Low interleukin-2 receptor levels in serum of patients with insulin-dependent diabetes

Interleukin-2 receptors are released in the circulation in response to antigenic or mytogenic stimulation of T-lymphocytes. Abnormal serum interleukin-2 receptor levels have been found in young children with type 1 diabetes and prediabetes. We measured interleukin-2 receptor levels in 17 patients with newly diagnosed type 1 diabetes, 21 patients with long-standing type 1 diabetes, 19 patients with long-standing type 2 diabetes, 19 islet-cell antibody positive nondiabetic polyendocrine patients, 12 islet-cell antibody-positive first-degree relatives of patients with type 1 diabetes and compared the results to age- and sex-matched normal controls. We found significantly lower interleukin-2 receptor levels in patients with newly diagnosed and long-standing type 1 diabetes compared to normal controls (87 ± 11 and 93 ± 11 vs. 142 ± 25 and 132 ± 40 U/ml, P < 0.001 and P < 0.01). There were no significant differences in interleukin-2 receptor levels between prediabetic groups and normal controls or patients with long-standing type 1 or type 2 diabetes. There was no correlation between glycosylated hemoglobin, blood glucose levels, and interleukin-2 receptor in the groups with long-standing type 1 or type 2 diabetes. We conclude that patients with type 1 diabetes have low interleukin-2 receptor serum levels. This phenomenon is acquired close to disease onset and is unlikely to be an early markers of type 1 diabetes.Abbreviations JDf Juvenile Diabetes foundation - ICA⁺ islet-cell antibody positive - IDDM insulin-dependent diabetes mellitus - IL-2R® interleukin-2 receptors - NIDDM non-insulin-dependent diabetes mellitus Correspondence to: R. Wagner     

二甲双胍对糖尿病前期患者血清C反应蛋白及胰岛素敏感指数的影响

目的:观察糖尿病前期患者应用二甲双胍降糖治疗或强化生活方式干预前后血清、高敏C反应蛋白(hs-CRP)及胰岛素敏感指数水平变化情况。方法:筛选糖尿病前期患者176例,随机分成二甲双胍治疗组、强化生活方式干预组和对照组,二甲双胍治疗组52例,在一般生活方式干预基础上给予二甲双胍片口服;强化生活方式干预组60例,根据个人饮食习惯为基础,制定热能。给予低脂饮食,控制饮食,配合适当的体育锻炼。对照组64例,仅给予一般生活方式干预。测定干预治疗前后的空腹血糖、餐后2 h血糖、糖化血红蛋白、体重指数、血脂、hs-CRP、胰岛素敏感指数变化。结果:经干预治疗2年后,对照组糖耐量转为正常21例(32.81%),转为糖尿病12例(18.75%);二甲双胍组糖耐量转为正常41例(78.85%),转为糖尿病3例(5.77%),强化生活方式干预组转为正常32例(53.33%),转为糖尿病4例(6.67%)。与对照组相比,二甲双胍组及强化生活方式干预组的糖尿病发生率差异有统计学意义(P<0.05)。干预治疗2年后,二甲双胍治疗组及强化生活方式干预组各项指标均有明显变化,且二甲双胍治疗组效果优于强化生活方式干预组(P<0.01)。结论:糖尿病前期时,血清hs-CRP水平已经开始升高,且胰岛素敏感性下降,二甲双胍降糖治疗或强化生活方式干预均能明显减低血糖,并降低血清C反应蛋白(CRP)水平,改善胰岛素敏感性,二甲双胍作用更明显。     

Association of body mass index with risk of prediabetes in Chinese adults: A population‐based cohort study

Aims/IntroductionOverweight and obesity in adults are strongly associated with an increased risk of prediabetes, and this study set out to gain a better understanding of the optimal body mass index (BMI) range for assessing the risk of prediabetes in the Chinese population.Materials and MethodsThe cohort study included 100,309 Chinese adults who underwent health screening. Participants were divided into six groups based on the cut‐off point for BMI recommended by the World Health Organization (underweight: <18.5 kg/m², normal‐weight: 18.5–24.9 kg/m², pre‐obese: 25.0–29.9 kg/m², obese class I: 30.0–34.9 kg/m², obese class II: 35.0–39.9 kg/m², and obese class III ≥40 kg/m²). The association of BMI with prediabetes and the shape of the correlation were modeled using multivariate Cox regression and restricted cubic spline regression, respectively.ResultsIn the multivariate Cox regression model, with normal weight as the control group, underweight people had a lower risk of developing prediabetes, whereas obese and pre‐obese people had a higher risk of prediabetes. Additionally, in the restricted cubic spline model, we found that the association of BMI with prediabetes follows a positive dose–response relationship, but does not conform to the pattern of obesity paradox. Among the general population in China, a BMI of 23.03 kg/m² might be a potential intervention threshold for prediabetes.ConclusionsThe national cohort study found that the association of BMI with prediabetes follows a positive dose–response relationship, rather than a pattern of obesity paradox. For Chinese people with normal weight, more attention should be paid to glucose metabolism when BMI exceeds 23.03 kg/m².     

