Cholesterol How To Decrease

Lower Your Cholesterol in 30 Days

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Natural Cholesterol Guide Summary


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Analysis Comparison Drug therapy versus placebo for Sibutramine FTAB fixed model random model rho Outcome HDL

Comparison 25 Drug therapy versus placebo for Sibutramine (FT+AB l-l3, fixed model l4-26, random model. rho 0.75) Outcome l2 HDL cholesterol Comparison 25 Drug therapy versus placebo for Sibutramine (FT+AB 1-13, fixed model l4-26, random model. rho 0.75) Outcome 13 Triglycerides

Lifestyle Treatments for High Cholesterol and Other Blood Fats

Several types of fats circulate in the blood and are commonly measured by doctors total cholesterol, LDL ( bad ) cholesterol, HDL ( good ) cholesterol, and triglycerides. In people with diabetes, total cholesterol and LDL cholesterol may be high. However, the most characteristic lipid changes in diabetes are increased triglyceride levels (triglycerides are another circulating fat in the blood) and a decreased HDL cholesterol level. Of the specific types of fat that circulate in the blood, both high LDL and low HDL cholesterol appear to be the most important with regard to future heart disease. Although LDL levels in people with diabetes tend to be in a similar range as in people without diabetes, the LDL particles are small and more likely to cause vascular disease. This combination of low HDL levels and small LDL particle size contributes to the increased risk of heart disease in the setting of diabetes. The availability of powerful new cholesterol-lowering drugs, called statins,...

Analysis Comparison Drug therapy versus placebo for Fluoxetine FT fixed model random mode wks rho Outcome HDL

Comparison 03 Drug therapy versus placebo for Fluoxetine (FT 1-7, fixed model 8-l4, random mode 8-l6 wks. rho 0.75) Outcome 06 HDL cholesterol Comparison 03 Drug therapy versus placebo for Fluoxetine (FT 1-7, fixed model 8-l4, random mode 8-l6 wks. rho 0.75) Outcome 07 Triglycerides

HMG CoA Reductase Inhibitors

Large clinical trials have determined that hydroxymethylglutaryl-coenzyme A reductase inhibitors ( statins ) significantly reduce cardiovascular morbidity and mortality. Furthermore, lipid-lowering therapy has been shown to improve endothelial function in several studies (204,205). Attempts to ameliorate the impaired endothelium-dependent vascular relaxation that occurs in diabetic patients with dyslipidemia are few and the results mixed. Impaired endothelium-dependent vasodilation in patients with type 2 DM with dyslipidemia has been reported to improve with fibrate therapy (206) (which lowers the serum triglyceride level) but not with simvastatin (206,207). 66. Clarkson P, et al. Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels. J Am Coll Cardiol 1996 28(3) 573-579. 77. Gilligan DM, et al. Selective loss of microvascular endothelial function in human hypercholesterolemia. Circulation...

Correction of dyslipidaemia

The evidence for cholesterol reduction in diabetes comes predominantly from subgroup analyses of clinical trials that included people with diabetes. In those with established cardiovascular disease, gemfibrozil and statins have shown significant reduction in coronary heart disease and cardiovascular events (Frick etal., 1987 Pyorala etal., 1997 Goldberg etal., 1998 Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group, 1998 Rubins etal., 1999 Heart Protection Study Group, 2002). In primary prevention, benefits have been shown with gemfibrozil (Frick etal., 1987 Koskinen etal., 1992) and a statin in a hypertensive population (Sever etal., 2003). In the only trial of primary prevention exclusively in diabetes, there was reduction in acute coronary events and strokes with atorvastatin (Colhoun etal., 2004). The primary target is lowering LDL-cholesterol and recent evidence supports rigorous goals (Heart Protection Study Group, 2002 Sever etal., 2003 Colhoun...

Lipid goals in patients who have diabetes

Diabetes is a CHD-risk equivalent, as defined by the ATPIII recommendations. Based on the evidence from the LDL-lowering clinical trials that were summarized above, most patients who have diabetes should have an LDL goal of less than 100 mg dL (Table 3). If LDL is grater than 130 mg dL, treatment with LDL-lowering drugs should be initiated simultaneously with therapeutic lifestyle changes (TLC) to achieve the LDL goal 1 . The American Diabetes Association (ADA) has the same recommendations for LDL goal 42 . In addition, the ADA recommends a triglyceride goal of less than 150 mg dL and an HDL cholesterol goal of greater than 40 mg dL in men and greater than 50 mg dL in women (see Table 3). According to ATPIII, however, when triglyceride levels are elevated (200-499 mg dL) after achieving LDL goal, non-HDL cholesterol should be the secondary target of therapy. No HDL goal is specified in ATPIII because of the lack of sufficient evidence. It is recommended that if HDL remains low after...

Effects of Antidiabetic Drugs on Risk Factor Pathways

Of interest, there is now abundant evidence that insulin-sensitising therapies appear to offer benefits beyond just glucose lowering. Metformin, for example, has positive effects on FFAs, HDL-cholesterol, PAI-1 and vascular function, and may also lower markers of inflammation (Grant, 1995 Grant, 2003 Haffner etal., 2005). Glitazones also benefit each of the above parameters, although their actions on HDL-cholesterol and inflammatory parameters are more pronounced and in addition they tend to raise adiponectin and lower the proportion of small, dense LDL particles (Haffner etal., 2002). By contrast, sulphonylureas have far less and often negligible effects on such markers. Such observations emphasise once again the multiple linkages of insulin resistance on other risk factor pathways. They also concur with the greater benefits of metformin (and to a lesser extent glitazones) on CVD risk (Johnson etal., 2005 Evans etal.,

Lipoprotein abnormalities associated with diabetes

In view of the compositional changes in lipo-proteins, the LDL cholesterol that is determined in routine assays tends to underestimate the LDL particle number, particularly in patients who have hypertriglyceridemia 9,10 . Therefore, it was proposed that the direct measurement of apolipopro-tein B (apoB) may provide a better estimate of risk in such patients 11 however, the assays for apoB are not well-standardized and are not widely available. An alternative that was proposed by ATPIII is the calculation of non-HDL cholesterol which estimates the cholesterol content in all atherogenic particles (VLDL, IDL, remnants, LDL, and lipoprotein LP(a) ). Non-HDL cholesterol was a good predictor for CVD in diabetes according to some population studies, such as the Strong Heart Study 12 and the Hoorn Study 13 . More evidence is needed from intervention trials before drawing definitive conclusions regarding its impact on lipid management. Similarly, whether the determination of postprandial...

Dyslipidaemic Lipid Profile

Patients with Type 2 diabetes have an abnormal lipid profile with high levels of LDL-cholesterol and triglycerides (TG) and a low level of HDL-cholesterol. Data from the Multiple Risk Factor Intervention Trial (MRFIT) (19) suggest that although levels of total cholesterol and LDL-cholesterol do not differ significantly between patients with and without diabetes, those with diabetes have higher concentrations of atherogenic small dense LDL-cholesterol particles.

Evaluation Of The Elderly Patient With Diabetes Igt Or

Fasting serum total cholesterol, HDL cholesterol and triglycerides Estimation of LDL cholesterol Serum uric acid Thyroid function tests smoking, hypertension, and lack of exercise. Elevated serum triglycerides and reduced HDL cholesterol are commonly found in patients with Type 2 diabetes. Clinical evidence of existing macrovascular disease should be sought i.e. ischaemic heart disease, cere-brovascular disease and peripheral vascular disease. Patients with diabetes should have a baseline glyco-sylated haemoglobin or fructosamine measured to give an integrated measure of recent glycaemic control and for monitoring progress.

What are the longterm effects of exercise in the body

Which demonstrates the great importance of regularly performed, repeated muscular activity for the achievement of beneficial effects on the body. Regular physical activity is also associated with beneficial effects on the lipid profile (increase in HDL-cholesterol, decrease in triglycerides and small decrease in LDL-cholesterol), decrease in arterial hypertension and contribution - in combination with proper nutrition -towards a decrease of body weight and mainly towards the maintenance of weight loss and free-fat-mass in obese persons.

Potential Mechanisms for Vascular Function Changes in Pregnancy

Investigations into the potential mechanisms for the vascular function changes during pregnancy are very few. Clearly, early circulating hormonal changes and a rise in HDL-cholesterol in the first half of pregnancy may beneficially influence vascular function at this stage. Beyond this, a recent

How is diabetic dyslipidaemia defined and what is its cause

The lipid profile in Type 1 DM depends, for the most part, on glycaemic control. Poor glycaemic control is associated with hypertri-glyceridaemia and, in certain cases, with increased LDL-cholesterol and reduced HDL-cholesterol concentrations. Hypertriglyceridaemia in poorly controlled Type 1 DM is due to two consequences of insulin shortage to increased VLDL production from the liver and to decreased clearance of these lipoproteins (as well as of chylomicrons) from the circulation, because of decreased activity of the LPL (the action of which is under the influence of insulin). The serum triglycerides levels can be extremely high ( 1600 mg dl 18.08 mmol L ), resulting in the likely appearance of skin xanthomata (see Chapter 18, Figure 18.5) from triglyceride deposition. This also increases the risk of acute pancreatitis. Improvement of DM control with the administration of insulin results in normalization of blood lipids. The typical dyslipidaemia in Type 2 DM includes a slight...

Lipid And Lipoprotein Metabolism In Insulin Resistant States

Insulin resistance is central to the dyslipidemia of type 2 diabetes (21). A simplified overview of the mechanisms of the dyslipidemia of diabetes is shown in Fig. 1. In the presence of insulin resistance there is an increased flux of free fatty acids from adipose tissue to the liver, as a result of decreased inhibition of the hormone-sensitive lipase. Fatty acids stimulate increased hepatic production and secretion of very low-density lipoprotein (VLDL), which is also increased by insulin resistance and hyperinsulinemia. Increased hepatic output of VLDL continues in the postprandial state and competes with exogenously-derived triglyceride carried in chylomicrons for the enzyme lipoprotein lipase. As a result, there is accumulation of triglyceride-rich lipoproteins and prolonged postprandial lipemia. The lipemia stimulates increased lipid transfer via cholesterol ester transfer protein (CETP) exchanging triglyceride for cholesterol ester between triglyceride-rich lipoproteins and...

