Reumatismo. 2012; 63(4): 238-45
Grassi W, De Angelis R

Gout is a metabolic disease characterized by hyperuricemia and the deposition of monosodium urate (MSU) crystals in the joints and soft tissues, consisting of a self-limited acute phase characterized by recurrent attacks of synovitis and a chronic phase in which inflammatory and structural changes of the joints and periarticular tissues may lead to persistent symptoms. Acute gout is characterized by a sudden monoarthritis of rapid onset, with intense pain, mostly affecting the big toe (50% of initial attacks), the foot, ankle, midtarsal, knee, wrist, finger, and elbow. Acute flares also occur in periarticular structures, including bursae and tendons. The presence of characteristic MSU crystals in the joint fluid, appearing needle-like and showing strong negative birefringence by polarized microscopy, is pivotal to confirm the diagnosis of gout. The time interval separating the first attack from subsequent episodes of acute synovitis may be widely variable, ranging from a few days to several years. During the period between acute attacks the patient is asymptomatic even if MSU deposition may continue to increase silently. The factors that control the rate, location, and degree of ongoing deposition in gouty patients are not well defined. Chronic gout is the natural evolution of untreated hyperuricemia in patients with gouty attacks followed by pain-free intercritical periods. It is characterized by the deposition of solid MSU crystal aggregates in a variety of tissues including joints, bursae and tendons. Tophi can occur in a variety of locations including the helix of the ear, olecranon bursa, and over the interphalangeal joints. Their development is usually related with both the degree and the duration of hyperuricemia. About 20% of patients with gout have urinary tract stones and can develop an interstitial urate nephropathy. There is a strong association between hyperuricaemia and the metabolic syndrome (the constellation of insulin resistance, hypertension, obesity and dyslipidaemia), and gouty patients often have a medical history of kidney disease, diabetes mellitus and signs of vascular illness such as coronary artery disease, heart failure and stroke, resulting with a poor overall quality of life.

Reumatismo. 2012; 63(4): 207-20
Ciancio G, Bortoluzzi A, Govoni M

Gout is the most common cause of inflammatory arthritis affecting at least 1% of the population in industrialized countries. It is closely associated with hyperuricemia and is characterized by formation and reversible deposition of monosodium urate crystals in joints and extra-articular tissues. Several studies suggest that the prevalence and incidence of gout are rising. Numerous risk factors may in part explain this increasing trend including dietary and lifestyle changes, genetic factors, diuretic use and comorbid conditions such as hypertension, diabetes, cardiovascular disease, chronic renal disease and the metabolic syndrome. Chondrocalcinosis is characterized by the deposition of calcium pyrophosphate crystals in articular tissues, most commonly fibrocartilage and hyaline cartilage. Sporadic chondrocalcinosis is a common condition in the elderly and frequently associates with osteoarthritis. Hereditary haemochromatosis, hyperparathyroidism and hypomagnesaemia are metabolic disorders that predispose to secondary chondrocalcinosis.The prevalence of chondrocalcinosis is still rather uncertain and varies depending on the diagnostic criterion used in different studies.

Ann Clin Psychiatry. 2012 Feb; 24(1): 69-81
McIntyre RS, Alsuwaidan M, Goldstein BI, Taylor VH, Schaffer A, Beaulieu S, Kemp DE

One goal of the Canadian Network for Mood and Anxiety Treatments (CANMAT) is to develop evidence-based and best practice educational programs and recommendations. Our group conducted a comprehensive literature review to provide evidence-based recommendations for treating metabolic comorbidity in individuals with major depressive disorder (MDD) and bipolar disorder (BD).We searched PubMed for all English-language articles published January 1966 to November 2010 using BD and MDD cross-referenced with metabolic syndrome, obesity, diabetes mellitus, hypertension, and dyslipidemia. That search was augmented by a review of articles reporting outcomes of an intervention targeting components of metabolic syndrome in individuals with MDD or BD.Consensus exists for the recommendation that individuals with MDD and BD should be routinely screened for risk factors that increase risk for metabolic syndrome. For excess weight, the best-studied pharmacologic approaches are metformin and topiramate, with emerging evidence for liraglutide and modafinil. For binge eating disorder, the best evidence in mood disorders was for cognitive-behavioral therapy as well as topiramate, zonisamide, and in select cases selective serotonin reuptake inhibitors. For dysglycemia, dyslipidemia, and hypertension, evidence supports cognitive-behavioral interventions and anti-diabetic, antilipidemic, and antihypertensive treatments.Comprehensive care of individuals with mood disorders should include routine evaluation of the risk and presence of metabolic syndrome and its components. Systematic evaluation of preventative and targeted treatments of metabolic syndrome in mood disorder populations is insufficient.

