Starting Insulin Treatment in Type 2 Diabetes

Type 2 diabetes is a disorder of glucose metabolism characterized by chronic hyperglycemia. Initially type 2 diabetes is characterized by insulin resistance and impaired function of beta cells, leading progressively to insulin deficiency. Type 2 diabetes is treated with diet and other lifestyle changes, and with medication modulating e.g. insulin resistance, liver glucose production and insulin secretion. Injectable insulin is added to the treatment when lifestyle changes and other medication are insufficient to maintain adequate control of hyperglycemia. The aim of the treatment is to remove the symptoms of diabetes and to prevent late complications of diabetes. Insulin was traditionally started at hospital wards, but from the early 1990’s also in outpatient care. The first substudy of this thesis examined retrospectively initiation practices and how successfully insulin treatment was introduced in 1990 – 1996 in Southwestern Finland. This study aimed also at identifying the best methods of controlling plasma glucose. It showed that in the 1990’s the incidence of insulin treatment increased and was initiated more often in outpatient care than previously. The use of combination treatment also increased, first with sulfonylureas and later with metformin as the oral drug. In combination therapy the insulin dose was smaller than with insulin monotherapy. HbA1c improved similarly in middle-aged and older age groups. Weight increase associated with insulin initiation was smaller when combined with oral agents. A prospective insulin initiation study (1994 – 1998) tested the hypothesis that hyperglycemia (fasting and postprandial hyperglycemia) may affect the outcome of insulin initiation. The type of hyperglycemia was determined by the relation of fasting plasma glucose to HbA1c. Treatment was initiated with insulin Lente or human NPH insulin. In patients treated with insulin monotherapy twice daily the decline in HbA1c was markedly greater for postprandial than fasting hyperglycemia patients suggesting that hyperglycemia type has significance in the selection of the insulin regimen. Another insulin initiation study showed that patients with fasting hyperglycemia starting on insulin (2004-2005) were significantly more prone to overweight than patients with postprandial hyperglycemia. Irrespective of the insulin preparation (insulin NPH or insulin glargine), patients with fasting hyperglycemia had a greater weight increase compared to patients with postprandial hyperglycemia. Special attention should be paid to prevention of weight increase in these patients.

Prevalence of retinopathy in Caucasian type 2 diabetic patients from the South of Brazil and relationship with clinical and metabolic factors

Diabetic retinopathy (DR) is a sight-threatening chronic complication of diabetes mellitus and is the leading cause of acquired blindness in adults. In this cross-sectional study, we investigated the prevalence of and the factors associated with DR in an analysis of 210 consecutive and unrelated Brazilian Caucasians with type 2 diabetes mellitus. Retinopathy was evaluated by ophthalmoscopy and/or biomicroscopy through dilated pupils. The relationship between clinical and metabolic variables and the presence of DR was assessed by logistic regression analysis. DR was detected in 99 of the 210 patients (47%). In the univariate logistic regression analyses, male sex, duration of diabetes, body mass index, glycated hemoglobin, C-peptide, LDL cholesterol, smoking, and albumin excretion rate were found to be associated with the presence of DR. However, the multiple logistic regression analysis showed that only duration of diabetes (odds ratio (OR) = 1.15, 95% CI = 1.09-1.22; P < 0.001), glycated hemoglobin (OR = 1.21, 95% CI = 1.01-1.46; P = 0.047) and albumin excretion rate >100 µg/min (OR = 12.72, 95% CI = 3.89-41.56; P < 0.001) were independently associated with DR. Although DR was found to be frequent among Brazilian type 2 diabetic patients, its prevalence was within the range observed in other Caucasian populations. Our findings emphasize the need for good glycemic control in order to prevent or delay the onset of DR, since the most well-known risk factors for the development of this complication in type 2 diabetes mellitus, such as duration of diabetes, glycated hemoglobin and albumin excretion rate were independently related to DR.

