Kegg Pathway: Type II diabetes mellitus

Curr Opin Drug Discov Devel. 2009 Nov; 12(6): 862-75
Shibasaki M, Kumagai N, Mashiko T

This review summarizes recent advances in the development of efficient routes based on enantioselective catalysis for the synthesis of optically active therapeutic agents. Particular emphasis is placed on research that has streamlined the large-scale production of therapeutics for the treatment of Type 2 diabetes mellitus (T2DM). Progress in the catalytic asymmetric hydrogenation and amination of unprotected substrates has enabled the establishment of concise synthetic routes for the production of the potent dipeptidyl peptidase 4 inhibitor sitagliptin, and the aldose reductase inhibitor ranirestat (Dainippon Sumimoto Pharma Co Ltd/Eisai Co Ltd/ Kyorin Pharmaceutical Co Ltd), both of which have attracted particular attention for their potential to treat T2DM and diabetic complications, respectively.

Rev Esp Salud Publica. 2009 Jul-Aug; 83(4): 567-75
Cabrera de León A, Castillo Rodríguez JC, Domínguez Coello S, Rodríguez Pérez Mdel C, Brito Díaz B, Borges Alamo C, Carrillo Fernández L, Almeida González D, Alemán Sánchez JJ, González Hernández A, Aguirre-Jaime A

Background: The Canary Islands population experiences the highest Type 2 diabetes (DM2) mortality in Spain. We studied lifestyle, unknown DM2 and treatment adherence in diabetics of these islands. Methods: cross-sectional study of 6729 subjects from the general population (age 18-75) that participate in the cohort study "CDC of the Canary Islands". We found out their medical problems, diet, physical activity, medications, smoking, etc. Results: Prevalence of DM2 was 12% in men and 10% in women (p=0.005). The disease was unknown in 22% of men and 9% of women (p < 0.001). Considering unknown DM2, lack of treatment and lack of adherence, 48% of men and 28% of women did not follow a regular treatment. Diabetics' men prevalences of smoking (28%; CI95%=23-33) and sedentariness (62%; CI95%=56-68) were similar to non diabetic men, but obesity was more frequent in diabetics (45 versus 25%; p < 0.001). Diabetics women showed a higher obesity (54 versus 27%; p < 0.001) and a lower smoking prevalence (11 versus 22%; p < 0,001) than non diabetics, but they presented a similar sedentariness (75%; CI95%=70-79). In both sexes, energy intake was lower in diabetics (p < 0.001), but 93% of them (CI95%=91-95) showed a high consumption of calories from saturated fat and 69% (CI95%=65-72) presented metabolic syndrome. Conclusions: The Canarian diabetics are a sedentary and obese population that show a high consumption of saturated fats and high prevalence of metabolic syndrome. The proportion of them following regular treatment is low, specially in diabetic men that, in addition, still smoke.

Aust Fam Physician. 2009 Oct; 38(10): 780-3
Spurling G, Askew D, Jackson C

BACKGROUND: Type 2 diabetes mellitus is an increasingly prevalent presentation in Australian general practice, where most patients receive their preventive care and management. OBJECTIVE: In this article we discuss the relevant issues for clinicians and the screening recommendations for diabetic and hypertensive retinopathy. DISCUSSION: Screening for diabetic retinopathy is a crucial component of preventive care, with early identification of change and timely treatment likely to prevent most blindness. Despite this, a quarter of Australians with diabetes are not appropriately screened. General practitioners must take a key role in initiating, delivering or monitoring their patient's diabetic retinopathy screening to reduce preventable blindness from diabetes mellitus. Hypertensive retinopathy indicates end organ disease but regular screening for hypertensive retinopathy is not routinely recommended.

