Acute hyperinsulinemia is associated with increased circulating levels of adrenomedullin in patients with type 2 diabetes mellitus

OBJECTIVE: To investigate the effect of acute hyperinsulinemia on the plasma levels of adrenomedullin (AM) in patients with type 2 diabetes mellitus. DESIGN: We measured the plasma levels of AM in 18 patients with type 2 diabetes mellitus and in 19 normal subjects before and during a euglycemic hyperinsulinemic clamp study (the goal was for blood sugar levels of 5.24 mmol/l and insulin levels of 1200 pmol/l). Both plasma AM and serum insulin were measured by immunoradiometric assays. RESULTS: Before the glucose clamp study there was no significant difference in the plasma levels of AM between patients with type 2 diabetes mellitus and normal subjects. During the glucose clamp study, the serum levels of insulin significantly increased (from 33.0+/-3.6 to 1344.6+/-67.8 pmol/ml, P<0.001), as did the plasma levels of AM (from 12.8+/-0.7 to 14.2+/-0.9 fmol/ml, P<0.03) only in patients with type 2 diabetes mellitus. There was a significant correlation between the change in circulating levels of insulin and AM (r=0.755, P<0.01). CONCLUSIONS: Acute hyperinsulinemia induced a significant increase in the plasma levels of AM in patients with type 2 diabetes mellitus. Increased insulin may regulate circulating levels of AM in patients with type 2 diabetes mellitus.     

Hyperhomocysteinemia is associated with visceral adiposity in Japanese patients with type 2 diabetes mellitus

This study aims to investigate the relationship between the circulating level of homocysteine and body adiposity in Japanese patients with type 2 diabetes mellitus. We measured the body mass index (BMI), waist and hip circumferences, visceral and subcutaneous adiposities, visceral/subcutaneous (V/S) adiposity ratio, and insulin resistance as assessed by the Homeostasis Model Assessment (HOMA) index in patients with hyperhomocysteinemia. The study group consisted of 17 Japanese patients with type 2 diabetes and hyperhomocysteinemia (age: 62+/-10 years, mean+/-S.D.), and the control group consisted of 24 age-matched type 2 diabetes patients with normohomocysteinemia (60+/-11 years). The visceral adiposity, HOMA index, and V/S ratio were significantly higher in the hyperhomocysteinemia group than in the normohomocysteinemia group (P<0.05). In contrast, the BMI, hip circumference, and subcutaneous adiposity were similar between the two groups (P>0.1). Furthermore, multiple regression analysis showed that hyperhomocysteinemia was closely related to insulin resistance and visceral adiposity. Our results indicate that the presence of hyperhomocysteinemia in our population of Japanese patients with type 2 diabetes-associated insulin resistance was associated with increased visceral but not subcutaneous adiposity.     

Circulating homocysteine levels in patients with type 2 diabetes mellitus

Background and aimPrevious studies have shown conflicting results regarding circulating homocysteine levels in patients with type 2 diabetes.Methods and resultsThis observational study included 2121 patients with angiographically proven coronary artery disease (507 patients with type 2 diabetes and 1614 patients without diabetes). Circulating homocysteine levels, methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, renal function, presence of coronary artery disease (CAD) diagnosed by coronary angiography, and circulating folate and vitamin B₁₂ status were assessed. Plasma homocysteine levels [median (25th; 75th percentile)] were significantly higher in patients with diabetes than in those without [12.4 μmol/L (9.9 μmol/L; 15.9 μmol/L) versus 11.7 μmol/L (9.6 μmol/L; 14.5 μmol/L), P = 0.011]. Diabetes affected homocysteine levels only in patients with a glomerular filtration rate <90 mL/min [13.0 μmol/L (10.5 μmol/L; 16.7 μmol/L) in patients with diabetes versus 12.2 μmol/L (10.1 μmol/L; 15.2 μmol/L) in patients without diabetes, P = 0.006] but not in those with a glomerular filtration rate ≥90 mL/min [10.1 μmol/L (8.1 μmol/L; 12.4 μmol/L) versus 10.2 μmol/L (8.8 μmol/L; 12.3 μmol/L), P = 0.267]. Multivariable analysis did not show an independent association between diabetes and homocysteine level (P = 0.342).ConclusionCirculating homocysteine levels are increased in patients with type 2 diabetes compared with non-diabetic patients due to a more diabetes-associated adverse risk profile rather than to diabetes itself.     

