Identification of variables influencing resistin serum levels in patients with type 1 and type 2 diabetes mellitus.

BACKGROUND: Resistin, a peptide hormone, has been discussed controversially as a missing link between obesity and insulin resistance. In contrast to resistin mRNA expression in adipose tissue, data on human serum levels in obesity and diabetes mellitus is scarce. The physiological range of serum resistin levels, reference values or adjusted percentiles have not yet been determined, making the interpretation of serum resistin concentrations quite difficult. METHODS: Resistin serum concentrations were measured systematically by ELISA in 216 healthy controls, 555 patients with type 2 diabetes and 114 patients with type 1 diabetes. Mean values, median, and range were determined, and BMI-, gender-, and disease-adapted percentiles were calculated for all subgroups. RESULTS: Age and gender did not have any influence on resistin levels. BMI and resistin levels were positively correlated in healthy controls (p = 0.02), albeit with a weak correlation coefficient. This correlation was absent in patients with type 1 and type 2 diabetes. In both genders, healthy controls had significantly higher resistin levels than patients with type 1 and type 2 diabetes (7.9 +/- 0.2 ng/ml vs. 5.7 +/- 0.2 ng/ml and 5.5 +/- 0.1 ng/ml, respectively; p < 0.0001). There was no correlation between resistin levels and occurrence of diabetic retinopathy or nephropathy. CONCLUSIONS: Serum resistin levels can be measured by ELISA over a broad range from 0.6 ng/ml up to 27.7 ng/ml, suggesting that percentiles might be helpful in the interpretation of an individuals resistin value. While age and gender do not influence resistin levels, BMI and occurrence of diabetes have to be considered.     

Inverse correlation between serum levels of selenoprotein P and adiponectin in patients with type 2 diabetes

Background

We recently identified selenoprotein P (SeP) as a liver-derived secretory protein that causes insulin resistance in the liver and skeletal muscle; however, it is unknown whether and, if so, how SeP acts on adipose tissue. The present study tested the hypothesis that SeP is related to hypoadiponectinemia in patients with type 2 diabetes.

Methodology/Principal Findings

We compared serum levels of SeP with those of adiponectin and other clinical parameters in 36 patients with type 2 diabetes. We also measured levels of blood adiponectin in SeP knockout mice. Circulating SeP levels were positively correlated with fasting plasma glucose (r = 0.35, P = 0.037) and negatively associated with both total and high-molecular adiponectin in patients with type 2 diabetes (r = −0.355, P = 0.034; r = −0.367, P = 0.028). SeP was a predictor of both total and high-molecular adiponectin, independently of age, body weight, and quantitative insulin sensitivity index (β = −0.343, P = 0.022; β = −0.357, P = 0.017). SeP knockout mice exhibited an increase in blood adiponectin levels when fed regular chow or a high sucrose, high fat diet.

Conclusions/Significance

These results suggest that overproduction of liver-derived secretory protein SeP is connected with hypoadiponectinemia in patients with type 2 diabetes.     

The effect of coenzyme Q10 administration on metabolic control in patients with type 2 diabetes mellitus.

A possible relationship between the pathogenesis of type 2 diabetes and coenzyme Q10 (CoQ10) deficiency has been proposed. The aim of this study was to assess the effect of CoQ10 on metabolic control in 23 type 2 diabetic patients in a randomized, placebo-controlled trial. Treatment with CoQ10 100 mg bid caused a more than 3-fold rise in serum CoQ10 concentration (p < 0.001). No correlation was observed between serum CoQ10 concentration and metabolic control. No significant changes in metabolic parameters were observed during CoQ10 supplementation. The treatment was well tolerated and did not interfere with glycemic control, therefore CoQ10 may be used as adjunctive therapy in patients with associated cardiovascular diseases.     