Preclinical evaluation of the antidiabetic effect of Eugenia jambolana seed powder in streptozotocin-diabetic rats

The world is facing an explosive increase in the incidence of diabetes mellitus and cost-effective complementary therapies are needed. The effects of Eugenia jambolana, a household remedy for diabetes, were studied. Streptozotocin diabetic female albino Wistar rats weighing 150-200 g (N = 6) were fed E. jambolana seed powder (250, 500 or 1000 mg/kg) for 15 days. Diabetic rats fed 500 and 1000 mg/kg seed powder showed an increase in body weight on day 20 in relation to day 5 (6 ± 4.7, 9 ± 7.8 vs diabetic control -16 ± 7.1 g, P < 0.001), a decrease in fasting blood glucose (75 ± 11.9, 123 ± 14.4 vs diabetic control -34 ± 12.1 mg/dl, P < 0.001), a difference in post-treatment fasting and peak blood glucose (38 ± 11.9, 36 ± 14.2 vs diabetic control 78 ± 11.9 mg/dl, P < 0.001), and a difference in liver glycogen (50 ± 6.8, 52 ± 7.5 vs normal control 90 ± 6.6 µg/g of liver tissue, P < 0.001). Tri-terpenoids, tannins, gallic acid, and oxalic acid were the chemical constituents detected in E. jambolana seed. The best results were obtained with an oral dose of 500 mg/kg. Subacute toxicity studies with a single administration of 2.5 and 5.0 g/kg seed powder showed no mortality or abnormality. These data on the antidiabetic effect of E. jambolana seed are adequate for approval of phase 2 clinical trials to evaluate this seed powder as complementary therapy in type 2 and type 1 diabetes.

The clinical impact of MTHFR polymorphism on the vascular complications of sickle cell disease

Sickle cell disease (SCD) is one of the most common inherited diseases in the world and the patients present notorious clinical heterogeneity. It is known that patients with SCD present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises, but also during the steady state of the disease. We determined if the presence of the factor V gene G1691A mutation (factor V Leiden), the prothrombin gene G20210A variant, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may be risk factors for vascular complications in individuals with SCD. We studied 53 patients with SCD (60% being women), 29 with SS (sickle cell anemia; 28 years, range: 13-52 years) and 24 with SC (sickle-hemoglobin C disease; 38.5 years, range: 17-72 years) hemoglobinopathy. Factor V Leiden, MTHFR C677T polymorphism, and prothrombin G20210A variant were identified by PCR followed by further digestion of the PCR product with specific endonucleases. The following vascular complications were recorded: stroke, retinopathy, acute thoracic syndrome, and X-ray-documented avascular necrosis. Only one patient was heterozygous for factor V Leiden (1.8%) and there was no prothrombin G20210A variant. MTHFR 677TT polymorphism was detected in 1 patient (1.8%) and the heterozygous form 677TC was observed in 18 patients (34%, 9 with SS and 9 with SC disease), a prevalence similar to that reported by others. No association was detected between the presence of the MTHFR 677T allele and other genetic modulation factors, such as alpha-thalassemia, ß-globin gene haplotype and fetal hemoglobin. The presence of the MTHFR 677T allele was associated with the occurrence of vascular complications in SCD, although this association was not significant when each complication was considered separately. In conclusion, MTHFR C677T polymorphism might be a risk factor for vascular complications in SCD.

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.

Activation of endogenous angiotensin converting enzyme 2 prevents early injuries induced by hyperglycemia in rat retina

Diabetic retinopathy (DR) is a serious complication of diabetes mellitus that may result in blindness. We evaluated the effects of activation of endogenous angiotensin converting enzyme (ACE) 2 on the early stages of DR. Rats were administered an intravenous injection of streptozotocin to induce hyperglycemia. The ACE2 activator 1-[[2-(dimethylamino) ethyl] amino]-4-(hydroxymethyl)-7-[[(4-methylphenyl) sulfonyl] oxy]-9H-xanthone 9 (XNT) was administered by daily gavage. The death of retinal ganglion cells (RGC) was evaluated in histological sections, and retinal ACE2, caspase-3, and vascular endothelial growth factor (VEGF) expressions were analyzed by immunohistochemistry. XNT treatment increased ACE2 expression in retinas of hyperglycemic (HG) rats (control: 13.81±2.71 area%; HG: 14.29±4.30 area%; HG+XNT: 26.87±1.86 area%; P<0.05). Importantly, ACE2 activation significantly increased the RCG number in comparison with HG animals (control: 553.5±14.29; HG: 530.8±10.3 cells; HG+XNT: 575.3±16.5 cells; P<0.05). This effect was accompanied by a reduction in the expression of caspase-3 in RGC of the HG+XNT group when compared with untreated HG rats (control: 18.74±1.59; HG: 38.39±3.39 area%; HG+XNT: 27.83±2.80 area%; P<0.05). Treatment with XNT did not alter the VEGF expression in HG animals (P>0.05). Altogether, these findings indicate that activation of ACE2 reduced the death of retinal ganglion cells by apoptosis in HG rats.

