Glycemic control and macrovascular disease in types 1 and 2 diabetes mellitus: Meta-analysis of randomized trials

Uncertainty persists concerning the effect of improved long-term glycemic control on macrovascular disease in diabetes mellitus (DM).

Long-term cardiovascular and non-cardiovascular mortality in women and men with type 1 and type 2 diabetes mellitus: a 30-year follow-up in Switzerland

While studies from other countries have shown an excess mortality in diabetic individuals when compared with the general population, comparable long-term data is not available for Switzerland.

[Insulin and type 2 diabetes mellitus]

Worldwide an increasing number of persons suffers from type 2 diabetes. Often treatment with oral hypoglycemic agents is not sufficient for adequate glycemic control and additional insulin treatment is necessary. Treatment with insulin is recommended if HbA1c levels below 7% cannot be achieved despite lifestyle measures and the proper use of oral hypoglycemic agents. In addition, pregnancy, periods pre and post major operations, treatment in intensive care units, glucocorticoid medication, severe peripheral neuropathy as well as contraindications of oral hypoglycaemic agents may be indications for insulin therapy irrespective of the actual glycemic control. The choice of the appropriate insulin regimen depends on the daily blood glucose profiles and patient needs.

Clinical outcome of patients with and without diabetes mellitus after percutaneous coronary intervention with the resolute zotarolimus-eluting stent: 2-year results from the prospectively pooled analysis of the international global RESOLUTE program

OBJECTIVES The aim of this study was to describe the process to obtain Food and Drug Administration (FDA) approval for the expanded indication for treatment with the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Inc., Santa Rosa, California) in patients with coronary artery disease and diabetes. BACKGROUND The R-ZES is the first drug-eluting stent specifically indicated in the United States for percutaneous coronary intervention in patients with diabetes. METHODS We pooled patient-level data for 5,130 patients from the RESOLUTE Global Clinical Program. A performance goal prospectively determined in conjunction with the FDA was established as a rate of target vessel failure at 12 months of 14.5%. In addition to the FDA pre-specified cohort of less complex patients with diabetes (n = 878), we evaluated outcomes of the R-ZES in all 1,535 patients with diabetes compared with all 3,595 patients without diabetes at 2 years. RESULTS The 12-month rate of target vessel failure in the pre-specified diabetic cohort was 7.8% (upper 95% confidence interval: 9.51%), significantly lower than the performance goal of 14.5% (p < 0.001). After 2 years, the cumulative incidence of target lesion failure in patients with noninsulin-treated diabetes was comparable to that of patients without diabetes (8.0% vs. 7.1%). The higher risk insulin-treated population demonstrated a significantly higher target lesion failure rate (13.7%). In the whole population, including complex patients, rates of stent thrombosis were not significantly different between patients with and without diabetes (1.2% vs. 0.8%). CONCLUSIONS The R-ZES is safe and effective in patients with diabetes. Long-term clinical data of patients with noninsulin-treated diabetes are equivalent to patients without diabetes. Patients with insulin-treated diabetes remain a higher risk subset. (The Medtronic RESOLUTE Clinical Trial; NCT00248079; Randomized, Two-arm, Non-inferiority Study Comparing Endeavor-Resolute Stent With Abbot Xience-V Stent [RESOLUTE-AC]; NCT00617084; The Medtronic RESOLUTE US Clinical Trial (R-US); NCT00726453; RESOLUTE International Registry: Evaluation of the Resolute Zotarolimus-Eluting Stent System in a 'Real-World' Patient Population [R-Int]; NCT00752128; RESOLUTE Japan-The Clinical Evaluation of the MDT-4107 Drug-Eluting Coronary Stent [RJ]; NCT00927940).

