Transcriptome meta-analysis of peripheral lymphomononuclear cells indicates that gestational diabetes is closer to type 1 diabetes than to type 2 diabetes mellitus.

We performed a meta-analysis of the transcription profiles of type 1, type 2 and gestational diabetes to evaluate similarities and dissimilarities among these diabetes types. cRNA samples obtained from peripheral blood lymphomononuclear cells (PBMC) of 56 diabetes mellitus patients (type 1 = 19; type 2 = 20; gestational = 17) were hybridized to the same whole human genome oligomicroarray platform, encompassing 44,000 transcripts. The GeneSpring software was used to perform analysis and hierarchical clustering, and the DAVID database was used for gene ontology. The gene expression profiles showed more similarity between gestational and type 1 diabetes rather than between type 2 and gestational diabetes, a finding that was not influenced by patient gender and age. The meta-analysis of the three types of diabetes disclosed 3,747 differentially and significantly expressed genes. A total of 486 genes were characteristic of gestational diabetes, 202 genes of type 1, and 651 genes of type 2 diabetes. 19 known genes were shared by type 1, type 2 and gestational diabetes, highlighting EGF, FAM46C, HBEGF, ID1, SH3BGRL2, VEPH1, and TMEM158 genes. The meta-analysis of PBMC transcription profiles characterized each type of diabetes revealing that gestational and type 1 diabetes were transcriptionally related.

Impaired cytokine production by peripheral blood mononuclear cells in type 1 diabetic patients.

AIMS: The objective of the present investigation was to study the production of IL-1, IL-6, IL-10, IFNgamma and TNFalpha in cultures of peripheral blood mononuclear cells (PBMC) taken from type 1 diabetic patients with inadequate metabolic control. METHODS: Seventeen type 1 diabetic patients and a gender- and age-matched group of 17 healthy individuals were studied. PBMC cultures were stimulated with phytohemagglutinin (PHA; 20 microg/ml) and lipopolysaccharide (LPS; 10 microg/ml), and enzyme immunoassay (Elisa) was used to measure IL-1, IL-6, IL-10, IFNgamma and TNFalpha in the cell-culture supernatants. RESULTS: IFNgamma levels in PHA-stimulated cultures were lower in the type 1 diabetics than in the non-diabetic controls (P<0.0001) while, in contrast, IL-10 levels were increased in the PHA-stimulated culture supernatants of the diabetics compared with the controls (P<0.0001). In addition, supernatant levels of the cytokines IL-1, IL-6 and TNFalpha released in the presence of LPS in the cell cultures from the diabetic patients were significantly lower than in the non-diabetic subjects (P<0.0001, P<0.0001 and P<0.03, respectively). CONCLUSIONS: The impaired production of IL-1, IL-6, TNFalpha and IFNgamma, and the increased production of IL-10, in PBMC cultures from type 1 diabetics with inadequate metabolic control compared with healthy subjects may be an indication of a deficiency in mononuclear cell activation and, consequently, a deficient immune cellular adaptive response that, in turn, may be the cause of the increased incidence of infections in people with type 1 diabetes.

Effect of metabolic control on interferon-gamma and interleukin-10 production by peripheral blood mononuclear cells from type 1 and type 2 diabetic patients.

The objective of the present study was to evaluate the production of cytokines, interferon-gamma (INF-gamma) and interleukin-10 (IL-10), in cultures of peripheral blood mononuclear cells (PBMC) from type 1 and type 2 diabetic patients and to correlate it with inadequate and adequate metabolic control. We studied 11 type 1 and 13 type 2 diabetic patients and 21 healthy individuals divided into two groups (N = 11 and 10) paired by sex and age with type 1 and type 2 diabetic patients. The PBMC cultures were stimulated with concanavalin-A to measure INF-gamma and IL-10 supernatant concentration by ELISA. For patients with inadequate metabolic control, the cultures were performed on the first day of hospitalization and again after intensive treatment to achieve adequate control. INF-gamma levels in the supernatants of type 1 diabetic patient cultures were higher compared to type 2 diabetic patients with adequate metabolic control (P < 0.001). Additionally, INF-gamma and IL-10 tended to increase the liberation of PBMC from type 1 and 2 diabetic patients with adequate metabolic control (P = 0.009 and 0.09, respectively). The increased levels of INF-gamma and IL-10 released from PBMC of type 1 and 2 diabetic patients with adequate metabolic control suggest that diabetic control improves the capacity of activation and maintenance of the immune response, reducing the susceptibility to infections.

[Skin lesions in diabetic patients]. / Dermatoses em pacientes com diabetes mellitus.