Aust Fam Physician. 2009 Sep; 38(9): 699-703
Phillips J, Phillips PJ

BACKGROUND: In recent years there has been a worldwide increase in the number of diagnoses of Type 2 diabetes mellitus (T2DM) in children and adolescents. This has become a major focus for the work of the International diabetes Federation. In Australia, most children and adolescents with diabetes have Type 1 diabetes. However, more young Australians are developing T2DM. OBJECTIVE: This article presents the case of a girl, Aroha, 13 years of age and of Polynesian descent, who presents with high random blood glucose levels. It outlines the diagnosis, treatment and prognosis of T2DM in children and adolescents. DISCUSSION: Type 2 diabetes is the consequence of a complex interaction between genes and the environment in a susceptible individual. Children with T2DM are generally overweight, often with central adiposity. Having one or more parents with T2DM gives offspring up to an 80% chance of developing T2DM. At risk children and adolescents should be screened for T2DM. It is important to check the glutamic acid decarboxylase (GAD) antibody to exclude Type 1 diabetes. Symptoms and signs of the metabolic syndrome should be sought. Child and adolescent patients with T2DM face the psychological burden of living a lifetime with a chronic disease. Management is team based and team members include the general practitioner, diabetes educator, dietician and endocrinologist. Goals include achieving and maintaining normoglycaemia, weight reduction and increased physical activity. Lifestyle modification alone may control minor hyperglycaemia and metformin can be added to control moderate hyperglycaemia. In severe hypoglycaemia, insulin may be required initially to achieve normoglycaemia and can be phased out and metformin phased in later. Insulin is likely to be required again later in the natural history of disease. Little is known about factors affecting complication risk in children and adolescents with T2DM but they essentially have a 'double whammy' of diabetes and the metabolic syndrome and are likely to develop macrovascular complications much earlier than adults who develop T2DM.

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2009 Oct; 34(10): 1011-6
Yang L, Zhou Z, DU T, Tan S, Zhnag Y, Jin P

Objective To explore the characteristics of T cell immunity in peripheral blood of patients with carboxypeptidase-H antibody (CPH-Ab).Methods Forty-two latent autoimmune diabetes in adults (LADA) patients with CPH-Ab(+) alone, 20 Type 2 diabetes mellitus patients (T2DM), and 22 healthy controls were selected and their peripheral blood mononuclear cells were isolated. Human recombinant carboxypeptidase (CPH) protein was expressed and further used as a stimulant in Enzyme-linked immunospot (ELISPOT) assay to detect IFN-gamma-Th1 and IL-4-Th2 cells in the 3 groups. Th1/Th2 ratios were also calculated. CPH-Ab and glutamic acid decarboxylase antibody (GAD-Ab) were determined by radioligand assay.Results Compared with healthy controls and T2DM, IFN-gamma-Th1 and IL-4-Th2 numbers did not increase significantly in CPH-Ab(+) group, nor did the Th1/Th2 ratios (P>0.05). We further divided the CPH-Ab(+) patients into a short duration group (n=22) and a long duration subgroup (n=20) according to the duration of 3 years. CPH-IL-4-T in the short duration subgroup was significantly higher than that in T2DM and healthy controls (1.8 vs. 0.2 and 0.3, both P<0.05) and we did not find any factor that was significantly correlated with the IL-4 spots number. There were not any significant differences in T cell responses to phaseolus vulgaris agglutinin (PHA) among all groups (P>0.05). Conclusion CPH does not directly involve in the cellular pathological mechanism of LADA. Anti-CPH immunity may be associated with more slowly aggressive beta cell autoimmunity.

J Alzheimers Dis. 2009 Nov 5;
Cocks G, Wilde JI, Graham SJ, Bousgouni V, Virley D, Lovestone S, Richardson J

In a recent clinical study, the thiazolidinedione (TZD) pioglitazone (Actos was reported to preserve cognitive function in patients with mild to moderate Alzheimer's disease and Type II diabetes mellitus. TZDs are agonists of the nuclear hormone receptor peroxisome proliferator-activated receptor-gamma (PPARgamma), are peripheral insulin sensitizers, and have recently been reported to increase mitochondrial biogenesis in the central nervous system and dendritic spine density. We report a transcriptional profile of the TZD pioglitazone and the non-TZD PPARgamma agonist GW347845 in primary cortical culture. We observed that pioglitazone, but not GW347845, increased cholesterol biosynthetic and lipogenic gene expression after 6 h, and the expression of the cholesterol efflux transporters Abca1 and Abcg1 after 24 h. Co-treatment of pioglitazone with the PPARgamma antagonist GW9662 did not significantly reduce these effects, suggesting a PPARgamma-independent mechanism. These findings suggest a novel effect of TZDs in neurons that may be of relevance as a novel approach against Alzheimer's disease.