Alphaglucosidase inhibitors

Chiasson and colleagues in Montreal conducted a small pilot study (n 18) of acarbose, an alpha-glucosidase inhibitor215, in people with IGT222. Acarbose delays intestinal absorption of glucose and lowers peak glucose and insulin levels after eating. After four months, subjects on acarbose showed lower post-meal and 12 h glucose and insulin profiles, with no change among those on placebo. During an insulin suppression test, post-treatment steady-state glucose levels were significantly lower at the same level of insulin, suggesting improved insulin sensitivity. No changes in BMI, HDL cholesterol or triglycerides, fasting glucose or insulin, HbA1c or BP were seen in either group. No comments were made concerning the side effects of acarbose, which is known to include increased flatulence and diarrhea215. Results in this short-term study suggest the utility of acarbose to improve glucose tolerance and insulin sensitivity, and led the authors to begin the STOP-NIDDM multicenter trial223 in...

Cardiovascular Abnormalities

Manderson et al. examined cardiovascular risk factors and markers of endothelial dysfunction (ICAM-1, VCAM-1, E-Selectin) among offspring of mothers with type 1 diabetes compared with offspring of nondiabetic pregnancies (35). The children were 5-11 years of age at the time of assessment, and pregnancy records were reviewed retrospectively. The offspring of mothers with type 1 diabetes did not differ significantly from the offspring of nondiabetic mothers on either socioeconomic or anthropometric parameters at the time of their examination. Despite similar levels of adiposity, children exposed to maternal type 1 diabetes in utero had increased insulin-like growth factor-1 (IGF-1), plasminogen activator inhibitor-1 (PAI-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-Selectin, as well as increased total cholesterol, LDL-cholesterol, and cholesterol HDL-cholesterol ratio. The results of this study suggest that exposure to maternal type 1...

What are the recommendations today for the prevention of DM

For Type 2 DM, the existing data show that it is possible to prevent or at least delay its development in high-risk individuals. Consequently, it is recommended to try and find individuals of high-risk and intervene to reduce this risk. As mentioned earlier, the best correlation of the risk for DM development has been found for individuals with glucose intolerance (IFG or IGT) and consequently it is recommended to find such individuals in the general population by measuring fasting plasma glucose and performing an oral glucose tolerance test. These tests should be focused on individuals with increased DM risk, such as those who are 45 years of age, especially with obesity (BMI 25 kg m2) or even in younger individuals with BMI 25 kg m2 who have additional risk factors as follows first degree relative with Type 2 DM sedentary lifestyle history of gestational DM or birth of a child with weight 4 kg (8.8 lb) presence of hypertension or dyslipidaemia (HDL-cholesterol 35 mg dl 0.91 mmol L...

Multifactorial Intervention in Type Diabetes mellitus

HbA1c (normal range 5.2-6.4 ) Fasting total cholesterol Fasting LDL cholesterol Fasting HDL cholesterol Fasting triglycerides Urinary albumin excretion rate The term dyslipidaemia covers many patterns of lipid changes from the normal values. The most common pattern in type 2 diabetic patients is elevated serum triglyceride levels and decreased serum HDL cholesterol levels. Evidence for a positive treatment effect of dyslipidaemia in type 2 diabetes mellitus comes from post-hoc analyses of diabetic patients participating in larger secondary intervention studies comprising patients with known cardiovascular disease. Since the risk of a first myocardial infarction in patients with type 2 diabetes is the same as the risk for a re-infarction in a nondiabetic subject, it seems reasonable to extrapolate from the overall results from these studies. The Cholesterol and Recurrent Events (CARE) trial was also a secondary intervention study including 4,159 patients with a fasting...

Biguanides including combinations

The metformin group showed small (-2 kg) but significant weight loss, less rise in fasting glucose, and marginally greater fall in fasting insulin, without changes in 2 h glucose or insulin. Lower LDL cholesterol, but no change in BP, triglycerides or HDL cholesterol were found. Of a number of hemostatic factors explored, the metformin group showed decreases in tissue plasminogen activator (tPA) antigen, and vonWillebrand factor209, but no change in plasminogen activator inhibitor-1 (PAI-1) activity or antigen not accounted for by weight loss. Five in the placebo group developed diabetes, versus none in the met-formin group (exact p 0.06, post-hoc analysis). The results are difficult to interpret since there was a 28 and 30 drop-out rate in the two groups at one year. While subjects who dropped out were similar to those remaining in the trial, unexplained bias could have accounted for the results. The investigators undertook a confirmatory study (BIGPRO-1.2) among 168 men who had...

Lipid lowering see also Chapter

The Heart Protection Study (HPS) included 20 536 patients aged 40 to 80 years at high risk of coronary disease but who did not fulfil existing criteria for cholesterol-lowering therapy in 1994. They included many subjects with diabetes. Preliminary results show that after five years of simvastatin treatment (40 mg daily) 2831 patients had died 1328 out of 10 269 (12.9 per cent) on simvastatin vs. 1503 out of 10 267 (14.6 per cent) on placebo (2p

Useful reportskey references

London King s Fund BDA Medical Research Council British Heart Foundation (2003) Heart Protection Study of cholesterol-lowering with simvastatin in 5963 individuals with diabetes a randomised placebo-controlled trial. Heart Protection Study Collaborative Group. Lancet 361 2005-16 Pierce M,Agarwal G, Ridout D (2000) A survey of diabetes care in general practice

Comments on figure

For equivalent amounts of alcohol, the Guinness beer raised my BG level, but the wine (Merlot) and spirits (V odka) had small effects. Since the beer includes carbohydrates, it is presumed that these simply overwhelmed any glucose-lowering effects of the alcohol. In the test with Merlot, some BG reduction was observed, but it is too small to define precisely. Dr. Bernstein notes that alcohol can indirectly lower BG of a type 1 diabetic if consumed at the time of a meal because it impairs the ability of the liver to convert protein to glucose. Fortunately a precise understanding of the operating mechanism is not essential to apply the response test results, and on the basis that red wine is also believed to raise high-density lipoprotein (HDL) cholesterol (the good cholesterol) I added it to my diet and regularly have a 4-oz glass with my dinner. Whether fortuitous or not my HDL level increased from 39 mg dL to 60 mg dL during the 12-month testing period.

Peroxisome Proliferator Activated Receptora Key Regulator of Fatty Acid Oxidation

PPAR-a is expressed in heart, liver, kidney, and skeletal muscle in which it plays a central role in the regulation of lipid, and especially fatty acid, metabolism (16). PPAR-a target genes participate in the conversion of fatty acids to acyl-coenzyme A derivatives, peroxisome P-oxidation, and apolipoprotein expression (A1, AII, and CIII) (10,17). Reminiscent of the story of PPAR-y, fibrates in clinical use for lowering triglycerides and raising high-density lipoprotein (HDL), namely gemfibrozil (Lopid) and fenofibrate (TriCor), were found to be PPAR-a agonists (18). Many insights into PPAR-a have come from the study of PPAR-a-deficient mice (19). For example, these mice lack

What are the lipids and what is their physiologic function in the body

The lipids constitute a heterogeneous group of substances, their main characteristic being that they are insoluble in water. They are split into two types the simple lipids (cholesterol, fatty acids) and the complex ones (triglycerides glycerin with three fatty acid molecules , cholesterol esters cholesterol with fatty acids , phospholipids glycerin with fatty acids and phosphorus and sphingolipids ceramides, sphingomyelins ). Depending on the number of double bonds that is contained in the molecules of their fatty acids, the lipids are distinguished by being saturated, mono-unsaturated or poly-unsaturated (with none, one or more double bonds, respectively). The poly-unsaturated fatty acids with their first double bond in the third carbon atom from the end of their carbonic skeleton (this is called 'o' omega carbon atom), are called o-3 (or n-3), whereas when the first double bond is found in the sixth from the end of the carbonic atom, they are called o-6 (or n-6) fatty acids. The...

Free Fatty Acids and Nitric Oxide

Increased levles of free FAs causes increased very LDL production and cholesteryl ester synthesis. The resulting increased triglycerides found in diabetic subjects, coupled with the lower high-density lipoprotein (HDL), have also been associated with endothe-lial dysfunction (134,135).

Practical considerations

The study of lipoprotein triglyceride fatty acid kinetics has been challenging because of the unavailability, until recently, of primary pool tracers. When chylomicron or VLDL triglycerides are labeled with a precursor (e.g. oral ingestion of a labeled triglyceride or fatty acid in the case of chylomicrons oral or intravenous administration of labeled glycerol in the case of VLDL), the rate of tracer appearance into the primary pool is not known. Measurement of kinetics under non-steady state conditions is problematic because there is often ongoing tracer appearance at an unknown rate and therefore simultaneous tracer disappearance at an unknown rate. This problem can be circumvented with the direct administration of labeled chylomicrons (or a surrogate thereof, such as a lipid emulsion) or labeled VLDL. The relatively recent availability of such tracers should improve the reliability of measurements made under steady state conditions and should also make it possible to attempt...

Effects Of Exercise In Prediabetic Syndromes Insulin Resistance Syndrome

The insulin resistance syndrome has been recognized as an important new risk factor associated with premature coronary artery disease. There seems to be a genetic trait because the underlying abnormality can also be demonstrated in offsprings of parents affected by this syndrome (49, 50). Cardiovascular risk factors, such as hypertension, glucose intolerance, elevated levels of triglycerides combined with low levels of high-density lipoproteins (HDL), and impaired fibrinolytic activity, are detected with a higher frequency in these individuals than expected. There is also considerable evidence that impaired aerobic exercise capacity is an important component of this syndrome. Muscle biopsies obtained from these individuals exhibit a reduction of mitochondrial and capillary density, not totally dissimilar from patients with congestive heart failure (51). It has been speculated that the limited aerobic capacity of skeletal muscles may induce these patients to select a more sedentary...

