Bezpieczeństwo i skuteczność dwufazowej insuliny aspart 30 (BIAsp30) u Irańczyków chorych na cukrzycę typu 2: otwarte, nierandomizowane, wieloośrodkowe badanie - irańska podgrupa badania IMPROVE™

Introduction: To evaluate the clinical profile of BIAsp 30 (30% soluble insulin aspart, 70% protamine-crystallized insulin aspart) (NovoMix®30) in type 2 diabetes patients in routine clinical practice in Iran. Material and methods: IMPROVE&#8482; was a 26-week, multinational, open-label, non-randomized study in patients with type 2 diabetes. The safety and efficacy of BIAsp 30 were assessed at baseline and at 13 and 26 weeks. The titration of BIAsp30 was at the physician&#8217;s discretion. Results: In Iran, 478 patients (47% male) previously treated with oral antidiabetic drugs (OADs) (N = 159, 33.3%) and/or insulin other than BIAsp30 (N = 317, 66.3%) or a few who were treatment-na&#239;ve (N = 2, 0.4%) participated in the study. After 26 weeks of treatment with BIAsp 30, the rate of reported major hypoglycaemic episodes was reduced by 88.1% from baseline (baseline v. Week 26: 0.303 v. 0.037 episodes/pt-year; p < 0.001). No significant differences in minor hypoglycaemic episodes between baseline and Week 26 were found. Glycaemic control was significantly improved from baseline to Week 26 with a mean HbA1c reduction of 1.2 &#177; 1.9%. Patients&#8217; quality of life as measured by the DiabMedSat questionnaire significantly improved from baseline (58.1) to the end of the study (75.4, p < 0.001). Conclusions: BIAsp 30 therapy appeared safe and effective and improved quality of life in Iranian patients with type 2 diabetes after 26 weeks of treatment. (Pol J Endocrinol 2010; 61 (4): 364-370)Wstęp: Celem badania była ocena profilu działania insuliny BIAsp 30 (30% rozpuszczalnej insuliny aspart, 70% insuliny krystalizowanej z protaminą) (NovoMix®30) u chorych na cukrzycę typu 2 w warunkach standardowej opieki zdrowotnej w Iranie. Materiał i metody: IMPROVE&#8482; było 26-tygodniowym, wieloośrodkowym, międzynarodowym, otwartym i nierandomizowanym badaniem z udziałem chorych na cukrzycę typu 2. Bezpieczeństwo i skuteczność insulin BIAsp 30 oceniano na początku badania oraz po 13 i 26 tygodniach. Dawkowanie insuliny BIAsp30 było zależne od zaleceń lekarskich. Wyniki: W irańskiej części badania uczestniczyło 478 chorych (47% stanowili mężczyźni) leczonych dotychczas doustnymi lekami hipoglikemizującymi (N = 159, 33,3%) i/lub insuliną inną niż BIAsp30 (N = 317, 66,3%) oraz nieliczna grupa pacjentów niestosujących wcześniej farmakoterapii (N = 2, 0,4%). Po 26 tygodniach leczenia insuliną BIAsp 30, częstość epizodów ciężkiej hipoglikemii zmniejszyła się o 88,1% (wartości wyjściowe v. tydzień 26: 0,303 v. 0,037 epizodów/pacjenta-rok; p < 0,001). Dane dotyczące częstości epizodów lekkiej hipoglikemii na początku badania i po 26 tygodniach leczenia nie różniły się istotnie. Odnotowano natomiast poprawę kontroli glikemii; po 26 tygodniach odsetek HbA1c obniżył się średnio o 1,2 &#177; 1,9% w stosunku do wartości wyjściowej. W okresie od rozpoczęcia do zakończenia badania nastąpiła istotna poprawa jakości życia chorych, oceniana przy użyciu kwestionariusza DiabMedSat; punktacja wynosiła odpowiednio 58,1 i 75,4 (p < 0,001). Wnioski: Terapia insuliną BIAsp 30 stosowana przez 26 tygodni u Irańczyków chorych na cukrzycę typu 2 okazała się bezpieczna i skuteczna, a ponadto spowodowała poprawę jakości życia pacjentów. (Endokrynol Pol 2010; 61 (4): 364-370

Genes Involved in Oxidative Stress Pathways Are Differentially Expressed in Circulating Mononuclear Cells Derived From Obese Insulin-Resistant and Lean Insulin-Sensitive Individuals Following a Single Mixed-Meal Challenge.