J Clin Endocrinol Metab. 2009 Nov 5;
Nair S, Wilding JP

Context: Sodium-glucose cotransporter 2 (SGLT2) expressed in the proximal renal tubules accounts for about 90% of the reabsorption of glucose from tubular fluid. Genetic defects of SGLT2 result in a benign familial renal glucosuria. Pharmacological agents that block SGLT2 are being tested as potential treatment for Type 2 diabetes mellitus. Evidence Acquisition: A Pubmed search was used to identify all relevant articles on the physiology of SGLTs as well as published preclinical and clinical experimental studies with SGLT2 inhibitors; a reference search of all retrieved articles was also undertaken. Evidence Synthesis: SGLT2 is almost exclusively expressed in the proximal renal tubules. Preclinical studies with selective SLGT2 inhibitors show dose-dependent glucosuria and lowering of blood glucose in models of Type 2 diabetes. Preliminary clinical studies of up to 3-month duration show dose-dependent lowering of glycosylated hemoglobin up to 0.9% along with modest weight loss. Side effects include an increase in genital fungal infection compared to placebo, increased urine volume (300-400 ml/24 h), and evidence of volume depletion consistent with mild diuretic effect. Conclusion: SGLT2 inhibitors are showing promise as a useful addition to the current therapeutic options in Type 2 diabetes mellitus. Results of ongoing phase III clinical trials are awaited and will determine whether the risk-benefit ratio will allow approval of this new class of drug for the management of Type 2 diabetes mellitus.

J Clin Endocrinol Metab. 2009 Nov 5;
Tan JT, Ng DP, Nurbaya S, Ye S, Lim XL, Leong H, Seet LT, Siew WF, Kon W, Wong TY, Saw SM, Aung T, Chia KS, Lee J, Chew SK, Seielstad M, Tai ES

Context: Novel Type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations. However, the association in other East Asian populations is less well characterized. Objective: To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore. Design: We genoTyped these candidate single-nucleotide polymorphisms (SNPs) in subjects from three major ethnic groups in Asia, namely, the Chinese (2196 controls and 1541 cases), Malays (2257 controls and 1076 cases), and Asian-Indians (364 controls and 246 cases). We also performed a metaanalysis of our results with published studies in East Asians. Results: In Chinese, SNPs in CDKAL1 [odds ratio (OR) = 1.19; P = 2 x 10(-4)], HHEX (OR = 1.15; P = 0.013), and KCNQ1 (OR = 1.21; P = 3 x 10(-4)) were significantly associated with T2DM. Among Malays, SNPs in CDKN2A/B (OR = 1.22; P = 3.7 x 10(-4)), HHEX (OR = 1.12; P = 0.044), SLC30A8 (OR = 1.12; P = 0.037), and KCNQ1 (OR = 1.19-1.25; P = 0.003-2.5 x 10(-4)) showed significant association with T2DM. The combined analysis of the three ethnic groups revealed significant associations between SNPs in CDKAL1 (OR = 1.13; P = 3 x 10(-4)), CDKN2A/B (OR = 1.16; P = 9 x 10(-5)), HHEX (OR = 1.14; P = 6 x 10(-4)), and KCNQ1 (OR = 1.16-1.20; P = 3 x 10(-4) to 3 x 10(-6)) with T2DM. SLC30A8 (OR = 1.06; P = 0.039) showed association only after adjustment for gender and body mass index. Metaanalysis with data from other East Asian populations showed similar effect sizes to those observed in populations of European ancestry. Conclusions: SNPs at T2DM susceptibility loci identified through GWAS in populations of European ancestry show similar effects in Asian populations. Failure to detect these effects across different populations may be due to issues of power owing to limited sample size, lower minor allele frequency, or differences in genetic effect sizes.