Clearing hepatitis C virus with direct antiviral agents reduces cardiovascular events in patients with prediabetes. Commentary to Sasso and colleagues

Liver health is a key determinant of cardiovascular risk (CVR). Hepatic fibrosis is the shared common result of chronic hepatitis, irrespective of aetiology. Fibrosis profoundly distorts liver tissue architecture and perturbs hepatic physiology, dictates the course of chronic liver disease and is increasingly recognized as a CVR factor. The relative weights of pre-diabetes and hepatic fibrosis as risk factors for major adverse cardiac events (MACE) in patients with HCV remain an open issue. Sasso and Colleagues answered this research question by treating approximately half of 770 HCV positive pre-diabetic patients with direct antiviral agents (DAAs), while the rest served as historical controls. Data have shown that achieving HCV clearance with DAAs was associated with a 60% reduced risk of MACE, thereby implying that this antiviral strategy is recommended in HCV positive pre-diabetic patients, regardless of the severity of liver disease and concurrent CVR factors. This study paves the way for additional studies addressing the molecular patho-mechanisms and changes in the clinical spectrum involved in cardio-metabolic protection following HCV eradication in patients with pre-diabetes.     

Perfil lipoproteico avanzado en individuos con metabolismo glucémico normal y alterado

Introduction and objectivesSeveral types of lipoproteins beyond low-density lipoproteins (LDL) are causally related to cardiovascular disease. We aimed to analyze an advanced lipoprotein profile in individuals with normal and impaired glucose metabolism from different cohorts of a Mediterranean region.MethodsCross-sectional study in 929 participants (463 normoglycemia, 250 prediabetes, and 216 type 2 diabetes mellitus) with normal renal function, free from cardiovascular disease, and without lipid-lowering treatment. Conventional and advanced (nuclear magnetic resonance [NMR] spectroscopy) lipoprotein profiles were analyzed.ResultsCompared with men, normoglycemic women showed lower serum triglyceride and LDL cholesterol concentrations, lower total LDL particles (P) as well as their subclasses and their cholesterol and triglyceride content, higher high-density lipoproteins (HDL)-P and all HDL-related variables (P  ≤  .05 for all comparisons). Compared with normoglycemic participants, diabetic participants showed higher large and small very LDL-P concentrations (P < .05) and lower total HDL-P and medium HDL-P concentrations (P < .05). Waist circumference and Fatty Liver Index were positively associated with a proatherogenic profile.ConclusionsWomen had a better advanced lipoprotein profile than did men. Adiposity indexes related to insulin-resistance were positively associated with a proatherogenic lipid profile. NMR revealed altered lipoprotein particles other than LDL in participants with diabetes, frequently associated with an increased cardiovascular risk. Our findings support the usefulness of extended lipoprotein analysis by NMR spectroscopy to uncover new therapeutic targets to prevent cardiovascular events in at-risk participants.     

Evaluation of serum zonulin level in prediabetic patients

BackgroundThis study aimed to investigate the relationship between lipopolysaccharide (LPS) and zonulin levels and also to show the effect of acute hyperglycemic stress induced by oral glucose tolerance testing (OGTT) on zonulin levels in pre-diabetic patients.MethodsFour groups were constituted according to the criteria of the American Diabetes Association (ADA), based on OGTT results: control group (n:40); prediabetic group (n:56), divided into two subgroups: impaired fasting glucose group (IFG) (n:36), and impaired glucose tolerance (IGT) + IFG group (n:20) and type-2 diabetes mellitus (T2DM) group (n:45).ResultsZonulin and LPS did not significantly differ between the prediabetes and control groups, but were significantly higher in the T2DM group compared to both the prediabetic and the control group (P < 0.001). After OGTT, zonulin and LPS were significantly higher in the prediabetes group compared to the control group (P < 0.01 and P < 0.05, respectively), and significantly lower in the IFG and IFG + IGT groups compared to the T2DM group (P < 0.001, P < 0.001 and P < 0.001, P < 0.001, respectively). A positive correlation was detected between fasting zonulin and 2-hour zonulin (r = 0.727, P < 0.001) and between fasting LPS (r = 0.555, P < 0.001) and 2-hour LPS (r = 0.567, P < 0.001) in the prediabetic group. Increased zonulin and LPS levels and the positive correlation between these levels during the prediabetic period although non significant suggests onset of intestinal permeability.ConclusionsDuring acute hyperglycemia in prediabetic patients, up-regulation of zonulin and LPS may affect intestinal function. The intestines may play a key role in up-regulation of glucose and the pathogenesis of diabetes.     

