Kegg Pathway: Type II diabetes mellitus

Gynecol Endocrinol. 2009 Jul 1; 1-6
Vrbikova J, Bendlova B, Vankova M, Dvorakova K, Grimmichova T, Vondra K, Pacini G

Aim. To study the impact of family history (FH) of Type 2 diabetes mellitus on beta-cell compensatory mechanism in women with polycystic ovary syndrome (PCOS). Subjects and methods. A total of 70 women with PCOS, 14 with first-degree relative with Type 2 diabetes mellitus (T2DM) (FH+), 56 with negative FH of T2DM (FH-) and 72 age and BMI matched control healthy women (CNT) underwent oral glucose tolerance test (OGTT). Insulin resistance was evaluated as oral glucose index (OGIS); insulin and C-peptide secretion as the insulinogenic index in 30th min of OGTT. Results. Fasting blood glucose levels were significantly higher in FH+ than in FH- (p < 0.05). Fasting insulin was higher in FH+ than in CNT (p < 0.05). Fasting C-peptide was significantly higher in both FH- and FH+ than in CNT (p < 0.05 and p < 0.01, respectively). OGIS was lower in FH+ than in FH- or in CNT (p < 0.05). Insulinogenic index calculated from C-peptide values (II-Cp) was lower in FH+ than in CNT (p < 0.05). Adaptation index calculated from the values of OGIS and insulinogenic index was significantly lower in FH+ than in CNT or in FH- (p < 0.0001 and p < 0.01, respectively). Conclusions. Insulin resistance and defective early-phase insulin secretion is present only in those PCOS-affected subjects who had positive FH of T2DM.

Cell Mol Life Sci. 2009 Jul 2;
Mascitelli L, Pezzetta F, Goldstein MR

Horm Res. 2009; 72(1): 25-32
Ku YH, Koo BK, Kwak SH, Cho YM, Shin HD, Lee HK, Kim Y, Choi JW, Oh B, Park KS

BACKGROUND/AIMS: Glucocorticoids play an important role in the pathogenesis of obesity and insulin resistance. 11beta-hydroxysteroid dehydrogenase Type 1 (HSD11B1), which converts inactive cortisone to active cortisol, has become an emerging therapeutic target for Type 2 diabetes mellitus and obesity. In this study, we examined the association between HSD11B1 polymorphisms and Type 2 diabetes and metabolic phenoTypes in Koreans. METHODS: We sequenced all exons including exon-intron boundaries and the promoter region of the HSD11B1 gene. Of 8 polymorphisms identified, we selected 4 common single-nucleotide polymorphisms (g.-19835G>A, g.-19609A>G, g.+27447G>C and g.+27810C>T) based on location, linkage disequilibrium and frequency and which were genoTyped in 757 subjects with Type 2 diabetes and 644 nondiabetic subjects. RESULTS: There was no association between the 4 common polymorphisms of HSD11B1 and Type 2 diabetes. g.-19835G>A and g.-19609A>G showed modest associations with fasting plasma glucose and body mass index but the significance of these associations was lost after adjustment for multiple comparison. With regard to promoter polymorphisms in the HSD11B1 gene, a haploType construct carrying both g.-19835A and g.-19609G showed significantly decreased promoter activity compared to other common haploType constructs. CONCLUSION: The variations in HSD11B1 were not associated with susceptibility to Type 2 diabetes or metabolic phenoTypes in Koreans. However, the common promoter variants of the gene might exert a polymorphic regulatory effect on HSD11B1 expression.

J Bone Joint Surg Am. 2009 Jul; 91(7): 1621-9
Marchant MH, Viens NA, Cook C, Vail TP, Bolognesi MP