Nephrol Dial Transplant. 2009 Nov 5;
Ito H, Takeuchi Y, Ishida H, Antoku S, Abe M, Mifune M, Togane M

BACKGROUND: The clinical characteristics of diabetic patients presenting with normoalbuminuria with decreased kidney functions were investigated. METHODS: A cross-sectional study was performed in 1197 patients with Type 2 diabetes mellitus. The estimated glomerular filtration rate (eGFR) was calculated using the formula recommended by the Japanese Society of Nephrology. RESULTS: The groups with normoalbuminuria, microalbuminuria, macroalbuminuria and renal failure consisted of 696 (58%), 229 (19%), 196 (16%) and 76 (6%) subjects, respectively. The frequencies of all diabetic micro- and macroangiopathies increased with progression of diabetic nephropathy stage. However, in the groups with chronic kidney disease (CKD) stage 3+4 (60 > eGFR >/= 15 mL/min/1.73 m(2)), the frequencies of diabetic neuropathy and macroangiopathies were not different among the groups staged by urinary albumin excretion. In the normoalbuminuria group, 223 (32%) cases showed CKD stage 3+4. Diabetic neuropathy and macroangiopathies were significantly more frequent in the groups presenting with normoalbuminuria with CKD stage 3+4 than in those with CKD stage 1+2 (eGFR >/= 60 mL/min/1.73 m(2)). The patients' age, duration of diabetes mellitus and frequency of hypertension were significantly higher in the groups presenting with normoalbuminuria with CKD stage 3+4. After adjustment by age, grade of albuminuria or both, CKD stage 3+4 was an independent risk factor for some diabetic complications. CONCLUSIONS: The combination of urinary albumin excretion and eGFR is useful for earlier detection of kidney and vascular damage in patients with diabetes mellitus. Evaluation of eGFR should be performed for all diabetic patients even if they show normoalbuminuria.

Prim Care diabetes. 2009 Nov 3;
Mohan V, Pranjali PP, Amutha A, Ganesan A, Datta M, Gayathri P

AIMS: To study the prevalence, and clinical profile of autosomal dominant (AD) inherited forms of Type 2 diabetes mellitus (T2DM). METHODS: Detailed pedigree charts were drawn on 510 consecutive T2DM subjects attending a tertiary care diabetes centre in South India. Clinical and biochemical features of T2DM subjects with and without AD inheritance were compared. RESULTS: Overall, 36.1% of T2DM had one parent with diabetes, in 10.6%, both parents had diabetes and 10.2% had features of AD. Age at diagnosis of diabetes was the lowest among AD group compared to other groups (p for trend <0.001). Only 22.6% of T2DM with AD inheritance had age at diagnosis of diabetes below 25 years and in 26.4%, it was diagnosed above 45 years. There were no significant differences in the clinical features, including prevalence of diabetic complications, between T2DM with and without AD inheritance. CONCLUSIONS: In this clinic-based study, 10.2% of T2DM subjects had evidence of AD inheritance. While the AD cases occurred at younger age, older age at diagnosis was not uncommon. Clinical features, including complications, did not differ between the T2DM patients with or without AD.

Am J Cardiol. 2009 Nov 15; 104(10): 1398-401
Ng AC, Delgado V, Bertini M, van der Meer RW, Rijzewijk LJ, Shanks M, Nucifora G, Smit JW, Diamant M, Romijn JA, de Roos A, Leung DY, Lamb HJ, Bax JJ

