Elevated Fasting Glucose Levels Research Articles

Metabolic Health of People Admitted to a Psychiatric Intensive Care Unit in Adelaide, South Australia

Metabolic Health of People Admitted to a Psychiatric Intensive Care Unit in Adelaide, South Australia

Who Should We Target for Diabetes Prevention and Diabetes Risk Reduction?

Screening for individual diabetes risk is crucial to identify adult and pediatric high-risk target populations for referral into successful diabetes prevention programs. Determination of impaired glucose tolerance or elevated fasting glucose levels has been the “gold standard” to classify subjects at increased risk for and/or to diagnose type 2 diabetes (T2DM). However, this led to ignoring many individuals prone to develop the disease. Therefore, using a stepped strategy consisting of a preliminary assessment of risk factors, by using risk scores such as the Finnish Diabetes Risk Score (FINDRISC) adapted to the respective population, followed by a single blood test determining blood glucose or hemoglobin A1c, respectively, or an oral glucose tolerance test is a feasible and pragmatic method to more accurately detect individuals at risk for T2DM. Inclusion of further risk factors into the assessment such as physical inactivity, waist circumference, and prenatal factors needs to be thoroughly discussed to establish a valid and reliable stepped approach applicable to real world health care. This article provides an overview of the current literature and is intentionally focused on the identification of high-risk populations (both adult and pediatric) that will help to address the key issues around the prevention of T2DM in health care settings.

Abnormal glucose tolerance testing after gastric bypass

BackgroundSymptoms secondary to dumping have been suggested to help patients refrain from simple carbohydrate ingestion after Roux-en-Y gastric bypass (RYGB). During follow-up examinations, we noted many patients with weight regain complaining of fatigue shortly after eating. Thus, we decided to study the glucose tolerance test (GTT) results in a cohort of post-RYGB patients. MethodsA total of 63 RYGB patients, >6 months postoperatively, were studied with a GTT and measurement of insulin levels. The mean age was 48.5 ± 10.8 years, mean preoperative body mass index was 49.0 ± 6.5 kg/m2, mean percentage of excess body mass index lost was 64.5% ± 29.0%, mean weight regain at follow-up was 11.6 ± 12.4 lb, and mean follow-up period was 47.9 months. ResultsOf the 63 patients, 49 had abnormal GTT results. Of the 63 patients, 6 were diabetic; however, only 1 of these patients had an elevated fasting glucose level. All 6 patients were diabetic preoperatively. Of the 63 patients, 43 had evidence of reactive hypoglycemia at 1–2 hours after the glucose load. Of these patients, 22 had a maximum/minimum glucose ratio >3:1, including 7 with a ratio >4:1. ConclusionThe results of the present study have demonstrated that an abnormal GTT result is a common finding after RYGB. Reactive hypoglycemia was found in 43 of 63 patients, with insulin values that do not support nesidioblastosis. It is our hypothesis, that rather than preventing simple carbohydrate ingestion, the induced hypoglycemia that occurs might contribute to weight regain and maladaptive eating in certain post-RYGB patients.

Breakfast patterns are associated with metabolic syndrome in Korean adults

The Korean diet, including breakfast, is becoming more Western, which could increase the risk of metabolic syndrome. Our aim was to assess whether breakfast patterns are associated with risk for metabolic syndrome in Korean adults. The study subjects (n = 371; 103 men, 268 women) were employees of Jaesang Hospital in Korea and their acquaintances, and all subjects were between 30 and 50 years old. The data collected from each subject included anthropometric measurements, three-day food intake, blood pressure (BP) and blood analyses. The three breakfast patterns identified by factor analysis were "Rice, Kimchi and Vegetables", "Potatoes, Fruits and Nuts" and "Eggs, Breads and Processed meat". The "Rice, Kimchi and Vegetables" pattern scores were positively correlated with systolic (SBP) and diastolic blood pressure (DBP) measurements in men (P < 0.05) and with serum triglyceride (TG) levels in women (P < 0.05). The "Eggs, Breads and Processed meat" pattern scores correlated positively with weight, body mass index (P < 0.05) and serum TGs (P < 0.01) in men. The "Potatoes, Fruits and Nuts" pattern was associated with lower risk of elevated BP (OR 0.49, 95% CI 0.28-0.88) and fasting glucose levels (OR 0.51, 95% CI 0.26-1.00). In contrast, the "Eggs, Breads and Processed meat" pattern was associated with increased risk of elevated TGs (OR 2.06, 95% CI 1.06-3.98). Our results indicate that reducing the consumption of eggs, western grains and processed meat while increasing fruit, nut and vegetable intake for breakfast could have beneficial effects on decreasing metabolic syndrome risk in Korean adults.