PLoS Negl Trop Dis. 2012 Jan; 6(1): e1488
Peacock SJ, Limmathurotsakul D, Lubell Y, Koh GC, White LJ, Day NP, Titball RW

Burkholderia pseudomallei is a Category B select agent and the cause of melioidosis. Research funding for vaccine development has largely considered protection within the biothreat context, but the resulting vaccines could be applicable to populations who are at risk of naturally acquired melioidosis. Here, we discuss target populations for vaccination, consider the cost-benefit of different vaccination strategies and review potential vaccine candidates.Melioidosis is highly endemic in Thailand and northern Australia, where a biodefense vaccine might be adopted for public health purposes. A cost-effectiveness analysis model was developed, which showed that a vaccine could be a cost-effective intervention in Thailand, particularly if used in high-risk populations such as diabetics. Cost-effectiveness was observed in a model in which only partial immunity was assumed. The review systematically summarized all melioidosis vaccine candidates and studies in animal models that had evaluated their protectiveness. Possible candidates included live attenuated, whole cell killed, sub-unit, plasmid DNA and dendritic cell vaccines. Live attenuated vaccines were not considered favorably because of possible reversion to virulence and hypothetical risk of latent infection, while the other candidates need further development and evaluation. Melioidosis is acquired by skin inoculation, inhalation and ingestion, but routes of animal inoculation in most published studies to date do not reflect all of this. We found a lack of studies using diabetic models, which will be central to any evaluation of a melioidosis vaccine for natural infection since diabetes is the most important risk factor.Vaccines could represent one strand of a public health initiative to reduce the global incidence of melioidosis.

PLoS One. 2012; 7(1): e30337
Wu HY, Hung KY, Huang TM, Hu FC, Peng YS, Huang JW, Lin SL, Chen YM, Chu TS, Tsai TJ, Wu KD

Effects of long-term glucose load on peritoneal dialysis (PD) patient safety and outcomes have seldom been reported. This study demonstrates the influence of long-term glucose load on patient and technique survival.We surveyed 173 incident PD patients. Long-term glucose load was evaluated by calculating the average dialysate glucose concentration since initiation of PD. Risk factors were assessed by fitting Cox's models with repeatedly measured time-dependent covariates.We noted that older age, higher glucose concentration, and lower residual renal function (RRF) were significantly associated with a worse patient survival. We found that female gender, absence of diabetes, lower glucose concentration, use of icodextrin, higher serum high density lipoprotein cholesterol, and higher RRF were significantly associated with a better technique survival.Long-term glucose load predicted mortality and technique failure in chronic PD patients. These findings emphasize the importance of minimizing glucose load in PD patients.

Indian J Pharm Sci. 2011 Mar; 73(2): 139-45
Viswanathaswamy AH, Koti BC, Gore A, Thippeswamy AH, Kulkarni RV

The present study was undertaken to investigate the antihyperglycemic and antihyperlipidemic effects of ethanol extract of Plectranthus amboinicus in normal and alloxan-induced diabetic rats. Diabetes was induced in Wistar rats by single intraperitoneal administration of alloxan monohydrate (150 mg/kg). Normal as well as diabetic rats were divided into groups (n=6) receiving different treatments. Graded doses (200 mg/kg and 400 mg/kg) of ethanol extract of Plectranthus amboinicus were studied in both normal and alloxan-induced diabetic rats for a period of 15 days. Glibenclamide (600 μg/kg) was used as a reference drug. Oral administration with graded doses of ethanol extract of Plectranthus amboinicus exhibited hypoglycemic effect in normal rats and significantly reduced the peak glucose levels after 120 min of glucose loading. In alloxan-induced diabetic rats, the daily oral treatment with ethanol extract of Plectranthus amboinicus showed a significant reduction in blood glucose. Besides, administration of ethanol extract of Plectranthus amboinicus for 15 days significantly decreased serum contents of total cholesterol, triglycerides whereas HDL-cholesterol, total proteins and calcium were effectively increased. Furthermore, effect of ethanol extract of Plectranthus amboinicus showed profound elevation of serum amylase and reduction of serum lipase. Histology examination showed ethanol extract of Plectranthus amboinicus exhibited almost normalization of damaged pancreatic architecture in rats with diabetes mellitus. Studies clearly demonstrated that ethanol extract of Plectranthus amboinicus leaves possesses hypoglycemic and antihyperlipidemic effects mediated through the restoration of the functions of pancreatic tissues and insulinotropic effect.

Genes Dev. 2012 Feb 1; 26(3): 259-70
Krishnan J, Danzer C, Simka T, Ukropec J, Walter KM, Kumpf S, Mirtschink P, Ukropcova B, Gasperikova D, Pedrazzini T, Krek W

Dietary obesity is a major factor in the development of type 2 diabetes and is associated with intra-adipose tissue hypoxia and activation of hypoxia-inducible factor 1α (HIF1α). Here we report that, in mice, Hif1α activation in visceral white adipocytes is critical to maintain dietary obesity and associated pathologies, including glucose intolerance, insulin resistance, and cardiomyopathy. This function of Hif1α is linked to its capacity to suppress β-oxidation, in part, through transcriptional repression of sirtuin 2 (Sirt2) NAD(+)-dependent deacetylase. Reduced Sirt2 function directly translates into diminished deacetylation of PPARγ coactivator 1α (Pgc1α) and expression of β-oxidation and mitochondrial genes. Importantly, visceral adipose tissue from human obese subjects is characterized by high levels of HIF1α and low levels of SIRT2. Thus, by negatively regulating the Sirt2-Pgc1α regulatory axis, Hif1α negates adipocyte-intrinsic pathways of fatty acid catabolism, thereby creating a metabolic state supporting the development of obesity.