Regional left ventricular (LV) myocardial functional changes in early diabetic cardiomyopathy have not been well documented. LV multidirectional strain and strain rate analyses by 2-dimensional speckle tracking were used to detect subtle myocardial dysfunction in 47 asymptomatic, male patients (age 57 +/- 6 years) with Type 2 diabetes mellitus. The results were compared to those from 53 male controls matched by age, body mass index, and body surface area. No differences were found in the LV end-diastolic volume index (40.7 +/- 8.9 vs 44.1 +/- 7.8 ml/m(2), p = NS), end-systolic volume index (16.0 +/- 4.8 vs 17.8 +/- 4.3 ml/m(2), p = NS), ejection fraction (61.0 +/- 5.5% vs 59.8 +/- 5.3%, p = NS). The transmitral E/A (0.95 +/- 0.21 vs 1.12 +/- 0.32, p = 0.007) and pulmonary S/D (1.45 +/- 0.28 vs 1.25 +/- 0.27, p = 0.001) ratios were more impaired in the patients with diabetes mellitus. Importantly, the diabetic patients had impaired longitudinal, but preserved circumferential and radial systolic and diastolic, function. diabetes mellitus was an independent predictor for longitudinal strain, systolic strain rate and early diastolic strain rate on multiple linear regression analysis (all p <0.001). In conclusion, the LV longitudinal systolic and diastolic function were impaired, but the circumferential and radial functions were preserved in patients with uncomplicated Type 2 diabetes mellitus.

Clin Chim Acta. 2009 Nov 2;
Iordanidou M, Tavridou A, Petridis I, Arvanitidis KI, Christakidis D, Vargemezis V, Manolopoulos VG

BACKGROUND: The serotonergic system contributes substantially to the regulation of glucose homeostasis and feeding. 5-HTTLPR is a serotonin transporter (5-HTT) gene linked polymorphic region that regulates the transcriptional activity of 5-HTT. Our aim was to investigate the possible association of 5-HTTLPR polymorphism with Type 2 diabetes mellitus and obesity. METHODS: Study population consisted of 252 subjects diagnosed with Type 2 DM and 211 non-diabetic patients, all Caucasians of Greek ethnic origin. Genomic DNA was extracted from peripheral blood and analyzed for 5-HTTLPR polymorphism with a novel PCR protocol. RESULTS: The frequency of SS and SL genoTypes of HTTLPR was significantly higher in the diabetic group (77%) than in the non-diabetic group (61.6%) (P<0.001). The genetic risk of Type 2 DM for subjects carrying at least one S allele was increased compared to non-diabetic subjects (OR=2.08, 95% CI=1.39-3.12). When subjects were divided according to BMI status, the frequency of S allele carriers was similar in obese and non-obese patients. CONCLUSIONS: The S allele of 5-HTTLPR is strongly associated with the presence of Type 2 DM. This association appears to be direct and not dependant on obesity status. Therefore, 5-HTTLPR LL genoType might be protective for development of Type 2 DM.

Pharmacogenomics. 2009 Nov; 10(11): 1781-7
Ragia G, Petridis I, Tavridou A, Christakidis D, Manolopoulos VG

AIMS: Hypoglycemia is a common adverse effect of sulfonylurea oral hypoglycemic agents. Impaired metabolism of sulfonylureas due to gene polymorphisms in the metabolic enzyme CYP2C9 might lead to hypoglycemia. In the present study we explored the association of the CYP2C9 variant alleles CYP2C9*2 and CYP2C9*3 with the incidence of hypoglycemic events in diabetic patients receiving the sulfonylureas glimepiride and gliclazide. MATERIALS & METHODS: A total of 92 Type 2 diabetes mellitus (T2DM) patients receiving sulfonylurea and reporting drug-associated hypoglycemia, and 84 T2DM patients receiving sulfonylurea and having never experienced hypoglycemia were included in the study. A sample of 283 nondiabetic controls that had been genoTyped earlier served as a second control group. CYP2C9*2 and *3 alleles were detected by use of PCR-RFLP analysis. RESULTS: Frequencies of CYP2C9*1/*3 genoType and CYP2C9*3 allele were significantly lower in T2DM patients than nondiabetic controls (p = 0.003 and p = 0.017, respectively). A total of 11 out of 92 subjects (12%) experiencing hypoglycemia carried the CYP2C9*3 allele, as opposed to only 1 out of 84 subjects (1.2%) free of sulfonylurea-induced hypoglycemia. In a model adjusted for age, BMI, mean daily dose of sulfonylurea, duration of T2DM and renal function, CYP2C9*1/*3 genoType increased the hypoglycemia risk in response to sulfonylurea (odds ratio: 1.687; p = 0.011). However, no differences in CYP2C9*2 allele frequency between the two groups were found. DISCUSSION & CONCLUSION: The presence of CYP2C9*3 appears to be protective for development of T2DM. Furthermore, in T2DM patients, CYP2C9*3 increases the risk of hypoglycemia when they are treated with sulfonylureas, possibly due to impaired metabolism of these drugs. CYP2C9 genotyping might thus be a useful tool for predicting adverse effects caused by sulfonylureas and help clinicians in safer prescribing of oral hypoglycemic agents. The potential T2DM protective effect of CYP2C9*3 allele requires further investigation.