BACKGROUND: As the prevalence of diabetes mellitus in people over the age of sixty years is expected to increase, the number of diabetic patients who undergo total hip and knee arthroplasty should be expected to increase accordingly. In general, patients with diabetes are at increased risk for adverse events following arthroplasty. The goal of the present study was to determine whether the quality of preoperative glycemic control affected the prevalence of in-hospital peri-operative complications following lower extremity total joint arthroplasty. METHODS: From 1988 to 2005, the Nationwide Inpatient Sample recorded over 1 million patients who underwent joint replacement surgery. The present retrospective study compared patients with uncontrolled diabetes mellitus (n = 3973), those with controlled diabetes mellitus (n = 105,485), and those without diabetes mellitus (n = 920,555) with regard to common surgical and systemic complications, mortality, and hospital course alterations. Additional stratification compared the effects of glucose control among patients with Type-I and Type-II diabetes. Glycemic control was determined by physician assessments on the basis of the American diabetes Association guidelines with use of a combination of patient self-monitoring of blood-glucose levels, the hemoglobin A1c level, and related comorbidities. RESULTS: Compared with patients with controlled diabetes mellitus, patients with uncontrolled diabetes mellitus had a significantly increased odds of stroke (adjusted odds ratio = 3.42; 95% confidence interval = 1.87 to 6.25; p < 0.001), urinary tract infection (adjusted odds ratio = 1.97; 95% confidence interval = 1.61 to 2.42; p < 0.001), ileus (adjusted odds ratio = 2.47; 95% confidence interval = 1.67 to 3.64; p < 0.001), postoperative hemorrhage (adjusted odds ratio = 1.99; 95% confidence interval = 1.38 to 2.87; p < 0.001), transfusion (adjusted odds ratio = 1.19; 95% confidence interval = 1.04 to 1.36; p = 0.011), wound infection (adjusted odds ratio = 2.28; 95% confidence interval = 1.36 to 3.81; p = 0.002), and death (adjusted odds ratio = 3.23; 95% confidence interval = 1.87 to 5.57; p < 0.001). Patients with uncontrolled diabetes mellitus had a significantly increased length of stay (almost a full day) as compared with patients with controlled diabetes (p < 0.0001). All patients with diabetes had significantly increased inflation-adjusted postoperative charges when compared with nondiabetic patients (p < 0.0001). CONCLUSIONS: Regardless of diabetes Type, patients with uncontrolled diabetes mellitus exhibited significantly increased odds of surgical and systemic complications, higher mortality, and increased length of stay during the index hospitalization following lower extremity total joint arthroplasty.

Metabolism. 2009 Jun 29;
Onat A, Can G, Ayhan E, Kaya Z, Hergenç G

The issue of whether or not incident Type 2 diabetes mellitus and coronary heart disease (CHD) can be predicted by high-density lipoprotein (HDL) cholesterol in both sexes needs investigation. A representative sample of 3035 middle-aged Turkish adults free of CHD at baseline was studied with this purpose prospectively over a mean of 7.8 years. High-density lipoprotein cholesterol levels were found to be correlated in women positively with plasma fibrinogen and weakly with waist girth and C-reactive protein, and to be not correlated with fasting insulin. High-density lipoprotein cholesterol protected men against future CHD risk (for a 12-mg/dL increment: relative risk = 0.80 [95% confidence interval, 0.69-0.95]) after multivariable adjustment in logistic regression analyses for age, smoking status, physical activity grade, hypertension, abdominal obesity, diabetes, and lipid-lowering drugs. However, men were not protected against risk of diabetes. In women, HDL cholesterol was not associated with risk for CHD, whereas intermediate (40-60 mg/dL) compared with lower HDL cholesterol levels proved protective against risk of diabetes (relative risk = 0.57 [95% confidence interval, 0.36-0.90]) after adjustments that included apolipoprotein A-I tertiles. Yet higher serum concentrations failed to yield protection against diabetes. It was concluded that HDL particles confer partially lacking protection against cardiometabolic risk among Turks, and this impairment is modulated by sex. This highly important observation may result from a setting of prevailing chronic subclinical inflammation.

Metabolism. 2009 Jun 29;
Mathias RA, Deepa M, Deepa R, Wilson AF, Mohan V

India is a major contributor to the global public health burden of diabetes. We have undertaken a family study of large multiplex families from Chennai, South India, and report on the familial aggregation of quantitative traits associated with Type 2 diabetes mellitus in these pedigrees. Five hundred twenty-four individuals older than 19 years from 26 large multiplex pedigrees were ascertained. Detailed questionnaires and phenoType data were obtained on all participating individuals including fasting blood glucose, fasting insulin, lipid profiles, height, weight, and other anthropometric and clinical measures. Heritability estimates were calculated for all quantitative traits at the univariate level, and bivariate analyses were done to determine the correlation in genetic and environmental control across these quantitative traits. Heritability estimates ranged from 0.21 to 0.72. The heritability estimates for traits most directly related to Type 2 diabetes mellitus were 0.24 +/- 0.08 for fasting blood glucose and 0.41 +/- 0.09 for fasting insulin. In addition, there was evidence for common genetic control for many pairs of these traits. These bivariate analyses suggested common genes for fasting insulin and central obesity measures (body mass index, waist, and hip), with complete genetic correlation between fasting insulin and waist. Quantitative traits associated with Type 2 diabetes mellitus have heritabilities suggestive of some familial or genetic effect. The evidence for pleiotropic control of insulin and central obesity-related traits supports the presence of an insulin resistance syndrome in South Asians with a tendency for central obesity.