Association between hepatic iron overload assessed by magnetic resonance imaging and glucose intolerance states in the general population

Background and aimWhile there is evidence that iron overload disorders are associated with type 2 diabetes, the relationship between hepatic iron overload and prediabetes remains unclear. We aimed to investigate the association between hepatic iron overload, as assessed by magnetic resonance imaging (MRI), and different glucose intolerance states in the population-based Study.Methods and resultsWe included data from 1622 individuals with MRI data, who did not have known type 2 diabetes (T2DM). Using an oral glucose tolerance testing, participants were classified as having isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG and IGT (IFG + IGT) or previously unknown T2DM. Hepatic iron and fat contents were assessed through quantitative MRI. We undertook linear and multinomial logistic regression models adjusted for potential confounders and MRI-assessed hepatic fat content to examine the association of hepatic iron overload with different glucose intolerance states or continuous markers of glucose metabolism.MRI-assessed hepatic iron overload was positively associated only with both 2-h plasma glucose (β = 0.32; 95%CI 0.04–0.60) and the combined IFG + IGT category (relative risk ratio = 1.87; 95%CI 1.15–3.06). No significant associations were found between hepatic iron overload and other glucose intolerance states or biomarkers of glucose metabolism, independently of potential confounders.ConclusionsMRI-assessed hepatic iron overload was associated with higher 2-h glucose concentrations and the combined IFG + IGT category, but not with other glucose intolerance states. Our findings suggest a weak adverse impact of hepatic iron overload on glucose metabolism, but further studies are needed to confirm these findings.     

Longitudinal Changes in Insulin Resistance,Beta-Cell Function and Glucose Regulation Status in Prediabetes

Background

The changes in insulin resistance and insulin secretion and their association with changes in glucose regulation status in Asians with prediabetes remain uncertain.

Prevención de ictus en pacientes con diabetes mellitus tipo 2 o prediabetes. Recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología

ObjectiveTo update the Spanish Society of Neurology's guidelines for stroke prevention in patients with type 2 diabetes or prediabetes, analysing the available evidence on the effect of metabolic control and the potential benefit of antidiabetic drugs with known vascular benefits in addition to conventional antidiabetic treatments in stroke prevention.DevelopmentPICO-type questions (Patient, Intervention, Comparison, Outcome) were developed to identify practical issues in the management of stroke patients and to establish specific recommendations for each of them. Subsequently, we conducted systematic reviews of the PubMed database and selected those randomised clinical trials evaluating stroke as an independent variable (primary or secondary). Finally, for each of the PICO questions we developed a meta-analysis to support the final recommendations.ConclusionsWhile there is no evidence that metabolic control reduces the risk of stroke, some families of antidiabetic drugs with vascular benefits have been shown to reduce these effects when added to conventional treatments, both in the field of primary prevention in patients presenting type 2 diabetes and high vascular risk or established atherosclerosis (GLP-1 agonists) and in secondary stroke prevention in patients with type 2 diabetes or prediabetes (pioglitazone).     

Obésité et diabète. Les variations des acides gras libres circulants sous charge orale en glucose

Résumé L'étude des variations des acides gras libres (AGL) du plasma est entreprise chez 58 sujets obèses et 18 sujets normaux témoins, mis dans des conditions d'exploration identiques. On constate chez les sujets obèses un comportement global des AGL qui est différent de celui des sujets normaux témoins dans la mesure où la dépression initiale de leur taux est plus lente et le maximum de chute est différé aux temps tardifs de l'épreuve. Il en résulte une tendance globale à une absence de réascension secondaire du taux des AGL circulants, à l'inverse de ce qui succède chez le sujet normal, où la valeur moyenne des AGL à la 4^ème h de l'épreuve est plus élevée que le taux moyen de base. Tant chez le sujet normal que chez le sujet obèse, on constate d'importantes variations individuelles. Les anomalies rencontrées chez les obèses sont d'autant plus évidentes que la tolérance glucidique se rapproche des conditions du diabète; cela laisse à penser qu'il existe, chez ces sujets, des relations étroites entre la dégradation de la tolérance glucidique et les anomalies du comportement des AGL circulants. Ce dernier problème est discuté en fonction des relations entre l'obésité et la maladie diabétique.

