The carotid body of the spontaneous insulin-dependent diabetic rat

The carotid bodies from adult spontaneous insulin-dependent diabetic rats (strain BB/S) were perfusion-fixed at normal arterial blood pressure with 3% phosphate-buffered glutaraldehyde and compared with the organs from control rats (strain BB/Sc) prepared in the same way. Serial 5-µm sections were cut, stained, and using an interactive image analysis system, were analysed to determine the volumes of the carotid body and its vascular and extravascular compartments. There was no evidence of systemic arterial disease in the carotid stem arteries in either group of animals, and the microvasculature of the organs appeared normal by light microscopy. The volume of the carotid body was unchanged 3 months after the onset of diabetes but was increased at 6 months. The total vascular volume of the organ was unchanged, but the volume of the small vessels (5-12 µm) was increased. In the control group the small vessels comprised 5% of the total volume of the carotid body, or about 44% of the vascular compartment. The percentage of small vessels increased at 3 months in the diabetic group, but had returned to normal at 6 months. The extravascular volume followed the same pattern as the total carotid body volume and so did not change appreciably when expressed as a percentage of the total volume of the organ. The increase in size of the carotid body in diabetic rats is due, therefore, to an augmented extravascular volume. In one diabetic specimen the carotid sinus nerve showed signs of diabetic neuropathy, axonal swelling and intramyelinic oedema. The clinical implications of these results are discussed.

Secondary prevention of type 1 diabetes mellitus: stopping immune destruction and promoting ß-cell regeneration

Type 1 diabetes mellitus results from a cell-mediated autoimmune attack against pancreatic ß-cells. Traditional treatments involve numerous daily insulin dosages/injections and rigorous glucose control. Many efforts toward the identification of ß-cell precursors have been made not only with the aim of understanding the physiology of islet regeneration, but also as an alternative way to produce ß-cells to be used in protocols of islet transplantation. In this review, we summarize the most recent studies related to precursor cells implicated in the regeneration process. These include embryonic stem cells, pancreas-derived multipotent precursors, pancreatic ductal cells, hematopoietic stem cells, mesenchymal stem cells, hepatic oval cells, and mature ß-cells. There is controversial evidence of the potential of these cell sources to regenerate ß-cell mass in diabetic patients. However, clinical trials using embryonic stem cells, umbilical cord blood or adult bone marrow stem cells are under way. The results of various immunosuppressive regimens aiming at blocking autoimmunity against pancreatic ß-cells and promoting ß-cell preservation are also analyzed. Most of these regimens provide transient and partial effect on insulin requirements, but new regimens are beginning to be tested. Our own clinical trial combines a high dose immunosuppression with mobilized peripheral blood hematopoietic stem cell transplantation in early-onset type 1 diabetes mellitus.

Lack of relationship between glycemic control and bone mineral density in type 2 diabetes mellitus

We assessed the effect of chronic hyperglycemia on bone mineral density (BMD) and bone remodeling in patients with type 2 diabetes mellitus. We investigated 42 patients with type 2 diabetes under stable control for at least 1 year, 22 of them with good metabolic control (GMC: mean age = 48.8 ± 1.5 years, 11 females) and 20 with poor metabolic control (PMC: mean age = 50.2 ± 1.2 years, 8 females), and 24 normal control individuals (CG: mean age = 46.5 ± 1.1 years, 14 females). We determined BMD in the femoral neck and at the L2-L4 level (DEXA) and serum levels of glucose, total glycated hemoglobin (HbA1), total and ionic calcium, phosphorus, alkaline phosphatase, follicle-stimulating hormone, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-OH-D), insulin-like growth factor I (IGFI), osteocalcin, procollagen type I C propeptide, as well as urinary levels of deoxypyridinoline and creatinine. HbA1 levels were significantly higher in PMC patients (12.5 ± 0.6 vs 7.45 ± 0.2% for GMC and 6.3 ± 0.9% for CG; P < 0.05). There was no difference in 25-OH-D, iPTH or IGFI levels between the three groups. BMD values at L2-L4 (CG = 1.068 ± 0.02 vs GMC = 1.170 ± 0.03 vs PMC = 1.084 ± 0.02 g/cm²) and in the femoral neck (CG = 0.898 ± 0.03 vs GMC = 0.929 ± 0.03 vs PMC = 0.914 ± 0.03 g/cm²) were similar for all groups. PMC presented significantly lower osteocalcin levels than the other two groups, whereas no significant difference in urinary deoxypyridine was observed between groups. The present results demonstrate that hyperglycemia is not associated with increased bone resorption in type 2 diabetes mellitus and that BMD is not altered in type 2 diabetes mellitus.