Adv Ther. 2009 Jun 30;
Matsumura M, Monden T, Miyashita Y, Kawagoe Y, Shimizu H, Nakatani Y, Domeki N, Yanagi K, Ikeda S, Kasai K

INTRODUCTION: In this study, we examined the effects of the alpha-glucosidase inhibitors acarbose and voglibose on postprandial plasma glucose and serum triglyceride levels in patients with Type 2 diabetes mellitus. METHODS: Twenty-one Japanese patients with Type 2 diabetes were enrolled in this study. Subjects had been treated with voglibose for at least 3 months. They underwent a 400 kcal balanced food meal tolerance test before and 8 weeks after the changeover from voglibose to acarbose. Subjects were divided into two groups: the first group (low-dose group; n=11) was changed over from 0.6 mg/day voglibose to 150 mg/day acarbose, and the other (high-dose group; n=10) from 0.9 mg/day voglibose to 300 mg/day acarbose. RESULTS: The increment rate of postprandial plasma glucose ([plasma glucose 2 hours after test meal - fasting glucose]/fasting glucose) decreased from 34.7%+/-23.9% to 25.0%+/-24.6% (P=0.13) in the low-dose group, and decreased significantly from 56.1%+/-53.1% to 31.5%+/-36.0% (P=0.03) in the high-dose group after changeover. However, there were no significant changes in blood glycated hemoglobin (HbA(1c)) levels before and after changeover in either group. The increment rate of postprandial serum triglyceride (TG) ([serum TG 2 hours after test meal - fasting TG]/fasting TG) decreased significantly only in the high-dose group (52.4%+/-60.0% to 24.3%+/-16.6%) (P=0.05). No significant changes in serum high-density lipoprotein cholesterol levels were observed in either group, whereas serum low-density lipoprotein cholesterol levels decreased significantly from 3.20+/-0.25 to 2.65+/-0.18 mmol/L (P=0.04), only in the highdose group. CONCLUSIONS: In patients with Type 2 diabetes our findings suggest that acarbose 300 mg/day is superior to voglibose 0.9 mg/day in improving postprandial hyperglycemia and hypertriglyceridemia.

Saudi J Gastroenterol. 2008 Jul; 14(3): 118-21
Singal AK, Ayoola AE

BACKGROUND/AIM: Type 2 diabetes mellitus (DM-2) is more common in patients with chronic liver disease (CLD) in general and chronic hepatitis C virus (HCV) infection in particular. We aimed to determine the prevalence and factors affecting the occurrence of DM-2 in Saudi patients with CLD. MATERIALS AND METHODS: Retrospective study at the King Fahd Central Hospital (KFCH), Gizan, Saudi Arabia. A total of 277 patients with either cirrhosis (CH) or hepatocellular carcinoma (HCC) were analyzed for patient demographics, severity of liver disease, HBsAg, and anti-HCV, associated diseases including DM-2, and presence of HCC. The prevalence of DM-2 was also estimated in 400 age- and sex-matched Saudi patients admitted for various nonliver diseases (control group). Chi-square test, univariate analysis, and multivariate regression. RESULTS: Prevalence of DM-2 in patients with CH was higher than in controls (19.2 vs. 9.2%; P = 0.001). Although those with HCC had a higher prevalence, the difference was not significant (10.9 vs. 9.2%; P = 0.5). Seventy-six percent of patients with HCC had associated CH. On multivariate analysis, age and hypertension were more common in diabetics. Although patients with HCV-related disease had a higher prevalence of DM-2 compared to HBV-related disease, the difference was not significant (26.3 vs. 15.7%; P > 0.05). CONCLUSIONS: DM-2 occurred more frequently in CLD patients, particularly in cirrhotics. Age and hypertension predicted the occurrence of DM-2. Small sample size of patients with HCV-related CH probably precluded higher prevalence of DM-2 in them.

