Family history of diabetes in both parents is strongly associated with impaired residual ß-cell function in Japanese type 2 diabetes patients.

AIMS/INTRODUCTION: The objective of the present study was to clarify the association of the type and number of first-degree family history of diabetes (FHD) with the clinical characteristics, especially with residual ß-cell function, in type 2 diabetes patients. MATERIALS AND METHODS: A total of 1,131 type 2 diabetes patients were recruited and divided into four groups according to FHD information as follows: (i) patients without FHD (FHD-); (ii) those with at least one sibling who had diabetes without parental diabetes (FHD+); (iii) those with one parent (FHD++); or (iv) those with both parents (FHD+++) who had diabetes with or without a sibling with diabetes. RESULTS: The percentages of the FHD-, FHD+, FHD++ and FHD+++ groups were 49.4%, 13.4%, 34.0% and 3.2%, respectively. Patients in the FHD++ and FHD+++ groups were significantly younger at the time of diabetes diagnosis (P < 0.001) than those in the FHD- and FHD+ groups, even after adjusting for confounding factors. In addition, the levels of insulin secretion were significantly lower in the patients in the FHD+, FHD++ and FHD+++ groups than those in the FHD- group (P < 0.05) after adjusting for confounding factors, and the patients in the FHD+++ group presented with the lowest levels of insulin secretion among the four groups. CONCLUSIONS: Our results showed that in type 2 diabetes patients, the degree of the associations between FHD and clinical characteristics differs according to the number and the type of FHD. In particular, FHD in both parents is most strongly associated with impaired residual ß-cell function.

Ratio of low molecular weight serum adiponectin to the total adiponectin value is associated with type 2 diabetes through its relation to increasing insulin resistance.

AIM: Among the three adiponectin isoforms, a lower ratio of high molecular weight (HMW) adiponectin to total adiponectin (TA) is well known to cause insulin resistance and type 2 diabetes (T2D). However, how the levels of other adiponectin isoforms, such as the middle molecular weight (MMW) and low molecular weight (LMW) isoforms, and their relative ratio to TA change in T2D subjects has not been determined. Therefore, we investigated the association of these adiponectin-related parameters with T2D. METHODS: We examined the associations between adiponectin-related parameters and diabetes in a group of 394 T2D subjects and 374 controls (1st group) randomly selected from among the participants in our previous study. The associations between these parameters and the HOMA-IR in a 2nd group, consisting of the subjects remaining in the 1st group after the exclusion of subjects receiving diabetic medication, were also examined. RESULT: In the 1st group, after adjusting for confounding factor, the levels of all the adiponectin isoforms and the HMW/TA ratio were significantly lower among the diabetic subjects than among the controls (all P values < 0.01). On the contrary, the LMW/TA ratio was significantly higher among the diabetic subjects (P < 0.01) and was positively associated with T2D (odds ratio = 8.64, P < 0.01). In the 2nd group, the HMW/TA ratio was inversely associated with the HOMA-IR; however, the LMW/TA ratio was positively associated with the HOMA-IR (ß for LMW/TA ratio = 0.89, SE = 0.24, P < 0.001), similar to the association with T2D. The MMW/TA ratio was not associated with T2D or the HOMA-IR. CONCLUSION: The current investigation demonstrated that, unlike the reduction in the levels of all the adiponectin isoforms and the HMW/TA ratio, an increased LMW/TA ratio was associated with T2D through its relation to insulin resistance.

FTO Gene Polymorphism Is Associated with Type 2 Diabetes through Its Effect on Increasing the Maximum BMI in Japanese Men.