Adipose Tissue Endocrine Functions

Adipose tissue is comprised of lipid-filled cells surrounded by a matrix of collagen fibers, vessels, fibroblasts, and immune cells. Its main function is the storage of triglycerides for times of energy deprivation. However, it secretes hormones and other products and is involved in various aspects of metabolism that directly affect the onset of obesity. It metabolizes sex steroids and glucocorticoids. For example, 17-beta-hydroxysteroid oxidoreductase converts androstene-dione to testosterone and estrone to estradiol. This may be important for fat distribution. Estrogens stimulate fat accumulation in the breast and subcutaneous tissue, while androgens promote central obesity. Alteration of these interconversions may predispose individuals to reproductive disorders and certain cancers (292,293).

Effects on Pancreatic Insulin Secretion

There are several potential mechanisms whereby thiazolidinediones might enhance P-cell function, in addition to simply lowering ambient levels of glycemia and reducing glucotoxic signaling abnormalities in P-cells. Recently, abnormal P-cell secretory responsiveness and potential cell death (apoptosis) have been attributed to chronic effects of accumulated triglycerides and FFA derivatives in the pancreatic islet cells in obesity with insulin resistance, a phenomenon that has been dubbed lipotoxicity 12,13 . This hypothesis also postulates that the effect of thiazolidinediones to redistribute fat stores in the body, including from the pancreatic islets, and to reduce circulating levels of FFA, may improve P-cell function 14 . In diabetes-prone, obese rodents, pre-clinical data has shown a potent effect of thiazolidinediones to restore P-cell insulin content and preventing loss of P-cell mass in models of type 2 diabetes 12,15,16 .

Risk Factors for Diabetic Retinopathy

Elevated Serum Cholesterol Triglycerides Several studies have suggested that elevated serum lipids increase the risk of vision loss from diabetic retinopathy (36-38). The Early Treatment Diabetic Retinopathy Study (ETDRS) and the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) found that elevated levels of cholesterol were associated with increased severity of hard exudates, which was a significant risk factor for moderate vision loss independent of macular edema. The presence of hard exudate was the strongest risk factor for the development of submacular fibrosis, an important cause of permanent vision loss. The ETDRS also found that elevated serum triglycerides is associated with a greater risk of developing high-risk PDR (39). Thus, it is imperative for ophthalmologists and diabetes specialists to carefully follow the patient's lipid profile and treat when necessary, to decrease the risk of visual morbidity as well as cardiovascular disease.

Mechanisms of Foam Cell Formation

Foam cells are the hallmark of the arteriosclerotic process. Diabetes appears to enhance foam cell lesion formation in experimental animals and in humans. In animal models, type 1 diabetes induced by autoimmune-mediated P-cell destruction or by toxins, alloxan, or streptozotocin increases fatty streak formation (98-100). Similarly, in human postmortem studies it has been shown that diabetes accelerates the formation of fatty streaks. The Pathobiological Determinants of Atherosclerosis in Youth study, a study in 3000 youths, ages 15 to 34 years, who died of trauma, showed that youths over 25 years of age with elevated levels of glycated hemoglobin ( 8 ), had significantly more fatty streaks in the right coronary artery than controls even when their lipid profiles were normal (101,102). A recent high-resolution ultrasound in vivo study of common carotid arteries of 11-year-old children with type 1 diabetes showed that these children had an increased intima-media thickness (IMT) compared...

Microalbuminuria And Cardiovascular Disease In Type Diabetes

Microalbuminuria is strongly predictive of the development of overt diabetic nephropathy and its associated excess of coronary, cerebrovascular and peripheral arterial disease in type 1 diabetes 17 . In prospective studies those with microalbuminuria have a significantly higher risk of dying from a cardiovascular cause. In a twenty three year follow up study of patients with type 1 diabetes and microalbuminuria those with microalbuminuria had a significantly higher mortality from a cardiovascular cause (Relative Risk 2.94 95 Confidence Interval 1.18 - 7.34) 18 . Rossing et al confirmed this in a ten-year observational follow up of 939 patients with type 1 diabetes, 593 with normal AER, 181 with microalbuminuria and 165 with overt nephropathy 19 . Age, smoking, microalbuminuria and overt nephropathy were significant predictors of cardiovascular mortality. Myocardial involvement may even be present at the stage of microalbuminuria, aerobic work capacity is reduced in patients with...

Implications for practice

Orlistat was associated with statistically significant improvements in total cholesterol, LDL, and triglycerides, that were sustained at 52 weeks follow-up. These changes in lipid levels have been noted by others (NHLBI 1998) and although modest improvements, they correspond to changes associated with a decrease in the incidence of ischemic heart disease (Law 1994). It remains unclear whether the improved glycemic control and lipid levels noted in this review could be maintained over the long-term to influence the risk of complications as demonstrated in large trials.

Acquired Organ Dysfunction

Also discussed later is a more recent suggestion that relates to another component of the diabetes phenotype, high circulating levels of triglycerides and fatty acids, as a cause of acquired organ abnormalities so-called lipotoxicity (42). There has also been interest in the combined effects of both elements, termed glucolipotoxicity (43,44).

Effects Of Exercise In Diabetics Metabolic Effects

During exercise at maximal levels energy demands may be 20-fold increased as compared to resting conditions. In order to maintain homeostasis and prevent hypoglycemia several regulatory mechanisms are activated. Initially skeletal muscles break down their own stores of glycogen, triglycerides, and free fatty acids derived from adipose tissue. In order to mobilize extramuscular stores adjustments on a hormonal basis are necessary. In the early phase of exercise hepatic glucose production is increased by a reduction of insulin levels in the presence of unchanged glucagon levels. In subsequent stages glucagon and catecholamine levels are elevated. As a result, glucose levels in healthy individuals remain fairly constant during exercise. In patients with diabetes type 2 exercise of moderate or high intensity regularly decreases blood glucose levels as a result of insulin-independent activation of glucose transport (7) as well as increased insulin sensitivity (8). Due to an exaggerated...

Pentose Phosphate Pathway

Secondly, NADPH as well as the PPP intermediate product GAP is also required for the synthesis of fatty acids in liver and adipose tissue. Consequently, since NADPH is also the key for the synthesis of fatty acids, it becomes of more concern to cancer cells grown under the above-mentioned hyperglycemic conditions (see book cover). As already described, we have seen a dramatic increase in vacuoles filled with lipid drops (positive staining with Nile red), when tumor cell lines were cultured under permanent high glucose concentrations (11 mM). When insulin was given additionally, the amount of triglycerides stored within those vacuoles was further increased. Since these cells were grown in standard culture medium, most of these fatty acids had to be synthesized by the tumor cells themselves. This indicates that those cells will have a shift towards the PPP followed by a noticeably increase in NADPH turnover. Indeed, first results showed a distinctive increase in glucose-6-phosphate...

Studies in Type Diabetes

When administered in physiologic doses to people with type 1 diabetes, injections of pramlintide result in sustained reductions in A1c associated with significant blunting of the glucose response to a standardized meal. In addition, significant reductions in the postprandial concentrations of triglycerides, and of several measures of oxidative stress

Regulation of endogenous glucose output during euglycaemic hyperinsulinaemia

Several metabolic conditions known to be associated with resistance of insulin induced suppression of endogenous glucose output should be considered when a clamp protocol is planned. For example, impaired glucose tolerance (Bavenholm etal. 2001), type 2 diabetes mellitus and obesity (Kolterman etal. 1981 DeFronzo etal. 1985 Butler etal. 1990 Staehr etal. 2001 Krssak etal. 2004), steroid therapy (Rizza etal. 1982), increased availability of free fatty acids and or triglycerides (Bajaj et al. 2002 Boden et al. 2002) and fat accumulation in the liver (Seppala-Lindroos etal. 2002 Krssak etal. 2004) are associated with defective insulin induced suppression of endogenous glucose output. In terms of a dose-response curve of insulin action on endogenous glucose output, the curve is shifted to the right under these metabolic conditions, indicative of hepatic insulin resistance (Kolterman etal. 1981). In line with these studies, the half maximal effective plasma insulin concentration to...

Species of Plants Reported to Be Used Traditionally to Treat Diabetes

Contains berberine (Soffar et al., 2001), which reduces levels of fasting blood glucose, triglycerides, and total cholesterol (Leng et al., 2004) and decreases glucose absorption (Pan et al., 2003) Berberine administration to impaired glucose tolerance rats reduces levels of fasting blood glucose, triglycerides and total cholesterol (Leng et al., 2004)

Comparison Of Different Sulfonylureas And Meglitinides

Increases in postprandial glucose were shown to be associated with elevated risk of cardiovascular disease in impaired glucose tolerance (Lancet Decode 1999). This was not shown as well among patients with manifest type 2 diabetes. The extrapolation of studies in impaired glucose tolerance suggest that near-normal control of glucose, both fasting and postprandial, should decrease the cardiovascular risk associated with type 2 diabetes back to the normal range. Although this is plausible, and is expressed in the current treatment guidelines, it has not yet been proven in prospective trials. Such trials would have to overcome the difficulty that it is presently much harder to lower blood glucose into the normal range than to lower blood pressure or elevated cholesterol levels. However, the impact of clinical studies demonstrating a substantial advantage of normalizing and not just lowering blood glucose would be enormous and would change current treatment practices.

