EOP - Metabolic Syndrome: Nature, Therapeutic Solutions And Options

Onat A.

Source

Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey. alt_onat@yahoo.com.tr

Abstract

INTRODUCTION: Metabolic syndrome (MetS) defines the clustering in an individual of multiple metabolic abnormalities, based on central obesity and insulin resistance. In addition to its five components, prothrombotic and proinflammatory states are essential features. The significance of MetS lies in its close association with the risk of type 2 diabetes and cardiovascular disease (CVD). This field being an evolving one necessitated the current review. AREAS COVERED: The areas covered in this review include the so far unproven concept that enhanced low-grade inflammation often leads to dysfunction of the anti-inflammatory and atheroprotective properties of apolipoprotein A-I (apoA-I) and HDL particles, which further increases the risk of diabetes and CVD. It was emphasized that lifestyle modification is essential in the prevention and management of MetS, which includes maintenance of optimal weight by caloric restriction, adherence to a diet that minimizes postprandial glucose and triglyceride fluctuations, restricting alcohol consumption, smoking cessation and engaging in regular exercise. Drug therapy should target the dyslipoproteinemia and the often associated hypertension or dysglycemia.Statins are the drugs of first choice, to be initiated in patients with MetS at high 10-year cardiovascular risk. Such treatment is inadequate if fasting serum triglycerides remain at > 150 mg/dl, when niacin should be combined. Fibrates, omega 3 fatty acids, metformin, angiotensin-converting enzyme inhibitors and pioglitazone are additional options in drug therapy. EXPERT OPINION: Research on MetS in subpopulations prone to impaired glucose tolerance and insulin resistance has indicated that proinflammatory state and oxidative stress are often prominently involved in MetS, to the extent that evidence of impaired function of HDL and apo A-I particles is discernible by biological evidence of functional defectiveness via outcomes studies and/or correlations with inflammatory and anti-inflammatory biomarkers. A sex difference has been clear in this development.

PMID:

 

21756201

 

[PubMed - indexed for MEDLINE]

DiaM – GLA in Prevention and Treatment of Diabetic Neruopathy

Jamal GA.

Source

Glasgow University Department of Neurology, Institute of Neurological Sciences, Scotland.

Abstract

A substantial disturbance of the metabolism of the n-6 essential fatty acids (EFAs) exists in both human and experimental diabetes mellitus. The process of conversion of dietary linoleic acid to gammalinolenic, dihomogammalinolenic and arachidonic acids, and other polyunsaturates is inadequate in diabetic patients. Disturbances of these EFAs and the 1- and 2-series prostaglandins derived from them cause a variety of microvascular, haemorheological, and other abnormalities leading to reduced blood flow and neural hypoxia. This will in turn produce an escalating cycle of further hypoxia through the generation of oxygen-free radicals and aggravation of neural capillary endothelial damage. Endoneurial hypoxia impairs axonal transport, produces demyelination, and reduces neural ATP-ase activity. Furthermore, depletion of polyunsaturated fatty acids derived from n-6 pathway may lead to abnormalities of myelin turnover, membrane-bound proteins (such as enzymes and receptors) and other axonal structural abnormalities. The disorders postulated here may synergistically interact with the metabolic changes described in both the glycosylation and the myoinositol hypotheses and may have important implications in the approach to treat diabetic neuropathy.

PMID:

 

8200197

 

[PubMed - indexed for MEDLINE]

JN – PUFAs Improve Insulin Action and Glucose Metabolism

Luo J, Rizkalla SW, Boillot J, Alamowitch C, Chaib H, Bruzzo F, Desplanque N, Dalix AM, Durand G, Slama G.

Source

Department of Diabetes, INSERM U341, University of Pierre et Marie Curie, Hôtel-Dieu Hospital, Paris, France.