AIM: Several studies have demonstrated that polymorphisms within the fat-mass and obesity-associated gene (FTO) are associated with type 2 diabetes (T2D). However, whether the effects of the FTO locus on T2D susceptibility are independent of fat-mass increases remains controversial. To investigate this issue, we examined the association of FTO variants with T2D and various aspects of BMI history during adult life in a Japanese population. METHODS: We genotyped SNPs within FTO (rs1121980 and rs1558902) in 760 Japanese patients with T2D who had reached a lifetime maximum BMI (BMImax) before or at the time of diagnosis and 693 control individuals with information regarding their BMImax. RESULTS: The BMImax showed the strongest association with T2D risk among the BMIs evaluated in this study. In the sex-combined analysis, FTO SNPs were not associated with any of the BMI variables or with T2D, but in sex-stratified analyses, both SNPs were significantly associated with the BMImax and rs1558902 was associated with T2D in men. The association of the SNPs with T2D remained significant after adjustments for the current BMI and age, whereas the T2D association of the SNP was no longer significant after adjustments for BMImax and age. CONCLUSIONS: These results suggest that the effects of FTO polymorphisms on T2D susceptibility in Japanese men are mediated through their effect on increasing the BMImax before or at the time of diagnosis.

Secretory units of islets in transplantation index is a useful predictor of insulin requirement in Japanese type 2 diabetic patients.

AIMS/INTRODUCTION: The objective of the present study was to clarify the validity of ß-cell function-related parameters for predicting the insulin requirement of Japanese type 2 diabetic patients. MATERIALS AND METHODS: In 188 patients with type 2 diabetes who had been admitted to the University of Toyama Hospital (Toyama, Japan) without receiving insulin therapy, we carried out a cross-sectional study examining the relationship between the homeostasis model assessment of ß-cell function (HOMA-ß) and C-peptide-based indices, and also carried out a retrospective study to examine the utility for predicting insulin requirement of several ß -cell function-related indices using a receiver operating characteristic (ROC) curve analysis. RESULTS: The secretory units of islets in transplantation index (SUIT) had the strongest correlation with HOMA-ß, followed by the fasting serum C-peptide immunoreactivity index (CPI); the fasting serum C-peptide immunoreactivity itself (F-CPR) had the least correlation. The CPI, HOMA-ß and SUIT were significantly lower in the insulin-requiring group than in the non-insulin-requiring group, even after adjustments for confounding factors (P < 0.01). The areas under the ROC curve for insulin requirement were 0.622, 0.774, 0.808, and 0.759 for F-CPR, CPI, SUIT, and HOMA-ß, respectively. The cut-off values of SUIT, CPI, and HOMA-ß for an over 80% specificity for the prediction of insulin therapy were 23.5, 1.00, and 14.9, respectively. CONCLUSIONS: The present study shows that SUIT is the best predictor of insulin requirement among these ß-cell function-related markers.

Visceral adipose tissue level, as estimated by the bioimpedance analysis method, is associated with impaired lung function.

UNLABELLED: Aims/Introduction: It has been reported that metabolic syndrome is associated with impaired lung function, and abdominal obesity is regarded as the most important determinant of this association. We evaluated the association between a component of metabolic syndrome, indices of body composition, including the total adipose tissue content, lean bodyweight and visceral adipose tissue content, as assessed by bioimpedance analysis, and lung function. MATERIALS AND METHODS: A total of 516 participants responded to our questionnaire to determine the smoking status and history of past diseases. Waist circumference, height, bodyweight, percent forced expiratory volume in 1 s (%FEV1) and percent forced vital capacity (%FVC) were measured. Fasting blood samples were obtained to determine the serum levels of high-density lipoprotein and triglyceride, and also the blood glucose. The body composition, including the total adipose tissue content and lean bodyweight, was measured, and the visceral adipose tissue content was estimated as the visceral adipose tissue level, by the bioimpedance analysis method. RESULTS: Waist circumference, estimated visceral adipose tissue level and blood pressure were significantly associated with the %FEV1, and the serum high-density lipoprotein cholesterol was significantly associated with the %FVC in men, after adjustment for age, smoking history, and past histories of bronchial asthma and ischemic heart disease. However, this association was not detected in women. CONCLUSIONS: We found an association between the visceral adipose tissue level as estimated by the bioimpedance analysis method and lung function. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00189.x, 2011).