Med Sci Sports Exerc. 2009 Jun 30;
Jennings AE, Alberga A, Sigal RJ, Jay O, Boulé NG, Kenny GP

PURPOSE:: Exercise is a possible means to increase resting energy expenditure, which could offset age-related metabolic declines and facilitate weight management, both of which are particularly important for people who have Type 2 diabetes mellitus. We sought to determine the effects of aerobic exercise training and resistance exercise training and the incremental effect of combined aerobic and resistance exercise training on resting metabolic rate (RMR) in previously sedentary individuals with Type 2 diabetes. METHODS:: After a 4-wk run-in period, 103 participants (72 male, 31 female, 39-70 yr, mean +/- SD body mass index = 32.9 +/- 5.7 kg.m) were randomly assigned to four groups for 22 wk: aerobic training, resistance training, combined aerobic and resistance exercise training, or waiting-list control. Exercise training was performed three times per week at community-based gym facilities. RMR was measured by indirect calorimetry for 30 min after an overnight fast. Body composition was assessed using bioelectrical impedance. These measurements were taken at baseline, at 3 months, and at 6 months of the intervention. RESULTS:: RMR did not change significantly in any group after accounting for multiple comparisons despite significant improvements in peak oxygen consumption and muscular strength in the exercising groups. Adjusting RMR for age, sex, fat mass, and fat-free mass in various combinations did not alter these results. CONCLUSION:: These results suggest that RMR was not significantly changed after a 6-month exercise program, regardless of modality, in this sample of adults with Type 2 diabetes.

Alzheimer Dis Assoc Disord. 2009 Jun 29;
Arvanitakis Z, Bennett DA, Wilson RS, Barnes LL

We examined the association of Type 2 diabetes mellitus to function in different cognitive systems in older black and white persons. Participants were 1437 persons (28.1% black; 72.9% women; mean age 78.4 y, education 14.5, Mini-Mental State Examination 27.9) free of dementia, enrolled in the Minority Aging Research Study or Memory and Aging Project, 2 epidemiologic, community-based cohort studies of aging and cognition. Summary measures of 5 cognitive domains and global cognition were derived from 19 neuropsychologic tests. diabetes, by medication inspection and history, was present in 15.3% participants, including 23.5% blacks and 12.1% whites (P<0.001). In linear regression models adjusted for age, sex, education, and race, diabetes was associated with a lower level of semantic memory (P=0.042), but not other cognitive domains (episodic memory, working memory, perceptual speed, and visuospatial ability) or global cognition. In separate analyses adjusted for age, sex, education, race, and diabetes, there was no interaction of diabetes with race (all P values >0.333). In summary, diabetes was associated with semantic memory impairment in both black and white persons. We found similar effects of diabetes on cognition in both racial groups. Because diabetes is twice as common in blacks, the burden of diabetes on cognition is higher in black than white persons.

Nephrol Dial Transplant. 2009 Jun 30;
Freedman BI, Hicks PJ, Bostrom MA, Comeau ME, Divers J, Bleyer AJ, Kopp JB, Winkler CA, Nelson GW, Langefeld CD, Bowden DW

BACKGROUND: Although MYH9 is strongly associated with biopsy-proven idiopathic and HIV-associated focal segmental glomerulosclerosis (FSGS) and clinically diagnosed 'hypertension-associated' end-stage renal disease (ESRD) in African Americans, its role in Type 2 diabetes mellitus (T2DM)-associated ESRD is unclear. METHODS: To assess whether MYH9 was associated with T2DM-ESRD, 751 African Americans with T2DM-ESRD, 227 with T2DM lacking nephropathy and 925 non-diabetic non-nephropathy controls were genoTyped for 14 MYH9 SNPs. Association analyses used SNPGWA and Dandelion. RESULTS: Comparing T2DM-ESRD cases with non-diabetic controls, single SNP associations were detected with 8 of 14 SNPs, gender- and admixture-adjusted P-values 0.047-0.005 [recessive model, odds ratio (OR) range 1.30-1.55]. The previously associated MYH9 E1 and L1 haploTypes were associated with T2DM-ESRD (E1: OR 1.27, 95% CI 1.04-1.56, P = 0.021 recessive and L1: OR 1.43, 95% CI 1.09-1.87, P = 0.009 dominant). Contrasting the 751 T2DM-ESRD cases with 227 T2DM non-nephropathy controls revealed that E1 haploType SNPs rs4821480, rs2032487 and rs4821481 were associated with kidney failure (OR 1.38-1.40 recessive, all P < 0.048). Among E1 and L1 risk homozygotes, respectively, mean (SD) diabetes duration prior to renal replacement therapy was 16.6 (9.7) and 16.4 (10.0) years, and 65% had diabetic retinopathy. CONCLUSIONS: Genetic dissection of T2DM-associated ESRD reveals that MYH9 underlies a portion of this clinically diagnosed disorder in African Americans. It is likely that a subset of African Americans with T2DM and coincident nephropathy have primary MYH9-related kidney disease (e.g. FSGS or global glomerulosclerosis), although renal biopsy studies need to be performed.