Development of impaired glucose tolerance and diabetes in follow-up offspring of Caribbean patients with type 2 diabetes: analysis of 5-year follow-up study

Several reports agreed that the antecedent markers for developing diabetes in offspring of type 2 diabetic patients involve excess body weight and insulin resistance. This study examined the pattern of changes in anthropometric and biochemical risk factors for developing diabetes in a follow-up offspring of Caribbean type 2 diabetic patients. Results of 46 offspring of type 2 diabetic patients who had received one-to-one individualized diet and exercise counseling for 5 years in our laboratory were analyzed. Changes in anthropometric (body weight, waist circumference) and biochemical (insulin, glucose, lipids, HOMA-insulin resistance, HOMA-percent beta-cell function) parameters over the 5-year period were analyzed using ANOVA tests. Of the 46 offspring, 10.9 and 2.2%, respectively, developed impaired glucose tolerance (IGT) and diabetes. Over the years, IGT offspring had a significant step-wise increase and decrease in fasting and 2-h postprandial plasma glucose levels (P < 0.05) and percent B-cell function (P < 0.001), respectively. Again, a non-significant step-wise increase was observed in body mass index, waist circumference and HOMA-insulin resistance levels (P > 0.05). While we await the results of medication-based intervention studies in different populations, exercise and diet counseling will remain the only available lifestyle intervention strategy for slowing IGT progression to diabetes.     

Relationship between psychopathological factors and metabolic control in children and adolescents with insulin-dependent diabetes mellitus

This paper provides a critical overview of the literature on the relationship between psychological/psychopathological factors and metabolic control in children and adolescents with insulin dependent diabetes mellitus (IDDM). We discuss studies on individual and family psychopathological factors, as well as reports on the effects of psychoeducational/psychotherapeutic interventions on glycemic control in patients with IDDM aged <18 years. The analysis of the literature indicates that while evidence on the relationship between individual factors and metabolic control is still mixed, in part due to methodological issues, results from family studies do suggest that patients in dysfunctional families and children of parents with high degrees of psychopathology present with poor glycemic control. As for the effects of psychoeducational/psychotherapeutic interventions, limited but increasing evidence shows that they can actually contribute to improve metabolic control. We finally suggest some future underexplored avenues of research in the field, including studies on the psychopathological and neurobiological mechanisms underlying the above mentioned findings. All this body of research should provide a strong empirical rationale for allocating resources in order to include psychiatrists within the interdisciplinary diabetes health care team.     

Anti-GAD-positive patients with type 1 diabetes mellitus have higher prevalence of autoimmune thyroiditis than anti-GAD-negative patients with type 1 and type 2 diabetes mellitus

The aim of our study was to evaluate antibodies against thyroglobulin (anti-TG) and thyroid peroxidase (anti-TPO) - markers of autoimmune thyroiditis - in several groups of adult patients with type 1 and type 2 diabetes mellitus (DM). We were particularly interested whether the presence of thyroid antibodies is related to the positivity of glutamic acid decarboxylase antibodies (anti-GAD). We found elevated anti-GAD in 46 % (97/210) patients with type 1 DM. All patients with type 2 diabetes were anti-GAD-negative. At least one thyroid antibody (anti-TG and/or anti-TPO) was found in 30 % (62/210) patients with type 1 DM and 27 % (22/83) type 2 diabetes patients. The patients with type 1 DM were further grouped according to their anti-GAD status. The anti-GAD-positive patients had a higher prevalence of anti-TG antibodies than the anti-GAD-negative patients (25 % vs. 12 %, p=0.03) as well as anti-TPO antibodies (32 % vs. 12 %, p<0.001). At least one thyroid antibody was detected in 39 % (38/97) of anti-GAD-positive but only in 21 % (24/113) of anti-GAD-negative patients with type 1 DM (p=0.006). No significant difference in the frequency of thyroid antibodies was found between anti-GAD-negative patients with type 1 and type 2 DM (21 % vs. 27 %, p=0.4). The groups with or without thyroid antibodies in both type 1 and type 2 diabetic patients did not differ in actual age, the age at diabetes onset, duration of diabetes, body mass index or HbA1c level. Patients with elevated thyroid antibodies had significantly higher levels of TSH than those without thyroid antibodies (1.86 vs. 3.22 mIU/l, p=0.04 in type 1 DM; 2.06 vs. 4.89 mIU/l, p=0.003 in type 2 DM). We conclude that there is a higher frequency of thyroid-specific antibodies in anti-GAD-positive adult patients with type 1 DM than in anti-GAD-negative patients or in patients with type 2 DM. Patients with or without thyroid antibodies do not differ in age, DM onset and duration, BMI or HbA1c. Thyroid antibodies-positive patients have higher levels of thyroid stimulating hormone (TSH).     