Neutrophil function and metabolism in individuals with diabetes mellitus

Neutrophils act as first-line-of-defense cells and the reduction of their functional activity contributes to the high susceptibilityto and severity of infections in diabetes mellitus. Clinical investigations in diabetic patients and experimental studies in diabetic rats and mice clearly demonstrated consistent defects of neutrophil chemotactic, phagocytic and microbicidal activities. Other alterations that have been reported to occur during inflammation in diabetes mellitus include: decreased microvascular responses to inflammatory mediators such as histamine and bradykinin, reduced protein leakage and edema formation, reduced mast cell degranulation, impairment of neutrophil adhesionto the endothelium and migration to the site of inflammation, production of reactive oxygen species and reduced release of cytokines and prostaglandin by neutrophils, increased leukocyte apoptosis, and reduction in lymph node retention capacity. Since neutrophil function requires energy, metabolic changes (i.e., glycolytic and glutaminolytic pathways) may be involved in the reduction of neutrophil function observed in diabetic states. Metabolic routes by which hyperglycemia is linked to neutrophil dysfunction include the advanced protein glycosylation reaction, the polyol pathway, oxygen-free radical formation, the nitric oxide-cyclic guanosine-3'-5'monophosphate pathway, and the glycolytic and glutaminolytic pathways. Lowering of blood glucose levels by insulin treatment of diabetic patients or experimental animals has been reported to have significant correlation with improvement of neutrophil functional activity. Therefore, changes might be primarily linked to a continuing insulin deficiency or to secondary hyperglycemia occurring in the diabetic individual. Accordingly, effective control with insulin treatment is likely to be relevant during infection in diabetic patients.

The reciprocal interaction between sleep and type 2 diabetes mellitus: facts and perspectives

Type 2 diabetes mellitus is a systemic disease characterized by intolerance to glucose and peripheral resistance to insulin. This endocrine disease affects fundamental mechanisms of the central nervous system and jeopardizes the balance of vital functions such as the cardiovascular and circadian rhythm. The increased prevalence of metabolic disorders in our society is aggravated by endemic voluntary postponement of bedtime and by the current sedentary lifestyle, leading to epidemic proportions of obese people. Diabetes and chronic loss of sleep share the fact that both affect millions and one is detrimental to the other. Indeed, sleep deficits have marked modulatory effects on glucose metabolism and insulin sensitivity and foster metabolic syndrome that culminates in sleep disorders like restless syndrome and sleep apnea, which in turn lead to poor sleep quality. We examine the hypothesis that these two worldwide emerging disorders are due to two interlinked cycles. In our paradigm, we establish an intimate relationship between diabetes and sleep disturbances and postulate possible mechanisms that provide support for this conjecture. In addition, we propose some perspectives about the development of the reciprocal interaction between predictor components of metabolic syndrome and sleep disturbances that lead to poor sleep quality. The ability to predict the development and identify or associate a given mode of sleep disturbance to diabetes would be a valuable asset in the assessment of both. Furthermore, major advances in care coupled with healthy lifestyles can ensure a higher quality of life for people with diabetes.

The role of K121Q ENPP1 polymorphism in diabetes mellitus and its complications

The aim of the present study was to analyze the frequency of K121Q polymorphism in the ENPP1 gene of Brazilian subjects according to ethnic origin and to determine its possible association with diabetes mellitus (DM) and/or diabetic complications. A cross-sectional study was conducted on 1027 type 2 DM patients and 240 anonymous blood donors (BD). Ethnicity was classified based on self-report of European and African descent. The Q allele frequency was increased in African descendant type 2 DM patients (KK = 25.9%, KQ = 48.2%, and QQ = 25.9%) and BD (KK = 22.0%, KQ = 53.8%, and QQ = 24.2%) compared to European descendant type 2 DM patients (KK = 62.7%, KQ = 33.3%, and QQ = 4.1%) and BD (KK = 61.0%, KQ = 35.6%, and QQ = 3.4%). However, there was no difference in genotype distribution or Q allele frequency between diabetic and non-diabetic subjects (European descendants: DM = 0.21 vs BD = 0.21, P = 0.966, and African descendants: DM = 0.50 vs BD = 0.51, P = 0.899). In addition, there were no differences in clinical, laboratory or insulin resistance indices among the three genotypes. The prevalence of DM complications was also similar. In conclusion, K121Q polymorphism is more common among Afro-Brazilian descendants regardless of glycemic status or insulin sensitivity indices. Likewise, insulin sensitivity and DM chronic complications appear not to be related to the polymorphism in this sample.