Background: Oxidative stress induced by nutritional overload has been linked to the pathogenesis of insulin resistance, which is associated with metabolic syndrome, obesity, type 2 diabetes and diabetic vascular complications. Postprandial changes in expression of oxidative stress pathway genes in obese vs. lean individuals, following intake of different types of meals varying in macronutrient composition have not been characterized to date. Here we aimed to test whether/how oxidative stress responses in obese vs. lean individuals are modulated by meal composition. Methods: High-carbohydrate (HC), high-fat (HF), or high-protein (HP) liquid mixed meals were administered to study subjects (lean insulin-sensitive, n = 9 and obese insulin-resistant, n = 9). Plasma levels of glucose and insulin, lipid profile, urinary F2-isoprostanes (F2-IsoP), and expression levels of genes of oxidative stress pathways were assessed in mononuclear cells (MNC) derived from fresh peripheral blood, at baseline and up to 6-h postprandial states. Differences in these parameters were compared between insulin-sensitive/resistant groups undergoing aforementioned meal challenges. Results: Obese individuals exhibited increased pro-oxidant (i.e., CYBB and CYBA) and anti-oxidant (i.e., TXN RD1) gene expression in the postprandial state, compared with lean subjects, regardless of meal type (P interaction for group × time < 0.05). By contrast, lean subjects had higher expression of NCF-4 gene (pro-oxidant) after HC meal and SOD1 gene (anti-oxidant) after HC and HF meals (P interaction for group × meal < 0.05). There was an increase in postprandial level of urinary F2-IsoP in the obese (P < 0.05) but not lean group. Conclusions: These findings may represent an adaptive oxidative response to mitigate increased stress induced by acute nutritional excess. Further, the results suggest an increased predisposition of obese subjects to oxidative stress. Chronic nutritional excess resulting in increases in body weight and adiposity might lead to decompensation leading to worsening insulin resistance and its sequel. Insights from this study could impact on nutritional recommendations for obese subjects at high-risk of cardiovascular diseases

RAPID REPORTS Population and social conditions. Pupils and students in the Community in 1990/91. 1993.9

<div><p>It is known that the macronutrient content of a meal has different impacts on the postprandial satiety and appetite hormonal responses. Whether obesity interacts with such nutrient-dependent responses is not well characterized. We examined the postprandial appetite and satiety hormonal responses after a high-protein (HP), high-carbohydrate (HC), or high-fat (HF) mixed meal. This was a randomized cross-over study of 9 lean insulin-sensitive (mean±SEM HOMA-IR 0.83±0.10) and 9 obese insulin-resistant (HOMA-IR 4.34±0.41) young (age 21–40 years), normoglycaemic Chinese men. We measured fasting and postprandial plasma concentration of glucose, insulin, active glucagon-like peptide-1 (GLP-1), total peptide-YY (PYY), and acyl-ghrelin in response to HP, HF, or HC meals. Overall postprandial plasma insulin response was more robust in the lean compared to obese subjects. The postprandial GLP-1 response after HF or HP meal was higher than HC meal in both lean and obese subjects. In obese subjects, HF meal induced higher response in postprandial PYY compared to HC meal. HP and HF meals also suppressed ghrelin greater compared to HC meal in the obese than lean subjects. In conclusion, a high-protein or high-fat meal induces a more favorable postprandial satiety and appetite hormonal response than a high-carbohydrate meal in obese insulin-resistant subjects.</p></div

Heredity of type 2 diabetes confers increased susceptibility to oxidative stress and inflammation.

INTRODUCTION AND OBJECTIVE: Heredity of type 2 diabetes mellitus (T2DM) is associated with greater risk for developing T2DM. Thus, individuals who have a first-degree relative with T2DM (FDRT) provide a natural model to study factors of susceptibility towards development of T2DM, which are poorly understood. Emerging key players in T2DM pathophysiology such as adverse oxidative stress and inflammatory responses could be among possible mechanisms that predispose FDRTs to develop T2DM. Here, we aimed to examine the role of oxidative stress and inflammatory responses as mediators of this excess risk by studying dynamic postprandial responses in FDRTs. RESEARCH DESIGN AND METHODS: In this open-label case-control study, we recruited normoglycemic men with (n=9) or without (n=9) a family history of T2DM. We assessed plasma glucose, insulin, lipid profile, cytokines and F2-isoprostanes, expression levels of oxidative and inflammatory genes/proteins in circulating mononuclear cells (MNC), myotubes and adipocytes at baseline (fasting state), and after consumption of a carbohydrate-rich liquid meal or insulin stimulation. RESULTS: Postprandial glucose and insulin responses were not different between groups. Expression of oxidant transcription factor NRF2 protein (p<0.05 for myotubes) and gene (pgroup=0.002, ptime×group=0.016), along with its target genes TXNRD1 (pgroup=0.004, ptime×group=0.007), GPX3 (pgroup=0.011, ptime×group=0.019) and SOD-1 (pgroup=0.046 and ptime×group=0.191) was upregulated in FDRT-derived MNC after meal ingestion or insulin stimulation. Synergistically, expression of target genes of inflammatory transcription factor nuclear factor kappa B such as tumor necrosis factor alpha (pgroup=0.001, ptime×group=0.007) was greater in FDRT-derived MNC than in non-FDRT-derived MNC after meal ingestion or insulin stimulation. CONCLUSIONS: Our findings shed light on how heredity of T2DM confers increased susceptibility to oxidative stress and inflammation. This could provide early insights into the underlying mechanisms and future risk of FDRTs for developing T2DM and its associated complications