Gluconeogenesis in moderately and severely hyperglycemic patients with type 2 diabetes mellitus

We tested the generally accepted concept that increased gluconeogenesis (GNG) and endogenous glucose production (EGP) are the main reasons for postabsorptive hyperglycemia in patients with type 2 diabetes mellitus (T2DM). GNG was measured with the (2)H(2)O method by use of both the C5-to-C2 ratio (C5/C2, with gas chromatography-mass spectrometry) and the C5-to-(2)H(2)O ratio (C5/(2)H(2)O, with isotope ratio mass spectrometry), and EGP was measured with 3-[(3)H]glucose in 27 patients with T2DM [13 with fasting plasma glucose (FPG) >10 mM and 14 with FPG <10 mM] and in 7 weight- and age-matched nondiabetic controls. The results showed 1) that GNG could be determined accurately with (2)H(2)O by using either C5/C2 or C5/(2)H(2)O; 2) that whereas after an overnight fast of 16 h, GNG was higher in the entire group of patients with T2DM than in controls (6.4 vs. 5.0 micromol. kg(-1). min(-1) or 60.4 vs. 51.4% of EGP, P < 0.02), GNG was within normal limits (less than the mean +/- 2 SD of controls or <65.3%) in 11/14 (79%) patients with mild to moderate hyperglycemia (FPG <10 mM) and in 5/13 (38%) of patients with severe hyperglycemia (FPG 10-20 mM); 3) that elevated GNG in T2DM was associated with a 43% decrease in prehepatic insulin secretion, i.e., with hepatic insulin deficiency; and 4) that FPG correlated significantly with glucose clearance (insulin resistance) (r = 0.70) and with GNG (r = 0.50) or EGP (r = 0.45). We conclude 1) that peripheral insulin resistance is at least as important as GNG (and EGP) as a cause of postabsorptive hyperglycemia in T2DM and 2) that GNG and EGP in T2DM are increased under conditions of significant hepatic insulin deficiency and thus probably represent a late event in the course of T2DM.     

Plasma resistin levels in patients with type 1 and type 2 diabetes mellitus and in healthy controls.

Resistin is a recently discovered hormone that is exclusively expressed in adipose tissue. Its expression in rodents was reported to be elevated or suppressed in genetic and diet-induced obesity, respectively. Resistin treatment impaired glucose tolerance and insulin action. Immunoneutralization of resistin improved insulin sensitivity, while thiazolidinedione treatment reduced resistin expression. Therefore, resistin could play a critical role in the development of obesity and type 2 diabetes. In this study were determined resistin plasma levels in humans suffering from type 1 and type 2 diabetes and in healthy controls. Plasma levels of resistin in healthy controls were 38.78 ng/ml. They were not statistically different in individuals with a broad BMI range. Resistin plasma levels in type 2 diabetes were 38.7 ng/ml, and 39.4 ng/ml in type 1 diabetes. Thiazolidinedione treatment did not influence resistin plasma levels. We conclude from our data: 1. resistin can be detected in human plasma, 2. plasma resistin levels are not different in type 1 and type 2 diabetes.     

Changes in HDL subfractions in patients with type I diabetes mellitus before and after metabolic control

In order to further investigate the behaviour of high density lipoproteins in diabetes mellitus, we studied HDL subclasses, HDL2 and HDL3, in 10 patients with newly detected, untreated insulin-deficient diabetes before starting insulin treatment and after getting a good metabolic control. We used the extractive method of Abell to determine HDL-cholesterol after LDL and VLDL precipitation with polyanions and HDL3-cholesterol after HDL2 precipitation with dextransulphate 15,000 m.w. After insulin therapy, we observed a significant increase in HDL-cholesterol and a decrease in serum triglycerides. Only HDL2-cholesterol, but not HDL3-cholesterol, raised; moreover, we found a significant inverse relationship between HDL-cholesterol (and also HDL2-cholesterol) and triglycerides. So, we think that an increase of lipoprotein lipase activity, owing to insulin treatment, could account for our results.     

Hormonal and metabolic counterregulation during and after high-dose insulin-induced hypoglycemia in diabetes mellitus type 2.