Incidence of and risk factors for severe hypoglycaemia in treated type 2 diabetes mellitus patients in the UK - a nested case-control analysis

AIMS To assess incidence rates (IRs) of and identify risk factors for incident severe hypoglycaemia in patients with type 2 diabetes newly treated with antidiabetic drugs. METHODS Using the UK-based General Practice Research Database, we performed a retrospective cohort study between 1994 and 2011 and a nested case-control analysis. Ten controls from the population at risk were matched to each case with a recorded severe hypoglycaemia during follow-up on general practice, years of history in the database and calendar time. Using multivariate conditional logistic regression analyses, we adjusted for potential confounders. RESULTS Of 130,761 patients with newly treated type 2 diabetes (mean age 61.7 �� 13.0 years), 690 (0.5%) had an incident episode of severe hypoglycaemia recorded [estimated IR 11.97 (95% confidence interval, CI, 11.11-12.90) per 10,000 person-years (PYs)]. The IR was markedly higher in insulin users [49.64 (95% CI, 44.08-55.89) per 10,000 PYs] than in patients not using insulin [8.03 (95% CI, 7.30-8.84) per 10,000 PYs]. Based on results of the nested case-control analysis increasing age [��� 75 vs. 20-59 years; adjusted odds ratio (OR), 2.27; 95% CI, 1.65-3.12], cognitive impairment/dementia (adjusted OR, 2.00; 95% CI, 1.37-2.91), renal failure (adjusted OR, 1.34; 95% CI, 1.04-1.71), current use of sulphonylureas (adjusted OR, 4.45; 95% CI, 3.53-5.60) and current insulin use (adjusted OR, 11.83; 95% CI, 9.00-15.54) were all associated with an increased risk of severe hypoglycaemia. CONCLUSIONS Severe hypoglycaemia was recorded in 12 cases per 10,000 PYs. Risk factors for severe hypoglycaemia included increasing age, renal failure, cognitive impairment/dementia, and current use of insulin or sulphonylureas.

Poorly controlled type 2 diabetes mellitus is associated with a decreased risk of incident gout: a population-based case-control study

OBJECTIVE The aim of this study was to explore the risk of incident gout in patients with type 2 diabetes mellitus (T2DM) in association with diabetes duration, diabetes severity and antidiabetic drug treatment. METHODS We conducted a case-control study in patients with T2DM using the UK-based Clinical Practice Research Datalink (CPRD). We identified case patients aged ���18 years with an incident diagnosis of gout between 1990 and 2012. We matched to each case patient one gout-free control patient. We used conditional logistic regression analysis to calculate adjusted ORs (adj. ORs) with 95% CIs and adjusted our analyses for important potential confounders. RESULTS The study encompassed 7536 T2DM cases with a first-time diagnosis of gout. Compared to a diabetes duration <1 year, prolonged diabetes duration (1-3, 3-6, 7-9 and ���10 years) was associated with decreased adj. ORs of 0.91 (95% CI 0.79 to 1.04), 0.76 (95% CI 0.67 to 0.86), 0.70 (95% CI 0.61 to 0.86), and 0.58 (95% CI 0.51 to 0.66), respectively. Compared to a reference A1C level of <7%, the risk estimates of increasing A1C levels (7.0-7.9, 8.0-8.9 and ���9%) steadily decreased with adj. ORs of 0.79 (95% CI 0.72 to 0.86), 0.63 (95% CI 0.55 to 0.72), and 0.46 (95% CI 0.40 to 0.53), respectively. Neither use of insulin, metformin, nor sulfonylureas was associated with an altered risk of incident gout. CONCLUSIONS Increased A1C levels, but not use of antidiabetic drugs, was associated with a decreased risk of incident gout among patients with T2DM.

Effect of large doses of parenteral vitamin D on glycaemic control and calcium/phosphate metabolism in patients with stable type 2 diabetes mellitus: a randomised, placebo-controlled, prospective pilot study.