J Med Assoc Thai. 2009 Sep; 92 Suppl5: S45-8
Pooruk P, Kittimanon N, Janthorn P, Bunyaratavej N

A comparison study of bone turnover between the diabetic Type 2 and the non-diabetic patients was conducted by using the age matching technique. The bone markers of the diabetic Type 2 patients showed CTx = 0.48 ng/ml, NMID osteocalcin = 24.62 ng/ml and PINP = 38.61 ng/ml. All study parameters of bone markers were higher than the control group. Thus, the diabetic cases with high bone turnover assuredly predisposed to osteoporosis. The bone change consistently monitored particularly in the diabetic cases could prevent osteoporosis. The high calcium diets and regular exercises were recommended for the diabetic patients.

Am J Cardiol. 2008 Dec 22; 102(12A): 41L-47L
Jones PH

Even with optimal statin therapy, many patients with Type 2 diabetes mellitus or metabolic syndrome fail to achieve all lipid targets and remain at high risk of cardiovascular events. Add-on lipid-modifying therapy that is effective in improving the triglyceride and high-density lipoprotein (HDL) cholesterol abnormalities characteristic of these conditions is a recommended approach to reduce this risk. Fibrates or niacin is a logical option, supported by clinical studies showing improved lipid control in combination with a statin. Of the fibrates, fenofibrate may offer microvascular benefits in Type 2 diabetes--as demonstrated by the diabetes Atherosclerosis Intervention Study (DAIS) and the Fenofibrate Intervention and Event Lowering in diabetes (FIELD) study--as well as a low risk of myopathy when combined with statins compared with gemfibrozil. Although there is good evidence that both agents favorably affect clinical outcome, we need to evaluate their impact against a baseline of statin therapy. We await data from ongoing large-scale studies to evaluate the efficacy and safety of these combinations and to determine the most appropriate option for reducing residual cardiovascular risk in this important patient population.

Am J Cardiol. 2008 Dec 22; 102(12A): 34L-40L
Sacks FM

The Fenofibrate Intervention and Event Lowering in diabetes (FIELD) study provides an extensive evidence base for the efficacy and tolerability of fenofibrate treatment in patients with Type 2 diabetes mellitus, predominantly in a primary prevention setting. The FIELD study did not show a significant effect with fenofibrate on the primary end point, coronary artery disease death or nonfatal myocardial infarction (p = 0.16). Treatment with fenofibrate did reduce all cardiovascular disease (CVD) events, the secondary end point (by 11%, p = 0.035). The primary end point was reduced by the same percentage. The modest percent reduction in the primary and secondary end points is probably a result of a number of study confounders, notably an excess of statin drop-in therapy and disproportionate treatment with other drugs for CVD prevention in the placebo arm. Estimates of relative risk reduction used by the FIELD investigators to equalize the use of statins in the fenofibrate and placebo groups suggest a true benefit of treatment on reduction of CVD events of 17%-21%. There was no excess of elevated serum liver enzymes and no cases of rhabdomyolysis in patients receiving both fenofibrate and a statin. Prevention of microvascular disease, specifically, reduction in the rate of laser treatment for retinopathy (by 30%, p = 0.0003), progression of albuminuria (p = 0.002), and nontraumatic amputations (by 38%, p = 0.011), may well be the most innovative finding of the FIELD study, especially in view of the current lack of effective preventative treatments for diabetic retinopathy and the need for additional treatments that slow the progression of diabetic nephropathy. These findings also give impetus to investigate mechanisms by which fenofibrate and peroxisome proliferator-activated receptor-alpha activation may protect the endothelium of small blood vessels in patients with Type 2 diabetes.