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m2], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

Genetic analysis of the ELOVL6 gene polymorphism associated with type 2 diabetes mellitus

Recent animal studies have indicated that overexpression of the elongation of long-chain fatty acids family member 6 (Elovl6) gene can cause insulin resistance and β-cell dysfunction. These are the major factors involved in the development of type 2 diabetes mellitus (T2DM). To identify the relationship between single nucleotide polymorphisms (SNP) ofELOVL6 and T2DM pathogenesis, we conducted a case-control study of 610 Han Chinese individuals (328 newly diagnosed T2DM and 282 healthy subjects). Insulin resistance and islet first-phase secretion function were evaluated by assessment of insulin resistance in a homeostasis model (HOMA-IR) and an arginine stimulation test. Three SNPs of the ELOVL6 gene were genotyped with polymerase chain reaction-restriction fragment length polymorphism, with DNA sequencing used to confirm the results. Only genotypes TT and CT of the ELOVL6 SNP rs12504538 were detected in the samples. Genotype CC was not observed. The T2DM group had a higher frequency of the C allele and the CT genotype than the control group. Subjects with the CT genotype had higher HOMA-IR values than those with the TT genotype. In addition, no statistical significance was observed between the genotype and allele frequencies of the control and T2DM groups for SNPs rs17041272 and rs6824447. The study indicated that the ELOVL6 gene polymorphism rs12504538 is associated with an increased risk of T2DM, because it causes an increase in insulin resistance.

Plasma levels and placental expression of vaspin in pregnant women with diabetes mellitus

The present study aimed to investigate visceral adipose tissue-specific serpin (vaspin) concentrations in serum and term placentas and relate these values to insulin resistance and lipid parameters in women with gestational diabetes mellitus (GDM). A total of 30 GDM subjects and 27 age-matched pregnant women with normal glucose tolerance (NGT, control) were included. Serum glucose, glycated hemoglobin (HbA1c), lipid profile, insulin, and vaspin were measured at the end of pregnancy, and homeostasis model of assessment-insulin resistance (HOMA-IR) values were calculated. Vaspin mRNA and protein levels in placentas were measured by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting, respectively. Serum vaspin levels were significantly lower in the GDM group than in controls (0.49±0.24 vs 0.83±0.27 ng/mL, respectively; P<0.01). Three days after delivery, serum vaspin levels were significantly decreased in subjects with GDM (0.36±0.13 vs0.49±0.24 ng/mL, P<0.01). However, in the GDM group, serum vaspin levels were not correlated with the parameters evaluated. In contrast, in the control group, serum vaspin levels were positively correlated with triglycerides (TG; r=0.45, P=0.02) and very low-density lipoprotein cholesterol (VLDL-C; r=0.42, P=0.03). Placental mRNA vaspin (0.60±0.32 vs0.68±0.32, P=0.46) and protein (0.30±0.08 vs0.39±0.26; P=0.33) levels in the GDM group did not differ significantly from those in the control group, but were negatively correlated with neonatal birth weight in the GDM group (r=-0.48, P=0.03; r=-0.88; P<0.01). Our findings indicated that vaspin may be an important adipokine involved in carbohydrate and lipid metabolism and may also play a role in fetal development.

Statistical Analysis of Diabetes Mellitus

Diabetes mellitus is a disease where the glucosis-content of the blood does not automatically decrease to a ”normal” value between 70 mg/dl and 120 mg/dl (3,89 mmol/l and 6,67 mmol/l) between perhaps one hour (or two hours) after eating. Several instruments can be used to arrive at a relative low increase of the glucosis-content. Besides drugs (oral antidiabetica, insulin) the blood-sugar content can mainly be influenced by (i) eating, i.e., consumption of the right amount of food at the right time (ii) physical training (walking, cycling, swimming). In a recent paper the author has performed a regression analysis on the influence of eating during the night. The result was that one ”bread-unit” (12g carbon-hydrats) increases the blood-sugar by about 50 mg/dl, while one hour after eating the blood-sugar decreases by about 10 mg/dl per hour. By applying this result-assuming its correctness - it is easy to eat the right amount during the night and to arrive at a fastening blood-sugar (glucosis-content) in the morning of about 100 mg/dl (5,56 mmol/l). In this paper we try to incorporate some physical exercise into the model.