Abstract

To study the effects of dietary fish oil on insulin-stimulated glucose metabolism in adipocytes of insulin-resistant rats (rats fed 50% sucrose and 30% fat), eighteen 5-wk-old Sprague-Dawley rats were fed, for 6 wk, a diet containing 30% fat as either fish oil (FO) or a mixture of vegetable and animal oils [control oils (CO)]. A third reference group was fed a standard diet (62% corn starch and 13% fat). At the end of the 6-wk period, the two experimental groups had comparable plasma glucose concentrations that were higher than that found in the reference group. FO feeding corrected the hyperinsulinemia of the experimental rats (P < 0.05) to reach values in the reference group. Plasma triacylglycerol (P < 0.01) and cholesterol (P < 0.001) concentrations were also lower in rats fed FO than in those fed CO. The body weights of FO-fed rats were similar to that of CO-fed rats, but epididymal adipose tissue weight was lower (P < 0.01). Adipocytes of FO-fed rats, compared with those of CO-fed rats, had high insulin-stimulated glucose transport (P < 0.05), oxidation (P < 0.001) and incorporation into total lipids (P < 0.05). The incorporation of (n-3) polyunsaturated fatty acids in adipocyte membrane phospholipids was higher in FO-fed rats than in those fed CO (P < 0.0001). Insulin action was positively correlated with the fatty acid unsaturation index in membrane phospholipids. Thus dietary fish oil has beneficial effects on insulinemia, plasma lipids and insulin-stimulated glucose metabolism in insulin-resistant slightly diabetic rats.

PMID:

 

8759367

 

[PubMed - indexed for MEDLINE] 

Diabetes – GLA For Management Of Impaired Nerve Function In Diabetes

Horrobin DF.

Source

Scotia Research Institute, Kentville, Nova Scotia, Canada.

Abstract

Impaired conversion of linoleic acid to gamma-linolenic acid (GLA) has been demonstrated in animal diabetes and inferred from blood fatty acid profiles in human diabetes. This impairment could theoretically lead to defective nerve function because metabolites of GLA are known to be important in nerve membrane structure, nerve blood flow, and nerve conduction. Administration of GLA corrects the impaired nerve function in animal models of diabetes. Two multicenter, randomized, placebo-controlled trials in humans with diabetic neuropathy have shown significant benefits of GLA as compared with placebo in neurophysiological parameters, thermal thresholds, and clinical sensory evaluations. Further work is needed to define the place of this therapeutic approach and its interactions with other treatment modalities.

PMID:

 

9285506

 

[PubMed - indexed for MEDLINE]

DC - Fish Oil And Glycemic Control In Diabetes

Friedberg CE, Janssen MJ, Heine RJ, Grobbee DE.

Source

Department of Internal Medicine, Ziekenhuis der Vrije Universiteit, Amsterdam, The Netherlands. c.friedberg.buro@vu.med.nl

Abstract

OBJECTIVE:

Hypertriglyceridemia is associated with cardiovascular disease in diabetes. Fibrates effectively lower, but do not always normalize, serum triglyceride levels. Fish oil supplements may then be added to lower serum triglyceride levels. Doubt remains whether the net effect of fish oil intake on glycemic control is beneficial in diabetes. We therefore performed a meta-analysis from published clinical trials.

RESEARCH DESIGN AND METHODS:

Data sources were Medline (Cologne, Germany), Excerpta Medica, Current Contents, review articles, and published reference lists. Publications of 26 trials were selected, and all trials included more than five diabetes (IDDM and NIDDM) patients and addressed the effects of fish oil (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) on serum lipids and glucose tolerance. We (C.E.F., M.J.F.M.J.) extracted data independently based on predetermined criteria. Studies were classified according to design.

RESULTS:

All studies combined showed a decrease in mean triglyceride concentrations in association with fish oil: -0.60 mmol/l (95% CI, -0.84 to -0.33, P < 0.01) and a slight but significant increase in serum LDL cholesterol: 0.18 mmol/l (95% CI, 0.04-0.32, P = 0.01), with both findings most prominent in NIDDM. No significant changes in HbA1c percentages occurred in diabetic subjects treated with fish oil. Fasting blood glucose levels were increased with borderline significance in NIDDM subjects (0.43 mmol/l [95% CI, 0.00-0.87], P = 0.06) and were significantly lower in IDDM subjects (-1.86 mmol/l [95% CI, -3.1 to -0.61], P < 0.05). Significant dose-response effects of EPA (g/day) on HbA1c and triglycerides and of DHA (g/day) on fasting blood glucose levels, HbA1c, and triglycerides were demonstrated only in NIDDM subjects.

CONCLUSIONS:

The use of fish oil has no adverse affects on HbA1c in diabetic subjects and lowers triglyceride levels effectively by almost 30%. However, this may be accompanied by a slight increase in LDL cholesterol concentration. Fish oil may be useful in treating dyslipidemia in diabetes.

PMID:

 

9571330

 

[PubMed - indexed for MEDLINE]

AJCN - Omega-3s With Type-2 Diabetes And High Blood Pressure

Woodman RJ, Mori TA, Burke V, Puddey IB, Watts GF, Beilin LJ.