Clin Chim Acta. 2009 Jun 27;
Selvaraj J, Muthusamy T, Srinivasan C, Balasubramanian K

BACKGROUND: Clinical and experimental data demonstrate that excess aldosterone and insulin interact at target tissues. It has been shown that increased levels of aldosterone contribute to development of insulin resistance and thus act as a risk factor for the development of Type-II diabetes mellitus. However, the molecular mechanisms involved are yet to be identified. The present study was designed to assess the impact of excess aldosterone on GLUT2 and GLUT4 gene expression and glucose uptake in liver and skeletal muscles (gracilis and quadriceps) of adult male rat. METHODS: Healthy adult male albino rats of Wistar strain (Rattus norvegicus), weighing 180-210g were used in the present study. The rats were divided into two groups (control and aldosterone treated) each consisting of five animals. Rats were treated with aldosterone at a dose of 10 mg/ kg body weight, subcutaneously, twice daily at 8 AM and 6 PM for 15 days. RESULTS: Excess aldosterone impaired the rate of glucose uptake through defective expression of GLUT2 and GLUT4 genes and also decreased translocation of GLUT4 to the plasma membrane. CONCLUSION: Excess aldosterone has adverse effect on glucose uptake in liver and skeletal muscle and defective expression of GLUT2 and GLUT4 appear to be responsible for such changes.

diabetes Metab Res Rev. 2009 Jun 29; 25(5): 417-419
Alfonso B, Liao E, Busta A, Poretsky L

This commentary reviews the current state of knowledge regarding the role of vitamin D in the pathogenesis of diabetes mellitus. In Type 1 diabetes mellitus or in adult onset latent autoimmune diabetes (LADA), vitamin D exhibits immunomodulatory actions, influencing the activity of lymphocytes and interleukins. In Type 2 diabetes mellitus vitamin D appears to act through different mechanisms, affecting insulin secretion and insulin sensitivity through its effects on the beta cells, mediators of inflammation and parathyroid hormone. Much work remains to be done in this new field of knowledge before the role of vitamin D in the pathogenesis of diabetes mellitus is completely understood. Copyright (c) 2009 John Wiley & Sons, Ltd.

Clin Biochem Rev. 2009 May; 30(2): 67-74
Nyunt O, Wu JY, McGown IN, Harris M, Huynh T, Leong GM, Cowley DM, Cotterill AM

Maturity Onset diabetes of Young (MODY) is a monogenic and autosomal dominant form of diabetes mellitus with onset of the disease often before 25 years of age. It is due to dysfunction of pancreatic ss cells characterised by non-ketotic diabetes and absence of pancreatic auto-antibodies. It is frequently mistaken for Type 1 or Type 2 diabetes mellitus. Diagnosis of MODY is important as the GCK subType has better prognosis and may not require any treatment. SubTypes HNF1A and HNF4A are sensitive to sulfonylureas, however diabetes complications are common if not treated early. Moreover, there is genetic implication for the patient and family. Rare MODY subTypes can be associated with pancreatic and renal anomalies as well as exocrine dysfunction of the pancreas. So far there are six widely accepted subTypes of MODY described but the list has grown to nine. Although the majority of diabetes mellitus in youth remains Type 1 and the incidence of Type 2 is rising, MODY should be considered in patients with non-ketotic diabetes at presentation, and in patients with a strong family history of diabetes mellitus without pancreatic auto-antibodies. Furthermore the diagnosis must be confirmed by molecular studies. With advancement in genomic technology, rapid screening for MODY mutations will become readily available in the future.