OBJECTIVE Vitamin D (D���) status is reported to correlate negatively with insulin production and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). However, few placebo-controlled intervention data are available. We aimed to assess the effect of large doses of parenteral D3 on glycosylated haemoglobin (HbA(���c)) and estimates of insulin action (homeostasis model assessment insulin resistance: HOMA-IR) in patients with stable T2DM. MATERIALS AND METHODS We performed a prospective, randomised, double-blind, placebo-controlled pilot study at a single university care setting in Switzerland. Fifty-five patients of both genders with T2DM of more than 10 years were enrolled and randomised to either 300,000 IU D��� or placebo, intramuscularly. The primary endpoint was the intergroup difference in HbA(���c) levels. Secondary endpoints were: changes in insulin sensitivity, albuminuria, calcium/phosphate metabolism, activity of the renin-aldosterone axis and changes in 24-hour ambulatory blood pressure values. RESULTS After 6 months of D��� supply, there was a significant intergroup difference in the change in HbA(���c) levels (relative change [mean �� standard deviation] +2.9% �� 1.5% in the D��� group vs +6.9% �� 2.1% the in placebo group, p = 0.041) as HOMA-IR decreased by 12.8% �� 5.6% in the D��� group and increased by 10% �� 5.4% in the placebo group (intergroup difference, p = 0.032). Twenty-four-hour urinary albumin excretion decreased in the D��� group from 200 �� 41 to 126 �� 39, p = 0.021). There was no significant intergroup difference for the other secondary endpoints. CONCLUSIONS D��� improved insulin sensitivity (based on HOMA-IR) and affected the course of HbA(���c) positively compared with placebo in patients with T2DM.

IA-2, a transmembrane protein of the protein tyrosine phosphatase family, is a major autoantigen in insulin-dependent diabetes mellitus.

IA-2 is a 105,847 Da transmembrane protein that belongs to the protein tyrosine phosphatase family. Immunoperoxidase staining with antibody raised against IA-2 showed that this protein is expressed in human pancreatic islet cells. In this study, we expressed the full-length cDNA clone of IA-2 in a rabbit reticulocyte transcription/translation system and used the recombinant radiolabeled IA-2 protein to detect autoantibodies by immunoprecipitation. Coded sera (100) were tested: 50 from patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) and 50 from age-matched normal controls. Sixty-six percent of the sera from patients, but none of the sera from controls, reacted with IA-2. The same diabetic sera tested for autoantibodies to islet cells (ICA) by indirect immunofluorescence and glutamic acid decarboxylase (GAD65Ab) by depletion ELISA showed 68% and 52% positivity, respectively. Up to 86% of the IDDM patients had autoantibodies to IA-2 and/or GAD65. Moreover, greater than 90% (14 of 15) of the ICA-positive but GAD65Ab-negative sera had autoantibodies to IA-2. Absorption experiments showed that the immunofluorescence reactivity of ICA-positive sera was greatly reduced by prior incubation with recombinant IA-2 or GAD65 when the respective antibody was present. A little over one-half (9 of 16) of the IDDM sera that were negative for ICA were found to be positive for autoantibodies to IA-2 and/or GAD65, arguing that the immunofluorescence test for ICA is less sensitive than the recombinant tests for autoantibodies to IA-2 and GAD65. It is concluded that IA-2 is a major islet cell autoantigen in IDDM, and, together with GAD65, is responsible for much of the reactivity of ICA with pancreatic islets. Tests for the detection of autoantibodies to recombinant IA-2 and GAD65 may eventually replace ICA immunofluorescence for IDDM population screening.

The 37/40-kilodalton autoantigen in insulin-dependent diabetes mellitus is the putative tyrosine phosphatase IA-2.