Lipid Abnormalities and Lipid Lowering in Diabetes

Secretory Pathway Lipoprotein

Apo Apoproteins C cholesterol CAD coronary artery disease CE cholesteryl esters CETP cholesteryl ester transfer protein CHD coronary heart disease CVD cardiovascular disease FFA free fatty acids, HDL-R high-density lipoprotein receptor HDL high-density lipoproteins HL hepatic lipase HMG-CoA hydroxy-methyl-gluta-ryl-CoA IDL intermediate density lipoproteins LCAT lecithin cholesterol acyltransfer-ase LDL-R LDL receptor (ApoB ApoE receptor) LDL low-density lipoproteins Lp(a) lipoprotein(a) LPL lipoprotein lipase LRP LDL receptor-related protein TG triglycerides UC unesterified cholesterol VLDL very low-density lipoproteins. When dietary measures (plus exercise) and hypoglycemic agents have failed to achieve acceptable lipid levels, drug therapy should be prescribed. Drugs currently in clinical use for the treatment of hyperlipidemias are listed in table 1, in which the distinction is made between drugs mainly lowering C, represented by the HMG-CoA reductase inhibitors statins (besides...

What is the effect of TZDs on serum lipids

Most studies agree that TZDs increase HDL-cholesterol by 10-14 percent, decrease free fatty acids and contribute to the increase in size of small-dense LDL molecules, which has a beneficial effect on the risk for atherosclerosis. Moreover, they do exert a mild hypotriglyceridaemic effect when the triglycerides are 200 mg dl (2.3 mmol L). It should also be mentioned that modern pharmaceutical research is directed towards the development of products that are simultaneously PPAR-g and-a agonists, affecting both the metabolism of glucose and lipids. A 48 year old woman with a 10 year history of Type 2 DM that has been treated for six years with metformin (at an escalating dose reaching 850 mg three times per day during the last year), presents to the Diabetes Clinic for a regular visit. She feels well and denies any dyspnoea, orthopnoea or ankle oedema, or any undesirable effect of metformin. Her weight is stable, as is her diet (roughly 1,400 kcal day). Because of her work she does not...

Can Weight Loss and Exercise Improve NAFLD

Dietary composition may be another important but frequently overlooked aspect related to excessive hepatic fat deposition, as been suggested in single case reports (361) and small case series (n 5) (362) in which low-carbohydrate diets were of particular benefit to rapidly reduce steatosis and elevated ALT in subjects with NAFLD. Recently, Ryan et al. (363) examined the effect of two hypocaloric diets containing either 60 carbohydrate 25 fat or 40 carbohydrate 45 fat (15 protein) for 16 weeks in 52 insulin-resistant obese subjects. While both diets resulted in significant decreases in weight, insulin resistance, and serum ALT concentrations, the low carbohydrate diet improved all three parameters significantly more than the high carbohydrate diet. Reduction of steatosis and of plasma triglycerides concentration by low carbohydrate diets is likely related to downregulation of hepatic sterol regulatoryelement-binding proteins (SREBP) activity by the amelioration of chronic...

Suketu Shah md Alina Gavrila md and Christos S Mantzoros md

Our understanding of the function of fat cells has changed dramatically with the realization of the endocrine function of adipose tissue. Initially thought to serve only as a repository for energy via storage of triglycerides, adipocytes are now known to secrete a variety of proteins with diverse metabolic functions. These proteins include leptin, TNF-a, plasminogen activator inhibitor-1, acylation-stimulating protein, resistin, and adiponectin (1,2). Adiponectin has received much attention for its putative role in diabetes and CVD. Besides being associated with the development of diabetes, it may also have a direct role in modulating inflammation and atherosclerosis and thereby be one of the factors that links obesity to CVD.

Start or Intensify Statin Dose

Recent evidence (Colhoun, 2004 Heart Protection Study Group, 2002) and ATPIII consensus guidelines (Grundy, 2004) suggest that statins are beneficial for high-risk patients with a 10-year risk of CV event of more than 20 , (e.g. CAD equivalency) even with baseline LDL of less than 100. Conclusion Grade I See Conclusion Grading Worksheet - Appendix B - Annotation 11B (Statin Use) . Use of moderate to high dose statins or other LDL lowering medications as needed to achieve an LDL value less than 70 is recommended for patients with CHD. Three pathways to improve lipids are (1) medical nutrition therapy, (2) increase physical activity, and (3) pharmacotherapy. Beneficial effects of statins on cardiovascular risk reduction may, in part, be independent of their effects on lipids. Diabetes has been considered a coronary artery disease equivalent. Risk calculators for type 2 diabetes can be found at the following URL http www. Small density LDL-cholesterol (more atherogenic) particles are...

Need For Improving Diabetes Care References

Type 2 diabetes (T2D) is the most common form of diabetes, a metabolic disorder characterized by hyperglycemia resulting from defects in insulin action, insulin secretion, or both. Early diagnosis of T2D and the high-risk category of pre-diabetes may help reduce the associated public health and clinical burden. Available diagnostic strategies include fasting plasma glucose, oral glucose tolerance test, and casual plasma glucose in the presence of symptoms of hyper-glycemia. Potential use of hemoglobin A1c as part of the strategy for screening and diagnosis has been recently proposed. Those with risk factors for T2D should be targeted including patients with overweight obesity, those with family history of T2D, those aged 45 years and older, race ethnic minorities (such as Native Americans, African Americans, Latinos, and Asian Americans), women with history of gestational diabetes, and those with metabolic syndrome abnormalities (high blood pressure, low HDL cholesterol, and high...

Presentations classic silent and diabetic ketoacidosis

Sympathomimetics Classification Table

DKA is characterized by complete lack of insulin production such that glucose use is crippled and triglycerides must be broken down to provide the body with energy. The resulting byproducts of fatty acid metabolism the ketones aceto-acetate and beta-hydroxybutyrate further exacerbate the osmotic diuresis and cause acidosis. Dehydration and poor perfusion also may lead to lactic acidosis. The consequences of insulin deficiency are shown in Fig. 2.

Tracers for the study of triglyceriderich lipoprotein kinetics Chylomicrons

Triglyceride uptake from the circulation can under some circumstances occur independent of enzymes such as LPL and hepatic lipase. Saturation of transport appears to occur at plasma triglyceride concentrations of 400mg dL-1 (Brunzell et al. 1973, 1979) or lower (Nikkila & Kekki 1973). It is important to note that chylomicron-sized lipid particles can be removed via nonenzymatic pathways, particularly the reticuloendothelial system (Seidner et al. 1989). When large amounts of a lipid emulsion were administered to rats by bolus injection, there was evidence of non-enzymatic lipid clearance (Lutz et al. 1989). Karpe et al. (1997) concluded that, during mild chylomicronaemia after a high fat meal in normal subjects, the removal of triglycerides by non-lipolytic tissues was negligible. Quantitatively significant reticuloendothelial uptake may occur only at plasma triglyceride concentrations above those at which maximal rates of LPL-mediated triglyceride hydrolysis are observed, i.e....

What are the lipoproteins and what are they used for in the body

Endogenous Lipoprotein Metabolism

Because lipids are insoluble in water, they cannot circulate freely in the blood. For this reason, they are linked with special proteins (the apolipo-proteins or apoproteins) and form complex substances (the lipoproteins) that are soluble in water and can be transported through the blood circulation all over the body. More specifically, the lipoproteins contain a lipid core (from free cholesterol, cholesterol esters, triglycerides and phospholipids) and a protein cover, the apolipoproteins. Lipoproteins are distinguished into five main categories (Table 23.1), depending on their density chylomicrons, very low density (VLDL), intermediate density (IDL), low density (LDL) and high density lipoproteins (HDL). There are many apolipoproteins (A-I, A-II, A-IV, B-48, B-100, C-I, C-II, C-III, D, E, apo(a)), which not only participate as structural components in the molecule of the various lipoproteins, but also have very important biologic participation in their metabolism. The lipoprotein...

Bitter Melon Momordica charantia

Laboratory studies have found that bitter melon extracts may enhance insulin secretion by the islets of Langerhans, reduces glycogenesis in liver tissue, enhances peripheral glucose utilization, and increases serum protein levels 29, 30 . In an animal study, alcohol-extracted charantin from bitter melon consists of mixed steroids and was found to be more potent than the oral hypoglycemic agent tolbutamide 31 . Bitter melon also contains an insulin-like polypeptide, polypeptide-P, similar in structure to bovine insulin. It was found to decrease blood sugar levels when injected subcutaneously into type 1 diabetic patients 32 . Bitter melon extracts may restore the altered histological architecture of the islets of Langerhans. Also, laboratory studies support the cholesterol-lowering properties of bitter melon, attributed, in part, to decreasing lipid peroxidation 33 . Bitter melon supplements used for type 2 diabetes should be a proprietary standardized to contain 10 charantins...

Preventing Microalbuminuria in Diabetes

In conclusion, there is now fairly good evidence from clinical trials that treatment with an ACE inhibitor should be started early in patients with type 2 diabetes and nor-moalbuminuria. Treatment should be initiated when systolic BP is more than 130 systolic mm Hg. Systolic BP elevation is very common in patients with type 2 diabetes and metabolic syndrome. This means that most type 2 diabetes mellitus patients would qualify for this type of treatment. These patients also often show sodium retention and therefore a combination with an ACE inhibitor and diuretics seems to be most effective in reducing microalbuminuria and BP (1). Now there seems to be a very good foundation for substantial improvements of the prognosis for patients with type 2 diabetes (1,14) and early treatment of hypertension leads to better prognosis, as does, but maybe to a lesser extent, improved euglycemic control (16). Clearly treatment with statins is also important, as documented in many studies, among others...