Non-obese type 2 diabetic subjects in good metabolic control (n=6, HbA1c 7.0 +/- 0.3%, mean diabetes duration: 5.7 +/- 1 years) and matched non-diabetic subjects (control; n = 6) were studied during hyperinsulinemic (approximately 3 nmol/l)-hypoglycemic (approximately 3.1 mmol/l) clamp tests (0-120 min) and the subsequent recovery period (120-240 min). Plasma glucagon rose gradually but not significantly, whereas norepinephrine and epinephrine similarly increased approximately 2 and approximately 25-fold in both groups. Islet amyloid polypeptide (IAPP) decreased to approximately 41% and approximately 24% of basal values during hypoglycemia and rapidly rose approximately 4.7-fold during the recovery period, while plasma C-peptide remained suppressed in both groups. Within 140 min, plasma free fatty acids similarly decreased to approximately 70 micromol/l (p < 0.05), but then rose to values being approximately 50% higher in diabetic than in control subjects (240 min: 907 +/- 93 vs. 602 +/- 90 micromol/l; p < 0.05). Glucose infusion rates were comparable during hypoglycemia, but approximately 40% lower during recovery in diabetic patients (1.88 +/- 0.27 vs. 3.44 +/- 0.27 mg x kg(-1) x min(-1), p < 0.001). These results demonstrate that (i) hypoglycemia induced by high-dose insulin largely abolishes the counterregulatory response of glucagon, but not of catecholamines in nondiabetic and well-controlled type 2 diabetic subjects, (ii) the rapid posthypoglycemic increase of plasma IAPP occurs independently of plasma insulin, and (iii) the superior rise in plasma free fatty acids may account at least in part for the posthypoglycemic insulin resistance of type 2 diabetic patients.     

Magnesium metabolism in type 2 diabetes mellitus, metabolic syndrome and insulin resistance

Type 2 diabetes is characterized by cellular and extracellular Mg depletion. Epidemiologic studies showed a high prevalence of hypomagnesaemia and lower intracellular Mg concentrations in diabetic subjects. Insulin and glucose are important regulators of Mg metabolism. Intracellular Mg plays a key role in regulating insulin action, insulin-mediated-glucose uptake and vascular tone. Reduced intracellular Mg concentrations result in a defective tyrosine-kinase activity, post-receptorial impairment in insulin action, and worsening of insulin resistance in diabetic patients. Mg deficit has been proposed as a possible underlying common mechanism of the "insulin resistance" of different metabolic conditions. Low dietary Mg intake is also related to the development of type 2 diabetes. Benefits of Mg supplementation on metabolic profile in diabetic subjects have been found in most, but not all clinical studies, and larger prospective studies are needed to support the potential role of dietary Mg supplementation as a possible public health strategy in diabetes risk.     

Relationship between IL-6, leptin and adiponectin and variables of fibrinolysis in overweight and obese hypertensive patients.

Impaired fibrinolysis is a common finding in obese humans. This condition is now considered as an established risk factor for thromboembolic complications. Furthermore, obesity is characterized by a specific pattern of circulating concentrations of fat-cell products interleukin-6 (IL-6), leptin, and adiponectin. The aim of our study was to investigate the relationship between these proteins and selected variables of the fibrinolytic system in 74 mildly hypertensive, overweight subjects. Circulating IL-6 and leptin levels showed a positive association with BMI (r = 0.24, p = 0.04 and r = 0.70, p < 0.0001), whereas adiponectin was not correlated to BMI. Interestingly, IL-6 was also positively associated with t-PA/PAI-1 complexes after adjustment for BMI and other anthropometric variables. Leptin was positively correlated with PAI-1 activity and antigen (r = 0.32, p = 0.006 and r = 0.37, p < 0.001, respectively) and negatively with t-PA activity (r = -0.27, p = 0.03). However, these associations lost significance after correction for BMI or HOMA, an insulin sensitivity index. In contrast, adiponectin levels were independently and negatively correlated with PAI-1 antigen (r = -0.26, p = 0.04, after correction for BMI). In conclusion, our study provides further evidence that IL-6, leptin, and adiponectin are associated with impaired fibrinolysis in overweight hypertensive humans.     