Major targets for autoantibodies associated with the development of insulin-dependent diabetes mellitus (IDDM) include tryptic fragments with a molecular mass of 37 kDa and/or 40 kDa of a pancreatic islet cell antigen of unknown identity. The assay identifying autoantibodies against the 37/40-kDa antigen in human sera is based on the immunoprecipitation of 35S-labeled rat insulinoma cell proteins with sera from IDDM patients, followed by limited trypsin digestion of the immunoprecipitated material. To identify cDNA clones coding for the 37/40-kDa antigen, we have screened a cDNA expression library from rat insulinoma cells with a serum from an IDDM patient that precipitated the 37/40-kDa antigen in our assay. Among the cDNA products that reacted with the IDDM serum, we identified one cDNA clone whose open reading frame encodes a protein with a predicted mass of 105 kDa that we termed "ICA105" for 105-kDa islet cell antibody. The deduced amino acid sequence has high homology to a recently cloned putative tyrosine phosphatase IA-2 from human and mouse cDNA libraries. Translation of the cDNA in vitro results in a polypeptide with the expected molecular mass of 105 kDa. The evidence that ICA105 is indeed the precursor of the 37/40-kDa tryptic fragments is based on the following three results: (i) Sera from IDDM patients containing autoantibodies to the 37/40-kDa antigen precipitate the in vitro translated polypeptide, whereas sera from healthy subjects as well as sera from IDDM patients not reactive with the 37/40-kDa antigen do not precipitate the cDNA product. (ii) Immunoprecipitation of the in vitro translated protein with sera containing autoantibodies to the 37/40-kDa antigen followed by limited trypsin digestion of the precipitated proteins results in a 40-kDa polypeptide. (iii) The protein derived from our cDNA but not from an unrelated control cDNA clone can block immunoprecipitation of the 37/40-kDa antigen from a labeled rat insulinoma cell extract. The availability of the cloned 37/40-kDa antigen should facilitate the identification of individuals at risk of IDDM with increased accuracy. Furthermore, the identification of the 37/40-kDa antigen as the putative tyrosine phosphatase IA-2 is of relevance in elucidating the role of this antigen in the development of IDDM.

Diabetes mellitus e c��ncer de cabe��a e pesco��o

O diabetes mellitus (DM) est�� associado com alguns tipos de c��ncer. No entanto, estudos realizados sobre a associa����o entre DM e c��ncer de cabe��a e pesco��o (CCP) apresentaram resultados controversos. Na avalia����o da associa����o entre DM e c��ncer, destaque deve ser dado �� metformina, medicamento utilizado no DM tipo 2, que se mostra inversamente associado a alguns tumores. O objetivo deste estudo foi avaliar a associa����o entre DM e CCP, bem como o impacto do uso de metformina no risco de CCP. Este estudo caso-controle incluiu 1021 casos de CCP com confirma����o histol��gica de carcinoma espino celular selecionados em cinco hospitais de grande porte no estado de S��o Paulo entre 2011 e 2014. Os 1063 controles foram recrutados nos mesmos hospitais, pareados por frequ��ncia com os casos por sexo e idade (em grupos de 5 anos). Para avaliar o risco de CCP associado ao DM, odds ratios (OR) e intervalos com 95 por cento de confian��a (IC 95 por cento ) foram estimados por meio de regress��o log��stica n��o condicional. Os participantes diab��ticos tiveram associa����o inversa com o CCP (OR = 0,68; IC 95 por cento : 0,49-0,95), e a prote����o foi maior entre diab��ticos usu��rios metformina (OR = 0,54; IC 95 por cento : 0,29-0,99). Diab��ticos usu��rios de metformina que eram fumantes (OR = 0,13; IC 95 por cento : 0,04-0,44), ou consumidores de ��lcool acima de 40 g/ dia (OR = 0,31; IC 95 por cento : 0,11-0,88) apresentaram prote����o ainda maior com rela����o ao CCP, comparado aos n��o diab��ticos. Em conclus��o, os indiv��duos diab��ticos apresentaram risco inverso de CCP e o uso de metformina pode explicar, ao menos parcialmente, esta associa����o.

Variables predictoras de las conductas de autocuidado en las personas con diabetes tipo 2