Plasma Protein and MicroRNA Biomarkers of Insulin Resistance: A Network-Based Integrative -Omics Analysis

Although insulin resistance (IR) is a key pathophysiologic condition underlying various metabolic disorders, impaired cellular glucose uptake is one of many manifestations of metabolic derangements in the human body. To study the systems-wide molecular changes associated with obesity-dependent IR, we integrated information on plasma proteins and microRNAs in eight obese insulin-resistant (OIR, HOMA-IR &gt; 2.5) and nine lean insulin-sensitive (LIS, HOMA-IR &lt; 1.0) normoglycemic males. Of 374 circulating miRNAs we profiled, 65 species increased and 73 species decreased in the OIR compared to the LIS subjects, suggesting that the overall balance of the miRNA secretome is shifted in the OIR subjects. We also observed that 40 plasma proteins increased and 4 plasma proteins decreased in the OIR subjects compared to the LIS subjects, and most proteins are involved in metabolic and endocytic functions. We used an integrative -omics analysis framework called iOmicsPASS to link differentially regulated miRNAs with their target genes on the TargetScan map and the human protein interactome. Combined with tissue of origin information, the integrative analysis allowed us to nominate obesity-dependent and obesity-independent protein markers, along with potential sites of post-transcriptional regulation by some of the miRNAs. We also observed the changes in each -omics platform that are not linked by the TargetScan map, suggesting that proteins and microRNAs provide orthogonal information for the progression of OIR. In summary, our integrative analysis provides a network of elevated plasma markers of OIR and a global shift of microRNA secretome composition in the blood plasma

PERTURBATION IN IMMUNE-METABOLIC FUNCTION ASSOCIATED WITH OBESITY INDUCED INSULIN RESISTANCE IN HUMANS

Ph.DDOCTOR OF PHILOSOPH

A high carbohydrate, but not fat or protein meal attenuates postprandial ghrelin, PYY and GLP-1 responses in Chinese men

Dataset for replication of work published by PLOS One entitled "A high carbohydrate, but not fat or protein meal attenuates postprandial ghrelin, PYY and GLP-1 responses in Chinese men

Heredity of type 2 diabetes confers increased susceptibility to oxidative stress and inflammation.

INTRODUCTION AND OBJECTIVE:Heredity of type 2 diabetes mellitus (T2DM) is associated with greater risk for developing T2DM. Thus, individuals who have a first-degree relative with T2DM (FDRT) provide a natural model to study factors of susceptibility towards development of T2DM, which are poorly understood. Emerging key players in T2DM pathophysiology such as adverse oxidative stress and inflammatory responses could be among possible mechanisms that predispose FDRTs to develop T2DM. Here, we aimed to examine the role of oxidative stress and inflammatory responses as mediators of this excess risk by studying dynamic postprandial responses in FDRTs. RESEARCH DESIGN AND METHODS:In this open-label case-control study, we recruited normoglycemic men with (n=9) or without (n=9) a family history of T2DM. We assessed plasma glucose, insulin, lipid profile, cytokines and F2-isoprostanes, expression levels of oxidative and inflammatory genes/proteins in circulating mononuclear cells (MNC), myotubes and adipocytes at baseline (fasting state), and after consumption of a carbohydrate-rich liquid meal or insulin stimulation. RESULTS:Postprandial glucose and insulin responses were not different between groups. Expression of oxidant transcription factor NRF2 protein (p<0.05 for myotubes) and gene (pgroup=0.002, ptime×group=0.016), along with its target genes TXNRD1 (pgroup=0.004, ptime×group=0.007), GPX3 (pgroup=0.011, ptime×group=0.019) and SOD-1 (pgroup=0.046 and ptime×group=0.191) was upregulated in FDRT-derived MNC after meal ingestion or insulin stimulation. Synergistically, expression of target genes of inflammatory transcription factor nuclear factor kappa B such as tumor necrosis factor alpha (pgroup=0.001, ptime×group=0.007) was greater in FDRT-derived MNC than in non-FDRT-derived MNC after meal ingestion or insulin stimulation. CONCLUSIONS:Our findings shed light on how heredity of T2DM confers increased susceptibility to oxidative stress and inflammation. This could provide early insights into the underlying mechanisms and future risk of FDRTs for developing T2DM and its associated complications

Additional file 2: Table S2. of Metabolic gene expression profile in circulating mononuclear cells reflects obesity-associated metabolic inflexibility

Primers used for SYBR Green Assay and their properties. (XLSX 11 kb

Incremental area-under-the-curve (iAUC) over 6 hours for plasma glucose, insulin, PYY, GLP-1, and ghrelin after ingestion of high-protein (HP), high-fat (HF) and high-carbohydrate (HC) meal.

<p>Incremental area-under-the-curve (iAUC) over 6 hours for plasma glucose, insulin, PYY, GLP-1, and ghrelin after ingestion of high-protein (HP), high-fat (HF) and high-carbohydrate (HC) meal.</p