, large scale studies emphasized the idea of an excess of metabolic and cardiovascular risk in patients currently considered to have normal glucose tolerance but showing an elevated 1 hour glucose (≥155mg/dl) during oral glucose tolerance test (OGTT). Material and Methods: 75 subjects with normal glucose tolerance or impaired glucose tolerance were completely investigated. We evaluated the clinical and biological markers associated to insulin resistance and we calculated the cardiovascular risk of the subjects using the SCORE charts. Results and Discussions: Our data found statistically significant correlations between subjects with normal glucose tolerance and elevated 1 hour glucose and the following markers of insulin resistance: triglycerides to HDL-cholesterol ratio (TG/HDL-chol), Homeostatic Model Assessment (HOMA-IR), The Quantitative Insulin Sensitivity Check Index (QUICKI), fasting insulin, fasting glucose to fasting insulin ratio. Also, the subjects with elevated 1 hour glucose had a greater cardiovascular risk compared to subjects with 1 hour glucose <155 mg/dl. Conclusions: This study identifies a category of subjects currently considered as normal glucose-tolerant individuals but with a special metabolic profile, an increased cardiovascular risk and an increased risk of developing diabetes.

Relationship between urinary metabolites and type 2 diabetes mellitus by proton nuclear magnetic resonance spectroscopy method (1H-NMR)

Control Group: 334 individuals (161 males, 173 females), averaged age of 38.3 years, ranging between 23-67 years old, without metabolic diseases such as diabetes, hypertension, urinary infection, clinical evidence of renal disease; without alcohol consumption for 24 h before sampling, in condition of no drugs administration. Biochemical determinations in Control Group: Urine Uro, Bil, Ket, pH, SG, Leu, Blood, Nitrite, Ascorbic Acid, Glu, Pro. Type 2 DM Group: 388 patients (173 males, 215 females), averaged age 55, ranging between 34-75 years old. The patients had a history of type 2 DM less than 5 years and were hospitalized in Craiova County Emergency Clinical Hospital, Department of Diabetes, Nutrition and Metabolic Diseases. Biochemical determinations in type 2 DM patients: Blood: urea (33.9±8.69 mg/dl), creatinine (0.84±0.14 mg/dl), fasting glycemia (179±54 mg/dl) and Glomerular Filtration Rate (eGFR)=101.56±9.55 ml/min/1.73m2. Urine Uro, Bil, Ket, pH, SG, Leu, Blood, Nitrite, Ascorbic Acid, Glu, Pro, Creatinine (154.14±32.05 mg/dl). Nuclear Magnetic Resonance Spectroscopy Method: NMR spectra recorded with 10 % D2O and 5 mM sodium 3-(trimethylsilyl)-[2,2,3,3-d4 ]-1-propionate (TSP) at 400 MHz Brucker Avance DRX spectrometer, in 5 mm NMR tubes, with 32 scans, and water presaturation. Statistical analysis: The data were calculated using Graph Pad Prism 5.0 and were given as mean±SD; P<0.05 was taken as significant. The results are evaluated in mmol/mol of Creatinine.