---

Summary The variations of plasma non-esterified fatty acids (NEFA) in 58 obese subjects and 18 normal controls have been studied in identical conditions of investigation. The overall behavior of NEFA in the obese differed from that in the controls in that the initial fall was slower and the maximum depression occurred late in the test. Hence the overall tendency was for the secondary rise in the NEFA level to be missing, which was the reverse of what happened in the normals, in whom the mean NEFA value at the 4th h was above the starting value. Both in normals and in obese subjects there was a considerable individual variation. The anomalies in the obese became more marked as carbohydrate tolerance approached diabetic level; this suggests that there is in these subjects a close connexion between the decline of carbohydrate tolerance and the anomalies of plasma NEFA behavior. The latter is discussed in terms of the relationships between obesity and diabetes.

---

Zusammenfassung Bei 58 Fettsüchtigen und 18 Normalpersonen wurden unter identischen Versuchsbedingungen die Variationen der freien Fettsäuren des Plasma (FFA) verfolgt. Bei Fettsüchtigen wurde ein von den Normalpersonen verschiedenes Gesamtverhalten der FFA festgestellt; der Unterschied ist umso grösser je langsamer die anfängliche Senkung des FFA-Spiegels bei den Fettsüchtigen erfolgt und je mehr das Maximum der Abnahme verzögert ist. Daraus ergibt sich eine Gesamttendenz zum Fehlen des sekundären Anstiegs des zirkulierenden FFA-Spiegels, im Gegensatz zu den Verhältnissen bei Normalpersonen, wo der Mittelwert der FFA in der 4. Stunde der Probe höher ist als der mittlere Ausgangswert. Sowohl bei Normalpersonen als auch bei Fettsüchtigen werden erhebliche individuelle Unterschiede beobachtet. Die bei Fettsüchtigen beobachteten Anomalien sind umso ausgesprochener je mehr sich ihre Kohlehydrattoleranz einer diabetischen Stoffwechsellage nähert; das lässt den Verdacht aufkommen, dass bei diesen Individuen eine enge Beziehung zwischen der verminderten Glukosetoleranz und dem abnormen Verhalten der zirkulierenden FFA besteht. Dieses Problem wird im Hinblick auf die Beziehungen zwischen Fettsucht und Diabetes mellitus besprochen.

---

Resumen Se emprendió el estudio de las variaciones de los ácidos grasos libres (AGL) del plasma en 58 individuos obesos y 18 testigos normales, puestos en idénticas condiciones de exploración Se constata que en los sujetos obesos un comportamiento global de los AGL es diferente al de los individuos testigos normales en la medida o la depresión de su porcentaje es más lento y el máximo de caída se difiere a los tiempos tardíos de la prueba. Resulta una tendencia global a una ausencia de reascensión secundaria del porcentaje de los AGL circulantes, al contrario de lo que sucede en el individuo normal, en el que el valor medio de los AGL a las cuatro horas de la prueba es más elevado que el porcentaje medio de base. Tanto en el sujeto normal como en el sujeto obeso, se comprueban importantes variaciones individuales. Las anomalías encontradas en los obesos son mucho más evidentes cuando la tolerancia se acerca a las condiciones de la diabetes; esto lleva a pensar que existe, en estos individuos, estrechas relaciones entre la degradación y la tolerancia glucídica y las anomalias del comportamiento de los AGL circulantes. Este último problema se discute en función de las relaciones entre la obesidad y la enfermedad diabética.

---

Riassunto Le variazioni dei NEFA plasmatici sono state studiate in 58 pazienti obesi e in 18 individui normali di controllo, posti in condizioni sperimentali identiche. Nei soggetti obesi è stato osservato un comportamento globale dei NEFA diverso da quello degli individui normali di controllo, nel senso che la depressione iniziale è più lenta e la massima caduta si verifica nelle fasi tardive della prova. Ne risulta una tendenza globale all'assenza di risalita secondaria dei NEFA circolanti, contrariamente a quanto avviene nel soggetto normale, in cui il valore medio dei NEFA alla 4^a ora del test è più elevato rispetto al livello medio di base. Sia nel soggetto normale che nell'obeso, si riscontrano importanti variazioni individuali. Le anomalie rilevate negli obesi sono tanto più evidenti quanto più la tolleranza al glucosio si avvicina alle condizioni esistenti nel diabete: ciò induce a ritenere che in questi soggetti esistano stretti rapporti tra la diminuzione della tolleranza al glucosio e le anomalie del comportamento dei NEFA circolanti. Quest'ultimo problema viene discusso alla luce delle relazioni tra obesità e malattia diabetica.