Gastrointestinal Autonomic Neuropathy Treatment of Gastric Atony

Diabetic diarrhea more commonly complicates type 1 than type 2 diabetes (153). The therapeutic approach to the management of diabetic diarrhea first involves the exclusion of other etiologies, such as functional bowel syndrome or sprue. A positive hydrogen breath test may indicate bacterial overgrowth secondary to intestinal hypomotility. A coarse of broad-spectrum antibiotics such as tetracycline, ampicillin, or metronidazole may be successful in about half the cases if given at the onset of the attack. If no improvement is observed, then bile salt binders (e.g., cholestyramine) may be tried. Clonidine has also proved to be useful in some cases. Severe, intractable diarrhea may respond to octreotide (100 g tid, sc), but care must be taken because the associated instability of diabetes control and randomized clinical trials have not yet been performed. When diarrhea is secondary to aberrant hypermotility, loperamide up to 16 mg d can be helpful (154).

Oral diabetes medications or oral hyperglycemic medications

Triglycerides Simple fatty acids found in both plants and animals. Vegetable oils contain triglycerides with unsaturated fatty acids and tend to be liquid at room temperature. Animal sources of triglycerides contain mostly saturated fatty acids and tend to be solid at room temperature.

Insulin Resistance and Its Relevance to Treatment

Catecholamines And Insulin Resistance

Insulin regulates several key metabolic steps (fig. 1). In doing so, insulin is opposed by the four counterregulatory hormones (the rapid-acting glucagon and catecholamines, and the slow-acting growth hormone and cortisol). Insulin affects the pathways of glucose utilization as well as the synthesis and degradation of macromolecules (glycogen, triglycerides and proteins) by regulating the activity of 'key enzymes'. Indeed, along each metabolic pathway, there is one or more key step(s) catalyzed by key enzymes. These are enzymes which, because of their low activity and sensitivity to regulatory factors (including hormones), regulate the overall rate of the pathway to which they belong. In particular, insulin (or, better, its prevalence over the counterregulatory hormones) exerts the following effects (fig. 1) Triglycerides

Hormonal Contraception

Hormonal contraception contains either a progestin compound alone or in conjunction with estrogen. They can be administered orally, intramuscularly, transdermally, and transvaginally. Some IUDs also contain progestin. Estrogen does not affect glucose tolerance (5), but progestins do increase insulin resistance and decrease glucose tolerance in a dose and potency fashion (6-8). Estrogen slightly increases blood pressure (9) by increasing angiotensin production while progestins have no effect. Estrogens produce an increase in clotting factors while progestins have no effect (10-14). Estrogens favorably affect lipid profiles, decreasing LDL-cholesterol and increasing HDL-cholesterol, while progestins produce an opposite effect (15-19). Estrogen increases triglycerides, while progestins have no effect. When estrogens and progestins are combined as in combination oral contraceptives (COC), the lower doses and less androgenic progestins generally produce milder and a more estrogen-dominant...

Fibrinolytic System in Diabetes Mellitus Plasminogen Activator Inhibitor

Elevated PAI-1 levels have been noted in patients with CAD and are strongly correlated with components of cardiometabolic syndrome (CMS) such as BMI, blood pressure, and triglycerides (2, 27). Festa et al. examined the relationship between new-onset diabetes and dynamic changes of PAI-1 and fibrinogen (39, 40). In nondiabetic, healthy individuals, increasing PAI-1 levels were associated with new cases of diabetes. Both fibrinogen and PAI-1 levels are elevated in prediabetic subjects however,

What is the Pathophysiology of Elevated Plasma FFAs

Adipocyte Lipolysis And Circulatory Ffa

Control of fatty acid uptake and release by adipose tissue. Insulin promotes FFA uptake into the adipocyte by stimulating the LPL-mediated release of FFA from lipoprotein triglyceride (1). Fatty acids enter the adipocyte both by diffusion down a concentration gradient as well as by facilitated transport by fatty acid transporters (2). Insulin also stimulates glucose transport into the adipocyte, thereby increasing the availability of glycerol-3P for triglyceride synthesis (3). Insulin may have a direct stimulatory effect on lipogenic enzymes such as DGAT (4). By inhibiting HSL and ATGL (5), it reduces the intracellular lipolysis of cytosolic triglycerides, thereby promoting adipocyte triglyceride storage. Parasympathetic output from the brain may inhibit lipolysis directly (6). ASP (7), whose action is complementary to that of insulin in the adipocyte, stimulates glucose uptake and fatty acid esterification and inhibits mobilization of stored triglycerides. Defective adipose...

Riddle Mc Hart J. Hyperglycemia Recognised And Unrecognised As A Risk Factor For Stroke And Transient Ischemic Attacks.

Heart Protection Study Collaborative Group (2002). MRC BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals a randomised placebo controlled trial. Lancet 360 7-22. Heart Protection Study Collaborative Group (2003). MRC BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes a randomised placebo-controlled trial. Lancet 361 2005-16. Hess DC, Demchuk AM, Brass LM, Yatsu FM (2000). HMG-CoA reductase inhibitors (statins). A promising approach to stroke prevention. Neurology 54 790-6. Iso H, Jacobs DR Jr, Wentworth D, Neaton JD, Cohen JD for the MRFIT Research Group (1989). Serum cholesterol levels and six year mortality from stroke in 350,977 men screened for the Multiple Risk Factor Intervention Trial. New England Journal of Medicine 320 904-10.

Glucose Metabolism Oxidative Phosphorylation versus Aerobe Glycolysis

Krebs Cycle Intermediates Anabolism

Scheme displaying the various aspects of glucose metabolism - supporting catabolic as well as anabolic pathways. Non-proliferating (healthy) cells consume glucose mainly for ATP production, via glycolysis (light blue) followed by TCA cycle (green) - accompanied by respiratory chain - resulting in 38 mol ATP per mol glucose. However, cancer cells are highly active in proliferation and therefore exhibit increased glucose consumption. But contrary to non-proliferating cells, cancer cells use major parts of glucose for anabolic processes. Especially the TCA intermediates will be used for the synthesis of non-essential amino acids as well as fatty acids, instead of being the main source for energy. Also the glycolysis intermediate GAP will be used in large parts for the synthesis of triglycerides. A further difference of tumor glucose consumption is the enormous increase of PPP activity (red). The PPP is the source of supply for RNA and DNA production, and secondly supplies cancer...

Fat Diversion from Adipose to Nonadipose Tissue and Lipotoxicity

Lipoatrophy, a genetic or acquired reduction or total absence of adipose tissue, in humans and animal models results in accumulation of cytosolic triglycerides to a massive extent in nonadipose tissues, and in extreme insulin resistance (117-120). In A-ZIP F-1 fatless mice, intramuscular and intrahepatic lipids were significantly reduced and insulin resistance alleviated by surgical re-implantation of adipose tissue (118,119). Shulman has proposed that insulin resistance develops because of an imbalance of fat distribution among tissues (121). A key issue is whether TGs accumulate in muscle tissue of insulin resistant individuals as a result of a primary defect in fatty acid oxidation, increased total FFA flux to muscle, or owing to an imbalance between FFA uptake, esterification, TG lipolysis, and fatty acid oxidation. Kelley has described inflexibility of insulin resistant skeletal muscle in switching between lipid and carbohydrate oxidation (122), whereas others have implicated...

When can DM cause reversible haziness of the lens

Laboratory evaluation showed the following Ht 36.1 percent, Hb 12.2 g dl, WBC 7000 ml, (polymorphonuclears 55 percent, lymphocytes 37 percent, monocytes 6 percent), Platelets 164,000 ml, ESR 23 mm hr, glucose 285 mg dl (15.8 mmol L), creatinine 0.76mg dl (67.2 mmol L), cholesterol 161 mg dl (4.16 mmol L), HDL-cholesterol 57 mg dl (1.47 mmol L), LDL-cholesterol 87 mg dl (2.17 mmol L),

Biguanides Metformin Case Study

The serum total cholesterol was 294 mg dl (7.6 mmol L) and the triglycerides 400 mg dl (4.52 mmol L). He had been recommended to follow a diet of 1,700 calories and to start exercising, as well as perform a cardiovascular system check up (exercise stress test, carotid ultrasound), 24-hour urine albumin excretion and serum TSH measurement. He was also prescribed a daily aspirin. The patient followed the diet, as well as a programme of relatively increased physical activity and lost 9 kg (19.8 lb), improving his blood examinations. During the last visit his arterial pressure was 130 80 mmHg, his fasting blood glucose 130-140 mg dl (7.2-7.8 mmol L), post-prandial glucose 190-210 mg dl (10.6-11.7 mmol L), HbA1c 8.9 percent, serum total cholesterol 212 mg dl (5.5 mmol L) and triglycerides 201 mg dl (2.3 mmol L). The 24-hour urine albumin excretion and the serum TSH were within normal range, as was a complete chemistry profile. The symptoms had completely...

What are the effects of exercise in a diabetic person

During exercise in normal persons, pancreatic insulin secretion decreases (as already mentioned) in response to the increased insulin sensitivity brought about by exercise. In persons with Type 1 DM, however, that use insulin injections for their treatment, this physiological decrease in insulin secretion cannot happen, because insulin has been exogenously administered. Circulating insulin suppresses the expected rise of hepatic glucose production and, on the contrary, aggravates the exercise-induced glucose uptake by the exercising muscles. This hyper-insulinaemia also hinders the normal mobilization of triglycerides from the adipose tissue during exercise, which results in a decreased supply of FFAs for use as a fuel from the muscles.

DPP and DPP Inhibitors

P-Cell Function and p-Cell Mass in Animal Studies with DPP-4 Inhibitors An important discussion focuses on whether DPP-4 inhibitors are able to influence the disease progression of type 2 diabetes advantageously by slowing or even inhibiting the loss of p-cell mass and function. Therefore the effect of sitagliptin and vildagliptin was investigated extensively in animal models. Diabetic mice treated with DPP-4 inhibitors in long-term studies showed a significant, dose-dependent reduction of glycemic parameters (postprandial and fasting hyperglycemia, hemoglobin A1c (HbA1c)) as well as lipid parameters (plasma triglycerides and free fatty acids). DPP-4 inhibitors increased the number of insulin-positive p cells in islets and the p-to a-cell ratio in different diabetic animals was normalized. Furthermore, islet insulin content was found to be increased and glucose-stimulated insulin secretion in isolated islets was found to be improved in comparison to glipizide-treated mice. According...