The Effects of Altitude Training on the AMPK-Related Glucose Transport Pathway in the Red Skeletal Muscle of Both Lean and Obese Zucker Rats

The skeletal muscle AMP-activated protein kinase (AMPK)-related glucose transport pathway is involved in glucose homeostasis. In this study, we examined whether obese control Zucker rats had abnormal expression of proteins in the LKB1-AMPK-AS160-GLUT4 pathway in red gastrocnemius muscle compared to that in lean (normal) control Zucker rats. We also compared the chronic training effects of exercise, hypoxia, and altitude training on this pathway in lean and obese rats. At sea level, lean and obese rats were divided into 4 groups for 6 weeks training as follows: 1) control; 2) exercise (progressive daily swimming-exercise training with comparable exercise signals between the two groups); 3) hypoxia (8 hours of daily 14% O2 exposure); and 4) exercise plus hypoxia (also called altitude training). Seven animals were used for each group. The obese rats in the control group had higher body weights, elevated fasting insulin and glucose levels, and higher baseline levels of muscle AMPK and AS160 phosphorylation compared with those of lean control rats. For obese Zucker rats in the exercise or hypoxia groups, the muscle AMPK phosphorylation level was significantly decreased compared with that of the control group. For obese Zucker rats in the altitude training group, the levels of AMPK, AS160 phosphorylation, fasting insulin, and fasting glucose were decreased concomitant with an approximate 50% increase in the muscle GLUT4 protein level compared with those of the control group. In lean rats, the altitude training efficiently lowered fasting glucose and insulin levels and increased muscle AMPK and AS160 phosphorylation as well as GLUT4 protein levels. Our results provide evidence that long-term altitude training may be a potentially effective nonpharmacological strategy for treating and preventing insulin resistance based on its effects on the skeletal muscle AMPK-AS160-GLUT4 pathway.

Prevalence of metabolic syndrome in the Canadian adult population

Metabolic syndrome refers to a constellation of conditions that increases a person's risk of diabetes and cardiovascular disease. We describe the prevalence of metabolic syndrome and its components in relation to sociodemographic factors in the Canadian adult population. We used data from cycle 1 of the Canadian Health Measures Survey, a cross-sectional survey of a representative sample of the population. We included data for respondents aged 18 years and older for whom fasting blood samples were available; pregnant women were excluded. We calculated weighted estimates of the prevalence of metabolic syndrome and its components in relation to age, sex, education level and income. The estimated prevalence of metabolic syndrome was 19.1%. Age was the strongest predictor of the syndrome: 17.0% of participants 18-39 years old had metabolic syndrome, as compared with 39.0% of those 70-79 years. Abdominal obesity was the most common component of the syndrome (35.0%) and was more prevalent among women than among men (40.0% v. 29.1%; p=0.013). Men were more likely than women to have an elevated fasting glucose level (18.9% v. 13.6%; p=0.025) and hypertriglyceridemia (29.0% v. 20.0%; p=0.012). The prevalence of metabolic syndrome was higher among people in households with lower education and income levels. About one in five Canadian adults had metabolic syndrome. People at increased risk were those in households with lower education and income levels. The burden of abdominal obesity, low HDL (high-density lipoprotein) cholesterol and hypertriglyceridemia among young people was especially of concern, because the risk of cardiovascular disease increases with age.