OBJECTIVE: It is yet unknown the relationship between diabetes and determinants or triggering factors of skin lesions in diabetic patients. The purpose of the present study was to investigate the presence of unreported skin lesions in diabetic patients and their relationship with metabolic control of diabetes. METHODS: A total of 403 diabetic patients, 31% type 1 and 69% type 2, underwent dermatological examination in an outpatient clinic of a university hospital. The endocrine-metabolic evaluation was carried out by an endocrinologist followed by the dermatological evaluation by a dermatologist. The metabolic control of 136 patients was evaluated using glycated hemoglobin. RESULTS: High number of dermophytosis (82.6%) followed by different types of skin lesions such as acne and actinic degeneration (66.7%), pyoderma (5%), cutaneous tumors (3%) and necrobiosis lipoidic (1%) were found. Among the most common skin lesions in diabetic patients, confirmed by histopathology, there were seen necrobiosis lipoidic (2 cases, 0.4%), diabetic dermopathy (5 cases, 1.2%) and foot ulcerations (3 cases, 0.7%). Glycated hemoglobin was 7.2% in both type 1 and 2 patients with adequate metabolic control and 11.9% and 12.7% in type 1 and 2 diabetic patients, respectively, with inadequate metabolic controls. A higher prevalence of dermatophytoses was seen in the both groups with inadequate metabolic control. CONCLUSIONS: The results showed a high prevalence of skin lesions in diabetic patients, especially dermatophytoses. Thus, poor metabolic control of diabetes increases patient's susceptibility to skin infections.

Proposed ratios and cutoffs for the assessment of lipodystrophy in HIV-seropositive individuals.

OBJECTIVES: To propose objective ratios using anthropometry and dual-energy X-ray absorptiometry (DXA) and to suggest cutoff points for them in order to classify lipodystrophy in male patients. METHODS: It is a cross-sectional study. DXA was applied and anthropometric measurements were performed in 100 men on highly active antiretroviral therapy. Receiver operating characteristic curves were used to propose cutoffs. Individuals were divided in without (lipo-) or with (lipo+) lipodystrophy and their metabolic parameters were compared. RESULTS: The following ratios were proposed: fat mass ratio by DXA (FMR), waist thigh ratio (WTR), waist calf ratio (WCR), and arm to trunk ratio (ATR). The best cutoffs observed for FMR, WTR and ATR were 1.26, 1.74 and 2.08, respectively. Using the proposed cutoff for FMR, we observed worse metabolic profile, with increased tryglicerides, fasting serum glucose and more hypercholesterolemia in the lipo+ group. WTR and ATR showed a significant correlation with FMR. CONCLUSIONS: Anthropometric ratios (WTR/ATR) and FMR can be used to aid the diagnosis of lipodystrophy in order to contribute to a more accurate and earlier diagnosis permitting intervention and even preventing metabolic disturbances.

Comparison of the homeostasis model assessment and quantitative insulin sensitivity check index with data from forearm metabolic studies for the in vivo assessment of insulin sensitivity.

The present study was designed to compare the homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) with data from forearm metabolic studies of healthy individuals and of subjects in various pathological states. Fifty-five healthy individuals and 112 patients in various pathological states, including type 2 diabetes mellitus, essential hypertension and others, were studied after an overnight fast and for 3 h after ingestion of 75 g of glucose, by HOMA, QUICKI and the forearm technique to estimate muscle uptake of glucose combined with indirect calorimetry (oxidative and non-oxidative glucose metabolism). The patients showed increased HOMA (1.88 +/- 0.14 vs 1.13 +/- 0.10 pmol/l x mmol/l) and insulin/glucose (I/G) index (1.058.9 +/- 340.9 vs 518.6 +/- 70.7 pmol/l x (mg/100 ml forearm)-1), and decreased QUICKI (0.36 +/- 0.004 vs 0.39 +/- 0.006 ( microU/ml + mg/dl)-1) compared with the healthy individuals. Analysis of the data for the group as a whole (patients and healthy individuals) showed that the estimate of insulin resistance by HOMA was correlated with data obtained in the forearm metabolic studies (glucose uptake: r = -0.16, P = 0.04; non-oxidative glucose metabolism: r = -0.20. P = 0.01, and I/G index: r = 0.17, P = 0.03). The comparison of QUICKI with data of the forearm metabolic studies showed significant correlation between QUICKI and non-oxidative glucose metabolism (r = 0.17, P = 0.03) or I/G index (r = -0.37, P < 0.0001). The HOMA and QUICKI are good estimates of insulin sensitivity as data derived from forearm metabolic studies involving direct measurements of insulin action on muscle glucose metabolism.

Predictors of restenosis after percutaneous coronary intervention using bare-metal stents: a comparison between patients with and without dysglycemia.