Objetivo general: - Conocer la prevalencia de d��ficit de conductas de autocuidado en la poblaci��n adulta con diabetes tipo 2 (DMT2) del ��rea de salud de C��ceres y determinar los factores o variables asociados a dicho d��ficit. Objetivos espec��ficos: - Describir el nivel de autocuidado de las personas adultas con DMT2 en relaci��n con la alimentaci��n, ejercicio, cuidado de los pies, control de la glucemia, tratamiento farmacol��gico, y asistencia a las consultas para su control, a partir de las formas en que expresan el cuidado de su enfermedad. - Determinar si existe asociaci��n entre el nivel de autocuidado y determinadas variables sociodemogr��ficas, de comorbilidad, de informaci��n y de zona b��sica de salud. - Conocer de qu�� fuentes y de qu�� forma las personas con DMT2 obtienen la informaci��n sobre las conductas de autocuidado. Material y m��todo: Estudio anal��tico observacional de corte transversal. La poblaci��n de estudio fueron las personas mayores de 40 a��os con diagn��stico de DMT2 que acuden a las consultas de enfermer��a de atenci��n primaria del ��rea de salud de C��ceres para su atenci��n. La muestra estuvo conformada por 260 personas. La obtenci��n de los datos fue a trav��s de la entrevista personal mediante un cuestionario estandarizado elaborado para esta investigaci��n que mide las acciones de autocuidado en cuanto al r��gimen terap��utico que la enfermedad impone. Resultados: Las caracter��sticas de la muestra fueron similares a las de otros estudios en poblaciones con DMT2. La media de edad fue de 68 a��os, con predominio de mujeres. S��lo un 15,8% ten��an normopeso, la mitad sin estudios, el 80% convive con alg��n miembro de su familia, m��s de un tercio son amas de casa y el 42% de los participantes fueron diagnosticados de diabetes hace m��s de 10 a��os. El d��ficit de autocuidado lo presentaron el 49,8% para el cuidado de los pies, el 26,6% para el ejercicio, el23,8% para el control de la glucemia, el 8,1% para la alimentaci��n, el 6,2% para la asistencia a los controles y el 1,2% para el tratamiento farmacol��gico. El d��ficit de autocuidado se asoci�� en la alimentaci��n con el sexo del paciente, el lugar de residencia y el sector profesional. En el ejercicio s��lo con la edad, decreciendo el d��ficit a medida que aumenta la edad de las personas. En el autocuidado de los pies se relacion�� con la situaci��n laboral, los antecedentes familiares, haber tenido complicaciones por la diabetes, ser fumador y la edad, siendo los mayores de 70 a��os los que menos d��ficit presentaron. En el control de la glucemia el autocuidado se relacion�� con la duraci��n de la diabetes, el ��ndice de masa corporal, la informaci��n dada por el m��dico y la informaci��n escrita. En la asistencia a las consultas de control se asoci�� con que el paciente hubiera tenido complicaciones derivadas de su enfermedad. No se observ�� asociaci��n entre el d��ficit de autocuidado en el tratamiento farmacol��gico y ninguna de las variables estudiadas. Para el 98,5% de los participantes, la principal fuente de informaci��n sobre los autocuidados de la diabetes fueron los profesionales sanitarios, manifestando el 92,3% que la informaci��n sobre los autocuidados recibida de la enfermera es suficiente. Todos hab��an recibido informaci��n individual y ninguno manifest�� haber recibido informaci��n en grupo. M��s de un tercio consider�� que la informaci��n escrita es insuficiente, as�� como la informaci��n recibida por los familiares. Conclusiones: Las personas con DMT2 presentan d��ficits de autocuidado, siendo especialmente relevantes en el tratamiento no farmacol��gico. La prevalencia de d��ficit de autocuidado se asoci�� a factores individuales: no modificables por el sistema sanitario como la edad, sexo y situaci��n laboral; modificables como el tabaquismo y el ��ndice de masa corporal. A factores derivados de la enfermedad como el tiempo de evoluci��n de la diabetes y padecer complicaciones. As�� mismo, la prevalencia de d��ficits de autocuidado se asoci�� a factores del entorno sanitario en cuanto a la informaci��n proporcionada por los profesionales, la informaci��n escrita recibida por los pacientes y la informaci��n facilitada a los familiares. La identificaci��n y comprensi��n de estos factores facilita dise��ar e implementar estrategias adecuando de forma m��s efectiva el proceso de intervenci��n educativa.