Circulating angiotensin II is associated with body fat accumulation and insulin resistance in obese subjects with type 2 diabetes mellitus

Adipocytes express all components of the renin-angiotensin system, and the renin-angiotensin system is involved in obesity and insulin resistance. Circulating angiotensin II (Ang II) is detectable in blood, but its significance in human obesity remains unknown. The aim of this study was to investigate plasma Ang II in obese patients with type 2 diabetes mellitus (T2D) and the change during weight loss. Fifty Japanese obese subjects with T2D (body weight, 75.0 ± 14.1 kg; body mass index, 29.1 ± 3.7 kg/m²; visceral fat area [VFA], 169.3 ± 54.3 cm²; hemoglobin A_1c, 7.6% ± 1.5%) were enrolled. The subjects were prescribed a diet of daily caloric intake of 20 kcal/kg for 24 weeks. Plasma Ang II was measured by radioimmunoassay. Leptin, adiponectin, and lipoprotein lipase mass in preheparin serum were also measured as adipocyte-derived factors. After 24 weeks of weight reduction diet, the mean body weight, VFA, and hemoglobin A_1c decreased significantly by 2.3%, 7.0%, and 8.3%, respectively. The mean plasma Ang II decreased by 24% (P < .0001) and correlated with body weight both at baseline (r = 0.425, P = .0018) and at 24 weeks (r = 0.332, P = .0181). The change in Ang II correlated with changes in body weight (r = 0.335, P = .0167) and VFA (r = 0.329, P = .0191). The change in Ang II also correlated positively with change in leptin (r = 0.348, P = .0127) and tended to correlate negatively with change in lipoprotein lipase mass in preheparin serum (r = −0.260, P = .0683), which is a marker of insulin sensitivity. Plasma Ang II is associated with body weight, decreases during weight loss, and is associated with markers of insulin resistance in obese subjects with T2D.     

Serum visfatin is associated with type 2 diabetes mellitus independent of insulin resistance and obesity

Objective

The aim of this study was to evaluate the association of serum visfatin, adiponectin and leptin with 2 diabetes mellitus (T2DM) in the context of the role of obesity or insulin resistance, which is not well understood.

Methods

A total of 76 newly-diagnosed T2DM patients and 76 healthy control subjects, matched for age, body mass index (BMI) and sex ratio, were enrolled. Anthropometric parameters, glycemic and lipid profile, insulin resistance (measured by homeostasis model assessment of insulin resistance index [HOMA-IR]), leptin, adiponectin, and visfatin were assessed.

Results

On the contrary to adiponectin, serum leptin and visfatin levels were higher in T2DM patients compared with controls (10.07 ± 4.5, 15.87 ± 16.4, and 5.49 ± 2.4 vs. 12.22 ± 4.9 μg/ml, 8.5 ± 7.8 ng/ml and 3.58 ± 2.2 ng/ml, respectively, P < 0.01). Waist circumference and BMI were correlated with leptin and adiponectin but not with visfatin. Leptin, adiponectin and visfatin all were associated with T2DM following adjusting for obesity measures. After controlling for HOMA-IR, visfatin remained as an independent predictor of T2DM (odds ratio = 1.32, P < 0.05). In a multiple regression analysis to determine visfatin only triglycerides and fasting glucose remained in the model (P < 0.05).

Conclusion

Elevation of visfatin in T2DM is independent of obesity and insulin resistance and is mainly determined by fasting glucose and triglycerides.     

Circulating leptin and insulin in obese patients with and without type 2 diabetes mellitus: relation to ghrelin and oxidative stress

Aim

This case control study aimed to investigate relationship between appetite hormones (ghrelin and leptin) and body mass index (BMI), insulin and oxidative stress in simple obese and type 2 diabetes (T2DM) obese patients.

Methods

Thirty healthy controls; 30 simple obese and 30 T2DM obese patients were enrolled. Demographic and clinical data of all participants were reported. Serum levels of fasting blood glucose (FBG), postprandial blood glucose (PBG), lipid peroxide (LPO) and nitric oxide (NO) were measured by chemical methods while, insulin, leptin and ghrelin by ELISA kits.

Results

Serum levels of insulin, leptin, LPO were significantly higher while, ghrelin was significantly lower in simple obese and obese patients with diabetes versus controls. Insulin resistance was found in 76.67% simple obese and 93.33% obese patients with diabetes. Ghrelin showed a positive correlation with PBG in controls; but negative correlation with BMI in simple obese and with NO in obese patients with diabetes. Positive correlations were found between LPO and FBG, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and between leptin and FBG in obese patients with diabetes.