Beneficial role of telmisartan on cardiovascular complications associated with STZ-induced type 2 diabetes in rats

We studied the effect of an eight-week treatment with telmisartan (5mg kg–1day–1) on cardiovascular complications that are associated with type 2 diabetes in a neonatal rat model. Type 2 diabetes was induced by the administration of 90mg/kg streptozotocin (STZ), ip, in two-day-old rats. The development of diabetes was checked 12 weeks after STZ administration, and the animals were divided into different groups. Telmisartan treatment was given for eight weeks. At the end of the eight-week treatment, various biochemical and cardiac parameters were measured. Diabetic rats exhibited hyperglycemia, hyperinsulinemia, hyperlipidemia, increased blood pressure and heart rate, increased creatinine, cardiac enzyme and C-reactive protein (CRP) levels, a reduction in the rate of pressure development and decay, cardiac hypertrophy and oxidative stress. Chronic treatment with telmisartan significantly prevented STZ-induced hypertension and tachycardia and elevated fasting glucose and insulin levels. It significantly prevented the dyslipidemia and significantly reduced the elevated creatinine and CRP levels and the levels of other cardiac enzyme markers, like lactate dehydrogenase and creatinine kinase, in diabetic rats. There was an increase in rate of blood pressure development and decay with telmisartan treatment. Telmisartan also produced beneficial effects by preventing cardiac hypertrophy, which was evident from left ventricular collagen levels, the cardiac hypertrophy index and the left ventricular hypertrophy index in diabetic rats. Telmisartan successfully prevented oxidative stress, which was evidenced by a decrease in malondialdehyde and an increase in glutathione, catalase, superoxide dismutase levels. In conclusion, our data suggest that telmisartan prevented STZ-induced metabolic abnormalities and cardiovascular complications in type 2 diabetes.

Clinical Predictors of Different Grades of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is one of the comorbidities related to obesity. Liver biopsy has been used as the "gold standard" for the diagnosis, grading, and prognosis of obese patients. The objective of the present study was to evaluate clinical predictors of more advanced stages of NAFLD. In this retrospective study we assessed several physical and laboratorial factors, including some cytokines, in morbidly obese patients submitted to Roux-en-Y gastric bypass that could be related to the diagnosis and staging of NAFLD. Fragments of the livers were obtained from wedge biopsies during operation. The medical records of 259 patients were studied. The patients were divided into four groups: normal hepatic biopsy, steatosis, mild nonalcoholic steatohepatitis (NASH), and moderate and severe NASH. There were no differences in cytokine levels among groups. The triglyceride levels were the only variable that could stratify the grades of NAFLD and also differentiate from normal livers in the female patients. Also in this group, the aminotransferases and GGT levels and fasting glucose were predictors of the more advanced stages of NASH, while BMI and weight were predictors of the more advanced stages of NASH in male patients. There are no available markers in clinical practice to detect the initial stages of NAFLD. It is very important to perform a liver biopsy in all patients submitted to bariatric surgery and in obese patients with no indication to be operated in the presence of elevated blood levels of aminotransferases, GGT, and fasting glucose.

Incretin effects on β-cell function, replication, and mass: the human perspective.