Effects of FFA and Islet Triglyceride Stores on Pancreatic Cells Acute Effects of FFAs on Insulin Secretion

P-cell lipotoxicity, a term coined by Unger in 1995, describes lipid-induced functional impairments in GSIS as well as reduction in P-cell mass, and is also linked to, but not necessarily caused by, intracellular TG accumulation (137). Insulin secretion is mainly regulated by glucose through the closure of ATP-sensitive K+ channels, leading to membrane depolarization, opening of voltage-dependent Ca2+ channels, increased intracellular Ca2+ concentration, subsequent activation of kinases, and exocytosis of secretory granules. A potential mechanism lies in the stimulation by FFAs of the ATP-sensitive K+ channels (200,201) leading to impaired mitochondrial function. Ongoing accumulation of FFAs may chronically prevent K+ channels from closure, thus contributing to the resistance. Intracellular stores of triglycerides can be hydrolyzed by hormone-sensitive lipase, which is expressed and active in P-cells (202) and, therefore, may constitute an additional in situ supply of long-chain fatty...

Structural Abnormalities In Type And Type

Diabetic Neuropathy Myelinated Axon

Primary demyelination is rare in type 1 DPN of the BB Wor-rat, but somewhat more common in both human and experimental type 2 DPN (1,31). The reason for this is not well known, although more common comorbidities in both human and experimental type 2 diabetes such as hypercholesterolemia and triglyceridemia have to be considered.

Species of Plants Reported to Be Used Traditionally to Treat

Reduces blood glucose (Ivorra et al., 1989) Used to treat diabetes (Lust, 1986) Reduces blood glucose level in blood of alloxan-treated rats (Lemus et al., 1999) Contains triterpenes with hypoglycemic activity (Reher et al., 1991) Contains triterpenes with hypoglycemic activity (Reher et al., 1991) Reduces blood glucose (Handa et al., 1989) Extracts reduce blood glucose, cholesterol and triglycerides in patients with type 2 diabetes that did not respond to conventional treatments (Herrera-Arellano et al., 2004) Used to treat diabetes (Winkelman,

Predictors Of Mortality

Verona Diabetes Study

The role of smoking, high blood pressure, low HDL cholesterol, high total cholesterol and obesity have not been studied extensively in elderly subjects. Among the surveys of elderly subjects, only a small number were prospective and the results controversial. Some studies suggest that the risk factors remain the same, while others found a smaller association or even no association at all (Castelli et al 1989 Beaglehole 1991 Krumholz et al 1994 Rossing et al 1996). Surveys showing positive associations consisted largely of subjects belonging to the 'young-old' age group (60-70 years), while negative studies recruited subjects aged 70 and over. In a Finnish study, smoking, high systolic blood pressure and low HDL cholesterol predicted cardiovascular events among elderly non-diabetic subjects, while total cholesterol did not (Kuusisto et al 1994). The risk factors for cardiovascular events remained substantially similar when non-diabetic subjects with previous myocardial infarction were...

Overcoming the Manifestations of Syndrome X

Dietary recommendations to reduce CHD have until quite recently been based upon the principle that hypercholesterolemia (more specifically, an elevated LDL cholesterol level) is the only CHD risk factor that needs to be addressed. The result has been almost total emphasis on the use of low-fat-high-carbohydrate (CHO) diets. More to the point, advice to replace saturated fat (SF) with CHO in order to lower LDL cholesterol concentrations continues to be given, regardless of how insulin resistant the individual. Unfortunately, this dietary approach will make all of the manifestations of syndrome X worse. The greater the CHO content in an isocaloric diet, the more insulin must be secreted in order to maintain glucose homeostasis. This poses no danger to insulin-sensitive individuals, but low-SF high-CHO diets will significantly increase the already high day-long plasma insulin concentrations in patients with syndrome X. As a consequence, fasting plasma TG concentrations will increase, as...

Deciphering lipid panel results

If your doctor wants to know the levels of all the fat particles in your child's bloodstream, your child has to fast for 12 hours before undergoing a test known as a lipid panel, but if he is satisfied with the results of a total cholesterol and the good cholesterol, no fasting is required before the test. Make sure that the doctor performs a lipid panel on your child once a year (or more often if the results aren't normal). A lipid panel is done with a blood specimen in which the various types of fat particles are measured. Your child's risk for coronary artery disease is greater if his HDL cholesterol is low and LDL is high. The famous Framingham study has shown that if you measure the total cholesterol and the HDL cholesterol and divide the total by the HDL, patients who have a ratio of 4.5 or less have a low incidence of heart attacks. Patients with ratios of greater than 4.5 are at higher risk, and the higher the ratio, the worse the risk. HDL Cholesterol Level Triglycerides...

Sometimes requires discontinuation Contraindicated in active hepatic renal and coronary artery disease

In the UKPDS, treatment with metformin (another drug that decreases hyperinsulinemia and insulin resistance) produced greater reduction in cardiovascular disease events and mortality than sulfonylureas and insulin 8 . The latter drugs decreased blood glucose level to a similar degree as metformin but did not decrease plasma insulin concentrations. This effect may have been mediated through a decrease in insulin resistance, although other effects of metformin, such as improvement in lipid profile, improved fibrinoly-sis, and prevention of weight gain, may be important 8 . Metformin has a favorable, albeit modest, effect on plasma lipids, particularly in decreasing triglycerides and low-density lipopro-tein (LDL) cholesterol however, it had little, if any, effect on HDL cholesterol levels 78 . Met-formin use was associated with decreased plas-minogen activator inhibitor (PAI-1) activity which led to improved endothelial dysfunction (see Table 1). Several studies observed the effects of...

Fatty Acids As Insulin Secretagogues

A new study using molecular and pharmacological tools suggests that the LC-CoA hypothesis may require re-evaluation (56). Recombinant adenovirus containing the cDNA-encoding malonyl-CoA decarboxylase (AdCMV-MCD), an enzyme that decar-boxylates malonyl CoA to acetyl-CoA, was employed in this approach. Treatment of INS-1 cells with AdCMV-MCD prevented the normal glucose-induced rise in malonyl-CoA levels, such that its concentration in AdCMV-MCD-treated cells at 20 mM glucose was lower than control cells at 3 mM glucose. That the normal link between glucose and lipid metabolism had been significantly disrupted by this approach was shown by the fact that in the presence of 20 mM glucose, AdCMV-MCD-treated cells were less effective at suppressing 1- 14C palmitate oxidation, and incorporated 43 less labeled palmitate and 50 less labeled glucose into cellular lipids than controls. In spite of the large metabolic changes caused by expression of malonyl-CoA decarboxylase (MCD), insulin...

Macrovascular Complications Protecting Your Heart

CAD is found in the arteries of people with T1DM who die of other causes as young as age 20 or even younger, and it's extensive in older people with T1DM who die of other causes. However, it's not found in everyone. Those folks with T1DM who don't have other risk factors, such as uncontrolled high blood pressure, cigarette smoking, a sedentary lifestyle, and high cholesterol levels, rarely have problems with coronary artery disease. A family history of coronary artery disease is another risk factor and one that you can do nothing about, but its effect is minimized when the other risk factors are avoided or controlled. Although there's no data yet in T1DM, studies have shown that lowering the LDL cholesterol and raising the HDL cholesterol (see Chapter 7) will prevent first heart attacks and decrease the occurrence of second heart attacks in the general population. Hopefully, data will soon be available that will allow a recommendation for treatment of blood fats in T1DM.

Biology and Atherosclerosis

Consistent with the effects seen in macrophages, PPAR-y agonists repress inflammatory cytokine production in T-lymphocytes (42). In ECs, PPAR-g may decrease adhesion molecule expression although the results are variable (43,44), pointing out a limitation of a field that has depended heavily on synthetic agonists as experimental tools, with all the attendant concerns of pharmacological studies physiological relevance, receptor dependence, dose dependence, and toxicity effects to name a few. One example of the potential complexities involved is evident in the relationship between PPAR-y ligands and plasminogen activator inhibitor 1 (PAI-1) levels. Several reports indicate PPAR-y ligands may increase expression of PAI-1, a pro-coagulant, pro-atherosclerotic response. Other laboratories find a PPAR-y-mediated repression of PAI-1 (45-47). Others report inhibition of PAI-1 expression (48). In humans, PPAR-y ligands clearly appear to decrease circulating PAI-1, although this may be a...

Alternative Hypothesis For The Hspg Alterations Findings From The Atherosclerosis Prospect

NEFA may come into contact with vascular cells in different ways. They are one of the main products of phospholipases and other lipases on lipids of apoB-lipoproteins entrapped in the intima. In addition, in the dyslipidemia associated with insulin resistance and type 2 diabetes the vasculature is permanently exposed to a high influx of albumin-bound NEFA originating from the hydrolysis of post-prandial lipoproteins and from increased lypolysis of adipose tissue triglycerides. How NEFA alter the structure and production of matrix PGs is still a subject of investigation. However, it is known that NEFA impair the use of fructose-6-phosphate in the glycolytic pathway, thus increasing its availability for the hexosamine pathway and consequently for the synthesis of glucosamine that may stimolate GAG synthesis. Alternatively, the overdriven hexosamine pathway may lead to the up-regulation of the synthesis

Transplantation Of Kidney And Pancreas Case Study

Despite the not particularly high level of glycosylated haemoglobin (HbAlc 7.7 percent), the daily blood glucose levels range between severe hypoglycaemia and heavy hyperglycaemia, often expressed with ketoacidosis. Laboratory results are as follows Hct 29.2 percent, Hb 9.5 g dl, WBC 5,900 mm3, PLT 373,000 mm3, glucose 108mg dl (6.0mmol L), urea 210mg dl (34.9 mmol L), creatinine 4.5 mg dl (397.8 mmol L), total cholesterol 253 mg dl (6.08 mmol L), LDL-cholesterol 141 mg dl (3.65 mmol L), HDL-cholesterol 69 mg dl (1.78 mmol L), triglycerides 124 mg dl (1.4 mmol L), uric acid 5.3 mg dl (0.32 mmol L), SGOT 16U L, SGPT 13 U L Urinalysis, protein 675 mg dl, glucose 1 g dl. Generally, the recipients of a pancreas and kidney transplant have lower levels of triglycerides and LDL-cholesterol and higher levels of HDL-cholesterol than the recipients of a kidney transplant alone.