Conclusions

Our results suggested that hyperinsulinemia and hyperleptinemia may be most important mechanisms in decreasing ghrelin and inducing oxidative stress in simple obese and T2DM obese patients.     

Circulating leptin and insulin in obese patients with and without type 2 diabetes mellitus: Relation to ghrelin and oxidative stress

AimThis case control study aimed to investigate relationship between appetite hormones (ghrelin and leptin) and body mass index (BMI), insulin and oxidative stress in simple obese and type 2 diabetes (T2DM) obese patients.MethodsThirty healthy controls; 30 simple obese and 30 T2DM obese patients were enrolled. Demographic and clinical data of all participants were reported. Serum levels of fasting blood glucose (FBG), postprandial blood glucose (PBG), lipid peroxide (LPO) and nitric oxide (NO) were measured by chemical methods while, insulin, leptin and ghrelin by ELISA kits.ResultsSerum levels of insulin, leptin, LPO were significantly higher while, ghrelin was significantly lower in simple obese and obese patients with diabetes versus controls. Insulin resistance was found in 76.67% simple obese and 93.33% obese patients with diabetes. Ghrelin showed a positive correlation with PBG in controls; but negative correlation with BMI in simple obese and with NO in obese patients with diabetes. Positive correlations were found between LPO and FBG, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and between leptin and FBG in obese patients with diabetes.ConclusionsOur results suggested that hyperinsulinemia and hyperleptinemia may be most important mechanisms in decreasing ghrelin and inducing oxidative stress in simple obese and T2DM obese patients.     

Magnesium deficiency and insulin resistance in patients with type 2 diabetes mellitus

Magnesium is a predominantly intracellular ion, and it is a cofactor in more than 300 enzymatic reactions, like tyrosinokinase activity. Its deficiency may increase insulin resistance, especially in patients with metabolic syndrome or type 2 diabetes. This study evaluated in 27 patients with poorly controlled type 2 diabetes if there was correlation between intracellular magnesium levels, laboratorial indexes of insulin resistance and glycemic control. Decreased serum and intracellular magnesium depletion were found in 75% and 30.8% of patients, respectively. A negative correlation between intracellular magnesium levels (ICMg) and BMI and HbA1 was found. The homeostasis model assessment for insulin resistance (HOMA-IR) was higher than 3.0 in 59.2% of patients and there was a tendency to negative correlation with ICMg levels, although without statistical significance. Despite the small number of patients, this study shows that magnesium deficiency is frequent in patients with diabetes and its correlation with insulin resistance should be more studied.     

Indexes of abdominal adiposity in patients with type 2 diabetes

OBJECTIVE: To assess the relationship of waist circumference and weight/height ratio with height, and their association with components of the metabolic syndrome, in Type 2 diabetic patients. DESIGN: multicenter cross-sectional survey on a cohort enrolled in a prospective observational study. SUBJECTS: 13,232 patients (6816 women and 6416 men) with Type 2 diabetes, not currently affected by macrovascular complications. MEASUREMENTS: height, weight, waist and hip circumference, waist/hip and waist/height ratios. RESULTS: waist circumference was significantly correlated with height after adjustment for potential confounders (adjusted r=0.19 and 0.23 in women and men, respectively), while waist/height ratio showed an inverse correlation with height (r=-0.14 and -0.15, respectively). Elevated waist/height ratio was more predictive of hypertension and hypertriglyceridemia, than waist circumference or waist/hip ratio. CONCLUSIONS: Waist circumference is correlated with height; thresholds for waist circumference could need adjustment for height. Waist/height ratio, although inversely correlated with height, could be a better predictor of abnormalities associated with abdominal adiposity than waist circumference alone.     

Increased serum resistin levels in patients with type 2 diabetes are not linked with markers of insulin resistance and adiposity

Abstract The role of resistin in human biology remains uncertain. We measured serum resistin levels in Japanese patients with (n=111) and without (n=98) type 2 diabetes mellitus and investigated the significance of this hormone in the pathophysiology of diabetes. The levels of serum adiponectin and leptin were also measured. Resistin levels were increased significantly in patients with type 2 diabetes compared with non-diabetic subjects (24.7±2.6 vs. 15.0±1.2 ng/ml, p=0.0013). However, there was no correlation in either patient group between serum resistin levels and markers of insulin resistance, obesity or hyperlipidaemia. These results were in direct contrast to the data of leptin or adiponectin, both of which were closely related to these clinical markers of diabetes. Multivariate regression analysis on the combined data of the two groups demonstrated that the presence of diabetes and HDL cholesterol levels were significant predictors of serum resistin levels (diabetes: =0.159, p=0.035; HDL: =-0.172, p=0.039). No correlation was observed between C-reactive protein and resistin adjusted for BMI. Taken together, these findings demonstrate that serum resistin levels are increased in patients with type 2 diabetes, but this increase is not linked to markers of insulin resistance or adiposity. Further studies are necessary to elucidate the significance of serum resistin concentration in human pathophysiology.     

Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus

The aim of the present study was to investigate the association of serum adiponectin concentration with regional adiposity and insulin resistance in subjects with type 2 diabetes mellitus. A total of 73 Japanese men with type 2 diabetes (aged 59 +/- 11 years and body mass index [BMI] 23.8 +/- 3.0 kg/m(2), mean +/- SD) were studied. Fasting serum adiponectin and leptin concentrations were determined by radioimmunoassay. Regional adiposity was measured by abdominal computed tomography (CT) at the umbilical level, and insulin resistance was estimated by homeostasis model assessment (HOMA-R). Univariate regression analysis showed that serum adiponectin levels were negatively correlated with subcutaneous and visceral fat areas. With multivariate regression analysis, visceral fat area was a predominant determinant of serum adiponectin levels. In contrast, subcutaneous fat area was strongly associated with serum leptin concentrations. Among subcutaneous and visceral fat areas, BMI, and serum leptin levels, both subcutaneous and visceral fat areas were independently associated with HOMA-R. In another model incorporating serum adiponectin levels, serum adiponectin levels were selected as an independent determinant of HOMA-R instead of visceral fat area. In conclusion, hypoadiponectinemia was associated with visceral fat accumulation rather than subcutaneous fat depot in Japanese men with type 2 diabetes mellitus. Both subcutaneous and visceral fat accumulation contribute to insulin resistance in these subjects, and the contribution of visceral fat may be mediated, in part, by hypoadiponectinemia.     

Serum resistin level is associated with insulin sensitivity in Japanese patients with type 2 diabetes mellitus

Impaired insulin secretion and decreased insulin sensitivity are the main pathophysiologic features responsible for development of hyperglycemia in type 2 diabetes mellitus. Insulin resistance is often associated with increased adipose tissue mass. To examine which variables influence insulin sensitivity, we compared metabolic parameters, serum resistin, leptin, and adiponectin concentrations to the insulin sensitivity, obtained by frequently sampled intravenous glucose tolerance test using the minimal model analysis, in 113 Japanese patients with type 2 diabetes mellitus. Duration of diabetes, fasting plasma glucose, fasting insulin, homeostasis model assessment of insulin resistance index, and serum resistin concentration were significantly higher in the insulin-resistant subgroup compared with the insulin-sensitive subgroup and correlated with insulin sensitivity. Stepwise regression analysis also identified these parameters as independent regulators of insulin sensitivity. The present study reconfirmed that fasting insulin level or homeostasis model assessment of insulin resistance would be a surrogate measure of insulin resistance and demonstrated that insulin resistance increases progressively after the onset of overt diabetes and that the serum resistin level is associated with insulin sensitivity, suggesting that resistin plays an important role in the development of insulin resistance in Japanese patients with type 2 diabetes mellitus.     

Plasma fatty acids, adiposity, and variance of skeletal muscle insulin resistance in type 2 diabetes mellitus.

Skeletal muscle insulin resistance (IR) is typically severe in type 2 diabetes mellitus (DM). However, the factors that account for interindividual differences in the severity of IR are not well understood. The current study was undertaken to examine the respective roles of plasma FFA, regional adiposity, and other metabolic factors as determinants of the severity of skeletal muscle IR in type 2 DM. Twenty-three subjects (12 women and 11 men) with type 2 DM underwent positron emission tomography imaging using [18F]2-fluoro-2-deoxyglucose during euglycemic insulin infusions (120 mU/min x m2) to measure skeletal muscle IR, using Patlak analysis of the tissue activity curves. Body composition analysis included body mass index, fat mass, and fat-free mass by dual energy x-ray tomography, and computed tomography determinations of visceral adiposity, thigh adipose tissue distribution, and muscle composition. Body mass index, fat mass, subfascial adiposity in the thigh, and visceral adipose tissue (VAT) were all significantly related to skeletal muscle IR (r = -0.48 to -0.63; P < 0.01). However, the strongest simple correlate of IR in skeletal muscle was insulin-suppressed plasma FFA (r = -0.81; P < 0.001). VAT was the sole component of adiposity that significantly correlated with insulin-suppressed plasma FFA concentration (r = 0.64; P < 0.001). These findings indicate that the severity of skeletal muscle IR in type 2 DM is closely related to the IR of suppressing lipolysis and that plasma fatty acids and VAT are key elements mediating the link between obesity and skeletal muscle IR in type 2 DM.     