Am J Cardiol. 2008 Dec 22; 102(12A): 28L-33L
Steiner G

Clinical guidelines highlight the importance of managing atherogenic mixed dyslipidemia to reduce the risk of premature cardiovascular disease in Type 2 diabetes mellitus and metabolic syndrome. The lipid-modifying activity of fenofibrate, as demonstrated in clinical studies, indicates its effectiveness in treating dyslipidemia characteristic of these conditions. Fenofibrate also has a favorable impact on a number of nonlipid residual risk factors associated with Type 2 diabetes and metabolic syndrome, mediated by peroxisome proliferator-activated receptor-alpha. In patients with Type 2 diabetes, fenofibrate is effective in reducing the progression of coronary artery disease, as demonstrated by the diabetes Atherosclerosis Intervention Study (DAIS). In the Fenofibrate Intervention and Event Lowering in diabetes (FIELD) study, the primary end point (major coronary events) was not significantly reduced by fenofibrate treatment. However, other findings from this study suggest that fenofibrate reduces cardiovascular risk. Both DAIS and the FIELD study also indicate that fenofibrate may offer additional vascular benefits, specifically affecting the progression of diabetes-related microvascular disease.

Am J Cardiol. 2008 Dec 22; 102(12A): 19L-27L
Davidson M

Current treatment guidelines recommend lowering elevated low-density lipoprotein (LDL) cholesterol levels with a statin as the primary lipid-modifying intervention to reduce cardiovascular risk in patients with Type 2 diabetes mellitus or metabolic syndrome. However, even with high-dose statin therapy or the combination of statin plus ezetimibe, many patients remain at substantial risk of a cardiovascular event. Increasingly, there is recognition of the importance of treating all components of the atherogenic dyslipidemic profile associated with both conditions, specifically low high-density lipoprotein cholesterol and elevated triglyceride levels, in addition to lowering LDL cholesterol. Both niacin (nicotinic acid) and fibrates are recommended as options for combination with a statin in this setting. Data from ongoing prospective outcomes studies are needed to evaluate the efficacy and safety of these combinations.

Am J Cardiol. 2008 Dec 22; 102(12A): 14L-18L
Stone NJ

Patients with Type 2 diabetes mellitus or metabolic syndrome typically exhibit atherogenic mixed dyslipidemia characterized by low levels of high-density lipoprotein cholesterol, elevated triglycerides, and an increase in small, dense low-density lipoprotein particles. Treatment guidelines recognize lifestyle intervention as a first step in the management of dyslipidemia in these patients. The aim of this article is to review evidence to support this approach. To achieve all recommended lipid goals in clinical practice, lifestyle intervention is likely to be adjunctive to pharmacotherapy.

Am J Cardiol. 2008 Dec 22; 102(12A): 5L-9L
Cannon CP

Metabolic syndrome and Type 2 diabetes mellitus are individually associated with increased cardiovascular risk; furthermore, the combination of metabolic syndrome with diabetes accentuates this risk. An atherogenic dyslipidemia characterized by elevated triglycerides, low high-density lipoprotein cholesterol, or both conditions is a key modifiable risk factor associated with both conditions. As the development of this atherogenic mixed dyslipidemia precedes the onset of overt glycemia and the clinical diagnosis of diabetes, early effective intervention is recommended to reduce the risk of premature cardiovascular disease morbidity and mortality.