Metformin in Combination Therapy

A 1-year randomized double-blind study in 639 type 2 diabetic patients 13 showed clinically equivalent improvements in glycaemic control for the combination therapy of metformin and SU (HbA1c decrease 1.36 ) or pioglitazone and SU (HbA1c decrease 1.20 ). Pioglitazone addition to SU significantly reduced triglycerides (-16 vs. -9 p 0.008) and increased HDL-cholesterol (14 vs. 8 p 0.001) compared with metformin

Abnormalities in the fibrinolytic system

Impaired fibrinolytic activity is characterized by low t-PA activity and high PAI-1 antigen and activity. Studies in man have shown that t-PA antigen concentration (associated with high PAI-1 and low basal or stimulated t-PA activity) may be high in subjects with preclinical atherosclerosis and a marker for the development of coronary and cerebrovascular events (276,277). Furthermore, t-PA antigen has been found to have a higher predictive value for mortality in patients with established CAD than cholesterol, triglycerides, fibrinogen, blood pressure, diabetes, or smoking (278). Like in nondiabetic subjects, impaired fibrinolysis is an independent risk factor for MI in diabetic subjects (279,280).

Intracellular calcium levels Decrease myocardial apoptosis post reperfusion

Finally, it is important to re-emphasize that, compared with a general population, therapy with primary angioplasty, thrombolysis, b-blockers, aspirin, ACE inhibitors, glycoprotein IIb IIIa inhibitors, and statins are at least as effective in patients who have DM. Despite this, there is significant underuse of these proven therapies in diabetic patients 62 . Sympathetic blockade inhibits lipolysis and the generation of circulating FFA, which compromises glycolysis in ischemic and nonischemic myocardium. Therefore, it is not surprising that b-blockers are particularly beneficial in diabetic patients. Recently, more complete sympathetic blockage with carvedilol was superior to b-blocker therapy with metoprolol in reducing mortality in patients who had congestive heart failure 63 . Unlike other commercially-available b-blockers, carvedilol therapy improved insulin resistance and may be more effective in reversing left ventricular remodeling by improving myocar-dial energetics. Although...

Complications Of Preeclampsia

Hypertension of 3.70 (95 CI 2.7-5.05) after 14.1 years mean follow-up, a relative risk of ischemic heart disease of 2.16 (95 CI 1.86-2.52) after 11.7 years, a relative risk of stroke of 1.81 (95 CI 1.45-2.27) after 10.4 years, and for venous thromboembolism 1.79 (95 CI 1.05-2.14) after 14.5 years. It is unclear whether the increased risk of cardiovascular disease subsequent to preeclampsia is due to the preeclampsia during pregnancy or due to underlying traits of the mother. In a study of 3,494 women of whom 133 developed preeclampsia, there was a positive association found with prepreg-nancy levels of triglycerides, total cholesterol, LDL, non-HDL cholesterol, and BP with the risk of preeclampsia, after adjusting for smoking, history of preeclampsia, and socioeconomic status (121). This study suggests that women with cardiovascular risk factors may be predisposed to preeclampsia. Interestingly several studies have suggested that patients with a history of preeclampsia are relatively...

Medical Complications

The altered nutritional state in obesity results in several alterations that have been linked as comorbidities of the disease. Hyperinsulinemia is strongly linked with cardiovascular diseases, Type 2 diabetes mellitus, hyperlipidemia, and hypertension (29). Obesity is associated with hypertension in 10 to 30 of children (30) regardless of age, gender, and duration. Obese children and adolescents tend to have elevated levels of total serum cholesterol, triglycerides, and low-density lipoprotein, and decreased levels of high-density lipo-proteins (30,31). They are also at increased risk for coronary heart disease (31-33). With few exceptions, the clinical features of cardiovascular heart disease are not apparent until the third or fourth decade of life. However, there is substantial evidence that the atherosclerotic process is initiated during childhood (32-34).

Clinical Emergencies in Diabetes Diabetic Ketoacidosis and Hyperosmolar Nonketotic Syndrome

The lack of insulin will also produce a high rate of lipolysis (insulin exerts an antilipolytic action by inhibiting the hormone-sensitive lipase), so that the adipose tissue releases large amounts of FFA with consequent hyperafflux of FFA to the liver. As outlined in figure 2 and its legend in chapter I, in the liver the FFA may be reesterified to triglycerides (in the cytosol) or p-oxidized to acetyl-CoA. Triglycerides so formed may be deposited in the hepatocytes (causing steatosis) or may be incorporated into VLDL which are secreted into the circulation. The p-oxidation of FFA to acetyl-CoA occurs after the transport of FFA into the mitochondria, effected by the enzyme CPT-1. Glucagon activates the latter mechanism (ketogenesis) both by enhancing the availability of carnitine (a metabolite required for the CPT-1 reaction) and, especially, by lowering the concentration of malonyl-CoA, a key regulatory compound which inhibits CPT-1. Glucagon lowers the malonyl-CoA...

Mechanisms responsible for the overexpression of pai in diabetes

Increased expression of PAI-1 in diabetes is undoubtedly multifactorial. A direct effect of insulin on the expression of PAI-1 has been suggested by a positive correlation between the concentration of insulin and PAI-1 in vivo (93,94,96,100-103,106). Triglycerides and their constituents (fatty acids) appear to contribute to the overexpression of PAI-1 in view of the fact that both insulin and triglycerides independently increase expression of PAI-1 by human hepatoma cells in vitro (105,107-109). Liver steatosis is another determinant of elevated concentrations of PAI-1, perhaps indicative of the response of both to derangements in the tumor necrosis factor signaling pathway (110). Insulin and triglycerides exert a synergistic increase in accumulation of PAI-1 in conditioned media when both are present in pathophysiological concentrations (105). Analogous results are obtained with insulin in combination with very low-density lipoprotein-triglyceride, emulsified triglycerides, or...

The Glucose Sensing System A Basic Model

How Model Diabetes Type

Fig. 1. (continued) Panel D illustrates the complexities of neuroendocrine regulation and drug actions in fuel-stimulated insulin release. Neural and endocrine factors may act by modifying rather than by initiating intracellular signaling pathways involved in substrate-controlled insulin release. Glucose activates the adenylate cyclase-protein kinase A (AC-PKA), phospholipase C-protein kinase C (PLC-PKC) and PKCaCM signaling pathways, all depending on cytosolic Ca2+ levels. The effect of glucose on cytosolic Ca2+ is thus critical for the understanding of this interconnected activation process. For example, the glucose-induced rise of cAMP is Ca2+ dependent, as is the glucose-induced elevation of DAG and IP3. Acetycholine and glucagon-like peptide (GLP-1) are striking examples. They greatly augment the cAMP, IP3 and DAG responses but are not able to initiate insulin release in the absence of fuel, most importantly glucose, because the substrate increase of the P-potential is an...

Individual drug review

A few unfavorable metabolic effects of bBs were reported. bBs might exacerbate glucose intolerance 5,45,46 , increase triglycerides, and decrease high-density lipoproteins 47 . These effects on surrogate end points should not prevent us from using bBs in diabetic patients who have hypertension. Caution should be taken when using bBs in diabetic patients who are at risk for severe hypoglycemia, although there is no convincing evidence that b1-selective blockers increase the risk of masking hypoglycemia symptoms 48-50 . High dosages of selective b1-block-ers should be avoided in patients who have asthma or severe obstructive lung diseases. bBs should not be used in patients who have advanced heart block or sinus node disease without a pacemaker.

How To Cure Buminuria

Cardiovascular benefits of multifactorial intervention in diabetes (Figure 5.6). One-hundred and sixty type 2 patients with microal-buminuria were randomised to receive conventional treatment in accordance to national Danish guidelines or to an intensive treatment arm. This involved stepwise implementation of behaviour modification and pharmacological treatment that targeted hyper-glycaemia, hypertension, dyslipidaemia, microalbuminuria and secondary prevention of cardiovascular disease with aspirin. At the end of the 7.8 year study period there were significant reductions in HbA1c , systolic and diastolic blood pressure, serum cholesterol and triglycerides, and urine albumin excretion in the treatment group. Patients receiving intensive treatment had a significantly lower risk of cardiovascular disease by about 50 . At the end of the treatment period all the patients were offered intensive treatment and were further followed up for an additional 5.5 years. Despite convergence of most...