Nat Rev Endocrinol. 2009 Jun 30;
Stolerman ES, Florez JC

Our understanding of the genetics of Type 2 diabetes mellitus (T2DM) has changed, in part owing to implementation of genome-wide association studies as a method for unraveling the genetic architecture of complex traits. These studies enable a global search throughout the nuclear genome for variants that are associated with specific phenoTypes. Currently, single nucleotide polymorphisms in about 24 different genetic loci have been associated with T2DM. Most of these genetic loci are associated with the insulin secretion pathway rather than insulin resistance. Study design, heritability differences and the intrinsic properties of in vivo insulin resistance measures might partially explain why only a few loci associated with insulin resistance have been detected through genome-wide association approaches. Despite the success of these approaches at detecting loci associated with T2DM, currently known associations explain only a small amount of the genetic variance involved in the disease. Compared with previous studies, larger cohorts might be needed to identify variants of smaller effect sizes and lower allele frequencies. Finally, the current list of genetic loci that are related to T2DM does not seem to offer greater predictive value in determining diabetes risk than do commonly used phenotypic risk factors and family history.

J Clin Gastroenterol. 2009 May-Jun; 43(5): 429-36
Hata N, Murata S, Maeda J, Yatani H, Kohno Y, Yokono K, Okano H

BACKGROUND: Previous studies have clearly demonstrated the delayed gastric emptying of solid meals in diabetics, whereas their gastric myoelectrical activity, which primarily determines gastric motility, has not yet been fully confirmed. GOALS: This study aimed to clarify the characteristics and potential predictors of gastric myoelectrical activity in Type 2 diabetics. STUDY: Twenty-eight diabetics and 18 healthy controls participated. Duodenal biopsy sample was used for reverse transcription-polymerase chain reaction to evaluate cholecystokinin and motilin mRNA contents. Electrogastrography was performed before and after the test meal, and was assessed in terms of dominant frequency; dominant frequency instability coefficient; and the percentage of bradygastria, normogastria, and tachygastria. RESULTS: Over the entire recording period, dominant frequency was significantly lower, and dominant frequency instability coefficient and the percentage of bradygastria were significantly higher in diabetics than in controls. In diabetics, the multiple regression analysis demonstrated that dominant frequency instability coefficient and the percentage of tachygastria in the fasting period were dependent on fasting plasma glucose level and HbA1c, respectively. Moreover, dominant frequency over the entire period and the postprandial percentage of bradygastria were significantly associated with body mass index; the fasting percentage of bradygastria and postprandial dominant frequency instability coefficient were associated with fasting serum leptin level; the postprandial percentage of bradygastria was also associated with cholecystokinin mRNA content. CONCLUSIONS: Gastric myoelectrical activity in Type 2 diabetics is impaired on dominant frequency, dominant frequency instability coefficient, and the percentage of bradygastria and predicted by body mass index, fasting serum leptin level, and cholecystokinin mRNA content besides the glycemic status.

diabetes Care. 2009 Jun 29;

Objective: The increased cardiovascular risk in diabetes mellitus has been linked to endothelial and renal dysfunction. The aim of this study was to investigate the role of stable fragments of the precursors of adrenomedullin, endothelin-1, vasopressin and atrial natriuretic peptide in progression of cardiovascular disease in patients with diabetes mellitus. Research design and Methods: Prospective, observational study design with a composite endpoint (death or unexpected admission to hospital due to cardiovascular event) on 781 patients with Type 2 diabetes (54 events, median duration of observation 15 months). The four stable precursor peptides MR-proADM, MR-proANP, CT-proET-1 and CT-proAVP (copeptin) were determined at baseline and their association to renal function and cardiovascular events was studied using stepwise linear, and Cox logistic regression analysis and ROC analysis, respectively. Results: MR-proADM, CT-proET-1, CT-proAVP and MR-proANP were all elevated in patients with future cardiovascular events and independently correlated to serum creatinine. MR-proADM and MR-proANP were significant predictors of a future cardiovascular event, with MR-proANP being the stronger (AUC 0.802 +/- 0.034, sensitivity 0.833, specificity 0.576, positive predictive value 0.132, negative predictive value 0.978 with a cutoff value of 75 pmol/L). Conclusions: The four serum markers of vasoactive and natriuretic peptides are related to both kidney function and cardiovascular events, thus linking two major complications of diabetes mellitus, diabetic nephropathy and cardiovascular disease.