There is a progressive deterioration in β-cell function in patients with type 2 diabetes. At diagnosis, islet function may be reduced by up to 50% compared with healthy control subjects, and there is also likely to be a reduction in β-cell mass of up to 60%. The reduction in β-cell mass is due to accelerated apoptosis. Currently, few pharmacological therapies address this reduction in β-cell mass and function. This means that patients are generally subjected to an increasing polypharmacy to control their diabetes, with most eventually being treated by insulin. Incretin hormones, which are released from the gastrointestinal tract after a meal, enhance glucose-dependent insulin secretion from the pancreas, aiding the overall regulation of glucose homeostasis in healthy subjects. In addition, these hormones, especially glucagon-like peptide (GLP)-1, have a number of protective effects on the β-cells, including a reduction in apoptosis and enhancement of β-cell proliferation and neogenesis. These benefits are lost to a significant extent in patients with diabetes. The recently developed diabetes therapies, GLP-1 receptor agonists, such as exenatide and liraglutide, appear to have beneficial effects on β-cell function and hence offer promise for durable glycemic control as well as potentially reducing the micro- and macrovascular complications associated with type 2 diabetes. The clinical course of type 2 diabetes is characterized by a progressive decline in β-cell mass and function. Although the elevated levels of fasting glucose and impairment of insulin action in peripheral tissues may predate the diagnosis of type 2 diabetes, chronic hyperglycemia only results after a prolonged period of β-cell degeneration, a process that may begin as much as 12 years before diagnosis, involving a progressive reduction in functionality and mass (1,2). In the UK Prospective Diabetes Study, it was estimated that, at diagnosis, type 2 diabetic patients may have already lost up …

Increased levels of bone remodeling biomarkers (osteoprotegerin and osteopontin) in hypertensive individuals

Objectives Osteoprotegerin (OPG) and osteopontin (OPN) are bone metabolism biomarkers which are involved in the regulation of vascular calcification processes and prediction of future adverse cardiac events. Design and methods OPG, OPN levels and classic risk factors were determined in 130 asymptomatic and hypertensive subjects. Receiver operator characteristic (ROC) analysis was performed and the area under the curve (AUC) was calculated. Results The hypertensive subjects had elevated OPG, OPN, fibrinogen, CRP and fasting glucose levels in comparison to the normotensive ones. There were significant correlations between age, CRP and OPG. Multiple regression analysis showed that as well as inflammation (CRP), age and hypertension were predictors of increased OPG levels. OPN increase was correlated with CRP and glucose levels. The AUCs were similar for OPG and OPG biomarkers. Conclusions Plasma OPG and OPN levels were significantly associated with inflammation and arterial hypertension. They might be useful as additional biomarkers for monitoring endothelial dysfunction and prognosis of cardiovascular diseases.

Exposure to the Chinese Famine in Early Life and the Risk of Metabolic Syndrome in Adulthood

OBJECTIVETo examine whether exposure to the Chinese famine during fetal life and early childhood is associated with the risks of metabolic syndrome and whether this association is modified by later life environment.RESEARCH DESIGN AND METHODSWe used data of 7,874 adults born between 1954 and 1964 from the 2002 China National Nutrition and Health Survey. Famine exposure groups were defined as nonexposed; fetal exposed; and early childhood, midchildhood, or late childhood exposed. Excess death rate was used to determine the severity of the famine. The ATP III criteria were used for the definition of metabolic syndrome (three or more of the following variables: elevated fasting triglyceride levels, lower HDL cholesterol levels, elevated fasting glucose levels, higher waist circumference, high blood pressure).RESULTSIn severely affected famine areas, adults who were exposed to the famine during fetal life had a higher risk of metabolic syndrome, as compared with nonexposed subjects (odds ratio 3.13 [95% CI 1.24–7.89, P = 0.016]). Similar associations were observed among adults who were exposed to the famine during early childhood, but not for adults exposed to the famine during mid- or late childhood. Participants who were born in severely affected famine areas and had Western dietary habits in adulthood or were overweight in adulthood had a particularly high risk of metabolic syndrome in later life.CONCLUSIONSExposure to the Chinese famine during fetal life or infancy is associated with an increased risk of metabolic syndrome in adulthood. These associations are stronger among subjects with a Western dietary pattern or who were overweight in adulthood.

Changes in blood glucose and cholesterol levels due to androgen deprivation therapy in men with non-metastatic prostate cancer.