Conocimientos de los criterios diagnósticos de diabetes mellitus tipo 2 en médicos de Barranquilla 2005

La Diabetes Mellitus (DM) es una enfermedad metabólica, crónica, no transmisible y de etiología multifactorial, causada por defectos en la secreción y acción de la insulina(1), constituye el 90-95 % de todos los casos de Diabetes(2). Es una enfermedad crónica que afecta a un gran número de personas, representando un problema personal y de salud pública de enormes proporciones. En Colombia está dentro de las 10 primeras causas de consulta y mortalidad, y la prevalencia en Bogotá en personas de 30-64 años es de 7.3% (3.7-10.9) en hombres y de 8.7 (5.2-12.3) en mujeres. Se estima que la mitad de los casos de Diabetes permanecen sin ser especificados. Muchos de estos pacientes presentan complicaciones crónicas en el momento del diagnóstico por lo que el inicio de la enfermedad antecede a su detección en varios años.

The genetics of diabetes mellitus

Genes play an important role in the development of diabetes mellitus. Putative susceptibility genes could be the key to the development of diabetes. Type 1 diabetes mellitus is one of the most common chronic diseases of childhood. A combination of genetic and environmental factors is most likely the cause of Type 1 diabetes. The pathogenetic sequence leading to the selective autoimmune destruction of islet beta-cells and development of Type 1 diabetes involves genetic factors, environmental factors, immune regulation and chemical mediators. Unlike Type 1 diabetes mellitus, Type 2 diabetes is often considered a polygenic disorder with multiple genes located on different chromosomes being associated with this condition. This is further complicated by numerous environmental factors which also contribute to the clinical manifestation of the disorder in genetically predisposed persons. Only a minority of cases of type 2 diabetes are caused by single gene defects such as maturity onset diabetes of the young (MODY), syndrome of insulin resistance (insulin receptor defect) and maternally inherited diabetes and deafness (mitochondrial gene defect). Although Type 2 diabetes mellitus appears in almost epidemic proportions our knowledge of the mechanism of this disease is limited. More information about insulin secretion and action and the genetic variability of the various factors involved will contribute to better understanding and classification of this group of diseases. This article discusses the results of various genetic studies on diabetes with special reference to Indian population.

Biodritin microencapsulated human islets of langerhans and their potential for type 1 diabetes mellitus therapy

Background. Microencapsulation of pancreatic islets with polymeric compounds constitutes an attractive alternative therapy for type 1 diabetes mellitus. The major limiting factor is the availability of a biocompatible and mechanically stable polymer. We investigated the potential of Biodritin, a novel polymer constituted of alginate and chondroitin sulfate, for islet microencapsulation. Methods. Biodritin microcapsules were obtained using an air jet droplet generator and gelated with barium or calcium chloride. Microencapsulated rat insulinoma RINm5F cells were tested for viability using the [3-(4,5-dimetyl-thiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide] [MTT] colorimetric assay. Microencapsulated rat pancreatic islets were coincubated with macrophages derived from mouse peritoneal liquid to assess the immunomodulatory potential of the microcapsules, using quantitative real time-PCR (qPCR). Biodritin biocompatibility was demonstrated by subcutaneous injection of empty microcapsules into immunocompetent Wistar rats. Insulin secretion by microencapsulated human pancreatic islets was evaluated using an electrochemoluminescent assay. Microencapsulated human islets transplanted into chemically induced diabetic mice were monitored for reversal of hyperglycemia. Results. The metabolic activity of microencapsulated RINm5F cells persisted for at least 15 days. Interleukin-1 beta expression by macrophages was observed during coculture with islets microencapsulated with Biodritin-CaCl2, but not with Biodritin-BaCl2. No statistical difference in glucose-stimulated insulin secretion was observed between nonencapsulated and microencapsulated islets. Upon microencapsulated islet transplantation, the blood glucose level of diabetic mice normalized; they remained euglycemic for at least 60 days, displaying normal oral glucose tolerance tests. Conclusion. This study demonstrated that Biodritin can be used for islet microencapsulation and reversal of diabetes; however, further investigations are required to assess its potential for long-term transplantation.