Int J Epidemiol. 2009 Jun 29;
Nagaya T, Yoshida H, Takahashi H, Kawai M

BACKGROUND: Fast heart rate and high blood pressure (BP) at rest may raise risk for the development of Type-2 diabetes mellitus (DM). We therefore investigated dose-response and interactive effects of resting heart rate and BP on the incidence of DM in a Japanese population. METHODS: A follow-up study was conducted for 16 828 men and 8368 women aged 30-59 years and apparently healthy at baseline. Incident DM was identified by 'fasting serum glucose >/=7.00 mmol/l (126 mg/dl)' or/and 'under medical treatment for DM'. Using Cox proportional hazard models, hazard ratio (HR) for incident DM were estimated according to the quartiles of heart rate, systolic or diastolic BP (SBP, DBP), and its linear trends were checked by computing the three indices as continuous variables. Subsequently, interactive effects of slow/fast heart rate (dichotomized by the median) and low/high SBP or DBP (dichotomized by the median) on HR were examined. Baseline age, body mass index, smoking, drinking, exercise and education were computed as conventional confounders. RESULTS: During the follow-up of 125 106 person-years for men and 59 616 person-years for women, 869 men and 224 women developed DM. The multivariate-adjusted HR for incident DM increased across quartiles of heart rate, SBP and DBP in both sexes (linear trend P<0.001 for all). Neither sex showed any significant interactive effects of heart rate and SBP or DBP on HR. CONCLUSIONS: Resting heart rate and BP proportionally raise the risk for DM in middle-aged healthy men and women. Moreover, the adverse effects of fast heart rate and high BP are independent of each other as well as of the influences of conventional confounders.

Curr Cardiol Rep. 2009 Jul; 11(4): 258-63
Gore MO, McGuire DK

Type 2 diabetes mellitus is a major and increasingly prevalent independent risk factor for cardiovascular morbidity and mortality worldwide. Glycemic control is a target of therapy and a principal marker of therapeutic success in diabetes, but whether lowering glucose is accompanied by a commensurate reduction in cardiovascular risk is a matter of ongoing controversy. It has become increasingly apparent from recent large-scale clinical outcome trials that glucose lowering is a poor predictor of cardiovascular outcome, and several instances of unexpectedly increased cardiovascular risk with antihyperglycemic drugs have sounded the alarm with regulatory agencies. This article reviews the critical facts that have led to a recent shift in the regulation of glucose-lowering drugs and makes the case for why new and existing antidiabetic medications should be assessed in clinical trials of cardiovascular outcome.

Eur J Clin Invest. 2009 Jun 26;
Kopp A, Gross P, Falk W, Bala M, Weigert J, Buechler C, Neumeier M, Schölmerich J, Schäffler A

Background Increasing data support the hypothesis of a local and systemic crosstalk between adipocytes and monocytes mediated by fatty acids. The aim of this study was to characterize the immunomodulatory effects of a large panel of fatty acids on cytokines and chemokines in monocytic THP-1 cells and primary human monocytes. We tested whether anti-inflammatory fatty acids are able to inhibit the binding of lipopolysaccharide (LPS) to its receptor, toll-like receptor/MD-2 (TLR4/MD-2). Materials and methods Resistin, monocyte chemoattractant protein-1 (MCP-1) and tumour necrosis factor (TNF) were measured by enzyme-linked immunosorbent assay. Proteins were analysed by Western blot. A designed Flag-tagged TLR4/MD-2 fusion protein (LPS trap) was used to investigate the effect of fatty acids on binding of LPS to its receptor. In 30 patients with Type 2 diabetes mellitus (T2D), the correlation of serum triglyceride levels with LPS-induced monocyte activation was analysed. Results Eleven fatty acids investigated exerted differential effects on the monocytic release of cytokines and chemokines. Eicosapentaenoic acid had potent anti-inflammatory effects on human primary monocytes and THP-1 cells; 100 and 200 muM eicosapentaenoic acid dose-dependently inhibited LPS binding to the LPS trap. LPS-induced release of monocytic MCP-1 and TNF was significantly and positively correlated with serum triglyceride levels in 30 patients with T2D. Conclusions Monocytic activation is differentially regulated by fatty acids and depends on triglyceride levels in T2D. The main finding of the present study shows that eicosapentaenoic acid inhibits the specific binding of LPS to TLR4/MD-2. Eicosapentaenoic acid represents a new anti-inflammatory LPS-antagonist. Eur J Clin Invest 2009.