To investigate the effects of androgen deprivation therapy (ADT) on blood glucose and cholesterol over 12 months in a prospective matched cohort study. English-speaking patients with non-metastatic prostate cancer attending the Princess Margaret Hospital were invited to participate in this study. Patients were divided into two cohorts: ADT users and controls. Androgen deprivation therapy users were frequency matched to controls on age, education and body mass index (BMI). The study consisted of two visits. Sociodemographic and clinical information, medication use, physical fitness, height and weight were collected before initiation of ADT. Twelve months later, fasting morning blood work was obtained to measure plasma glucose, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides. Statistical analyses included univariate and multivariable linear regression. We recruited 75 patients (mean age 68.9), 38 of whom were undergoing ADT. Twelve patients with prior diabetes and 29 patients taking cholesterol-lowering medication at baseline were excluded from the glucose and cholesterol analysis, respectively. In adjusted analyses, ADT users had a significantly higher glucose level compared to controls (5.88 vs. 5.52 mmol/L, p = 0.024). Overall, ADT users had higher levels of total cholesterol, HDL, LDL, and triglycerides than controls, although none of the differences reached statistical significance. One year of ADT use is associated with elevated fasting glucose levels and may increase all lipid fractions in men with prostate cancer.

ADT and the metabolic syndrome: no good deed goes unpunished

Although androgen deprivation therapy (ADT) has been used for more than half a century to treat prostate cancer, its mechanism and associated side effects are continuously updated. Androgens are key players in glucose homeostasis and lipid metabolism. In fact, lower total testosterone predicts a higher incidence of the metabolic syndrome, a cluster of risk factors predisposing patients to late onset diabetes mellitus, atherosclerosis and cardiovascular (CVS) morbidity and mortality.1 Since CVS disease is the most common competing cause for mortality, we should make all efforts to minimize our iatrogenic contribution to the metabolic syndrome and familiarize ourselves with the growing body of evidence linking ADT to the metabolic syndrome.2,3 Mohamedali and colleagues present their experience with the impact of long-term ADT on blood glucose levels in non-diabetic prostate cancer patients. The authors demonstrated that 1 year of ADT use is associated with elevated fasting glucose levels.4 This data is in line with a recent review of the ADT/metabolic syndrome which showed a clear casual association between ADT and diabetes mellitus, but the causal association is not as strong with CVS morbidity.5 The link needs to be better explored as novel ADT strategies are about to change our practice. In recent years it has become clear that current modes of castration are far from optimal in achieving complete androgen deprivation in prostate cancer cells. Multiple pre-clinical evidences suggest that prostate cancer cells can produce androgens which activate the androgen receptor already in concentrations lower than those traditionally defined as castrated serum testosterone levels (<20 ng/dL). Accordingly, although not completely validated, clinical observations suggest the lower the testosterone level under ADT, the longer the survival;6 it is possible that even lower levels of testosterone within and it is possible that even transient events of testosterone break through within the framework of ADT can accelerate disease progression.7 Hence, the current trend in ADT is a more strict deprivation of androgens in castrate resistant prostate cancer, and what we used to define as maximal androgen blocked (MAB) will certainly be expanded with the introduction of novel products, such as arbiraterone and MDV3100. It is reasonable to expect that novel therapeutic strategies that induce more effective testosterone suppression will reciprocally accentuate the metabolic side effect profile of ADT. Data comparing the long-term metabolic side effect of different modes of castration is currently limited,8 but once available, should better guide us in treating patients with known risk factors for CVS disease. We should incorporate routine baseline and follow-up assessments of metabolic measurements (fasting glucose levels, lipids, BMI) and advocate lifestyle modification for our ADT patients. We should also stay tuned for potentially more detrimental metabolic side effects with more strict MAB regimens.