Intimal redox stress: Accelerated atherosclerosis in metabolic syndrome and type 2 diabetes mellitus. Atheroscleropathy

Metabolic syndrome, insulin resistance, prediabetes, and overt type 2 diabetes mellitus are associated with an accelerated atherosclerosis (atheroscleropathy). This quartet is also associated with multiple metabolic toxicities resulting in the production of reactive oxygen species. The redox stress associated with these reactive oxygen species contribute to the development, progression, and the final fate of the arterial vessel wall in prediabetic and diabetic atheroscleropathy. The prevention of morbidity and mortality of these intersecting metabolic diseases can be approached through comprehensive global risk reduction.     

SUMO4基因多态性与2型糖尿病的关系

为了探讨北京汉族人群小泛素样修饰蛋白4(Small ubiquitin-like modifier 4,SUMO4)基因多态性与2型糖尿病(Type 2 diabetes mellitus,T2DM)的关系,文章采用病例对照设计,选取404例T2DM患者(T2DM组)以及年龄、性别匹配的500例健康对照者(Control组)作为研究对象,应用聚合酶链反应-高分辨熔解曲线(PCR-HRM)技术结合测序验证法,检测SUMO4基因3个单核苷酸多态性位点(rs237025、rs237024及rs600739)的基因型与等位基因分布情况,比较T2DM组糖化血红蛋白(Hemoglobin A1c,HbA1c)在各基因型间的分布,并进行单倍型分析。结果显示:①rs237025的G等位基因在T2DM组出现的频率更高(0.334 vs.0.282,P=0.017);GA基因型携带者患T2DM的风险是AA基因型携带者的1.563倍(P=0.001;OR,1.563;95%CI,1.189-2.053);在显性模型(GG+GA vs.AA)分析中,G等位基因携带者(GG+GA)患T2DM的风险是AA基因型携带者的1.525倍(P=0.002;OR,1.525;95%CI,1.169-1.989)。而rs237024和rs600739多态性未发现与T2DM的易感性相关(P>0.05)。②在T2DM组,rs237025的G等位基因携带者、rs237024的TT基因型携带者及rs600739的GG基因携带者具有较高的HbA1c水平,但各基因型携带者之间HbA1c水平并无统计学差异(P>0.05)。③单倍型AAC、AGC及GGT与T2DM的易感性正相关(OR>1);而单倍型AAT、GAC与T2DM的易感性负相关(OR<1)。据此得出结论:rs237025多态性与北京汉族人群T2DM的易感性相关,rs237024和rs600739多态性可能与T2DM的易感性不相关。     

Phagocytic activity is impaired in type 2 diabetes mellitus and increases after metabolic improvement

Objective

1) To evaluate whether peripheral blood mononuclear cells (PBMCs) from type 2 diabetic patients present an impairment of phagocytic activity; 2) To determine whether the eventual impairment in phagocytic activity is related to glycemic control and can be reversed by improving blood glucose levels.

Methods

21 type 2 diabetic patients and 21 healthy volunteers were prospectively recruited for a case-control study. In addition, those patients in whom HbA1c was higher than 8% (n = 12) were hospitalized in order to complete a 5-day intensification treatment of blood glucose. Phagocytic activity was assessed by using a modified flow cytometry procedure developed in our laboratory based on DNA/RNA viable staining to discriminate erythrocytes and debris. This method is simple, highly sensitive and reproducible and it takes advantage of classic methods that are widely used in flow cytometry.

Results

Type 2 diabetic patients showed a lower percentage of activated macrophages in comparison with non-diabetic subjects (54.00±18.93 vs 68.53±12.77%; p = 0.006) Significant negative correlations between phagocytic activity and fasting glucose (r = −0.619, p = 0.004) and HbA1c (r = −0.506, p = 0.019) were detected. In addition, multiple linear regression analyses showed that either fasting plasma glucose or HbA1c were independently associated with phagocytic activity. Furthermore, in the subset of patients who underwent metabolic optimization a significant increase in phagocytic activity was observed (p = 0.029).

Conclusions

Glycemic control is related to phagocytic activity in type 2 diabetes. Our results suggest that improvement in phagocytic activity can be added to the beneficial effects of metabolic optimization.