The objective of this study was to identify intravascular ultrasound (IVUS), angiographic and metabolic parameters related to restenosis in patients with dysglycemia. Seventy consecutive patients (77 lesions) selected according to inclusion and exclusion criteria were evaluated by the oral glucose tolerance test and the determination of insulinemia after a successful percutaneous coronary intervention (PCI) with a bare-metal stent. The degree of insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR). Six-month IVUS and angiogram follow-up were performed. Thirty-nine patients (55.7%) had dysglycemia. The restenosis rate in the dysglycemic group was 37.2 vs 23.5% in the euglycemic group (P = 0.299). The predictors of restenosis using bivariate analysis were reference vessel diameter (RVD): pound2.93 mm (RR = 0.54; 95%CI = 0.05-0.78; P = 0.048), stent area (SA): <8.91 mm(2) (RR = 0.66; 95%CI = 0.24-0.85; P = 0.006), stent volume (SV): <119.75 mm(3) (RR = 0.74; 95%CI = 0.38-0.89; P = 0.0005), HOMA-IR: >2.063 (RR = 0.44; 95%CI = 0.14-0.64; P = 0.027), and fasting plasma glucose (FPG): < or =108.8 mg/dL (RR = 0.53; 95%CI = 0.13-0.75; P = 0.046). SV was an independent predictor of restenosis by multivariable analysis. Dysglycemia is a common clinical condition in patients submitted to PCI. The degree of insulin resistance, FPG, RVD, SA, and SV were correlated with restenosis. SV was inversely correlated with an independent predictor of restenosis in patients treated with a bare-metal stent.

Effect of the glycemic control on intracellular cytokine production from peripheral blood mononuclear cells of type 1 and type 2 diabetic patients.

AIMS: To evaluate the intracellular production of tumor necrosis factor (TNF-alpha), interleukine-6 (IL-6), INF-gamma, IL-8 and IL-10 in peripheral blood lymphomononuclear cells from type 1 and type 2 diabetic patients, stratified according to the glycemic control. METHODS: Thirty-five diabetic patients (17 type 1 and 18 type 2) and nine healthy individuals paired to patients in terms of sex and age were studied. Nine patients of each group were on inadequate glycemic controls. Intracellular cytokines were evaluated using flow cytometry. Cell cultures were stimulated with LPS to evaluate TNF-alpha and IL-6 or with PMA and Ionomycin to evaluate IFN-gamma, IL-8 and IL-10 intracellular staining. RESULTS: The percentages of CD33(+) cells bearing TNF-alpha and CD3(+) cells bearing IL-10 were increased in type 1 diabetic patients with inadequate glycemic control in relation to those with adequate control. In contrast, the percentage of CD3(+) cells bearing IL-8 was decreased in type 2 patients under inadequate glycemic control. CONCLUSIONS: The glycemic control is important for the detection of intracellular cytokines, and may contribute towards the susceptibility to infections in diabetic patients.

Predictors of restenosis after percutaneous coronary intervention using bare-metal stents: a comparison between patients with and without dysglycemia

The objective of this study was to identify intravascular ultrasound (IVUS), angiographic and metabolic parameters related to restenosis in patients with dysglycemia. Seventy consecutive patients (77 lesions) selected according to inclusion and exclusion criteria were evaluated by the oral glucose tolerance test and the determination of insulinemia after a successful percutaneous coronary intervention (PCI) with a bare-metal stent. The degree of insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR). Six-month IVUS and angiogram follow-up were performed. Thirty-nine patients (55.7 percent) had dysglycemia. The restenosis rate in the dysglycemic group was 37.2 vs 23.5 percent in the euglycemic group (P = 0.299). The predictors of restenosis using bivariate analysis were reference vessel diameter (RVD): £2.93 mm (RR = 0.54; 95 percentCI = 0.05-0.78; P = 0.048), stent area (SA): <8.91 mm² (RR = 0.66; 95 percentCI = 0.24-0.85; P = 0.006), stent volume (SV): <119.75 mm³ (RR = 0.74; 95 percentCI = 0.38-0.89; P = 0.0005), HOMA-IR: >2.063 (RR = 0.44; 95 percentCI = 0.14-0.64; P = 0.027), and fasting plasma glucose (FPG): ≤108.8 mg/dL (RR = 0.53; 95 percentCI = 0.13-0.75; P = 0.046). SV was an independent predictor of restenosis by multivariable analysis. Dysglycemia is a common clinical condition in patients submitted to PCI. The degree of insulin resistance, FPG, RVD, SA, and SV were correlated with restenosis. SV was inversely correlated with an independent predictor of restenosis in patients treated with a bare-metal stent.