A Novel PAX4 Mutation in a Japanese Patient with Maturity-Onset Diabetes of the Young

Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous type of diabetes mellitus, characterized by early onset (often before 25 years of age) and absence of pancreatic autoimmunity markers. Paired-homeodomain transcription factor 4 (PAX4) functions as a transcriptional repressor and is involved in the differentiation of insulin-secreting β-cells. Here we identified a novel PAX4 mutation in a Japanese patient with MODY. A 15-year-old, non-obese boy was admitted to our hospital because of polyuria and polydipsia. Laboratory evaluation showed an elevated fasting glucose level; however, islet cell antibodies and glutamic acid decarboxylase antibodies were not detected in the patient's serum. The proband's father had been diagnosed as having type 2 diabetes at age of 30 years. We therefore analyzed several candidate genes of MODY, and identified a novel mutation of a 39-base heterozygous deletion in exon 3 (c.374-412 del39) of PAX4 in the proband and his father. This mutation may cause exon 3 skipping that results in a frameshift, thereby producing a premature stop codon in exon 5. As this mutant PAX4 lacks a part of the homeodomain that is critical for binding to the target gene, this mutant was thought to lose the transcriptional repressor function. As expected, luciferase-reporter assays revealed that the mutant PAX4 could not repress the activities of insulin and glucagon gene promoters, unlike the wild-type PAX4 that repressed the promoter activities. The present study demonstrates that a novel mutation of PAX4 is likely to be associated with diabetes in this Japanese family.

Risk factors associated with metabolic syndrome in type 2 diabetes mellitus patients according to World Health Organization, Third Report National Cholesterol Education Program, and International Diabetes Federation definitions

Risk factors associated with metabolic syndrome in type 2 diabetes mellitus patients according to World Health Organization, Third Report National Cholesterol Education Program, and International Diabetes Federation definitions Angel Rodr&iacute;guez1, Helena Delgado-Cohen1, Jes&uacute;s Reviriego1, Manuel Serrano-R&iacute;os21Clinical Research Department, Eli Lilly and Company, Madrid, Spain; 2Department of Internal Medicine II, Hospital Clinico San Carlos, Madrid, SpainBackground: The availability of several definitions of the metabolic syndrome has created potential confusion concerning its prognostic utility. At present, little data exist about the risk factors associated with metabolic syndrome in diabetic patients.Aim: To identify risk factors associated with metabolic syndrome in patients with type 2 diabetes mellitus according to three diagnostic criteria: World Health Organization (WHO), Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults &ndash; Adult Treatment Panel III (NCEP-ATP III), and International Diabetes Federation (IDF).Subjects and methods: A logistic regression model was used to identify demographic, clinical, and lifestyle variables related with metabolic syndrome (N = 1259).Results: Hypertension, dyslipidemia, and glycosylated hemoglobin (HbA1c) &ge;7% were associated with increased risk of WHO-defined metabolic syndrome (odds ratio [OR], 2.33; 95% confidence interval [CI]: 1.60&ndash;3.40; OR, 1.79 95% CI: 1.25&ndash;2.55; and OR, 1.58; 95% CI: 1.12&ndash;2.22, respectively). The risk of presenting metabolic syndrome according to NCEP-ATP III criteria was increased in female patients (OR, 2.02; 95% CI: 1.37&ndash;2.97), elevated fasting glucose levels (OR, 5.99; 95% CI: 3.56&ndash;10.07), dyslipidemia (OR, 2.28; 95% CI: 1.57&ndash;3.32), hypertension (OR, 2.36; 95% CI: 1.59&ndash;3.53), and endocrine disorders (OR, 1.64; 95% CI: 1.06&ndash;2.57). For the IDF criteria, female patients and patients with left ventricular hypertrophy or insulin treatment were at higher risk of metabolic syndrome (OR, 4.00; 95% CI: 2.35&ndash;6.80; OR, 2.72 95% CI: 1.22&ndash;6.04; and OR, 1.96 95% CI: 1.24&ndash;3.11, respectively).Conclusions: The risk factors for metabolic syndrome in type 2 diabetes mellitus patients are highly dependent on the criteria used to define the syndrome, supporting the need for a single clinically useful and epidemiologically useful definition.Keywords: metabolic syndrome, type 2 diabetes mellitus, epidemiologic studies, risk factors

Risk factors associated with metabolic syndrome in type 2 diabetes mellitus patients according to World Health Organization, Third Report National Cholesterol Education Program, and International Diabetes Federation definitions