Circulation. 2012 Feb 1;
Kim JK

Insulin resistance is a major characteristic of type 2 diabetes and develops in multiple organs including skeletal muscle, liver, adipose tissue, and heart(1). Insulin resistance is caused by obesity and therefore establishes an important causal relationship between obesity and type 2 diabetes(2). Insulin resistance also develops in aging, but this process is less well understood. Obesity is a complex physiological state with alterations in lipid metabolism, dysregulated production of hormones, ectopic accumulation of fat, mitochondrial dysfunction, and chronic low-grade inflammation(3,4). All of these abnormalities may independently cause insulin resistance and affect glucose homeostasis, which make insulin resistance as equally complex as obesity itself. (SELECT FULL TEXT TO CONTINUE).

Circ Res. 2012 Feb 3; 110(3): 483-95
Creemers EE, Tijsen AJ, Pinto YM

In the past few years, the crucial role of different micro-RNAs (miRNAs) in the cardiovascular system has been widely recognized. Recently, it was discovered that extracellular miRNAs circulate in the bloodstream and that such circulating miRNAs are remarkably stable. This has raised the possibility that miRNAs may be probed in the circulation and can serve as novel diagnostic markers. Although the precise cellular release mechanisms of miRNAs remain largely unknown, the first studies revealed that these circulating miRNAs may be delivered to recipient cells, where they can regulate translation of target genes. In this review, we will discuss the nature of the stability of miRNAs that circulate in the bloodstream and discuss the available evidence regarding the possible function of these circulating miRNAs in distant cell-to-cell communication. Furthermore, we summarize and discuss the usefulness of circulating miRNAs as biomarkers for a wide range of cardiovascular diseases such as myocardial infarction, heart failure, atherosclerosis, hypertension, and type 2 diabetes mellitus.

Circ Res. 2012 Feb 3; 110(3): 378-80
Bugger H, Abel ED

Exp Biol Med (Maywood). 2012 Feb 2;
Cahova M, Palenickova E, Papackova Z, Dankova H, Skop V, Kazdova L

Epinephrine controls many important and sometimes opposite processes. This pleiotropic effect is achieved via coupling to different receptor/effector systems. In epididymal white adipose tissue (EWAT) of Wistar rats, we showed that epinephrine stimulated protein kinase B (PKB) phosphorylation on Ser(473). Epinephrine further increased the glucose incorporation into glyceride-glycerol without decreasing glucose availability for other metabolic pathways (i.e. lactate production). Wortmannin (phosphatidylinositol 3-kinase inhibitor) treatment significantly decreased glucose incorporation into glyceride-glycerol and elevated the epinephrine-induced release of free fatty acids (FFA) from the adipose tissue without any change in the intensity of lipolysis measured as glycerol release. Using specific cyclic adenosine monophosphate (cAMP) analogs we demonstrated that cAMP-protein kinase A (PKA) signalling resulted in a strong PKB dephosphorylation and significantly lowered the glucose availability in EWAT. Specific activation of the Epac (exchange protein activated by cAMP)-dependent pathway had only a moderately negative effect on PKB phosphorylation and glucose metabolism. In contrast, α(1) agonist methoxamine increased PKB phosphorylation and lactate production. This effect of methoxamine was additive to the effect of insulin and it was abolished by wortmannin treatment. In EWAT of spontaneously dyslipidemic hereditary hypertriglyceridemic (HHTg) rats, we demonstrated significantly lower epinephrine-induced glucose utilization but higher sensitivity to its lipolytic effect. We conclude that in EWAT, epinephrine controls two opposite processes (FFA release and FFA retention) via two different effector systems. The impairment of α(1)-dependent, epinephrine-stimulated, glycolysis-dependent FFA esterification may contribute to the establishment of dyslipidemia in insulin resistance.

J Genet Couns. 2012 Feb 3;
Waxler JL, O'Brien KE, Delahanty LM, Meigs JB, Florez JC, Park ER, Pober BR, Grant RW

Advances in genetic epidemiology have increased understanding of common, polygenic preventable diseases such as type 2 diabetes. As genetic risk testing based on this knowledge moves into clinical practice, we propose that genetic counselors will need to expand their roles and adapt traditional counseling techniques for this new patient set. In this paper, we present a genetic counseling intervention developed for a clinical trial [Genetic Counseling/Lifestyle Change for Diabetes Prevention, ClinicalTrials.gov identifier: NCT01034319] designed to motivate behavioral changes for diabetes prevention. Seventy-two phenotypically high-risk participants received counseling that included their diabetes genetic risk score, general education about diabetes risk factors, and encouragement to participate in a diabetes prevention program. Using two validated genetic counseling scales, participants reported favorable perceived control and satisfaction with the counseling session. Our intervention represents one model for applying traditional genetic counseling principles to risk testing for polygenetic, preventable diseases, such as type 2 diabetes.