The effect of a diet education with six iso-caloric meals on the body weight and blood glucose of diabetes type 2 patients

The treatment of Diabetes should not only be sought through drug administration; diet is also a part of its treatment. The aim of this study was to determine the effect of a diet with six meals having equal calories on the body weight and blood glucose on diabetes type 2 patients. This research is an Experimental study conducted in 2009 on 181 patients with diabetes. The patients visited the IDSF (Iranian Diabetes Society of Fars) weekly and the patients to be studied were randomly divided into two groups of 85 and 96 patients, respectively. The participants were repeatedly requested to consume their calculated calorie in six equal parts. The average age in the Experimental and Control groups were 51.2 ± 13.3 and 53.1 ± 9.4, respectively. The mean body weight and fasting blood glucose at the beginning of the study in Experimental and Control groups were 66.3 ± 9.4 and 69.1 ± 11.1 kg, 198.9 ± 35.1, and 199.8 ± 39.1 mg.dL-1, respectively. At the end of the study, however, the values were 63.5 ± 7.5 and 66.98 ± 9 kg, 139.5 ± 34.6 and 164.2 ± 22.1 mg.dL-1, respectively. Only the mean fasting blood glucose at the end of the study revealed a significant difference (p-value = 0.001). The results show that educating those afflicted with Diabetes Type 2 aiming at changing their diet can greatly help them manage their blood glucose.

Prevalência de diabetes mellitus em pacientes renais crônicos sob hemodiálise em Porto Alegre, Brasil

INTRODUÇÃO: A causa mais frequente de insuficiência renal crônica (IRC) nos pacientes iniciando tratamento dialítico nos países desenvolvidos é o diabetes mellitus (DM), com índices crescentes e que hoje se aproximam de 50%. No Brasil, os dados disponíveis indicam que essa prevalência é inferior, em torno de 27%, embora venha aumentando. OBJETIVOS: Estimar a prevalência de DM na população adulta de pacientes em tratamento hemodialítico por IRC em Porto Alegre, Brasil. MÉTODOS: Estudo transversal descritivo, quantitativo e analítico, com inquérito sobre a prevalência de DM entre os 1.288 pacientes em tratamento por hemodiálise (HD) crônica nas 15 clínicas do município nos meses de junho e julho de 2009. Resultados: 488 pacientes diabéticos foram identificados, uma prevalência de 37,9%, variando de 21 - 75% nas diferentes clínicas da cidade. CONCLUSÕES: A prevalência de DM entre pacientes em HD crônica em Porto Alegre é muito superior ao que tem sido atribuído como causa de IRC no país, o que indica a possibilidade de que essa etiologia de IRC possa estar sendo subestimada.

Computerized Tomography Contrast Induced Nephropathy (CIN) among adult inpatients

Introduction: Contrast induced nephropathy (CIN) is one of the complications of the use of intravascular contrast agents, being defined as a reduction of the glomerular filtration rate caused by the iodinated contrast. Most CIN data derive from the cardiovascular literature, which identified as the most consistent risk factors pre-existing chronic renal insufficiency and diabetes mellitus. However, these studies limit their conclusions to a more specific patient population. Computerized tomography as a cause of CIN has been studied less often. Objective: To report on the incidence of computerized tomography contrast induced nephropathy (CIN) in an inpatient population of a tertiary general hospital, identifying potentially avoidable risk factors. Methods: We performed a prospective cohort study with inpatients admitted at a tertiary hospital requiring contrast-induced CT. The primary outcome was the development of CIN, measure by the alteration of serum creatinine or glomerular filtration rate in 48 or 72 hours. Through clinical interview, we verified possible risk factors and preventive measures instituted by the medical team and their association with development of CIN. Results: Of a total of 410 patients, 35 (8.5%) developed CIN. There was a positive correlation between CIN and the presence of diabetes mellitus (OR = 2.15; 95%CI 1.35-4.06; p = 0.02), heart failure (OR = 2.23; 95%CI 1.18-8.8; p = 0.022), and renal failure (OR = 3.36; 95%CI 1.57- 7.17; p = 0.002) Conclusion: Incidence of CIN varies according to the population. Diabetes mellitus, heart failure and renal failure were independent risk factors for the development of CT-associated CIN. Further studies are needed to better understand and treat CT-associated CIN.