Background:The availability of several definitions of the metabolic syndrome has created potential confusion concerning its prognostic utility. At present, little data exist about the risk factors associated with metabolic syndrome in diabetic patients.Aim:To identify risk factors associated with metabolic syndrome in patients with type 2 diabetes mellitus according to three diagnostic criteria: World Health Organization (WHO), Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults – Adult Treatment Panel III (NCEP-ATP III), and International Diabetes Federation (IDF).Subjects and methods:A logistic regression model was used to identify demographic, clinical, and lifestyle variables related with metabolic syndrome (N = 1259).Results:Hypertension, dyslipidemia, and glycosylated hemoglobin (HbA1c) ≥7% were associated with increased risk of WHO-defined metabolic syndrome (odds ratio [OR], 2.33; 95% confidence interval [CI]: 1.60–3.40; OR, 1.79 95% CI: 1.25–2.55; and OR, 1.58; 95% CI: 1.12–2.22, respectively). The risk of presenting metabolic syndrome according to NCEP-ATP III criteria was increased in female patients (OR, 2.02; 95% CI: 1.37–2.97), elevated fasting glucose levels (OR, 5.99; 95% CI: 3.56–10.07), dyslipidemia (OR, 2.28; 95% CI: 1.57–3.32), hypertension (OR, 2.36; 95% CI: 1.59–3.53), and endocrine disorders (OR, 1.64; 95% CI: 1.06–2.57). For the IDF criteria, female patients and patients with left ventricular hypertrophy or insulin treatment were at higher risk of metabolic syndrome (OR, 4.00; 95% CI: 2.35–6.80; OR, 2.72 95% CI: 1.22–6.04; and OR, 1.96 95% CI: 1.24–3.11, respectively).Conclusions:The risk factors for metabolic syndrome in type 2 diabetes mellitus patients are highly dependent on the criteria used to define the syndrome, supporting the need for a single clinically useful and epidemiologically useful definition.

Metabolic syndrome and new onset diabetes after transplantation in kidney transplant recipients

Metabolic syndrome (MS) and new onset diabetes after transplant (NODAT) are common in kidney transplant patients. We studied the relationship between the two conditions and their impact on metabolic and cardiovascular risk profiles. All non-diabetic patients transplanted between 1999 and 2005 who were followed up to 2006 were included. MS and NODAT were determined. Kaplan-Meier survival and various regression analyses were performed to determine the clinical correlates for both conditions and their association with various cardiovascular risk factors. Among 591 patients, 314 (53.1%) had MS and 90 (15.2%) developed NODAT. The two conditions were highly associated with each other as 84 patients with NODAT also had MS (14.2%). Elevated body mass index and fasting glucose levels at transplant were risk factors for both conditions, whereas weight gain after transplant was associated only with MS. African American, old age, and hypertension-related ESRD were risk factors for NODAT. Finally, the presence of MS was associated with reduced kidney function and elevated uric acid levels, whereas the presence of NODAT with elevated pulse pressure. MS and NODAT are highly prevalent and significantly associated with impaired metabolic and cardiovascular risk profiles. Early identification of such conditions may facilitate targeted therapeutic intervention.

Abdominal adiposity in rheumatoid arthritis: Association with cardiometabolic risk factors and disease characteristics