Source

Department of Medicine, The University of Western Australia, Perth, Australia. rwoodman@cyllene.uwa.edu.au

Abstract

BACKGROUND:

n-3 Fatty acids lower blood pressure, improve lipids, and benefit other cardiovascular disease risk factors. Effects on glycemia in patients with type 2 diabetes are uncertain.

OBJECTIVE:

We determined whether purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have differential effects on glycemic control, including insulin sensitivity and stimulated insulin secretion; 24-h ambulatory blood pressure; and serum lipids in type 2 diabetic patients with treated hypertension.

DESIGN:

In a double-blind, placebo-controlled trial of parallel design, 59 subjects were randomly assigned to consume 4 g EPA, DHA, or olive oil/d for 6 wk while continuing to consume their usual diet.

RESULTS:

Thirty-nine men and 12 postmenopausal women with a mean (+/- SE) age of 61.2 +/- 1.2 y completed the study. In comparison with the change from baseline in fasting glucose in the olive oil group, fasting glucose in the EPA and DHA groups increased 1.40 +/- 0.29 mmol/L (P = 0.002) and 0.98 +/- 0.29 mmol/L (P = 0.002), respectively. Neither EPA nor DHA had significant effects on glycated hemoglobin, fasting insulin or C-peptide, insulin sensitivity or secretion, or blood pressure. Serum triacylglycerols in the EPA and DHA groups decreased 19% (P = 0.022) and 15% (P = 0.022), respectively. There were no significant changes in serum total, LDL, or HDL cholesterol, although HDL(2) cholesterol in the EPA and DHA groups increased 16% (P = 0.026) and 12% (P = 0.05), respectively. HDL(3) cholesterol decreased 11% (P = 0.026) with EPA supplementation.

CONCLUSIONS:

EPA and DHA had similar benefits on lipids but adverse effects on short-term glycemic control in hypertensive diabetic patients. The overall implications for cardiovascular disease require long-term evaluation.

PMID:

 

12399272

 

[PubMed - indexed for MEDLINE]

Circ - Fish and Omega-3 FA Reduce Risk of Heart Disease in Diabetic Women

1. Frank B. Hu, MD; 
2. Eunyoung Cho, ScD; 
3. Kathryn M. Rexrode, MD;
4. Christine M. Albert, MD; 
5. JoAnn E. Manson, MD

Author Affiliations

1. From the Departments of Nutrition (F.B.H.) and Epidemiology (F.B.H., J.E.M.), Harvard School of Public Health, the Channing Laboratory (F.B.H., E.C., J.E.M.), the Division of Preventive Medicine (J.E.M., K.M.R., C.M.A.), Department of Medicine, Brigham and Women’s Hospital, and the Cardiology Division (C.M.A.), Massachusetts General Hospital, Harvard Medical School, Boston, Mass.

1. Correspondence to Dr Frank Hu, Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115. E-mailfrank.hu@channing.harvard.edu

 

Next Section

Abstract

Background— Although several prospective cohort studies have found an inverse association between fish consumption and risk of coronary heart disease (CHD) or sudden cardiac death in the general population, limited data are available among diabetic patients.

Methods and Results— We examined prospectively the association between intake of fish and ω-3 fatty acids and risk of CHD and total mortality among 5103 female nurses with diagnosed type 2 diabetes but free of cardiovascular disease or cancer at baseline. Between 1980 and 1996 (45 845 person-years of follow-up), we documented 362 incident cases of CHD (141 CHD deaths and 221 nonfatal myocardial infarctions) and 468 deaths from all causes. Compared with women who seldom consumed fish (<1 serving/mo), the relative risks (RRs) (95% CI) of CHD adjusted for age, smoking, and other established coronary risk factors were 0.70 (0.48 to 1.03) for fish consumption 1 to 3 times per month, 0.60 (0.42 to 0.85) for once per week, 0.64 (0.42 to 0.99) for 2 to 4 times per week, and 0.36 (0.20 to 0.66) for 5 or more times per week (P for trend=0.002). Higher consumption of fish was also associated with a significantly lower total mortality (multivariate RR=0.48 [0.29 to 0.80] for ≥5 times per week [P for trend=0.005]). Higher consumption of long-chain ω-3 fatty acids was associated with a trend toward lower incidence of CHD (RR=0.69 [95% CI 0.47 to 1.03], P for trend=0.10) and total mortality (RR=0.63 [95% CI, 0.45 to 0.88], P for trend=0.02).

Conclusions— A higher consumption of fish and long-chain ω-3 fatty acids was associated with a lower CHD incidence and total mortality among diabetic women.