The relative benefits of endurance and strength training on the metabolic factors and muscle function of people with type 2 diabetes mellitus

Objective: To compare the effects of a 4-month strength training (ST) versus aerobic endurance training (ET) program on metabolic control, muscle strength, and cardiovascular endurance in subjects with type 2 diabetes mellitus (T2D). Design: Randomized controlled trial. Setting: Large public tertiary hospital. Participants: Twenty-two T21) participants (I I men, I I women; mean age +/- standard error, 56.2 +/- 1.1 y; diabetes duration, 8.8 +/- 3.5y) were randomized into a 4-month ST program and 17 T2D participants (9 men, 8 women; mean age, 57.9 +/- 1.4y; diabetes duration, 9.2 +/- 1.7y) into a 4-month ET program. Interventions: ST (up to 6 sets per muscle group per week) and ET (with an intensity of maximal oxygen consumption of 60% and a volume beginning at 15min and advancing to a maximum of 30min 3X/wk) for 4 months. Main Outcome Measures: Laboratory tests included determinations of blood glucose, glycosylated hemoglobin (Hb A(1c)), insulin, and lipid assays. Results: A significant decline in Hb A, was only observed in the ST group (8.3% +/- 1.7% to 7.1% +/- 0.2%, P=.001). Blood glucose (204 +/- 16mg/dL to 147 +/- 8mg/dL, P &lt;.001) and insulin resistance (9.11 +/- 1.51 to 7.15 +/- 1.15, P=.04) improved significantly in the ST group, whereas no significant changes were observed in the ET group. Baseline levels of total cholesterol (207 +/- 8mg/dL to 184 +/- 7mg/dL, P &lt;.001), low-density lipoprotein cholesterol (120 +/- 8mg/dL to 106 +/- 8mg/dL, P=.001), and triglyceride levels (229 +/- 25mg/dL to 150 +/- 15mg/dL, P=.001) were significantly reduced and high-density lipoprotein cholesterol (43 +/- 3mg/dL to 48 +/- 2mg/dL, P=.004) was significantly increased in the ST group; in contrast, no such changes were seen in the ET group. Conclusions: ST was more effective than ET in improving glycemic control. With the added advantage of an improved lipid profile, we conclude that ST may play an important role in the treatment of T2D.

Diastolic dysfunction is a manifestation of ventricular-vascular interaction in patients with type 2 diabetes mellitus

Vascular disease is accelerated in patients with Type 2 diabetes mellitus (T2DM). Since the systemic vasculature plays a pivotal role in myocardial loading, this study aimed to determine the effect of arterial characteristics on left ventricular (LV) morphology and function in patients with T2DM. Conventional echocardiography and tissue Doppler imaging were performed in 172 T2DM patients (95 men; aged 55��11y) with preserved ejection fraction (62��5%). Patients were stratified into groups based on LV geometric pattern (normal [n = 79], concentric remodeling [n = 33], concentric hypertrophy [n = 29], eccentric hypertrophy [n = 31]). Total arterial compliance (TAC) was recorded by simultaneous radial tonometry and aortic outflow pulsed wave Doppler. Arterial (brachial and carotid) structure and function were determined by standard ultrasound methods. There were no significant differences between the LV geometric groups in demographic or clinical parameters. The concentric hypertrophy group had significantly increased carotid artery diameter (6.0��0.7mm versus 6.5��0.7mm; p < 0.05) and stiffness (1912��1203 dynes/cm2mm versus 2976��2695 dynes/cm2mm��10���6; p < 0.05) compared to those with normal geometry. However, TAC did not differ between groups. LV diastolic function, as determined by the ratio of diastolic mitral inflow velocity to mitral annulus tissue velocity (E/E_), was significantly associated with carotid artery relative wall thickness and intima media thickness (p < 0.05). Moreover, E/E_ was independently predicted by carotid artery relative wall thickness (�� = 22.9; p = 0.007). We conclude that structural characteristics of the carotid artery are associated with abnormal LV structure and function in patients with T2DM. The LV functional irregularities may be a downstream consequence of amplified pressure wave reflections effecting sub-optimal ventricular-vascular interaction.