Effect of metabolic control on interferon-gamma and interleukin-10 production by peripheral blood mononuclear cells from type 1 and type 2 diabetic patients

The objective of the present study was to evaluate the production of cytokines, interferon-g (INF-g) and interleukin-10 (IL-10), in cultures of peripheral blood mononuclear cells (PBMC) from type 1 and type 2 diabetic patients and to correlate it with inadequate and adequate metabolic control. We studied 11 type 1 and 13 type 2 diabetic patients and 21 healthy individuals divided into two groups (N = 11 and 10) paired by sex and age with type 1 and type 2 diabetic patients. The PBMC cultures were stimulated with concanavalin-A to measure INF-g and IL-10 supernatant concentration by ELISA. For patients with inadequate metabolic control, the cultures were performed on the first day of hospitalization and again after intensive treatment to achieve adequate control. INF-g levels in the supernatants of type 1 diabetic patient cultures were higher compared to type 2 diabetic patients with adequate metabolic control (P < 0.001). Additionally, INF-g and IL-10 tended to increase the liberation of PBMC from type 1 and 2 diabetic patients with adequate metabolic control (P = 0.009 and 0.09, respectively). The increased levels of INF-g and IL-10 released from PBMC of type 1 and 2 diabetic patients with adequate metabolic control suggest that diabetic control improves the capacity of activation and maintenance of the immune response, reducing the susceptibility to infections.

Dermatoses em pacientes com diabetes mellitus / Skin lesions in diabetic patients

Ainda é desconhecida a relação do diabetes com fatores determinantes ou precipitantes de lesões dermatológicas em pacientes diabéticos. Assim, o objetivo do estudo foi investigar a presença de lesões cutâneas, não referidas pelo paciente diabético e sua relação com o controle metabólico da doença. MÉTODOS: Foram examinados 403 pacientes, dos quais 31 por cento eram diabéticos do tipo 1 e 69 por cento do tipo 2. Em ambulatório de um hospital universitário, os pacientes foram atendidos por endocrinologista para a avaliação endócrino-metabólica e por dermatologista para a avaliação dermatológica. O grau de controle metabólico foi documentado em 136 pacientes por meio da dosagem de hemoglobina glicada. RESULTADOS: Houve predomínio de dermatofitoses (82,6 por cento), seguido de grupo de dermatoses como acne e degeneração actínica (66,7 por cento), piodermites (5 por cento), tumores cutâneos (3 por cento) e necrobiose lipoídica (1 por cento). Entre as dermatoses mais comuns em diabéticos, foram confirmados com exame histológico: dois diagnósticos de necrobiose (0,4 por cento), cinco de dermopatia diabética (1,2 por cento) e três casos de mal perfurante plantar (0,7 por cento). Os valores da hemoglobina glicada foram: 7,2 por cento em pacientes com controle metabólico adequado nos dois tipos de diabetes e de 11,9 por cento e 12,7 por cento nos tipos 1 e 2, respectivamente, com controle inadequado. Nos pacientes com controle metabólico inadequado foi observada freqüência maior de dermatofitoses, em ambos os tipos de diabetes. CONCLUSÕES: Os dados revelaram freqüência elevada de lesão dermatológica nos pacientes diabéticos, especialmente dermatofitoses. Dessa forma, o descontrole metabólico do diabético propicia maior suscetibilidade a infecções cutâneas.

Comparison of the homeostasis model assessment and quantitative insulin sensitivity check index with data from forearm metabolic studies for the in vivo assessment of insulin sensitivity

The present study was designed to compare the homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) with data from forearm metabolic studies of healthy individuals and of subjects in various pathological states. Fifty-five healthy individuals and 112 patients in various pathological states, including type 2 diabetes mellitus, essential hypertension and others, were studied after an overnight fast and for 3 h after ingestion of 75 g of glucose, by HOMA, QUICKI and the forearm technique to estimate muscle uptake of glucose combined with indirect calorimetry (oxidative and non-oxidative glucose metabolism). The patients showed increased HOMA (1.88 ñ 0.14 vs 1.13 ñ 0.10 pmol/l x mmol/l) and insulin/glucose (I/G) index (1.058.9 ñ 340.9 vs 518.6 ñ 70.7 pmol/l x (mg/100 ml forearm)-1), and decreased QUICKI (0.36 ñ 0.004 vs 0.39 ñ 0.006 (æU/ml + mg/dl)-1) compared with the healthy individuals. Analysis of the data for the group as a whole (patients and healthy individuals) showed that the estimate of insulin resistance by HOMA was correlated with data obtained in the forearm metabolic studies (glucose uptake: r = -0.16, P = 0.04; non-oxidative glucose metabolism: r = -0.20. P = 0.01, and I/G index: r = 0.17, P = 0.03). The comparison of QUICKI with data of the forearm metabolic studies showed significant correlation between QUICKI and non-oxidative glucose metabolism (r = 0.17, P = 0.03) or I/G index (r = -0.37, P < 0.0001). The HOMA and QUICKI are good estimates of insulin sensitivity as data derived from forearm metabolic studies involving direct measurements of insulin action on muscle glucose metabolism.