Microalbuminuria, cardiovascular autonomic dysfunction, and insulin resistance in patients with type 2 diabetes mellitus

Urinary albumin excretion/microalbuminuria and cardiovascular autonomic dysfunction are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the presence of microalbuminuria would correlate with cardiovascular autonomic dysfunction and insulin resistance in type 2 diabetic patients. The study group consisted of 15 Japanese patients with type 2 diabetes and microalbuminuria (age: 56 +/- 10 years, mean +/- SD). The control group consisted of 19 age-matched patients with normalbuminuria (56 +/- 7 years). Cardiovascular autonomic function was assessed by baroreflex sensitivity (BRS), heart rate variability, plasma norepinephrine concentration, and cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy. BRS was lower in the microalbuminuria group than in the normalbuminuria group (P < .05). Early and delayed 123I-MIBG myocardial uptake values were lower (P < .05 and P < .005, respectively) and the percent washout rate of 123I-MIBG was higher (P < .0005) in the microalbuminuria group than in the normalbuminuria group. Fasting plasma glucose (P < .05) and insulin concentrations (P < .05), and the homeostasis model assessment (HOMA) index (P < .01) were higher in the microalbuminuria group than in the normalbuminuria group. Multiple regression analysis showed that urinary albumin excretion was independently predicted by the myocardial uptake of 123I-MIBG at delayed phase, fasting plasma insulin concentration, and the HOMA index. Our results indicate that the presence of microalbuminuria in our Japanese patients with type 2 diabetes is characterized by depressed cardiovascular autonomic function and insulin resistance, and that the myocardial uptake of 123I-MIBG at delayed phase, fasting plasma insulin, and HOMA index are independent predictors of urinary albumin excretion.     

老年2型糖尿病患者静息心率与胰岛素抵抗、皮质醇相关性研究

目的 探讨老年2型糖尿病(T2DM)患者静息心率(RHR)与胰岛素抵抗(IR)、血皮质醇(Cor)的关系. 方法 2009年9月至2011年12月住院治疗的78例T2DM患者,按RHR不同,分为3组(R1组≤70次/min,R2组71～84次/min,R3组≥85次/min),测定患者的RHR、血压、三酰甘油(TG)、空腹血糖(FPG)、空腹胰岛素浓度(FINS)、晨8时和下午4时血Cor水平. 结果 老年T2DM患者随着RHR的增加,IR程度、Cor水平也增加.相关分析显示,RHR与IR、Cor呈正相关. 结论 老年T2DM患者的RHR随IR程度、Cor水平增加而增加.     

Relationship between the serum concentrations of C-reactive protein and parameters of adiposity and insulin resistance in patients with type 2 diabetes mellitus

Serum C-reactive protein (CRP) concentrations have been reported to be associated with body fat, especially visceral fat accumulation, but most studies up to now have been conducted on non-diabetic subjects. In this study, we investigated the association between the serum CRP concentrations and parameters of adiposity and insulin resistance in both Japanese type 2 diabetes patients and non-diabetic subjects. A total of 248 Japanese subjects (140 type 2 diabetes patients and 108 non-diabetic subjects) were enrolled for the study. The degree of insulin resistance was estimated by the homeostasis model assessment (HOMA-R) method. Fat accumulation was evaluated by measuring visceral and subcutaneous fat areas at the level of the umbilicus in abdominal CT scans. To assess hepatic fat content, the ratio of CT attenuation value of the liver to that of the spleen (L/S ratio) was calculated. Serum CRP was found to be significantly correlated with various indices of adiposity, including L/S ratio, visceral fat area (VFA), subcutaneous fat area (SFA), and HOMA-R, in both the diabetic patients and the non-diabetic subjects. After adjustment for five variables (age, gender, serum CRP, HbA1c, and smoking), serum CRP was still significantly correlated with L/S ratio, VFA, SFA, and HOMA-R in the diabetic patients. We also found that changes in serum CRP concentrations were correlated with changes in the VFA and SFA at 1 year after the baseline in 24 diabetic patients. We conclude that serum CRP may be closely related to the degree of liver steatosis and visceral fat accumulation in Japanese type 2 diabetes mellitus patients.