Mechanisms Underlying Endothelial Dysfunction in Diabetes

Two conditions leading to uncoupling of eNOS have been described. These include BH4 (eNOS co-factor) deficiency and intracellular L-arginine (eNOS substrate) depletion (77). In conditions of BH4 deficiency, eNOS remains in an uncoupled state and preferentially produces superoxide rather than NO. NO in turn is thought to be a superoxide scavenger. Superoxide product peroxynitrite has been shown to rapidly oxidize the active eNOS cofactor BH4 to inactive dihydrobiopterin (BH2) (80). In addition, uncoupled eNOS and L-arginine depletion is characteristically found in conditions where high oxidative stress is encountered, as observed in patients with diabetes (77), hypercholesterolemia (81), and in chronic smokers (82). Thus, hyperglycemia-induced uncoupling of eNOS leads to increased formation of ROS resulting in increased oxidative stress, which has been shown to be a strong stimulus for PKC activation (see Fig. 3). 1s Triglycerides 1s Triglycerides

Early treatment in type diabetic patients without complications

Type 2 diabetic patients with established nephropathy aggressive treatment In the past, once hypertension and increased serum cholesterol had been identified as risk factors, the effect of treatment specifically aimed to lower these risk factors was tested in randomized trials -and several antihypertensive and cholesterol lowering drugs proved to be effective in reducing end-organ damage. Evidence from the large trials in type 2 diabetic nephropathy is now available showing the importance of proteinuria as a modifiable risk factor. In particular, this is underscored by the finding that the degree of proteinuria reduction predicts the efficacy of end-organ protection. Recent studies suggest that the view on normal ranges for blood pressure, albuminuria, and cholesterol needs to be reconsidered. Data from the Framingham Heart study in persons without apparent cardiovascular disease show that even within the normal range for blood pressure, those persons with a high-normal blood pressure...

Brent Van Dorsten Introduction

The alarming global increase in the prevalence of overweight and obesity is now a worldwide health epidemic (Hill et al., 1995 Popkin and Doak, 1998 Wadden et al., 2002). Obesity appears closely associated with several major health risks including hypertension, diabetes, high cholesterol, cardiovascular disease, and certain cancers (Must et al., 1999), and may shorten life expectancy in even young adults (Fontaine et al., 2003). A persistent increase in obesity prevalence has been observed in the United States over the past three decades despite increased awareness. Mokdad et al. (1999) reported an increase in the prevalence of obesity (body mass index (BMI) 30kg m2) from 12 per cent (1991) to 17.9 per cent (1998), and a recent review of National Health and Nutrition Examination Survey (NHANES) data report that 64.5 per cent of the US population is currently overweight (BMI 25 kg m2), with the prevalence of obesity now reaching 30.5 per cent (Flegal et al., 2002). Most recently,...

Perturbation of metabolic flux control the role of substrate overabundance

It is well known that increased circulating triglycerides and FFA are frequently associated with pathophysiology of insulin resistance and diabetes mellitus. Searching for the mechanism of their action on glucose metabolism, Sir Randle et al. (1963) observed that elevated circulating free fatty acids (FFA) impair skeletal muscle glucose uptake. The results of his studies allowed him to postulate the hypothesis that substrate competition for mitochondrial oxidation is the major mechanism involved in this action. According to this hypothesis, experimental challenge by FFA would first increase the intracellular glucose-6-phosphate

Epidemiology Of Dyslipidemia In Type Diabetes

The hallmarks of diabetic dyslipidemia are moderate hypertriglyceridemia (usually 1.5 to 3-fold increased) and reduced HDL cholesterol (approximately 10-20 ) total and low-density lipoprotein (LDL) cholesterol are generally not different quantitatively from non-diabetics. For example, in the prospective cardiovascular munster (PROCAM) study in the North of Germany 39 of patients with diabetes had triglyceride concentrations 200 mg dL ( 2.3 mmol L), versus 21 in non-diabetics, and 27 had low HDL cholesterol i.e.

Pulsatility Of Ffa Release

Because FFAs are released into the circulation by lipolysis of adipose tissue triglycerides in relation to the size of the fat depot, the greater overall fat mass of adipose tissue in obese individuals will result in an elevation of fatty acid flux to nonadipose tissues, even in the absence of a qualitative abnormality in adipose tissue metabolism (62). It is worth noting that not all fat depots make an identical contribution to the plasma pool of FFAs. Upper body fat (ie fat in the visceral and subcutaneous abdominal region), but not lower body fat is strongly associated with insulin resistance and increased risk of cardiovascular events (63-67) although the causal nature of this relationship and the relative importance of visceral versus subcutaneous abdominal fat (68,69) are still debated (70,71). The question as to whether the transport of FFA into cells occurs through a passive diffusion process or by a facilitated mechanism involving fatty acid transport protein (FATP) remains...

Risk factors for coronary heart disease CHD the role of oxidative stress

Endothelial Dysfunction Diabetic Foot

Two hypotheses can be suggested to explain why hypercholesterolaemia enhances oxidative stress (Fig. 5.1, panel A,B). Cholesterol has been recently shown to activate the metabolism of the arachidonic acid pathway,31 which in turn seems to be associated with NAD(P)H oxidase activation.26 This hypothesis has been recently underscored by our group showing that platelet incubation with cholesterol enhanced O2* production and that inhibition of PLA2 or NADPH oxidase enzymes significantly reduced O2 formation (Fig. 5.1 panel B).31 The cascade of cholesterol biosynthesis may represent another pathway leading to enhanced oxidative stress. Intracellular metabolism of mevalonate leads, in fact, to the formation of protein isoprenylation, which has a key role in the production of proinflammatory and pro-oxidant cytokines such as tumor necrosis factor alpha (TNF Fig. 5.1, panel A).32 Accordingly, treatment of hypercholesterolaemic patients with an inhibitor of HMG-CoA-reductase was associated...

Counseling and Preconception Care Recommendations to Reduce Maternal and Fetal Risks of Preexisting Diabetes What Are

Pregnancy is known to increase triglyceride levels markedly in the second and third trimesters (59). One dangerous complication of hyperlipidemia in pregnancy occurs in severe familial hypertriglyceri-demia, where pancreatitis has been known to complicate pregnancies with devastating results. Therefore, it is important that during preconception women are screened for lipid disorders and that women with severe hypertriglyceridemia have sequential measurements of triglycerides during pregnancy (60).

Dietary prevention of sudden cardiac death SCD the role of dietary fatty acids alcohol and antioxidants

Whereas PUFA of either the n-6 or n-3 family reduce that risk.4 6 Many (but not all) epidemiological studies have shown consistent associations between the intake of saturated fatty acids and CHD mortality.26 However, the SCD endpoint is usually not analysed in these studies. In addition, a clear demonstration of a causal relationship between dietary saturated fatty acids and SCD would require the organisation of a randomised trial, which is not ethically acceptable. Thus, besides the effect of saturated fatty acids on blood cholesterol levels, the exact mechanism(s) by which saturated fats increase CHD mortality remain unclear. If animal data, demonstrating a proarrhythmic effect of saturated fatty acids, are confirmed in humans, the first thing to do in order to prevent SCD in humans would be to drastically reduce the intake of saturated fats. In fact, this has been done in randomised dietary trials and, as expected, the rate of SCD decreased in the experimental groups.18'19...

Dietary Modifications

The focus of treating a patient with type 2 diabetes, obesity, cancer, or any other condition should be on the impact of multiple nutritional imbalances (both excess and deficiency) in the individual. Various nutrients specific for an individual's biochemistry may help to modulate factors associated with disease. Using dietary changes and nutritional supplements to help bring homeostasis back to the individual's biochemical makeup is of upmost importance. Dietary factors have effects on inflammatory signaling, independent of smoking, hypercholesterolemia, and hypertension. Diets low in glycemic index load that use whole grain products versus refined flours have been associated with decreased concentrations of inflammatory markers and increased adiponectin levels among diabetic patients. These associations appear to be independent of body weight, glycemic control, and other cardiovascular risk factors. The protective effects of low glycemic load and whole grains on systemic...

Repercussions of DM in sexual life

Erectile dysfunction is associated, in most cases, with diseases that affect the blood vessels, causing atherosclerosis. Thus, hypertension, hypercholesterolaemia, DM and smoking increase the risk of the problem. At the same time, it can be also due to psychological or emotional factors. Finally, the use of medicines (diuretics, beta-blockers) but also psychotropic substances (alcohol, marijuana, cocaine, etc.) can cause erectile dysfunction.

Prevention Of Type Diabetes

Post-challenge) Low insulin secretion Insulin resistance syndrome (low HDL-C, high triglycerides, hypertension, fibrinolytic defects, glucose intolerance) Low magnesium level Low chromium level High plasma non-esterified fatty acids Low sex hormone binding globulin Low physical activity Cigarette smoking

Diabetic dyslipidemia

Lipid disorders assume a position of utmost importance in patients with diabetes because of the high risk of macrovascular disease in this condition. Patients with well controlled type 1 diabetes mellitus (DM) have lipoprotein concentrations similar to the background non-diabetic population. With poor control, increased concentrations of triglyceride-rich lipopro-teins are seen giving rise to hypertriglyceridemia. The most common lipoprotein abnormality in type 2 diabetes is an elevation in triglycerides and very-low-density lipoprotein (VLDL) caused by an overproduction of VLDL triglyceride. Lipoprotein lipase activity is probably decreased in type 2 diabetes, possibly as a manifestation of insulin resistance, and this may be a direct cause of elevated VLDL levels. No consistent changes in low-density lipoprotein (LDL) cholesterol are seen in type 2 diabetes, but a number of potentially atherogenic changes in LDL composition have been observed particularly a predominance of small...

Recent Developments

2 A novel approach to increasing HDL-cholesterol is by inhibiting CETP. A recent trial with the inhibitor torcetrapib reported increased HDL-cholesterol of 46 when used alone and 61 when used with atorvastatin (Figure 32.1).6 The drug also increased the mean size of both LDL and HDL lipoprotein particles. 3 A major theme of current nutritional research is the interaction between dietary components and the expression of genes or the activity of metabolic pathways in vivo. Conjugated linoleic acids have been proposed as regulators of lipid metabolism and insulin resistance.7 There has been interest in diets that include a small amount of walnuts.8 These contain a high proportion of polyunsaturated fats including a-linoleic acid as well as the antioxidant 7-tocopherol. Compared with a control diet, a diet that included 30 grams of walnuts per day significantly increased HDL-cholesterol and decreased LDL-cholesterol.

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