Patienters upplevelser av livskvalitet vid nydiagnostiserad typ 2 Diabetes Mellitus : En intervjustudie

Syfte: Att undersöka patienters upplevelser av livskvalitet vid nydiagnostiserad typ 2 Diabetes Mellitus. Metod: En empirisk studie med en kvalitativ ansats som innefattade tio deltagare med nydiagnostiserad typ 2 Diabetes Mellitus. Semistrukturerade intervjuer genomfördes utifrån en intervjuguide där insamlad data analyserades med kvalitativ manifest innehållsanalys. Resultat: Studien resulterade i fyra huvudkategorier och tio subkategorier. Upplevelsen av att få ett diagnosbesked varierade mellan deltagarna, för vissa deltagarna var beskedet inte förvånande medan andra upplevde känslor av chock och förnekelse. Deltagarna upplevde positiva förändringar, exempelvis viktnedgång och förbättrad hälsa men även negativa förändringar, exempelvis att vara beroende av läkemedel. Vissa upplevde ingen förändring alls. Typ 2 Diabetes Mellitus påverkade inte deltagarnas fysiska eller psykiska hälsa i de flesta fall. Deltagarna ansåg det som viktig att få stöd från både omgivningen och hälso- och sjukvården. Konklusion: Känslorna över ett diagnosbesked kunde variera men upplevelsen av livskvalitet påverkades inte av Typ 2 Diabetes Mellitus i de flesta fall i studien. Patientens inställning till att leva med Typ 2 Diabetes Mellitus inverkade på förmågan till att utföra egenvård, och distriktsköterskans stöd och engagemang ansågs vara betydelsefullt i sjukdomsprocessen.

Avaliação do retinol em parturientes com diabetes mellitus gestacional no pós parto imediato

Micronutrient deficiencies affect individuals mainly in developing countries, where vitamin A deficiency is a public health problem worldwide more worrying, especially in groups with increased physiological needs such as children and women of reproductive age. Vitamin A is supplied to the body through diet and has an important role in the visual process, cell differentiation, maintenance of epithelial tissue, reproductive and resistance to infection. The literature has demonstrated the relationship between vitamin A and diabetes, including gestational, leading to a risk to both mother and child. Gestational diabetes is any decrease in glucose tolerance of variable magnitude diagnosed each the first time during pregnancy, and may or may not persist after delivery. Insulin resistance during pregnancy is associated with placental hormones, as well as excess fat. Studies have shown that retinol transport protein produced in adipose tissue in high concentrations, this would be associated with resistance by interfering with insulin signaling. Therefore, this study aimed to evaluate the concentration of retinol in serum and colostrum from healthy and diabetic mothers in the immediate postpartum period. One hundred and nine parturient women were recruited, representing seventy-three healthy and thirty-six diabetic. Retinol was extracted and subsequently analyzed by High Performance Liquid Chromatography. Among the results highlights the mothers with gestational diabetes were older than mothers healthy, had more children and a higher prevalence of cases of cesarean section. Fetal macrosomia was present in 1.4% of healthy parturient women and in 22.2% of diabetic mothers. The maternal serum retinol showed an average of 39.7 ± 12.5 mg/dL for healthy parturients 35.12 ± 15 mg/dL for diabetic and showed no statistical difference. It was observed that in the group of diabetic had 17% vitamin A deficiency, whereas in the healthy group, only 4% of the women were deficentes. Colostrum, the concentration of retinol in healthy was 131.3 ± 56.2 mg/dL and 125.3 ± 41.9 mg/dL in diabetic did not differ statistically. This concentration of retinol found in colostrum provides approximately 656.5 mg/day for infants born to healthy mothers and 626.5 mg/day for infants of diabetic mothers, based on a daily consumption of 500 mL of breast milk and need Vitamin A 400 mg/day, thus reaching the requirement of the infant. The diabetic mothers showed significant risk factors and complications related to gestational diabetes. Although no 11 difference was found in serum retinol concentration and colostrum among women with and without gestational diabetes, the individual analysis shows that parturients women with diabetes are 4.9 times more likely to develop vitamin A deficiency than healthy parturients. However, the supply of vitamin A to the newborn was not committed in the presence of gestational diabetes