Abdominal adiposity, especially visceral adiposity, is emerging as a recognized cardiometabolic risk factor. This study was undertaken to investigate how abdominal fat is distributed in rheumatoid arthritis (RA), and its RA-related determinants. Men and women with RA were compared with non-RA controls from the Multi-Ethnic Study of Atherosclerosis. Participants underwent anthropometric studies and quantification of visceral and subcutaneous fat areas (VFA and SFA) using abdominal computed tomography. A total of 131 RA patients were compared with 121 controls. Despite similar body mass index and waist circumference between the RA and control groups, the adjusted mean VFA was 45 cm2 higher (+51%) in male RA patients versus male controls (P = 0.005), but did not significantly differ by RA status in women. The adjusted mean SFA was 119 cm2 higher (+68%) in female RA patients versus female controls (P < 0.001), but did not significantly differ by RA status in men. Elevated VFA (≥75th percentile) was associated with a significantly higher adjusted probability of having an elevated fasting glucose level, hypertension, or meeting the composite definition of the metabolic syndrome in the RA group compared with controls. Within the RA group, rheumatoid factor seropositivity and higher cumulative prednisone exposure were significantly associated with a higher mean adjusted VFA. Higher C-reactive protein levels and lower Sharp/van der Heijde scores were significantly associated with both VFA and SFA. The distribution of abdominal fat differs significantly by RA status. Higher VFA in men with RA, and the more potent association of VFA with cardiometabolic risk factors in men and women with RA, may contribute to cardiovascular risk in RA populations.

Cyclic GMP Kinase I Modulates Glucagon Release From Pancreatic α-Cells

OBJECTIVEThe physiologic significance of the nitric oxide (NO)/cGMP signaling pathway in islets is unclear. We hypothesized that cGMP-dependent protein kinase type I (cGKI) is directly involved in the secretion of islet hormones and glucose homeostasis.RESEARCH DESIGN AND METHODSGene-targeted mice that lack cGKI in islets (conventional cGKI mutants and cGKIα and Iβ rescue mice [α/βRM] that express cGKI only in smooth muscle) were studied in comparison to control (CTR) mice. cGKI expression was mapped in the endocrine pancreas by Western blot, immuno-histochemistry, and islet-specific recombination analysis. Insulin, glucagon secretion, and cytosolic Ca2+ ([Ca2+]i) were assayed by radioimmunoassay and FURA-2 measurements, respectively. Serum levels of islet hormones were analyzed at fasting and upon glucose challenge (2 g/kg) in vivo.RESULTSImmunohistochemistry showed that cGKI is present in α- but not in β-cells in islets of Langerhans. Mice that lack α-cell cGKI had significantly elevated fasting glucose and glucagon levels, whereas serum insulin levels were unchanged. High glucose concentrations strongly suppressed the glucagon release in CTR mice, but had only a moderate effect on islets that lacked cGKI. 8-Br-cGMP reduced stimulated [Ca2+]i levels and glucagon release rates of CTR islets at 0.5 mmol/l glucose, but was without effect on [Ca2+]i or hormone release in cGKI-deficient islets.CONCLUSIONSWe propose that cGKI modulates glucagon release by suppression of [Ca2+]i in α-cells.

Cardiovascular Risk in Patients With Fasting Blood Glucose Levels Within Normal Range

Fasting glucose levels elevated beyond the normal range have been associated with increased cardiovascular risk. However, it is unknown whether this association exists for variations of fasting glucose within the normal range. The present study was conducted using the computerized database of the Sharon-Shomron District of Clalit Health Services. Included in the present study were subjects with fasting glucose levels within the normal range (< 100 mg/dl). We excluded patients with a history of cardiovascular disease or diabetes. The primary outcome was the incidence of coronary revascularization with either percutaneous coronary intervention or coronary artery bypass grafting. The 28,263 participants (age 53.7 ± 12.2 years) were divided into quartiles according to the fasting glucose level (75.4 ± 4.5, 83.6 ± 1.7, 88.9 ± 1.4, and 95.1 ± 2.2 mg/dl). During a mean follow-up of 5.9 ± 0.7 years, 424 subjects required coronary revascularization. A progressive increase was seen in the risk of coronary revascularization as the fasting glucose levels increased within the normal range (hazard ratio 1.73, 95% confidence interval 1.3 to 2.3, p > 0.001, between the fourth and first quartiles). However, this association lost its statistical significance after adjustments for the conventional coronary risk factors (hazard ratio 1.17, 95% confidence interval 0.85 to 1.62, p = 0.328). In conclusion, elevated fasting glucose levels within the normal range were associated with an increased cardiovascular risk. This association was caused by the greater prevalence of the other conventional risk factors and not by the glucose level itself.