Cirurgia bariátrica e metabólica e complicações microvasculares do diabetes mellitus tipo 2 (DM2)

ResumoIntrodução:O diabetes mellitus tipo 2 (DM2) é caracterizado por uma desregulação metabólica, originando complicações microvasculares, mais especificamente a retinopatia, nefropatia e a neuropatia. A prevenção e tratamento das complicações são alvo da farmacoterapia, porém, evidências demonstram que a cirurgia bariátrica/metabólica é superior ao melhor tratamento farmacológico, pois apresenta melhor controle da glicemia, hipertensão e dislipidemias.Métodos:Por meio de pesquisa no PubMed, são discutidas as recentes publicações que evidenciam o efeito positivo das intervenções cirúrgicas sobre as complicações microvasculares, como melhora da microalbuminúria e mesmo preservação de função renal.Discussão:Existem evidências de benefício das operações bariátricas/metabólicas sobre a nefropatia diabética. Os dados sobre retinopatia são ainda ambivalentes. Na literatura, há uma diferença significativa no benefício da cirurgia em neuropatia.Conclusão:Apesar de resultados surpreendentes e positivos, para que se estabeleça definitivamente o papel da cirurgia bariátrica/metabólica nas complicações micovasculares do DM2, há a necessidade de novos estudos randomizados controlados e prospectivos.

Bearing-spesific complications of total hip arthroplasty: characterization and treatment

Hip resurfacing arthroplasty (HRA) and large head metal-on-metal total arthroplasty (LDH MoM THA) gained popularity during the last decade. Adverse reaction to metal debris (ARMD) is a unique complication of metal bearings. ARMD is a complex reaction caused by metal debris from metal-on- metal bearing surfaces and from trunnion corrosion of modular junctions. We analyzed survivorship of 8059 LDH MoM THAs based on data of the Finnish Arthroplasty Register. We found relatively high short-term survivorship for some LDH MoM THAs, but there were remarkable differences between the devices studied. After some alarming reports of failing MoM THAs, we studied the first 80 patients who had received a ReCap-M2a-Magnum implant at our institution and evaluated the prevalence of ARMD. We found a high prevalence of pseudotumors, and, because of this, we discontinued the use of MoM bearings and followed up all patients with a MoM THA. Bone loss due infection, osteolysis or fracture poses a great challenge for reconstructive and fracture surgery. Onlay allografting for both revision and fracture surgery provides mechanical stability and increases bone stock. Bone loss and implant stability must be assessed preoperatively and adequately classified; this provides guidelines for the operative treatment of periprosthetic fractures and revision THA. In our studies on structural allografts union rates were high, although the rates of infections and dislocations were marked. In summary, early results of the use of LDH MoM devices were encouraging. However, the survival of the LDH MoMs varied. The prevalence of adverse reaction to metal debris was high after application of the ReCap-Magnum THA. New implants should be introduced carefully and under close surveillance by University clinics and arthroplasty registers.

La participación de la familia en el control del paciente con diabetes mellitus tipo 2

Tesis (Maestria en Trabajo Social) UANL

Factores personales, apoyo social y estilo de vida del paciente con diabetes mellitus tipo 2

Tesis (Maestría en Ciencias de Enfermería con Énfasis en Salud Comunitaria) UANL

Ejercicio de resistencia muscular en adultos con diabetes mellitus tipo 2

Tesis (Maestría en Ciencias de Enfermería con Énfasis en Salud Comunitaria) UANL