[Metabolic syndrome].

The metabolic syndrome means the state of glucose intolerance caused by insulin resistance, and develops lipid abnormality and high blood pressure. Recently, life style is changed to excessive energy intake by a high fat diet and physical activity according to the spread of automobiles decline in. Then, the appearance of disease of obesity and the metabolic syndrome increases. In this text, a basic pathogenesis of the metabolic syndrome and the clinical application of PPARgamma agonist to the metabolic syndrome are outlined.

The effect of angiotensin II receptor blockade on an end-stage renal failure model of type 2 diabetes.

The effect of olmesartan medoxomil (OLM), an angiotensin II receptor blocker (ARB), on advanced nephropathy and mortality was evaluated in Zucker Diabetic Fatty (ZDF) rats, a type 2 diabetes model. OLM was administered from 36 weeks of age, when the animals developed advanced proteinuria. OLM effectively suppressed the progression of proteinuria. The ZDF rats started to die at 50 weeks of age, which was accompanied by abrupt increase in blood urea nitrogen, suggesting that the cause of death was renal insufficiency. OLM suppressed increases in blood urea nitrogen and increased the survival rate of the ZDF rats. The histological examination revealed that the renal damage was ameliorated by OLM. The macrophage infiltration and monocyte chemoattractant protein-1 (MCP-1) expression was increased in the glomeruli and tubulointerstitium of the ZDF rat kidneys, and the increase was lessened by OLM. In a separate study, albumin increased MCP-1 release from cultured tubular epithelial cells. These results suggest that protein leakage from the glomeruli stimulates MCP-1 production in tubular cells and that MCP-1 released into the interstitial space induces macrophage infiltration and inflammation. It is conceivable that the beneficial actions of ARB on diabetic nephropathy are, at least in part, due to decrease of proteinuria and the subsequent reduction of inflammatory changes in tubular cells.

Severity of hyperlipidemia does not affect antiatherosclerotic effect of an angiotensin II receptor antagonist in apolipoprotein E-deficient mice.

The purpose of this study was to clarify whether severity of hyperlipidemia affects the antiatherosclerotic effect of angiotensin II receptor blockers (ARBs). The effect of olmesartan medoxomil, an ARB, on atherosclerotic lesion was examined in apolipoprotein E-deficient (ApoEKO) mice fed a normal diet (ND) or a high-fat-supplemented diet (FD) for 25 weeks. ApoEKO mice have high plasma cholesterol levels, which were further increased by feeding of an FD. Both the atherosclerotic lesion area of the aortic luminal surface and the atherosclerotic lesion thickness in the aortic valves were significantly greater in the FD mice than in the ND mice. Olmesartan medoxomil did not affect the plasma cholesterol levels in either the ND or FD ApoEKO mice; however, it reduced effectively both the atherosclerotic lesion surface area and the lesion thickness even in FD ApoEKO mice. It is concluded that the antiatherosclerotic effect of ARBs is not weakened by the high plasma cholesterol level, suggesting the usefulness of ARBs in the treatment of atherosclerosis, even in a situation in which the plasma cholesterol level is not fully controlled.

Role of K+ channels in the PACAP-induced catecholamine secretion from the rat adrenal gland.

We eluciated whether K+ channels modulate adrenal catecholamine secretion induced by pituitary adenylate cyclase-activating polypeptide (PACAP) in the isolated perfused rat adrenal gland. PACAP (100 nM) increased adrenal epinephrine output. The PACAP-induced responses were enhanced by treatment with apamin (10-100 nM) in a concentration-dependent manner. In the presence of nifedipine (3 microM), apamin (1 microM) did not enhance the PACAP-induced responses. Charybdotoxin (1-100 nM) had little influence on the PACAP-induced responses. These results suggest that small-conductance Ca2+-activated K+ channels interfere with L-type voltage-dependent Ca2+ channels to counteract the PACAP-induced adrenal catecholamine secretion.